A robotic arm pipetting system for a microfluidic sample processing device

Abstract

The present invention discloses a mechanical arm liquid transfer system of a microfluidic sample processing device, which is convenient for realizing automatic processing of microfluidic samples. A mechanical arm liquid transfer system of a microfluidic sample processing device comprises: a mechanical arm having a gun head for loading a chip fixture, wherein the gun head is provided with an air flow channel for connecting to the inner cavity of the chip fixture; a lifting device, which is used to drive the gun head to lift and lower to load the chip fixture or insert or detach the chip fixture from a reagent; and a translation device, which is used to drive the gun head to move above the chip fixture or above the reagent; wherein the mechanical arm is arranged on the translation device and connected to the lifting device.

Description

Technical Field

[0001] The invention belongs to the technical field of biological detection, and relates to a mechanical arm liquid transfer system of a microfluidic sample processing device. Background Art

[0002] Microfluidics is an important method for sorting and analyzing cells or biomolecules, such as capturing circulating tumor cells (CTCs). It has the advantages of simple operation and small amount of antibodies required. Microfluidics chips are the core components of microfluidics. Microfluidics chips have microchannels and are attached with specific antibodies, which are used to intercept and capture target cells or biomolecules of samples flowing through them. These captured cells or biomolecules often need to undergo a series of post-processing before they can be used for analysis, such as washing, primary or secondary antibody treatment, staining, etc. At present, most of these treatments are performed manually, which is cumbersome and inconvenient, with low efficiency and low degree of automation. Summary of the invention

[0003] The object of the present invention is to provide a mechanical arm liquid transfer system for a microfluidic sample processing device, which is convenient for realizing automatic processing of microfluidic samples.

[0004] In order to achieve the above object, the technical solution adopted by the present invention is:

[0005] A mechanical arm liquid transfer system for a microfluidic sample processing device, comprising:

[0006] A mechanical arm having a gun head for loading a chip fixture, wherein the gun head is provided with an air flow channel for communicating with an inner cavity of the chip fixture;

[0007] A lifting device, which is used to drive the gun head to lift and lower to load the chip fixture or insert or remove the chip fixture from the reagent; and

[0008] A translation device, used for driving the gun tip to move above the chip fixture or above the reagent;

[0009] Wherein, the mechanical arm is arranged on the translation device and connected to the lifting device.

[0010] Preferably, the robotic arm further comprises a shell and a lifting rod slidably disposed on the shell in an up-and-down direction, and the gun head is fixedly disposed at the lower end of the lifting rod.

[0011] More preferably, the lifting device includes a lifting shaft assembly driven to rotate by a lifting power mechanism, one or more circles of teeth are formed on the outer circumferential surface of the lifting shaft assembly, the lifting rod has a rack portion extending in the up and down directions, and the rack portion and the teeth on the lifting shaft assembly are meshed with each other.

[0012] Furthermore, the lifting shaft assembly includes a lifting shaft driven to rotate by the lifting power mechanism and one or more gears rotating with the lifting shaft, a polygonal hole is opened on the gear, the lifting shaft is inserted into the polygonal hole and can allow the gear to move horizontally relative to the lifting shaft.

[0013] Furthermore, the gear is fixedly disposed in the housing.

[0014] Furthermore, the translation device includes an x-direction component for driving the mechanical arm to move along the left and right directions, and the mechanical arm is arranged on the x-direction component.

[0015] Specifically, the x-axis component includes a mounting plate and a lead screw extending in the left-right direction. The lead screw can be rotatably arranged on the mounting plate around its own axis. The lead screw passes through the robotic arm and is threadedly connected to the robotic arm. A guide component extending in the left-right direction is arranged on the mounting plate, and the shell of the robotic arm can be slidably arranged on the guide component in the left-right direction.

[0016] Specifically, the translation device also includes a y-axis component for driving the mechanical arm to move along the front-rear direction, and the x-axis component is arranged on the y-axis component.

[0017] More preferably, the lifting rod is hollow, and the upper end of the lifting rod is arranged at a joint for connecting to a negative pressure liquid suction device.

[0018] In one embodiment, the gun head includes a body, a first flange and a second flange extending outwardly from an outer surface of a lower portion of the body, wherein the first flange is located a distance above the second flange.

[0019] More preferably, the outer diameter of the first flange is smaller than the outer diameter of the second flange.

[0020] In a further preferred embodiment, the robotic arm pipetting system further comprises a negative pressure pipetting device for providing the gun tip with negative pressure for aspirating liquid and positive pressure for discharging liquid.

[0021] More preferably, the negative pressure liquid suction device comprises a piston driven by a negative pressure motor to reciprocate along a straight line and a piston shell provided with a gas cavity, and the piston is inserted in the gas cavity of the piston shell.

[0022] More preferably, the negative pressure liquid suction device also includes an air duct, one end of which is fixedly connected to the piston shell and communicated with the gas chamber, and the other end of the air duct is fixedly connected to the robotic arm.

[0023] In another further preferred embodiment, the robotic arm pipetting system further comprises a fault detection device for detecting whether the robotic arm exceeds a maximum set stroke.

