US20040166022A1 - Apparatus and method for transporting sample well trays - Google Patents

Abstract

An apparatus for transporting sample well trays with respect to a heating device is provided. The apparatus includes a sample well tray holder, a rotational actuator, and a biasing mechanism. The sample well tray holder includes a plate in which a sample well tray may be positioned. The sample well tray holder is configured to rotate about a first rotational axis. The rotational actuator is configured to rotate the sample well tray holder about the first rotational axis. The biasing mechanism is configured to urge the sample well tray holder in a generally upward direction along the first rotational axis.

Description

BACKGROUND OF THE INVENTION
• 1. Field of the Invention[0001]
• The present invention relates to an apparatus and method for transporting sample well trays. In certain embodiments, the apparatus places sample well trays into a heating device and removes the sample well trays therefrom.[0002]
• 2. Description of the Related Art[0003]
• Biological testing has become an important tool in detecting and monitoring diseases. In the biological testing field, thermal cycling is often utilized in order to amplify nucleic acids by, for example, performing polymerase chain reactions (PCR) and other reactions.[0004]
• It is desirable to increase the throughput of such biological testing. One method for increasing throughput is to provide real-time detection capability during thermal cycling. Providing real-time detection increases the efficiency of the biological testing because the samples can be tested while in the thermal cycling device, therefore not requiring removal of the sample well tray prior to testing the samples. An additional method of increasing throughput of biological testing is to automatically load sample well trays into the heating device, perform a heating operation such as thermal cycling, and then automatically remove the sample well tray using a robotic mechanism. However, existing robotic mechanisms are not particularly suited for thermal cycling devices with real-time detection units. In particular, existing robotic mechanisms are not particularly configured for accessing the thermal cycling device without interfering with the detection units.[0005]
• It is desirable to provide a sample well tray manipulating apparatus and method that is compatible for use with thermal cycling devices having real-time detection units in order to increase throughput.[0006]
SUMMARY OF THE INVENTION
• The advantages and purposes of the invention will be set forth in part in the description which follows, and in part will be apparent from the description, or may be appreciated by practice of the invention. The advantages and purposes of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.[0007]
• In one aspect, the invention includes an apparatus for transporting sample well trays with respect to a heating device. In certain embodiments, the apparatus includes a sample well tray holder, a rotational actuator, and a biasing mechanism. The sample well tray holder includes a plate in which a sample well tray may be positioned. The sample well tray holder is configured to rotate about a first rotational axis. The rotational actuator is configured to rotate the sample well tray holder about the first rotational axis. The biasing mechanism is configured to urge the sample well tray holder in a generally upward direction along the first rotational axis.[0008]
• In another aspect, the invention includes a robotic manipulator for transporting sample well trays between at least two positions. The robotic manipulator includes a robotic arm, a rotational mechanism, and a biasing mechanism. The robotic arm includes a sample well tray holder configured to support a sample well tray therein. The sample well tray holder includes a recess for the sample well tray. The rotational mechanism is configured to impart rotational motion on the robotic arm, and includes a motor. The biasing mechanism is configured to provide force on the sample well tray holder in a direction away from an adjacent sample block.[0009]
• In a further aspect, the invention includes a system for manipulating sample well trays. The system includes a robot configured to transport a sample well tray to a first location, a loading mechanism, and a heating device. The loading mechanism is configured to take a sample well tray from the first location, place the sample well tray into the heating device, for example, a thermal cycler at a second location and then later remove the sample well tray from the heating device and return the sample well tray to the first location. The loading mechanism includes a sample well tray holder in which a sample well tray may be positioned therein, a rotational actuator configured to rotate the sample well tray holder, and a biasing member configured to urge the sample well tray and sample well tray holder in a direction away from a sample block. The heating device includes an opening for receiving the sample well tray therein.[0010]
• In yet another aspect, the invention includes a method of manipulating sample well trays. The method includes the step of placing the sample well tray into a sample well tray holder of a first robot mechanism located at a first position. The method further includes the step of rotating the sample well tray holder of the first robot mechanism about a rotational axis in a first rotational direction to insert the sample well tray holder into a heating device at a second position. The sample well tray holder is lowered in a direction toward a sample block of the heating device so that the sample well tray engages the sample block. After undergoing thermal cycling or other operations, the sample well tray disengages from the sample block so that the sample well tray does not directly contact the sample block. The method further includes lifting the sample well tray holder and sample well tray from the heating device by a biasing mechanism so that the sample well tray is capable of rotation away from the sample block and heating device without interference, and then rotating the sample well tray holder of the first robot mechanism in a second rotational direction toward the first position to remove the sample well tray holder from the heating device. The sample well tray may then be removed from the sample well tray holder. The method further includes, prior to placing the sample well tray in a sample well tray holder, the steps of picking up a sample well tray with a second robot mechanism, such as a rotational robot, and rotating the sample well tray to place the sample well tray in the first position.[0011]
• It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.[0012]
BRIEF DESCRIPTION OF THE DRAWINGS
• The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention. In the drawings, FIG. 1 shows a perspective view of a sample well tray handling apparatus according to the invention;[0013]
