CN118922523A

CN118922523A - Automatic control system and automatic control method for biochip

Info

Publication number: CN118922523A
Application number: CN202280094275.9A
Authority: CN
Inventors: 洪艳; 邝皓妍; 于群; 李泉水; 孙晓锋; 何福涛; 许军强; 沈梦哲; 陈奥; 黎宇翔; 章文蔚; 徐讯
Original assignee: BGI Shenzhen Co Ltd
Current assignee: Stomics Co ltd
Priority date: 2022-09-30
Filing date: 2022-09-30
Publication date: 2024-11-08
Also published as: WO2024065608A1

Abstract

A biochip automation control system (1) and an automation control method thereof. The biochip automation control system (1) comprises: a working area (4), comprising: at least one biochip reaction area (406), a biochip box (6) for accommodating at least one biochip (7), the biochip box (6) being provided with a concave cavity (61), the concave cavity (61) being configured to accommodate the biochip (7); a reagent loading area (409, 413), storing various types of reagents; and a liquid transfer mechanism (302), being configured to be movable on the plane where the working area (4) is located and to be able to rise and fall in a direction perpendicular to the plane, so as to reach the reagent loading area (409, 413) to suck the reagent and add the reagent to the biochip (7). The biochip automation control system (1) can realize automatic scheduling and control of multiple chips (7), meeting the high utilization rate and high throughput processing requirements of the biochip (7). The automation control method of the biochip automation control system (1) is used for the capture and product collection of transcriptomes and the labeling, capture and product collection of proteomes.

Description

Automatic control system and automatic control method for biochip

Technical Field

The present disclosure relates to the field of biochip automation control, and in particular, to an automation control system and an automation control method for a biochip.

Background

The space transcriptome (Spatial Transcriptomics) is to measure total mRNA of a whole tissue section, combine the space information of the total mRNA with morphological content, and draw the occurrence positions of all gene expression to obtain a gene expression map with complex and complete biological process. The method can be combined with microscopic imaging and sequencing technology to obtain gene expression data and simultaneously reserve spatial position information of samples to the greatest extent, and provides important information for cell functions, phenotypes and positional relationship in tissue microenvironment.

Spatial transcriptome techniques obtain spatial location and corresponding gene expression information, and by performing analysis on the spatial transcriptome data, it is known which signaling pathways are activated by certain cells. Scientists can select genes of interest from data generated by spatial transcriptomics techniques and display their spatially distinct expression on original tissue sections. Since all mRNA is captured, it is no longer limited to viewing only a single gene, but any number of genes can be selected in any combination for viewing and analysis together. These research processes all require the conversion of information within biological tissues into a detectable form by biochemical reactions involving a variety of reagents and often require cumbersome manual operations to repeat biochemical reactions of multiple rounds or steps of different principles.

The existing spatial study technology is mainly based on microfluidic chips, laser microdissection, targeted multiplex staining, capture chips with oligonucleotide chain modification, and the like. Wherein 10X genomics provides mainly manual-based solutions, providing the supporting instrument solutions: laser capture microdissection (Laser capture dissection) of NanoString corporation with Leica-based Bond RX immunohistochemical staining apparatus and GeoMx platform to perform multiple staining and imaging; akoya company is based on PhenoCycler-Fusion multiplex staining and in situ imaging. The above steps are difficult to be considered in terms of high automation degree of biochemical reaction, high spatial resolution, large sample processing flux, wide capture range and the like, either based on semiautomatic biochemical operation+microscopic imaging+sequencing, or based on full-automatic microscope and manual biochemical operation, or based on single Zhang Xinpian full-automatic multiple staining+microscopic imaging.

In addition, the existing space group science matched instruments on the market are mainly concentrated on multiple staining, imaging after staining or combination of the multiple staining and imaging, and the instruments can only process standard glass slides with the length of 25mm and the width of 75mm, and cannot be compatible with the automatic control methods of chips with other sizes. Planar chips for other non-slides are also not adaptable. Meanwhile, only the interested region can be selected to collect the target object, and large-scale total collection of the product is difficult to realize. For example, the function of overall product collection cannot be performed for centimeter-level long and wide tablet chips.

In addition, the inventors found that the protocol involving collection of samples to perform mixed sequencing requires manual time-consuming selection of regions of interest (ROIs), can only be performed at lower throughput, and cannot perform multi-biochip, high throughput processing. Existing instruments generally require additional areas for sealing and/or clamping of the target slide or chip, which does not allow for both high chip utilization and minimizing reagent consumption. Personnel intervention is required.

Disclosure of Invention

The present disclosure provides an automated control system of a biochip, comprising:

A workspace, comprising: at least one biochip reaction zone, arranged with a biochip cartridge containing at least one biochip, the biochip cartridge being provided with a concave cavity configured to contain the biochip; the reagent feeding area is used for storing various types of reagents; and

And a pipetting mechanism configured to be movable in a plane in which the working area is located and to be liftable in a direction perpendicular to the plane so as to reach the reagent loading area to aspirate and apply the reagent onto the biochip.

In some embodiments, the automated control system of the biochip comprises at least one of:

a liquid-transferring gun head feeding area is stored with the liquid-transferring gun head;

A product collection zone for collecting product in the concave cavity;

A biochip loading area in which a biochip cartridge accommodating at least one biochip is stored;

A biochip blanking area in which the biochip cartridge is taken away;

a pipette tip discard area where used pipette tips are discarded;

A sealing cover plate area for storing a sealing cover plate configured to seal the biochip cartridge, the reagent loading area and/or the product collection area;

A code scanning area for scanning codes of the biochip cartridge and the biochip accommodated therein, respectively;

a product storage area for storing the collected product;

The cover is arranged in the biochip reaction area in an openable and closable manner so as to seal the biochip box; and

And the temperature control cover plate area is used for storing the temperature control cover plate, and the temperature control cover plate is configured to cover the reagent feeding area, the product collecting area and the biochip reaction area.

the temperature of the low-temperature reagent feeding area is lower than that of the normal-temperature reagent feeding area;

The temperature control area comprises a low-temperature reagent feeding area, a product storage area and/or at least one biochip reaction area, and the temperature of the temperature control area can be regulated and controlled;

A cover with heating function.

In some embodiments, the concave cavity includes a bottom surface configured to place the biochip thereon and a circumferential wall on which a trough is provided, the trough being configured to be further away from the bottom surface than other portions of the circumferential wall to facilitate extraction of the product from the concave cavity by the pipetting mechanism.

In some embodiments, the groove portion includes an arcuate segment and/or at least two beveled segments intersecting along the circumference of the concave cavity.

In some embodiments, at least two groove portions are uniformly spaced along the circumference of the concave cavity.

In some embodiments, the product collection region is configured to enable the biochip cartridge to be tiltable relative to a plane in which the product collection region resides.

In some embodiments, the inclination angle of the biochip cartridge is no less than 15 degrees.

In some embodiments, the product collection region includes a tilting mechanism configured to tilt the biochip cartridge relative to a plane in which the product collection region resides.

