US20090180931A1 - Integrated robotic sample transfer device - Google Patents

Abstract

Embodiments include integrated robotic sample transfer devices and components thereof which are used for reliably and accurately transferring small samples of material from one registered position to another registered position. Such transfers of material may be carried out by a single pin tool or an array of pin tools of a pin tool head assembly of robotic sample transfer devices. Some embodiments also include automated cleaning of the pin tools used to transfer the sample material. Some embodiments are fully integrated units having internal fluid supply and waste tanks, vacuum source, fluid pumps, controllers and user interface devices.

Description

RELATED APPLICATIONS
• This application claims priority under 35 U.S.C. section 119(e) from U.S. provisional application Ser. No. 60/972,879 filed Sep. 17, 2007, by R. Silbert et al. titled “Integrated Robotic Sample Transfer Device” which is incorporated by reference herein in its entirety.
FIELD OF THE INVENTION
• Embodiments of the present invention generally relate to robotic sample transfer devices and methods which may be used for reliably and consistently transferring large numbers of small samples of material from one registered position to another registered position. Such transfers of material may be carried out by a single pin tool or an array of regularly spaced pin tools on a pin tool head assembly. Some embodiments include automated cleaning of the pin tools used to transfer the sample material between sample transfer steps.
BACKGROUND
• In recent years, developments in the field of life sciences have proceeded at a very rapid pace. Universities, hospitals and newly formed companies have made groundbreaking scientific discoveries and advances that promise to reshape the fields of medicine, agriculture, and environmental science. However, the success of these efforts depends, in part, on the development of sophisticated laboratory tools that will automate and expedite the testing and analysis of biological samples. Only upon the development of such tools can the benefits of these recent scientific discoveries be fully achieved.
• At the forefront of these efforts to develop better analytical tools is an effort to expedite the analysis of complex biochemical structures. This is particularly true for human genomic DNA, which is comprised of at least about one hundred thousand genes located on twenty four chromosomes. Each gene codes for a specific protein, which fulfills a specific biochemical function within a living cell. Changes in a DNA sequence are known as mutations and can result in proteins with altered or in some cases even lost biochemical activities; this in turn can cause a genetic disease. More than 3,000 genetic diseases are currently known. In addition, growing evidence indicates that certain DNA sequences may predispose an individual to any of a number of genetic diseases, such as diabetes, arteriosclerosis, obesity, certain autoimmune diseases and cancer. Accordingly, the analysis of DNA is a difficult but worthy pursuit that promises to yield information fundamental to the treatment of many debilitating and life threatening diseases.
• Analysis of DNA is made particularly cumbersome due to size and the fact that genomic DNA includes both coding and non-coding sequences (e.g., exons and introns). As such, traditional techniques for analyzing chemical structures, such as the manual pipeting of source material to create samples for analysis, are of little value. To address the scale of the necessary analysis, scientists have developed parallel processing protocols for DNA diagnostics.
• Robotic pin tool devices used for the accurate and efficient transfer of materials from sample wells to sample test sites have been used for the processing of materials for a great variety of applications. Such devices are frequently used for the processing of fluid DNA samples for mass spectrometry, including MALDI mass spectrometry, genotyping, quantitative gene expression including PCR methods, methylation analysis and SNP discovery. For such processes, a small amount of fluid is taken up by a pin tool from a pre-determined well of a microtiter plate and mapped and deposited to a pre-determined location on another surface, such as a mass spectrometry chip. The control software for the robotics of the robotic pin tool generally will track the transfer of samples from each well of the microtiter plate to the corresponding location on the chip such that a comprehensive mapping of samples is maintained. Once a set of samples have been transferred, the pins may undergo a washing process and may then be used to transfer another set of samples. Such tools and processes greatly enhance the efficiency and reliability of sample handling and processing where a large number of small volume samples need to be processed.
• Current devices that perform these procedures are useful, but are generally large, heavy and expensive machines that require the use of large external fluid storage tanks, external computing devices, including desktop units with corresponding keyboard and monitor devices, external plumbing to facility utilities and the like. As a result, a standard pin tool sample transfer machine may take up a large amount of space within a laboratory in which it is being used. In addition, standard pin tool sample transfer devices may be inconvenient to operate and maintain. What has been needed is a robotic sample transfer machine that is small in size and weight relative to existing machines and less expensive than the currently available sample transfer devices. What has also been needed is a robotic sample transfer device that is user friendly, easy and reliable to operate and economical to maintain.
SUMMARY
• Some embodiments of robotic sample transfer devices include a substantially horizontal work surface and a three axis robotic positioning assembly. The three axis robotic positioning assembly has a fixed mount portion secured in fixed relation with the work surface, a translatable carrier configured to be translatable in three different axes with respect to the fixed mount portion and working surface. The three axis robotic positioning assembly has a stepper motor and corresponding linear encoder assembly for at least one axis. A controller is in communication with the stepper motor of each of the three axes and linear encoder of the three axis robotic positioning assembly.
• Some embodiments of a robotic sample transfer device include a housing, a substantially horizontal work surface disposed within the housing and a three axis robotic positioning assembly disposed within the housing having a fixed mount portion secured in fixed relation with the work surface and a translatable carrier member translatable in three different axes with respect to the fixed mount portion and work surface. The robotic sample transfer device also includes at least one pin tool coupled to the translatable carrier having a shaft and a sample reservoir in a distal end of the shaft. A plurality of functional elements may be disposed on the work surface having a nominal upper surface at substantially the same z-axis height. The robotic sample transfer assembly may also include a controller operatively coupled to the three axis robotic positioning assembly.
• For some embodiments, the functional elements disposed on the work surface include a vacuum drying station, a fluid rinse station, a self-leveling ultrasonic cleaning well, a microtiter plate having an array or regularly space sample supply wells and a chip having an array of regularly spaced sample deposition sites. For some embodiments, the controller of the robotic sample transfer device includes at least one processor which is disposed within the housing at a level which is above the level of the work surface.
• Some embodiments of an integrated robotic sample transfer device include a housing, a substantially horizontal work surface and a three axis robotic positioning assembly disposed within the housing. The three axis robotic positioning assembly may include a fixed mount portion, a translatable carrier which is translatable in three different axes with respect to the fixed mount portion, and a stepper motor for each axis. Some embodiments may include a linear encoder for at least one of the axes. A pin tool head assembly may be secured to the translatable carrier member and have an array of regularly spaced pin tools which have sample reservoirs disposed in the distal ends thereof and which are configured for axial displacement relative to a pin head body secured to the translatable carrier of the three axis robotic positioning assembly. The substantially horizontal work surface is disposed within the housing and is secured in fixed relation to the fixed mount portion of the three axis positioning assembly. The work surface may have a plurality of functional components disposed thereon which may include a fluid rinse station, a vacuum drying station including a plurality of regularly spaced vacuum drying ports corresponding to the regular spacing of the array of pin tools, a self-filling ultrasonic cleaning well and a microtiter plate mount block. The microtiter plate mount block is configured to releasably secure a pre-selected microtiter plate sample well thereto. A chip mount block may also be disposed on the work surface and have a nominal upper surface at substantially the same level as at least one or more of the functional components. A controller including a processor is disposed within the housing at a position which is above the level of the work surface. A rinse fluid supply tank is in fluid communication with the fluid rinse station and disposed within the housing. A waste water tank is in fluid communication with an overflow basin of the fluid rinse station and disposed within the housing. A vacuum source is in fluid communication with the vacuum drying station and an ultrasonic cleaning fluid supply reservoir is in fluid communication with the self-filling ultrasonic cleaning well.
• Some embodiments of a method of registering a position of a pin tool head assembly of a robotic sample transfer device relative to sample deposition sites on a chip include providing a robotic sample transfer device having a work surface with a plurality of functional elements, at least two of which have a nominal upper surface at substantially the same level. For some embodiments, a nominal upper surface of all the functional elements may be at the same z-axis level. For some embodiments, the functional elements that require a substantially precise positional alignment of pin tools being used at the functional element may be at substantially the same z-axis level. The robotic sample transfer device may also have a three axis positioning system with a camera secured to a translatable carrier thereof and the pin tool head assembly secured to a translatable carrier thereof. The nominal upper surfaces of functional components disposed on work surface are imaged by the camera and the image data of the nominal upper surfaces of the functional elements processed by an image processor to determine the approximate position of the pin tool head assembly relative to the functional elements. The approximate position data is then used to move the field of view of the camera to a first chip having an array of regularly spaced sample deposition sites and an array of regularly spaced fiducial marks disposed between the sample deposition sites. The fiducial marks on the first chip are imaged by the camera and the image data of fiducial marks on the first chip processed by an image processor. Feedback may then be obtained regarding a position of the pin tool head assembly from one or more linear encoders of three axes of a three axis robotic positioning system. Linear encoder feedback may then be compared with image processing feedback and look up table data to determine the precise position of the pin tools of the pin tool head assembly with respect to the sample deposition sites on the first chip. For some embodiments, the process may be repeated for two or more chips to determine the position of the pin tools of the pin tool head assembly with respect to sample deposition sites of the two or more chips.
• Some embodiments of a method of dispensing calibration material onto a chip include providing a chip having a first array of regularly spaced sample deposition sites disposed on a substantially flat working surface thereof and at least one sample deposition site for receiving calibration material which is also disposed on the flat working surface of the chip and which is off pitch with respect to the regular spacing of the array of regularly spaced sample deposition sites of the chip. A robotic sample transfer device is provided which has a pin tool head assembly with an array of regularly spaced pin tools having distal ends which are substantially coplanar with each other in a relaxed state. The regular spacing of the pin tools corresponds to the regular spacing of the first array of sample deposition sites or an integer multiple thereof and is configured to align with the array of regularly spaced sample deposition sites of the chip or a subset thereof. Sample reservoirs of the pin tools of the array of regularly spaced pin tools of the robotic sample transfer device are loaded with calibration material. Calibration material is dispensed from the pin tools of the robotic sample transfer device to the at least one sample deposition site for receiving calibration material such that the pin tools which are not aligned with sample deposition sites for receiving calibration material are off pitch with respect to the first array of regularly spaced sample deposition sites of the chip and do not contact any of the regularly spaced sample deposition sites of the first array. For some embodiments, the chip may include a second array of regularly spaced sample deposition sites for receiving calibration material sample which are off pitch with respect to the first array of regularly spaced sample deposition sites. For such embodiments, calibration material from sample reservoirs of the pin tools of the robotic sample transfer device may be dispensed to the second array of sample deposition sites for receiving calibration material such that the pin tools which are not aligned with sample deposition sites for receiving calibration material of the second array are off pitch with respect to the first array of regularly spaced sample deposition sites of the chip and do not contact any of the regularly spaced sample deposition sites of the first array.
• Some embodiments of a pin tool displacement block for selectively displacing at least one pin tool of a pin tool head assembly of a robotic sample transfer device include a block body portion having a top surface and a bottom surface which is substantially parallel to the top surface and a plurality of parallel slots formed into the block body portion. The pin tool displacement block also includes one or more relieved portions in the slots corresponding to the location of pins that are to remain in use when the pin tool displacement block is engaged with the pin tools of the pin tool head. For some embodiments, the parallel slots formed into the body portion have a width to allow passage and movement of a pin tool shafts but not a collar member secured to the pin tool shaft so as to displace the pin in a retracted position. Relieved portions in the slots are configured to allow passage and movement of the collar members so as not to displace the corresponding pin tools in a retracted position located in positions corresponding to pin tools which are to remain usable after deployment of the block in a pin tool head assembly. Some embodiments of the pin tool displacement block have a reversible configuration wherein when the block is oriented in a first direction a first set of pins or pin is active and oriented a second way a second set of pins or pin is active which is different from the first set.
• Some embodiments of a method for selectively displacing at least one pin tool of a pin tool head assembly of a robotic sample transfer device, include providing a pin tool displacement block with a block body portion having a top surface and a bottom surface which is substantially parallel to the top surface, a plurality of parallel slots formed into the block body portion and one or more relieved portions in the slots corresponding to the location of pins that are to remain in use when the pin tool displacement block is engaged with the pin tools of the pin tool head. An array of pin tools of a pin tool head assembly are displaced by depressing the pin tools against a flat surface. The pin tool displacement block is deployed into the pin tool head assembly such that the parallel slots of the pin tool displacement block slide over rows of the array of pin tools of the pin tool head assembly and the pin tools are allowed to return to a relaxed state by retracting the pin tool head assembly from the flat surface.
• Some embodiments of a method of dispensing calibration material onto a chip may include providing a chip having an array of regularly spaced sample deposition sites disposed on a substantially flat working surface thereof. The chip may also haveat least one sample deposition site for receiving calibration material which is also disposed on the flat working surface of the chip. A robotic sample transfer device may be provided having a pin tool head assembly with an array of regularly spaced pin tools having distal ends which are substantially coplanar in a relaxed state and which have a regular spacing which is the same as the regular spacing of the first array of sample deposition sites or an integer multiple thereof. The pin tools of the pin tool head assembly may be configured to align with the array of regularly spaced sample deposition sites of the chip or a subset thereof. At least one of the pin tools of the pin tool head assembly may be axially displaced with a pin tool displacement block and a sample reservoir of at least one un-displaced pin tool of the robotic sample transfer device loaded with calibration material. Calibration material may be dispensed from the at least one un-displaced pin tool of the robotic sample transfer device to the at least one sample deposition site for receiving calibration material such that the pin tools which are displaced by the pin tool displacement block do not contact the chip.
• These features of embodiments will become more apparent from the following detailed description when taken in conjunction with the accompanying exemplary drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a perspective view of an embodiment of a robotic sample transfer device.
• FIG. 2 is a rear elevation view with a rear panel of the housing not shown.
• FIG. 3 is a front elevation view of the robotic sample transfer device ofFIG. 1 with the processing chamber cover and tank chamber front cover not shown.
• FIG. 4 is a perspective view of a three axis positioning system and work surface of the robotic sample transfer device ofFIG. 1.
• FIG. 5 is a perspective view of an x-axis translation assembly of the three axis positioning system.
• FIG. 6 is a perspective view of the y-axis carrier and z-axis carrier of the three axis positioning system.
• FIG. 6A is an enlarged view in partial section of a bottom plate, pin tool shaft, helical spring clip and washer of a pin tool head assembly embodiment.
• FIG. 6B is a top view in partial section of a shaft of a pin tool in sliding engagement with a cover plate.
• FIG. 7 is a perspective view of a work surface and functional components of the robotic sample transfer device ofFIG. 1.
• FIG. 7A is an elevation view in partial section of an embodiment of a wash fluid reservoir.
• FIG. 7B is a transverse cross section of the wash fluid reservoir ofFIG. 7A taken alonglines7B-7B inFIG. 7A.
• FIG. 7C is a perspective view of an embodiment of a calibration material supply vessel.
• FIG. 7D is a perspective view of an embodiment of a calibration material supply vessel.
• FIG. 8 is a top view of a work surface and functional components of the robotic sample transfer device ofFIG. 1.
• FIG. 9 is an exploded view of the work surface and functional components of the robotic sample transfer device ofFIG. 1.
• FIG. 10 is an elevation view of the work surface and functional components of the robotic sample transfer device ofFIG. 1.
• FIG. 11 is an enlarged perspective view of a ultrasound energy generator of the ultrasonic cleaning well disposed on the work surface.
• FIG. 11A is a top view of an embodiment of a chip having an array of sample deposition sites disposed thereon.
• FIG. 11B is a bottom view of the chip ofFIG. 11A.
• FIG. 12 is an elevation view of a pump housing with a rear cover of the housing not shown for clarity of illustration.
• FIG. 13 is a perspective view of a waste fluid tank.
• FIG. 14 is a perspective view of a fluid supply tank.
• FIG. 15 is a perspective view of a pin tool displacement block for selectively displacing a pin tool of a pin tool head assembly.
• FIG. 15A is a sectional view of the block ofFIG. 15 taken alonglines15A-15A.
• FIG. 16 is a top view of the pin tool displacement block ofFIG. 15.
• FIG. 17 is an elevation view of a pin tool head assembly embodiment including two spring loaded pin tools.
• FIG. 17A is a front view of the pin tool head assembly ofFIG. 17.
• FIG. 18 is an elevation view of the pin tool head assembly ofFIG. 17 with the pin tools displaced in a proximal direction.
• FIG. 19 is an elevation view of the pin tool head assembly with the pin tool displacement block engaged.
• FIGS. 20A-20D illustrate an embodiment of a pin tool displacement block, single pin configuration.
• FIGS. 21A-21D illustrate an embodiment of a pin tool displacement block, six pin configuration.
• FIG. 22 is a perspective view from a first side of a reversible pin tool displacement block embodiment.
• FIG. 23 is an elevation view of the reversible pin tool displacement block ofFIG. 22.
• FIG. 24 is a view from a second side of the reversible pin tool displacement block ofFIG. 22.
• FIG. 25 is an enlarged perspective view of a portion of a sample chip showing sample deposition sites and sample reservoirs of a pin tool head assembly disposed over calibration sites.
• FIGS. 26-34 show screen image representations of a graphic user interface embodiment for communicating instructions and information to a controller of a robotic sample transfer device.
• FIGS. 35A-35D illustrate an embodiment of a pin tool displacement block, single pin configuration.
• FIGS. 36A-36D illustrate an embodiment of a pin tool displacement block, six pin configuration.
• FIGS. 37A-37C illustrate an embodiment of a pin protection block tool assembly.
• FIG. 38A is a top view of an outer collar for use with a plunger mechanism embodiment.
• FIG. 38B is a cross section view of an outer collar for use with a plunger mechanism embodiment.
• FIG. 39A is a front view of a plunger handle for use with a plunger mechanism embodiment.
• FIG. 39B is a cross section view of a plunger handle for use with a plunger mechanism embodiment.
• FIGS. 40A-40C illustrate an embodiment of a dry station plate assembly, single in configuration.
• FIGS. 41A-41C illustrate an embodiment of a dry station plate assembly, six pin configuration.
• FIG. 42 illustrates the functional coupling of components which enable selective displacement of pin tools in the pin tool head.
DETAILED DESCRIPTION
• As discussed above, currently available robotic sample transfer devices are generally large, heavy and expensive machines that require the use of large external fluid storage tanks, external computing devices, including desktop units with corresponding keyboard and monitor devices, external plumbing to facility utilities and the like. As a result, a standard pin tool sample transfer machine may take up a large amount of space within a laboratory in which it is being used. In addition, standard pin tool sample transfer devices may be inconvenient and expensive to operate and maintain.
• As such, a robotic sample transfer device that is relatively small in size and weight may be particularly useful. In addition, a robotic sample transfer device that is user friendly, easy and reliable to operate and can be simply maintained may also be particularly useful. Embodiments of robotic sample transfer devices described herein may be directed to integrated configurations that have a relatively small footprint with internal storage tanks, internal controllers and processors, internal plumbing all disposed within a housing that encloses a processing chamber. Such embodiments take up less laboratory space and are easy to use and maintain.
• A graphic user interface may be disposed on an outer surface of the housing of some embodiments which allows a user to easily program and use the robotic sample transfer device while keeping the processing chamber closed. Embodiments of the graphic user interface may include touch screen displays allowing intuitive user input without the need for a computer keyboard or mouse, although such alternative interface tools may be supported in some embodiments via USB ports or the like. A substantially horizontal work surface may include a plurality of functional elements with two or more of the functional elements having nominal upper surfaces at approximately the same level which allows an imaging camera to easily image the functional elements of the work surface as well as providing a work surface at a consistent level for easy access and navigation. Such imaging of the functional elements may be used or otherwise processed in some embodiments to quickly determine the position of pin tools or pin tool head assemblies with respect to the functional elements with a high degree of precision.
• Some robotic sample transfer device embodiments may be used for the accurate and efficient transfer of materials from one position to another position may be useful for the processing of samples and the like for a great variety of applications. Some embodiments may be used for the processing of fluid DNA samples for mass spectrometry, including MALDI mass spectrometry, genotyping, quantitative gene expression including PCR methods, methylation analysis and SNP discovery. Commonly owned U.S. Pat. No. 6,730,517, filed Oct. 5, 2000 by Koster et al., issued May 4, 2004, titled “Automated Process Line”, describes automated modular analytical systems and methods of analysis of samples and is hereby incorporated by reference herein in its entirety. Some or all of the robotic sample transfer device embodiments discussed herein may be configured to perform some or all of the analytical processes discussed in U.S. Pat. No. 6,730,517. Embodiments of the robotic sample transfer device may be used to transfer samples that include liquids, solids, gels and the like, or any combination thereof.