• FIG. 2 shows a top view of the sample well tray handling apparatus of FIG. 1;[0014]
• FIG. 3 shows a sectional view of the sample well tray handling apparatus along line Ill-Ill of FIG. 2;[0015]
• FIG. 4 shows a perspective view of a sample well tray holder of the sample well tray handling apparatus of FIG. 1;[0016]
• FIG. 5 shows a top view of a system including the sample well tray handling apparatus of FIG. 1 in addition to a heating device and a robot, the sample well tray handling apparatus in a first position for having a sample well tray transferred from the robot;[0017]
• FIG. 6 shows a top view of the system of FIG. 5, the sample well tray handling apparatus rotated relative to the first position of FIG. 5 so that the sample well tray is located in the heating device;[0018]
• FIG. 7 shows a side view of an urging mechanism positioned on a bottom surface of the sample well tray holder of FIG. 1;[0019]
• FIG. 8 is a bottom view of the urging mechanism of FIG. 7;[0020]
• FIG. 9A is a schematic sectional view illustrating a cover and sample well tray in an open position; and[0021]
• FIG. 9B is a schematic sectional view illustrating the cover and sample well tray of FIG. 9A in a closed position.[0022]
DESCRIPTION OF THE PREFERRED EMBODIMENTS
• Reference will now be made in detail to the present preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.[0023]
• In accordance with the present invention, an apparatus for transporting sample well trays with respect to a heating device is provided. In certain embodiments of the present invention, the apparatus includes a sample well tray holder, a rotational actuator configured to rotate the sample well tray holder, and a biasing mechanism configured to urge the sample well tray holder in a generally upward direction. In certain embodiments, the invention is directed toward a system which additionally includes a robot device for transporting a sample well tray to the sample well tray holder, and a heating device with an opening for receiving the sample well tray therein. As embodied herein and shown in FIGS.[0024]1-9, thehandling apparatus10 for transporting sample well trays includes a samplewell tray holder12, arotational actuator14, and abiasing mechanism16.
• [0025]Handling apparatus10 may be used to load and unload sample well trays into a wide variety of types of heating devices. In certain embodiments, the heating device may be a PE Biosystems 5700 and 7700 Detection Instrument, as well as a variety of other types of instruments. One example of a suitable heating device is described in U.S. Pat. No. 5,928,907 to Woudenberg et al., which is assigned to the assignee of the present invention, the contents of which are hereby incorporated by reference herein for any purpose. Theheating device100 shown in FIGS.5-6 is preferably configured for use with 96-well and 384-well sample trays, in addition to microcard sample trays. One example of a 384-well sample tray is illustrated in FIGS. 9A and 9B as asample well tray208 with a plurality ofsample wells210. Examples of sample well trays suitable for use in the apparatus of the present invention are described in WO00/25922 to Moring et al., which is assigned to the assignee of the present invention, the contents of which are hereby incorporated by reference herein for any purpose. Examples of microcard sample trays suitable for use in the apparatus of the present invention are described in WO97/36681 to Woudenberg et al., which is assigned to the assignee of the present invention, the contents of which are hereby incorporated by reference herein for any purpose. Sample well trays having any number of sample wells and sample well sizes may also be used. In the example shown in the figures, the volume of the sample wells may vary anywhere from 0.01 μl to thousands of microliters (μl), with a volume between 10 to 500 μl being typical. The detection instrument may be used for a variety of applications, such as, but not limited to, fluorescent PCR-based detection.
• As embodied herein and shown in FIGS. 5, 6,[0026]9A, and9B, theheating device100 includes asample block102 or other type of surface for receiving a sample well tray, such assample well tray208, from thehandling apparatus10. As shown in FIGS. 5, 6,9A, and9B,sample block102 includes a plurality ofopenings104 in a top portion thereof for receivingsample wells210 of the sample well tray. Each of thesample block openings104 may have a conical shape which is sized to fit with a sample well of a sample well tray. The sample block openings may be other shapes such as cylindrical or hemispherical, depending on the shape of the mating sample wells. Sample blocks are well known in the art. The sample block will typically have openings of a number matching the number of sample wells of the sample well tray. The sample block shown in FIG. 5 has384 openings arranged in a 16×24 array, however, any number of openings may be provided. Other common configurations include 96 and 60-well sample blocks, although the present invention is suitable for sample well trays having anywhere from one sample well to several thousand sample wells. The sample block is preferably constructed of a heat-conducting material such as gold-plated silver and aluminum, although other common materials may also be it suitable.
• Likewise, although the description discusses trays with sample wells, the present invention is suitable for use with sample trays that do not include wells. These trays may have a flat surface on which a sample of biological material is placed. The flat surface on which the sample is placed may be similar to a microscope slide for a sample. In this type of sample tray, a liquid may be dropped onto the tray at a plurality of positions, and then a film or cover positioned on the top surface of the tray over the samples. Alternately, a sample tray may include a porous material such a frit on the top surface, instead of sample wells, for holding samples of biological material. Therefore, although the description refers to sample well trays throughout, it should be understood that the present invention is also suitable for sample trays that do not have sample wells.[0027]
• The[0028]heating device100 further includes a cover which lowers and applies pressure to the top of the sample well tray after the sample well tray is inserted into the heating device. In an exemplary embodiment shown in FIGS. 9A and 9B, aheated cover150 includes acentral cover portion152 and anouter cover portion154. In the embodiment shown in FIGS. 9A and 9B, thecentral cover portion152 has a plurality ofopenings156 for the optical detection of reactions that occur in the sample wells of the sample well tray. The present invention is also suitable for use in a thermal cycler or other heating apparatus without optical detection capabilities. In one embodiment, theouter cover portion154 is movable in an upward and downward direction relative to thecentral cover portion152. The cover may be any of a variety of types. For example, in certain embodiments, the cover is physically actuated to and from a closed position by a motor. In other embodiments, the cover is slid into and out of a closed position by manual physical application. The cover may also include at least one heated platen (not shown) for pressing against the top surface of the sample well trays in order to reduce condensation from occurring on the sample well trays.
