阅读说明：本技术 一种试剂自动分配装置 (Reagent automatic distribution device ) 是由 罗国安 马立东 王乙同 王义明 于 2020-08-06 设计创作，主要内容包括：本发明公开了一种试剂自动分配装置,包括无菌级正压/负压系统、工作液进样单元、稀释液进样单元、电动选项阀单元、分液单元、XY位移载物台单元；所述无菌级正压/负压系统为工作液进样单元和稀释剂进样单元提供精密预压；所述工作液进样单元和稀释液进样单元连接所述分液单元的进液口,所述稀释液进样单元与分液单元之间设置有所述电动选向阀单元,分液单元的出液口位于所述XY位移载物台单元的上方,所述分液单元能够沿Z轴方向进行运动,所述XY位移载物台单元能够沿X轴或Y轴方向进行运动。通过各结构的优化设计和协同能够全自动、快速、精准和按需一步生成试剂的任意溶度且能实现多种试剂按比例任意组合。(The invention discloses an automatic reagent distribution device which comprises an aseptic-grade positive pressure/negative pressure system, a working liquid sample introduction unit, a diluent sample introduction unit, an electric option valve unit, a liquid separation unit and an XY displacement objective table unit, wherein the aseptic-grade positive pressure/negative pressure system comprises a sample introduction unit, a diluent sample introduction unit, an electric option valve unit, a liquid separation unit and an XY displacement; the sterile positive pressure/negative pressure system provides precise prepressing for the working solution sample injection unit and the diluent sample injection unit; the working solution sample introduction unit and the diluent sample introduction unit are connected with a liquid inlet of the liquid separation unit, the diluent sample introduction unit and the liquid separation unit are arranged between the electric direction selection valve unit, a liquid outlet of the liquid separation unit is located above the XY displacement objective table unit, the liquid separation unit can move along the Z-axis direction, and the XY displacement objective table unit can move along the X-axis or Y-axis direction. Through the optimal design and the cooperation of each structure, the arbitrary solubility of the reagent can be generated automatically, rapidly, accurately and in one step as required, and the arbitrary combination of various reagents in proportion can be realized.)

1. An automatic reagent distribution device is characterized by comprising an aseptic-grade positive pressure/negative pressure system, a working solution sample introduction unit, a diluent sample introduction unit, an electric option valve unit, a liquid separation unit and an XY displacement objective table unit;

the sterile positive pressure/negative pressure system provides precise prepressing for the working solution sample injection unit and the diluent sample injection unit;

the working solution sample introduction unit and the diluent sample introduction unit are connected with a liquid inlet of the liquid separation unit, the diluent sample introduction unit and the liquid separation unit are arranged between the electric direction selection valve unit, a liquid outlet of the liquid separation unit is located above the XY displacement objective table unit, the liquid separation unit can move along the Z-axis direction, and the XY displacement objective table unit can move along the X-axis or Y-axis direction.

2. The automatic reagent dispensing device of claim 1, further comprising a main body and a shield assembly, wherein the shield assembly is fixed on the main body by a rotating shaft assembly;

the rotating shaft assembly comprises a magnet fixing ring rotating along the axis of the rotating shaft assembly, a Hall sensor is arranged on the rotating shaft assembly, and the distance between the magnet fixing ring and the Hall sensor is changed to cause the magnetic field sensed by the Hall sensor to change so as to obtain the opening and closing state of the protective cover assembly.

3. The automatic reagent distribution device of claim 1, wherein the working solution sample introduction unit comprises a Z-axis lifting mechanism, a gas path manifold, an adapter and a liquid storage tube;

the gas circuit bus board is fixed on the Z-axis lifting mechanism and moves along the Z axis; the adapter is detachably mounted on the gas circuit bus board;

when the Z-axis lifting mechanism rises to the maximum height, the bottom of a liquid inlet needle in the adapter is positioned above the opening of the liquid storage pipe; when the Z-axis lifting mechanism is lowered to the lowest height, the adapter is in sealing connection with the liquid storage pipe;

the gas circuit cylinder manifold is provided with a plurality of cylindrical cavities and L-shaped gas circuits, the inner wall of each cylindrical cavity is provided with an internal thread structure, and the bottom of each cylindrical cavity is provided with an outlet of a circular vertical through hole and an L-shaped gas circuit.

4. The automatic reagent dispensing device of claim 3, wherein the adapter comprises an adapter body, a liquid inlet needle, a first sealing ring, a second sealing ring, a third sealing ring and a fourth sealing ring;

first main part upper portion of adaptation is provided with the external screw thread stair structure, external screw thread stair structure top is provided with first ring recess, second ring recess and third ring recess respectively by the outside axle center, first ring recess and third ring recess are used for installing first sealing washer and second sealing washer respectively, second ring recess bottom is provided with ventilative through-hole, third ring recess axle center department is provided with the liquid needle that advances that link up, the outside of first main part lower part of adaptation is provided with fourth ring recess and fifth ring recess respectively and is used for installing third sealing washer and fourth sealing washer.

5. The automatic reagent dispensing device of claim 1, wherein the dispensing unit comprises a dispensing head and a dispensing head base moving along the Z-axis, the dispensing head being detachably connected to the dispensing head base;

the bottom of the liquid separation head base is provided with a light emitting diode array and a light transmitting plate lighting assembly;

the liquid separation head comprises a plurality of liquid separation electromagnetic valves and liquid separation spray heads detachably connected with the liquid separation electromagnetic valves, and the liquid separation electromagnetic valves receive reagents from the working solution sample injection unit and the diluent sample injection unit and convey the reagents to the XY displacement objective table unit;

the liquid separation head further comprises a top cover plate and a base component, wherein a liquid separation electromagnetic valve leading-out port is arranged at the position, corresponding to the liquid separation electromagnetic valve, of the top cover plate, and a liquid separation spray head leading-out hole is arranged at the position, corresponding to the liquid separation spray head, of the base component.

6. The automatic reagent dispensing device of claim 5, wherein the bottom of the liquid-separating nozzle is detachably connected with a microfluidic confluence liquid-separating head;

microfluid converges and divides liquid head inside to contain multiunit microfluid passageway, every group microfluid passageway all is equipped with divides liquid shower nozzle adaptation passageway and converges the microchannel, divide liquid shower nozzle adaptation passageway and converge the microchannel and be connected, the reagent stream that divides the liquid solenoid valve to receive divides liquid shower nozzle, divide liquid shower nozzle adaptation passageway and converge the microchannel and get into after converging divide liquid shower nozzle export hole.

7. The automatic reagent distribution device according to claim 6, wherein the confluence micro-channel is a curved structure in the shape of a wavy line, the multiple groups of confluence micro-channels are vertically converged at the bottom of the microfluidic confluence liquid separation head, the width of the convergence structure is not more than 3mm, and the lengths of the multiple groups of confluence micro-channels are the same.

