WO2024065608A1 - Automatic control system of biochip and automatic control method therefor - Google Patents

Abstract

Provided are an automatic control system (1) of a biochip and an automatic control method therefor. The automatic control system (1) of the biochip comprises: a working area (4), comprising: at least one biochip reaction zone (406) that is provided with a biochip box (6) for accommodating at least one biochip (7), the biochip box (6) being provided with a concave cavity (61), and the concave cavity (61) being configured for accommodating the biochip (7); reagent feeding areas (409, 413) for storing various types of reagents; and a pipetting mechanism (302) configured to be movable on a plane where the working area (4) is located and to be liftable in a direction perpendicular to the plane so as to reach the reagent feeding areas (409, 413) to pipette the reagents and add the reagents onto the biochip (7). The automatic control system (1) of the biochip can achieve automatic scheduling and control of the plurality of biochips (7), meeting the requirements for high-utilization rate and high-throughput processing of the biochips (7). The automatic control method for the automatic control system (1) of the biochip is used for capturing and product collection of a transcriptome, as well as labeling, capturing and product collection of a proteome.

Description

Automatic control system of biochip and automatic control method thereof Technical Field

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

Background technique

Spatial Transcriptomics measures the total mRNA of a complete tissue section, combines the spatial information of the total mRNA with the morphological content, and plots the locations where all gene expressions occur, obtaining a complex and complete gene expression map of the biological process. Microscopic imaging and sequencing technology can be combined to obtain gene expression data while retaining the spatial location information of the sample to the greatest extent, providing important information on the relationship between cell function, phenotype, and location in the tissue microenvironment.

Spatial transcriptomics technology obtains spatial location and corresponding gene expression information. By analyzing spatial transcriptomics data, we can know which signal transduction pathways are activated in certain cells. Scientists can select genes of interest through the data generated by spatial transcriptomics technology and display their spatially discernible expression on the original tissue sections. Since all mRNAs are captured, they are no longer limited to viewing only a single gene, but can select any number of genes in any combination to view and analyze together. These research processes require biochemical reactions to convert information in biological tissues into a detectable form, which involves multiple reagents and usually requires cumbersome manual operations to repeat multiple rounds or steps of biochemical reactions with different principles.

Existing spatial research technologies are mainly based on microfluidic chips, laser microdissection, targeted multiple staining, capture chips with oligonucleotide chain modifications, etc. Among them, 10X Genomics mainly provides solutions based on manual operation, and the supporting instrument solutions include: NanoString's laser capture microdissection (Laser capture dissection) based on Leica's Bond RX immunohistochemical stainer and GeoMx platform for multiple staining and imaging; Akoya's multiple staining and in situ imaging based on PhenoCycler-Fusion. The above are either based on semi-automatic biochemical operations + microscopic imaging + sequencing, or based on fully automatic microscopes and manual biochemical operations, or based on fully automatic multiple staining + microscopic imaging on a single chip. It is difficult to take into account the high degree of automation of biochemical reactions, high spatial resolution, large sample processing throughput, and wide capture range.

In addition, the existing spatial omics instruments on the market mainly focus on multiple staining, or imaging after staining, or a combination of the two. These instruments can only process standard glass slides with a length and width of 25mm*75mm, and are not compatible with the automated control methods of chips of other sizes. They are also not compatible with other flat chips that are not glass slides. At the same time, only the area of interest can be selected to collect the target object, making it difficult to achieve large-scale collection of all products. For example, the function of overall product collection cannot be performed for flat chips with a length and width of centimeters.

In addition, the inventors found that the scheme including collecting samples for mixed sequencing requires time-consuming manual selection of regions of interest (ROI), which can only be performed at a lower throughput and cannot perform multi-biochip, high-throughput processing. Existing instruments generally require the target slide or chip to have additional areas for sealing and/or clamping, which cannot simultaneously take into account the high utilization rate of the chip and the minimization of reagent consumption. Human intervention is required.

Summary of the invention

The present disclosure provides an automatic control system for a biochip, comprising:

The working area includes: at least one biochip reaction area, in which a biochip box for accommodating at least one biochip is arranged, the biochip box is provided with a concave cavity, and the concave cavity is configured to accommodate the biochip; a reagent loading area, in which various types of reagents are stored; and

The liquid transfer mechanism is constructed to be movable on the plane where the working area 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 to suck the reagent and add the reagent to the biochip.

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

The pipette tip loading area is used to store the pipette tips;

A product collection area, used for collecting the product in the concave cavity;

A biochip loading area storing a biochip box containing at least one biochip;

the biochip unloading area, where biochip cassettes are removed;

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

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

A code scanning area, in which the biochip box and the biochip contained therein are scanned respectively;

A product storage area for storing collected products;

A cover, which is openably disposed in the biochip reaction area to seal the biochip box; and

The temperature control cover area is used to store the temperature control cover. The temperature control cover is constructed to cover the reagent loading area, the product collection area, and the biochip reaction area.

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

A low-temperature reagent loading zone and a normal-temperature reagent loading zone on the reagent loading zone, wherein the temperature of the low-temperature reagent loading zone is lower than the temperature of the normal-temperature reagent loading zone;

A temperature control zone, including a low-temperature reagent loading zone, a product storage zone and/or at least one biochip reaction zone, wherein the temperature of the temperature control zone can be controlled;

Heated lid.

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

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

In some embodiments, at least two grooves are evenly spaced apart along the circumference of the concave cavity.

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

In some embodiments, the biochip box has a tilt angle of no less than 15 degrees.

In some embodiments, the product collection area includes a tilt mechanism configured to allow the biochip cartridge to be tilted relative to a plane in which the product collection area is located.

In some embodiments, the tilting mechanism includes a driving device and a bracket holding the biochip box, and the bracket is drivingly connected to the driving device to rotate the biochip box.

In some embodiments, the driving device includes a motor, a driving wheel drivingly connected to the motor, and a driven wheel drivingly connected to the driving wheel, and the driven wheel is connected to the bracket.

In some embodiments, the automated control system of the biochip includes:

The grabbing mechanism is constructed to grab the biochip box and move it on the plane where the working area is located and to be able to rise and fall in a direction perpendicular to the plane, so as to grab the biochip box and send it to at least one of the code scanning area, reagent loading area, chip loading area, chip unloading area, biochip reaction area and product collection area.