[0024] More preferably, the fault detection device comprises at least one detection unit, wherein the detection unit comprises a pair of spaced-apart photoelectric detection switches and a baffle moving with the robot arm, wherein the baffle is disposed between the pair of photoelectric detection switches.

[0025] Furthermore, the fault detection device also includes a controller, which is electrically connected to each of the photoelectric detection switches, and the controller is used to control the robotic arm to stop moving after any one of the photoelectric detection switches is triggered.

[0026] Furthermore, the fault detection device also includes a fault indicator light, the controller is electrically connected to the fault indicator light, and the controller is also used to control the fault indicator light to switch light color after any one of the photoelectric detection switches is triggered.

[0027] Furthermore, the fault detection device also includes a sound alarm device, the controller is electrically connected to the sound alarm device, and the controller is also used to control the sound alarm device to emit a warning sound after any one of the photoelectric detection switches is triggered.

[0028] The present invention adopts the above solution, which has the following advantages compared with the prior art:

[0029] The mechanical arm liquid transfer system of the microfluidic sample processing equipment of the present invention has a gun head that can load a chip fixture and absorb and discharge liquid, and is combined with a lifting device and a translation device to lift and translate the gun head, so that the microfluidic chip in the chip fixture undergoes capture, fixation, antibody incubation, staining and other treatments, automatically realizing the above series of treatments for the microfluidic sample, reducing manual intervention, having a high degree of automation, and improving processing efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solution of the present invention, the accompanying drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative work.

[0031] Figure 1 It is a three-dimensional schematic diagram of a microfluidic sample processing device;

[0032] Figure 2a is a schematic diagram of the internal structure of a microfluidic sample processing device, wherein part of the housing is not shown;

[0033] Figure 2b yes Figure 2a A partial enlarged view of the middle A;

[0034] Figure 3 is a top view of a microfluidic sample processing device, wherein a portion of the housing is not shown;

[0035] Figure 4 is a front view of a microfluidic sample processing device, wherein a portion of the housing is not shown;

[0036] Figure 5 , 6 , 7 are three-dimensional schematic diagrams of the tray device, wherein Figure 7 Part of the upper plate and baffle are not shown;

[0037] Figure 8 It is a three-dimensional schematic diagram of the robotic arm;

[0038] Fig. 9 is a schematic diagram of a single robotic arm;

[0039] Fig.10 is a schematic diagram of a single robotic arm, wherein the housing is not shown;

[0040] Fig.11 It is a partial cross-sectional view of the mechanical arm, the lifting device and the translation device;

[0041] Fig.12 It is a cross-sectional view of the negative pressure liquid suction device.

[0042] In the above-mentioned figures,

[0043] 1. Frame; 10. Housing; 101. Door;

[0044] 2. Test kit; 20. Box body; 21. Waste liquid collection hole; 22. Fixative hole; 23. Buffer hole; 24. First primary antibody hole; 25. Second primary antibody hole; 26. Secondary antibody hole; 27. Staining liquid hole; 28. Chip recovery hole;

[0045] 3. chip fixture; 30. body; 31. flow guide tube; 32. barrel;

[0046] 4. Tray device; 40. Mounting slot; 41. Bottom plate; 42. Upper plate; 421. Left and right extensions; 422. Front and rear extensions; 423. Slot; 424. Positioning protrusion; 43. Baffle;

[0047] 5. Mechanical arm; 50. Shell; 51. Gun head; 511. First flange; 512. Second flange; 52. Lifting rod; 521. Rack portion; 53. Joint;

[0048] 6. Negative pressure liquid suction device; 61. Negative pressure motor; 611. Push plate; 62. Piston; 63. Piston shell; 631. Gas chamber; 64. Photoelectric detection switch; 65. Blocking piece;

[0049] 7. lifting device; 71. lifting shaft; 72. gear; 721. square hole; 73. lifting motor;

[0050] 8. Translation device; 81. Mounting plate; 811. Guide rail; 82. X-axis motor; 83. Lead screw; 84. Y-axis motor; 85. Synchronous belt transmission mechanism; 86. Slide rail; 87. Slider;

[0051] 9. Fault detection device; 91. First photoelectric detection switch; 92. First baffle; 93. Second photoelectric detection switch; 94. Second baffle; 95. Third photoelectric detection switch; 96. Fault indicator light. DETAILED DESCRIPTION

[0052] The preferred embodiments of the present invention are described in detail below in conjunction with the accompanying drawings so that the advantages and features of the present invention can be more easily understood by those skilled in the art. It should be noted that the description of these embodiments is used to help understand the present invention, but does not constitute a limitation of the present invention.