8. The automatic reagent distribution device according to claim 6, wherein the confluence microchannel is of a wavy-line-shaped curved structure, the curve of the curved structure in the confluence microchannel is of a smooth circular arc-shaped structure, a plurality of groups of the confluence microchannels converge at the bottom of the microfluidic confluence liquid-separating head, the included angle between a convergence outlet and the horizontal plane is 15-45 degrees, the width of the convergence outlet is not more than 3mm, and the lengths of the plurality of groups of the confluence microchannels are the same.

9. The automatic reagent dispensing apparatus according to claim 1, wherein the XY-displacement stage unit includes a stage, a Y-axis displacement assembly, and an X-axis displacement assembly;

the object stage is provided with a pore plate device for receiving the reagents discharged after the liquid separation units converge, an opening structure for grabbing and placing the pore plate device is arranged on the periphery of the object stage, the width of the opening structure is 10-50mm, and the edge of the object stage is provided with a spring thimble structure for fixing the pore plate device;

the object stage is arranged on the Y-axis displacement assembly and can reciprocate along the Y axis, the Y-axis displacement assembly is arranged on the X-axis displacement assembly and can drive the object stage to reciprocate along the X axis, and the Y-axis displacement assembly is further provided with a Y-axis cover plate capable of emitting light.

10. The automatic reagent dispensing device according to claim 1, wherein the waste liquid collecting unit is configured to collect waste liquid discharged from the liquid separating unit and discharge the waste liquid to the discharging device, and the waste liquid collecting unit includes a waste liquid collecting tank;

the waste liquid collecting tank comprises a washing liquid cavity and a waste liquid cavity, a washing liquid inlet is formed in the bottom of the washing liquid cavity, a waste liquid outlet is formed in the bottom of the waste liquid cavity, the bottom surface of the washing liquid cavity is higher than that of the waste liquid cavity, and an inclined surface structure is arranged on one side of the waste liquid cavity and close to the bottom of the washing liquid cavity.

Technical Field

The invention belongs to the technical field of reagent distribution, and particularly relates to an automatic reagent distribution device.

Background

At present, the preparation of a concentration gradient solution in biochemical experiments is one of the most basic operations, and in cell experiments and drug screening experiments, reagents such as biomolecules and drugs with different concentrations have great differences on cell behaviors and toxicity. Therefore, when examining the effect of different concentrations of biomolecules and drug doses on cell behavior and toxicity, a group of target solutions with gradient concentration distribution needs to be prepared. The traditional manual concentration gradient preparation method needs accurate calculation, weighing and solution dilution and mixing for many times, a plurality of required reagent containers and complex operation, and the complex operation steps easily cause experiment errors and even errors, so that the accuracy of the experiment result is influenced to a certain extent, and a great amount of time of laboratory workers is occupied. Although most of the automatic pipetting workstations provide the function of configuring the concentration gradient at present, the required concentration gradient is usually obtained by adopting a continuous dilution method, the process usually adopts an electric pipette tip to gradually transfer a certain amount of solution to a next stage and mix the solution uniformly to the required concentration, the operation process is relatively time-consuming, and the superposition of instrument solution distribution errors caused by the gradual dilution process further influences the accuracy of the experimental result. In addition, the air piston type liquid separation principle of the electric pipette head in the automatic pipetting workstation is limited, the micro-solution reagent is difficult to distribute, and the solution with any low concentration is difficult to be accurately prepared in one step, so that the application range of the solution is greatly limited.

On the other hand, the research of in vitro drug combination becomes more and more important, the occurrence and development of diseases are usually comprehensive manifestations of various pathologies when a human body is used as a complex functional system, the specific target of single drug intervention cannot meet the treatment requirements of complex diseases, the in vitro optimization of various drug combinations and the formulation of drug treatment schemes aiming at individual patients become a new trend of modern drug research and development, and the in vitro drug combination has wide development and application prospects. The main bottleneck faced by the research of the combined medicine is the insufficient understanding of the complex interaction of different medicines, one of the important reasons is that the number of the medicines and the dosage combination thereof is huge, and the huge workload caused by manual operation of the medicines is often prohibitive for a large number of potential researchers. Although some high-end automated pipetting workstations currently on the market have the function of configuring multiple drug combinations, the work flow is complex and time-consuming, each drug solution needs to be repeatedly sucked and distributed to a designated position, and the complex operation flow further limits the requirement of high throughput of drug combination experiments. In addition, each liquid medicine is required to be equipped with an independent electric pipetting unit to avoid cross contamination, which not only increases the complexity of instrument control but also brings high instrument selling price. It is worth noting that the same is limited by the air piston type dispensing principle of the electric pipette tip in the automated pipetting station, which is difficult to achieve dispensing of micro-solution reagents, and further limits its ability to generate precise drug dose combinations, causing non-negligible effects on experimental results.

In view of the above, the present invention is particularly proposed.

Disclosure of Invention

The invention aims to provide a reagent automatic distribution device, which solves the problems of difficulty in distributing trace solution reagents, complex reagent distribution workflow, long time consumption and large error of combined medicine dosage.

In order to achieve the purpose, the invention provides an automatic reagent distribution device which comprises an aseptic-level positive pressure/negative pressure system, a working solution sample introduction unit, a diluent sample introduction unit, an electric option valve unit, a liquid separation unit and an XY displacement objective table unit;

the sterile positive pressure/negative pressure system provides precise prepressing for the working solution sample injection unit and the diluent sample injection unit;

the working solution sample introduction unit and the diluent sample introduction unit are connected with a liquid inlet of the liquid separation unit, the diluent sample introduction unit and the liquid separation unit are arranged between the electric direction selection valve unit, a liquid outlet of the liquid separation unit is located above the XY displacement objective table unit, the liquid separation unit can move along the Z-axis direction, and the XY displacement objective table unit can move along the X-axis or Y-axis direction.

Furthermore, the device also comprises a main machine body and a shield assembly, wherein the shield assembly is fixed on the main machine body through a rotating shaft assembly;

the rotating shaft assembly comprises a magnet fixing ring rotating along the axis of the rotating shaft assembly, a Hall sensor is arranged on the rotating shaft assembly, and the distance between the magnet fixing ring and the Hall sensor is changed to cause the magnetic field sensed by the Hall sensor to change so as to obtain the opening and closing state of the protective cover assembly.