• Some robotic sample transfer device embodiments may include a substantially horizontal work surface that has a plurality of functional elements disposed on the work surface. The functional elements may be configured for the processing of small samples of material. A three axis robotic positioning assembly may have a fixed mount portion which is secured in a fixed relation with the work surface to provide mobility of tools and other devices over and in contact with the work surface and functional elements thereof. The three axis robotic positioning assembly may include one or more translatable carriers, at least one of which may be configured to be translatable in three different axes with respect to the fixed mount portion and working surface. For some embodiments, the three different axes of the translatable carrier may be substantially orthogonal to each other. Certain tools or other devices may be secured to the translatable carrier in order to provide high precision mobility of the tools and other devices with respect to the work surface and functional elements on the work surface. Some of the tools and devices that may be coupled to the translatable carrier include pin tools, pin tool head assemblies, cameras, bar code readers and the like. For some embodiments, upper nominal surface or surfaces of the functional elements may form the work surface.
• While some translatable carrier embodiments may be movable and be positioned in three axes, the three axis robotic positioning assembly may include other translatable carrier embodiments, to which these same tools and devices may be coupled, that are moveable and may be positioned in only one axis or two axes. The three axis robotic positioning assembly may include a stepper motor for imparting motion and a corresponding linear encoder assembly for providing positional feedback or information for one or more of the three axes of the three axis robotic positioning assembly. As discussed above, one of the tools that may be moved in three axes above the work surface is a pin tool which may be coupled to the translatable carrier of the three axis robotic positioning assembly. The pin tool may be coupled to the translatable carrier such that the pin tool is substantially perpendicular to the work surface. For embodiments that include a pin tool head assembly, multiple pin tools of a pin tool head assembly which is coupled to a translatable carrier may also be oriented substantially perpendicular to the work surface.
• A controller may be used in communication, such as electrical or optical communication, with the stepper motor and the linear encoder assembly of one or more of the axes of the three axis robotic positioning assembly in order to provide controllable movement to the one or more pin tools or other devices coupled to the translatable carrier or carriers. Such a controller may include one or more processors and data storage units in communication with the processor or processors. Some controller embodiments may also include one or more data input ports or terminals which allow a user to input data or other programming information in order to have the controller carry out desired instructions or processing protocols. A graphic user interface on a housing of the device may be in communication with such a terminals or ports of the controller. Some embodiments of the robotic sample transfer device may have the controller and associated components and electronics of the controller disposed above the vertical level of the work surface to avoid damage to these components from spillage of liquids on or around the work surface and associated functional components.
• The controller may receive position data from the linear encoder assemblies as well as other sources and provide actuation signals and power to the stepper motors of the three axes in order to produce predetermined motion and positioning of the translatable carrier and tools coupled thereto with respect to the work surface and functional elements and with a high degree of precision. Position data generated by one of the linear encoder assemblies may include the position of a translatable carrier relative to a corresponding rail member upon which the translatable carrier moves. For such embodiments, an optical linear encoder strip may be disposed on the rail member and be positioned to be read by a linear encoder reader disposed on the corresponding translatable carrier.
• Sometimes a housing may be disposed about the work surface, three axis robotic positioning assembly and controller as well as other components of robotic sample transfer device embodiments. Embodiments of the housing may include a skin material disposed on a frame structure. The skin material may be made of suitable polymers, composites, metals or the like in order to provide an enclosed controlled processing chamber and to protect the components of the robotic sample transfer device disposed therein. As discussed above, a graphic user interface may be disposed on or otherwise accessible from an exterior of the housing and be operatively coupled to the controller for providing user input, instructions, data or the like to the controller.
• Some embodiments of a robotic sample transfer device may include a housing and a substantially horizontal work surface disposed within the housing. A three axis robotic positioning assembly may also be disposed within the housing for such embodiments and have a fixed mount portion secured in fixed relation with the work surface. The three axis robotic positioning assembly may include one or more translatable carrier members, including a translatable carrier member that is translatable in three different axes with respect to the fixed mount portion and work surface. At least one pin tool is coupled to the translatable carrier. The pin tool has a shaft and a sample reservoir in a distal end of the shaft. A variety of suitable reservoir embodiments may be used which may be configured to draw and store small volume liquid samples, generally in the nanoliter range of volume, into the reservoir by capillary action or other suitable mechanisms.
• A plurality of functional elements may be disposed on the work surface with each functional element having a nominal upper surface. For some embodiments, an upper nominal surface or surfaces of the functional elements may form the work surface. For some embodiments, two or more of the nominal upper surfaces the functional elements may be disposed at substantially the same z-axis level or height. Such a configuration may be useful in order to facilitate imaging of the functional elements and positioning of the pin tool with respect to the nominal upper surface of each functional element. This may be particularly true in embodiments wherein an imaging camera is disposed on one or more of the translatable carriers of the robotic positioning assembly and is used for imaging the functional elements disposed on the work surface.
• For such embodiments, it may be useful to have the imaging camera disposed on a translatable carrier embodiment that is translatable only in the X-Y plane, substantially parallel to the work surface. For such a camera with a fixed Z-axis position, the distance between the camera lens and the work surface or upper nominal surfaces of functional elements disposed on the work surface may be substantially fixed. Thus, camera embodiments having a fixed focal length and narrow range of focus may be positioned on the translatable carrier at the appropriate focal distance from the work surface for consistent focused imaging of the upper nominal surfaces of the functional elements. In this way, the upper nominal surfaces of the functional elements disposed at substantially the same z-axis level will remain in focus and be clearly imaged as the translatable carrier moves about over the work surface. The pin tool or other devices coupled to a translatable carrier which may be positioned in three axes may be moved independently of the camera in the Z-axis direction.
• For some embodiments, the functional elements disposed on the work surface may include a vacuum drying station, a fluid rinse station, a self-leveling gravity fed ultrasonic cleaning well, a microtiter plate having an array or regularly space sample supply wells and a chip having an array of regularly spaced sample deposition sites. A controller may be operatively coupled to the three axis robotic positioning assembly as well as any of the functional elements on the work surface or components thereof. Such a controller may include one or more processors and data storage units in communication with the processor or processors which are disposed within the housing at a level which is above the level of the work surface.
• For some embodiments, the pin tool which is coupled to the translatable carrier may be part of a pin tool head assembly having an array of regularly spaced pin tools which is secured or otherwise coupled to the translatable carrier. For some embodiments, the vacuum drying station may include a plurality of regularly spaced vacuum drying ports corresponding to the spacing of the pin tools of the pin tool head assembly. For some embodiments, the fluid rinse station may include individual rinse tubes corresponding to each of the pin tools of the array of regularly spaced pin tools of the pin tool head assembly.
• For some embodiments, an ultrasonic cleaning fluid reservoir may be disposed in fluid communication with the ultrasonic cleaning well. The ultrasonic cleaning fluid reservoir may have an enclosed and fluid tight interior volume in fluid communication with a supply port configured to couple in fluid communication to an inlet port of the ultrasonic cleaning well. For some embodiments of such a configuration, the supply port of the ultrasonic cleaning fluid reservoir may be open to fluid flow when coupled into fluid communication with the inlet port of the ultrasonic cleaning well and be substantially sealed when the removed from the inlet port of the ultrasonic cleaning well. Some particular embodiments may include a ball valve which is configured to seal the supply port when the fluid reservoir is removed from the inlet port of the ultrasonic cleaning well.
• Some embodiments of an integrated robotic sample transfer device may include a housing and a three axis robotic positioning assembly disposed within the housing having a fixed mount portion and a translatable carrier which is translatable in three axes with respect to the fixed mount portion and a substantially horizontal work surface. A stepper motor and corresponding linear encoder assembly may be included for one or more of the axes of the three axis robotic positioning assembly. Each stepper motor may be configured to provide motion in the direction of each respective axis and each linear encoder assembly may be used to provide position data in the direction of each respective axis. A pin tool head assembly may be secured to the translatable carrier member which has an array of regularly spaced pin tools with sample reservoirs disposed in the distal ends thereof. The pin tools may be configured for axial displacement relative to a pin head body which is secured to the translatable carrier of the three axis robotic positioning assembly. Some embodiments of the robotic sample transfer device may also include a door on the housing which is configured to cover an opening to a processing chamber disposed within the housing.
• The substantially horizontal work surface may be disposed within the housing and secured in fixed relation to the fixed mount portion of the three axis robotic positioning assembly. The work surface may have one or more functional elements which may include a fluid rinse station, a vacuum drying station including a plurality of regularly spaced vacuum drying ports corresponding to the regular spacing of the array of pin tools, a self-leveling ultrasonic cleaning well and a microtiter plate mount block configured to releasably secure a sample well disposed thereon. For some embodiments, the upper nominal surfaces of two or more of the functional elements may form the work surface. For some of these embodiments, a nominal upper surface of the fluid rinse station, nominal upper surface of the vacuum drying station, nominal upper surface of the ultrasonic cleaning well, nominal upper surface of a chip disposed in the chip mount block and microtiter plate/sample well mounted in the sample well mount blocks are all disposed at substantially the same z-axis level. For some embodiments of the robotic sample transfer device, the entire dry weight of the device is less than about 150 pounds. For some embodiments, functional elements such as the ultrasonic cleaning well that do not require precise alignment in the x-y plane may be disposed at a z-axis level that differs from the z-axis level of the remaining functional elements or subset of functional elements having an upper nominal surface disposed at substantially the same z-axis level.
• A controller may be disposed within the housing. Such a controller may include one or more processors and data storage units in addition to an assembly of other electronics and logic circuits in communication with the processor or processors which may be disposed within the housing at a level which is above the level of the work surface. The controller, electronics associated with the controller as well as other components of the robotic sample transfer device may be powered by a universal power supply in communication with the controller that produces a constant or substantially constant output voltage with varied input voltages. Such a universal power supply may allow the robotic sample transfer device to operate in a variety of countries with little or no modification.
• Embodiments of the robotic sample transfer device may include a humidity sensor disposed within the processing chamber of the device in communication with the controller which is configured to sense the humidity within the processing chamber. For some of these embodiments, a closed loop feedback of sensed humidity levels within the processing chamber may be used in conjunction with a humidity control device for maintaining a substantially constant humidity within the processing chamber.
• Embodiments of the robotic sample transfer device may include a temperature sensor disposed within the processing chamber of the sample transfer device in communication with the controller which is configured to sense the temperature within the processing chamber. For some of these embodiments, a closed loop feedback of sensed temperature levels within the processing chamber may be used in conjunction with a temperature control device for maintaining a substantially constant temperature within the processing chamber.
• A graphic user interface may be disposed on an outer surface of the housing or in another convenient location and in communication with the controller. Some embodiments of the robotic sample transfer device may include an imaging camera which may be coupled to an image processing controller, a bar code reader head and bar code reader processor in communication with the bar code reading head and controller.
• The fluid rinse station may include an array of regularly spaced individual rinse tubes having a regular spacing corresponding to the regular spacing of the pin tools of the pin tool head assembly. A rinse fluid supply tank may be disposed within the housing and in fluid communication with the fluid rinse station. Some embodiments of the sample transfer device may include a rinse fluid supply pump disposed within the housing, in fluid communication with the rinse fluid supply tank and fluid rinse station and configured to pump rinse fluid from the rinse fluid supply tank to the fluid rinse station. Some embodiments of the sample transfer device include a rinse fluid supply tank fluid level indicator. Such an indicator may be used to provide users with information with regard to the fluid level within the rinse fluid supply tank so the tank may be refilled prior to running out of rinse fluid.
• A waste fluid tank may be disposed within the housing in fluid communication with an overflow basin of the fluid rinse station. Some embodiments of the sample transfer device may include a waste fluid tank fluid level indicator. Such an indicator may be used to provide users with information with regard to the waste fluid level within the waste fluid supply tank so the tank may be emptied prior to overflowing with waste fluid.
• An ultrasonic cleaning fluid reservoir may be disposed within the housing in fluid communication with the self-leveling ultrasonic cleaning well. For some embodiments, the ultrasonic cleaning fluid reservoir includes a gravity feed reservoir having a supply port configured to couple into fluid communication with an inlet port of the ultrasonic cleaning well. The supply port may be configured to allow fluid flow when coupled to the inlet port of the ultrasonic cleaning well and be substantially sealed when the removed from the inlet port of the ultrasonic cleaning well.
• A vacuum source may be disposed within the housing in fluid communication with the vacuum drying station. Some embodiments of the sample transfer device may also include a vacuum drying supply tank in fluid communication with the vacuum drying ports of the vacuum drying station. The vacuum drying supply tank may be a gas tight pressure vessel having an interior volume that may be partially emptied of air so as to provide a large volume of low pressure which can be used to draw air through the vacuum tubes of the vacuum drying station. Some of these embodiments may include a vacuum pump in fluid communication with the vacuum drying supply tank.
• FIGS. 1-14 illustrate an embodiment of an integrated roboticsample transfer device10 that may have features, dimensions and materials which are similar to or the same as the features, dimensions and materials of the robotic sample transfer device embodiments discussed above. The integrated roboticsample transfer device10 may be used for reliably transferring large numbers of samples from one position on a work surface of the device to second position on the work surface of the device. The integrated robotic sampletransfer device embodiment10 shown includes a compact and user friendly configuration in that it does not require any external tanks or other major peripheral equipment in order to operate. The ultrasonic wash station, rinse station and vacuum drying station are all supplied by tanks that are disposed within the housing of the transfer device. In addition, any waste fluid generated by these stations drains to a waste fluid tank also disposed within the housing. Although the wash fluid and waste tanks include coupling ports to allow a user to connect the tanks to larger external tanks if desired, having these primary wash fluid supply and waste tanks disposed within the housing allows a user having minimum work space to efficiently and effectively use the sample transfer device.
• Thetransfer device10 includes ahousing12 having an outer sheathing that provides anenclosed processing chamber14 that may be accessed by a hinged lid ordoor16. The door may include a window with transparent sheathing material to allow a user to view the processes taking place within theprocessing chamber14 while keeping the processing chamber enclosed and substantially isolated from the outside environment. The transparent sheathing of the window of thedoor16 may include materials such as acrylic, PVC, polycarbonate and the like and have a thickness of about 0.1 inches to about 0.4 inches, for some embodiments. Such a configuration may allow the transparent material of thedoor16 to be somewhat flexible and take on a curved shape or configuration. A safety interlock device (not shown) may include an interlock switch that is coupled between thedoor16 and the remainder of thehousing12. The interlock device may be configured to detect when thedoor16 is open or closed in order to prevent operation of thedevice10, and particularly arobotic positioning system18 of the device, while thedoor16 is open. The sheathing or skin of thehousing12 may be formed from multiple panels of thin materials such as polymers, composites, metals, such as aluminum, and the like and may be secured to a frame structure of thehousing12. For some embodiments, the side panels of thehousing12 may be removable in order to provide greater access to theprocessing chamber14 during the loading and unloading of samples or devices from within theprocessing chamber14. An air port (not shown) may also be disposed on one or more of the panels, such as the side panels, of thehousing12 in order to provide an access port into the interior of thehousing12 andprocessing chamber14. Such an air port may be used to force conditioned air into the processing chamber in order to control the temperature and humidity within theprocessing chamber14.
• Theprocessing chamber14 may be sized adequately to house the three axis robotic positioning system,work surface22 and functional elements of thework surface22. In addition, it may be desirable to have access by a user to some or all of these components in order to facilitate loading and unloading of samples, microtiter plates, chips, cleaning fluids and the like. The outer shape of thehousing12 is generally rectangular, with a sloping front surface formed by thedoor16 that is hinged across the top edge of thedoor16 which is configured to swing up and down. One or more pressurizedgas damping pistons24 may pivotally secured between thedoor16 and a portion of thehousing12 beneath the door. The dampingpistons24 may be configured to offset the weight of thedoor16 and provide damping of movement between thedoor16 and the remainder of thehousing12 to prevent rapid movement of thedoor16 and keep thedoor16 open until manually closed by a user. Some embodiments of thehousing12 may have a height of about 12 inches to about 30 inches, more specifically, about 20 inches to about 26 inches, a width of about 20 inches to about 40 inches, more specifically, about 25 inches to about 30 inches, and a depth of about 12 inches to about 30 inches, more specifically, about 20 inches to about 26 inches.
• Agraphic user interface26 that includes a touch screen user interface is disposed on an outside surface of thehousing12. The touchscreen user interface26 may be a graphic screen coupled to acontroller28 which is shown inFIG. 2. The touchscreen user interface26 allows a user to turn on, program, turn off and generally interact with thecontroller28 and other features of the device through a menu driven interface that is displayed on the touch screen. Thecontroller28 may be used or programmed generally to control the use, motion or both of the active components of thesample transfer device10. In particular, the controller may be used or otherwise programmed to control the use of the functional elements and supporting element or components of the functional elements of thework surface22. For example, thecontroller28 may be used or otherwise programmed to control the movement of fluids, such as rinse water supply and waste, pressurized gases, vacuum sources, such as drying vacuum sources, and the administration of cleaning energy, such as ultrasonic cleaning energy for cleaning the pin tools of a pin tool head assembly and the like. Thecontroller28 may be used to control the movement of the translatable carriers of the three axisrobotic positioning system18 and the use and control of imaging devices secured to or otherwise associated with the translatable carriers, such as imaging cameras, bar code readers and the like.FIG. 2 is a rear elevation view of the sampletransfer device embodiment10 with a rear panel of thehousing12 not shown for purposes of illustration. With the rear panel of the housing removed, thecontroller28 and some of the associated electronics thereof are visible.
• Thecontroller28 may include aprocessor32, such as a computer processor, a memory storage unit and suitable accompanying circuitry such as logic circuits and the like. Some embodiments include auniversal power supply34 coupled to thecontroller28 and other electrical components of the sample transfer device that is configured to supply a substantially constant operating voltage to thecontroller28 and other electrical components of the device for a variety of input voltages. Such auniversal power supply34 allows embodiments of the roboticsample transfer device10 to be used with a variety of input power supply voltages without the need for modification. A customizedPCB board36 that includes signal routing switches, motor controllers, an amplifier for ultrasonic energy generation, as well as other components is mounted adjacent theprocessor32. A coolingfan38 is disposed between thePCB board36 andprocessor32 for cooling the portion of thehousing12 that houses thecontroller28.
• Thetouch screen feature26 allows a user to interact and make menu selections directly on thetouch screen26. For the embodiment shown, the touchscreen user interface26 is disposed on a hinged cover or door that is disposed over the front of a lowerstorage tank chamber44 which is shown inFIG. 3. The lowerstorage tank chamber44 is a volume disposed within the housing below awork surface22 of thesample transfer device10.FIG. 3 shows a front elevation view of thesample transfer device10 with the hingedcover42 of the lowerstorage tank chamber44 removed for purposes of illustration.
• FIG. 4 illustrates an enlarged perspective view of some of the active processing components disposed within theprocessing chamber14 of the sampletransfer device embodiment10. These active processing components are shown in an isolated view without the housing or other components for clarity. Generally, thework surface22 and functional elements disposed on thework surface22 provide locations to secure samples and other materials in a first registered position so that they can be moved or moved in part to a second registered position, for example, moving a portion of a sample fluid from a known well of a microtiter plate to a sample deposition site of a spectrometry chip with a pin tool. The three axisrobotic positioning system18 provides the system for generating precise motion relative to the registered positions of thework surface22, such as by providing precise known motion and positioning of a pin tool relative to thework surface22 and functional elements thereof. Thework surface22 and functional elements may also provide the necessary tools to clean the pin tool or other transfer devices such that they may be used for many consecutive transfer cycles.
