Disclosure of Invention
The invention aims at overcoming the defects in the prior art, and provides a sample processing device with a double-turntable structure, which reduces the risk of cross contamination possibly generated in a sample liquid processing system through the reasonable design of a layout structure and can also meet the design requirement of low cost.
In order to achieve the above purpose, the technical scheme provided by the invention is as follows:
The sample processing device with the double-turntable structure is characterized by comprising a first turntable 10, a plurality of transfer liquid receiving units are arranged in the circumferential direction of the first turntable 10, a second turntable 20 is arranged in the center of the first turntable 10, N consumable receiving frames 201 are arranged on the second turntable 20, a pipetting module 30 is further included, the pipetting module 30 comprises at least one pipetting subunit, the pipetting module 30 ingests and installs at least one consumable on one consumable receiving frame 201 of the second turntable 20, and sample liquid transfer or consumable unloading is carried out in an area outside the second turntable 20.
Preferably, the transfer liquid receiving unit includes a receiving portion 101, and a deep hole plate is connected to the receiving portion 101 through a first clamping portion 1011.
Preferably, the Tip of the pipette is connected to the consumable receiving frame 201 through the second engagement portion 2011.
Preferably, the first turntable 10 and the second turntable 20 have independent driving structures, so that the two turntables can rotate independently.
Preferably, the first rotary table 10 is driven by a first motor through a meshing gear pair transmission, and the second rotary table 20 is driven by a second motor through a pulley transmission.
Preferably, the meshing gear pair is in a low-tooth-number, high-tooth-number configuration.
Preferably, the high-tooth number gear is supported by not less than two auxiliary supporting wheels.
Preferably, the first turntable and the second turntable are located on the same horizontal plane, and central axes of the two turntables are substantially coincident.
Preferably, when the first rotary table (10) completes one rotation, the second rotary table (20) rotates by not less than 1/N.
Preferably, the number of the transfer liquid receiving units is 6, and the number N of the consumable receiving racks (201) is 2.
Compared with the prior art, the invention has the following advantages:
1. According to the scheme, the plurality of sample liquid receiving units are arranged in the circumferential direction of the outer ring turntable, the inner ring turntable is arranged in the center of the outer ring, N consumable receiving frames are arranged, the consumable can be a pipetting head used by a pipetting device, and a pipetting part consisting of at least 1 pipetting subunit is arranged on one consumable receiving frame in the center position, at least one pipetting head consumable is ingested and installed on the consumable receiving frame in the center position, and sample liquid transfer, consumable unloading and other operations are performed in an area outside the center of the first turntable, so that the space overlapping between the process of loading the Tip head and the process of pipetting or unloading the Tip head is avoided, and the cross contamination risk possibly caused by overlapping of a used Tip head moving path and a new loading path is avoided.
2. The sample liquid receiving unit is arranged as a consumable material of a deep hole plate (for example, a deep hole plate with more sample receiving hole sites of a 96 hole plate 16), so that the compatibility of a pretreatment system is ensured, the consumable material receiving unit can be matched with different nucleic acid extractors and other nucleic acid extractors such as a GeneRotex nucleic acid extractor of Tianlong technology, and the consumable material receiving rack at the central part can meet the requirement of processing a larger amount of samples.
3. According to the invention, different rotation requirements of the inner ring and the outer ring are met through independent driving sources such as independent motor driving, the whole double-turntable system can reliably run without mutual interference through the cooperation of gears and belt wheel transmission, more transferring liquid receiving units can be compatible through the cooperation of high teeth number and low teeth number, the position adjustment of smaller angles can also be adapted, the stable and reliable running of the whole transmission system is realized through the cooperation of auxiliary supports of at least two auxiliary supporting wheels, the two turntables are basically positioned on the same horizontal plane, the central shafts of the two turntables are basically overlapped, and the design ensures that excessive operation errors cannot exist in the operation such as transferring and picking of a liquid transfer device, and the reliability of the whole system is ensured.
4. According to the invention, after the double turntables complete a whole circle of rotation movement according to the outer ring turntables, the inner ring turntables rotate at least 1/N circle, so that the relative immobilization of the installation consumable of the pipettor and the replacement installation of new consumable is realized, the continuity of the installation and the unloading of the sample liquid receiving unit is ensured, and the compatibility receiving of different types of deep pore plates of different companies is realized by matching with the pipetting subunit with variable spacing.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present application more apparent, the technical solutions of the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application, and it is apparent that the described embodiments are some embodiments of the present application, but not all embodiments of the present application. The components of the embodiments of the present application generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.