Furthermore, the working liquid sample introduction unit comprises a Z-axis lifting mechanism, a gas circuit bus board, a switching adapter and a liquid storage pipe;

the gas circuit bus board is fixed on the Z-axis lifting mechanism and moves along the Z axis; the adapter is detachably mounted on the gas circuit bus board;

when the Z-axis lifting mechanism rises to the maximum height, the bottom of a liquid inlet needle in the adapter is positioned above the opening of the liquid storage pipe; when the Z-axis lifting mechanism is lowered to the lowest height, the adapter is in sealing connection with the liquid storage pipe;

the gas circuit cylinder manifold is provided with a plurality of cylindrical cavities and L-shaped gas circuits, the inner wall of each cylindrical cavity is provided with an internal thread structure, and the bottom of each cylindrical cavity is provided with an outlet of a circular vertical through hole and an L-shaped gas circuit.

Further, the adapter comprises an adapter main body, a liquid inlet needle, a first sealing ring, a second sealing ring, a third sealing ring and a fourth sealing ring;

first main part upper portion of adaptation is provided with the external screw thread stair structure, external screw thread stair structure top is provided with first ring recess, second ring recess and third ring recess respectively by the outside axle center, first ring recess and third ring recess are used for installing first sealing washer and second sealing washer respectively, second ring recess bottom is provided with ventilative through-hole, third ring recess axle center department is provided with the liquid needle that advances that link up, the outside of first main part lower part of adaptation is provided with fourth ring recess and fifth ring recess respectively and is used for installing third sealing washer and fourth sealing washer.

Furthermore, the liquid separation unit comprises a liquid separation head and a liquid separation head base moving along the Z axis, and the liquid separation head is detachably connected with the liquid separation head base;

the bottom of the liquid separation head base is provided with a light emitting diode array, a light transmitting plate and other lighting components;

the liquid separation head comprises a plurality of liquid separation electromagnetic valves and liquid separation spray heads detachably connected with the liquid separation electromagnetic valves, and the liquid separation electromagnetic valves receive reagents from the working solution sample injection unit and the diluent sample injection unit and convey the reagents to the XY displacement objective table unit;

the liquid separation head further comprises a top cover plate and a base component, wherein a liquid separation electromagnetic valve leading-out port is arranged at the position, corresponding to the liquid separation electromagnetic valve, of the top cover plate, and a liquid separation spray head leading-out hole is arranged at the position, corresponding to the liquid separation spray head, of the base component.

Furthermore, the bottom of the liquid-separating spray head is detachably connected with a micro-fluid converging and liquid-separating head;

microfluid converges and divides liquid head inside to contain multiunit microfluid passageway, every group microfluid passageway all is equipped with divides liquid shower nozzle adaptation passageway and converges the microchannel, divide liquid shower nozzle adaptation passageway and converge the microchannel and be connected, the reagent stream that divides the liquid solenoid valve to receive divides liquid shower nozzle, divide liquid shower nozzle adaptation passageway and converge the microchannel and get into after converging divide liquid shower nozzle export hole.

Preferably, the confluence micro-channel is a wavy line-shaped curved structure, the multiple groups of confluence micro-channels vertically converge at the bottom of the microfluidic confluence liquid-separating head, the width of the convergence structure is not more than 3mm, and the lengths of the multiple groups of confluence micro-channels are the same.

Preferably, the confluence microchannel is a wavy linear curved structure, the corner of the curved structure in the confluence microchannel is a smooth arc-shaped structure, the multiple groups of confluence microchannels are converged at the bottom of the microfluidic confluence liquid-separating head, the included angle between a convergence outlet and the horizontal plane is 15-45 degrees, the width of the convergence outlet is not more than 3mm, and the lengths of the multiple groups of confluence microchannels are the same.

Further, the XY displacement stage unit comprises a stage, a Y-axis displacement assembly and an X-axis displacement assembly;

the object stage is provided with a pore plate device for receiving the reagents discharged after the liquid separation units converge, an opening structure for grabbing and placing the pore plate device is arranged on the periphery of the object stage, the width of the opening structure is 10-50mm, and the edge of the object stage is provided with a spring thimble structure for fixing the pore plate device;

the object stage is arranged on the Y-axis displacement assembly and can reciprocate along the Y axis, the Y-axis displacement assembly is arranged on the X-axis displacement assembly and can drive the object stage to reciprocate along the X axis, and the Y-axis displacement assembly is further provided with a Y-axis cover plate capable of emitting light.

Preferably, the waste liquid collecting unit is used for collecting the waste liquid discharged from the liquid separating unit and discharging the waste liquid to the device, and the waste liquid collecting unit comprises a waste liquid collecting tank;

the waste liquid collecting tank comprises a washing liquid cavity and a waste liquid cavity, a washing liquid inlet is formed in the bottom of the washing liquid cavity, a waste liquid outlet is formed in the bottom of the waste liquid cavity, the bottom surface of the washing liquid cavity is higher than that of the waste liquid cavity, and an inclined surface structure is arranged on one side of the waste liquid cavity and close to the bottom of the washing liquid cavity.

The automatic reagent distribution device provided by the invention has the following beneficial effects:

1. the invention relates to an automatic reagent distribution device, which is characterized in that a sterile positive pressure/negative pressure system, a precision pressure regulating unit, an electromagnetic valve group unit, a working liquid sample introduction unit, a diluent sample introduction unit, an electric direction selection valve unit, a liquid separation unit, an XY displacement objective table unit and a waste liquid collection unit are arranged, so that a reagent is distributed according to needs through precision prepressing, and is not contacted with a substrate in the distribution process to realize non-contact distribution, the distribution speed is high, the precision is high, the pollution is small, and the distribution requirement of large-scale volume (nano liter to milliliter) is met; in addition, the XY displacement objective table unit is linked with the liquid separation unit, so that reagent distribution at any position can be realized, and the whole reagent distribution process is fully automatic;

2. according to the automatic reagent distribution device, the detachable micro-fluid confluence liquid distribution head is arranged in the liquid distribution unit, so that the effect that any concentration of the reagent can be generated in one step as required or a plurality of reagents with different proportions can be combined into any micropore of the pore plate in the XY displacement objective table unit in one step as required can be realized, the XY displacement objective table unit does not need to independently address each liquid distribution spray head, and the time required by reagent distribution is greatly saved; in addition, the required reagent concentration or the combination of a plurality of reagents in different proportions is generated in one step, so that the problem that the accuracy of an experimental result is further influenced by the superposition of instrument solution distribution errors caused by a step-by-step dilution process is avoided;

3. according to the automatic reagent distribution device, the optimized detachable microfluid confluence liquid-separating head is arranged in the liquid-separating unit, the multiple groups of confluence microchannels are converged at the bottom of the microfluid confluence liquid-separating head, and the included angle alpha between the convergence outlets and the horizontal plane is 15-45 degrees, so that the functions in the beneficial effects can be realized, the impact force of the distributed reagent liquid can be effectively guided to the hole wall of the hole plate by setting the convergence outlets at the bottom of the microfluid confluence liquid-separating head to form a certain angle with the horizontal plane, the impact and disturbance of high-speed liquid generated in the reagent distribution process on 2D or 3D cultured cells in the hole plate are further reduced, and the cells are prevented from being blown out of a designated culture area, or are prevented from being damaged or even necrotized to different degrees due to extremely high fluid shearing force;