In some embodiments, the tilting mechanism includes a drive device and a carriage that holds the biochip cartridge, the carriage being drivingly coupled to the drive device to rotate the biochip cartridge.

In some embodiments, the drive means comprises a motor, a drive wheel drivingly connected to the motor, and a driven wheel drivingly connected to the drive wheel, the driven wheel being connected to the carrier.

In some embodiments, an automated control system of a biochip includes:

The grabbing mechanism is configured to grab the biological chip box to move on the plane where the working area is located and to be capable of lifting in the direction perpendicular to the plane, so that the biological chip box is grabbed and sent to at least one of the code scanning area, the reagent feeding area, the chip discharging area, the biological chip reaction area and the product collecting area.

In some embodiments, an automated control system of a biochip includes:

and a waste liquid pumping mechanism comprising a waste liquid pumping component which is configured to pump waste liquid reacted on the biochip, wherein the waste liquid pumping component is movable on a plane where the working area is located and is liftable in a direction perpendicular to the plane so as to reach at least one biochip reaction area to pump waste liquid from the biochip cartridge and drain the waste liquid.

In some embodiments, the waste extraction mechanism comprises a suction pump in communication with the waste extraction component, the suction pump comprising at least one of: air pump, diaphragm pump and plunger pump; and/or the waste extraction component comprises a needle or pipette tip.

In some embodiments, the automated control system of the biochip includes a washing zone for the waste extraction mechanism to drain waste thereon, wash the waste extraction mechanism, and/or drain condensate from the temperature control zone.

In some embodiments, an automated control system of a biochip includes:

The negative pressure adsorption component is configured to adsorb the biochip, can move on the plane of the working area and can lift in the direction perpendicular to the plane so as to reach the code scanning area, the biochip feeding area and/or the biochip discharging area.

In some embodiments, the pipetting mechanism is configured to be movable to a reagent loading zone, a pipetting gun head loading zone, and at least one biochip reaction zone such that the pipetting mechanism is capable of moving to the pipetting gun head loading zone to prick the pipetting gun head, to aspirate reagent into the reagent loading zone, to move to the plurality of biochip reaction zones, and to add aspirated reagent onto the biochip.

In some embodiments, the temperature of the cryogenic reagent loading zone is no greater than 4 degrees celsius.

In some embodiments, the pipette tip loading zone is configured as at least two sets of push-pull containers, each set of containers comprising a multi-cartridge pipette tip.

In some embodiments, the pipetting mechanism includes a plurality of pipettes, each capable of independently lifting and changing the pipette tips.

In some embodiments, each of the pipettes may be equidistant from or near each other along the length or width of the work area.

In some embodiments, the pipetting mechanism comprises a first movement mechanism capable of moving with the pipetting mechanism and the waste pumping mechanism comprises a second movement mechanism capable of moving with the waste pumping member, the first and second movement mechanisms being independent of each other or integrated.

In some embodiments, the first and second movement mechanisms each comprise a boom that is movable on a plane of the work area and that is liftable in a direction perpendicular to the plane.

In some embodiments, the grasping mechanism comprises a jaw.

In some embodiments, the biochip cartridge is provided with a plurality of concave cavities arranged in at least one row.

In some embodiments, at least the biochip reaction zone comprises a plurality of biochip reaction zones, the temperatures of the plurality of biochip reaction zones being controlled independently of each other.

In some embodiments, the grasping mechanism is configured to perform one of the following steps to confirm whether the corresponding association of the biochip and biochip cartridge is accurate:

When the bottom of the biochip box is transparent, the grabbing mechanism grabs the biochip box containing the biochip and scans the biochip and the biochip box in the scanning direction respectively;

When the bottom of the biological chip box is opaque, the grabbing mechanism grabs the biological chip box to sweep the codes in the chip blanking area, and the negative pressure adsorption component adsorbs the biological chips one by one to sweep the codes.

In some embodiments, the automated control system of the biochip comprises a biochip placed in a concave cavity having a floor area greater than an area of the biochip such that a gap is formed between a circumferential wall of the concave cavity and the biochip.

The present disclosure also provides an automated control method of an automated control system of a biochip, the automated control system of the biochip being used for transcriptome capture and product collection, the transcriptome capture and product collection being achieved comprising at least one of the following operational steps:

incubation: absorbing the incubation reagent through a pipetting mechanism, adding the incubation reagent into the biochip through the pipetting mechanism, and pumping the waste liquid through a waste liquid pumping mechanism after incubation is performed;

Tissue permeabilization: sucking the permeabilization reagent through a pipetting mechanism, adding the permeabilization reagent into the biochip through the pipetting mechanism, and pumping the waste liquid through a waste liquid pumping mechanism after permeabilization is finished;

reverse transcription: sucking a reverse transcription reagent through a pipetting mechanism, adding the reverse transcription reagent into the biochip through the pipetting mechanism, and pumping waste liquid through a waste liquid pumping mechanism after reverse transcription is completed;

Tissue removal: absorbing the tissue removing reagent through a liquid transferring mechanism, adding the tissue removing reagent into the biochip by a liquid transferring gun head which is carried by the liquid transferring mechanism and absorbs the tissue removing reagent, and pumping the waste liquid by a waste liquid pumping mechanism after the tissue is removed;

Nucleic acid release: absorbing nucleic acid release reagent by a pipetting mechanism, and then adding the nucleic acid release reagent to the biochip by a pipetting gun head carried by the pipetting mechanism and absorbing the nucleic acid release reagent to finish nucleic acid release;

and (3) collecting products: the released nucleic acid is aspirated by a pipetting mechanism and stored.

In some embodiments, the washing is performed between the incubation step and the tissue permeabilization step and/or between the tissue permeabilization step and the reverse transcription step and/or between the reverse transcription step and the tissue removal step and/or between the tissue removal step and the nucleic acid release step.

In some embodiments, the cleaning step is: the cleaning reagent is sucked by the pipetting mechanism, then the pipetting gun head which is carried by the pipetting mechanism and sucked with the cleaning reagent adds the cleaning reagent into the biochip, and then the waste liquid is pumped by the waste liquid pumping component.

The present disclosure provides an automated control method of an automated control system of a biochip, the automated control system of the biochip being used for labeling and capturing of proteomes and product collection, the labeling and capturing of proteomes and the product collection being achieved comprising at least one of the following operation steps:

Closing: the sealing liquid is sucked through the liquid transferring mechanism, then the sealing liquid is added into the biochip by the liquid transferring gun head which is carried by the liquid transferring mechanism and sucked with the sealing liquid, and the waste liquid is pumped away by the waste liquid pumping mechanism after the sealing is finished;

Antibody incubation: absorbing antibody reagent by a pipetting mechanism, adding antibody reagent to the biochip by a pipetting gun head carrying the antibody reagent absorbed by the pipetting mechanism, and pumping waste liquid by a waste liquid pumping mechanism after incubation;

and (3) drying: drying the biochip after the waste liquid is pumped out in a biochip reaction area;

In some embodiments, the washing is performed between the blocking step and the antibody incubation step and/or between the antibody incubation step and the drying step and/or between the drying step and the tissue permeabilization step and/or between the tissue permeabilization step and the reverse transcription step and/or between the reverse transcription step and the tissue removal step and/or between the tissue removal step and the nucleic acid release step.