Thus, the following detailed description of the embodiments of the application, as presented in the figures, is not intended to limit the scope of the application, as claimed, but is merely representative of selected embodiments of the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
It should be noted that like reference numerals and letters refer to like items in the following figures, and thus once an item is defined in one figure, no further definition or explanation thereof is necessary in the following figures.
Example 1
Fig. 1 is a schematic diagram of a double-turntable structure, which includes a plurality of transfer fluid receiving units arranged in the circumferential direction of a first turntable 10, and the in-vitro diagnosis technology using human body secretions, excreta, blood, amniotic fluid, nasal swab, pharyngeal swab, anal swab and the like as targets has become an early rapid diagnosis scheme for detecting infection of a certain disease of a target, so that the method plays an increasingly important role in public safety, medical diagnosis, criminal investigation and the like due to the advantages of high sensitivity, early discovery time and the like, the transfer fluid receiving units in the system of the embodiment 1 are the most used deep pore plates in molecular diagnosis, and a nucleic acid extraction reaction system can be automatically established by using the sample processing system, thereby greatly reducing manual operation amount and ensuring the reliability of the detection result. The deep well plate herein may be of different capacity types, such as a sample processing volume of 1mL, 1.5mL, 2mL, 2.5mL, 3mL, etc. Of course, the dual carousel sample processing system of this embodiment may be used as a stand alone product, and then used in conjunction with nucleic acid extraction products to complete a fully automated extraction process, such as in conjunction with a GeneRotex nucleic acid extractor of Tianlong technology, or in conjunction with other company nucleic acid extraction equipment, as not limited herein. It may also be a sub-module of an automated analysis device to complete a fully automated solution from sample addition to final result output, without limitation. The first turntable 10 includes a plurality of receiving portions 101, which can receive 5, 6, 7, 8, 9 and so on deep-hole plates, the deep-hole plates are the most widely used 96-hole 16-sample structures, and in order to be compatible with deep-hole plates with different capacities, the plurality of receiving portions 101 of the first turntable 10 each include elastic clamping portions 1011, which can be arranged in pairs, and the opening degrees of different sizes can be formed by using the adjustable characteristics of the elastic members so as to accept deep-hole plates of different manufacturers or different models. A second turntable 20 is further disposed at the center of the first turntable, and the second turntable includes N consumable receiving racks 201 (where N is an integer not less than 1), which illustrates a case where n=2, and N may be 3, 4, 5, etc. in actual use, which is not limited herein. The consumable material is disposable, wherein the most typical Tip of the pipettor is the Tip of the commercialized Tip which is most commonly used is also made into a batch mode of box packing 96, in order to be compatible with a batch commercial mode of 96pcs, the second turntable 20 utilizes the clamping part 2011 to ensure that N pipetting tips with corresponding quantity are installed, in order to ensure the establishment of the reliability of an extraction system, the PK & IC liquid storage part 110 is arranged at the periphery of the first turntable 10, thereby meeting the effects of removing nuclease and buffering in DNA and RNA preparation to ensure that the reaction condition of a reaction liquid does not change too fast, and the like, and the specific structure is not limited.
Example 2
Fig. 2 is a schematic cross-sectional view of a structure of a double turntable provided by the invention, wherein the rotation of the double turntable is driven by two independent motors, so that two different rotation angles, different rotation time sequence arrangements and even no interference adjustment in different rotation directions can be realized. The first driving motor 11 is connected with the output gear 112 through an output shaft, so that the output gear 112 is driven to rotate, the output gear 112 is meshed with the driving gear 113 of the first rotating disc 10, the driving gear 113 can be directly connected with the first rotating disc 10 through at least 1 connecting piece 114, and the two can realize rotary motion without relative motion, so that the rotation transmission of the first driving motor 11 is completed and the rotation of the first rotating disc 10 is converted. In order to ensure that the rotation of the first turntable 10 has the most refined adjustment angle, the driving gear 113 and the output gear 112 adopt a design with high gear ratio, for example, the gear ratio of the driving gear 113 and the output gear 112 can be in a range of 3:1-10:1. In one case, of course, the first driving motor 11 may perform a continuous rotation of a predetermined angle, for example, 60 °, 40 ° or the like, each time, and then stop for a certain time to reserve the time required for pipetting operations or the like, and then continue to rotate, so that a high-precision continuous operation in which the position of the operation hole of the pipettor is substantially fixed and the positions of the upper and lower samples are substantially fixed is achieved. The second driving motor 21 is connected with the output belt pulley 211 through an output shaft, and is connected to a driving belt pulley 213 of the second turntable 20 at the central position through a belt 212, and the driving belt pulley 213 drives a rotating shaft 214 directly connected with the second turntable 20 to rotate, so that the rotation driving of the second turntable 20 at the central position is realized. The first rotary table 10 and the second rotary table 20 are basically positioned on the same horizontal plane, and the central axes of the two rotary tables are basically coincident, so that the simplification of the control of the pipettor matched with the double rotary tables is ensured, and the realization of a low-cost and low-complexity mode of the system is ensured.