4. according to the automatic reagent distribution device, the liquid distribution head and the liquid distribution head base in the liquid distribution unit are designed to be detachable, so that the liquid distribution head is convenient for a user to detach and maintain in the later period, the liquid distribution head can be provided with various types according to different structural styles, more flexible selection and additional functions are provided for the user, and the later-period use cost of the user can be effectively reduced;

5. according to the automatic reagent distribution device, the Z-axis lifting mechanism, the gas path collecting plate, the adapter and other components are arranged in the working liquid sample introduction unit, so that a user can disassemble and assemble the reagent liquid storage pipe and perform subsequent operations such as replacement or reagent addition by only one hand, the design greatly reduces the complexity and difficulty of the user in operating the device, and improves the working efficiency of the user;

6. the automatic liquid changing device can automatically, quickly and accurately generate any solubility of the reagent in one step as required through the optimized design and cooperation of all the structures, can realize the random combination of various reagents in proportion, and can meet the increasing requirements of cell experiments, drug screening experiments and in-vitro drug combination research. The invention can be used for cell experiments, drug screening, tumor organoid chemotherapy drug sensitivity detection and the like.

Drawings

FIG. 1 is a schematic view of the overall configuration of an automatic reagent dispensing apparatus according to this embodiment;

FIG. 2 is a block diagram showing the structure of an automatic reagent dispensing apparatus according to the present embodiment;

FIG. 3 is an exploded view of the spindle assembly of the present embodiment;

FIG. 4 is a schematic plan view of the spindle assembly of the present embodiment;

FIG. 5 is an exploded view of the working fluid sample injection unit according to the present embodiment;

fig. 6 is a schematic structural diagram of the gas path bus plate according to the present embodiment;

fig. 7 is a bottom view of the gas path bus plate of the present embodiment;

FIG. 8 is an exploded view of the adaptor adapter of the present embodiment;

FIG. 9 is a top view of the adaptor adapter of the present embodiment;

FIG. 10 is a center cross-sectional view of the adaptor adapter of the present embodiment;

FIG. 11 is a side view of the working fluid sample introduction unit of the present embodiment at the maximum elevation;

FIG. 12 is a side view of the working fluid sample introduction unit of this embodiment at a lowermost lowered height;

FIG. 13 is a schematic structural view of a liquid separation unit according to this embodiment;

FIG. 14 is an exploded view of the base of the dispensing head according to this embodiment;

FIG. 15 is an exploded view of the dispensing head according to this embodiment;

FIG. 16 is a schematic structural view of a microfluidic confluent droplet separating head with a confluent microchannel converging outlet perpendicular to a horizontal plane according to this embodiment;

FIG. 17 is a schematic structural view of a microfluidic confluent droplet separating head with an included angle of 15-45 degrees between a confluent microchannel convergence outlet and a horizontal plane according to this embodiment;

FIG. 18 is a bottom view of the dispensing head of this embodiment;

FIG. 19 is a side view of the dispensing head of this embodiment after mounting a microfluidic confluent dispensing head;

FIG. 20 is a front view of the dispensing head of this embodiment after mounting a microfluidic confluent dispensing head;

fig. 21 is a schematic structural view of the XY-displacement stage unit of the present embodiment;

fig. 22 is a schematic structural view of the stage according to the present embodiment;

FIG. 23 is an exploded view of the Y-axis displacement assembly of this embodiment;

FIG. 24 is a cross-sectional view of the Y-axis displacement assembly of this embodiment;

FIG. 25 is a schematic view showing the connection of piping of the waste liquid collecting unit according to the present embodiment;

fig. 26 is a schematic structural view of a waste liquid collecting tank according to the present embodiment.

In the figure:

1. a main body; 2. a transparent shield assembly; 21. a transparent shield body; 22. a rotating shaft assembly; 221. a rotating shaft cover; 222. a rotating shaft gasket; 223. a rotating shaft connecting frame; 224. a damping rotating shaft; 225. a magnet fixing ring; 2251. a cylindrical magnet; 226. a Hall sensor support; 227. a Hall sensor; 3. an aseptic-grade positive/negative pressure system; 4. a precise voltage regulating unit; 5. an electromagnetic valve group unit; 6. a working liquid sample introduction unit; 61. a Z-axis lifting mechanism; 62. a gas circuit bus board; 621. a circular vertical through hole; 622. an L-shaped gas circuit; 623. a cylindrical cavity; 63. adapting the adapter; 631. an adapter body; 6311. a first annular groove; 6312. a second annular groove; 6313. a third annular groove; 6315. a ventilation through hole; 6316. a fourth annular groove; 6317. a fifth annular groove; 632. a liquid inlet needle; 633. a first seal ring; 634. a second seal ring; 635. a third seal ring; 636. a fourth seal ring; 64. a liquid storage pipe; 65. a filter holder; 66. an in-line filter; 67. quick-release or hand-screw; 7. a diluent sample introduction unit; 8. an electric direction selection valve unit; 9. a liquid separation unit; 901. a reagent combination zone; 902. a reagent dilution zone; 91. a liquid separation head; 911. a top cover plate; 912. a base member; 913. a circuit board assembly; 914. the circuit connects the female/male plug soon; 915. a liquid separation electromagnetic valve; 9151. a liquid separation spray head; 9152. a microfluidic confluence and diversion head; 91520. a microfluidic channel; 91521. the liquid separation spray head is matched with the channel; 91522. a sink flow microchannel; 9153. a microfluidic confluence and diversion head; 91530. a microfluidic channel; 91531. the liquid separation spray head is matched with the channel; 91532. a sink flow microchannel; 916. quick release/hand screw; 917. a bottom dust cover plate; 9171. a liquid separation spray head leading-out hole; 9172. a cylindrical magnet; 918. left and right dust-proof cover plates; 919. frosted/transparent light guide posts; 92. a liquid separation head base; 921. a circuit board; 922. the circuit is connected with a male/female plug quickly; 923. an array of light emitting diodes; 924. a bottom cover plate; 925. frosted/transparent light-transmitting panels; 10. an XY-displacement stage unit; 101. an object stage; 1010. an orifice plate assembly; 1011. an open structure; 1012. a spring thimble structure; 10121. a threaded outer shell; 10122. a spring; 10123. telescopic steel balls; 10124. a groove; 102. a Y-axis displacement assembly; 1021. a Y-axis cover plate; 10211. a strip-shaped light transmission hole; 1022. a light guide plate; 10221. a light emitting diode assembly; 1023. an object stage support; 10231. a rectangular light-shielding portion; 1024. a slider; 1025. a guide rail; 1026. a Y-axis base; 10261. a driving wheel; 10262. a driving wheel; 10263. a drive motor; 10264. a limit sensor; 103. an X-axis displacement assembly; 11. a waste liquid collection unit; 111. a waste liquid collecting tank; 1111. a wash solution inlet; 1112. a waste liquid outlet; 1113. a wash chamber; 1114. a waste fluid chamber; 1115. a bevel structure; 112. washing a liquid pump; 113. a lotion bottle; 114. a waste liquid pump; 115. waste liquid bottle.