In some embodiments, the cleaning step comprises: the cleaning reagent is sucked by the pipetting mechanism, then the pipetting gun head which is carried by the pipetting mechanism and sucked with the cleaning reagent adds the cleaning reagent into the biochip, and then the waste liquid is pumped by the waste liquid pumping component.

The automatic control system and the application of the biochip provided by the disclosure can realize the extensible automatic scheduling and control of a plurality of chips, realize the marking and capturing of biological information in tissues, realize the collection function of capturing products, and can be suitable for the analysis of multiple groups of students such as transcriptomes, proteomes, immune groups and the like. The method and the system provided by the disclosure meet the processing requirements of multiple biochips, high utilization rate, high throughput and high automation degree.

Drawings

FIG. 1 is an overall schematic diagram of an automated control system for a biochip of the present disclosure;

FIG. 2 is a schematic layout of the working area of the automated control system of the biochip of the disclosure;

FIG. 3 is a schematic diagram of an operating arm system of an automated control system for a biochip of the present disclosure;

FIG. 4 is a schematic view of a pipetting mechanism;

FIG. 5 is a schematic view of a waste extraction mechanism and a grasping mechanism of the pipetting mechanism;

FIG. 6 is a schematic diagram of a chip loading zone 414, a chip unloading zone 416, and a biochip cartridge of the automated control system of the biochip of the disclosure;

FIG. 7 is a schematic diagram of a seal cover region 410 of an automated control system of a biochip of the present disclosure;

FIG. 8 is a schematic diagram of a tilting mechanism 4081 of a product collection zone 408 of an automated control system of a biochip of the present disclosure;

fig. 9 is a schematic view of a biochip cartridge 6 of the present disclosure containing a biochip 7;

FIG. 10 is a flow chart of performing transcriptome capture and collection using the automated control system of the biochip of the present disclosure;

FIG. 11 is a flow chart of performing proteome capture and collection using the automated control system of the biochip of the present disclosure.

Reference numerals illustrate:

1, an automatic control system of a biochip; 2, a shell, 3, an operating arm system; 4, a working area; 5, an indicator lamp; 6, a biological chip box; 7, a biochip; 61, a concave cavity; 612, concave cavity floor; 613, concave cavity circumferential wall; 611, groove portion; 6111, a first bevel segment; 6112, a second bevel segment; 401, a working platform; 402, a drawing type container, 403, a pipette tip feeding area, 404 and a sensor; 405, a pipette tip discard area; 406, a biochip reaction zone; 4061, a lid; 407, a washing zone, 408, a product collection zone; 4081, a tilting mechanism; 40811, motor; 40812, brackets; 40814, driving wheels; 40815, driven wheel; 409, a normal temperature reagent feeding area; 410, sealing the cover plate area; 4101, sealing a cover plate; 4102, multiple stacked racks; 411, a temperature controlled cover plate area; 4111, temperature control cover plate; 412, a product storage area; 413, a low temperature reagent feeding area; 414, chip loading area; 4141, a multi-layered rack; 415, a code scanning area, 416 and a chip blanking area; 301, a bracket, 302, a pipetting mechanism, 303, a grabbing mechanism, 304 and a waste liquid pumping mechanism; 306, a negative pressure adsorption member; 3051, a first movement mechanism; 3052, a second movement mechanism; 3021, pipetting tips; 3022, a pipette; 3031, clamping jaws; 3041, a waste liquid extraction member.

Detailed Description

The following detailed description of the present disclosure is made in connection with the specific embodiments, and the examples are given solely for the purpose of illustration and are not intended to limit the scope of the disclosure.

As shown in fig. 1, the automation control system 1 of the present disclosure includes a housing 2, an operating arm system 3, a work area 4, and an indicator light 5. A plurality of stations and devices for biochemical experiments of chips are arranged on the working area 4, and the operating arm system 3 is used for automatically operating the steps of each biochemical experiment in the working area 4 according to instructions. The indicator lamp 5 is used for informing a user whether the automatic control system 1 is in a working state, a stopping state, a normal working state, an abnormal working state and the like at present.

In some embodiments, as shown in fig. 2, the working area 4 includes a working platform 401, where the working platform 401 is provided with: the disposable pipette tip can be selected for the pipette tip 3021 in the pipette tip loading area 403, the chip loading area 414, the chip unloading area 416, the sealing cover area 410, the temperature control cover area 411, the low temperature reagent loading area 413, the normal temperature reagent loading area 409, the reagent warm bath area (optional), the biochip reaction area 406, the pipette tip discarding area 405, the cleaning area 407, the code scanning area 415, the product collecting area 408, the product storing area 412, and the like.

The present disclosure achieves fully automatic operations of washing, tissue permeabilization, reverse transcription, tissue removal, nucleic acid release, and product collection by precisely controlling pipetting mechanism extraction/addition of liquid and waste liquid extraction mechanism 304 extraction of waste liquid on work platform 401 of work area 4 by operating arm system 3.

In some embodiments, as shown in fig. 3 and 4, the operation arm system 3 includes a holder 301, a pipetting mechanism 302, a gripping mechanism 303, a waste liquid sucking mechanism 304, a negative pressure adsorbing member 306, and a moving mechanism thereof in the XYZ-axis direction (X is the horizontal long-side direction of the work area, Y is the horizontal short-side direction, and Z is the vertical height direction). The support 301 supports the operation arm system 3 on the working platform 401, the pipetting mechanism 302 comprises four-channel pipetting devices 3022 with variable pitches, each pipetting device 3022 can independently control lifting and replacing a pipetting gun head 3021, has a function of empty suction detection and needle blocking detection, has a function of liquid level detection, can independently control movement on a plane where the working platform is located and follow-up liquid suction and spitting along a Z-axis action, the four-channel pipetting devices 3022 are arranged along a Y-axis direction, and can realize synchronous movement in an XY-axis direction and equidistant opening and closing of each channel in the Y-axis direction with adjustable pitch movement. All pipettes 3022 may cover the pipette tip loading area 403, the biochip reaction area 406, the product storage area 412, the normal temperature reagent loading area 409, the low temperature reagent loading area 413, the pipette tip discarding area 405, and the like.

In some embodiments, as shown in fig. 5, the grabbing mechanism 303 may include a clamping jaw 3031, and may be automatically controlled, where the opening and closing range is adapted to a standard pore plate, and the clamping target includes a biochip cartridge 6, a sealing cover 4101, a temperature control cover 4111, and the like, and has an in-place judging function, and the stroke covers a chip feeding area 414, a chip discharging area 416, a code scanning area 415, a sealing cover area 410, a temperature control cover area 411, a product collecting area 408, a product storing area 412, a low-temperature reagent feeding area 413, a biochip reaction area 406, and the like. Specifically, the clamping jaw 3031 clamps the biochip cartridge 6 to the biochip reaction area 406 for biochemical reaction, and clamps the temperature control cover 4111 to cover the product storage area 412, the low temperature reagent feeding area 413, and/or the biochip reaction area 406.