In some embodiments, the automated control system of the biochip includes:

The waste liquid extraction mechanism includes a waste liquid extraction component that is configured to extract waste liquid from the reaction on the biochip. The waste liquid extraction component can move on the plane where the working area is located and can be raised and lowered in a direction perpendicular to the plane so as to reach at least one biochip reaction area to extract waste liquid from the biochip box and discharge the waste liquid.

In some embodiments, the waste liquid extraction mechanism includes a suction pump, which is connected to the waste liquid extraction component, and the suction pump includes at least one of the following: an air pump, a diaphragm pump and a plunger pump; and/or the waste liquid extraction component includes a needle or a pipette tip.

In some embodiments, the automated control system of the biochip includes a cleaning area for the waste liquid extraction mechanism to discharge waste liquid thereon, to clean the waste liquid extraction mechanism and/or to discharge condensed water from the temperature control area.

In some embodiments, the automated control system of the biochip includes:

The negative pressure adsorption component is configured to adsorb the biochip and is movable on the plane where the working area is located and can be raised and lowered in a direction perpendicular to the plane so as to reach the code scanning area, the biochip loading area and/or the biochip unloading area.

In some embodiments, the pipetting mechanism is configured to be movable to reach the reagent loading area, the pipette tip loading area and at least one biochip reaction area, so that the pipetting mechanism can move to the pipette tip loading area to pierce the pipette tip, move to the reagent loading area to aspirate the reagent, move to multiple biochip reaction areas and add the aspirated reagent to the biochip.

In some embodiments, the temperature of the low temperature reagent loading zone is no higher than 4 degrees Celsius.

In some embodiments, the pipette tip loading area is configured into at least two groups of push-pull containers, each group of containers including multiple boxes of pipette tips.

In some embodiments, the pipetting mechanism includes a plurality of pipettes, each of which can independently raise and lower and replace a pipette tip.

In some embodiments, each pipette is arranged along the length or width direction of the working area, and each pipette can be equidistant from or equidistant from each other.

In some embodiments, the pipetting mechanism includes a first moving mechanism capable of moving the pipetting mechanism, and the waste liquid extraction mechanism includes a second moving mechanism capable of moving the waste liquid extraction component, and the first moving mechanism and the second moving mechanism are independent of each other or integrated together.

In some embodiments, the first moving mechanism and the second moving mechanism both include an arm, and the arm can move on the plane where the working area is located and rise and fall in a direction perpendicular to the plane.

In some embodiments, the gripping mechanism includes a clamping jaw.

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

In some embodiments, at least the biochip reaction area includes a plurality of biochip reaction areas, and the temperatures of the plurality of biochip reaction areas are controlled independently of each other.

In some embodiments, the gripping mechanism is configured to perform one of the following steps to confirm whether the corresponding association between the biochip and the biochip box 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 code scanning area respectively;

When the bottom of the biochip box is opaque, the gripping mechanism grabs the biochip box in the chip unloading area to scan the code, and the negative pressure adsorption component adsorbs each biochip one by one to scan the code.

In some embodiments, an automated control system for a biochip includes a biochip placed in a concave cavity, wherein the bottom area of the concave cavity is larger than the area of the biochip, so that a gap is formed between the circumferential wall of the concave cavity and the biochip.

The present disclosure also provides an automated control method for an automated control system of a biochip, wherein the automated control system of the biochip is used for capturing transcriptomes and collecting products, and the capturing of transcriptomes and collecting products includes at least one of the following operation steps:

Incubation: The incubation reagent is sucked by the pipetting mechanism, and then the incubation reagent is added to the biochip by the pipetting mechanism. After the incubation, the waste liquid is pumped away by the waste liquid pumping mechanism;

Tissue permeabilization: The permeabilization reagent is sucked by the pipetting mechanism, and then added to the biochip by the pipetting mechanism. After the permeabilization is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Reverse transcription: The reverse transcription reagent is sucked up by the pipetting mechanism, and then added to the biochip by the pipetting mechanism. After the reverse transcription is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Tissue removal: The tissue removal reagent is sucked by the pipetting mechanism, and then the pipetting mechanism carries the pipette tip that has sucked the tissue removal reagent to add the tissue removal reagent to the biochip. After the tissue removal is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Nucleic acid release: The nucleic acid release reagent is sucked by the pipetting mechanism, and then the pipetting mechanism carries the pipette tip that has sucked the nucleic acid release reagent to add the nucleic acid release reagent to the biochip to complete the nucleic acid release;

Product collection: The released nucleic acid is sucked up by a pipetting mechanism and the released nucleic acid is stored.

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

In some embodiments, the cleaning step is: aspirating the cleaning reagent through the pipetting mechanism, then using the pipetting mechanism to carry the pipette tip that has absorbed the cleaning reagent to add the cleaning reagent to the biochip, and then using the waste liquid extraction component to extract the waste liquid.

The present disclosure provides an automated control method for an automated control system of a biochip, wherein the automated control system of the biochip is used for labeling and capturing a proteome and collecting a product, and implementing labeling and capturing a proteome and collecting a product includes at least one of the following operation steps:

Blocking: The blocking solution is sucked by the pipetting mechanism, and then the pipetting mechanism carries the pipette tip that has sucked the blocking solution to add the blocking solution to the biochip. After the blocking is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Antibody incubation: The antibody reagent is sucked by the pipetting mechanism, and then the pipetting mechanism carries the pipette tip with the antibody reagent sucked to add the antibody reagent to the biochip. After the incubation is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Drying: Drying the biochip in the biochip reaction area after the waste liquid is removed;

Tissue permeabilization: The permeabilization reagent is sucked by the pipetting mechanism, and then added to the biochip by the pipetting mechanism. After the permeabilization is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Reverse transcription: The reverse transcription reagent is sucked up by the pipetting mechanism, and then added to the biochip by the pipetting mechanism. After the reverse transcription is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Tissue removal: The tissue removal reagent is sucked by the pipetting mechanism, and then the pipetting mechanism carries the pipette tip that has sucked the tissue removal reagent to add the tissue removal reagent to the biochip. After the tissue removal is completed, the waste liquid is sucked away by the waste liquid extraction mechanism;

Nucleic acid release: The nucleic acid release reagent is sucked by the pipetting mechanism, and then the pipetting mechanism carries the pipette tip that has sucked the nucleic acid release reagent to add the nucleic acid release reagent to the biochip to complete the nucleic acid release;

Product collection: The released nucleic acid is sucked up by a pipetting mechanism and the released nucleic acid is stored.