• The[0029]handling apparatus10 may receive the-sample well trays either-manually or automatically. In certain embodiments, thehandling apparatus10 receives sample well trays from a robot, such asrobot200 shown in FIGS. 5 and 6. Therobot200 may be any type of robot, such as a rotational robot that rotates about asingle axis202. One example of a rotational robot that is suitable for use with thehandling apparatus10 is a Zymark™ Twister robot. In certain embodiments, therobot200 includes anarm204 and arobot hand206 for gripping asample well tray208. The rotational robot picks up a singlesample well tray208 and then rotates about therotational axis202 to bring the sample well tray to the position shown in FIG. 5. In the position shown in FIG. 5, thesample well tray208 may be transferred to handlingapparatus10. Thehandling apparatus10 then inserts the sample well tray intosample block102 ofheating device100 as shown in FIG. 6 and the samples in the sample well tray are thermally cycled. The handling apparatus removes the sample well tray from the heating device and rotates back to FIG. 5 so that the sample well tray may be picked up from the handling apparatus by therobot200. The heating device may be any type known in the art. The specific heating devices discussed in relation to the present invention are described for purposes of illustration only.
• The present invention is directed at the handling apparatus, as well as the overall system. In accordance with the present invention, the[0030]handling apparatus10 includes a samplewell tray holder12 for supporting a sample well tray therein. As embodied herein and shown in FIGS.1-4, the samplewell tray holder12 is in the shape of a flat plate with amain body portion20 and anarm portion22. In the example shown in the figures, themain body portion20 is in a rectangular shape. Themain body portion20 defines a rectangular opening orrecess24 sized and shaped for receiving a sample well tray. The sample well tray holder is preferably made out of a material with poor heat conduction characteristics and a low thermal mass. In certain embodiments, the material selected for the sample well tray holder is a polycarbonate. Other suitable materials are also acceptable, including a hybrid metal/plastic sample tray holder.
• The[0031]rectangular opening24 of the sample well tray holder is configured so that thesample well tray208 may rest on the sample well tray holder. Therectangular opening24 is defined by a taperedwall26 which tapers downward from thetop surface28 of the samplewell tray holder12. The taperedwall26 tapers until it meets afloor portion30 which extends from the tapered wall. Thefloor portion30 generally extends along a bottom surface of the sample well tray holder. Thefloor portion30 defines a rectangular opening that is smaller than the size of a sample well tray. Therefore, when a sample well tray is placed in therectangular opening24, abottom surface212 ofouter side walls214 of thesample well tray208 rest on a top surface of thefloor portion30, as best illustrated in FIG. 9A. The provision of the taperedwall26 permits thesample well tray208 to center itself in therectangular opening24 as the sample well tray is placed in the rectangular opening.
• In certain embodiments, the[0032]arm portion22 of the samplewell tray holder12 projects on the same plane as themain body portion20. In the embodiment shown in FIGS.1-9, the arm portion includes a plurality offasteners32 such as bolts for fastening the samplewell tray holder12 to anextension arm34 which is connected to therotational actuator14 andbiasing mechanism16. As shown in FIG. 3, theextension arm34 is a flat plate with a thinlower portion36 on which thearm portion22 of the sample well tray holder may be mounted. Thefasteners32 pass through thearm portion22 of the samplewell tray holder12 into a threadedconnector38 on the thinlower portion36 of the extension arm. Thearm portion22 of the samplewell tray holder12 and theextension arm34 are preferably configured so that there is minimal movement between thearm portion22 andextension arm34. In certain embodiments, the ends of thearm portion22 andextension arm34 are flat surfaces that abut against each other as shown in FIG. 2. Additionally, in certain embodiments, the sample well tray holder may include one or more holes to engage with pins in the thinlower portion36 ofextension arm34. In one embodiment, illustrated for example in FIGS. 1 and 2, the sample well tray holder includes a locatinghole29 and a locatingslot31 for engaging with pins projecting from the top surface of the thinlower portion36 ofextension arm34. Alternately, thearm portion22 andextension arm34 could be an integral piece, thereby reducing the number of parts for the apparatus.
• In other embodiments, the connection between the[0033]arm portion22 andextension arm34 may be configured so that thearm portion22 is adjustable on theextension arm34. In such a configurations, the arm portion or extension arm might include two parallel slots for a connector so that the arm distance may be adjusted.
• The sample[0034]well tray holder12 may further include an urging mechanism for urging the sample well tray away from the sample block upon opening of the cover. As embodied herein and shown in FIG. 3, the urging mechanism may include any suitable type of mechanism such as a spring device for pressing upward on the sample holder and sample well tray when the cover is opened. In the example shown1-8, the urging mechanism includes a plurality ofsprings40 positioned on thebottom surface42 of the samplewell tray holder12. As shown in FIGS. 3, 7, and8, thesprings40, in one example, may be a strip of folded springs commonly referred to as RF gaskets, positioned in parallel relationship to each other. Thebase44 of each spring may be attached to thebottom surface42 of the samplewell tray holder12 by adhesive46 or any other suitable attachment method. Thespring portion48 of thespring40 includes a curved member that imparts an upward force on the samplewell tray holder12 when it is compressed.