Example 3
Fig. 3 is a schematic diagram of a partial optimization design of a gear transmission provided by the present invention, in order to ensure precise angle control of the first turntable, the driving gear 113 needs to have a higher number of teeth, so that it is required to ensure that the driving gear 113 has a sufficient radius, so that during long-term operation, the gear engagement may be unreliable or even fail due to the effects of radial force, etc., and therefore, the driving gear 113 with a high number of teeth is supported by at least two auxiliary supporting wheels 1131 and 1132, so as to ensure reliable operation of the system during the whole equipment service period, and achieve both engagement precision and operation reliability at low cost. The multiple transfer liquid receiving units can be optimally set as six deep hole plate receiving parts in combination with fig. 1, so that 96 sample size disposable treatment can be completed when full-load deep hole plate positions are realized, meanwhile, the second turntable at the center part comprises consumable receiving frames, the number N of consumable receiving frames is 2, so that when all deep hole plates on the outer ring turntable 10 accurately receive sample liquid of corresponding hole positions, the first turntable 10 completes one circle of rotation, tip head consumable materials on one consumable receiving frame corresponding to the first turntable is consumed, at the moment, the second turntable 20 can rotate for 1/2 circle, new consumable material supply is rotated to the original position, new pipetting operation can be started without complex control of readjustment of a pipetting device pick-up track, new consumable materials can be reloaded by using the completed consumable receiving frames, and when the first turntable 10 completes one circle of rotation, the second turntable 20 rotates not less than 1/N circle when N is other value, continuity of the whole operation flow is ensured, and rationality of the whole configuration is ensured.
Example 4
Fig. 4 is a schematic diagram of a motion track of a lower pipette with a dual-turntable structure, an outer ring is a first turntable 10, a plurality of pipette receiving parts are arranged on the first turntable 10, a second turntable 20 is arranged in a central area of the outer ring, N consumable receiving frames are contained on the second turntable 20, 30 is a pipette module, which can contain 2,3, 4 and other pipette subunits for transferring sample liquid, 401 is an oscillation mixing subunit and can uniformly mix and transfer the sample liquid, in an actual pipetting process, firstly, the pipette enters the range of an inner ring area of the second turntable 20 along a first track of S10, the pipette does not have any used Tip, so that the pollution risk caused by entering a new consumable area with the used Tip is avoided, then the new pipette Tip is ingested through the driving of a motion motor, the unused Tip does not influence the pipette receiving parts after the ingestion, then the Tip is directly unloaded to a sample liquid receiving part along a pipetting hole position along a position corresponding to the oscillation receiving part of S202, and finally, the Tip is directly unloaded to a sample liquid is recovered along a pipetting hole position of the pipette receiving part, and finally, the Tip is directly unloaded to a sample liquid is recovered along the pipetting hole position after the Tip is completely moved to the consumable receiving part. The transfer operation of low pollution risk of all sample liquid can be completed through circulation for many times, under the layout, the new Tip head and the used Tip head consumable track are almost not overlapped, the risk of cross pollution is avoided to the maximum extent, in addition, the completed Tip head consumable track does not relate to the central area where the second turntable 20 is located at all, the risk of cross pollution between the new Tip head and the old Tip head is avoided to the maximum extent, the Tip head consumable area can keep a fixed low pollution risk area, and in practice, the pipetting track can also be a combined S20 track, which is not limited in the place. After the transfer of the samples from all the hole sites of the sample liquid receiving part is completed, the first rotary disk 10 can be rotated by a predetermined angle to enable the new sample liquid receiving part which does not receive any sample liquid to be rotated to the previous hole site, so that the simplification of the control of the movement track of the pipette is realized, the accuracy of the pipetting operation is also ensured, the second rotary disk 20 inside can also be designed similarly, the second rotary disk 20 can be rotated by another preset angle after the consumable on one sample rack is used, and the switching of the consumable rack is realized.