In some embodiments, 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.

In some embodiments, the cleaning step includes: sucking the cleaning reagent through the pipetting mechanism, then using the pipetting mechanism to carry the pipette tip that has sucked the cleaning reagent to add the cleaning reagent to the biochip, and then using the waste liquid extraction component to extract the waste liquid.

The automated control system of the biochip provided by the present disclosure and its application can realize the scalable automated scheduling and control of multiple chips, realize the labeling and capture of biological information in the tissue, and realize the collection function of the captured products, and can be applied to the analysis of multiple omics such as transcriptome, proteome, and immunology. The method and system provided by the present disclosure meet the processing requirements of multiple biochips, high utilization, high throughput, and high automation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is an overall schematic diagram of an automated control system of a biochip disclosed herein;

FIG2 is a schematic diagram of the layout of the working area of the automatic control system of the biochip disclosed in the present invention;

FIG3 is a schematic diagram of a manipulator system of an automated control system for a biochip disclosed herein;

FIG4 is a schematic diagram of a pipetting mechanism;

FIG5 is a schematic diagram of a waste liquid extraction mechanism and a grasping mechanism of a liquid transfer mechanism;

FIG6 is a schematic diagram of a chip loading area 414, a chip unloading area 416 and a biochip box of the automated control system of the biochip disclosed in the present invention;

FIG. 7 is a schematic diagram of a sealing cover plate area 410 of an automated control system for a biochip disclosed herein;

FIG8 is a schematic diagram of a tilting mechanism 4081 of a product collection area 408 of an automated control system of a biochip disclosed herein;

FIG9 is a schematic diagram of a biochip box 6 containing a biochip 7 according to the present disclosure;

FIG10 is a flow chart of performing transcriptome capture and collection using the automated control system of the biochip disclosed herein;

FIG. 11 is a flow chart showing the process of performing proteome capture and collection using the automated control system of the biochip disclosed herein.

Description of reference numerals:

1. Automatic control system of biochip; 2. Shell; 3. Manipulator system; 4. Working area; 5. Indicator light; 6. Biochip box; 7. Biochip; 61. Concave cavity; 612. Bottom of concave cavity; 613. Peripheral wall of concave cavity; 611. Groove; 6111. First slope section; 6112. Second slope section; 401. Working platform; 402. Pull-out container; 403. Pipette tip loading area; 404. Sensor; 405. Pipette tip discarding area; 406. Biochip reaction area; 4061. Cover; 407. Cleaning area; 408. Product collection area; 4081. Tilt mechanism; 40811. Motor; 40812. Bracket; 40814, driving wheel; 40815, driven wheel; 409, normal temperature reagent loading area; 410, sealing cover area; 4101, sealing cover; 4102, multi-layer stacking rack; 411, temperature control cover area; 4111, temperature control cover; 412, product storage area; 413, low temperature reagent loading area; 414, chip loading area; 4141, multi-layer stacking rack; 415, code scanning area, 416, chip unloading area; 301, bracket, 302, pipetting mechanism, 303, grabbing mechanism, 304, waste liquid extraction mechanism; 306, negative pressure adsorption component; 3051, first moving mechanism; 3052, second moving mechanism; 3021, pipetting gun tip; 3022, pipette; 3031, clamp; 3041, waste liquid extraction component.

Detailed ways

The present disclosure is further described in detail below in conjunction with specific implementation modes. The examples given are only for illustrating the present disclosure but not for limiting the scope of the present disclosure.

As shown in FIG1 , the automatic 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. The work area 4 is provided with a plurality of stations and devices for chip biochemical experiments, and the operating arm system 3 is used to automatically operate the steps of each biochemical experiment in the work area 4 according to instructions. The indicator light 5 is used to inform the user whether the automatic control system 1 is currently in working state, shutdown state, normal working state, abnormal working state, etc.

In some embodiments, as shown in Figure 2, the working area 4 includes a working platform 401, on which are provided: a pipette tip loading area 403, a chip loading area 414, a chip unloading area 416, a sealing cover area 410, a temperature control cover area 411, a low-temperature reagent loading area 413, a room temperature reagent loading area 409, a reagent warm bath area (optional), a biochip reaction area 406, a pipette tip discarding area 405, a cleaning area 407, a code scanning area 415, a product collection area 408 and a product storage area 412, etc. The pipette tip 3021 can be a disposable pipette tip.

The present invention uses the operating arm system 3 to accurately control the pipetting mechanism to extract/add liquid and the waste liquid extraction mechanism 304 to extract waste liquid on the working platform 401 of the working area 4, thereby realizing fully automatic operations such as cleaning, tissue permeabilization, reverse transcription, tissue removal, nucleic acid release and product collection.

In some embodiments, as shown in FIGS. 3 and 4 , the manipulator system 3 includes a bracket 301, a pipetting mechanism 302, a gripping mechanism 303, a waste liquid extraction mechanism 304, a negative pressure adsorption component 306, and a moving mechanism thereof in the XYZ axis direction (X is the horizontal long side direction of the working area, Y is the horizontal short side direction, and Z is the vertical height direction). The bracket 301 supports the manipulator system 3 on the working platform 401, and the pipetting mechanism 302 includes a four-channel variable-distance pipette 3022. Each pipette 3022 can independently control the lifting and replacement of the pipette tip 3021, and has the functions of empty suction detection and needle blockage detection, and has the function of liquid level detection. It can independently control the movement on the plane where the working platform is located and the follow-up suction and discharge of liquid along the Z axis. The four-channel pipette 3022 is arranged along the Y axis direction, and can realize synchronous movement in the XY axis direction and equidistant opening and closing of each channel in the Y axis direction with adjustable spacing. All pipettes 3022 can cover the pipette tip loading area 403, the biochip reaction area 406, the product storage area 412, the room temperature reagent loading area 409, the low temperature reagent loading area 413, the pipette tip discarding area 405, etc.