In some embodiments, the gripper mechanism 303 may perform rotational adjustment under control of a motor or a transmission mechanism to better place the gripper object into the work area 4.

In one embodiment, as shown in fig. 2, optionally, the temperature-controlled cover 4111 has a heating function, and can be grasped and transported by the grasping claw 3031 from the multi-layered rack of the temperature-controlled cover area 411, for example, to cover the sealing cover 4101 on the sealed biochip cartridge 6, or directly cover the biochip cartridge 6, so that the temperature-controlled cover 4101 heats the top area of the biochip cartridge 6, and the condensed water generated in the biochip cartridge 6 due to the temperature difference between the top area of the biochip cartridge 6 and the bottom area of the biochip cartridge 6 heated by the temperature-controlled area is reduced. One temperature control cover 4111 may be placed on each layer of the multi-layer stack of the temperature control cover zone 411, which is identical to the multi-layer stacks 4141 and 4102 shown in fig. 6 and 7.

In some embodiments, as shown in fig. 5, the waste liquid pumping mechanism 304 includes a waste liquid pumping component 3041, a suction pump, a connecting pipeline and a fixing piece, the waste liquid pumping component 3041 is connected with the suction pump through the pipeline, and independent XYZ axial motion control is provided, and the pipeline can move along with the waste liquid pumping component 3041 without interference. The suction pump is, for example, an air pump, a diaphragm pump or a plunger pump. The movement range of the waste liquid pumping member 3041 covers the washing region 407 and the biochip reaction region 406, and the waste liquid pumping member 3041 may be a needle.

In some embodiments, negative pressure suction component 306 is used to suction a chip, such as performing a chip scan. Wherein each negative pressure adsorption member 306 is arranged along the Y-axis direction and is independently movable in the Z-axis direction. During the movement of the negative pressure adsorption component 306 along the X, Y, Z axis direction, the pipeline can move along with the pipeline, and the stroke covers the chip blanking area 416 and the code scanning area 415. The negative pressure suction member 306 may be a vacuum chuck. As shown in fig. 5, the negative pressure adsorbing member 306 may be integrated with the waste liquid extracting member 3041, or may be provided separately from the waste liquid extracting member 3041.

In some embodiments, the biochip reaction area 406 includes a cover 4061, and the cover 4061 is disposed in the biochip reaction area 406 in an openable and closable manner to enclose the biochip cartridge 6. Optionally, the cover 4061 has a heating function, and can independently control the temperature rise and fall within the range of 25-100 ℃ for heating the biochip cartridge 6 and/or the sealing cover 4101, thereby reducing the generation of condensed water due to temperature difference.

In some embodiments, the temperature control region includes two low temperature regions, which are a low temperature reagent feeding region 413 and a product storage region 412, respectively, and three biochip reaction regions 406, a constant temperature can be set in the range of 0-25 ℃ and condensed water generated at low temperature is discharged through a pipe. The three biochip reaction areas 406 can perform temperature rising and lowering during biochip reaction, can accurately and independently control respective temperatures within a range of 25-70 ℃, and has the highest control temperature higher than 90 ℃, and the cover 4061 is matched with the sealing cover 4101 to seal the biochip cartridge 6, specifically, the cover 4061 is in contact with the sealing cover 4101 to transfer heat, so that condensate water is prevented from being generated on the lower surface of the sealing cover 4101, evaporation capacity is effectively reduced, and normal biochemical reaction is ensured. .

In some embodiments, control of the waste extraction mechanism 304, condensate collection zone, pump, switch, and rotary valve may enable condensate draining functions of the waste extraction mechanism 304 in the wash zone 407 and in the low temperature zone.

In some embodiments, the product collection region 408 is configured to have a tiltable function to adjust the angle of the biochip cartridge 6 thereon relative to the plane of the working region 4 for tilting the biochip cartridge 6 during nucleic acid collection, which is advantageous for reducing residual liquid.

In some embodiments, as shown in fig. 8, a tilting mechanism 4081 is provided on the product collection region 408, the tilting mechanism 4081 including a drive device and a carriage 40812 holding the biochip cartridge 6, the drive device being drivingly connected to the carriage 40812 to rotate the biochip cartridge 6 so that the cartridge 6 tilts.

In some embodiments, as shown in fig. 8, the driving device includes a motor 40811, a driving wheel 40814 drivingly connected to the motor 40811, a driven wheel 40815 drivingly connected to the driving wheel 40814 by a belt 40816, and the driven wheel 40815 is connected to a bracket 40812, and when the motor 40816 drives the bracket 40812 to rotate by the driving wheel 40814, the belt 40816, and the driven wheel 40815, the biochip cartridge 6 reciprocates along with the bracket 40812 within an angle range that ensures that the inclination angle of the biochip cartridge 6 is not less than 15 degrees, and at the same time, that the motor has no risk of leakage of liquid, which can allow the clamping jaw 3031 to clamp the biochip cartridge 6 between the bracket 40812 and other stations. The driving device can also drive the bracket 40812 to rotate in a gear transmission mode, a chain transmission mode and the like.

In some embodiments, as shown in fig. 8, the biochip cartridge 6 is provided with a plurality of concave cavities 61, and the biochip is accommodated in the concave cavities 61. The concave chamber 61 includes a bottom surface 612 and a circumferential wall 613, the biochip is placed on the bottom surface 612, a groove portion 611 is provided on the circumferential wall 613, the groove portion 611 is shaped to facilitate the extraction of the product from the concave chamber 61 by the pipetting mechanism 302, and the groove portion 611 is further away from the bottom surface 612 or the biochip than other portions of the circumferential wall 613 than the groove portion 611, which facilitates the extraction of the product from the concave chamber 61 by the pipetting mechanism 302.

In some embodiments, as shown in fig. 9, the biochip 7 is placed in a concave cavity 61 of the biochip cartridge 6. Only one row of biochips 7 is shown placed, the area of the biochips 7 being smaller than the area of the bottom surface 612, such that there is a gap between the biochips 7 and the circumferential wall 613 along the circumference of the bottom surface 612 of the concave cavity 61, such that the gap forms a channel for the flow of the product when the biochip cartridge 6 is tilted, so that the product flows from the high side to the low side.

In some embodiments, as shown in fig. 9, the groove 611 includes a first ramp segment 6111 and a second ramp segment 6112 that circumferentially intersect with the circumferential wall 613. In some embodiments, the number of bevel segments may be greater than two. In some embodiments, the groove 611 may include arcuate segments, such as circular arcs, in addition to the ramp segments.

In some embodiments, at least two groove portions 61 are uniformly spaced along the circumference of the concave cavity 61. As shown in fig. 8, at least two groove portions 61 are arranged at regular intervals along the circumferential direction of the concave chamber 61, which facilitates the pipetting mechanism 302 to withdraw the product from different directions.