Example 5
Fig. 5 shows a sample fluid pretreatment system comprising a double-turntable structure of the present invention, which comprises a sample tube loading unit 60 to which a number of sample tubes, for example, 96, 192, 288, 384, etc., can be added for a single treatment. The sample tube transferring gripper 50 is used for gripping or unloading the sample tube from the sample tube receiving portion of the sample loading unit 60, in order to ensure that the transferred sample fluid can contain a sufficient detected object, proper oscillation mixing is usually required for the sample fluid, more automatic systems in the prior art directly integrate an oscillation device on the sample loading unit to meet the requirement of sample oscillation mixing, however, such design has the requirement of simultaneously oscillating all sample tubes, and the sample tube amount of the sample loading unit 60 in the batch processing system is larger, so that it is unlikely to realize all the one-time simultaneous transfer design, and the requirement of the overall system design cost is higher for maintaining the turbulence degree is also higher for the reliability of the system operation due to the direct design of the oscillation system. The sample liquid pretreatment system may include two or more sample oscillation mixing submodules 401, and the transfer grip 50 includes a Z-axis up-down running track 511 and a Y-axis front-back running track 512, and may also include an X-axis left-right running track, which is not limited herein, so that any position in the sample liquid treatment system may be covered. The transfer gripper 50 can grasp the sample tube in the sample loading unit 60 to the oscillation mixing subunit, and the oscillation mixing subunit can mix the sample liquid according to a predetermined turbulence degree, and of course, the transfer gripper 50 can grasp the sample tube from the returned oscillation mixing subunit after completing the sample liquid transfer, so that the transferred sample tube is returned to the corresponding hole site before the sample loading unit 60.
Example 6
The shaking and mixing subunit is conveyed to the lower part of the switch cover unit 100 after the shaking and mixing is completed by combining with fig. 7, and the shaking and mixing process can be performed simultaneously in the process of transferring the sample tube or can be directly performed by arranging a specific time sequence. The switch cover unit 100 includes two switch cover units 1001 and 1002, which are consistent with the number of sample tubes in the oscillator subunit, and include a switch cover clamping jaw and a tube body fixing clamping jaw matched with the tube body, although a scheme of arranging a clamp and a fixing part in the oscillator subunit to match the switch cover clamping jaw can be adopted, the method is not limited to any one of two modes for opening the cover of the sample tubes, and the two switch cover units 1001 and 1002 can simultaneously complete the cover opening operation of two sample tubes, or can respectively complete the liquid sucking operation of the liquid dispenser after one sample tube is opened and then open the other sample tube. After the sample tube is opened, the pipette 30 can perform pipetting operation, before which the pipette can complete the operation of taking Tip consumables at the central second turntable 20 of the double turntable structure, wherein the pipette 30 comprises two sub-pipetting units 301 and 302 for matching the requirement of rapidly transferring sample liquid of the oscillating mixing sub-unit, further for ensuring that the transfer liquid can better adapt to the size characteristics of the pipetting receiving part, the distance between the two pipetting sub-units can be adjusted, the distance between the two pipetting sub-units can be 20mm-70mm, the pipette 30 also comprises a X, Y, Z-axis motion driving mechanism, and the X-axis of the pipette and the sample tube transfer fixture share a motion track for ensuring the simplicity and cost reduction and reliability requirements of the system design. The pipette 30 can be matched with the Tip head to absorb the sample liquid in the sample tube simultaneously or respectively, then moves to the position above the corresponding hole site of the deep hole plate for receiving the sample liquid along the central area where the non-second turntable 20 is located, then simultaneously or respectively eliminates the transferred sample liquid to the corresponding hole site of the deep hole plate to finish transferring, the cover of the sample tube after the transfer is covered by the cover opening and closing module, the sample tube is conveyed to be unloaded by the vibration mixing subunit, and the pipette also moves to the unloading hole site along the track which cannot infect the central area to unload the Tip head. Of course, before pipetting, the pipettor can transfer a proper amount of PK & IC liquid from the PK & IC storage part 110 to the corresponding hole site to establish the reliability of the extraction system, so that the liquid is a more general reagent and has no influence on the transfer of the subsequent sample liquid, thereby ensuring the simplicity of the design of the pipetting system.
Example 7
Fig. 6 is a sample fluid processing system under another view angle, which includes a sample information obtaining unit 70, which can identify a barcode, a two-dimensional code, a FRID, and the like of a sample tube, for example, it can be matched with the cover opening and closing device in fig. 7 to perform identification and obtaining of sample information, the cover opening and closing device can grasp the sample tube and then make the sample tube be in a field of view of the information obtaining unit 70, the sample tube is driven to rotate by the cover opening and closing to identify corresponding information of the sample, although other schemes can be adopted to complete the obtaining of sample information, the sample information is not limited herein, a used consumable Tip is unloaded at a consumable receiving hole 801 after the pipetting device completes pipetting, a Tip consumable recycling position is set at the front part of the pretreatment system, the used waste Tip is recycled by adopting a drawer-like design for subsequent centralized processing, the low pollution risk of the system is guaranteed, the pretreatment system is further includes an ultraviolet sterilization unit 90, thereby guaranteeing the operational environment in the process, the pollution risk of the whole sample processing process is eliminated by matching with the basic full-automatic operation, and the used Tip can be set in the drawer to perform disinfection and the like.