[0053] Figures 1 to 11 A microfluidic sample processing device is shown, which uses the robotic arm liquid transfer system of this embodiment. Figures 1 to 11 As shown, the robot arm liquid transfer system mainly includes a robot arm 5, a negative pressure liquid suction device 6, a lifting device 7 and a translation device 8. The robot arm 5, the negative pressure liquid suction device 6 and the translation device 8 are all arranged on the frame 1 of the microfluidic sample processing device. The outer cover of the frame 1 is provided with a shell 10, and the above-mentioned devices are all covered in the shell 10. The microfluidic sample processing device mainly includes a tray device 4, which is used to accommodate reagents and a chip fixture 3 with a microfluidic chip installed; the robot arm 5 has a gun head 51 for loading the chip fixture 3, and the gun head 51 is provided with an air flow channel for connecting the inner cavity of the chip fixture 3; the negative pressure liquid suction device 6 is used to provide air pressure for the air flow channel of the gun head 51, including negative pressure for liquid suction and positive pressure for liquid discharge; the lifting device 7 is used to drive the gun head 51 to rise and fall to load the chip fixture 3 or to insert or detach the chip fixture 3 from the reagent; the translation device 8 is used to drive the gun head 51 to move above the chip fixture 3 or above the reagent. The tray device 4 is located below the robot arm 5, and the robot arm 5 is arranged on the translation device 8 and connected to the lifting device 7. Specifically, one or more reagent kits 2 are installed on the tray device 4, and the reagent kit 2 contains a chip fixture 3, and the microfluidic chip is installed in the chip fixture 3 and fixed by the chip fixture 3. Figure 1As shown, a door 101 is provided on the housing 10 , and the door 101 can be slid up and down. The door 101 is arranged opposite to the tray device 4 . When the door 101 slides upward, the tray device 4 is exposed, so that the reagent kit 2 can be easily installed or replaced.

[0054] In this embodiment, the tray device 4 is equipped with a plurality of reagent kits 2 arranged in parallel along the left-right direction (such as Figure 3 As shown, four reagent kits 2 can be installed in the tray device 4 at one time). Figure 5 As shown, the reagent kit 21 includes a box body 20, and the box body 20 is provided with a waste liquid collection hole 21 for inserting the chip fixture 3 and storing waste liquid, one or more reagent holes for storing reagents, and a chip recovery hole 28 for recovering the chip fixture 3. The reagent holes specifically include a fixing liquid hole 22 for storing a fixing liquid, a buffer hole 23 for storing a buffer, a primary antibody hole for storing a primary antibody, a secondary antibody hole 26 for storing a secondary antibody, and a staining liquid hole 27 for storing a staining liquid. Among them, the primary antibody hole specifically includes a first primary antibody hole 24 for storing a first primary antibody and a second primary antibody hole 25 for storing a second primary antibody. The waste liquid collection hole 21 and the chip recovery hole 28 are respectively stepped holes with an upper aperture larger than a lower aperture to match the shape of the chip fixture 3, so as to facilitate the insertion of the chip fixture 3. The chip recovery hole 28 is a long hole or a waist-shaped hole, and the length direction of the chip recovery hole 28 is consistent with the length direction of the box body 20. In the reagent kit 21, the reagents and chip fixture 3 are used once in the reagent kit 21; it can handle multiple steps such as pipetting, sorting, and waste liquid; and it is operated internally, so the risk of contamination is low. Moreover, the reagent kit 21 is designed as an overall unit, and the reagents in the reagent wells are stored separately without mixing, which is suitable for different usage concentrations in different steps and can be used for long-term storage. The reagent storage area and the reagent kit 21 are an integral structure, which makes the reagent storage more stable and more stable during operation. The waste liquid collection hole 21 in the reagent kit 21 is both the installation position of the chip fixture 3 and the waste liquid treatment position, which saves space for the reagent kit 21 and does not require the operator to prepare additional containers to collect waste liquid.

[0055] The waste liquid collection hole 21 and the chip recovery hole 28 are respectively located at the front and rear ends of the box body 20, the fixative hole 22, the buffer hole 23 and the primary antibody hole are sequentially arranged between the waste liquid collection hole 21 and the chip recovery hole 28, and the secondary antibody hole 26 and the staining liquid hole 27 are arranged side by side between the primary antibody hole and the chip recovery hole 28. In other words, the waste liquid collection hole 21, the fixative hole 22, the buffer hole 23, the primary antibody hole, the secondary antibody hole 26 or the staining liquid hole 27, and the chip recovery hole 28 are sequentially arranged in intervals along the length direction (i.e., the front and rear direction) of the box body 20. In this embodiment, the waste liquid collection hole 21 is used to store samples (such as blood, urine, tissue fluid, cerebrospinal fluid and other body fluids), reagents, etc. discharged from the microfluidic chip; the fixative hole 22 stores the fixative; the buffer hole 23 stores the PBS buffer; the first primary antibody hole 24 stores the primary antibody A, and the second primary antibody hole 25 stores the primary antibody B; the secondary antibody hole 26 stores the secondary antibody; and the staining liquid hole 27 stores the DAPI staining liquid.

[0056] Reference Figure 8 As shown, the chip fixture 3 includes a body 30 and a guide tube 31 for aspirating and discharging liquid. The microfluidic chip is installed in the inner cavity of the body 30, and the guide tube 31 extends downward from the body 30 and is connected to the inner cavity. The upper part of the body 30 is formed with a barrel portion 32 for the lower end of the robot arm 5 to be inserted. The barrel portion 32 is hollow and is connected to the inner cavity of the body 30. The body 30 of the chip fixture 3 can store samples, and the guide tube 31 at the lower part can discharge waste liquid and absorb reagents, divert waste liquid flowing through the microfluidic chip and absorb reagents to make it flow through the microfluidic chip for incubation or cleaning, etc., which can facilitate the microfluidic chip to capture target cells or biological molecules in the sample and can easily absorb or discharge reagents.