• FIGS. 5 and 6 illustrate components of the three axisrobotic positioning system18 in more detail. As shown, the three axisrobotic positioning system18 is disposed substantially above thework surface22 and includes a fixedmount portion46 which is secured in a fixed relation with thework surface22. Both the fixedmount portion46 and thehorizontal work surface22 may be secured in fixed relation to each other on aframe structure48 which may, in turn, be secured to or otherwise mounted to thehousing12 or frame structure of thehousing12. For the embodiment shown, theframe structure48 of thework surface22 and three axisrobotic positioning system18 is mounted to thehousing12 with vibration isolating rubber mounts52. Also for the embodiment shown, a base portion of thex-axis rail54 serves as the fixedmount portion46 of the three axisrobotic positioning system18.
• The three axisrobotic positioning system18 includes a z-axistranslatable carrier56 which is disposed above thework surface22 and which may be controllably positioned in three different axes relative to thework surface22. The z-axistranslatable carrier56 is coupled to the fixedmount portion46 of the system or base of thex-axis rail54 through two other translatable carriers that provide the x-axis and y-axis components of the three axis motion. The three axes of translation of the translatable carrier of the three axis positioning system shown are substantially orthogonal to each other, however, some embodiments may use non-orthogonal axes. The z-axistranslatable carrier56 may be translated in either direction along each of the three axes independently. The movement of the translatable carrier in either direction along each axis may be actuated by a stepper motor actuator which is configured to impart linear motion along the direction of each respective axis.
• Position information regarding the position of the translatable carrier along one or more of the three axes may be measured by a linear encoder assembly, such as an optical linear encoder assembly, corresponding to one or more of the axes or by any other suitable method. A linear encoder assembly may include a linear encoder reader head such as an optical linear encoder reader head and a linear encoder strip such as an optical linear encoder strip that are coupled to the controller and may provide position feedback to the controller. A homing switch system may also be used to facilitate the determination of position of the translatable carriers along each of their respective axes. Such a homing switch may be mounted at or near an end of the length of travel or motion of a respective translatable carrier such that the homing switch is activated to open or close an electrical loop, optical loop or the like as the translatable carrier reaches the end of travel at a pre-determined and repeatable position. The electrical or optical loop of the homing switch may be coupled to thecontroller28 such that thecontroller28 may be programmed to move a translatable carrier to the “home” position which mechanically activates the homing switch at the beginning of a transfer cycle or at any other desired time. For some embodiments, thecontroller28 may home one or more of the translatable carriers by sending a home command to one or more motor controllers corresponding to each of the respective stepper motors. Such motor controllers may be located onboard36 or in any other suitable location. Once the home position has been determined, thecontroller28 may use the stepper function of the stepper motor actuator to track the number of motion pulses in each direction along the axes in order to calculate or otherwise track the position along each of the axes.
• Thex-axis rail54 of the three axisrobotic positioning system18 extends across theprocessing chamber14 and is coupled to anx-axis carrier58 which is coupled to a y-axis carrier62 which is coupled to the z-axis carrier. The x-axis carrier is configured to translate on the x-axis rail, the y-axis carrier62 is configured to translate relative to the x-axis carrier in a y-axis direction and the z-axis carrier is configured to translate in a z-axis direction relative to the y-axis carrier62. All three of the carriers and corresponding carrier rails upon which the carriers move may be respectively coupled together by high precision bearings that are configured to promote low friction linear movement with high precision. The z-axis carrier56 may be positioned in three axes which are substantially orthogonal to each other for such a configuration. The pintool head assembly64 is secured to the z-axis carrier56 and may also be positioned in the three substantially orthogonal axes. Various embodiments of the rails of the three axisrobotic positioning system18 may include models SR20, RSR12W and HSR20, manufactured by THK Company, Japan.
• As discussed above, the z-axistranslatable carrier56 is translatable in the x, y and z axes and is coupled to the fixed mount portion46 (or base of the x-axis rail) through the y-axistranslatable carrier62 and the x-axis translatable carrier with each translatable carrier configured to move independently of the other carriers in its respective direction. The pintool head assembly64 is secured directly to the z-axistranslatable carrier56 which moves up and down on the z-axis rail66 relative to the y-axistranslatable carrier62 andhorizontal work surface22. The y-axistranslatable carrier62 moves in a y-axis direction front to back on a y-axis track relative to the x-axistranslatable carrier58 and thehorizontal work surface22. The x-axistranslatable carrier58 moves in an x-axis direction side to side relative to the fixedmount portion46 on thex-axis rail54. The superposition of movement in each of the x-axis, y-axis and z-axis directions allows the z-axistranslatable carrier56 and pintool head assembly64 secured directly thereto to be positioned in three dimensions with respect to thehorizontal work surface22 and functional components disposed on thework surface22. There may be no need for movement in a rotational orientation as thepin tools68 of the pintool head assembly64 are generally applied at a right angle or perpendicular to nominal upper surfaces of the functional components of thework surface22. However, an additional axis or axes of motion could be added to therobotic positioning system18. In addition, although the base portion of thex-axis rail54 serves as the fixedmount portion46 and the z-axistranslatable carrier56 serves as a three axis translatable carrier, the various carriers may be mixed and matched as desired in order to achieve the three axes of movement. For example, a base portion of a rail of either the x, y or z axis of a robotic positioning system could serve as the fixedmount portion46 that is mounted in fixed relation to thework surface22. Also, either the x, y or z translatable carrier may serve as the three axis translatable carrier of arobotic positioning system18, so long as the three axis translatable carrier is coupled to the fixed mount portion through translatable carriers of the other two axes.
• Referring toFIG. 5, thex-axis rail assembly70 includes aframe72 that includes a bottom portion which is secured in fixed relation to theframe structure48 beneath therail assembly70. Thework surface22 is also secured in fixed relation to thesame frame structure48. As such, the bottom of thex-axis rail assembly70 serves as the fixedmount portion46 of the three axisrobotic positioning system18. Thex-axis rail assembly70 includes a first x-axis rail74 upon which bearingcars76 are slidingly engaged and free to translate along the x-axis direction. Thex-axis rail assembly70 includes asecond x-axis rail78 upon which a bearingcar76 is slidingly engaged and free to translate along the x-axis direction. The x-axistranslatable carrier58 is secured to the bearing cars of thex-axis rail assembly70 and thus the x-axistranslatable carrier58 is free to move along the x-axis direction riding on the multiple bearingcars76. A threadedrod82 is secured between end plates84 and85 of thex-axis rail assembly70.X-axis stepper motor86 has a threadedcollar88 that is in threaded engagement with the threadedrod82. The threadedcollar88 is configured to rotate with a rotor of thestepper motor86 but remain stable in an axial direction relative to the stepper motor body. Thestepper motor86 thus moves along and relative to the threadedrod82,frame70 and x-axis when thestepper motor86 drives the threadedcollar88 which rotates relative to the threadedrod82. Thex-axis stepper motor86 is also secured in fixed relation to the x-axistranslatable carrier58 and thus drives the x-axistranslatable carrier58 along the x-axis direction when actuated. For such an arrangement, the threadedcollar88 of thestepper motor86 may include an anti-backlash device in order to maintain high precision linear movement of the x-axistranslatable carrier58. Anlinear encoder strip92 is disposed on a front surface of therail assembly70 as shown inFIG. 4, which may be read by anencoder head94 which is secured to the x-axis translatable carrier as shown inFIG. 3. Thelinear encoder strip92 may include model RGS40S, manufactured by Renishaw Corporation located in Gloucestershire, England. The linearencoder reader head94 may include model RGH41, also manufactured by Renishaw Corporation. The linear encoder systems may have a resolution of about 0.5 microns to about 5 microns, more specifically, about 0.8 microns to about 1.5 microns, for some embodiments. The various stepper motor embodiments may include model series 57000,size 23, and model series 43000,size 17, manufactured by Hayden Switch and Instrument Company, Waterbury, Conn.
• Referring toFIG. 4, a y-axis rail assembly96 is secured to the x-axistranslatable carrier58. The y-axis rail assembly96 includes a frame95 y-axis rail98 upon which a bearing car (not shown) is slidingly engaged and free to move along the y-axis direction. The y-axistranslatable carrier62 is secured to the bearing car of the y-axis rail assembly96 and thus the y-axistranslatable carrier62 is free to move along the y-axis direction riding on the bearing car. A threadedrod102 is secured betweenend plates104 and105 of the y-axis rail assembly96. Y-axis stepper motor106 has a threadedcollar108 that is in threaded engagement with the threadedrod102. The threadedcollar108 is configured to rotate with a rotor of thestepper motor106 but remain stable in an axial direction relative to the stepper motor body. Thestepper motor106 thus moves along and relative to the threadedrod102,frame95 and y-axis when the stepper motor drives the threadedcollar108 which rotates relative to the threadedrod102. As with thex-axis assembly70, the threadedcollar108 of thestepper motor106 may include an anti-backlash device in order to maintain high precision linear movement of the y-axistranslatable carrier62. A y-axislinear encoder strip112 is disposed along a top portion of the y-axis rail assembly96. A y-axis linear encoder reader head (not shown) may be disposed on the y-axistranslatable carrier62 and configured to read the y-axislinear encoder strip112. Theencoder strip112 and reader head may be the same as or similar to thex-axis encoder strip92 andreader head94 discussed above.
• A z-axis rail assembly114 is secured to the y-axistranslatable carrier62 to provide controllable high precision movement along the z-axis direction in combination with x-axis and y-axis movement provided by the respectivetranslatable carriers58 and56 in those axes. The z-axis rail assembly114 includes a z-axis rail116 upon which one or more bearing cars (not shown) are slidingly engaged and free to translate along the z-axis direction with high precision. The z-axistranslatable carrier56 is secured to the bearing car of the z-axis rail assembly114 and thus the z-axistranslatable carrier56 is free to move along the z-axis direction riding on the bearing cars. A threadedrod118 is secured to the z-axis translatable carrier. Z-axis stepper motor122 is secured to the y-axistranslatable carrier62 by amount bracket124 and includes a threadedcollar126 that is in threaded engagement with the threadedrod118. Thus, when the z-axis stepper motor122 is actuated and the threadedcollar126 rotated, the threadedrod118 and z-axistranslatable carrier56 is moved along z-axis relative to the y-axistranslatable carrier62. As with the x-axis and y-axis assemblies, the threadedcollar126 of thestepper motor122 may include ananti-backlash device56 in order to maintain high precision linear movement of the z-axistranslatable carrier56.
• The positioning of the z-axistranslatable carrier56 along the z-axis direction may be determined by the use of a homing switch as discussed above. For the embodiment shown, a homingswitch128 is disposed in fixed relation to the y-axistranslatable carrier62 near the top end of the z-axis motion of the z-axis carrier56 such that the z-axis carrier56 activates the homingswitch128 at the top of the z-axis travel. The homingswitch128 is coupled to thecontroller28 which may then “home” the z-axistranslatable carrier56 at the beginning of each sample transfer cycle, or at any other desired time, in order to determine the position of the z-axistranslatable carrier56 thereafter. Such a homing position determination process may also be manually selected by a user. The z-axis rail assembly114 may also optionally include a linear encoder assembly, such as the linear encoder assemblies discussed above with regard to thex-axis rail assembly70 and y-axis rail assembly96, if greater precision is desired for the determination of the position of the z-axistranslatable carrier56.
• Thex-axis rail54 andtranslatable carrier58 may be configured to provide about 10 inches to about 30 inches of travel in the x-axis direction, more specifically, about 20 inches to about 25 inches of travel in the x-axis direction. The y-axis rail98 andtranslatable carrier62 may be configured to provide about 8 inches to about 16 inches of travel in the y-axis direction, more specifically, about 10 inches to about 12 inches of travel in the y-axis direction. The z-axis rail116 andtranslatable carrier56 may be configured to provide about 2 inches to about 10 inches of travel in the z-axis direction, more specifically, about 3 inches to about 5 inches of travel in the z-axis direction.
• As shown inFIG. 6, animaging camera132 is secured to the y-axistranslatable carrier62. Theimaging camera132 may be configured to have a focal length or range of focus that matches the distance from theimaging camera132 to a plane below thecamera132 that is substantially at the level or plane of nominal upper surfaces of the functional elements of thework surface22. For some embodiments, thework surface22 may be configured such that some or all of the functional components thereof have a nominal upper surface that is at substantially the same z-axis level or position. This configuration may serve to simplify the programming of thecontroller28 for sample transfer procedures. This configuration may also allow theimaging camera132 in a fixed z-axis position to remain in focus while imaging a nominal upper surface of the functional components in order to better control the sample transfer process. A barcoder reader head134, as shown inFIG. 2, may also secured to the y-axistranslatable carrier62, y-axis rail98 or any other suitable portion of therobotic positioning system10. The same arrangement may be desirable for easy scanning of bar codes disposed on chips, microtiter plates or the like that are placed on mount blocks of thework surface22 for easy identification and obtaining accurate position data of such components. The barcode reader head134 may include model NLV-1001, manufactured by Opticon Corporation, Japan.
• Referring toFIG. 6, the pintool head assembly64 is secured to the z-axistranslatable carrier56 by fasteners such as screws or bolts and is movable and may be positioned in all three x, y and z axes. The pintool head assembly64 includes a substantiallyrigid frame structure136 having a firstvertical support plate137 and a secondvertical support plate138 spaced laterally from the firstvertical support plate137 and disposed substantially parallel to the firstvertical support plate137. Abottom plate139 is secured at a first end to the firstvertical support plate137 and secured at a second end to the secondvertical support plate138. Thebottom plate139 has a top surface and a bottom surface that is substantially parallel to the top surface. Thebottom plate139 may have a thickness of about 0.05 inches to about 0.5 inches, more specifically, about 0.1 inches to about 0.2 inches, for some embodiments. Thebottom plate139 may be oriented substantially perpendicular to both the first and secondvertical support plates137 and138. Acover plate140 is disposed opposite and spaced vertically from thebottom plate139. Thecover plate140 is secured to top surfaces of upper ends of the first and secondvertical support plates137 and138 in an orientation that is substantially perpendicular to both the first and second vertical support plates. Thecover plate140 may have a thickness of about 0.05 inches to about 0.5 inches, more specifically, about 0.1 inches to about 0.2 inches, for some embodiments. An open cavity or window is formed in the middle of therigid frame136 between the upper surface of thebottom plate139, a lower surface of thecover plate140, and interior surfaces of both the first and secondvertical support plates137 and138.
• An array ofpin tools68 is mounted on thebottom plate139 andcover plate140 with a configuration that allows axial translation of thepin tools68 relative to theframe structure136 in an upward direction. Thepin tools68 have anelongate shaft142, a nominal shaft portion and an enlarged portion of theshaft142 that may include anenlarged portion143 in the form of acollar member144 to stop axial movement of thepin tool shaft142 against either thebottom plate137 orcover plate140 of theframe structure136. For the embodiment shown, thepin tools68 are disposed in a 4 by 6 pin array with spacing or pitch between adjacent pin tools of about 3 mm to about 10 mm, more specifically, about 4 mm to about 5 mm. Thepin tools68 are disposed in close fitting holes in thebottom plate139 that have an inside diameter or transverse dimension that corresponds to an outer transverse dimension or diameter of the nominal shaft portion of theelongate shaft142 of eachrespective pin tool68. The amount of clearance between an outer surface of eachpin tool68 and an insider surface of the respective hole in the bottom plate may be about 0.0002 inches to about 0.001 inches. Eachpin tool68 is also disposed in a mating hole or slot in thecover plate140 which may have similar clearance and may provide additional longitudinal stability for axial movement of thepin tool shaft142 within theframe structure136.
• Either or both of the pin tool shaft holes or slots in thebottom plate139 orcover plate140 may have a keyed configuration that matches a keyed configuration of an outside surface of thepin tool shaft142 so as to prevent rotation of thepin tool shafts142 relative to theframe structure136, but allow unimpeded axial movement of thepin tool shafts142 relative to theframe structure136. Atop portion146 of thepin tool shafts142 shown have a “D” shaped transverse cross section which mates with a respective “D” shaped hole in thecover plate140. Although the pintool head assembly64 embodiment shown has a 4 by 6 pin tool array, other configurations are also contemplated. For example, some arrays ofpin tools68 of a pintool head assembly64 may have a row of about 1 pin tool to about 15 pin tools in conjunction with columns of about 2 pin tools to about 30 pin tools, for some embodiments. Some embodiments may have a row of about 3 pin tools to about 10 pin tools in conjunction with columns of about 2 pin tools to about 15 pin tools.
• For some embodiments, anenlarged portion143 of thepin tool shaft142 may be integrally formed into theshaft142. For the pin tool embodiments shown, anenlarged portion143 of theelongate shaft142 of thepin tools68 is formed by theseparate collar member144 which may be secured to theelongate shaft142 by a variety of suitable methods such as a compression fit, adhesive, solder or the like. Thecollar members144 shown are clips that are secured by compression fit into circumferential slots orgrooves148 formed into theshafts142 of thepin tools68. As thecollar member144 is larger than the pin tool shaft holes in the bottom plate, the enlarged portion orcollar member144 comes to a hard stop against the upper surface of thebottom plate139 at the end of downward axial translation of thepin tool shaft142. Theenlarged portion143 of theelongate shafts142 of thepin tools68 may be biased in an axial direction against thebottom plate139 of theframe structure136 by gravity, a resilient bias member, such as ahelical spring152, or by any other suitable device or method. For the embodiment shown, eachpin tool68 is biased against thebottom plate139 by ahelical spring152 which is disposed over eachelongate shaft142 between the lower surface of thecover plate140 and an upper surface of thecollar member142 of each pin tool. A washer or bushing may be disposed adjacent thecollar members144 between thecollar member144 andspring152 to provide a uniform surface for thespring152 to push against. Thehelical spring152 may have a length in a relaxed uncompressed state that is longer than the distance between the upper surface of thebottom plate139 and lower surface of thecover plate140 so as to provide continuous resilient bias against upward axial translation of thepin tool68. The bias against upward axial translation may also increase as thespring member152 becomes compressed.
• For some embodiments, thepin tool shafts142 may have a length of about 1 inch to about 4 inches, more specifically, about 2 inches to about 3 inches. Theelongate shafts142 of thepin tools68 may have an outer transverse dimension or diameter of about 0.03 inches to about 0.1 inches, more specifically, about 0.05 inches to about 0.07 inches, for some embodiments.
• Sample reservoirs156 may be disposed in distal ends orportions158 of theelongate shafts142 of thepin tools68, distal of theenlarged portion143 of theshaft142 such which may include thecollar member144. Thecollar member144 is disposed and mechanically captured in the window of theframe structure136 with thedistal end158 of thepin tool shafts142 extending below the pin tool shaft holes in thebottom plate139. In this way, the distal ends158 andsample reservoirs156 of thepin tools68 extend below thebottom plate139 and may be used to access samples, such as arrays of samples disposed in vessels such as microtiter plates. The distal ends andsample reservoirs156 of thepin tools68 may also be used to access sample deposition sites, such as arrays of sample deposition sites disposed on a spectrometry chip. For some embodiments, the width of aslot162 of the sample reservoir of the pin tools may be sized to be greater than an outer lateral transverse dimension of a matrix deposit of a sample deposition site of a spectrometry chip. In this way, a sample from the sample reservoir of the pin tool may be deposited onto the matrix deposit of the chip without the pin tool structure making contact with the matrix material. In other words, the slot of the sample reservoir may be configured to straddle the matrix material of the sample deposition site.
• Some embodiments of thesample reservoir156 may include athin slot162 having a width of about 0.2 mm to about 0.5 mm, more specifically, about 0.25 mm to about 0.4 mm, and may have a length of about 0.1 inches to about 0.5 inches, more specifically, about 0.18 inches to about 0.22 inches, depending on the desired amount of liquid volume to be delivered. Theframe structure136 andpin tools68 may be configured, particularly with regard to the placement of thecollar member144 relative to thedistal end158 of thepin tools68, such that the distal ends158 of thepin tools68 of a pin tool array are coplanar and all lie substantially in a plane that is substantially parallel to thework surface22. Eachpin tool68 of the array may also be substantially perpendicular to thework surface22.
• Thework surface22 is generally configured to be disposed in a substantially horizontal orientation and may include one or more functional elements disposed thereon. Because some of the functional elements of thework surface22 may include fluids disposed in enclosures, the substantially horizontal orientation of thework surface22 may serve to prevent spillage of the fluids and provide more consistent operation and sample transfer generally.FIG. 7 shows an enlarged perspective view of awork surface embodiment22 and functional elements disposed thereon.FIGS. 8-11 show additional views and details of thework surface22 and functional element embodiments associated therewith.
• Thecontroller28 as well as other electronics that control the movement of the pin tool head assembly64 (that may include a controller with a processor and other sensitive electronic components) as well as control and operation of other components of thetransfer device10 may be disposed above the level of thework surface22 of the transfer device. With such a configuration, any accidental spills of fluid that occur on thework surface22 will not compromise the integrity of such electronics.
• For the embodiment shown, thework surface22 is disposed beneath the three axistranslatable carrier56 of the three axisrobotic positioning assembly18 and includes a substantially flat rectangular surface of a rectangular plate upon which the functional elements may be directly or indirectly secured or otherwise mounted. For some embodiments, thework surface22 itself may be formed from one or more upper nominal surfaces of one or more functional elements discussed herein without the inclusion of a separate flat rectangular surface or plate. For some embodiments, the rectangular plate of thework surface22 may have a width of about 4 inches to about 16 inches, more specifically, about 5 inches to about 10 inches and may have a length of about 10 inches to about 30 inches, more specifically, about 15 inches to about 20 inches. The plate of thework surface22 may be secured to framemembers48 which may in turn be secured to the frame of thehousing12 or other structural members of thesample transfer device10 with solid mounts orvibration absorbing mounts52 such as the rubber mounts shown.