In some embodiments, as shown in FIG5 , the gripping mechanism 303 may include a clamping claw 3031, and may be automatically controlled, with an opening and closing range adapted to a standard well plate, and the gripping targets include a biochip box 6, a sealing cover plate 4101, and a temperature control cover plate 4111, etc., and has a function of determining the position, and the travel covers the chip loading area 414, the chip unloading area 416, the code scanning area 415, the sealing cover plate area 410, the temperature control cover plate area 411, the product collection area 408, the product storage area 412, the low temperature reagent loading area 413, the biochip reaction area 406, etc. Specifically, the clamping claw 3031 grips the biochip box 6 to the biochip reaction area 406 for biochemical reaction, and grips the temperature control cover plate 4111 to seal the product storage area 412, the low temperature reagent loading area 413, and/or the biochip reaction area 406.

In some embodiments, the gripping mechanism 303 can perform rotation adjustment under the control of a motor or a transmission mechanism to better place the gripped object into the working area 4 .

In one embodiment, as shown in FIG2 , the temperature control cover plate 4111 optionally has a heating function, and can be grabbed and transported by the clamping claw 3031 from the multi-layer stacking rack of the temperature control cover plate area 411, for example, to cover the sealing cover plate 4101 on the sealed biochip box 6, or directly cover the biochip box 6, so that the temperature control cover plate 4101 heats the top area of the biochip box 6, reducing the condensation water generated in the biochip box 6 due to the temperature difference between the top area of the biochip box 6 and the bottom area of the biochip box 6 heated by the temperature control area. Each layer of the multi-layer stacking rack of the temperature control cover plate area 411 can be placed with a temperature control cover plate 4111, and the multi-layer stacking rack is the same as the multi-layer stacking racks 4141 and 4102 shown in FIGS. 6 and 7 .

In some embodiments, as shown in FIG5 , the waste liquid extraction mechanism 304 includes a waste liquid extraction component 3041, a suction pump, a connecting pipeline and a fixing member. The waste liquid extraction component 3041 is connected to the suction pump through a pipeline, and has independent XYZ axial motion control. The pipeline can follow the movement of the waste liquid extraction 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 extraction component 3041 covers the cleaning area 407 and the biochip reaction area 406, and the waste liquid extraction component 3041 can be a needle-shaped member.

In some embodiments, the negative pressure adsorption component 306 is used to adsorb the chip, for example, to perform chip scanning. Each negative pressure adsorption component 306 is arranged along the Y-axis direction and can move independently in the Z-axis direction. During the movement of the negative pressure adsorption component 306 along the X, Y, and Z-axis directions, the pipeline can follow the movement, and the stroke covers the chip unloading area 416 and the scanning area 415. The negative pressure adsorption component 306 can be a vacuum suction cup. As shown in Figure 5, the negative pressure adsorption component 306 is integrated with the waste liquid extraction component 3041, and can also be independently set with the waste liquid extraction component 3041.

In some embodiments, the biochip reaction area 406 includes a cover 4061, which is disposed in the biochip reaction area 406 in an openable and closable manner and is used to seal the biochip box 6. Optionally, the cover 4061 has a heating function, and can independently control the temperature rise and fall within the range of 25-100° C., and is used to heat the biochip box 6 and/or the sealing cover plate 4101 to reduce condensation water generated due to temperature difference.

In some embodiments, the temperature control area includes two low temperature areas and three biochip reaction areas 406. The two low temperature areas are respectively a low temperature reagent loading area 413 and a product storage area 412. A constant temperature can be set within the range of 0-25°C, and the condensed water generated at low temperature is discharged through a pipeline. The three biochip reaction areas 406 can perform temperature rise and fall during the biochip reaction, and can accurately and independently control their respective temperatures within the range of 25-70°C. The maximum control temperature is higher than 90°C. The cover 4061 cooperates with the sealing cover plate 4101 to seal the biochip box 6. Specifically, the cover 4061 and the sealing cover plate 4101 are in contact with each other for heat transfer, so as to avoid the generation of condensed water on the lower surface of the sealing cover plate 4101, effectively reducing the evaporation amount and ensuring the normal progress of the biochemical reaction. .

In some embodiments, the control of the waste liquid extraction mechanism 304, the condensed water collection area, the pump, the switch and the rotary valve can realize the functions of cleaning the waste liquid extraction mechanism 304 and discharging the condensed water in the low temperature area in the cleaning area 407.

In some embodiments, the product collection area 408 is constructed with a tilting function to adjust the angle of the biochip box 6 thereon relative to the plane where the working area 4 is located, so as to tilt the biochip box 6 when collecting nucleic acids, which is beneficial to reduce residual liquid.

In some embodiments, as shown in FIG8 , a tilting mechanism 4081 is provided on the product collection area 408 , and the tilting mechanism 4081 includes a driving device and a bracket 40812 for holding the biochip box 6 , and the driving device is connected to the bracket 40812 to rotate the biochip box 6 so that the chip box 6 is tilted.

In some embodiments, as shown in FIG8 , the driving device includes a motor 40811, a driving wheel 40814 connected to the motor 40811, and a driven wheel 40815 connected to the driving wheel 40814 through a belt 40816, and the driven wheel 40815 is connected to the bracket 40812. When the motor 40816 drives the bracket 40812 to rotate through the driving wheel 40814, the belt 40816 and the driven wheel 40815, the biochip box 6 reciprocates with the bracket 40812 within a certain angle range, and the angle range ensures that the inclination angle of the biochip box 6 is not less than 15 degrees, and at the same time ensures that there is no risk of leakage of the motor, and allows the clamp 3031 to clamp the biochip box 6 and transfer it between the bracket 40812 and other stations. The driving device can also use gear transmission, chain transmission, etc. to drive the bracket 40812 to rotate.

In some embodiments, as shown in FIG8 , the biochip box 6 is provided with a plurality of concave cavities 61, and the biochip is accommodated in the concave cavities 61. The concave cavity 61 includes a bottom surface 612 and a circumferential wall 613, the biochip is placed on the bottom surface 612, and a groove portion 611 is provided on the circumferential wall 613, the shape of the groove portion 611 is designed to facilitate the pipetting mechanism 302 to extract the product from the concave cavity 61, and compared with other parts of the circumferential wall 613 except the groove portion 611, the groove portion 611 is further away from the bottom surface 612 or the biochip, so that the pipetting mechanism 302 is convenient to extract the product from the concave cavity 61.

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

In some embodiments, as shown in FIG9 , the groove portion 611 includes a first slope segment 6111 and a second slope segment 6112 that intersect the circumferential wall 613. In some embodiments, the number of slope segments may be greater than two. In some embodiments, in addition to the slope segment, the groove portion 611 may also include an arc segment, such as a circular arc.