Detailed Description

The present invention will be described in further detail with reference to specific embodiments in order to make the technical field better understand the scheme of the present invention.

The invention can be used for cell experiments, drug screening, tumor organoid chemotherapy drug sensitivity detection and the like.

As shown in fig. 1-2, an automatic reagent distribution device includes a main body 1, a shield assembly, a sterile positive/negative pressure system 3, a precision pressure regulating unit 4, an electromagnetic valve unit 5, a working solution sample injection unit 6, a diluent sample injection unit 7, an electric option valve unit 8, a liquid separation unit 9, an XY displacement stage unit 10, and a waste liquid collection unit 11. The protection cover assembly is connected with a main machine body through a rotating shaft assembly 22, the sterile positive pressure/negative pressure system 3 is sequentially connected with a precision pressure regulating unit 4 and an electromagnetic valve group unit 5 through pneumatic pipelines, the electromagnetic valve group unit 5 is further connected with a working liquid sampling unit 6 and a diluent sampling unit 7 through pneumatic pipelines respectively, the working liquid sampling unit 6 is further connected with a liquid separating unit 9 through a solution pipeline, the diluent sampling unit 7 is further connected with an electric direction selecting valve unit 8 and a liquid separating unit 9 through a solution pipeline sequentially, the liquid separating unit 9 can move up and down along the Z-axis direction, the XY displacement objective table unit 10 is located below the liquid separating unit 9 and can move front and back and left and right along the X-axis direction or the Y-axis direction, and the waste liquid collecting unit 11 is located below the XY displacement objective table unit 10. The main machine body 1 is provided with an action executing mechanism, the action executing mechanism sends an instruction to the action executing mechanism of the lower computer control system through the computer human-computer interface control mechanism, the computer human-computer interface control mechanism can control the action executing mechanism to drive the liquid separating unit 9 to descend to the lowest part and to be close to the waste liquid collecting unit 11, the positive pressure system in the aseptic-level positive pressure/negative pressure system 3 is controlled to start working, and set precise prepressing is provided for the working liquid sample injection unit 6 and the diluent sample injection unit 7 through the precise pressure regulating unit 4 and the electromagnetic valve group unit 5. The computer human-computer interface control mechanism is connected with each component device of the automatic reagent distribution device through a wired or wireless network.

As shown in fig. 3-4, the shield assembly comprises a shield body and a rotating shaft assembly 22, wherein the shield body can be made of transparent material to form a transparent shield body 21, and in this case, the shield assembly is a transparent shield assembly 2. The transparent shield body 21 of the transparent shield assembly 2 is fixed on the main body 1 by the rotation shaft assembly 22, and the rotation shaft assembly 22 includes a rotation shaft cover 221, a rotation shaft gasket 222, a rotation shaft connection frame 223, a damping rotation shaft 224, a magnet fixing ring 225 and a hall sensor bracket 226. One end of the rotating shaft connecting frame 223 is fixedly connected to the transparent shield main body 21 by using a screw, the other end of the rotating shaft connecting frame 223 is connected to the main body 1 through a damping rotating shaft 224 and a magnet fixing ring 225, the damping rotating shaft 224 and the magnet fixing ring 225 are arranged on the inner side and the outer side of the casing of the main body 1, and the magnet fixing ring 225 rotates around the axis of the damping rotating shaft 224 along with the rotation of the rotating shaft connecting frame 223; the spindle connection frame 223 and the damping spindle 224 are located outside the main body 1, the spindle cover 221 covers the connection position of the spindle connection frame 223 and the main body 1, and a spindle gasket 222 is arranged between the spindle cover 221 and the spindle connection frame 223; the magnet fixing ring 225 is located inside the housing of the main body 1, and a cylindrical magnet 2251 is embedded inside the magnet fixing ring 225. The hall sensor support 226 surrounds the magnet fixing ring 225, and two hall sensors 227 are provided on the hall sensor support 226, and the axial centers of the two hall sensors 227 are perpendicular to each other, by which the two hall sensors 227 can sense the fully closed position and the fully open position of the transparent shield main body 21; when the transparent shield main body 21 is opened, the damping rotating shaft 224 and the magnet fixing ring 225 are driven by the rotating shaft connecting frame 223 to rotate, the distance between the cylindrical magnet 2251 in the magnet fixing ring 225 and the hall sensor 227 is changed, and then the hall sensor 227 senses the change of the magnetic field, and after one of the hall sensors 227 senses the change of the magnetic field, the pressure container in the automatic reagent dispensing device is controlled to unload the pressure, and the lighting system is started for other operations, so that the operation of a user is facilitated while the user can be protected; when the transparent shield main body 21 is completely opened, the other hall sensor 227 senses the change of the magnetic field and informs a user through a system interface that the operation of replacing or adding the reagent and the like can be performed on the working solution sample introduction unit 6.

The working solution sample introduction unit 6 is used for accommodating a reagent mother solution required by the device for distributing the reagent and is responsible for introducing a precision prepressure into the reagent container to drive the reagent to perform subsequent distribution and other operations.

As shown in fig. 5-12, the working fluid sampling unit 6 includes a Z-axis lifting mechanism 61, a gas path confluence plate 62, a switching adapter 63, a liquid storage tube 64, a filter support 65, an on-line filter 66 and a quick-release or manually-screwed screw 67, the Z-axis lifting mechanism 61 is installed on the main body 1 and controlled to lift by an action actuator, the Z-axis lifting mechanism 61 is provided with a slider connection frame for the gas path confluence plate 62 to be fixed on the Z-axis lifting mechanism 61 and to lift along the Z-axis, the upper portion of the switching adapter 63 is detachably installed on the gas path confluence plate 62, the lower portion of the switching adapter 63 can be embedded into the upper opening portion of the liquid storage tube 64, the on-line filter 66 is detachably fixed on the gas path confluence plate 62 through the filter support 65 and the quick-release or manually-screwed screw 67.