[0057] The microfluidic sample processing device has a waste liquid collection state, a chip recovery state and a liquid transfer state. When the microfluidic sample processing device is in the waste liquid collection state, the chip fixture 3 is inserted into the waste liquid collection hole 21 of the reagent box 21, and its body 30 is located at the upper part of the step hole, and the guide tube 31 is inserted into the lower part of the step hole. Figures 5 to 7 When the microfluidic sample processing device is in the chip recovery state, the chip fixture 3 is inserted into the chip recovery hole 28 of the reagent box 21, and its body 30 is located at the upper part of the step hole, and the guide tube 31 is inserted into the lower part of the step hole. Figures 5 to 7 When the microfluidic sample processing device is in the pipetting state, the chip fixture 3 is separated from the waste liquid collection hole 21, the chip fixture 3 is located above one of the reagent holes, and the flow guide tube 31 is inserted into the reagent hole.

[0058] Specifically, combined Figures 5 to 7As shown, the tray device 4 is provided with a plurality of mounting slots 40 arranged in parallel along the left-right direction, and a reagent box 2 is inserted in each mounting slot 40. In this embodiment, the tray device 4 includes a bottom plate 41 fixedly arranged on the frame 1 and an upper plate 42 fixedly arranged on the bottom plate 41, and the upper plate 42 includes left and right extensions 421 and a plurality of front and rear extensions 422 extending forward from the left and right extensions 421, and the plurality of front and rear extensions 422 are arranged in parallel and at intervals along the left-right direction, and the mounting slots 40 with the front side and the upper side open are respectively formed between any two adjacent front and rear extensions 422. Each front and rear extension 422 is respectively provided with a slot 423 extending in the front-to-back direction, and the slots 423 on the two adjacent front and rear extensions 422 are arranged oppositely, and the left and right side edges of the reagent box 2 are inserted in the corresponding two slots 423. The upper plate 42 is specifically formed by stacking two upper and lower layers of plates, and the slot 423 is formed between the upper and lower layers of plates.

[0059] The upper plate 42 is provided with a positioning mechanism for positioning the reagent box 2. Figure 7 As shown, the positioning mechanism includes a positioning protrusion 424 extending upward formed on the upper plate 42, and a concave portion facing downward is provided on the reagent box. When the reagent box is installed in place, the positioning protrusion 424 is inserted into the concave portion of the reagent box, and the reagent box is fixed in the installation slot 40 with the slots 423 on both sides to prevent the reagent box from shaking. When installing, the left and right side edges of the reagent box 2 are inserted into the slots 423 on both sides, and it is pushed in from the front side of the installation slot 40 until it is stuck on the positioning protrusion 424.

[0060] Furthermore, the tray device 4 also includes a baffle 43, and part of the chip recovery hole is located directly below the baffle 43. The baffle 43 is specifically fixedly arranged on the bottom plate 41 or the frame 1, and the baffle 43 is located above the upper plate 42 and partially blocks the chip recovery hole 28 of the reagent kit below, and is used to prevent the chip fixture 3 from detaching from the chip recovery hole 28. When the microfluidic sample processing equipment is in a waste liquid collection state, the chip fixture 3 can be slidably inserted into the chip recovery hole 28 in the front-to-back direction. When recovering the microfluidic chip, the chip fixture 3 is inserted into the chip recovery hole 28 from the front end of the chip recovery hole 28 (such as Figures 5 to 7 Then, the chip recovery hole 28 is moved to the rear end thereof (such as Figures 5 to 7 The chip fixture 3 is located at the third chip fixture 3 on the left side of the middle), and is restricted in the chip recovery hole 28 by the baffle 43, so that the chip fixture 3 is removed from the robot arm 5.

[0061] In this embodiment, the number of the mechanical arms 5 is multiple, such as Figure 8 The plurality of robotic arms 5 are arranged in parallel along the left-right direction and correspond one by one to the plurality of reagent kits 2 below. Figures 8 to 11As shown, each robot arm 5 comprises a housing 50, a lifting rod 52 movably disposed on the housing 50 in the up-down direction, a gun head 51 disposed on the lower end of the lifting rod 52, and a joint 53 disposed on the upper end of the lifting rod 52. The joint 53 is used to connect to the joint 53 of the negative pressure liquid suction device 6. The lifting rod 52 is hollow, and the negative pressure liquid suction device 6 provides the gun head 51 with air pressure for liquid suction or liquid discharge.

[0062] like Fig. 9 As shown, the gun head 51 includes a body 30, a first flange 511 and a second flange 512 extending outwardly from the outer surface of the lower part of the body 30, the first flange 511 is located a distance above the second flange 512, and the outer diameter of the first flange 511 is smaller than the outer diameter of the second flange 512. The lower end of the gun head 51 is generally gourd-shaped, and when it is inserted into the barrel portion 32 of the chip fixture 3, the connection is relatively firm, preventing the chip fixture 3 from falling off the gun head 51.