In some embodiments, at least two grooves 61 are evenly spaced along the circumference of the concave cavity 61. As shown in Fig. 8, at least two grooves 61 are evenly spaced along the circumference of the concave cavity 61, which facilitates the pipetting mechanism 302 to extract products from different directions.

In some embodiments, the low temperature reagent loading area 413 and the normal temperature reagent loading area 409 are used to store reagents under different temperature conditions. The low temperature reagent loading area is suitable for storing reagents that are relatively stable at a temperature lower than room temperature (e.g., about 4°C), and the temperature is controlled in combination with the temperature-controlled low temperature area, while the normal temperature reagent loading area 409 is suitable for storing reagents that are relatively stable at room temperature.

In some embodiments, the pipette tip loading area 403 is composed of, for example, 4 boxes as a group, which can be divided into multiple groups (for example, two groups) and placed in drawer-type containers, which can be pushed and pulled in and out of the working area 4 as a whole. The two groups of gun tip box drawers, the chip loading area 414, the chip unloading area 416, the sealing cover area 410, and the temperature control cover area 411 all have sensors to detect whether they are in place. The code scanning area 415 can be provided with multiple code scanners, which can realize the code scanning function in two forms, including the container side and the chip bottom.

In some embodiments, the biochip box 6 is removed by the clamping jaws 3031 of the second moving mechanism 3052, so as to transfer the biochip box 6 without damaging the biochip; the sealing cover plate 4101 is grasped by the clamping jaws 3031 to seal the biochip box 6. As shown in Fig. 7, in the sealing cover plate area 410, multiple sealing cover plates 4101 are placed in a multi-layer stacking rack 4102, and a sealing cover plate 4101 is placed on each layer of the multi-layer stacking rack 4102, so that multiple sealing cover plates 4101 are stacked up and down in the multi-layer stacking rack 4102, so that it is convenient to take multiple sealing cover plates 4101 in sequence from top to bottom.

In some embodiments, the low-temperature reagent loading area 413 and the product collection area 408 are both thermostatically controlled to achieve refrigeration of reagents and preservation of products; the biochip reaction area 406 adopts variable temperature control to improve work efficiency; the structural design takes into account the convenience of user operation, convenient replacement of consumables and reagents, and also reserves reagent space for potential application expansion. There is no need to transfer a single active biochip separately in the working area 4, and there is no need to reserve additional space on the biochip, ensuring the maximum utilization area of the biochip. The biochip is placed in the biochip box 6. A single biochip box 6 can accommodate multiple (e.g., 8) chips. The working area 4 can accommodate multiple (e.g., 3) biochip reaction areas 406. The reaction temperature in each biochip reaction area 406 can be independently controlled, and a single chip can achieve precise pipetting control, thereby maximizing the throughput.

In some embodiments, as shown in FIG6 , the biochip box 6 includes a plurality of concave cavities 61 for accommodating a plurality of biochips (e.g., 8 10 mm*10 mm sheets), and each of four concave cavities 61 is a row. The back code of the chip is associated with the two-dimensional code of the biochip box by scanning the code, and then the entire biochip box is manually placed in the chip loading area 414. The biochip box 6 and the chip number are entered into the system by identifying the two-dimensional code on the side of the biochip box 6. The shape of the biochip box 6 satisfies the need to be gripped by the gripper 3031 of the gripping mechanism. As shown in FIG6 , in the chip loading area 414 and the chip unloading area 416, a plurality of biochip boxes 6 are placed in a multi-layer stacking rack 4141, and a biochip box 6 is placed on each layer of the multi-layer stacking rack 4141, so that a plurality of biochip boxes 6 are stacked up and down in the multi-layer stacking rack 4141, so that it is convenient to take a plurality of biochip boxes 6 in sequence from top to bottom.

In some embodiments, the first corresponding association of the biochip and the biochip box 6 by scanning the code can be achieved by scanning the code, for example, manually scanning the code to associate the chip and the biochip box and then sending them to the chip loading area 414.

In some examples, the corresponding association between the chip and the biochip box is confirmed by scanning the code. The corresponding association is confirmed by one of the following methods:

(1) For a biochip box 6 with a transparent bottom, the grabbing mechanism 303 grabs the biochip box 6 containing the biochip and scans the biochip and the biochip box in the code scanning area 415 respectively;

(2) For a biochip box 6 with an opaque bottom, when the biochip box 6 is taken out from the chip unloading area 416, the code is scanned by respectively adsorbing the biochip box 6 and each biochip one by one with the negative pressure adsorption component 30.

The automated control system of the biochip according to the present disclosure can provide at least one of the following technical advantages:

Complete automated labeling and capture processes for different omics applications;

Improve the collection rate of captured products;

Process multiple full-chip samples simultaneously, with high throughput per day;

No touching of active chip surface, 100% chip utilization; and

The automation level is high and no human intervention is required.

In some embodiments, as shown in FIG. 10 , an automated control system using a biochip is provided to achieve transcriptome capture and product collection.

After tissue patch pre-treatment, the biochip enters the biochip box 6. A single biochip box 6 includes 8 concave cavities 61 for accommodating 8 chips. The code on the back of each chip is associated with the QR code of the biochip box 6 by scanning the code, and then the entire biochip box 6 is manually placed in the chip loading area 414. The clamp 3031 moves the biochip box 6 to the scanning area 415 to scan and identify the QR code on the side of the biochip box 6, and the number of the biochip box 6 and the corresponding chip is entered into the system together.

Manually place the prepared low-temperature reagents and room-temperature reagents in the corresponding low-temperature reagent loading area 413 and room-temperature reagent loading area 409, and load the pipette tip 3021, the sealing cover plate 4101 and the temperature control cover plate 4111. The software prompts to confirm the status of consumables and chips according to the in-place signal sensed by the sensor 404. After manually setting and determining the experimental conditions corresponding to different chips in the software, click Run, and the clamp 3031 transfers the biochip box 6 from the chip loading area 414 to the biochip reaction area 406, and performs all or part of the following steps, as shown in Figure 10.

Cleaning steps: control the pipette 3022 to move to the pipette tip loading area 403, pick up the pipette tip 3021, run to the position corresponding to the cleaning reagent in the reagent loading area, descend along the Z axis to execute the liquid level detection function of the pipette 3022, and after success, absorb the set volume of cleaning reagent, then the pipette 3022 runs to the biochip reaction area 406, and descends along the Z axis to a certain height at the corresponding concave cavity 61 of the biochip box 6 to accurately discharge the liquid.