The air path collecting plate 62 is provided with a plurality of cylindrical cavities 623 and an L-shaped air path 622, the inner wall of each cylindrical cavity 623 is provided with an internal thread structure, the bottom center axis of each cylindrical cavity 623 is provided with a circular vertical through hole 621, the circular vertical through hole 621 is connected with the outlet of the L-shaped air path 622, and the inlet direction of the L-shaped air path 622 faces one side of the Z-axis lifting mechanism 61.

The adapter 63 comprises an adapter main body 631, a first sealing ring 633, a second sealing ring 634, a third sealing ring 635, a fourth sealing ring 636 and a liquid inlet needle 632 penetrating through the adapter main body, wherein an external thread step structure 6318 matched with an internal thread structure of the cylindrical cavity 623 is arranged on the upper portion of the adapter main body 631, the adapter main body 631 is detachably screwed in the cylindrical cavity 623 at the bottom of the gas path confluence plate 62, a first circular groove 6311, a second circular groove 6312 and a third circular groove 6313 are arranged at the top of the external thread step structure 6318 from the outside to the axis, the first circular groove 6311 and the third circular groove 6313 are used for mounting the first sealing ring 633 and the second sealing ring 634, a gas-permeable through hole 6315 penetrating through the adapter main body 631 is arranged at the bottom of the second circular groove 6312, and a through hole is arranged at the axis of the third circular groove 6313 and used for penetrating through the liquid inlet needle 632. The lower outer side of the adapter main body 631 is provided with a fourth annular groove 6316 and a fifth annular groove 6317 arranged in parallel for mounting the third sealing ring 635 and the fourth sealing ring 636, respectively.

The distance from the center of the circular vertical through hole 621 at the bottom of the cylindrical cavity 623 to the outlet center of the L-shaped air passage 622 is equal to the distance from the center of the air permeable through hole 6315 to the center of the liquid inlet needle 632, and the inner diameter of the circular vertical through hole 621 is larger than the outer diameter of the liquid inlet needle 632 so that the liquid inlet needle 632 can penetrate through the circular vertical through hole 621.

The precision prepressing is conducted into the liquid storage pipe 64 through the air through hole 6315 through the compact L-shaped air passage 622 in the air passage collecting plate 62, no additional pneumatic pipeline is needed on the periphery, the complexity of the working liquid sample injection unit 6 is reduced, and the later maintenance is facilitated. The adapter 63 and the liquid storage pipe 64 adopt a detachable structure, and the design is convenient for replacing the special adapter 63 for the liquid storage pipes 64 of different models; the liquid storage pipe 64 can be directly inserted into or pulled out of the adapter 63, the airtight installation of the liquid storage pipe can be completed without complicated actions such as rotating, screwing and the like, and the operation of a user is more convenient.

As shown in fig. 11, when the Z-axis lifting mechanism 61 is lifted to the maximum height, the working height D from the bottom of the liquid inlet pin 632 to the main body 1 is greater than the height of the liquid storage tube 64, so that a larger operable space is provided for the use, and the liquid storage tube 64 can be conveniently and smoothly mounted on the adapter 63; as shown in fig. 12, when the Z-axis lifting mechanism 61 descends to the lowest height, the liquid storage tube 64 is installed on the adapter 63, the bottom of the liquid storage tube 64 just contacts with the working surface of the main machine body 1, the design can realize the self-locking function of the liquid storage tube 64, and the bottom of the liquid storage tube 64 abuts against the working surface of the main machine body 1 when applying precise pre-pressing, so as to further prevent the liquid storage tube 64 from being separated from the adapter 63, and further prevent precious reagents from leaking or causing danger to an operator due to reagent outflow.

As shown in fig. 13 to 20, the liquid distribution unit 9 is used for dilution distribution or combined distribution of a plurality of reagents, the liquid distribution unit 9 includes a detachable liquid distribution head 91 and a liquid distribution head base 92, so that the liquid distribution head 91 can be detached and maintained in the later period, and the liquid distribution head 91 can be designed into a plurality of models with different structures, thereby providing more flexible selection and additional functions and effectively reducing the later-period use cost; the action executing mechanism of the main body 1 drives the liquid separation head base 92 to perform lifting movement in the Z-axis direction.

The dispenser base 92 includes, internally, a circuit board 921, a circuit quick connect male/female plug 922, a light emitting diode array 923, a bottom cover plate 924, and a light transmissive plate 925, which may be a frosted or transparent light transmissive plate. The quick-connection male/female circuit plug 922 is arranged above the circuit board 921, the light emitting diode array 923 is arranged below the circuit board 921, an empty frame provided with a light transmitting plate 925 is arranged on the bottom cover plate 924, light emitted by the light emitting diode array 923 can pass through the light transmitting plate 925, so that the bottom of the liquid distribution head base 92 has an illumination function, and a better operation view is provided for an operator.

Liquid separation head 91 is including the top apron 911 of shape assorted that from top to bottom distributes, circuit board assembly 913 and base part 912, top apron 911 top is equipped with the protection apron 918 of the components of a whole that can function independently about the detachable, circuit board assembly 913 is trapezoidal, circuit board assembly 913 is connected with the quick female/male plug 914 of circuit in wide department, the intermediate position of the narrower department of circuit board assembly 913 is equipped with a plurality of liquid solenoid valves 915 that divide, the quick female/male plug 914 of circuit in the circuit and the quick male/female plug 922 phase-match of circuit, the bottom of dividing liquid solenoid valve 915 is equipped with detachable liquid distribution shower nozzle 9151, the narrower department lower part of base part 912 is equipped with the bottom shield who can split 917.

The protection apron 918 demountable assembly who realizes with the top through embedding a plurality of cylindrical magnet 9111 in the periphery on the top apron 911 is equipped with a plurality of minute liquid solenoid valve outlet 9112 in the position department that corresponds of dividing liquid solenoid valve 915 on the top apron 911, is equipped with on the top apron 911 between minute liquid solenoid valve outlet 9112 and cylindrical magnet 9111 and divides the light trap 9113 that the outlet 9112 quantity is the same. A plurality of cylindrical cavities 9121 for accommodating the liquid-separating solenoid valves 915 are arranged on the base part 912, screws 916 are arranged on two sides of the base part 912 and used for fixing the liquid-separating head 91 on the liquid-separating head base 92, and the screws 916 can be screws which can be quickly detached or screwed by hands. The department is equipped with branch liquid shower nozzle eduction hole 9171 in the corresponding position department that divides liquid shower nozzle 9151 on the dustproof apron 917 in bottom, the dustproof apron 917 in bottom still is provided with a plurality of cylindrical magnet 9172 and realizes the removable assecmbly with base part 912, be equipped with a plurality of leaded light posts 919 in the position department that corresponds light trap 9113 on the protection apron 918, the light signal of leaded light post 919 feeds back the operating condition who divides liquid solenoid valve 915 to the operator through light trap 9113, the operator's of being convenient for debugging and maintenance.