Example 8
Fig. 8 is a schematic diagram of a functional module of a sample processing system with a dual turntable structure, which can be divided into four basic sub-functional units, including a functional module of a sample loading unit U01, mainly responsible for detecting sample loading and whether the sample loading is in place, and includes a sample tube and a sample rack for receiving batch input by a sample input unit 60 (which may also be referred to as a sample loading unit), and may include a plurality of in-place sensors located at different positions, which may be of a photoelectric or mechanical type, and is not limited herein, and the sample loading unit U01 is ready after detecting the sample loading. The transfer unit U02 is mainly responsible for transferring the sample tube, and the portion of the transfer unit is responsible for bridging before pipetting, and includes a sample tube clamp 50 for transferring a new sample tube into the oscillation subunit 40, or removing the sample tube after pipetting from the oscillation subunit 40, where the oscillation subunit can have both functions of conveying and mixing. The pipetting unit U03 is mainly used for completing transfer of a sample liquid after identifying and acquiring the sample liquid information, and comprises a sub-scanning unit 70, so that on one hand, the sample information can be acquired, on the other hand, whether the system has a correct reagent to receive the sample liquid can be verified, the switch cover unit 100 also comprises two basic functions, 1) a cover of a sample tube is opened or closed, 2) the sub-scanning unit 70 is assisted to acquire the sample tube information, and the pipetting module 30 can comprise a plurality of sub-pipettors to aspirate the sample liquid and discharge the sample liquid to a target hole site. The system establishment unit U04 includes a system establishment unit U04, in which a system establishment for completing a subsequent operation, for example, an extraction system establishment in the system, including a double turntable subunit, a deep-hole plate carrying turntable located on the outer ring first turntable 10, a consumable rack receiving part located on the center inner ring second turntable 20, and other micro reagent storage subunits 110 that need to be added in the reaction process, which may be PK & IC liquids required in the extraction process in this embodiment, but is not limited thereto.
Example 9
Fig. 9 is a schematic diagram of an operation flow of a sample processing system provided by the present invention, along with starting an operation program of the whole sample processing system, a loading unit receives a sample tube rack manually added or transferred from a refrigerating unit by an automated mechanical arm, so as to complete a step of loading the sample tube into a receiving unit, a plurality of sensors are arranged in the loading unit to detect whether the sample tube rack is loaded in place or not, whether the sample tube is loaded correctly, after the sample tube is loaded correctly, the sample tube is clamped by a sample tube clamp and transferred to an oscillator unit to complete full mixing, and then a cover opening and closing mechanism can cooperate with a sample tube identification unit to identify and acquire sample tube information, on one hand, the acquired barcode information is utilized to establish data information of a detection object including, but not limited to, object identity, detection disease type, sample state information, whether urgent processing is needed, etc., and on the other hand, sample tube barcode information verification including, but not limited to sample test item verification, whether system experiment related reagents are correct, whether sample liquid is acquired correctly, etc. is performed. After verification, if the sample tube is matched and the correct system reagent is acquired, the subsequent steps can be carried out, the established database information can be transmitted to other matched equipment through a local area network or the like, if the database information is not satisfied, warning information is generated, the system can continue to operate and only generate warning signals under some conditions, the warning signals are generated under the condition that some systems cannot solve the system, at the moment, operators can execute intervention processing to solve the problem, and of course, the code scanning identification step can be arranged before the sample liquid oscillation mixing step. After information acquisition and verification are completed, the cover opening and closing unit performs cover opening operation, during or before the cover opening operation, the Tip head consumable at the center position of the inner ring is taken up by the liquid transfer device, a sample liquid transfer step is performed along a liquid transfer path in a cover opening state, sample liquid is transferred to a corresponding hole site of the deep hole plate at the sample liquid receiving part, the transferred sample tube performs cover closing operation, the oscillation mixing unit conveys the sample tube to an unloading position and then to be transferred back to an initial position, the liquid transfer device after the transfer of the sample liquid is completed is operated to a Tip head consumable recovery hole site, and the transfer of the sample liquid is completed by unloading the used Tip head consumable. Of course, the double turntable structure of the present invention can also be used in a fully-automatic sample analysis system to complete the processing analysis and final result output of the sample liquid under the condition of low pollution risk, which is not limited herein.
It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that the above embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the spirit and scope of the invention, which is defined in the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.