Waste liquid extraction step: control the clamp 3031 to transfer the sealing cover on the biochip box 6 to the sealing cover area 410, the waste liquid extraction component 3041 runs to the corresponding concave cavity 61 of the biochip box 6, descends along the Z axis and controls the waste liquid pump, opens the valve of the waste liquid pump for 3-10s, lifts up along the Z axis and runs to the cleaning area 407, starts the cleaning pump to inject water to clean the outer wall of the waste liquid extraction component 3041, and starts the waste liquid pump to pump water to clean the inner wall of the waste liquid extraction component 3041.

Tissue permeabilization step: control the pipette 3022 to take the pipette tip 3021 and extract the permeabilization reagent, add the permeabilization reagent to 4 chips as a group at the same time, and the software records the exact time of adding the permeabilization reagent and starts timing. According to the difference in permeabilization time, the pipette extracts the permeabilization termination reagent before the end of the permeabilization time, adds it to the concave cavity 61 of the biochip box 6 at a precise time point, and terminates the permeabilization reaction; or removes the reaction waste liquid at the specified permeabilization time, and quickly adds the cleaning reagent, and then removes the waste liquid. The entire pipetting process is controlled within 3 minutes so that the chips of adjacent groups can be processed separately.

Reverse transcription: After tissue permeabilization, add reverse transcription reagent to the cleaned chip and incubate at a certain temperature (e.g., 42°C) for more than 3 hours. If reverse transcription reagent is added in advance to meet the needs of processing chips with different permeabilization times in the same biochip box 6, then adjust the temperature to 42°C after all concave cavities 61 in the biochip box 6 have been added, and incubate at 42°C for more than 3 hours.

Tissue removal: After reverse transcription, add tissue removal reagent to the washed chip and incubate at 55°C for more than 10 minutes.

Nucleic acid release: After tissue removal, add nucleic acid release reagent to the cleaned chip and incubate at 55°C for more than 3 hours.

Nucleic acid collection: Use the clamp 3031 to transfer the biochip box 6 that has completed nucleic acid release to the product collection area 408, tilt it about 20 degrees, take the pipette tip 3021 with the pipette, and lower it along the Z axis above the product collection area 408 until it touches the product surface in the concave cavity 61. The pipette extracts the released nucleic acid and transfers the collected product to the well plate in the product storage area 412 for storage. Replace the new pipette tip 3021 to extract the cleaning solution again, rinse the concave cavity 61, and collect the product again, and transfer the collected product to the corresponding well of the same well plate to merge with the product collected last time.

When multiple biochip boxes 6 are running simultaneously, the second and third biochip boxes 6 will respectively start to perform the cleaning steps on the second and third biochip boxes 6 when the previous biochip box 6 enters the reverse transcription step and incubates for a long time, ensuring that the steps before the reverse transcription step are not interrupted and the permeabilization time can be strictly controlled.

After the collection products are collected, subsequent library construction and sequencing will be performed to ensure that the nucleic acids obtained, including the spatial positioning sequences and captured products, can be read and relocated to the original spatial structure, thereby performing reconstruction and precise positioning of spatial information.

In some embodiments, as shown in FIG. 11 , an automated control system using a biochip is provided to achieve protein group labeling and capture product collection.

After the tissue patch pre-treatment, the biochip enters the biochip box 6. A single biochip box 6 includes a concave cavity 61 for 8 chips. The code on the back of each chip is associated with the QR code of the biochip box 6 by scanning the code, and then the entire biochip box 6 is manually placed in the chip loading area 414. The clamp 3031 moves the biochip box 6 to the scanning area 415 to scan and identify the QR code on the side of the biochip box 6, and the number of the biochip box 6 and the corresponding chip is entered into the system together.

Manually place the prepared proteome-related reagents in the corresponding reagent loading area, and load the pipette tip 3021, the sealing cover plate 4101 and the temperature control cover plate 411. The software prompts to confirm the status of the consumables and the chip according to the in-place signal sensed by the sensor 404. After manually setting and determining the experimental conditions corresponding to different chips in the software, click Run, and the clamp 3031 transfers the biochip box 6 from the chip loading area 414 to the biochip reaction area 406, and starts to execute all or part of the following steps.

Cleaning steps: control the pipette to move to the pipette tip loading area 403, pick up the pipette tip 3021, move to the position corresponding to the cleaning reagent 1 in the reagent loading area, descend along the Z axis to perform the liquid level detection function of the pipette, and after success, absorb the set volume of cleaning reagent 1, then the pipette moves to the biochip reaction area 406, and descends along the Z axis to a certain height at the corresponding concave cavity 61 of the biochip box 6, and accurately discharges the liquid. Repeat the cleaning 3 times.

Waste liquid extraction step: control the clamp 3031 to transfer the sealing cover on the biochip box 6 to the sealing cover area 410, the waste liquid extraction component 3041 runs to the corresponding concave cavity 61 of the biochip box 6, descends along the Z axis and controls the waste liquid pump, opens the valve of the waste liquid pump for 3-10s, lifts up along the Z axis and runs to the cleaning area 407, starts the cleaning pump to inject water to clean the outer wall of the waste liquid extraction component 3041, and starts the waste liquid pump to pump water to clean the inner wall of the waste liquid extraction component 3041.

Sealing: Control the pipette to move to the pipette tip loading area 403, pick up the pipette tip 3021, move to the position corresponding to the sealing liquid in the reagent loading area, descend along the Z axis to perform the liquid level detection function of the pipette, and after success, absorb the set volume of sealing liquid, then the pipette moves to the biochip reaction area 406, and descends along the Z axis to a certain height at the corresponding concave cavity 61 of the biochip box 6, and accurately discharges the liquid. Incubate at room temperature for 30 minutes.

Antibody incubation: After removing the blocking solution, control the pipette to move to the pipette tip loading area 403, pierce the pipette tip 3021, move to the position corresponding to the antibody reagent in the reagent loading area, accurately absorb 50-100 μL of the antibody reagent prepared in advance, then move the pipette to the biochip reaction area 406, and descend to a certain height along the Z axis at the corresponding concave cavity 61 of the biochip box 6, accurately spit the liquid so that the antibody reagent evenly covers the chip surface, control the clamp 3031 to grab the sealing cover 4101 to seal the biochip box 6, and incubate at room temperature for 45 minutes.