In some embodiments, the low temperature reagent loading zone 413 and the ambient temperature reagent loading zone 409 are used for storage of reagents under different temperature conditions. The low-temperature reagent feeding area 409 is suitable for storing a reagent which is more stable at a temperature lower than room temperature (for example, about 4 ℃), and is suitable for storing a reagent which is more stable at room temperature by combining with the temperature control of the temperature control low-temperature area to control the temperature.

In some embodiments, the pipette tip loading area 403 is formed by a group of, for example, 4 cartridges, and may be respectively placed in a drawer type container in multiple groups (for example, two groups) to be pushed and pulled into and out of the working area 4, and the two groups of gun tip cartridge drawers, the chip loading area 414, the chip unloading area 416, the sealing cover plate area 410 and the temperature control cover plate area 411 all have sensors to detect whether the two groups of gun tip cartridges are in place. The code scanning area 415 can be provided with a plurality of code scanning devices, and can realize the code scanning function of two forms including the side surface of the container and the bottom of the chip.

In some embodiments, transferring the biochip cartridge 6 without damaging the biochip is achieved by removing the biochip cartridge 6 at the jaws 3031 of the second movement mechanism 3052; the sealing cover plate 4101 is grasped by the clamping jaw 3031, so that the sealing of the biological chip box 6 is realized. As shown in fig. 7, in the sealing cover region 410, a plurality of sealing covers 4101 are placed in the multi-layered stack 4102, one sealing cover 4101 is placed on each layer of the multi-layered stack 4102, so that the plurality of sealing covers 4101 are stacked up and down in the multi-layered stack 4102, which facilitates taking the plurality of sealing covers 4101 in order from top to bottom.

In some embodiments, the low-temperature reagent feeding area 413 and the product collecting area 408 are controlled at constant temperature, so that the reagent refrigeration and the product preservation are realized; the biochip reaction area 406 adopts temperature change control to improve the working efficiency; the convenience of user operation is considered in the structural design, consumable materials and reagents are convenient to replace, and meanwhile, a reserved reagent space is expanded for potential application. The transfer of a single active biochip is not required to be carried out independently in the working area 4, extra space is not reserved on the biochip, the maximum utilization area of the biochip is ensured, the biochip is arranged in the biochip cartridge 6, the single biochip cartridge 6 can accommodate a plurality of (e.g. 8) chips, the working area 4 can accommodate a plurality of (e.g. 3) biochip reaction areas 406, the reaction temperature in each biochip reaction area 406 can be controlled independently, and the single Zhang Xinpian can realize accurate pipetting control, thereby realizing flux maximization.

In some embodiments, as shown in fig. 6, the biochip cartridge 6 includes a plurality of concave cavities 61 for accommodating a plurality of biochips (e.g., 8 10 mm), each four concave cavities 61 being in a column, the chip back side codes and the biochip cartridge two-dimensional codes are correspondingly associated by scanning the codes, then the entire biochip cartridge is manually placed in the chip loading area 414, and the biochip cartridge 6 is entered into the system along with the chip numbers by identifying the two-dimensional codes on the sides of the biochip cartridge 6. The biochip cartridge 6 is shaped to be gripped by the gripping jaws 3031 of the gripping mechanism. As shown in fig. 6, in the chip loading area 414 and the chip unloading area 416, a plurality of biochip cartridges 6 are placed in the multi-layered stack 4141, and one biochip cartridge 6 is placed on each layer of the multi-layered stack 4141, so that a plurality of biochip cartridges 6 are stacked one on top of another in the multi-layered stack 4141, which facilitates taking the plurality of biochip cartridges 6 in sequence from top to bottom.

In some embodiments, the first corresponding association of the biochip and biochip cartridge 6 to each other by scanning the code may be accomplished by scanning the code, e.g., manually, to correspondingly associate the chip and biochip cartridge and then feeding the chip to the chip loading area 414.

In some examples, confirming whether the corresponding associations of chips and biochip cartridges are accurate by scanning the code confirms whether the associations with each other are accurate by one of:

(1) For the biochip cartridge 6 with transparent bottom, the biochip cartridge 6 containing the biochip is grasped by the grasping mechanism 303, and the biochip cartridge are scanned in the scanning area 415, respectively;

(2) For the biochip cartridge 6 with opaque bottom, when the biochip cartridge 6 is removed from the chip blanking area 416, the codes are scanned by adsorbing each biochip one by one to the biochip cartridge 6 and by the negative pressure adsorbing member 30, respectively.

According to the automated control system of the biochip of the present disclosure, at least one of the following technical advantages may be provided:

completing the automatic marking and capturing processes of different university applications;

The collection rate of the captured products is improved;

Simultaneously processing a plurality of full-chip samples, and the single-day processing flux is high;

the surface of the active chip is not touched, and the chip utilization rate is hundred percent; and

The degree of automation is high, and manual intervention is not needed in the middle.

In some embodiments, as shown in fig. 10, an automated control system employing a biochip is provided to enable transcriptome capture and product collection.

The biochip gets into biochip box 6 after tissue paster pretreatment, and single biochip box 6 is including 8 spill chambeies 61 that hold 8 chips, through sweeping the code with the code at every chip back and the two-dimensional code of biochip box 6 are associated correspondingly, then manually place whole biochip box 6 in chip loading area 414, clamping jaw 3031 moves and gets biochip box 6 to sweep the code area 415 and sweeps the two-dimensional code of code discernment biochip box 6 side, with the serial number of biochip box 6 and corresponding chip together type the system.

The prepared low-temperature reagent and normal-temperature reagent are manually placed in the corresponding low-temperature reagent feeding area 413 and normal-temperature reagent feeding area 409 respectively, and the pipette tip 3021, the sealing cover plate 4101 and the temperature control cover plate 4111 are loaded. The software prompts for confirmation of consumable and chip status based on the in-place signal sensed by sensor 404. After setting and determining the experimental conditions corresponding to the different chips in the software manually, clicking the operation, the clamping jaw 3031 transfers the biochip cartridge 6 from the chip loading area 414 to the biochip reaction area 406, and all or part of the following steps are performed, as shown in fig. 10.

And (3) cleaning: the pipette 3022 is controlled to move to the pipette tip feeding area 403, the pipette tip 3021 is pricked and moved to a position corresponding to the cleaning agent in the reagent feeding area, the liquid level detection function of the pipette 3022 is performed by descending along the Z axis, after success, the cleaning agent of the set volume is sucked, and then the pipette 3022 is moved to the biochip reaction area 406 and descends to a certain height along the Z axis at the position corresponding to the concave cavity 61 of the biochip cartridge 6, and accurate liquid discharge is performed.

Waste liquid pumping step: the control claw 3031 transfers the sealing cover plate on the biological chip box 6 to the sealing cover plate area 410, the waste liquid pumping component 3041 moves to the corresponding concave cavity 61 of the biological chip box 6, descends along the Z axis and controls the waste liquid pump, the valve of the waste liquid pump is opened for 3-10s, the waste liquid pump is lifted along the Z axis and moves to the cleaning area 407, the cleaning pump is opened to fill water to clean the outer wall of the waste liquid pumping component 3041, and the waste liquid pump is opened to pump water to clean the inner wall of the waste liquid pumping component 3041.