• Although the urging mechanism is shown as being an RF gasket in the figures, any other type of suitable urging mechanism may alternately be used. Examples of other types of urging mechanism are described in co-pending U.S. application Ser. No. 09/496,408, filed Feb. 2, 2000, assigned to the assignee of the present application, the contents of which are hereby incorporated by reference herein. The urging mechanism of the present invention may be made out of any of a variety of force imparting devices such as one or more coil springs, leaf springs, hydraulic dampeners, elastomeric springs, or other conventional spring devices. The urging mechanism is typically designed to provide sufficient force to overcome the sticking force between the sample well tray and the sample block upon opening of the cover of the heating device. Sticking may result because of deformation of the sample well tray during heating. In one example, the urging mechanism imparts an upward force on the sample well tray holder of approximately 15-20 lbs. The amount of force required depends on the specific application. The urging mechanism should preferably loosen the sample well tray from the sample block so that the sample well tray can be easily removed either robotically or manually.[0035]
• In certain embodiments, particularly those with sample wells having relatively small volumes, it may be desirable to place a thin compliant cover (not shown) between[0036]central cover portion152 and the top ofsample well tray208. An example of a suitable compliant cover is disclosed in the specification and figures (FIGS.11-13) of co-pending U.S. application Ser. No. 09/499,408, the contents of which are incorporated by reference herein. The compliant cover typically includes detection holes aligned with each of thesample wells210 of the sample well tray. The compliant cover may assist in evenly distributing the downward force imparted by the cover onto the sample well tray. In embodiments with a compliant cover, it may be helpful to further provide a boss or rib (not shown) on thetop surface28 of themain body portion20 of samplewell tray holder12 for engaging with the bottom surface ofouter cover portion154 when theouter cover portion154 is lowered relative to thecentral cover portion152. An example of a suitable boss or rib to be used in conjunction with the compliant cover is disclosed in the specification and figures (FIGS.11-13) of co-pending U.S. application Ser. No. 09/499,408, the contents of which are incorporated by reference herein The downward movement of theouter cover portion154 results in theouter cover portion154 pressing downward on themain body portion20 ofsample tray holder12 so that the upper surface of thefloor portion30 of the sample tray holder will become spaced from thebottom surface212 of thesample well tray208. This spacing between the sample well tray and the surface of the floor portion of the sample tray holder isolates thesample well tray208 from the spring force generated by thesprings40 of the urging mechanism. In certain embodiments, this configuration assists in eliminating the upward force of thesprings40 from the sample tray in order to reduce the amount of volume loss due to bending of the sample tray.
• In certain embodiments of the present invention, the[0037]handling apparatus10 removes the sample well tray robotically after the urging mechanism has loosened the sample well tray from the sample block. Alternately, in certain embodiments, urging mechanisms of the type described above could be attached to the sample block instead of the bottom surface of the sample well tray holder. In other embodiments, the urging mechanism may be entirely eliminated because the biasing mechanism16 (to be described in greater detail later) will provide sufficient force to loosen the sample well tray from the sample block.
• In accordance with the present invention, the[0038]handling apparatus10 includes a rotational actuator for rotating the sample well tray holder about a first rotational axis, and a biasing mechanism configured to urge the sample well tray holder in a generally upward direction along the first rotational axis. As embodied herein and shown in FIGS.1-8, arotational actuator14 is provided for rotating the sample well tray aboutrotational axis50. As shown in FIGS.1-9, therotational actuator14 includes amotor52, aspline shaft54, and aspline bushing56. The rotational actuator allows thehandling apparatus10 to be rotated about an axis so that the sample well tray may be transported between at least two predetermined positions.
• In the example shown in FIGS.[0039]1-9, themotor52 may be any type of motor capable of providing sufficient force to rotate the samplewell tray holder12 through an approximately 90 degrees rotation. In certain embodiments, the motor is a stepper motor. Other types of rotational force generating devices such as servo motors (with an encoder), rotary solenoids, spring loaded devices, etc. may also be used. In one example, the motor is a 5 volt, 1 amp stepper motor rated at 200 steps per revolution, which may be micro-stepped to provide 1,600 steps per revolution. It is preferable that the motor be controlled accurately so that it provides precise rotation of the sample well tray holder from a first position to a second position, and back to the first position.
• In certain embodiments, a rotational position sensing device may be provided in order to enhance the accuracy of the rotational actuator. For example, a rotational[0040]position sensing device58 such as a rotary encoder may be used to control the amount of rotation of the motor. In certain embodiments, the rotational position sensing device includes asensor60 that detects the number ofslots62 on adisk64 that have rotated past the sensor. Other types of rotational position sensing devices are known in the art, and are suitable with the present invention.
• As shown in FIG. 3,[0041]motor output shaft65 ofmotor52 may be attached to a second shaft such as aspline shaft54. In the example shown,spline shaft54 transmits rotational movement to aspline bushing56 positioned around the spline shaft. Thespline shaft54 transmits rotation to thespline bushing56 while still allowing relative axial movement between the spline bushing and spline shaft. The spline shaft and bushing are configured so that the spline bushing may move axially along the spline shaft, but remain rotationally fixed to the spline shaft. In certain embodiments, a ball spline and bushing are employed to minimize rotational backlash in the mechanism. Other configurations such as a simple spline configuration with an axial projection and a groove are also suitable with the present invention.
• As best shown in FIG. 3, the[0042]spline bushing56 includes an axially extendingcylindrical member66 and aflange member68 at an end thereof. In the example shown,flange member68 has an outer diameter greater than the axially extendingcylindrical member66. In certain embodiments,flange member68 of the spline bushing, which is in the shape of a disk, includes a plurality ofholes70 for receiving bolts to fasten thespline bushing56 to theextension arm34. In the embodiment shown in FIGS.1-8,spline bushing68 includes fourholes70 through whichbolts72 may pass through into mating holes74 in theextension arm34. As shown in FIG. 3,extension arm34 is configured to include a hole35 with an inside diameter corresponding to the outside diameter of the axially extendingcylindrical member66 of the spline bushing. Alternately, theextension arm34 may be attached to the spline bushing by any number of conventional methods, or could be made integral with the spline bushing.