The bottom of the liquid separation spray head 9151 is connected with a detachable microfluid confluence liquid separation head 9152, the inside of the microfluid confluence liquid separation head 9152 comprises 2-8 groups of microfluid channels, each group of microfluid channels 91520 is provided with a liquid separation spray head adapting channel 91521 and a confluence microchannel 91522, the liquid separation spray head adapting channel 91521 is used for being inserted into the liquid separation spray head 9151 and the liquid separation spray head adapting channel 91521 is connected with the confluence microchannel 91522, the confluence microchannel 91522 is of a wavy line-shaped curved structure, and the corner of the curved structure in the confluence microchannel 91522 is of a smooth arc-shaped structure so as to reduce the resistance of fluid in the microchannel and reduce reagent residues. The multiple groups of converging micro-channels 91522 are vertically converged at the bottom of the microfluidic converging and liquid distributing head 9152, and the width W of the converging structure is less than or equal to 3mm, so that multiple paths of distributed reagents are converged at the bottom through the microfluidic converging and liquid distributing head 9152, multiple reagents can be simultaneously distributed into a single micropore in a pore plate on a bottom objective table, extra displacement action is not needed, each micropore in the pore plate can be subjected to position switching aiming at each liquid distributing spray head 9151, the reagent distribution time is further reduced, and the reagent distribution efficiency is improved; in addition, the width W of the convergence structure is set to be less than or equal to 3mm, so that the width of the convergence structure at the bottom of the microfluidic confluence liquid-separating head 9152 is less than the diameter of micropores in multiple pore plate types such as 6, 12, 24, 48, 96 and 384, the microfluidic confluence liquid-separating head 9152 can be compatible with reagent dispensing operation of multiple pore plate types, the use cost is further reduced, and in addition, the channel lengths of multiple groups of confluence microchannels 91522 are set to be the same, so that the flow resistance of liquid paths dispensed by each path of reagent is the same, and the minimum dispensing amount of each path of reagent is the same under the same precise pre-pressure.

The bottom of the liquid separating spray head 9151 can be connected with another optimized detachable microfluid converging and liquid separating head 9153, the inside of the microfluid converging and liquid separating head 9153 comprises 2-8 groups of microfluid channels, each group of microfluid channels is provided with a liquid separating spray head adapting channel 91531 and a converging microchannel 91532, the liquid separating spray head adapting channel 91531 is used for being inserted into the liquid separating spray head 9151, the liquid separating spray head adapting channel 91531 is connected with the converging microchannel 91532, the converging microchannel 91523 is a wavy linear curved structure, the turning part of the curved structure in the converging microchannel 91523 is a smooth circular arc-shaped structure, a plurality of groups of converging microchannels 91532 converge at the bottom of the microfluid converging and liquid separating head 9153, the included angle alpha range of the converging outlet and the horizontal plane is 15-45 degrees, the width W of the converging outlet is less than or equal to 3mm, and the channel lengths; the microfluidic confluent and liquid-separating head 9153 can realize all functions of the microfluidic confluent and liquid-separating head 9152 through the arrangement, and the impact force of the distributed reagent liquid can be effectively guided to the hole wall of the hole plate by arranging the convergence outlet at the bottom of the microfluidic confluent and liquid-separating head 9153 to form a certain angle with the horizontal plane, so that the impact and disturbance of high-speed liquid generated in the reagent distribution process on 2D or 3D cultured cells in the hole plate are further reduced, and the cells are prevented from being blown out of a specified culture area or from being damaged or even necrotized to different degrees due to extremely high fluid shearing force.

The liquid separation spray head 9151 at the bottom of the liquid separation head 91 is divided into a reagent combination area 901 which is longitudinally arranged and a reagent dilution area 902 which is transversely arranged according to different reagent distribution functions; when a plurality of drug reagent combination tests are carried out, the reagent combination area 901 can be selectively inserted into the microfluid confluence liquid-separating head 9152/9153 of 3-8 groups of microfluid channels according to the types of the distributed reagents so as to synchronously distribute the plurality of reagents; when performing multiple drug reagent dilution assays, the reagent dilution zone 902 is inserted into a microfluidic manifold head 9152/9153 with 2 sets of microfluidic channels for simultaneous dispensing of working reagents and diluents.

The XY-displacement stage unit 10 is located below the liquid separation unit 9, and the well plate device 1010 mounted therein is moved back and forth and left and right in the X-axis or Y-axis direction and is linked with the liquid separation unit 9, so that reagent dispensing at any position can be realized and the whole reagent dispensing process can be automated.

As shown in fig. 21 to 24, the XY-displacement stage unit 10 includes a stage 101, a Y-axis displacement assembly 102, and an X-axis displacement assembly 103, wherein the stage 101 is disposed on the Y-axis displacement assembly 102 and can reciprocate along the Y-axis, and the Y-axis displacement assembly 102 is disposed on the X-axis displacement assembly 103 and can drive the stage 101 to reciprocate along the X-axis.

The object stage 101 is provided with 4 opening structures 1011 on four peripheral sides, the width range of the opening structures 1011 is 10-50mm, enough space is reserved for a user to conveniently grab and place the orifice plate device 1010 in the object stage 101, the object stage 101 is provided with spring thimble structures 1012 symmetrically distributed on the surrounding sides on any two adjacent sides, the spring thimble structures 1012 are used for positioning and fixing the orifice plate device 1010, each spring thimble structure 1012 comprises a threaded shell 10121, a spring 10122 and a telescopic steel ball 10123, the outer side of the bottom of the threaded shell 10121 is provided with a groove 10124 in any shape such as a straight shape, a cross shape, a hexagonal shape or a star shape, and the like, so that the clamping degree of the spring thimble structures 1012 on the orifice plate device 1010 can be conveniently adjusted through a screwdriver.

The Y-axis displacement assembly 102 comprises a Y-axis cover 1021 and a Y-axis base 1026, the Y-axis cover 1021 is provided with a long strip-shaped light-transmitting hole 10211, a light guide plate 1022 and a light-emitting diode assembly 10221 are arranged at the bottom of the Y-axis cover 1021 for indicating the working state of the device, the Y-axis base 1026 is provided with a stage support 1023, a slide block 1024, a guide rail 1025, a driven wheel 10261, a driving wheel 10262, a driving motor 10263 and a limit sensor 10264, at least 2 slide blocks 1024 are arranged on the guide rail for installing the stage support 1023, a protruding rectangular shading part 10231 is arranged at the tail part of the stage support 1023, the slide block 1024, the guide rail 1025, the driven wheel 10261 and the driving wheel 10262 are located on the same central axis CC, and the width Hw of the slide block 1024 is smaller than the effective diameters.