Cleaning after antibody incubation: Control the pipette to use the pipette tip 3021 to extract 300 μL of cleaning reagent 2, add it to the corresponding concave cavity 61 of the biochip box 6, and then perform the waste liquid extraction operation. Repeat the cleaning and waste liquid extraction for more than 3 times; then repeat the aforementioned cleaning steps using cleaning solution 1 and the waste liquid extraction steps.

Drying: After the waste liquid is drawn out, the chip is placed in the biochip reaction area 406 at 42° C. for 10 minutes.

Proteome labeling and capture and product collection also include tissue permeabilization, reverse transcription, tissue removal, nucleic acid release, product collection and other steps, which are the same as the corresponding steps of transcriptome capture and product collection. The collected products will be processed for subsequent sequencing interpretation to ultimately obtain the spatial distribution of complementary proteins corresponding to specific antibodies with spatial localization information, thereby obtaining the spatial localization information of the proteome.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present disclosure, rather than to limit them. Although the present disclosure has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or perform equivalent replacements on some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present disclosure.

Claims (34)

An automatic control system for a biochip, comprising: The working area (4) comprises: at least one biochip reaction area (406) arranged with a biochip box (6) for accommodating at least one biochip, 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 The pipetting mechanism (302) is constructed 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. The automated control system for a biochip according to claim 1, comprising at least one of the following: A pipette tip loading area (403) storing pipette tips (3021); A product collection area (408) for collecting the product in the concave cavity (61); A biochip loading area (414) storing the biochip box (6) containing the at least one biochip (7); A biochip unloading area (416), in which the biochip box (6) is removed; a pipette tip discarding area (405), in which the used pipette tips (3021) are discarded; A sealing cover plate area (410) storing a sealing cover plate (4101) configured to seal the biochip box (6); A code scanning area (415), in which the biochip box (6) and the biochip (7) contained therein are respectively scanned; a product storage area (412) for storing the collected product; A cover (4061) is openably disposed on the biochip reaction area (406) to seal the biochip box (6); and The temperature control cover area (411) stores the temperature control cover (4111), and the temperature control cover is constructed to cover the reagent loading area (413), the product collection area (408), and/or the biochip reaction area (406). The automated control system for a biochip according to claim 2, comprising at least one of the following: A low-temperature reagent loading zone (413) and a normal-temperature reagent loading zone (409) on the reagent loading zones (409, 413), wherein the temperature of the low-temperature reagent loading zone (413) is lower than the temperature of the normal-temperature reagent loading zone (409); A temperature control zone, including the low-temperature reagent loading zone (413), the product storage zone (412) and/or the at least one biochip reaction zone (406), wherein the temperature of the temperature control zone can be controlled; The lid (4061) has a heating function. An automated control system for a biochip according to any one of claims 1 to 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 portion (611) being provided on the circumferential wall (613), the groove portion (611) being configured to be further away from the bottom surface (612) than other portions of the circumferential wall (613) to facilitate the pipetting mechanism (302) to extract the product from the concave cavity (61). According to the automated control system of the biochip according to claim 4, the groove portion (611) includes an arc segment and/or at least two inclined surface segments (6111, 6112) intersecting along the circumference of the concave cavity. According to the automatic control system of the biochip according to claim 4 or 5, at least two grooves (61) are evenly spaced along the circumference of the concave cavity (61). An automated control system for a biochip according to any one of claims 2-6, wherein the product collection area (408) is configured to enable the biochip box (6) to be tilted relative to a plane where the product collection area (408) is located. According to the automatic control system of the biochip according to claim 7, the inclination angle of the biochip box (6) is not less than 15 degrees. According to the automated control system of the biochip according to claim 7 or 8, the product collection area (408) includes a tilting mechanism (4081) configured to allow the biochip box (6) to be tilted relative to the plane where the product collection area (408) is located. According to the automated control system of the biochip according to claim 9, the tilting mechanism (4081) comprises a driving device and a bracket (40812) for holding the biochip box (6), and the bracket (40812) is connected to the driving device to rotate the biochip box (6). According to the automated control system of the biochip according to claim 10, the driving device comprises a motor (40811), a driving wheel (40814) drivingly connected to the motor (40811), and a driven wheel (40815) drivingly connected to the driving wheel (40814), and the driven wheel (40815) is connected to the bracket (40812). The automated control system of a biochip according to any one of claims 1 to 11, comprising: The gripping mechanism (303) is configured to grip the biochip box (6) so that it can move on the plane where the working area (4) is located and can be raised and lowered in a direction perpendicular to the plane, so as to grip the biochip box (6) and deliver it to at least one of the code scanning area (415), the reagent loading area (409, 413), the chip loading area (414), the chip unloading area (416), the biochip reaction area (406) and the product collection area (408). The automated control system of a biochip according to any one of claims 1 to 12, comprising: The waste liquid extraction mechanism (304) comprises a waste liquid extraction component (3041) configured to extract waste liquid from the reaction on the biochip. The waste liquid extraction component (3041) is movable on the plane where the working area (4) is located and can be raised and lowered in a direction perpendicular to the plane so as to reach at least one biochip reaction area (406) to extract waste liquid from the biochip box (6) and discharge the waste liquid. The automated control system of the biochip according to claim 13, wherein the waste liquid extraction mechanism (304) comprises a suction pump, the suction pump is connected to the waste liquid extraction component (3041), and the suction pump comprises at least one of the following: an air pump, a diaphragm pump and a plunger pump; and/or The waste liquid extraction component (3041) includes a needle-shaped part or a pipette tip (3021). The automated control system of the biochip according to claim 13 or 14 comprises a cleaning area (407) for the waste liquid extraction mechanism (304) to discharge the waste liquid thereon, to clean the waste liquid extraction mechanism (304) and/or to discharge condensed water from the temperature control area. The automated control system of a biochip according to any one of claims 2 to 15, comprising: The negative pressure adsorption component (306) is configured to adsorb the biochip and is movable on the plane where the working area (4) is located and can be raised and lowered in a 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). An automated control system for a biochip according to any one of claims 2 to 16, wherein the pipetting mechanism (302) is configured to be movable to reach the reagent loading area (409, 413), the pipette