• As shown in FIGS.[0043]1-3 and5-6, acylindrical stop member80 is attached to the end of thespline shaft54. Thecylindrical stop member80 prevents thespline bushing56 from moving axially along therotational axis50 beyond a predetermined point. Thecylindrical stop member80 may be any structure that prevents thespline bushing56 from moving axially beyond a predetermined point. In the embodiment shown in FIGS.1-9, the cylindrical stop member is an annular member with an annular recess or counterbore82 matching the outer diameter of thespline shaft54. Thecylindrical stop member80 may be attached to the end of thespline shaft56 by any known method, such as fasteners, threads, interference fit, glue, etc.
• The spline bushing may move axially downward on the spline shaft along[0044]axis50. Abiasing mechanism16 is provided to urge-the spline bushing in an upward direction to resist movement of the spline bushing in the downward direction in FIG. 3. Thebiasing mechanism16 is configured to urge the samplewell tray holder12 and sample welltray208 away from thesample block102 when the cover of theheating device100 is opened. As embodied herein and shown schematically in FIGS. 1 and 3, a spring device such as ahelical spring84 is provided. It should be understood thathelical spring84 is shown schematically for purposes of illustration only. The helical spring may be a variety of sizes and spring constants, depending on the size constraints and the amount of force desired. In one embodiment, the helical spring is approximately 1.75 inches in length, and 1.0 inch in diameter.
• In the embodiment of FIGS.[0045]1-9,helical spring84 is positioned concentric to therotational axis50 and surrounds a portion of the length of thespline shaft54. A bottomannular stop member86 is positioned on an opposite end of thespline shaft54 thancylindrical stop member80. The bottomannular stop member86 is provided on thespline shaft54 as shown in FIG. 3, and is in the shape of a disk with an inside bore mating with the outer surface of thespline shaft54. In the embodiment shown, the annular stop member also includes acounterbore88 on the top surface thereof for engaging an outer periphery of the bottom portion of thehelical spring84. The counterbore assists in provide a reliable securement of the bottom end of the helical spring. Likewise, thebottom surface90 of theextension arm34 includes acounterbore92 for engaging an outer periphery of the top end of thehelical spring84.
• Other types of biasing mechanisms such as elastomeric sleeves may be used instead of helical springs. One or several spring devices such as leaf springs, conical helical springs, elastomers, and other springs which impart an axial force when compressed are also suitable with the present invention. In addition, other spring-like devices suitable for use in the present invention include, for example, air cylinders, fluid cylinders, dampeners, belleville washers, and electrical solenoids. The size and type of spring device depend on the specific design constraints of the handling apparatus.[0046]
• Helical springs, also called coil springs, such as shown in the figures are particularly suitable in applications where relatively large compression stroke lengths are desired, whereas an elastomeric sleeve may be suitable if short compression stroke lengths are preferred. In one example, the[0047]helical spring84 is compressed about 0.5 inches. In applications with a large compression stroke for the biasing mechanism, a helical spring may be better suited than an elastomeric sleeve. The biasing mechanism is typically configured so that the sample well tray may be pushed downward a slight distance by the cover of the heating device after the sample well tray is aligned with the sample block. As shown for example in FIG. 9B, thecover150 of the heating device typically presses downward on thesample well tray208 so that thesample wells210 of the sample well tray are firmly pressed against surfaces of thesample block openings104 in thesample block102.
• As the sample well tray holder is pressed downward, the[0048]helical spring84 is compressed a slight distance. Because the spring constant of the helical spring is small relative to the downward force of the cover, the upward force imparted by the helical spring will not bend the sample well tray. The force imparted by the helical spring of the biasing mechanism will be sufficient to lift the loosened sample well tray away from the sample block, after the urging mechanism has loosened the sample wells from the sample block openings, so that the bottoms of thesample wells210 do not interfere with the correspondingopenings104 in the sample block. FIG. 9A shows the position of the sample well tray after the biasing mechanism lifts the sample well tray from the sample block. In one example, the biasing mechanism imparts an upward force of approximately six lbs on the sample well tray holder. The biasing mechanism cooperates with thesprings40 of the urging mechanism to lift the sample well tray completely out of the sample block recesses after thesprings40 of the urging mechanism have overcome the sticking force between the sample wells and the sample block.
• The operation of the handling apparatus for one typical embodiment corresponding to FIGS.[0049]1-9 will now be more completely described below. First, a robot such asrotational robot200 shown in FIG. 5 grasps asample well tray208 with a grasper such asrobot hand206. Therobot arm204 androbot hand206 then rotate the sample well tray aboutrotational axis202 to the position shown in FIG. 5. Therotational robot200 opensrobot hand206 to drop thesample well tray208 into therectangular opening24 of the samplewell tray holder12 of thehandling apparatus10. As shown in FIG. 5, thehandling apparatus10 is located in a first position so that therectangular opening24 is aligned with thesample well tray208 in therobot hand206. Preferably, therectangular opening24 includes tapered walls so that thesample well tray208 slides downward into therectangular opening24 of samplewell tray holder20 and is centered in the rectangular opening.