[0063] Combination Figure 3 , Figure 4 , Fig.10 and Fig.11 As shown, the lifting device 7 includes a lifting shaft assembly driven to rotate by a lifting power mechanism, one or more circles of teeth are formed on the outer circumferential surface of the lifting shaft assembly, and the lifting rod 52 has a rack portion 521 extending in the up and down directions, and the rack portion 521 and the teeth on the lifting shaft assembly are meshed with each other. Specifically, the above-mentioned lifting power mechanism is specifically a lifting motor 73, and the lifting shaft assembly includes a lifting shaft 71 driven to rotate by the lifting motor 73 and one or more gears 72 that rotate with the lifting shaft 71. A polygonal hole is opened on the gear 72, and the lifting shaft 71 is inserted into the polygonal hole and can allow the gear 72 to move horizontally relative to the lifting shaft 71. The gear 72 is fixedly arranged in the shell 50. The number of the above-mentioned gears 72 corresponds to the number of the robotic arms 5, that is, a gear 72 is fixedly arranged in the shell 50 of each robotic arm 5. As shown Fig.11 As shown, the polygonal hole is specifically a square hole 721, and the cross section of the lifting shaft 71 is correspondingly square. The lifting shaft 71 extends in the left-right direction and sequentially passes through the square holes 721 of the gears 72 in the plurality of mechanical arms 5. When the lifting shaft 71 rotates, the gears 72 can be driven to rotate, and the lifting rod 52 can be driven to move up and down under the cooperation of the gear rack. At the same time, when the mechanical arm 5 is subjected to the left or right force applied by the translation device 8, the gears 72 can be allowed to slide on the lifting shaft 71, so that the mechanical arm 5 can move in the left-right direction under the drive of the translation device 8.

[0064] Combination Figure 3 , Figure 4 and Fig.11As shown, the translation device 8 includes an x-axis component for driving the robot arm 5 to move in the left-right direction and a y-axis component for driving the robot arm 5 to move in the front-back direction, wherein the robot arm 5 is arranged on the x-axis component, the x-axis component is arranged on the y-axis component, and the y-axis component is arranged on the frame 1. Specifically, the x-axis component includes a mounting plate 81 and a lead screw 83 extending in the left-right direction, the lead screw 83 can be rotatably arranged on the mounting plate 81 around its own axis, the lead screw 83 is passed through the robot arm 5 and is connected to the robot arm 5 by a thread. A guide rail 811 extending in the left-right direction is fixedly arranged on the mounting plate 81, and each robot arm 5 can be slidably arranged on the guide rail 811 in the left-right direction, specifically, the housing 50 of the robot arm 5 is connected to the guide rail 811 in a sliding manner. The x-axis component also includes an x-axis motor 82 for driving the lead screw 83 to rotate. The lead screw 83 and the lifting shaft 71 are arranged in parallel, and the lead screw 83 is located above the lifting shaft 71. The lead screw 83 passes through the upper part of the robot arm 5, and the lifting shaft 71 passes through the lower part of the robot arm 5. The y-axis component includes a slide rail 86 extending in the front-back direction and a slider 87 slidably arranged on the slide rail 86. The slide rail 86 is fixedly arranged on the frame 1, and the mounting plate 81 of the x-axis component is fixedly arranged on the slider 87. The y-axis component also includes a y-axis motor 84 and a synchronous belt transmission mechanism 85 driven by the y-axis motor 84. The synchronous belt transmission mechanism 85 is connected to the slider 87.

[0065] Combination Figure 2b and Fig.12 As shown, the negative pressure liquid suction device 6 includes a piston 62 driven by a negative pressure motor 61 to reciprocate along a straight line and a piston shell 63 provided with a gas chamber 631, the piston shell 63 is fixedly arranged on the mounting plate 81, and the piston 62 is movably inserted in the gas chamber 631 of the piston shell 63. The negative pressure liquid suction device 6 also includes an air guide tube (not shown in the figure), one end of the air guide tube is fixedly connected to the piston shell 63 and communicated with the gas chamber 631, and the other end of the air guide tube is fixedly connected to the mechanical arm 5. In this embodiment, the number of pistons 62, gas chambers 631 and air guide tubes is multiple, corresponding to the number of mechanical arms 5. That is to say, a plurality of independent gas chambers 631 are opened in the piston shell 63, and a piston 62 is slidably arranged in each gas chamber 631. When the negative pressure motor 61 drives the piston 62 to reciprocate, the air pressure in the gas chamber 631 and the gun head 51 communicated with the gas chamber 631 through the air guide tube changes accordingly, so that the reagent can be sucked or discharged. The negative pressure liquid suction device 6 uses the piston 62 principle to generate pressure to control the absorption or discharge of liquid in a closed state. When the head is below the liquid surface, the piston 62 moves backward to generate negative pressure to achieve the purpose of absorbing liquid. On the contrary, when there is liquid in the gun head 51, the piston 62 moves forward to generate positive pressure to discharge the liquid. A rubber pad is provided at the front end of the piston 62 to increase the airtightness.