Tissue permeabilization step: the pipette 3022 is controlled to take the pipette tip 3021 and withdraw the permeabilization reagent, 4 chips are combined into a group, the permeabilization reagent is added simultaneously, and the software records the precise time for adding the permeabilization reagent and starts timing. According to the difference of the permeabilization time, extracting a permeabilization stopping reagent by a liquid dispenser before the permeabilization time is finished, and adding the reagent into the concave cavity 61 of the biological chip box 6 at a precise time point to stop the permeabilization reaction; or pumping out the reaction waste liquid at a specified permeabilization time, rapidly adding a cleaning reagent, and pumping out the waste liquid. The entire pipetting process is controlled to within 3 minutes to enable adjacent groups of chips to be handled separately.

Reverse transcription: the reverse transcription reagent is added on the washed chip after tissue permeabilization is finished, and the chip is incubated for more than 3 hours at a certain temperature (for example, 42 ℃). If the reverse transcription reagent is added in advance in order to satisfy the chips of different permeabilization times in the same biochip cartridge 6, the temperature is adjusted to 42 ℃ after all the concave cavities 61 in the biochip cartridge 6 are added, and incubated at 42 ℃ for more than 3 hours.

Tissue removal: tissue removal reagents were added to the washed chip after completion of reverse transcription, and incubated at 55℃for 10 minutes or more.

Nucleic acid release: adding nucleic acid release reagent on the washed chip after tissue removal, and incubating at 55 ℃ for more than 3 hours.

Nucleic acid collection: the released nucleic acid cartridge 6 is transferred to the product collection area 408 with the jaw 3031, tilted about 20, the pipette draws the pipette tip 3021 down the Z-axis above the product collection area 408 until it hits the surface of the product in the concave cavity 61, the pipette withdraws the released nucleic acid, and the collected product is transferred into the well plate in the product storage area 412 for storage. The new pipette tip 3021 is replaced to re-withdraw the wash solution and flush the concave cavity 61 and re-collect the product and transfer the re-collected product to the corresponding well of the same well plate for combination with the previously collected product.

When a plurality of biochip cartridges 6 are simultaneously operated, the second and third biochip cartridges 6 start to perform a washing step on the second and third biochip cartridges 6 when the previous biochip cartridge 6 is incubated for a long time in the reverse transcription step, respectively, ensuring that the steps preceding the reverse transcription step are not broken and that the permeabilization time can be strictly controlled.

Subsequent library construction and sequencing will be performed after collection of the collected products to ensure that the resulting nucleic acid, including spatially localized sequences and captured products, can be read and relocated to the original spatial structure, thereby performing reconstruction and accurate localization of spatial information.

In some embodiments, as shown in fig. 11, an automated control system employing a biochip is provided to enable labeling of proteomes and capture product collection.

The biochip enters the biochip box 6 after tissue chip pretreatment, the single biochip box 6 comprises a concave cavity 61 of 8 chips, codes on the back of each chip are correspondingly associated with two-dimensional codes of the biochip box 6 through code scanning, then the whole biochip box 6 is manually placed in a chip feeding area 414, a clamping jaw 3031 moves the biochip box 6 to a code scanning area 415 to scan the two-dimensional codes on the side face of the biochip box 6, and the codes of the biochip box 6 and the corresponding chips are recorded into a system together.

The prepared proteome-related reagents are manually placed in the corresponding reagent loading areas respectively, and the pipette tips 3021, the sealing cover plate 4101 and the temperature control cover plate 411 are loaded. The software prompts for confirmation of consumable and chip status based on the in-place signal sensed by sensor 404. After setting and determining experimental conditions corresponding to different chips in the software manually, clicking and running, the clamping jaw 3031 transfers the biochip cartridge 6 from the chip loading area 414 to the biochip reaction area 406, and all or part of the following steps are started to be executed.

And (3) cleaning: the pipette is controlled to move to a pipette tip feeding area 403, the pipette tip 3021 is pricked, the pipette tip 3021 is moved to a position corresponding to the cleaning reagent 1 in the reagent feeding area, the liquid level detection function of the pipette is performed by descending along the Z axis, the cleaning reagent 1 with a set volume is sucked after success, then the pipette is moved to a biochip reaction area 406, and the pipette tip 3021 is moved down to a certain height along the Z axis at a position corresponding to the concave cavity 61 of the biochip cartridge 6, and accurate liquid discharge is performed. The washing was repeated 3 times.

Closing: the pipette is controlled to move to a pipette tip feeding area 403, the pipette tip 3021 is pricked, the pipette tip is moved to a position corresponding to the sealing liquid in the reagent feeding area, the liquid level detection function of the pipette is performed by descending along the Z axis, the sealing liquid with a set volume is sucked after success, then the pipette is moved to a biochip reaction area 406, and the pipette tip is moved to a certain height along the Z axis at a position corresponding to the concave cavity 61 of the biochip cartridge 6, so that the liquid is accurately poured. Incubate for 30 minutes at room temperature.

Antibody incubation: after removing the sealing liquid, controlling the liquid-transferring device to move to the liquid-transferring gun head feeding area 403, pricking the liquid-transferring gun head 3021, operating to a position corresponding to the antibody reagent in the reagent feeding area, accurately sucking 50-100 mu L of the antibody reagent prepared in advance, then operating the liquid-transferring device to the biochip reaction area 406, and descending to a certain height along the Z axis at the position corresponding to the concave cavity 61 of the biochip cartridge 6, accurately spitting the liquid, enabling the antibody reagent to uniformly cover the surface of the chip, controlling the clamping jaw 3031 to grab the sealing cover plate 4101 to seal the biochip cartridge 6, and incubating for 45 minutes at room temperature.

Washing after antibody incubation: controlling the pipette to extract 300 mu L of cleaning reagent 2 by using the pipette tip 3021, adding the cleaning reagent 2 into the corresponding concave cavity 61 of the biochip cartridge 6, then performing waste liquid pumping operation, and repeating cleaning and waste liquid pumping for more than 3 times; the foregoing washing step using the washing liquid 1 and the waste liquid extracting step are repeated.

And (3) drying: the waste-pumped chip was placed in the biochip reaction area 406 at 42℃for 10 minutes.

Proteome labeling and capturing and product collection also includes tissue permeabilization, reverse transcription, tissue removal, nucleic acid release, product collection, and the like, which are identical to the corresponding steps of transcriptome capturing and product collection. The collected products are processed for subsequent sequencing and interpretation to finally obtain the spatial distribution of complementary proteins corresponding to the specific antibodies with the spatial localization information, thereby obtaining the spatial localization information of the proteome.

Finally, it should be noted that: the above embodiments are merely for illustrating the technical solution of the present disclosure, and are not limiting thereof; although the present disclosure has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or equivalent substitutions can be made to some technical features thereof; such modifications and substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present disclosure.