• Referring toFIG. 7, acleaning block assembly164 is disposed on and secured to the work surface plate. Thecleaning block assembly164 may have one or more functional elements which are configured to clean each pin tool of apin tool68 array of a pintool head assembly64 simultaneously. The cleaningblock assembly embodiment164 may be machined from a monolithic block of a strong stable material, such as polymers, such as Delrin®, composites and metals, such as stainless steel, aluminum, which may be anodized, and the like. Thecleaning block assembly164 may include functional elements in the form of a self-fillingultrasonic wash station166 that is self-filled by a gravityfeed supply reservoir168, pin tool wash or rinsestation172 that includes an array of regularly spaced rinse tubes orfountains174 that may correspond to eachpin tool68 of the pintool head assembly64. The rinsestation172 is disposed between theultrasonic wash station166 and avacuum drying station176.
• Thevacuum drying station176 includes an array of regularly spacedvacuum drying orifices178 that may correspond to each pin tool of thepin tool68head assembly64. Although not necessary, it may be desirable for the rinsestation172 andvacuum drying station176 to have an array of rinsetubes174 or vacuum ports ororifices178 with a regular spacing that corresponds to the regular spacing of the pin tool array of a pintool head assembly64 to be used with these stations and an array size at least as big as the array ofpin tools68 of the pintool head assembly64. Even though it may be acceptable for somepin tools68 of an array which are laterally displaced from a functional element of thecleaning block164 to press against a surface adjacent a rinsetube174 orvacuum orifice178, it may be desirable for allpin tools68 of an array to be cleaned simultaneously. As such, it may also be desirable for anultrasonic bath182 to have inner transverse dimensions that are greater than corresponding outer transverse dimensions of an array of pin tools to be washed in theultrasonic wash station166. It may also be desirable for the rinsestation172 andvacuum drying station176 to have at least as many rinsetubes174 andvacuum drying orifices178 as there arepin tools68 in a pintool head assembly64 to be cleaned.
• In general, a pin tool array that has been used for transferring samples, such as liquid samples, may then be moved over thework surface22 so as to align the array with theultrasonic bath182 of theultrasonic wash station166. Thesample reservoirs156 anddistal sections158 of thepin tools68 generally, may then be lowered into theultrasonic bath182 such that any portion of thepin tools68 that have been exposed to sample material, will be submerged in theultrasonic bath182. Anultrasonic actuator184 disposed below theultrasonic bath182 and cleaningblock164 may be activated to as to emit ultrasonic energy into thebath182 and promote cleaning and rinsing of eachpin tool68 of the array. Thepin tools68 may be soaked in theultrasonic bath182 with ultrasonic energy agitating the water and surface of thepin tool68 for about 1 second to about 2 minutes, more specifically, about 5 seconds to about 30 seconds, for some process embodiments. The ultrasonic energy emitted into thebath182 may have a power of about 10 watts to about 100 watts, more specifically, about 20 watts to about 40 watts, and a frequency of about 20 kHz to about 60 kHz, more specifically, about 30 kHz to about 50 kHz, and even more specifically, about 35 kHz to about 45 kHz. The ultrasonic wash fluid used in theultrasonic bath182 may include de-ionized water, alcohol, and the like in a volume of about 10 ml to about 1000 ml, more specifically, about 20 ml to about 100 ml.
• Referring toFIGS. 7 and 10, an uppernominal surface186 of theultrasonic wash bath182 is disposed evenly with a nominal upper surface188 of thecleaning block assembly164. The wash bath is disposed below the uppernominal surface186 between side walls formed into the cleaning block and atop actuator surface192 of an ultrasonic energy generator ortransducer194. Theultrasonic energy generator194interior volume182 is disposed below theultrasonic bath182 and secured thereto by multiple fasteners in a sealed arrangement such that theultrasonic generator194 is coupled directly to the wash fluid within theultrasonic bath182.
• Theultrasonic wash bath182 of theultrasonic wash station166 is self-filled by a self-leveling gravity feed system supplied by awash fluid reservoir168. Thewash fluid reservoir168, as seen inFIG. 7A, may include a generallycylindrical bottle196 having aball valve198 that allows a user to refill thereservoir168 and couple anoutlet port202 of the reservoir to aninlet port204 of theultrasonic wash station166 without spilling a significant amount of the wash fluid. Thewash fluid reservoir168 is shown tipped up with the outlet port of thereservoir168 coupled into theinlet port204 of thewash station166. Theinlet port204 of thewash station168 is in fluid communication with theultrasonic wash bath182 via a fluid tight conduit (not shown) that extends between theinlet204 port and washbath182 underneath the upper nominal surface188 of thecleaning block164. Theball valve198 may include aspherical ball206 made of an inert material such as Viton® rubber or the like which is configured to seal against an inside lip of thereservoir bottle196 and provide a seal. It may be important for theball206 of theball valve198 to have an overall density which is greater than the density of the cleaning fluid to be used in thereservoir168. As such, it may be desirable for theball206 to have a density which is greater than water, ethanol alcohol, and other suitable cleaning fluids. Theoutlet port202 of thewash fluid reservoir168 may include a cylindrically shapedportion208 extending from abottom surface212 of thereservoir168. The cylindrically shapedportion208 may also have an o-ring or similarly configuredresilient seal214 that may seal between the cylindrically shapedportion208 and aninside surface216 of theinlet port204 of theultrasonic wash station166. Thewash fluid reservoir168 may have a capacity of about 20 ml to about 1 liter, more specifically, about 40 ml to about 60 ml, for some embodiments.
• After the ultrasonic wash bath fluid has been used one or more times, and the operator determines that the wash fluid needs to be changed, the used wash fluid may then be drained through adrain port218 in theultrasonic wash bath182 that is in communication with a flexible fluid tight tube that is coupled to anoptional pump222. When thepump222 is activated by thecontroller28 or other user input, the fluid in theultrasonic wash182 shown inFIGS. 2 and 12 may be actively drained from thewash bath182 through thepump222 and into awaste fluid tank224 which is disposed below theprocessing chamber14 and shown inFIG. 2. The drainage of thewash bath182 may also be controlled by a solenoid valve or the like which may optionally be coupled to and controlled by thecontroller28.
• Thus, thecontroller28 may be programmed to drain theultrasonic wash bath182 fluid after a predetermined number of uses. As thewash bath182 is being drained, new clean ultrasonic wash fluid begins to refill thewash bath182 by force of gravity from thewash fluid reservoir168 through the fluid tight conduit and into thewash bath182. As thewash bath182 begins to fill, the back pressure on theoutlet port202 of thereservoir168 increases until equilibrium is achieved within the interior volume of thereservoir168 and wash fluid ceases to flow from thereservoir168 into thewash bath182. When the wash fluid becomes dirty again after use, the cycle may be repeated until thereservoir168 runs out of wash fluid. As such, it may be desirable to construct thebottle196 of thereservoir168 from a transparent or translucent material or materials that will make the fluid level within thereservoir168 visible to a user of thesample transfer device10. Thefluid reservoir168 also serves to maintain theultrasonic bath182 at a desired pre-determined level during use and can be used to automatically add additional cleaning fluid to replace cleaning fluid lost through evaporation, adherence to pintools68 and pintool sample reservoirs156 after a cleaning cycle or the like.
• Anoptional overflow channel226 is disposed around theinlet port204 of thewash fluid reservoir168, theultrasonic wash bath182 and the rinsetubes174 of the rinsetube station172. Theoverflow channel226 may serve to confine any spilled cleaning fluid to thechannel226 and allow the spilled cleaning fluid to drain down the rinse station drain228 by force of gravity. Theoverflow channel226 may be cut into the upper nominal surface188 of thecleaning block164 to a depth of about 0.05 inches to about 0.4 inches, more specifically, about 0.1 inches to about 0.2 inches. Alip232 of the upper nominal surface188 of thecleaning block164 surrounds theultrasonic bath cavity182 and forms the upper nominal surface of theultrasonic wash station166.
• The rinsestation172 includes a plurality of rinsetubes174 arranged with a regular pre-determined spacing that may be configured to match the regular spacing of thepin tools68 of a pin tool array to be used with the rinsestation182. The upper ends234 of the rinsetubes178 may lie substantially in a plane disposed at substantially the same z-axis level. The upper ends234 of the rinsetubes174 may also be at substantially the same z-axis level as the nominal upper level188 of thecleaning block164 and form the nominal upper surface of the rinsetube station172. The rinsetubes174 may be elongate hollow tubes having aninner lumen236 with an inner transverse dimension or diameter of about 0.05 inches to about 0.2 inches, more specifically, about 0.07 inches to about 0.1 inches. Theinner lumens236 of the rinsetubes174 may be coupled by a manifold assembly to a fluid tight tube in fluid communication with a rinsepump238 which is in turn in fluid communication with a washfluid supply tank242 shown inFIG. 3. Once the pin tool orpin tools68 of a pintool head assembly64 are disposed within the rinsetubes174, rinse fluid may then be expelled vertically from the rinsetubes174 to provide a continuous flow of rinse fluid over thesample reservoirs156 anddistal section158 generally of thepin tools68. The flow of rinse fluid may be maintained for about 1 seconds to about 10 seconds, more specifically, about 3 seconds to about 5 seconds, for some embodiments. The amount of flow of rinse fluid through each individual rinsetube174 may be about 20 ml per minute to about 100 ml per minute, more specifically, about 20 ml per minute to about 30 ml per minute.
• The rinse fluid may include de-ionized water, alcohol including ethanol, or any other suitable cleaning fluid. After the rinse fluid has been expelled from the rinsetubes174, it flows by force of gravity over the sides of the rinsetubes174, into theoverflow channel226 discussed above and down the rinse station drain228. Theoverflow channel226 surrounding the rinsetubes174 may have a depth of about 0.2 inches to about 1 inch, more specifically, about 0.3 inches to about 0.5 inches, for some embodiments. The rinse station drain228 is a relatively large bore drain that is coupled to thewaste fluid tank224 by a flexible tubing. The bore of the rinse station drain228 may have a transverse dimension or diameter of about 0.2 inches to about 1 inch, more specifically, about 0.3 inches to about 0.8 inches.
• Thevacuum drying station176 includes a plurality of substantially parallelvertical holes244 disposed in thecleaning block164 arranged in a regularly spaced array that may be configured to match the regular spacing of thepin tools68 of a pintool head assembly64 to be dried by thevacuum drying station176. Thevertical holes178 are formed directly into the material of thecleaning block164 having upper apertures ororifices178 that lie in substantially the same plane as the uppernominal surface246 of thevacuum drying station176. Thevertical holes244 may have an inner transverse dimension or diameter that is larger or just slightly larger than an outer transverse dimension or diameter of thepin tools68 to be used in thevacuum drying station176. For some embodiments, thevertical holes244 may have an inner transverse dimension or diameter of about 0.04 inches to about 0.1 inches, more specifically, about 0.07 inches to about 0.1 inches. Thevertical holes244 may have a depth of about 0.1 inches to about 1 inch, more specifically about 0.3 inches to about 0.5 inches.
• A bottom end or bottom orifice (not shown) of eachvertical hole244 may be coupled to a manifold which is coupled to avacuum holding tank248, shown inFIG. 2, disposed below thework surface22 in thelower chamber44 by a length of flexible tubing (not shown). The flexible tubing may have a wall thickness and mechanical integrity suitable for holding a vacuum or partial vacuum for some embodiments. A valve, such as a solenoid valve (not shown), which may be coupled to and controlled by thecontroller28, may be coupled to the flexible tubing in fluid communication with thevacuum storage tank248 andvertical holes244 in a configuration that allows the application of stored vacuum in thetank248 to be applied to thevertical holes244 when thepin tools68 of a pintool head assembly64 are disposed within thevertical holes244. If thevacuum storage tank248 has been emptied of most of the air within thestorage tank248, air will be drawn through thevertical holes244 at a high rate of flow and through the flexible tubing when the solenoid valve is opened in order to fill the vacuum within thevacuum storage tank248. For some embodiments, thevacuum storage tank248 may have an interior volume of about 1 liter to about 3 liters, more specifically, about 1.5 liters to about 2 liters. For some embodiments, the vacuum may be applied to thevertical holes244 for dryingpin tools68 disposed therein for about 0.1 seconds to about 0.8 seconds, more specifically, about 0.2 seconds to about 0.4 seconds.
• A relieved slot orchannel252 may be formed into a front surface of thecleaning block164 in front of thevacuum drying station176. Theslot252 may be configured to accept arail feature254 of a multi-well calibrationmaterial supply vessel256 shown inFIG. 7C. Thesupply vessel256 may be detachably disposed into theslot252 by sliding therail feature254 of thesupply vessel256 vertically downward into theslot252 until it hits a stop point. One or more calibration materials may be disposed in theindividual wells258 of the supply vessel and thesupply vessel256 then placed in theslot252 of thecleaning block164. Thecontroller28 may be programmed to dip one ormore pin tools68 to be used for calibration purposes into a pre-determined well of thesupply vessel256 in order to draw in calibration material into thesample reservoir156 of thepin tool68 to be used for calibration. Once the calibration material runs out or gets low, or the user decides to use another type of calibration material, thesupply vessel256 may be manually removed from thecleaning block164 and replaced with anotherfull supply vessel256. For some embodiments, thesupply vessel256 may have about 1 well to about 10 wells, more specifically, about 2 wells to about 8 wells.FIG. 7D illustrates and embodiment of asupply vessel256′ having asingle well258′ and arail feature254′ that may also be configured to engageslot252.
• Theslot252 of thecleaning block164 andrail feature254 and254′ of thesupply vessel embodiments256 and256′ may be configured such that respective uppernominal surfaces262 and262′ of the supply vessel embodiments are disposed above the upper nominal surface188 of thecleaning block164 for some embodiments. This allows thepin tools68 to be used for calibration purposes to dip into thewells258 of the supply vessels without the remainder of thepin tools68 making contact with adjacent cleaning block elements or structures. As such, therail feature embodiments254 and254′ andslot252 may be configured such that the height of thenominal surface262 of thesupply vessel256 may be disposed above the nominal upper surface188 of thecleaning block164 by a distance that is at least the length of apin tool68 that needs to be inserted into the calibration material plus the distance below the upper nominal surface of the supply vessel embodiments of the calibration material.
• Some of the functional elements of thework surface22 may be secured to the plate by fasteners such as machine screws or the like and some functional elements, such as microtiter plates, chips and chip mount blocks may be releasably secured to the work surface, or mount block disposed thereon, with elements such as spring loaded toggles, clips, magnets or the like to allow the easy and convenient exchange of such functional elements. Functional elements such as microtiter plates, chips and chip mount blocks may contain samples to be transferred or sample deposition sites that need to be changed as processing takes place and progresses. The work surface shown inFIG. 7 includes two microtiter plate mount blocks264 disposed adjacent achip mount block266. The microtiter plate mount blocks264 are configured to releasablysecure microtiter plates268 having a uniform and standardized configuration with an array ofsample wells270. This allows such astandardized microtiter plate268 to be easily mounted and removed from thework surface22 with some of the important aspects of the microtiter plate268 (such as sample well location and upper nominal surface location) disposed in a consistent position with respect to thework surface22.
• Thechip mount block266 may also be releasably secured to amount platform272 which is secured to thework surface22 and configured to releasably secure thechip mount block266 thereto with spring loaded toggles or the like. This allows thechip mount block266 to be preloaded with one or more chips, such as thespectrometry chip274 shown inFIGS. 11A and 11B, away from thework surface22. Thechip mount block266 that has been preloaded withchips274 may then be releasably secured to themount platform272 on thework surface22 by thetoggles276. Themount platform272 may be sized to have a thickness or otherwise be configured to position an uppernominal surface278 of the chip mount block266 (andchips274 mounted thereto for some embodiments) at a level which is even with upper nominal surfaces188 of thecleaning block164 and other functional elements disposed on thework surface22.
• Thechip mount block266 may have one or morechip mount sites288 or wells which are configured to releasably secure one ormore chips274, such as mass spectrometry chips, having at least one array of sample deposition sites disposed thereon. Thechips274 may be mounted tochip mount sites282 thechip mount block266 by gravity, friction, spring loaded toggles, magnets and the like. Thechip mount block266 may also secure thechips274 thereto by having eachchip274 disposed within a cavity of thechip mount sites282 formed in an upper surface of thechip mount block266 which is sized to substantially conform to an outer edge of pre-selected embodiments ofchips274. Such cavities may be used to partially mechanically capture the mountedchips274 and prevent lateral movement of thechips274 relative to thechip mount block266. For the embodiment shown, each chip mount cavity well282 has a magnetic source, such as aferrous magnet284 disposed in a bottom surface of the chip mount well282. Eachchip274 to be used for such an embodiment, may have a layer of ferrous metal, such as adisc286 made of steel or the like, secured to arear surface288 of thechip274 as shown inFIGS. 11A and 11B. When such achip embodiment274 is placed in a chip mount well282, themagnet284 of the chip mount well282 attracts thedisc286 secured to thechip274 and holds thechip274 in the chip mount well232. By having themagnet284 of the chip mount well282 offset from the position of theferrous metal disc286, thechip274 may also be pulled laterally into a corner of the chip mount well282 in order to register the position of the corner of thechip274 to a known corner of the chip mount well282 and provide a reliable positioning of thechip274 within the chip mount well282.
• Referring toFIGS. 11A and 11B, eachchip274 may include one or more arrays ofsample deposition sites292 which are regularly spaced from each other at periodic intervals on aflat working surface293 of thechip274. Also, as discussed above, eachchip274 may have a ferrous metal disc orlayer286 disposed on therear surface288 of thechip274 for releasable mounting purposes. For some embodiments, an array ofsample deposition sites292 on achip274 may be configured as a square orthogonal array ofsample deposition sites292 wherein eachsample deposition site292 is disposed an equal distance away from theadjacent sample sites292 along orthogonal axes that transect thesample sites292. Such an orthogonal array ofsample sites292 may have a spacing between adjacent sample sites of about 1 mm to about 3 mm, more specifically, about 1.1 mm to about 1.4 mm. For some embodiments, achip274 may include two, three or more arrays ofsample deposition sites292, each array having a regular spacing ofsample deposition sites292. Each of the multiple arrays ofsample deposition sites292 may be square orthogonal, linear or have any other desirable configuration. It may also be desirable for one or more arrays ofsample deposition sites292 to have a regular spacing that is different from one or more other arrays ofsample deposition sites292. It may also be desirable for one or more arrays ofsample deposition sites292 to have a regular spacing that is off pitch or out of phase from the pitch or phase one or more other arrays ofsample deposition sites292. For some embodiments, theferrous metal disc286 may be made from steel, stainless steel, nickel as well as other suitable ferrous metals. Thedisc286 may have a thickness of about 0.01 inches to about 0.1 inches, and a surface area of about 0.08 square inches to about 0.15 square inches.
• For some embodiments of thechips274, thesample deposition sites292 may include mass spectrometry sample deposition sites, such as MALDI sample deposition sites, which may be arranged in one or more regularly spaced patterns or arrays. For some embodiments, thechip274 may include a first array ofsample deposition sites292 for sample processing and a second array ofsample deposition sites292 for calibration of the processing equipment. For some embodiments, the regular spacing of the second array of calibrationsample deposition sites292 may be off-pitch from the regular spacing of the first array, as will be discussed in more detail below.
• For many of the applications of the roboticsample transfer device10, it is very important to determine the position of thetranslatable carriers56,58 and62, and particularly, the three axistranslatable carrier56 relative to thework surface22 and functional elements of thework surface22. This is very important so that each pin tool of the pintool head assembly64 may be moved to a known position relative to the functional elements with which it must interact in order to transfer samples from one location to another, as well as be moved to known positions of the elements of thecleaning block164 for proper cleaning of thepin tools68. For example, it may be important for some sample transfer methods to dip aparticular pin tool68 or set ofpin tools68 intosample wells270 of amicrotiter plate268 to a pre-determined depth below the upper nominal surface of themicrotiter plate268 and take up a known amount of sample material. Thepin tool68 must then be accurately moved to asample deposition site292, such as a spectrometry sample deposition site on achip274, without hitting or otherwise interfering with any other elements or components on thework surface22. Thepin tool68 be brought into precise contact with a pre-determinedsample deposition site292 of thechip274 with a pre-determined amount of force to deposit a known amount of sample onto thesample deposition site292. Thepin tool68 may then be precisely moved to the functional elements of thecleaning block164 and be moved through the progression of cleaning functional elements including theultrasonic bath182, rinsestation172 andvacuum drying station176. Each of these steps requires that thepin tool68 be moved over thebath182, respective rinsetube174 and respective vertical hole orchannel244 of thevacuum drying station176 and moved vertically downward into functional coupling with these elements without making contact with adjacent structures.
• For some embodiments ofchips274, such as some of the spectrometry chip embodiments discussed above, it may be desirable to use features of thechip274 to facilitate the process of locating or positioning the three axis translatable carrier with respect to thework surface22 and functional elements of thework surface22. Some methods of registering the position of a pintool head assembly64, andpin tools68 thereof, of a roboticsample transfer device10 relative to sampledeposition sites292 on achip274 include making use of functional elements having an upper nominal surface at the same z-axis level, for sample transfer device embodiments that have this feature. That is, some embodiments of roboticsample transfer devices10 have awork surface22 with a plurality of functional elements, at least two, three, four or more of which have nominal upper surfaces at substantially the same z-axis level. Such roboticsample transfer devices10 may also have a three axisrobotic positioning system18 with animaging camera132 and pintool head assembly64 secured to a translatable carrier thereof. For such embodiments, the nominal upper surfaces of functional elements disposed onwork surface22 may be imaged with thecamera132 and the image data of the nominal upper surfaces of the functional elements from the camera processed by an image processor or the like to determine the approximate position of the pintool head assembly64 relative to the functional elements.
• For some embodiments of the roboticsample transfer device10, thecontroller28 may include an image processor either as a separate component or built into the processor thereof which may be coupled to theimaging camera132. The approximate position data obtained by theimaging camera132 may be used to move thecamera132 to afirst chip274 having an array of regularly spacedsample deposition sites292 and an array of regularly spacedfiducial marks294 disposed between thesample deposition sites292. Thereafter, thefiducial marks294 on the first chip may be imaged with theimaging camera132 and the image data offiducial marks294 on thefirst chip274 processed by the image processor. As thefiducial marks294 on thechip274 are at known positions relative to thesample deposition sites292 on thechip274, the positions of thesample deposition sites292 may then be determined to a high degree of accuracy. After the fiducial marks have been imaged, feedback regarding a position of the pintool head assembly64 may be obtained from one or more linear encoders of three axes of a three axis robotic positioning system. Position may also be obtained from thecontroller28 which has tracked the movement of a translatable carrier, such astranslatable carrier56 after carrying out the homing procedure discussed above.