[0066] The negative pressure liquid suction device 6 also includes a piston detection mechanism for monitoring the displacement of the piston 62. Figure 2b As shown, the piston detection mechanism includes a photoelectric detection switch 64 fixedly arranged on the piston housing 63 and a baffle 65 that moves synchronously with the piston 62. When the piston 62 moves to the maximum set displacement, the baffle 65 moves to the photoelectric detection switch position 64, and the photoelectric detection switch 64 is triggered to send a detection signal. The photoelectric detection switch 64 of the piston detection mechanism is electrically connected to the controller through a wire, and the negative pressure motor 61 is electrically connected to the controller through a wire. When the photoelectric detection switch 64 is triggered, a detection signal is sent. The controller receives the detection signal and sends a control signal to stop the operation to the negative pressure motor 61. The negative pressure motor 61 stops operating in response to the control signal, and the piston 62 stops moving. Specifically, the negative pressure motor 61 is installed on the piston housing 63, and the motor shaft of the negative pressure motor 61 is connected to a push plate 611 and drives the push plate 611 to reciprocate along a straight line. A plurality of pistons 62 are fixedly arranged on the push plate 611 and driven to move synchronously by the push plate 611. The baffle 65 is fixedly arranged on the push plate 611.

[0067] The robotic arm pipetting system also includes a fault detection device 9. The fault detection device 9 includes at least one detection unit, and the detection unit includes a pair of spaced-apart photoelectric detection switches and a baffle that moves with the gun tip 51, and the baffle is arranged between the pair of photoelectric detection switches. The baffle is specifically a metal baffle. Specifically in this embodiment, the number of detection units is three, namely a first detection unit, a second detection unit and a third detection unit. The first detection unit is used to detect the moving distance of the gun tip 51 in the up and down direction, the second detection unit is used to detect the moving distance of the gun tip 51 in the left and right direction, and the third detection unit is used to detect the moving distance of the gun tip 51 in the front and back direction. Figure 8 As shown, the first detection unit includes a pair of first photoelectric detection switches 91 and a first baffle 92. The pair of first photoelectric detection switches 91 are arranged near the mechanical arms 5, and are specifically fixedly arranged on the housing 50 of one of the mechanical arms 5. The two are arranged in the up-down direction and have a first interval. The first interval is greater than the maximum set stroke of the lifting rod 52 moving in the up-down direction. The first baffle 92 is fixedly connected to the lifting rod 52 and is located between the pair of first photoelectric detection switches 91. Figure 3 As shown, the second detection unit includes a pair of second photoelectric detection switches 93 and a second baffle 94. The pair of second photoelectric detection switches 93 are arranged near the robot arm 5, and are specifically fixedly arranged at a position near the robot arm 5 on the mounting plate 81. The two are arranged in the left-right direction and have a second interval. The second interval is greater than the maximum set stroke of the robot arm 5 moving in the left-right direction. The second baffle 94 is fixedly connected to one of the robot arms 5 (specifically, the housing 50 of the robot arm 5) and is located between the pair of second photoelectric detection switches 93. Figure 2b and Figure 3 As shown, the third detection unit includes a pair of third photoelectric detection switches 95 and a third baffle (not shown in the figure). The pair of third photoelectric detection switches 95 are fixedly arranged at a position close to the slider 87 of the frame 1, specifically arranged beside the slide rail 86. The two are arranged along the front-to-back direction and have a third interval. The third interval is greater than the maximum set stroke of the robot arm 5 moving along the front-to-back direction. The third baffle is fixedly connected to the slider 87 and is located between the pair of third photoelectric detection switches 95.

[0068] The fault detection device 9 also includes a controller, which is electrically connected to each photoelectric detection switch, and the controller is used to control the robot arm 5 to stop moving after any photoelectric detection switch is triggered. The fault detection device 9 also includes a fault indicator light 96, and the controller is electrically connected to the fault indicator light 96, and the controller is also used to control the fault indicator light 96 to switch the light color after any photoelectric detection switch is triggered. Specifically, the controller is electrically connected to a pair of first photoelectric detection switches 91, a pair of second photoelectric detection switches 93, and a pair of third photoelectric detection switches 95 through wires, respectively, and the controller is also electrically connected to the lifting motor 73, the x-direction motor 82, and the y-direction motor 84 through wires, respectively. When the robot 5 moves in the up-down direction beyond the maximum set displacement, the first baffle 92 moves to a first photoelectric detection switch 91, triggering the first photoelectric detection switch 91 to send a fault signal. After receiving the fault signal, the controller sends a first control signal to stop the operation of the lifting motor 73, the x-direction motor 82 and the y-direction motor 84. At the same time, the controller also sends a second control signal to switch the indication color to the fault indicator 96. In response to the first control signal, the lifting motor 73, the x-direction motor 82 and the y-direction motor 84 stop running. In response to the second control signal, the color of the fault indicator 96 changes from green to red. Figure 1 As shown, the fault indicator light 96 is specifically arranged on the housing 10, and includes a long strip of LED lights; when the microfluidic sample processing device operates normally, the color of the fault indicator light 96 is displayed in green; when the movement of the mechanical arm 5 in any direction exceeds the maximum set stroke, the microfluidic sample processing device is judged to be faulty, each motor stops running, the mechanical arm 5 stops moving, and the fault indicator light 96 is displayed in red. Avoid the erroneous operation of the mechanical arm 5 to damage the sample and the machine itself.