• After the[0050]sample well tray208 is seated in therectangular opening24 of the samplewell tray holder12, therotational actuator14 of thehandling apparatus10 rotates the samplewell tray holder12 aboutrotational axis50 from a first position shown in FIG. 5 to a second position shown in FIG. 6. In the rotational actuator described above, for example,motor52 rotatesmotor output shaft65 andspline shaft54.Spline shaft54 transmits torque to splinebushing56 andextension arm34. Theextension arm34 is connected to armportion22 of samplewell tray holder12 and transmits rotational motion to the samplewell tray holder12. The samplewell tray holder12 is thereby rotated approximately ninety degrees aboutrotational axis50 from the first position shown in FIG. 5 to a second position shown in FIG. 6. This is a clockwise rotation as viewed in FIGS. 5 and 6.
• At the second position shown in FIG. 6, the[0051]sample well tray208 is roughly aligned with thesample block102 ofheating device100. Each of the plurality ofsample wells210 of the sample well tray are aligned with arespective opening104 in the sample block, as shown for example in FIG. 9A. Thesample well tray208 is initially positioned over thesample block102 at a first height so that the sample wells of the sample well tray have clearance over the sample block so that the sample well tray holder can be swung into position. This initial position is shown for example in FIG. 9A.
• A[0052]cover150 of the heating device, initially positioned over the sample well tray may then be lowered, pressing against the top surface of the sample well tray and sample well tray holder so that the sample wells of thesample well tray208 are lightly pressed against the recesses of thesample block102. As the sample well tray holder lowers to this second height, thehelical spring84 of thebiasing mechanism16 is compressed. Thespline bushing56 is thereby lowered so that a space is created between the top of the spline bushing and the bottom surface ofstop member80. As thecover150 continues to be lowered, thesprings40 of the urging mechanism are then compressed until the samplewell tray holder20 reaches a third height shown in FIG. 9B, and the cover is completely closed. At this third height shown in FIG. 9B, thesample wells210 of thesample well tray208 are firmly pressed against theopenings104 of the sample block.
• The heating device, such as[0053]thermal cycler100, thereafter heats the liquid sample in the sample well tray to undergo a PCR or other type of chemical reaction. After the thermal cycling and/or other operations are completed, thecover150 is opened. As the cover is opened, the cover will no longer press against the top of the sample well tray. Simultaneously, thesprings40 of the urging mechanism will impart an upward force on thebottom surface42 of the sample well tray, thereby urging thesample wells210 upward so that they no longer press against the surface of theopenings210 of the sample block. The springs should impart sufficient force so that the sample well tray becomes loosened from the sample block. At this second height, the sample wells are still positioned in the recesses in the sample block, consequently, the sample well tray holder cannot be rotated away from the sample block without interfering with the sample block.
• The provision of the[0054]biasing mechanism16 permits for the immediate raising of the sample well tray out of the sample block above the second height.Helical spring84 of biasingmechanism16 presses upward on thespline bushing56 so that the sample well tray holder returns to its first height (FIG. 9A). At the first height, the top of thespline bushing56 typically abuts a bottom surface of thestop member80. The first height corresponds to a height at which the sample well tray can be rotated away from the sample block without interference. This is shown for example in FIG. 9A. Consequently, the samplewell tray holder12 can now be rotated from the second position shown in FIG. 6 to the first position shown in FIG. 5 by the rotational actuator.
• The rotational actuator rotates the sample well tray holder in the opposite direction (counterclockwise as viewed in FIGS. 5 and 6) as it was previously rotated. When the sample well tray holder and sample well tray are returned to the first position shown in FIG. 5, the[0055]robot hand206 of therobot200 may grasp thesample well tray208 and remove it from the samplewell tray holder12. Thereafter, therobot200 may rotate and bring the sample well tray to a receiving position, for example, a position on the robot. Therobot200 may then grab another sample well tray on or adjacent the robot, within the radius of the robot arm, and repeat the above operation.
• As is clear from the above description, the present invention includes a method of manipulating sample well trays. The method includes the step of placing the sample well tray into a sample well tray holder of a first robot mechanism located at a first position. The method further includes the step of rotating the sample well tray holder of the first robot mechanism about a rotational axis in a first rotational direction to insert the sample well tray holder into a heating device at a second position. The sample well tray engages with a cover of the heating device to lower the sample well tray holder in a direction toward a sample block of the heating device so that the sample wells of the sample well tray firmly engage the corresponding openings in the sample block. The sample well tray then undergoes a heating operation such as thermal cycling. After the heating operation is completed, the cover of the heating device is opened so that the sample well tray and sample wells disengage from the sample block. As a result, the sample well tray no longer directly contacts the sample block. The method further includes lifting the sample well tray holder and sample well tray from the sample block openings by a biasing mechanism so that the sample well tray is capable of rotation away from the sample block and heating device without interference. The sample well tray holder is then rotated in a second rotational direction toward the first position to remove the sample well tray holder from the heating device. The method further comprises, prior to placing the sample well tray in a sample well tray holder, the steps of picking up a sample well tray with a second robot mechanism, such as a rotational robot, and rotating the sample well tray to place the sample well tray in the first position.[0056]
• The system and method according to the present invention may be used to transport a large number of sample well trays into a thermal cycler having detection capabilities. This may increase throughput and improve safety for operators of thermal cyclers. With such a handling apparatus, it is unnecessary to manually load the sample well trays into a thermal cycler.[0057]
• It will be apparent to those skilled in the art that various modifications and variations can be made in the apparatus and method for handling sample well trays, use of the apparatus of the present invention, and in construction of this apparatus, without departing from the scope or spirit of the invention.[0058]
• Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.[0059]