• The position data feedback may then be compared with image processing feedback and look up table data to determine the precise position of thepin tools68 of the pintool head assembly64 relative to thesample deposition sites292 on thefirst chip274. This process may then be repeated for one or moreother chips274. Such methods may be used to determine the precise position of thepin tools68 of the pintool head assembly64 with respect to thesample deposition sites292 on thefirst chip274 is determined to within about 1 micron to about 10 microns for some embodiments.
• For some embodiments, the location of one or more of thepin tools68 of the pintool head assembly64 is known with respect to the position of the center of field of view or other reference point in the field of view of theimaging camera132. This position information may be stored in a look up table or the like of the processor. For these embodiments, once theimaging camera132 images a known feature of a functional element, for example a sample well in the “A-1” position of a microtiter plate, in the center of field of view of the camera the position information may then be used to calculate the position the one ormore pin tools68 in the center of the A-1 well for future processing methods. If the relative position or positions of other features on thework surface22 are known relative to the imaged feature, then the position of these features may also be calculated. For example, once the position of the “A-1” sample well of a selected microtiter plate is known, then the relative positions of the remaining wells of the microtiter plate may also be calculated.
• If the position of the other functional elements of thework surface22, such as theultrasonic bath182, rinsetubes174,vertical holes244 of thevacuum drying station176, microtiter places268 mounted to microtiter plate mount blocks264 in addition to thewells270 of theplates268 are known with respect to the position of the imaging camera center of field of view or some other reference position in the imaging camera field of view and this position data is stored in a look up chart, then the position of any of the functional elements relative to one or more of thepin tools68 of the pintool head assembly64 can be determined by thecontroller28. Thus, the controller may then use the position information to move one or more of thepin tools68 or other devices secured to the z-axis translatable carrier to the functional elements for various processing methods. The initial positioning of the center of field of view or other reference point of theimaging camera132 may be carried out manually in order to teach the controller with regard to the position of each of the functional elements. For some functional element embodiments, such as embodiments of theultrasonic bath182 of the ultrasonic wash station, precise position data may not need to be generated as the bath is sufficiently large to accommodate thepin tools68 of the pintool head assembly64 with a relatively large amount of space around thepin tools68
• The washfluid supply tank242 may be disposed in the lowerstorage tank chamber44 below thework surface22 andprocessing chamber14 as shown inFIG. 3. An external wash fluid supply tank coupling may be disposed on or in fluid communication with the washfluid supply tank242 for optionally coupling additional capacity to the internalwash fluid tank242. As discussed above, thewash fluid tank242 is coupled to the rinsetubes174 of the rinsestation172 by flexible tubing through afluid pump238 shown inFIG. 12. The washfluid supply tank242, as shown in more detail inFIG. 14 may have a substantially rectangular shape having a length of about 10 inches to about 25 inches, a width of about 5 inches to about 10 inches, and a height of about 4 inches to about 8 inches. Thewash fluid tank242 may be made from lightweight durable polymer materials such as polyethylene, polypropylene and the like and may have a capacity of about 1 liter to about 10 liters, more specifically, about 2 liters to about 4 liters. Thewash fluid tank242 may include a liquid level sensor disposed in a wall of thetank242 that is configured to measure the level of fluid disposed within the tank. The tank may also include a removable access cover or plate that is generally disposed on a top surface of the tank and configured to allow access by an operator to the interior volume of the tank for cleaning, maintenance etc. The tank may also include two or more orifices for fluid communication with fill tubes, drain tubes and the like.
• The wastefluid storage tank224 may also be disposed in the lowerstorage tank chamber44 below thework surface22 andprocessing chamber14 adjacent the rinsefluid supply tank242, as shown inFIG. 3. An external waste fluid storage tank coupling may be disposed on or otherwise in fluid communication with the wastefluid storage tank224 for optionally coupling additional capacity to the internal wastefluid storage tank224. As discussed above, thewaste fluid tank224 is in fluid communication with the gravity drain228 of the rinsestation172 by flexible tubing. Thewaste fluid tank224 is also in fluid communication with theultrasonic wash bath182 of theultrasonic cleaning station166 through a flexible tubing andfluid pump222 that may be used to drain theultrasonic bath182. The wastefluid storage tank224, as shown in more detail inFIG. 13 may have a substantially rectangular shape having a length of about 10 inches to about 25 inches, a width of about 5 inches to about 10 inches, and a height of about 4 inches to about 8 inches. Thewash fluid tank224 may be made from lightweight durable polymer materials such as polyethylene, polypropylene and the like and may have a capacity of about 1 liters to about 100 liters, more specifically, about 2 liters to about 4 liters. Thewaste fluid tank224 may include a liquid level sensor disposed in a wall of thetank224 that is configured to measure the level of fluid disposed within the tank. The tank may also include a removable access cover or plate that is generally disposed on a top surface of the tank and configured to allow access by an operator to the interior volume of the tank for cleaning, maintenance etc. Thetank224 may also include two or more orifices for fluid communication with fill tubes, drain tubes and the like. Either or both of the washfluid supply tank224 andwaste fluid tank242 may be coupled to visual tank fluid level indicators (not shown) on side walls of thehousing12 in order to allow an operator of the system to quickly and intuitively check the fluid levels of thetanks224 and242. For some embodiments, the visual indicators may include lengths of clear tubing coupled to the interior cavity of the tanks and extending along a vertical slot cut in the respective side wall of the housing with the end of the clear tubing extending to a location above the top of the tank to which it is coupled. The clear tubing disposed adjacent the vertical slot may also contain a floating ball to visually highlight the level of liquid in the clear tubing.
• Referring again toFIG. 12, thepump housing assembly296 is shown that includes thefluid pump238 used for moving rinse fluid from the wash fluid supply tank to the rinsetubes174 of the fluid rinsestation172. Avacuum pump298 coupled to thevacuum storage tank248 and configured to generate a vacuum within an interior volume of thevacuum storage tank248 is also disposed within thepump housing296. Thefluid pump222 coupled between theultrasonic wash bath182 and wastefluid storage tank224 is also disposed within thehousing296. Asolenoid valve299 for coupling the vacuum within the interior volume of thevacuum storage tank248 to thevacuum drying orifices178 of thevacuum drying station176 is also disposed in thepump housing assembly296. The rinsefluid pump238,vacuum pump298,solenoid valve299 and ultrasonicbath emptying pump222 may all be coupled to and controlled by thecontroller28 so as to be activated and stopped at appropriate times or intervals for proper cleaning ofpin tools68 or other end results.
• For some applications of system calibration as well as other methods of use of the robotic sampletransfer device embodiments10, it may be desirable to have asingle pin tool68 of a pin tool array of a pintool head assembly64 deployed or otherwise configured for use. It may also be desirable to have a reduced number ofpin tools68 of a pin tool array configured for use, while the remaining pin tools of the pin tool array are disposed in a retracted state in an upward direction or otherwise deactivated from use. For some embodiments of pintool head assemblies64, a pin tool displacement block may be used to selectively retract one ormore pin tools68 of a pin tool array in a proximal or upward direction so as to leave only the desiredactive pin tools68 extending downward and configured for use.
• Some embodiments of a pin tool displacement block for selectively displacing at least onepin tool68 of a pintool head assembly64 of a roboticsample transfer device10 in an axial direction include a block body having a bottom surface and a plurality of parallel slots formed into the block body portion. The parallel slots may be substantially perpendicular to the bottom surface with a predetermined regular spacing configured to correspond to regular spacing ofpin tools68 of a pintool head assembly64. The parallel slots may have a transverse dimension which is sized to allow easy movement of a width of a nominal shaft of the pin tools in the slots but restrictive of movement of an enlarged portion of the shaft of the pin tools.
• The block body portion may also include at least one relieved portion or channel that may extend from the top surface of the block body portion in a direction which is substantially perpendicular to the bottom surface in one or more of the parallel slots. The relieved portion may have a transverse dimension sized to allow easy movement in an axial downward direction of not only the nominal shaft portion of arespective pin tool68 but also and enlarged portion of a pin tool shaft and be configured to mechanically capture the enlarged portion of a pin tool disposed therein in a lateral direction. The enlarged portion of the pin tool shaft may be greater in transverse dimension than the transverse dimension of the slot but less in transverse dimension than a transverse dimension or diameter of the relieved portion and which extends from a top surface of the block body towards the bottom surface. For some embodiments, the parallel slots may have a width of about 0.04 inches to about 0.2 inches, more specifically, about 0.07 inches to about 0.1 inches, and a spacing or pitch of about 0.1 inches to about 0.5 inches, more specifically, about 0.15 inches to about 0.2 inches. Some embodiments may have a slot length of about 0.2 inches to about 2 inches, more specifically, about 0.5 inches to about 1.2 inches, and even more specifically, about 0.7 inches to about 1 inch. For some embodiments, the relieved portion or channel may have a diameter or transverse dimension of about 0.1 inches to about 0.3 inches, more specifically, about 0.15 inches to about 0.25 inches, and even more specifically, about 0.18 inches to about 0.22 inches.
• For some embodiments, the enlarged portion of a shaft of apin tool68 may include a collar member and the stop surface of the at least one relieved portion may be configured to prevent axial movement of the collar member and mechanically capture a collar disposed therein member to prevent lateral displacement of the block body when the block is deployed in a pintool head assembly64. If more than one relieved portions or channels are disposed in a single block body portion, it may be desirable for the relieved portions to have a regular spacing that corresponds to a regular spacing of thepin tools68 of a pintool head assembly64 for which the block is to be used.
• For some embodiments, the relieved portion or channel may extend either partially or completely from the top surface of the block body portion to the bottom surface of the block body portion. For some embodiments wherein the relieved portion extends only partially from the top surface of the block body portion, the relieved portion may terminate at a stop surface which is spaced from the bottom surface. The top surface and bottom surface of the block body portion may be substantially flat and substantially parallel to each other for some embodiments. Some embodiments of pin tool displacement blocks may have a reversible configuration wherein when the block is oriented in a first direction and deployed, a first pin or set of pins is active and when flipped over 180 degrees or otherwise oriented a second direction and deployed, a second pin or set of pins is active which is different from the first set. For such embodiments, it may be desirable for the relieved portions to extend only partially from a first surface to a second surface of the block body portion.
• Embodiments of the block body portion may optionally include a handle member extending from and secured to the body portion for more convenient handling by a user of the device. The handle member may be a thin but rigid extension of the material of the block body portion that is easily gripped by a user and extends away from the block body portion with material relieved from both the top surface and bottom surface to allow easy access and gripping. The block body may be made from an inert material, such as Teflon®, Delrin® or the like and may have a width of about 0.4 inches to about 3 inches, more specifically, about 0.8 inches to about 1.2 inches, a length of about 0.5 inches to about 4 inches, more specifically, about 1.5 inches to about 2.5 inches, and a height or thickness of about 0.2 inches to about 1.5 inches, more specifically, about 0.3 inches to about 0.7 inches.
• FIGS. 15 and 16 illustrate a simplified pintool displacement block300 having asingle slot302 with a single relieved portion orchannel304 disposed in theslot302. Therelieved portion304 extends from atop surface306 of theblock body308 portion towards a bottom surface of the block body portion and extends through theblock body portion308 completely from thetop surface306 to abottom surface312, as shown inFIG. 16. The pintool displacement block300 may have the same or similar features, dimensions or materials as the features, dimensions or materials of the pin tool displacement block embodiments discussed above.
• FIG. 17 is an elevation view of a simplified pintool head assembly314 having afirst pin tool316 andsecond pin tool318 mounted in aframe322 of the pintool head assembly314. Theframe322 includes afirst side plate324, asecond side plate326, abottom plate328 and acover plate330. All four plates are secured to adjacent plates at their ends in a perpendicular orientation. The first andsecond side plates324 are substantially parallel to each other and thecover plate328 andbottom plate330 are substantially parallel to each other. Thepin tools316 and318, which may have the same or similar features, dimensions or materials as the features, dimensions or materials of thepin tool embodiments68 discussed above, have a “D” shaped transverse cross section in an upper portion that mates with a corresponding “D” shaped hole in thecover plate330. A resilient member in the form of ahelical spring152 is disposed over eachpin tool316 and318 between thecover plate330 andwasher154 disposed towards the bottom of eachpin tool316 and318. Thewashers152 of thepin tools316 and318 are held axially in place by compression clips orcollar members144 that are secured tocircumferential grooves148 in an outer surface of eachpin tool shaft142. As such, eachpin tool316 and318 is resiliently biased in a downward direction both by the weight of the pin tool itself and thehelical spring152. Thehelical springs152 have an axial length in a relaxed uncompressed state that is longer than the distance between an inside surface of thecover plate330 and inside surface of thebottom plate328.
• FIGS. 18 and 19 illustrate an embodiment of a method of displacing a pin tool of the pintool head assembly314 of a robotic sample transfer device with the pintool displacement block300 discussed above. As shown inFIG. 18, the pintool head assembly314 is brought down vertically into contact with aflat surface332 in order to displace thepin tools316 and318 axially in an upward direction. In this position, the enlarged portions of the pin tool shafts or collar members are displaced axially from the inside surface of thebottom plate328 as shown. Theslot302 of the pintool displacement block300 is then aligned with the row ofpin tools316 and318 and advanced into the pintool head assembly314 as shown by arrow inFIG. 18. Once therelieved portion304 in theslot302 of the pintool displacement block300 is aligned coaxially in a vertical direction with the first pin tooshaft316, the pintool head assembly314 may then be raised and retracted from theflat surface332 to allow thepin tools316 and318 of thepin tool head314 assembly to resume a relaxed state. As thepin tool shafts316 and318 return to their nominal relaxed positions, thecollar member144 of thefirst pin tool316 passes through therelieved portion304 of the pintool displacement block144 and comes to rest on the inside surface of thebottom plate328. However, thecollar member144 of thesecond pin tool318 comes to rest on the upper surface of the pintool displacement block300 in an axially retracted state with the distal tip of the pin tool axially retracted from the plane of the first pin tool by a length, indicated byarrow334, which is substantially equal to the thickness or height of the pintool displacement block300.
• FIGS. 20A-20D illustrate an embodiment of a pintool displacement block336 for use with a 6×4 pin tool array of a pintool head assembly64. The pintool displacement block336 includes 6parallel slots338 that have a regular spacing that is configured to match that of an array of pin tools of a pintool head assembly64. A singlerelieved channel342 is disposed in a secondparallel slot338 of theblock336 in order to allow a single pin tool in a 2-2 position of the array to be configured for use after deployment of the pin tool displacement block into the pin too head assembly. The pintool displacement block336 may have some or all of the features, dimensions or materials as the features, dimensions or materials of any of the pin tool displacement blocks discussed above. The pintool displacement block336 includes a first parallel slot, a second parallel slot, a third parallel slot, a fourth parallel slot, a fifth parallel slot and a sixth parallel slot. The pin tool displacement block includes ablock body334 having abottom surface346 with the 6 parallel slots formed into theblock body portion344 substantially perpendicular to thebottom surface346 with a predetermined regular spacing that may be configured to correspond to regular spacing ofpin tools68 of a pintool head assembly64. Theparallel slots338 may have a transverse dimension which is sized to allow easy movement of a width of a nominal shaft of thepin tools68 in theslots338 but restrictive of movement of anenlarged portion143 of the shaft of thepin tools68. For some embodiments, theparallel slots338 may have a width of about 0.04 inches to about 0.02 inches, more specifically, about 0.07 inches to about 0.1 inches, and a spacing or pitch of about 0.1 inches to about 0.5 inches, more specifically, about 0.15 inches to about 0.2 inches. Some embodiments may have aslot338 length of about 0.2 inches to about 2 inches, more specifically, about 0.5 inches to about 1.2 inches, and even more specifically, about 0.7 inches to about 1 inch. For some embodiments, the relieved portion orchannel342 may have a diameter or transverse dimension of about 0.1 inches to about 0.3 inches, more specifically, about 0.15 inches to about 0.25 inches, and even more specifically, about 0.18 inches to about 0.22 inches.
• Therelieved channel342 extends from thetop surface348 completely through theblock body portion344 in a direction which is substantially perpendicular to thebottom surface346. The relieved channel orportion342 may have a transverse dimension sized to allow easy movement in an axial downward direction of not only the nominal shaft portion of arespective pin tool68 but also andenlarged portion143 of a pin tool shaft and be configured to mechanically capture theenlarged portion143 of apin tool68 disposed therein in a lateral direction. Embodiments of theblock body portion344 may optionally include ahandle member352 extending from and secured to the body portion for more convenient handling by a user of the device. Thehandle member352 may be a thin but rigid extension of the material of theblock body portion344 that is easily gripped by a user and extends away from the block body portion with material relieved from both thetop surface348 andbottom surface346 to allow easy access and gripping. Theblock body344 may be made from an inert material, such as Teflon®, Delrin® or the like and may have a width of about 0.4 inches to about 3 inches, more specifically, about 0.8 inches to about 1.2 inches, a length of about 0.5 inches to about 4 inches, more specifically, about 1.5 inches to about 2.5 inches, and a height or thickness of about 0.2 inches to about 1.5 inches, more specifically, about 0.3 inches to about 0.7 inches.
• FIGS. 21A-21D illustrate an embodiment of a pintool displacement block360 for use with a 6×4 pin tool array. The pintool displacement block360 includes 6parallel slots362 that may have a regular spacing that is configured to match that of an array of pin tools of a pintool head assembly64. Tworelieved channels364 are disposed in each of a second parallel slot, a fourth parallel slot, and a sixth parallel slot in order to allow six pin tools to be configured for use after deployment of the pin tool displacement block into the pin too head assembly. Other than the 6relieved channels364, the pin tool displacement block ofFIGS. 21A-21D may have the same features, dimensions or materials as those of the pin tool displacement block ofFIGS. 20A-20D discussed above. The relieved channels of the pin tool displacement block are disposed at the 2-2, 2-4, 4-2, 4-4, 6-2 and 6-4 positions of the array and extend completely through the block body portion of the pintool displacement block360.
• For some embodiments, a method for selectively displacing at least onepin tool68 of a pintool head assembly64 of a roboticsample transfer device10 may include the use of a pintool displacement block370 having a block body with a bottom surface and a plurality of parallel slots formed into the block body portion. The parallel slots may be substantially perpendicular to the bottom surface with a predetermined regular spacing configured to correspond to regular spacing ofpin tools68 of a pintool head assembly64. The parallel slots may have a transverse dimension sized to allow easy movement of a width of a nominal shaft of thepin tools68 in the slots but restrictive of movement of an enlarged portion of the shaft of the pin tools. The pin tool displacement block may also include at least one relieved portion or channel in a slot which has a transverse dimension sized to allow easy downward movement of the enlarged portion of a pin tool shaft which is greater than the transverse dimension of the slot and which extends from a top surface of the block body towards the bottom surface. An array of pin tools of a pintool head assembly64 are axially displaced by depressing the distal ends of thepin tools68 against a flat surface. The pin tool displacement block may then be deployed into the pin tool head assembly such that the parallel slots of the pin tool displacement block slide over rows of the array of pin tools of the pin tool head assembly. Thepin tools68 are then allowed to return to a relaxed state by retracting the pin tool head assembly from the flat surface with at least one of the pin tools remaining displaced in an axially retracted and relaxed state.
• FIGS. 22-24 illustrate an embodiment of a reversible pintool displacement block370. The reversible pintool displacement block370 may have some or all of the features, dimensions or materials as those of the pin tooldisplacement block embodiments300,336 and360, discussed above. The reversible pintool displacement block370 essentially combines the functions of the pin tool displacement blocks336 and360 ofFIGS. 20A-20D andFIGS. 21A-21D discussed above. When theblock370 is oriented in a first direction and deployed, a first pin tool or set of pin tools is active and when the block is flipped over 180 degrees or otherwise oriented a second direction and deployed, a second pin tool or set of pin tools is active which is different from the first set. The reversible pin tooldisplacement block embodiment370 shown allows a single pin tool to be configured for used while deployed on afirst side372 while maintaining all remaining pin tools of a 6×4 pin tool array in a retracted state. The reversible pintool displacement block370 allows 6 pin tools to be configured for used while deployed on asecond side374 while maintaining all remaining pin tools of a 6×4 pin tool array in a retracted state.
• For the reversible pin tooldisplacement block embodiment370, it may be desirable for relieved portion orportions376 to extend only partially through theblock body portion370 and terminate at astop surface378 which is spaced from a surface of the block opposite the opening of therelieved channel376. Thefirst surface372 andsecond surface374 of theblock body370 portion may be substantially flat and substantially parallel to each other for some embodiments.FIG. 22 illustrates the pintool displacement block370 with thefirst side372 up showing 6 relieved channels380 that allow sixpin tools68 to be active or usable when thepin tool block370 is deployed on thesecond side374 with the second side down.FIG. 24 illustrates the pintool displacement block370 withsecond side374 up showing a singlerelieved channel382 that allow a single pin tool to be active or usable on the first side when the first side is down.
• Some method embodiments of dispensing calibration material onto achip274, such as a spectrometry chip, may include the use of achip274 having an array of regularly spacedsample deposition sites292 disposed on a substantially flat workingsurface293 of thechip274. Thechip274 may also include at least onesample deposition site292 for receiving calibration material which is also disposed on theflat working surface293 of thechip274. The method embodiments may include the use of a roboticsample transfer device10 having a pintool head assembly64 with an array of regularly spacedpin tools68. Distal ends158 of thepin tools68 of the pintool head assembly64 are disposed substantially coplanar in a relaxed state and have a regular spacing which is the same as or otherwise matched to the regular spacing of the first array ofsample deposition sites292 of the chip. The spacing of thepin tools68 may also be an integer multiple of the spacing of the sample deposition sites of thechip274 and configured to align with the array of regularly spacedsample deposition sites292 of thechip274 or a subset thereof.