[0069] The detection principle of the photoelectric detection switch used in this embodiment is: when the baffle moves to the photoelectric detection position, it blocks the detection light of the photoelectric detection switch, so that the photoelectric detection switch is triggered. The photoelectric detection switch is typically an infrared detection switch, and the infrared detection switch is triggered when the baffle blocks the infrared light emitted by the infrared detection switch.

[0070] In some other embodiments, the fault detection device 9 further includes a sound alarm device, and the controller is electrically connected to the sound alarm device. The controller is also used to control the sound alarm device to emit a warning sound after any photoelectric detection switch is triggered.

[0071] In the fault detection device 9, there is a small distance between the normal operating range of the mechanical arm 5 and the photoelectric detection switch, which greatly reduces the probability of the photoelectric detection switch being triggered by mistake. Once the mechanical arm 5 fails, the baffle reaches the position of the photoelectric detection switch, and the mechanical arm 5 will stop moving immediately, effectively improving the safety of the machine. The operation is simple and the fault response is intuitive.

[0072] The working process of the robotic arm pipetting system is:

[0073] 1. Load the reagent kit 2 into the mounting slot 40 of the tray device 4. The translation device 8 drives the mechanical arm 5 to move horizontally so that each gun tip 51 is directly above the corresponding chip fixture 3. The lifting device 7 drives the mechanical arm 5 to lift and lower so that the lower end of the gun tip 51 is inserted into the barrel portion 32 of the chip fixture 3, and the chip fixture 3 is loaded on the gun tip 51. At this time, the chip fixture 3 is initially located in the waste liquid collection hole 21, and the sample (body fluid, such as blood, urine, tissue fluid, cerebrospinal fluid, etc.) is stored in the upper section of the chip fixture 3. After the mechanical arm is inserted into the barrel portion 32, it can carry the entire chip fixture 3 to move, and during insertion, the negative pressure liquid suction device 6 provides positive pressure to push the sample into the inner cavity of the chip fixture 3 to flow through the microfluidic chip for cell capture. After the waste liquid passes through the microfluidic chip, it flows out from the lower end guide tube 31 of the chip fixture 3 and remains in the waste liquid collection hole 21. The waste liquid involved in the subsequent operations is recovered into the waste liquid collection hole 21.

[0074] 2. The lifting device 7 drives the robot arm to move upward and moves the chip fixture 3 out of the waste liquid collection hole 21 as a whole; the y-axis motor 84 of the translation device 8 is activated, so that the robot arm 5 drives the chip fixture 3 to move above the fixing liquid hole 22; the lifting device 7 is running, so that the robot arm 5 drives the chip fixture 3 to move downward, and the guide tube 31 is inserted into the fixing liquid hole 22, and the negative pressure liquid suction device 6 provides negative pressure to make the guide tube 31 absorb the fixing liquid in the fixing liquid hole 22, and the fixing liquid passes through the chip from bottom to top to fix the cells captured on the chip; the y-axis motor 84 of the translation mechanism is activated, and the robot arm 5 moves back to above the waste liquid collection hole 21, and the negative pressure liquid suction device 6 provides positive pressure to discharge the fixing liquid to the waste liquid collection hole 21, and the waste liquid treatment in subsequent steps is the same here.

[0075] 3. The robot arm 5 controls the chip fixture 3 to move to the top of the buffer hole 23, and inserts the guide tube 31 into the buffer hole 23 to absorb the PBS buffer and clean the chip. The robot arm 5 moves back to the top of the waste liquid collection hole 21, and the waste liquid is processed to the waste liquid collection hole 21. Repeat twice.

[0076] 4. The robot arm 5 controls the chip fixture 3 to move to the top of the first primary antibody well 24 in sequence, and the guide tube 31 is inserted into the first primary antibody well 24 to absorb the primary antibody A. The chip is incubated with the primary antibody A for 60 minutes. After the waste liquid is discharged from the waste liquid collection well 21, it returns to the buffer well 23, washes twice, and moves to the second primary antibody well 25. Incubate the primary antibody B for 60 minutes. After the waste liquid is discharged from the waste liquid collection well 21, it returns to the buffer well 23, washes twice, moves to the secondary antibody well 26, incubates the secondary antibody for 60 minutes, after the waste liquid is discharged from the waste liquid collection well 21, it returns to the buffer well 23, washes twice, moves to the staining liquid well 27, DAPI staining for 5 minutes, after the waste liquid is discharged from the waste liquid collection well 21, it returns to the buffer well 23, and washes twice.

[0077] 5. The translation device 8 is actuated, so that the robot arm drives the chip fixture 3 to move to the front end of the chip recovery hole 28; the lifting device 7 is actuated, and the robot arm 5 drives the chip fixture 3 to move downward and insert it into the front end of the chip recovery hole; the y-axis motor 84 of the translation device 8 is operated, so that the robot arm 5 drives the chip fixture 3 to move in the chip recovery hole to the rear end of the chip recovery hole, at which time part of the chip fixture 3 is located directly below the baffle 43; the lifting device 7 is actuated, the robot arm 5 moves upward, and the chip fixture 3 is blocked by the baffle 43 and remains in the chip recovery hole, thereby realizing the separation of the chip fixture 3 and the gun head 51.