Claims (36)

What is claimed is:

1. An apparatus for transporting sample well trays with respect to a heating device, comprising:

a sample well tray holder comprising a plate in which a sample well tray may be positioned, said sample well tray holder configured to rotate about a first rotational axis;

a rotational actuator configured to rotate the sample well tray holder about the first rotational axis; and

a biasing mechanism configured to urge the sample well tray holder in a generally upward direction along the first rotational axis.

2. The apparatus ofclaim 1, wherein the rotational actuator comprises a motor.

3. The apparatus ofclaim 2, wherein the motor is configured to rotate the sample well tray holder approximately ninety degrees.

4. The apparatus ofclaim 2, wherein the rotational actuator further comprises a shaft attached to the motor.

5. The apparatus ofclaim 4, wherein the motor comprises a stepper motor.

6. The apparatus ofclaim 4, wherein the shaft attached to the motor is a spline shaft, the rotational actuator further comprising a spline bushing for engaging with the spline shaft so that the spline bushing is rotationally fixed but axially moveable relative to the spline shaft.

7. The apparatus ofclaim 6, wherein the spline bushing is rotationally fixed to the sample well tray holder.

8. The apparatus ofclaim 7, further comprising an extension arm for attaching the spline bushing to the sample well tray holder.

9. The apparatus ofclaim 1, wherein the plate of the sample well tray holder includes a recess for positioning the sample well tray therein.

10. The apparatus ofclaim 9, wherein the recess is defined by tapered side walls for receiving the sample well tray, the tapered side walls configured so that the sample well tray rests on the tapered side walls.