• Generally, it is desirable to dispense calibration material very selectively to only thosesample deposition sites292 that are intended for use with calibration materials. As such, it is desirable to avoid dispensing calibration material or otherwise contaminatingsample deposition sites292 which are not intended for use in calibration with calibration material. For some method embodiments, it may be useful to use a reduced number ofpin tools68 of a pintool head assembly64 in order to avoid such contamination or inadvertent material transfer. For some such method embodiments, all but one of thepin tools68 of the pintool head assembly64 is displaced to a retracted non-usable state by deploying a pintool displacement block336, such as pin tool displacement block shown inFIGS. 20A-20D, into the pintool head assembly64. Thepin tool block336 may be deployed in the pintool head assembly64 as shown inFIGS. 18 and 19 and discussed in the accompanying text above. Asample reservoir156 of theusable pin tool68 of the roboticsample transfer device10 may then be loaded with calibration material by dipping thepin tool68 into a well containing calibration material. The calibration material may then be dispensed from theusable pin tool68 of the roboticsample transfer device10 to asample deposition site292 for receiving calibration material. During the deposition of the calibration material to thesample deposition site292, the functioningpin tool68 containing the calibration material extends distally below thepin tools68 that are held in a retracted state by the pintool displacement block336. As such, while the functioningpin tool tip156 is moved distally into contact with thesample deposition site292 for deposition of the calibration material, thepin tools68 which are displaced by the pintool displacement block336 do not contact the chip.
• In addition to dispensing calibration materials by methods that include controlling the number ofactive pin tools68 of apin tool array64, calibration material may also be deposited on selectedsample deposition sites292 of achip274 or the like by using a full array ofpin tools68. The full array ofpin tools68 may be used with achip274 having a first array of regularly spacedsample deposition sites292 disposed on a substantially flat workingsurface293 of thechip274. Thechip274 may also have at least onesample deposition site292 for receiving calibration material which is also disposed on theflat working surface293 of thechip274 and which is off pitch with respect to the regular spacing of the first array of regularly spacedsample deposition sites292 of thechip274, as shown inFIGS. 11A and 11B.
• A roboticsample transfer device10 having a pintool head assembly64 may also be used for the calibration method. The pintool head assembly64 may have an array of regularly spacedpin tools68 withdistal ends158 which are substantially coplanar with each other in a relaxed state. Thepin tools68 of the pin tool array also have a regular spacing which is the same as or otherwise corresponds to the regular spacing of the first array ofsample deposition sites292 or an integer multiple thereof. The regular spacing of thepin tools68 is also configured to align with the array of regularly spacedsample deposition sites292 of thechip274 or a subset thereof.
• During a calibration process embodiment,sample reservoirs156 of the array of regularly spacedpin tools68 of the roboticsample transfer device10 may be loaded with calibration material. Only the pin tool reservoir orreservoirs156 that will be depositing the calibration material onto the desired calibration material sample deposition site will be loaded with calibration material for some embodiments. The calibration material may then be dispensed from thepin tools68 of the roboticsample transfer device10 to the at least onesample deposition site292 for receiving calibration material. During deposition of the calibration material, thepin tools68 which are not aligned withsample deposition sites292 for receiving calibration material are off pitch with respect to the first array of regularly spacedsample deposition sites292 of the chip. As such, thepin tools68 do not contact any of the regularly spacedsample deposition sites292 of the first array.FIG. 25 illustrates two pin tool distal ends158 disposed oversample deposition sites292 of a second array of sample deposition sites which are regularly spaced and off pitch from the first array. Thesample deposition sites292 of the second array are configured to receive calibration material which is being dispensed from thesample reservoirs156 of thedistal tips158 of thepin tools68 to the calibrationsample deposition sites292 of thechip274 as shown. Also shown are two pin tool distal ends158 disposed between and not aligned with the sample deposition sites of the first array ofsample deposition sites292 for receiving normal sample deposition. For some embodiments, the first array of regularly spaced sample deposition sites includes an array of regularly spaced mass spectrometry sample deposition sites.
• FIG. 26 illustrates a main screen of an embodiment of theuser interface26 discussed above. The main screen or main menu is arrived at after a user logs onto thedevice10 by entering a user name and password into the system through theuser interface26. From the main screen of theuser interface26, a user may navigate the various programming controls of thedevice10 in a convenient and user friendly manner. For the embodiment shown, along the top row of the screen, a “home”button400 may be touched by the user to manually send the pintool head assembly64 of thedevice10 to a home position located generally towards the front and left side of theprocessing chamber14. A “system status”button402 takes the user to a screen that provides detailed information regarding the current status of the integratedrobotic positioning device10. Status data such as the identification of the current user, computer identification, hard drive capacity, volatile memory capacity, software version, x, y, and z positions of the pintool head assembly64, safety interlock status, temperature and humidity within theprocessing chamber14, washfluid tank242 andwaste fluid tank224 fluid levels as well as other information may be displayed on the status screen or screens. The “exit”button404 takes the user back to the fundamental operating system interface of theprocessor32. For example, forprocessor embodiments32 using a Windows® type operating system, theexit button404 will return the user back to a Windows® desktop. A “help”button406 allows the user to access a help database with information regarding the programming, use and operation of thedevice10 with regard to the type of options available on the screen displaying thehelp button406. Generally, for some embodiments, each screen of theuser interface26 may have ahelp button406. At the bottom row of the main screen, a “log off”button408 is used to log off the current logged on user of thesystem10. A “shut down”button410 shuts down thesystem10.
• A “maintenance”button412 on the main screen takes a logged on user to a maintenance screen illustrated inFIG. 27. The maintenance screen includes thestatus button402,exit button404 andhelp button406 discussed above. The maintenance screen also includes a “load chips and MTPs”button414, a “load solution”button416, a “fill supply tank”button418, a “clean pins” button420, a “complete cycle”button422, a “drain solution”button424, an “drain supply tank” button,426 and a “condition pins”button428. The load chips andMTPs button414 moves the pintool head assembly64 of thesystem10 to a far left and rear position in order to make room for the user to loadsample chips274 or achip block266 onto thework surface22 of thedevice10. Theload solution button416 moves the pintool head assembly64 to the far right and rear position of theprocessing chamber14 in order to make room for a user to load or unload thesupply reservoir168. The fillsupply tank button418 prompts the user to position the fluid valves in the lowerstorage tank chamber44 in communication with the supply tank such that thesupply tank242 may be filled from an external tank. After the user is prompted to manually configure the valves, de-ionized water may be pumped into the supply tank with a self priming pump disposed within thehousing12. The pump may be configured to automatically turn off once thetank242 is filled. The user may then be prompted to switch the valves manually back normal operating mode. The controller may then execute a priming routine to clean out air from the tubing or lines between thetank242 and the rinse station. To accomplish this, the water may be pumped to the rinse station at about 5 percent to about 10 percent normal flow using a pulsed modulation technique. For this pulsed technique, the pump may be run at full speed for a short period of time and then stopped for an interval before restarting again. For some embodiments, the pump may be run for about 5 msec to about 15 msec and stopped for about 85 msec to about 95 msec. The pulse intervals are short enough that the pump appears to run continuously to the user, but is only achieving a 5 percent to 10 percent duty cycle.
• The clean pins button420 runs a protocol for cleaning thepins68 of the pintool head assembly64 by immersing the pins in the ultrasonic bath for an extended period of time. For some embodiments, thepin tools64 may be soaked for about 15 minutes to about 45 minutes, more specifically, for about 25 minutes to about 35 minutes. During the soaking process, the ultrasonic bath may contain a cleaning solution such as pure ethanol. The pin tools may be treated with a subsequent standard cleaning cycle after the soak that may include a water rinse in the rinse station, drying in the vacuum drying station, ultrasonic cleaning with water in the ultrasonic bath and a final drying in the vacuum drying station.
• Acomplete cycle button422 initiates a standard cleaning cycle, as discussed above, including a water rinse in the rinse station, drying in the vacuum drying station, ultrasonic cleaning with water and alcohol in the ultrasonic bath and a final drying in the vacuum drying station. For some embodiments, an equal mix of de-ionized water and ethanol alcohol may be used for the ultrasonic cleaning bath. Thedrain solution button424 turns on thepump222 and drains the ultrasonic bath of the ultrasonic wash station. As the ultrasonic bath is drained, it may be refilled by thereservoir168 until the reservoir is emptied.
• The drainsupply tank button426 turns on the rinse fluid pump continuously until the rinsefluid supply tank242 is emptied. This may be used to lighten thedevice10 in anticipation of transporting thedevice10, performing maintenance in the lower chamber or the like. The condition pinsbutton428 initiates a protocol whereby thepins68 of the pintool head assembly64 are soaked in a cleaning solution, such as a 1 molar solution of NaOH which may be disposed within selected wells of a microtiter plate. Thepins68 may be soaked for about 5 minutes to about 15 minutes and then treated with a standard clean cycle as discussed above. This process may be carried out every week or so in order to condition thepins68.
• Referring back toFIG. 26, a “mapping”button430 takes the user to a mapping screen shown inFIG. 28. The mapping screen allows the user to input some preliminary information about the sample transfer process desired. For example, for some embodiments, the user may be prompted with a request to select a microtiter plate format, such as a 96 or 384 well plate. Next, the user may be prompted to select a chip format and thereafter the number of the chips to be used. Once this information has been entered, mapping information presented visually by agrid432 representing the microtiter plate wells andgrid434, representing the chip sample deposition sites, may be selected and stored by a “save”button436 to track the mapping to be used.Chip buttons438 may be used to select the chip number to be loaded with samples taken and the “MTP”arrow buttons439 may be used to select the microtiter plate from which to load samples. The “exit”button440 may be used to exit the mapping screen. In addition, a two dimensional bar code of a selectedchip274 may be tied to a bar code of a specific microtiter plate by the controller. The controller may also store the mapping configuration selected between the chip and microtiter plate along with some additional data including time stamp data, microtiter plate and chip configuration data and the like. All of this data may be transferred to a sample tracking database server or other data storage device.
• Referring again toFIG. 26, a “methods”button442 takes the user to a methods screen shown inFIG. 29. The methods screen includes theexit button404,status button402 andhelp button406 on the top row which may have the same functions as discussed above. Also on the top row of the methods screen are an “open”button442 and a “save”button444. Theopen button442 allows a user to open a predetermined set of method transfer parameters and thesave button444 allows a user to save a predetermined set of method transfer parameters. A “run transfer”button443 takes the user to the “run transfer” screen shown inFIG. 30 and discussed below. At the bottom of the methods screen are three tabs, with the “setup”tab445 being selected for the methods screen embodiment shown. Within a “mapping file”section446 of the methods screen for setup, a user may select a predetermined mapping file as generated from the mapping screen ofFIG. 28 for use in a transfer method. A “browse”button448 may be used to browse a plurality of predetermined mapping files created by a user. An “analysis”section450 of the methods screen includes a “volume check”check box452 and a “sample tracking”check box454. If the user selects thevolume check box452, each sample deposited onto a sample deposition site of achip274 may be imaged by the imaging camera and the image taken processed in order to estimate the volume of each sample deposited onto a sample deposition site. The volume check parameters of a deposited sample may be determined by the volume, average diameter, y-axis direction diameter, x-axis direction diameter, circumference and area of one or more deposited samples. The average volume for samples deposited and standard deviation of volume of samples deposited may also be determined. If the sample tracking box is checked by a user, bar code data associated withmicrotiter plates268 andcorresponding chips274 will be saved to a file that may be later accessed by a user in order to confirm a transfer method.
• A “scout plate”section456 allows a user to select a particular chip type from the number of chips such as a 4 chip scout plate or a 10 chip scout plate. A “spectrochips”section458 includes “chip selection”buttons460 numbered 1-10 for a 10 chip mount block (or 1-4 if a 4 chip mount block was selected in section456) which allows a user to select a particular chip from the number of chips of the chip mount block type previously selected to receive transferred samples for a particular method.
• Referring again to the bottom of the methods screen, if the “cleaning”tab462 is selected for the screen, additional sections (not shown) are available to the user which allow a user to set cleaning cycle parameters such as dwell time in a particular cleaning station functional element and the like. The “aspirate/dispense”tab464 provides options on a screen (not shown) for the amount of time that the sample reservoir of thepin tools68 dwell in a sample reservoir while aspirating a sample, the depth to which apin tool68 is moved into a sample well of a microtiter plate and the speed of thepin tool68 as it enters and leaves a sample well of a microtiter plate. The user may also set the dwell time of apin tool68 as it contacts a sample deposition site of a chip, the speed of the pin tool as it approaches a surface of the chip and the length of compression of the resilient member which biases thepin tool68 against the upper surface of the chip once the tip of thepin tool68 makes contact. These parameters may affect the amount of sample aspirated or taken up by apin tool68 and the amount of sample deposited to a sample deposition site. These parameters may also affect the speed and efficiency of the transfer method and prevent damage to thechips274 or microtiter plates as well as prevent loss of samples or contamination due to splashing as a result of excessive speed of thepin tool68 during a transfer.
• Referring again toFIG. 26, a “transfer”button466 takes the user to a run transfer screen shown inFIG. 30. A top row on the run transfer screen again includes theexit button404,status button402, andhelp button406 that may have he same functions as discussed above. An “open method”button470 at the top of the screen allows a user to open a previously determined set of method parameters. A “flow”button472 allows a user to access the method screen while running a transfer and change method parameters during the transfer process. A “volume check”button474 allows a user to access and review volume check data for data collected when thevolume check box452 on the method screen is selected.
• A live video image of the transfer process may be displayed in video block476 as well as a graphic of the transfer status of sample deposition onchips274 of a selected chip mount block shown on achip status block478. Microtiter plate status blocks480 and482 show the transfer status of two selectedmicrotiter plates268 in current use including a graphic display of sample wells that have already been transferred and which wells are full and have not yet been transferred to a sample deposition site of achip274. “Stop”, “pause”, “step” and “run” buttons are disposed at the bottom of the run transfer screen which allow a user to stop, pause or run a selected transfer process. The step button may pause after every dispense cycle to allow the user to update method parameters or view volume check data. The use may then press the step button again to continue the cycle in the transfer or press the run button to finish the transfer process without automatically pausing after each dispense cycle.
• Referring back toFIG. 26, a “configure”button486 takes the user to a configure screen shown inFIG. 31. A top row on the configure screen again includes theexit button404,status button402, andhelp button406 that may have he same functions as discussed above. Also on the top row of the configure screen are an “open”button442 and a “save”button444. Theopen button442 allows a user to open a predetermined set of method transfer parameters and thesave button444 allows a user to save a predetermined set of method transfer parameters.
• At the bottom of the configure screen, a row of tabs allows the user to select sub-screens that provide options for selecting movement parameters for various predetermined process steps that thedevice10 may carry out. The tabs at the bottom of the configure screen include a “calibrant”tab490, a “dry rinse”tab492, a “dry wash”tab494, a “MTP” ormicrotiter plate tab496, a “rinse”tab498, a “spectochip”tab500 and a “wash”tab502. A tab with a set of laterally oriented arrows may be selected to show additional tabs (not shown) including a “general” tab, a “bar code” tab and a “calibration” tab. For each of these tabs, generally, motion parameters for the pin tool head assembly for the process corresponding to each tab may be selected or preset. for example, for the configure screen show in which thecalibrant tab490 is selected, the z axis motion acceleration, z axis motion velocity, z down position and calibrant dip time may be preset and saved. These settings may be determined by moving a slidingsetting bar503A disposed in a setting box or by directly entering numerical data in adata box503B disposed below the sliding setting bar. Once these settings are selected and saved, they may be tested for each process indicated by the tabs by actuating the “test”button504. Some additional features include functions of the barcode tab which allow a user to turn the bar code reader function on and off. The bar code reader function may be carried out by the bar code reader head for scanning linear bar codes onmicrotiter plates268 as well as the imaging camera which may be used to scan two dimensional bar codes disposed on thechips274.
• The general tab screen has a variety of settings and also includes a button which allows a user to reset all of the settings of the configure screens to the factory default settings. The calibration tab screen provides the user with predetermined settings that may not be changed often. For example, the calibration tab screen may provide a data box to enter the position offset of apre-selected pin tool68 of the pintool head assembly64, such as pin tool “A-1”, with respect to the position of the center of the field of view of the imaging camera. Once this is properly set, any feature, functional element or the like which is imaged by the imaging camera in the center of the field of view may then be accessed by a pin tool by instructing the processor to move thepin tool68 in the distance and direction of the known offset, which may serve as a single entry look up table for such motion.
• Referring toFIG. 26, a “motion”button510 takes the user to a motion screen shown inFIG. 32. A top row on the motion screen again includes theexit button404,status button402, andhelp button406 that may have he same functions as discussed above. Also on the top row of the configure screen is a “save”button444 that may be used to store settings. Ahome button400 is also disposed on the motion screen to have the pin tool head assembly moved to the home position.
• The motion screen ofFIG. 32 allows a user to select general motion parameters for motion acceleration, velocity and large move distance for translation of the pin tool head assembly in the x, y and z axes, with the buttons for selecting the axis of interest indicated bybuttons512,514 and516 respectively. Data selections for these parameters may be entered by clicking and moving a sliding bar518 or by direct data entry into adata box520 disposed below the sliding bar518.Arrows522 disposed on either side of the data boxes allow a user to click the arrows and adjust the parameters in the data boxes by fixed increments. A set ofarrows524 are disposed on the right hand side of the screen and allow a user to manually move or jog the pin tool head assembly by predetermined increments. Atoggle button526 allows users to select between large movement increments and small movement increments, each of the increments being selected or set by the slidingbar528 or by direct data entry intodata box530. One of the uses of the functions on the motion screen is to teach the processor of thedevice10 where the locations of the various components or functional elements reside on the work surface. For example, a user may wish to teach the processor the location of a first microtiter plate disposed on the microtiter plate mount block of the work surface. The user may use thejog buttons524 in either large movement or small movement mode to position the pintool head array64 above the predetermined corner of the first microtiter plate. Fine adjustments may be made with visual feedback by the user to align thepin tools68 with the predetermined wells of the microtiter plate.
• Once this positioning has been achieved, the user may select a “check”button532 disposed at the top of the motion screen which then takes the user to the “deck plate” screen shown inFIG. 33. A top row on the deck plate screen includes theexit button404,status button402, andhelp button406 that may have he same functions as discussed above. Also on the top row of the deck plate screen are an “open”button442 and a “save”button444. Theopen button442 allows a user to open a predetermined set of method transfer parameters and thesave button444 allows a user to save a predetermined set of method transfer parameters.
• The deck plate screen also includes a variety of buttons that may be used to allow a user to store position data generated from the position sensors such as the encoder strip assemblies and store that known position data so as to associate the position data to a known component of functional element of the work surface. There are two basic approaches to use of the deck plate screen. The first is a manual teach mode which may be entered from the check savebutton532 of the motion screen wherein know position data is stored so as to correspond to know functional elements or components of thedevice10. A manual mode in the deck plate screen allows a user to direct the pin tool head to a known, pre-programmed position and also allows the used to carry out basic single event procedures, such as washing, drying, rinsing etc.
• If the position information for each of the functional elements of thework surface22 is taught to the processor, a database or lookup type table may be generated for use as to absolute and relative positions of the functional elements as well as other components. For example, from the motion screen ofFIG. 32, the pin tool head array may be moved by a user using thejog buttons524 to the A-1 position of the first microtiter plate disposed on the work surface of the device. Once the pin tools are properly positioned, a “microtiter plate type”button536 may be touched and toggled so as to select a microtiter plate type that matches the type mounted to the work surface. For some embodiments, the toggle choices may include a 96 well or 384 well microtiter plate. A “first microtiter plate”button538 may then be touched to indicate that thepin tools68 are disposed in the first microtiter plate and not the second microtiter plate which may be selected by “second microtiter plate”button540. A graphic image of the first microtiter plate is displayed onblock542 and the second microtiter plate onblock544. If the position data and component selection has been properly made, the user may then select the “check save”button546 at the top of the screen which saves the data to the memory storage unit of thecontroller28 or other suitable device. This same procedure may be applied to the teaching of position data of the pin tool head assembly andpin tools68 thereof by using the “pin tool”button548, the bar code reader head assembly by using the “bar code reader”button550, and the camera by using the “camera”button552. These position data teaching procedures generally apply to the pintool head assembly64 and microtiter plates, however, the same or similar procedures for teaching position data to thecontroller28 may also be used for the pintool head assembly64 with respect to thechips274.