[0078] The microfluidic sample processing device of this embodiment integrates functions such as cell or biological molecule capture, fixation, cleaning, antibody incubation, and staining, and automatically realizes the above-mentioned series of processing of microfluidic samples, reduces human intervention, has a high degree of automation, and improves processing efficiency; it can also perform synchronous operation on multiple chip fixtures 3 at the same time, facilitates parallel experiments, and further improves processing efficiency; in addition, the structure is compact and the layout is reasonable, which reduces the space occupied by the equipment.

[0079] The above embodiment is only for illustrating the technical concept and features of the present invention, and is a preferred embodiment. Its purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and it cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A mechanical arm pipetting system for a microfluidic sample processing device, characterized in that: include: A mechanical arm, which has a gun head for loading a chip fixture, wherein the gun head is provided with an air flow channel for communicating with the inner cavity of the chip fixture; the mechanical arm also includes a shell and a lifting rod slidably arranged on the shell in an up-and-down direction, wherein the gun head is fixedly arranged at the lower end of the lifting rod; A lifting device, which is used to drive the gun head to lift and lower to load the chip fixture or insert or remove the chip fixture from the reagent, the lifting device includes a lifting shaft assembly driven to rotate by a lifting power mechanism, one or more circles of teeth are formed on the outer circumferential surface of the lifting shaft assembly, the lifting rod has a rack portion extending in the up and down direction, the rack portion and the teeth on the lifting shaft assembly are meshed with each other, the lifting shaft assembly includes a lifting shaft driven to rotate by the lifting power mechanism and one or more gears rotating with the lifting shaft, a polygonal hole is opened on the gear, the lifting shaft is inserted in the polygonal hole and can allow the gear to move horizontally relative to the lifting shaft; and A translation device, used for driving the gun tip to move above the chip fixture or above the reagent; The mechanical arm is arranged on the translation device and connected to the lifting device so as to be located above a tray device; one or more reagent kits are installed in the tray device, and the reagent kits include a box body, and the box body is provided with a chip recovery hole for recovering the chip fixture, and the chip recovery hole is a long hole or a waist-shaped hole; the tray device also includes a baffle, and the baffle partially blocks the chip recovery hole below; The robot arm is configured to carry the chip fixture and be inserted into the chip recovery hole slidably along the front-back direction. When recovering the chip fixture, the robot arm carries the chip fixture and inserts it into the chip recovery hole from the front end thereof, and then drives it to move backward along the chip recovery hole to its rear end. The chip fixture is restricted in the chip recovery hole by the baffle. When the robot arm moves upward, the chip fixture is separated from the gun head, and the chip fixture and the microfluidic chip with captured cells fixed therein are maintained in the chip recovery hole; The chip fixture comprises a body and a guide tube, the microfluidic is installed in the inner cavity of the body, the guide tube extends downward from the body and is connected to the inner cavity; a cylinder part is formed on the upper part of the body for the lower end of the mechanical arm to be inserted, the cylinder part is hollow and is connected to the inner cavity; The box body is also provided with a waste liquid collection hole; the chip fixture is initially located in the waste liquid collection hole, and the upper section of the chip fixture stores a sample. When the gun head is inserted into the barrel portion, the sample is pushed into the inner cavity and flows through the microfluidic chip for cell capture. After the waste liquid passes through the microfluidic chip, it flows from the guide tube into the waste liquid collection hole.

2. The robotic arm liquid transfer system according to claim 1, characterized in that: The gear is fixedly arranged in the housing.

3. The robotic arm liquid transfer system according to claim 1, characterized in that: The translation device comprises an x-direction component for driving the mechanical arm to move along the left and right directions, and the mechanical arm is arranged on the x-direction component.

4. The robotic arm liquid transfer system according to claim 3, characterized in that: The x-axis component includes a mounting plate and a lead screw extending in the left-right direction. The lead screw can be rotatably arranged on the mounting plate around its own axis. The lead screw passes through the robotic arm and is connected to the robotic arm by a thread. A guide component extending in the left-right direction is arranged on the mounting plate, and the shell of the robotic arm can be slidably arranged on the guide component in the left-right direction.

5. The robotic arm liquid transfer system according to claim 3, characterized in that: The translation device also includes a y-direction component for driving the mechanical arm to move along the front-rear direction, and the x-direction component is arranged on the y-direction component.

6. The robotic arm liquid transfer system according to claim 1, characterized in that: The lifting rod is hollow, and the upper end of the lifting rod is arranged at a joint for connecting with a negative pressure liquid suction device.

7. The robotic arm liquid transfer system according to claim 1, characterized in that: The robotic arm liquid transfer system further comprises a negative pressure liquid transfer device for providing the gun head with negative pressure for liquid transfer and positive pressure for liquid discharge and / or a fault detection device for detecting whether the robotic arm exceeds a maximum set stroke.

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