Therefore, the structure of the Y-axis displacement assembly 102 is more compact and lighter, and the loading moment of the Y-axis displacement assembly to the X-axis displacement assembly 103 is reduced to the maximum extent, so that the positioning precision of the XY-displacement stage unit 10 is further improved.

The waste liquid collecting unit 11 is disposed on the main body 1, the waste liquid collecting unit 11 is located below the XY-displacement stage unit 10, and the waste liquid collecting unit 11 is used for collecting waste liquid discharged from the liquid separating head 91 during cleaning or bubble removing of the device and discharging the device, and the degree of cleanliness thereof is crucial to maintain the sterile environment in the device.

As shown in fig. 25 to 26, the waste liquid collecting unit 11 includes a waste liquid collecting tank 111, a washing liquid pump 112, a washing liquid bottle 113, a waste liquid pump 114, and a waste liquid bottle 115, wherein a washing liquid inlet 1111 of the waste liquid collecting tank 111 is sequentially connected to the washing liquid pump 112 and the washing liquid bottle 113 through a pipeline, and a waste liquid outlet 1112 of the waste liquid collecting tank 111 is sequentially connected to the waste liquid pump 114 and the waste liquid bottle 115 through a pipeline.

Waste liquid collecting tank 111 is provided with lotion chamber 1113 and waste liquid chamber 1114, and lotion chamber 1113 bottom links to each other with vertically lotion entry 1111, and lotion chamber 1113's bottom surface is higher than the physical isolation of the bottom surface in order to realize lotion chamber and waste liquid chamber of waste liquid chamber 1114, and one side that lotion chamber 1113's bottom is close to waste liquid chamber 1114 is equipped with inclined plane structure 1115 for flow guide effect with lotion inflow waste liquid chamber 1114 in lotion chamber 1113, and waste liquid chamber 1114 bottom links to each other with vertical waste liquid export 1112. Above-mentioned design additionally provides the lotion for waste liquid collection unit 11 on the waste liquid is collected the function basis and washes the function, makes waste liquid collection unit 11 remain clean sterile condition throughout, avoids polluting whole device system.

The specific work flow of the automatic reagent distribution device is as follows:

(1) when a plurality of drug reagent combination tests are carried out, a reagent combination area 901 at the bottom of a liquid separation head 91 is selectively inserted into a microfluid confluence liquid separation head 9152/9153 of 3-8 groups of microfluid channels according to the types of distributed reagents, an instruction is sent to an automatic reagent distribution device of a lower computer control system through a computer human-computer interface control mechanism, a liquid separation unit 9 is lowered to the lowest part and is close to a waste liquid collection unit 11, a positive pressure system in an aseptic level positive pressure/negative pressure system 3 starts to work and provides set precision prepressing for a working liquid sample injection unit 6 through a precision pressure regulating unit 4 and an electromagnetic valve group unit, then liquid separation electromagnetic valves 915 needing to distribute the reagents in the reagent combination area 901 are sequentially opened and air bubbles are discharged according to the pipeline volume preset by the system, and meanwhile, the waste liquid collection unit 11 works and starts to wash liquid after all the air bubbles are discharged by the liquid separation electromagnetic valves 915, then the liquid separation unit 9 is lifted to the working position, namely above the objective table 101 of the XY displacement objective table unit 10, the XY displacement objective table unit 10 drives the orifice plate device 1010 in the objective table 101 to be displaced to the working position below the liquid separation head 91, a program of reagent distribution work is designed, a plurality of reagent combinations with different proportions are further generated to be arranged in any micropore of the orifice plate device 1010 according to the program, after the reagent distribution work is completed, the XY displacement objective table unit 10 further drives the objective table 101 to carry out rapid reciprocating or rotating motion, so that the plurality of reagent combinations in the orifice plate device 1010 are further mixed completely, finally, a negative pressure system in the aseptic-level positive pressure/negative pressure system 3 starts to work and provides set precise negative pressure for the working liquid sampling unit 6 through the precise pressure regulating unit 4 and the electromagnetic valve group unit, so that the reagent which is not distributed in the pipeline flows back to the liquid storage pipe 64 in the working liquid sampling unit 6, further reducing the waste of reagents and saving the experiment cost.

(2) When a plurality of drug reagent dilution tests are carried out, a required number of microfluid confluence liquid dividing head 9152/9153 with 2 groups of microfluid channels is selectively inserted into a reagent diluting area 902 at the bottom of the liquid dividing head 91 according to the number of types of distributed reagents, an instruction is sent to an automatic reagent distributing device of a lower computer control system through a computer human-computer interface control mechanism, a liquid dividing unit 9 is lowered to the lowest part and is close to a waste liquid collecting unit 11, a positive pressure system in a sterile-level positive pressure/negative pressure system 3 starts to work and provides set precision prepressing for a working liquid sample injection unit 6 and a diluent sample injection unit 7 through a precision pressure regulating unit 4 and an electromagnetic valve group unit, then liquid dividing electromagnetic valves 915 needing reagent distribution in the reagent diluting area 902 are sequentially opened and discharge air bubbles according to the preset pipeline volume of the system, and during the waste liquid collecting unit 915 works simultaneously and starts to wash liquid after all the liquid dividing electromagnetic valves discharge air bubbles, next, the liquid separation unit 9 is lifted to a working position, that is, above the objective table 101 of the XY displacement objective table unit 10, the XY displacement objective table unit 10 drives the orifice plate device 1010 in the objective table 101 to be displaced to a working position below the liquid separation head 91, a program of reagent distribution work is designed, any required concentration of the generated reagent is set to any micropore of the orifice plate device 1010 in one step according to the program, the subsequent work flow is consistent with the work flow when a plurality of pharmaceutical reagent combination tests are performed, and details are not repeated herein.

The distribution frequency of the invention can reach 1000 times per second at most, the liquid separating electromagnetic valves in the reagent combination area 901 or the reagent dilution area 902 can be distributed at the same time, the minimum single distribution amount can reach 1-50 nanoliters, the maximum continuous distribution amount can reach 50 milliliters by precisely adjusting the sample injection pressure of the sterile positive pressure/negative pressure system 3 and replacing the microfluid confluence liquid separating head 9152/9153 with different flow resistances, the reagent distribution accuracy and precision are controlled within 1 percent, the precise reagent distribution in the global range is realized, and the precision of reagent combination or reagent dilution is further ensured.

The inventive concept is explained in detail herein using specific examples, which are given only to aid in understanding the core concepts of the invention. It should be understood that any obvious modifications, equivalents and other improvements made by those skilled in the art without departing from the spirit of the present invention are included in the scope of the present invention.