• For such a procedure, the pin tool head may be manually moved to a predetermined location with respect to achip274 mounted in a chip mount block on the work surface. Such positioning may be carried out by using manual jogging movement from the position screen discussed above. Once thepin tools68 are properly positioned with respect to a component for functional element, the component or functional element may be identified by touching the corresponding button, such as the “pin tool”button553. Thereafter, the type ofchip274 being used may be selected by the “chip type”button554 to select between a 384 site chip, a 96 site chip or any other suitable configuration. Thespecific chip274 over which thepin tools68 are located may then be selected by touching one of the “chip number”buttons556 that correspond to the chip being used. If the position data and component selection has been properly made, the user may then select the “check save”button546 at the top of the screen which saves the data to the memory storage unit of thecontroller28 or other suitable device. This same procedure may be applied to the teaching of position data of the pin tool head assembly andpin tools68 thereof, as well as the position of other components, by using other buttons on the screen. For example, position data for the 2-d bar code on a chip may be taught by using the “bar code reader”button558, and the camera by using the “camera”button560. The position data related to thecalibration material vessel256 may be taught by using the “calibration vessel”button562.
• Once one or more position data sets have been taught to thecontroller28, there are other features on the deck plate screen that allow a user to carry out basic functions on an as needed basis. For example, a user may initiate a wash cycle by touching “wash cycle”button564, a rinse cycle by touching “rinse cycle”button566 or a dry cycle by touching “dry cycle”button568. A “calibration vessel home”button570 may be used to move the pintool head assembly64 to thecalibration vessel256. A “pin tool selection”button572 may be used to select or toggle between various pin tool array configurations, such as a single pin tool, 6 pin tool array or 24 pin tool array as well as others. A “configuration screen”button574 may be touched by a user to jump to the configuration screen, a “motion screen”button576 may be used to jump to the motion screen and a “vision screen”button575 may be used to jump to the vision screen shown inFIG. 34.
• The vision screen includes controls that allow a user to turn theimaging camera132 on and off and move the camera to a desired position manually with a set ofjog arrows580 which may be toggled between large movement steps and small movement steps with a “toggle”button582. The live video image block584 allows the user to see thework surface22 and functional elements and components thereof through the imaging camera lens while the camera is being positioned with thejog arrow buttons580. The vision screen may also be used in conjunction with the deck plate screen for manual teaching of positions and relative positions of the pin tool head, bar code reader and imaging camera with respect to thework surface22 and functional elements thereof. Work surface components may be viewed on the video image block584 and aligned with a crosshair centering reticle586 positioned in the center of the field of view of the imaging camera so that the position of the viewed and aligned component may be know with regard to the position of theimaging camera132. If the position of the center of field of view of the imaging camera is know with respect to other components of thedevice10, this positioning data may be stored or otherwise used to calculate the position of other components. If the imaging camera is aligned with a component at a position that is useful to be taught to thecontroller28, the “check”button532 may be selected to take the user to the deck plate screen discussed above for manual teaching of position as discussed above.
• A top row on the vision screen includes theexit button404,status button402, andhelp button406 that may have he same functions as discussed above. Also on the top row of the vision screen are an “open”button442 and a “save”button444. Theopen button442 allows a user to open a predetermined set of method transfer parameters and thesave button444 allows a user to save a predetermined set of method transfer parameters. A “configuration”button588 allows a user to set a variety of imaging parameters such as exposure, gain and further adjustment of jog movement parameters such as the length of the large and small movement jog steps. Thesafety interlock indicator590 indicates whether the safety interlock switch is engaged or disengaged. An “illuminator”button592 toggles an illumination light source for theimaging camera132 on and off. A “zoom”button594 zooms the field of view in the live image block584 in and out and a “video on”button596 toggles theimaging camera132 on and off.
• A set of “chip type”buttons598 allows a user to select the type ofchip274 being imaged or otherwise used on thework surface22. A selection may be made between a 96 site chip and a 384 site chip. A set ofselection arrows600 allow a user to choose from a menu of predeterminedimage processing algorithms601 which may be used to confirm the position of the imaging camera relative to a feature or component of interest. Examples of the algorithms include a 2-d bar code algorithm, an align a 96 site chip algorithm, an align a 384 site chip algorithm, an align a 96 well microtiter plate algorithm, an align a 384 well microtiter plate algorithm, a calibrate pins algorithm, a calibrate pixels algorithm, and a volume check algorithm. The calibrate pins algorithm determines the center of the field of view of the imaging camera with respect to the position of a particular pin tool, such as the A1 positioned pin tool. The calibration of pixels algorithm uses the known distance between two fiducial marks on achip274 to calculate the number of pixels of the imaging camera per millimeter on the plane of the work surface. The “measure”button602 may be used or selected in order to initiate a selected algorithm process once the camera has been positioned in a desired location. The “run”button604 may be selected to move the pin tool head assembly, bar code reader or camera to a position on thework surface22 corresponding to the algorithm selected to be run.
• In addition to embodiments described above, other similar embodiments, such as those discussed below, may also be used in the same or similar manner as discussed above. For some embodiments, a pin protection block tool assembly for selectively displacing at least onepin tool68 of a pintool head assembly64 of a roboticsample transfer device10 may be used. Using the pin protection block tool allows the user to select any number of active pin tools by selective deactivation of the pin tools not being used in the standard 24pin tool head64. For instance, if the user wants only a single pin tool active, the user may use the pin protection block tool assembly in conjunction with a pin tool displacement block having a single pin configuration to selectively deactivate all but one of the pin tools68 (e.g., deactivate23 of24). The pin protection block tool assembly, as shown inFIGS. 37A-37C, is used for upwards axial displacement of thepin tools68 andpin tool collars143 within the pintool head assembly64 prior to insertion of a pin tool displacement block. The pin protection block tool assembly hasbody610 which is substantially rectangular in shape and has raisededges614 which act as a hard stop to the downward movement of the lower surface, which in turn may prevent the user from over compressing the pins and damaging the pin array and holder, while allowing adequate room for inserting a pin tool displacement block (also referred to as a pin too displacement comb) of pintool head assembly64 of roboticsample transfer device10. The pin protection block tool assembly has a top surface and a bottom surface which is substantially parallel to the top surface, and a plurality of non penetrating cylindrical bores machined into the block body, arranged with a predetermined regular spacing configured to correspond to regular spacing ofpin tools68 of a pintool head assembly64. At least two pins extending from or through the bottom surface of the pin protection block tool assembly are configured to register the pin protection block tool assembly in fixed lateral alignment with the holes of thevacuum drying station176. The pins serve to secure the pin protection block tool assembly to thevacuum drying station176, for use in selectively displacing one or more pins in the pin toohead assembly64. Pin protection blocktool assembly body610 also hasspacing element612 which fits into the channel machined into vacuum drying station176 (seeFIG. 7) that allows proper orientation and fitting of the pin protection block tool assembly for selectively displacing one or more pins in the pin toohead assembly64. Spacingelement612 acts as a keying feature such that the pin protection block assembly may only be inserted in one orientation, thus preventing the user from incorrectly mounting the pin protection block assembly and potentially damaging thepin tools68 or thepin tool head64. The pin protection block tool assembly embodiment may be machined from a monolithic block of a strong stable material, such as polymers, such as Delrin®, composites and metals, such as stainless steel, aluminum, which may be anodized, and the like.
• The regularly spaced cylindrical bores in the upper surface of the pin protection block tool assembly may be of sufficient diameter to allow a lower part of the taperedportion158 and slottedtip162 ofpin tool shaft142 to enter the opening, yet narrow enough for the upper tapered portion ofpin tool shaft142 to come to rest against the edge and inner wall surface of the cylindrical bores in the pin protection block tool assembly (seeFIG. 42). The pin tools resting on an upper part of the taperedportion158 of slotted pin too tip162 may prevent damage to the lower slotted portion of thepin tool68, by focusing downward pressure on the sturdier upper part of the taperedportion158 ofpin tool68. The diameter of pin protection block tool assembly holes maybe in the range of about 0.01 to about 0.1 inches, and more specifically in the range of about 0.05 to about 0.06 inches in diameter. The depth of the holes in the pin protection block tool assembly maybe greater than the length of the tapered portion of the pin tool shaft, such that when the pintool head assembly64 comes to rest on the raisededges614 of the pin protection blocktool assembly body610, thepin tools68 may be suspended above the bottom of the machined holes and the pin tools may be held in place by contact an upper part of the taperedportion158 ofpin tool shaft142 and the edges of the cylindrical bores in the pin protection block tool assembly body. The depth of the non-penetrating cylindrical bores of the pin protection block tool assembly may be in the range of about 0.1 to about 1 inch and more specifically in the range of about 0.3 to about 0.4 inches in depth.
• In some embodiments, the pin protection block tool assembly is used in conjunction with a plunger mechanism assembly, as shown inFIGS. 38A-38B and39A-39B. The plunger mechanism assembly may be useful for downward displacement of the z-axis carrier and pin tool assembly which translates to upwards axial displacement of thepin tools68, relative to pintool head64, to allow insertion of various comb insert blocks, which allow the selective displacement of one ormore pin tools68 in a pintool head assembly64. The plunger mechanism assembly includes acollar620 and plunger handle630.
• Referring now toFIGS. 38A-38B,plunger mechanism collar620 is substantially cylindrical with a central concentric stepped cylindrical bore in the material of the collar. The plunger mechanism assembly embodiment may be machined from a monolithic block of a strong stable material, such as polymers, such as Delrin®, composites and metals, such as stainless steel, aluminum, which may be anodized, and the like. Theouter diameter622 of the plunger mechanism collar may be in the range of about 0.5 to about 3 inches and more specifically in the range of about 1.5 to about 2 inches in diameter. The central concentric stepped cylindrical bore has two different diameters (624,626), which when viewed from a top down position assumes the configuration shown inFIG. 38A. The larger of the twoinner diameters624 may be machined to a depth from the top of the collar in the range of about 1.20 to about 1.45 inches, and more specifically about 1.35 to about 1.39 inches. The diameter of this larger of the inner bores may be in the range of about 0.1 to about 1 inch and more specifically in the range of about 0.4 to about 0.6 inches. The smaller of the twodiameters626 may be formed from the bottom of the larger diameter to the bottom of the collar forming an opening with a diameter in the range of about 0.1 to about 0.4 inches and more specifically in the range of about 0.23 to about 0.27 inches in diameter. Plungermechanism assembly collar620 allows functional coupling to both theplunger630 of the plunger mechanism assembly and the threadedrod118 of the z-axistranslatable carrier56, which carriespin tool assembly64. In some embodimentsplunger mechanism collar620 functions as an additional positional stop to prevent over compressing theaxial springs152 or thepin tool tips156 of the pin tools. In some embodimentsplunger mechanism collar620 functions as a guide to prevent lateral displacement of the threadedshaft118, thus minimizing the potential for damage to the z-axis translatable carrier mechanism by bending or flexing threadedshaft118, during axial displacement. In someembodiments plunger mechanism620 provides both functions.
• Referring now toFIG. 39A-39B,plunger630 of the plunger mechanism assembly may be configured to allow fitment into plungermechanism assembly collar620.Plunger630 may be in the range of about 1 to about 4 inches in height, and more specifically in the range of about 1.55 to about 1.85 inches in height.Plunger630 may be formed with amain shaft634 with a diameter in the range of about 0.3 to about 0.7 inches, and more specifically in the range of about 0.4 to about 0.6 inches in diameter. This main shaft enlarges to a cylindrical plunger handle632 with a diameter in the range of about 0.5 to about 3.0 inches and more specifically in the range of about 1.5 to about 2 inches in diameter. The base of theplunger handle shaft634 contains acylindrical bore636 with a diameter in the range of about 0.1 to about 0.4 and more specifically in the range of about 0.23 to about 0.27 inches in diameter. The depth ofcylindrical bore636 may be in the range of about 0.01 to about 0.2 inches and more specifically in the range of about 0.08 to about 0.12 inches in depth. The plunger mechanism assembly handle630 may be so configured to allow functional coupling to both the plungermechanism assembly collar620 and the threadedrod118 of the z-axistranslatable carrier56, which carriespin tool assembly64.
• FIG. 38B is a cross sectional view of the central concentric stepped cylindrical bore of theplunger mechanism collar620 which shows where theplunger handle630 and the threadedrod118 of z-axistranslatable carrier56 are brought into functional coupling in the interior ofcollar620 of the plunger mechanism assembly. In some embodiments the plunger mechanism assembly may be assembled and functionally coupled to the threadedshaft118 of z-axistranslatable carrier56 to enable upwards axial displacement of thepin tool tools68, relative to thepin tool head64, to allow insertion of various comb insert blocks, enabling the selective displacement of one ormore pin tools68 in a pintool head assembly64. As described previously, the pintool head assembly64 may be placed on a hard surface with the tips of the pin tools resting directly on the hard surface (seeFIG. 18 andFIG. 19). For some embodiments the comb insert block assembly may be used to suspend the tips of thepin tools68 over the machined cylindrical bores of the comb insert block assembly with the main shaft of thepin tools68 supporting the pin tools as the threadedcollar118 in functional contact with pintool head assembly64 may be depressed using the plunger mechanism assembly functionally coupled to the threadedshaft118 or z-axistranslatable carrier56, causing the upwards axial displacement of the pintool collar member143, relative to thepin tool head64. Use of the comb insert block assembly reduces the possibility of damage to thepin tools68 by eliminating placing the taperedportion158 and slottedtip162 ofpin tool shaft142 in direct contact with a hard surface.
• As described previously, it may be desirable to selectively alter the number of pins being used in thepinhead tool64, without physically changing out the pinhead tool. For some embodiments, a method for selectively displacing at least onepin tool68 of a pintool head assembly64 of a roboticsample transfer device10 may optionally include providing a pin protection block tool assembly and a plunger mechanism assembly in addition to the pin tool insert block. Such a method embodiment may be initiated using theuser interface26 and navigating the various programming controls ofdevice10. The commands for altering pin tool configuration are located in the “Maintenance Screen” accessed from the main menu. Once in the “Maintenance Screen”, the “Change Insert” button may be selected to initiate the method for selectively displacing at least oncepin tool68 in the pintool head assembly64.
• Upon program initiation, the pin tool head may be moved away from thevacuum drying station176 of the cleaning and drying portion ofdevice10, facilitating removal of any vacuum plates or calibration wells, and allowing positioning of the pin protection block tool assembly. The pin protectionblock tool body610 of the pin protection block tool assembly may be positioned using the aligningelement612 and pins616.Pins616 are reversibly operationally coupled with holes in thevacuum drying station176. Once the pin protection block tool assembly is in place, “Continue” may be selected using theuser interface26 anddevice10 movespin tool head64 over the pin protection block tool assembly.Pin tool head64 is automatically lowered approximately 5 mm, placing the narrowest part of the taperedportion158 ofpin tools68 within the cylindrical bores of the pin protection block tool assembly. The user may then functionally couple the plunger mechanism to the threadedshaft118, and apply downward pressure to compress thepin tool head64 the remaining distance to bring thebottom plate139 ofpin tool head64 in contact with pin protection block assembly raisededges614, as illustrated inFIG. 42.FIG. 42 illustrates the functional coupling of the comb insertion block assembly,pin tool head64, threadedshaft118, Z-axis step motor126, y-axistranslatable carrier62, z-axis translatable carrier,plunger mechanism collar620, andplunger630, all used in concert to allow selective displacement ofpin tools68 in apin tool head64. Downward pressure, as shown by the downward arrow inFIG. 42, may be applied toplunger630 through plunger handle632 which pushespin tools68 against the pin protection block tool assembly which in turn serves to push thepin tool collars143 up, relative to pintool head64, allowing the insertion of a pin tool insert comb. After the pin tool comb insert (336 or360) is inserted, the plunger mechanism assembly may be removed, which allows the pin tool head to come back to a relaxed state. “Continue” may be selected on theuser interface26, anddevice10 completes the pin tool selection program. In some embodiments,device10 may provide the user with visual prompts. In someother embodiments device10 may provide the user with auditory prompts. In yet other embodiments,device10 may provide the user with video clips showing the procedure being performed. In someembodiments device10 may provide a combination of visual prompts, auditory prompts, and video clips to aid the user in completing the pin tool displacement block insert procedure.
• As previously described and illustrated inFIGS. 20A-20D andFIGS. 21A-21D, pin tool displacement blocks may be used that enable the selective displacement of one ormore pin tools68 in a pintool head assembly64.FIGS. 35A-35D andFIGS. 36A-36D illustrate embodiments of pin tool displacement blocks.Pin tool comb336′ and360′ ofFIGS. 35A-35D and36A-36D may have features, dimensions, or materials that are the same or similar to those of336 and360 inFIGS. 20A-20D and21A-21D. Additionally the methods useable for insertion of the previously described and illustrated pin tool displacement blocks maybe the same as the methods used to insert the additional embodiments of the pin tool displacement blocks.
• Referring now toFIG. 35A-35D, in some embodiments a pin tool comb insert allowing the displacement of all but onepin tool68 is provided. This embodiment of a pin tool displacement block (pin tool comb insert) has raisededges339 which act as an orientation keying feature which prevents the pin tool displacement block from being inserted incorrectly. That is, raisededges339 may confer a unidirectional orientation to the pin tool displacement block. Pintool comb insert336′ may also be configured to have a chamfered forward upper edge to allow the user easier insertion into thepin tool head64.
• Referring now toFIG. 36A-36D, in some embodiments a pin tool comb insert allowing the displacement of all but sixpin tools68 is provided. This embodiment of a pin tool displacement block (pin tool comb insert) has raisededges363 which act as an orientation keying feature which prevents the pin tool displacement block from being inserted incorrectly. That is, raisededges363 may confer a unidirectional orientation to the pin tool displacement block. Pintool comb insert360′ may also be configured to have a chamfered forward upper edge to allow the user easier insertion into thepin tool head64.
• While pin tool displacement blocks have been described herein for applications that selectively displace all but one or all but 6 pin tools, pin tool numbers other than 1, 6 or 24 maybe used. The number and pattern of pin tools selectively displaced and thereby inactivated may be 1, 2, 3, 4, 5, 6, 7 . . . up to 23, when using a 24 pin tool head. This may be achieved by an alternative configuration of pin tool displacement blocks, and the disclosure herein is not meant to limit the embodiments contemplated to 1, 6, or 24active pin tools68.
• In some embodiments where the number of pin tools being actively used has been selectively altered, a dry station plate assembly may be provided that may be configured to correspond to the pattern of the pin tools selected to be active. The dry station plate assembly allows for selective use of thevacuum drying station176vertical holes178 as drying orifices. This allows the user to direct the vacuum to only thosepin tools68 actively being used in any particular application. The dry station plate assembly may be machined from a monolithic block of a strong stable material, such as polymers, such as Delrin®, composites and metals, such as stainless steel, aluminum, which may be anodized, and the like. The dry station plate assembly may also be cut or machined from Lucite®, polycarbonates, acrylic and the like. Dry station plate assemblies for any number of openings corresponding to a desired number of selectively activatedpin tools68 are contemplated herein as well as the embodiments described below. In general the dry station plate assembly (640,650) may be substantially rectangular in shape, the size and shape corresponding with the size and shape ofpin tool head64. The height of the dry station plate assembly body (642,652) may be in the range of about 0.01 to about 1 inch, more specifically in the range of about 0.1 to about 1 inch and most specifically be in the range of about 0.2 to about 0.5 inches in height. The dry station plate assemblies may have at least 3 holes machined through the body to allow insertion of seating pin dowels, the holes being of sufficient diameter to allow the use of pin dowels (644,654) that fit within the nominal diameter of the vacuumdry station176vertical holes178, and allow functional coupling of the dry station plate assembly to the vacuum drying station. The use of dry station plate assemblies may reduce the waste of vacuum in the vacuum holding tank by channeling vacuum to only theopenings178 that correspond toactive pin tools68, and blocking off all other openings through which vacuum might be wasted. Additionally, if the unused holes are not blocked using the dry station plate assemblies, all vacuum flow will be through the unblocked holes and minimal flow will be through the holes containing pin tools. This may cause the pins to not be sufficiently dried, which in turn may lead to cross contamination of samples.
• Referring now toFIGS. 40A-40C, in some embodiments a vacuum dryingstation plate assembly640 which blocks all but onevertical hole178 in thevacuum drying station176 is provided. Vacuum dryingstation plate assembly640 includesplate body642, pin dowels644 andpin tool opening646. The embodiment of drystation plate assembly640 may be used in conjunction with the pin tool insert comb that selectively displaces or deactivates all but onepin tool68.
• Referring now toFIGS. 41A-41C, in some embodiments a vacuum dryingstation plate assembly650 which blocks all but sixvertical holes178 in thevacuum drying station176 is provided. Vacuum dryingstation plate assembly650 includesplate body652, pin dowels654 andpin tool openings656. The embodiment of drystation plate assembly650 may be used in conjunction with the pin tool insert comb that selectively displaces or deactivates all but sixpin tools68.
• In general, a wide variety of techniques can be implemented consistent with the principles the invention and no attempt is made herein to describe all possible techniques. With regard to the above detailed description, like reference numerals used therein refer to like elements that may have the same or similar dimensions, materials and configurations. While particular forms of embodiments have been illustrated and described, various modifications can be made without departing from the spirit and scope of the embodiments of the invention. Accordingly, it is not intended that the invention be limited by the forgoing detailed description.