Claims

An automated control system for a biochip, comprising:

A work area (4) comprising: at least one biochip reaction zone (406) arranged with a biochip cartridge (6) containing at least one biochip, the biochip cartridge (6) being provided with a concave cavity (61), the concave cavity (61) being configured to contain the biochip (7); reagent loading areas (409, 413) for storing various types of reagents; and

A pipetting mechanism (302) configured to be movable in a plane in which the working area (4) is located and to be liftable in a direction perpendicular to the plane so as to reach the reagent feeding area (409, 413) for aspirating a reagent and applying the reagent onto the biochip.
The automated control system of a biochip of claim 1, comprising at least one of:

a pipette tip loading area (403) in which pipette tips (3021) are stored;

A product collection zone (408) for collecting product in the concave cavity (61);

A biochip loading area (414) in which the biochip cartridge (6) accommodating the at least one biochip (7) is stored;

a biochip blanking area (416) where the biochip cartridge (6) is taken away;

a pipette tip discard area (405) where used pipette tips (3021) are discarded;

A sealing cover region (410) storing a sealing cover (4101) configured to seal the biochip cartridge (6);

A code scanning area (415) in which codes are scanned respectively for the biochip cartridge (6) and the biochip (7) accommodated therein;

A product storage area (412) for storing the collected product;

A cover (4061) which is openably and closably provided in the biochip reaction area (406) to close the biochip cartridge (6); and

A temperature controlled cover region (411) storing a temperature controlled cover (4111) configured to cover the reagent loading region (413), the product collection region (408), and/or the biochip reaction region (406).
The automated control system of a biochip of claim 2, comprising at least one of:

A low temperature reagent feeding zone (413) and a normal temperature reagent feeding zone (409) on the reagent feeding zone (409, 413), the temperature of the low temperature reagent feeding zone (413) being lower than the temperature of the normal temperature reagent feeding zone (409);

a temperature control zone comprising the low temperature reagent loading zone (413), the product storage zone (412) and/or the at least one biochip reaction zone (406), the temperature of the temperature control zone being controllable;

-said cover (4061) with heating function.
An automated control system for a biochip according to any of claims 1-3, wherein the concave cavity (61) comprises a bottom surface (612) and a circumferential wall (613), the bottom surface (612) being configured to place the biochip (7) thereon, a groove (611) being provided on the circumferential wall (613), the groove (611) being configured to be further away from the bottom surface (612) than other portions of the circumferential wall (613) in order to facilitate extraction of product from the concave cavity (61) by the pipetting mechanism (302).
The automated control system of a biochip according to claim 4, wherein the trough (611) comprises an arcuate segment and/or at least two beveled segments (6111,6112) intersecting along the circumference of the concave cavity.
The automated control system of a biochip according to claim 4 or 5, wherein at least two groove portions (61) are arranged at uniform intervals along the circumference of the concave cavity (61).
The automated control system of a biochip according to any of claims 2-6, wherein the product collection region (408) is configured to enable tilting of the biochip cartridge (6) relative to a plane in which the product collection region (408) lies.
The automatic control system of a biochip according to claim 7, wherein the inclination angle of the biochip cartridge (6) is not less than 15 degrees.
The automated control system of a biochip according to claim 7 or 8, wherein the product collection region (408) comprises a tilting mechanism (4081) configured to tilt the biochip cartridge (6) relative to a plane in which the product collection region (408) lies.
The automated control system of a biochip according to claim 9, wherein the tilting mechanism (4081) comprises a drive means and a carriage (40812) holding the biochip cartridge (6), the carriage (40812) being drivingly connected to the drive means for rotating the biochip cartridge (6).
The automated control system of a biochip according to claim 10, wherein the drive means comprises a motor (40811), a drive wheel (40814) drivingly connected to the motor (40811), and a driven wheel (40815) drivingly connected to the drive wheel (40814), the driven wheel (40815) being connected to the carriage (40812).
The automated control system of a biochip according to any of claims 1-11, comprising:

And the grabbing mechanism (303) is configured to grab the biological chip box (6) to be movable on the plane where the working area (4) is located and to be liftable in the direction perpendicular to the plane, so as to grab the biological chip box (6) and send the biological chip box to at least one of the code scanning area (415), the reagent feeding areas (409, 413), the chip feeding area (414), the chip discharging area (416) and the biological chip reaction area (406) and the product collecting area (408).
The automated control system of a biochip according to any of claims 1-12, comprising:

A waste extraction mechanism (304) comprising a waste extraction member (3041) configured to extract waste from the reactions on the biochip, the waste extraction member (3041) being movable in a plane in which the working area (4) is located and being liftable in a direction perpendicular to the plane so as to reach the at least one biochip reaction area (406) to extract waste from the biochip cartridge (6) and to drain the waste.
The automated control system of a biochip according to claim 13, wherein the waste extraction mechanism (304) comprises a suction pump in communication with the waste extraction component (3041), the suction pump comprising at least one of: air pump, diaphragm pump and plunger pump; and/or

The waste extraction component (3041) includes a needle or pipette tip (3021).
The automated control system of a biochip according to claim 13 or 14, comprising a washing zone (407) for the waste extraction mechanism (304) to drain the waste thereon, to wash the waste extraction mechanism (304) and/or to drain condensed water from the temperature control zone.
The automated control system of a biochip according to any of claims 2-15, comprising:

And the negative pressure adsorption component (306) is configured to adsorb the biochip, can move on the plane of the working area (4) and can lift in the direction perpendicular to the plane so as to reach the code scanning area (415), the biochip loading area (414) and/or the biochip unloading area (416).
The automated control system of a biochip according to any of claims 2-16, wherein the pipetting mechanism (302) is configured to be movable to the reagent loading zone (409, 413), the pipetting gun head loading zone (403) and the at least one biochip reaction zone (406) such that the pipetting mechanism (302) is capable of moving to the pipetting gun head loading zone (403) to prick pipetting gun heads (3021), to the reagent loading zone (409, 413) to aspirate the reagent, to the plurality of biochip reaction zones (406) and to add the aspirated reagent onto the biochip.
The automated control system of a biochip according to any of claims 3-17, wherein the temperature of the low temperature reagent loading zone (413) is no higher than 4 degrees celsius.
The automated control system of a biochip according to any of claims 2-18, wherein the pipette tip loading zone (403) is configured as at least two sets of push-pull containers, each set of containers comprising a multi-cartridge pipette tip (3021).
The automated control system of a biochip according to any of claims 1-19, wherein the pipetting mechanism (302) comprises a plurality of pipettes (3022), each of the pipettes (3022) being independently liftable and replaceable with the pipetting gun head (3021).
The automated control system of a biochip according to claim 20, wherein each of the pipettes (3022) is arranged along the length or width of the working area (4), each of the pipettes (3022) being equally spaced apart or close to each other.
The automated control system of a biochip according to claim 20 or 21, wherein the pipetting mechanism (302) comprises a first movement mechanism (3051) capable of moving with the pipetting mechanism (302), the waste pumping mechanism (304) comprises a second movement mechanism (3052) capable of moving with a waste pumping component (3041), the first movement mechanism (3051) and the second movement mechanism (3052) being independent of each other or integrated together.
The automated control system of a biochip according to claim 22, wherein the first movement mechanism (3021) and the second movement mechanism (3021) each comprise a boom that is movable on a plane of the working area (4) and that is liftable in a direction perpendicular to the plane.
The automated control system of a biochip according to any of claims 12-23, wherein the grasping mechanism (303) comprises a jaw (3031).
The automated control system of a biochip according to any of claims 2-24, wherein the biochip cartridge (6) is provided with a plurality of concave cavities (61), the plurality of concave cavities (61) being arranged in at least one row.
The automated control system of a biochip according to any of claims 1-25, wherein the at least biochip reaction zone (406) comprises a plurality of biochip reaction zones (406), the temperatures of the plurality of biochip reaction zones (406) being controlled independently of each other.
The automated control system of a biochip according to any of claims 12-26, wherein the grasping mechanism (303) is configured to be able to perform one of the following steps to confirm whether the corresponding association of the biochip (7) and the biochip cartridge (6) is accurate:

When the bottom of the biochip box (6) is transparent, the grabbing mechanism (303) grabs the biochip box (6) containing the biochip (7) and scans codes of the biochip (7) and the biochip box (6) in the code scanning area (415) respectively;

When the bottom of the biochip box (6) is opaque, the grabbing mechanism (303) grabs the biochip box (6) in the chip blanking area (416) to sweep codes, and the negative pressure adsorption component (306) adsorbs all the biochips (7) one by one to sweep codes.
The automated control system of a biochip according to any of claims 1-27, comprising the biochip (7) placed in the concave cavity (61), the concave cavity (61) having a floor area larger than the area of the biochip (7) such that a gap is formed between a circumferential wall (612) of the concave cavity (61) and the biochip (7).
An automated control method of an automated control system of a biochip, using the automated control system of a biochip according to any one of claims 1 to 28 for transcriptome capture and product collection, the transcriptome capture and product collection comprising at least one of the following operations:

Incubation: absorbing the incubation reagent through a pipetting mechanism (302), adding the incubation reagent into the biochip (7) through the pipetting mechanism (302), and pumping the waste liquid through a waste liquid pumping mechanism (304) after incubation is performed;

Tissue permeabilization: sucking a permeabilization reagent through the pipetting mechanism (302), adding the permeabilization reagent into the biochip (7) through the pipetting mechanism (302), and pumping the waste liquid through the waste liquid pumping mechanism (304) after permeabilization;

Reverse transcription: sucking a reverse transcription reagent through the pipetting mechanism (302), adding the reverse transcription reagent into the biochip (7) through the pipetting mechanism (302), and pumping waste liquid through the waste liquid pumping mechanism (304) after reverse transcription is completed;

Tissue removal: the tissue removing reagent is sucked by the pipetting mechanism (302), then the pipetting gun head (3021) which is carried by the pipetting mechanism (302) and sucked with the tissue removing reagent adds the tissue removing reagent into the biochip (7), and after tissue removal is finished, the waste liquid is pumped away by the waste liquid pumping mechanism (304);

Nucleic acid release: sucking a nucleic acid release reagent through the pipetting mechanism (302), and then adding the nucleic acid release reagent to the biochip (7) by a pipetting gun head (3021) carrying the sucked nucleic acid release reagent by the pipetting mechanism (302) and completing nucleic acid release;

and (3) collecting products: the released nucleic acid is aspirated by the pipetting mechanism (302) and stored.
The automated control method of an automated control system for a biochip according to claim 29, wherein washing is performed between the incubating step and the tissue permeabilizing step and/or between the tissue permeabilizing step and the reverse transcription step and/or between the reverse transcription step and the tissue removing step and/or between the tissue removing step and the nucleic acid releasing step.
The automated control method of an automated control system for a biochip of claim 30, wherein the washing step comprises: the cleaning reagent is sucked by the pipetting mechanism (302), then the pipetting gun head (3021) carrying the sucked cleaning reagent by the pipetting mechanism (302) adds the cleaning reagent to the biochip (7), and then the waste liquid is pumped by the waste liquid pumping component (3041).
An automated control method of an automated control system of a biochip, applying the automated control system of a biochip according to any one of claims 1 to 28 to labelling and capturing of proteomes and to collection of products, the labelling and capturing of proteomes and the collection of products being achieved comprising at least one of the following operative steps:

Closing: the sealing liquid is sucked through the liquid transferring mechanism (302), then the sealing liquid is added into the biochip (7) through a liquid transferring gun head (3021) which is carried by the liquid transferring mechanism (302) and is sucked by the liquid sucking mechanism (304), and after the sealing is finished, the waste liquid is sucked by the liquid sucking mechanism;

Antibody incubation: the antibody reagent is sucked by the pipetting mechanism (302), then the pipetting gun head (3021) carrying the sucked antibody reagent by the pipetting mechanism (302) adds the antibody reagent into the biochip (7), and after incubation, the waste liquid is pumped by the waste liquid pumping mechanism (304);

And (3) drying: drying the biochip (7) from which the waste liquid is extracted in the biochip reaction area (406);

Tissue permeabilization: sucking a permeabilization reagent through the pipetting mechanism (302), adding the permeabilization reagent into the biochip (7) through the pipetting mechanism (302), and pumping the waste liquid through the waste liquid pumping mechanism (304) after permeabilization;

Reverse transcription: sucking a reverse transcription reagent through the pipetting mechanism (302), adding the reverse transcription reagent into the biochip (7) through the pipetting mechanism (302), and pumping waste liquid through the waste liquid pumping mechanism (304) after reverse transcription is completed;

Tissue removal: the tissue removing reagent is sucked by the pipetting mechanism (302), then the pipetting gun head (3021) which is carried by the pipetting mechanism (302) and sucked with the tissue removing reagent adds the tissue removing reagent into the biochip (7), and after tissue removal is finished, the waste liquid is pumped away by the waste liquid pumping mechanism (304);

Nucleic acid release: sucking a nucleic acid release reagent through the pipetting mechanism (302), and then adding the nucleic acid release reagent to the biochip (7) by a pipetting gun head (3021) carrying the sucked nucleic acid release reagent by the pipetting mechanism (302) and completing nucleic acid release;

and (3) collecting products: the released nucleic acid is aspirated by the pipetting mechanism (302) and stored.
The automated control method of an automated control system for a biochip according to claim 32, wherein washing is performed between the blocking step and the antibody incubation step and/or washing is performed between the antibody incubation step and the drying step and/or washing is performed between the drying step and the tissue permeabilization step and/or washing is performed between the tissue permeabilization step and the reverse transcription step and/or washing is performed between the reverse transcription step and the tissue removal step and/or washing is performed between the tissue removal step and the nucleic acid release step.
The automated control method of an automated control system for a biochip of claim 33, wherein the washing step comprises: the cleaning reagent is sucked by the pipetting mechanism (302), then the pipetting gun head (3021) carrying the sucked cleaning reagent by the pipetting mechanism (302) adds the cleaning reagent to the biochip (7), and then the waste liquid is pumped by the waste liquid pumping component (3041).