11. The apparatus ofclaim 10, wherein the recess is rectangular.

12. The apparatus ofclaim 9, wherein the plate of the sample well tray holder includes a first portion having the recess and a second portion comprising an arm for connecting the first portion with the rotational actuator.

13. The apparatus ofclaim 1, wherein the biasing mechanism comprises a spring member.

14. The apparatus ofclaim 13, wherein the rotational actuator further comprises an output shaft that is rotatably fixed relative to the sample well tray holder, the spring member comprising a helical spring positioned around the first rotational axis and the output shaft.

15. The apparatus ofclaim 7, wherein the biasing mechanism comprises a helical spring positioned around the first rotational axis and surrounding a portion of the spline bushing.

16. The apparatus ofclaim 1, further comprising a robot configured to grasp a sample well tray and transport the sample well tray to the sample well tray holder.

17. The apparatus ofclaim 1, further comprising a heating device with an opening for the sample well tray to be placed therein.

18. The apparatus ofclaim 1, further comprising a heating device for conducting thermal cycling.

19. The apparatus ofclaim 18, wherein the thermal cycling results in nucleic acid amplification.

20. The apparatus ofclaim 1, wherein the sample well tray comprises a 96-well microtiter tray.

21. The apparatus ofclaim 1, wherein the sample well tray comprises a 384-well microtiter tray.

22. The apparatus ofclaim 1, wherein wells of the sample well tray are conical.

23. The apparatus ofclaim 1, wherein wells of the sample well tray are sized to have a fluid volume in the range of 10 to 500 μl.

24. A robotic manipulator for transporting sample well trays between at least two positions, comprising:

a robotic arm having a sample well tray holder configured to support a sample well tray therein, the sample well tray holder comprising a recess for the sample well tray;

a rotational mechanism configured to impart rotational motion on the robotic arm, the rotational mechanism comprising a motor; and

a biasing mechanism configured to provide force on the sample well tray holder in a direction away from an adjacent sample block.

25. The robotic manipulator ofclaim 24, wherein the biasing mechanism comprises at least one helical spring positioned partially surrounding a shaft of the rotational mechanism.

26. The robotic manipulator ofclaim 25, further comprising a sleeve member positioned around the shaft of the rotational mechanism and partially surrounded by the helical spring, the sleeve member being rotationally fixed to the shaft of the rotational mechanism and axially slidable relative to the shaft, the biasing mechanism configured to urge the sleeve member in the direction away from the adjacent sample well block.

27. The robotic manipulator ofclaim 25, wherein the sleeve member comprises a spline bushing configured to engage a spline on the shaft of the rotational mechanism.

28. The robotic manipulator ofclaim 26, further comprising a stop member positioned on the shaft of the rotational mechanism, the stop member configured to prevent the sleeve member from axially moving beyond a predetermined position on the shaft of the rotational mechanism.

29. A system for manipulating sample well trays, comprising:

a robot configured to transport a sample well tray to a first location;

a loading mechanism configured to take a sample well tray from the first location, place the sample well tray into a heating device at a second location and then later remove the sample well tray from the heating device and return the sample well tray to the first location, the loading mechanism comprising a sample well tray holder in which a sample well tray may be positioned therein, a rotational actuator configured to rotate the sample well tray holder, and a biasing member configured to urge the sample well tray and sample well tray holder in a direction away from a sample block; and

a heating device having an opening for receiving the sample well tray therein.

30. The system ofclaim 29, wherein the heating device is a heater and the rotational actuator comprises a motor for rotating a shaft and a spline bushing positioned in a rotationally fixed manner on the shaft.

31. A method of manipulating sample well trays, comprising:

placing a sample well tray into a sample well tray holder of a first robot mechanism located at a first position;

rotating the sample well tray holder of the first robot mechanism about a rotational axis in a first rotational direction to insert the sample well tray holder into a heating device at a second position;

lowering the sample well tray holder in a direction toward a sample block of the heating device so that the sample well tray engages the sample block;

disengaging the sample well tray from the sample block so that the sample well tray does not directly contact the sample block;

lifting the sample well tray holder and sample well tray from the heating device by a biasing mechanism so that the sample well tray is capable of rotation away from the sample block and heating device without interference; and

rotating the sample well tray holder of the first robot mechanism in a second rotational direction toward the first position to remove the sample well tray holder from the heating device.

32. The method ofclaim 31, wherein the lowering of the sample well tray holder comprises engaging the sample well tray with a cover of the heating device in order to lower the sample well tray holder.

33. The method ofclaim 31, further comprising, prior to placing the sample well tray in a sample well tray holder, the step of picking up a sample well tray with a second robot mechanism, and rotating the sample well tray to place the sample well tray in the first position.

34. The method ofclaim 31, wherein the biasing mechanism that lifts the sample well tray holder comprises a helical spring that urges the sample well tray away from the sample block.

35. The method ofclaim 31, wherein the step of disengaging the sample well tray from the sample block includes providing an upward force on the sample well tray holder by an urging mechanism positioned between the sample well tray holder and the sample block.

36. The method ofclaim 35, wherein the urging mechanism comprises at least one spring device.

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