Claims (54)

1. A robotic sample transfer device, comprising:

a substantially horizontal work surface including a plurality of functional elements configured for small sample processing;

a three axis robotic positioning assembly having a fixed mount portion secured in fixed relation with the work surface, a translatable carrier configured to be translatable in three axes with respect to the fixed mount portion and working surface and having a stepper motor corresponding to each axis and at least one linear encoder assembly configured to generate position data for at least one axis;

at least one pin tool coupled to the translatable carrier; and

a controller in communication with the stepper motors of each of the three axes of the three axis robotic positioning assembly and the at least one linear encoder assembly.

2. The sample transfer device ofclaim 1 further comprising a housing disposed about the work surface, three axis robotic positioning assembly and controller.

3. The sample transfer device ofclaim 2 further comprising a graphic user interface on an exterior of the housing and operatively coupled to the controller for providing user input to the controller.

4. The sample transfer device ofclaim 1 wherein the three axes of the three axis robotic positioning assembly are substantially orthogonal to each other.

5. The sample transfer device ofclaim 1 wherein the three axis robotic positioning assembly further comprises a bar code reader.

6. The sample transfer device ofclaim 1 wherein the three axis robotic positioning assembly further comprises an imaging camera translatable in at least two axes and operatively coupled to an image processor.

7. The sample transfer device ofclaim 1 wherein the controller comprises at least one processor which is disposed within the housing at a level which is above the level of the work surface.

8. A robotic sample transfer device, comprising:

a housing;

a substantially horizontal work surface disposed within the housing;

a three axis robotic positioning assembly disposed within the housing having a fixed mount portion secured in fixed relation with the work surface and a translatable carrier member translatable in three different axes with respect to the fixed mount portion and work surface;

at least one pin tool coupled to the translatable carrier having a shaft and a sample reservoir in a distal end of the shaft;

a plurality of functional elements disposed on the work surface having a nominal upper surface at substantially the same height; and

a controller operatively coupled to the three axis robotic positioning assembly.

9. The sample transfer system ofclaim 8 further comprising an imaging camera movable in at least the x-y plane substantially parallel to the work surface and having a shallow range of focus and focused at the nominal upper surface of the functional elements.

10. The sample transfer device ofclaim 8 wherein the functional elements comprise a vacuum drying station, a fluid rinse station, a microtiter plate having an array or regularly space sample supply wells and a chip having an array of regularly spaced sample deposition sites.

11. The sample transfer device ofclaim 8 further comprising a pin tool head assembly having an array of regularly spaced pin tools secured to the translatable carrier and wherein the vacuum drying station includes a plurality of regularly spaced vacuum drying ports corresponding to the spacing of the pin tools of the pin tool head assembly, the fluid rinse station includes individual rinse tubes corresponding to each of the pin tools of the array of regularly spaced pin tools of the pin tool head assembly.

12. The sample transfer device ofclaim 10 further comprising a self-leveling gravity fed ultrasonic cleaning well and an ultrasonic cleaning fluid reservoir having a supply port configured to couple into fluid communication with the ultrasonic cleaning well when coupled to an inlet port of the ultrasonic cleaning well and be substantially sealed when the removed from the inlet port of the ultrasonic cleaning well.

13. The sample transfer device ofclaim 10 wherein the ultrasonic cleaning fluid reservoir further comprises a ball valve which is configured to seal the supply port when the fluid reservoir is removed from the inlet port of the ultrasonic cleaning well.

14. The sample transfer device ofclaim 8 wherein the controller comprises at least one processor which is disposed within the housing at a level which is above the level of the work surface.

15. An integrated robotic sample transfer device, comprising:

a housing;

a three axis robotic positioning assembly disposed within the housing having a fixed mount portion, a translatable carrier translatable in three axes with respect to the fixed mount portion and working surface and having a stepper motor corresponding to each axis and at least one linear encoder assembly for generating position data for at least one axis of the translatable carrier;

a pin tool head assembly secured to the translatable carrier member having an array of regularly spaced pin tools with sample reservoirs disposed in the distal ends thereof and configured for axial displacement relative to a pin head body secured to the translatable carrier of the three axis robotic positioning assembly;

a substantially horizontal work surface disposed within the housing and secured in fixed relation to the fixed mount portion of the three axis positioning assembly and having a fluid rinse station, a vacuum drying station including a plurality of regularly spaced vacuum drying ports corresponding to the regular spacing of the array of pin tools, a self-leveling ultrasonic cleaning well and a microtiter plate mount block configured to releasably secure a sample well;

a controller including a processor disposed within the housing at a position which is above the level of the work surface;

a rinse fluid supply tank in fluid communication with the fluid rinse station and disposed within the housing;

a waste fluid tank in fluid communication with an overflow basin of the fluid rinse station and disposed within the housing;

a vacuum source in fluid communication with the vacuum drying station; and

an ultrasonic cleaning fluid reservoir in fluid communication with a self-leveling ultrasonic cleaning well.

16. The sample transfer device ofclaim 15 wherein in the ultrasonic cleaning fluid reservoir comprises a gravity feed reservoir having a supply port configured to couple into fluid communication with the ultrasonic cleaning well when coupled to an inlet port of the ultrasonic cleaning well and be substantially sealed when the removed from the inlet port of the ultrasonic cleaning well.

17. The sample transfer device ofclaim 15 further comprising a rinse fluid supply tank fluid level indicator.

18. The sample transfer device ofclaim 15 further comprising a rinse fluid supply pump disposed within the housing, in fluid communication with the rinse fluid supply tank and fluid rinse station and configured to pump rinse fluid from the rinse fluid supply tank to the fluid rinse station.

19. The sample transfer device ofclaim 15 further comprising a waste fluid tank fluid level indicator.

20. The sample transfer device ofclaim 15 further comprising a vacuum drying supply tank in fluid communication with the vacuum drying ports of the vacuum drying station.

21. The sample transfer device ofclaim 20 further comprising a vacuum pump in fluid communication with the vacuum drying supply tank.

22. The sample transfer device ofclaim 15 wherein a nominal upper surface of the fluid rinse station, nominal upper surface of the vacuum drying station, nominal upper surface of the ultrasonic cleaning well, nominal upper surface of a chip disposed in the chip mount block and microtiter plate/sample well mounted in the sample well mount blocks all being at substantially the same z-axis level.

23. The sample transfer device ofclaim 15 further comprising an imaging camera and image processing controller.

24. The sample transfer device ofclaim 15 further comprising a bar code reader head and bar code reader processor in communication with the bar code reading head and controller.

25. The sample transfer device ofclaim 15 wherein the fluid rinse station comprises an array of regularly spaced individual rinse tubes having a regular spacing corresponding to the regular spacing of the pin tools of the pin tool head assembly.

26. The sample transfer device ofclaim 15 further comprising a door on the housing covering an opening to a processing chamber disposed within the housing.

27. The sample transfer device ofclaim 15 wherein the controller comprises an assembly of electronics and logic circuits which are disposed within the housing at a position which is above the level of the work surface.

28. The sample transfer device ofclaim 15 further comprising a universal power supply in communication with the controller that produces a constant output voltage with varied input voltage to allow device to operate in varying countries.

29. The sample transfer device ofclaim 15 wherein the entire dry weight of the device is less than about 150 pounds.

30. The sample transfer device ofclaim 15 further comprising a graphic user interface disposed on an outer surface of the housing and in communication with the controller.

31. The sample transfer device ofclaim 15 further comprising a humidity sensor disposed within the processing chamber of the device and in communication with the controller which is configured to sense the humidity within the processing chamber.

32. The sample transfer device ofclaim 31 further comprising closed loop feedback from the humidity sensor with the controller in conjunction with a humidity control device for maintaining a substantially constant humidity within the processing chamber.

33. The sample transfer device ofclaim 15 further comprising a temperature sensor disposed within the processing chamber of the sample transfer device in communication with the controller which is configured to sense the temperature within the processing chamber.

34. The sample transfer device ofclaim 33 further comprising closed loop feedback from the temperature sensor with the controller and a temperature control device for maintaining a substantially constant temperature within the processing chamber.

35. A method of registering the position of a pin tool head assembly of a robotic sample transfer device relative to sample deposition sites on a chip, comprising:

providing a robotic sample transfer device having a work surface with a plurality of functional elements with a nominal upper surface at substantially the same level and a three axis positioning system with a camera and pin tool head assembly secured to a translatable carrier thereof;

imaging the nominal upper surfaces of functional elements disposed on work surface with the camera;

processing the image data of the nominal upper surfaces of the functional elements from the camera to determine the approximate position of the pin tool head assembly relative to the functional elements;

using the approximate position data to move the camera to a first chip having an array of regularly spaced sample deposition sites and an array of regularly spaced fiducial marks disposed between the sample deposition sites;

imaging fiducial marks on the first chip;

processing the image data of fiducial marks on the first chip;

obtaining feedback regarding a position of the pin tool head assembly from linear encoders of three axes of a three axis robotic positioning system;

comparing encoder feedback with image processing feedback and look up table data to determine the precise position of the pin tools of the pin tool head assembly with respect to the sample deposition sites on the first chip.

36. The method ofclaim 35 further comprising repeating the process for multiple chips.

37. The method ofclaim 35 wherein the precise position of the pin tools of the pin tool head assembly with respect to the sample deposition sites on the first chip is determined to within about 1 micron to about 10 microns.

38. A method of dispensing calibration material onto a chip, comprising:

providing a chip having a first array of regularly spaced sample deposition sites disposed on a substantially flat working surface thereof and at least one sample deposition site for receiving calibration material which is also disposed on the flat working surface of the chip and which is off pitch with respect to the regular spacing of the first array of regularly spaced sample deposition sites of the chip;

providing a robotic sample transfer device having a pin tool head assembly with an array of regularly spaced pin tools having distal ends which are substantially coplanar in a relaxed state and which have a regular spacing which is the same as the regular spacing of the first array of sample deposition sites or an integer multiple thereof and configured to align with the array of regularly spaced sample deposition sites of the chip or a subset thereof;

loading sample reservoirs of the array of regularly spaced pin tools of the robotic sample transfer device with calibration material;

dispensing calibration material from the pin tools of the robotic sample transfer device to the at least one sample deposition site for receiving calibration material such that the pin tools which are not aligned with sample deposition sites for receiving calibration material are off pitch with respect to the first array of regularly spaced sample deposition sites of the chip and do not contact any of the regularly spaced sample deposition sites of the first array.

39. The method ofclaim 38 wherein the chip comprises a second array of regularly spaced sample deposition sites for receiving calibration material sample which are off pitch with respect to the first array of regularly spaced sample deposition sites and further comprising dispensing calibration material from pin tools of the robotic sample transfer device to the second array of sample deposition sites for receiving calibration material such that the pin tools which are not aligned with sample deposition sites for receiving calibration material of the second array are off pitch with respect to the first array of regularly spaced sample deposition sites of the chip and do not contact any of the regularly spaced sample deposition sites of the first array.

40. The method ofclaim 38 wherein the first array of regularly spaced sample deposition sites comprises an array of regularly spaced mass spectrometry sample deposition sites.

41. A pin tool displacement block for selectively displacing at least one pin tool of a pin tool head assembly of a robotic sample transfer device in an axial direction, comprising:

a block body having a bottom surface and a plurality of parallel slots formed into the block body portion substantially perpendicular to the bottom surface with a predetermined regular spacing configured to correspond to regular spacing of pin tools of a pin tool head assembly and having a transverse dimension sized to allow easy movement of a width of a nominal shaft of the pin tools in the slots but restrictive of movement of an enlarged portion of the shaft of the pin tools; and

at least one relieved portion in a slot which has a transverse dimension sized to allow easy downward movement of the enlarged portion of a pin tool shaft which is greater than the transverse dimension of the slot and which extends from a top surface of the block body towards the bottom surface.

42. The pin tool displacement block ofclaim 41 wherein the at least one relieved portion terminates at a stop surface which is spaced from the bottom surface.

43. The pin tool displacement block ofclaim 41 wherein the at least one relieved portion extends completely from the top surface to the bottom surface and is configured to allow the enlarged portion of a pin tool shaft to pass completely through the block body.

44. The pin tool displacement block ofclaim 41 wherein the relieved portion is configured to mechanically capture the enlarged portion of a pin tool disposed therein in a lateral direction.

45. The pin tool displacement block ofclaim 41 wherein the enlarged portion of a shaft of a pin tool comprises a collar member and the stop surface of the at least one relieved portion is configured to prevent axial movement of the collar member and mechanically capture a collar disposed therein member to prevent lateral displacement of the block body when the block is deployed in a pin tool head assembly.

46. The pin tool displacement block ofclaim 41 wherein the top surface and bottom surface of the block body are substantially flat and substantially parallel to each other.

47. The pin tool displacement block ofclaim 41 wherein the block body comprises an inert material.

48. The pin tool displacement block ofclaim 46 wherein the inert material comprises Delrin.

49. The pin tool displacement block ofclaim 41 further comprising a handle member secured to the block body.

50. The pin tool displacement block ofclaim 41 having a reversible configuration wherein when the block is oriented in a first direction a first pin or set of pins is active and when oriented a second way a second pin or set of pins is active which is different from the first set.

51. The pin tool displacement block ofclaim 50 wherein the first direction is about 180 degrees from the second direction.

52. A method for selectively displacing at least one pin tool of a pin tool head assembly of a robotic sample transfer device, comprising:

providing a pin tool displacement block including a block body having a bottom surface and a plurality of parallel slots formed into the block body portion substantially perpendicular to the bottom surface with a predetermined regular spacing configured to correspond to regular spacing of pin tools of a pin tool head assembly and having a transverse dimension sized to allow easy movement of a width of a nominal shaft of the pin tools in the slots but restrictive of movement of an enlarged portion of the shaft of the pin tools, and at least one relieved portion in a slot which has a transverse dimension sized to allow easy downward movement of the enlarged portion of a pin tool shaft which is greater than the transverse dimension of the slot and which extends from a top surface of the block body towards the bottom surface;

displacing an array of pin tools of a pin tool head assembly by depressing the pin tools against a flat surface;

deploying the pin tool displacement block into the pin tool head assembly such that the parallel slots of the pin tool displacement block slide over rows of the array of pin tools of the pin tool head assembly; and

allowing the pin tools to return to a relaxed state by retracting the pin tool head assembly from the flat surface with at least one of the pin tools axially displaced in the relaxed state.

53. A method of dispensing calibration material onto a chip, comprising:

providing a chip having an array of regularly spaced sample deposition sites disposed on a substantially flat working surface thereof and at least one sample deposition site for receiving calibration material which is also disposed on the flat working surface of the chip;

providing a robotic sample transfer device having a pin tool head assembly with an array of regularly spaced pin tools having distal ends which are substantially coplanar in a relaxed state and which have a regular spacing which is the same as the regular spacing of the first array of sample deposition sites or an integer multiple thereof and configured to align with the array of regularly spaced sample deposition sites of the chip or a subset thereof;

axially displacing at least one of the pin tools of the pin tool head assembly with a pin tool displacement block;

loading a sample reservoir of at least one un-displaced pin tool of the robotic sample transfer device with calibration material;

dispensing calibration material from the at least one un-displaced pin tool of the robotic sample transfer device to the at least one sample deposition site for receiving calibration material such that the pin tools which are displaced by the pin tool displacement block do not contact the chip.

54. The method ofclaim 53 wherein the array of regularly spaced sample deposition sites comprises an array of regularly spaced mass spectrometry sample deposition sites.

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