tip loading area (403) and the at least one biochip reaction area (406), so that the pipetting mechanism (302) can move to the pipette tip loading area (403) to pick up the pipette tip (3021), move to the reagent loading area (409, 413) to aspirate the reagent, move to the multiple biochip reaction areas (406) and add the aspirated reagent to the biochip. An automated control system for a biochip according to any one of claims 3-17, wherein the temperature of the low-temperature reagent loading area (413) is not higher than 4 degrees Celsius. According to the automated control system of the biochip described in any one of claims 2-18, the pipette tip loading area (403) is constructed into at least two groups of push-pull containers, and each group of containers includes multiple boxes of pipette tips (3021). An automated control system for a biochip according to any one of claims 1 to 19, wherein the pipetting mechanism (302) comprises a plurality of pipettes (3022), each of which can independently lift and replace the pipette tip (3021). According to the automated control system of the biochip according to claim 20, each of the pipettes (3022) is arranged along the length or width direction of the working area (4), and each of the pipettes (3022) can be equidistant from or close to each other. According to the automated control system of the biochip according to claim 20 or 21, the pipetting mechanism (302) includes a first moving mechanism (3051) capable of moving the pipetting mechanism (302), the waste liquid extraction mechanism (304) includes a second moving mechanism (3052) capable of moving the waste liquid extraction component (3041), and the first moving mechanism (3051) and the second moving mechanism (3052) are independent of each other or integrated together. According to the automated control system of the biochip according to claim 22, the first moving mechanism (3021) and the second moving mechanism (3021) both include an arm, and the arm can move on the plane where the working area (4) is located and rise and fall in a direction perpendicular to the plane. An automated control system for a biochip according to any one of claims 12-23, wherein the gripping mechanism (303) comprises a clamp (3031). An automated control system for a biochip according to any one of claims 2 to 24, wherein the biochip box (6) is provided with a plurality of concave cavities (61), and the plurality of concave cavities (61) are arranged in at least one row. An automated control system for a biochip according to any one of claims 1-25, wherein at least the biochip reaction zone (406) comprises a plurality of biochip reaction zones (406), and the temperatures of the plurality of biochip reaction zones (406) are controlled independently of each other. According to any one of claims 12 to 26, the automatic control system for a biochip, wherein the gripping mechanism (303) is configured to be capable of performing one of the following steps to confirm whether the corresponding association between the biochip (7) and the biochip box (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 the biochip (7) and the biochip box (6) in the code scanning area (415); When the bottom of the biochip box (6) is opaque, the grabbing mechanism (303) grabs the biochip box (6) in the chip unloading area (416) to scan the code, and the negative pressure adsorption component (306) adsorbs each of the biochips (7) one by one to scan the code. The automated control system of a biochip according to any one of claims 1 to 27 comprises the biochip (7) placed in the concave cavity (61), the bottom area of the concave cavity (61) being larger than the area of the biochip (7), so that a gap is formed between the circumferential wall (612) of the concave cavity (61) and the biochip (7). An automated control method for an automated control system of a biochip, wherein the automated control system of the biochip according to any one of claims 1 to 28 is used for transcriptome capture and product collection, and the transcriptome capture and product collection include at least one of the following steps: Incubation: The incubation reagent is sucked by the liquid transfer mechanism (302), and then the liquid transfer mechanism (302) adds the incubation reagent to the biochip (7), and after the incubation, the waste liquid is pumped away by the waste liquid pumping mechanism (304); Tissue permeabilization: the permeabilization reagent is sucked by the liquid transfer mechanism (302), and then the permeabilization reagent is added to the biochip (7) by the liquid transfer mechanism (302), and after the permeabilization is completed, the waste liquid is sucked away by the waste liquid extraction mechanism (304); Reverse transcription: the reverse transcription reagent is sucked up by the pipetting mechanism (302), and then the reverse transcription reagent is added to the biochip (7) by the pipetting mechanism (302), and after the reverse transcription is completed, the waste liquid is sucked away by the waste liquid sucking mechanism (304); Tissue removal: The tissue removal reagent is sucked by the pipetting mechanism (302), and then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the tissue removal reagent to add the tissue removal reagent to the biochip (7), and after the tissue removal is completed, the waste liquid is sucked away by the waste liquid extraction mechanism (304); Nucleic acid release: The nucleic acid release reagent is sucked by the pipetting mechanism (302), and then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the nucleic acid release reagent to add the nucleic acid release reagent to the biochip (7) to complete the nucleic acid release; Product collection: The released nucleic acid is sucked up by the pipetting mechanism (302) and the released nucleic acid is stored. The automated control method of the automated control system of a biochip according to claim 29, wherein cleaning is performed between the incubation step and the tissue permeabilization step and/or cleaning is performed between the tissue permeabilization step and the reverse transcription step and/or cleaning is performed between the reverse transcription step and the tissue removal step and/or cleaning is performed between the tissue removal step and the nucleic acid release step. According to the automated control method of the automated control system of the biochip as described in claim 30, the cleaning step comprises: sucking the cleaning reagent through the pipetting mechanism (302), then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the cleaning reagent to add the cleaning reagent to the biochip (7), and then the waste liquid is sucked away by the waste liquid extraction component (3041). An automated control method for an automated control system of a biochip, wherein the automated control system of the biochip according to any one of claims 1 to 28 is applied to the labeling and capture of a proteome and the collection of products, and the labeling and capture of a proteome and the collection of products include at least one of the following steps: Blocking: The blocking liquid is sucked by the pipetting mechanism (302), and then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the blocking liquid to add the blocking liquid to the biochip (7), and after the blocking is completed, the waste liquid is sucked away by the waste liquid extraction mechanism (304); Antibody incubation: The antibody reagent is sucked by the pipetting mechanism (302), and then the antibody reagent is added to the biochip (7) by the pipetting mechanism (302) carrying the pipette tip (3021) that has sucked the antibody reagent. After the incubation is completed, the waste liquid is sucked away by the waste liquid extraction mechanism (304); Drying: drying the biochip (7) after the waste liquid is removed in the biochip reaction area (406); Tissue permeabilization: the permeabilization reagent is sucked by the pipetting mechanism (302), and then the permeabilization reagent is added to the biochip (7) by the pipetting mechanism (302), and after the permeabilization is completed, the waste liquid is sucked away by the waste liquid sucking mechanism (304); Reverse transcription: the reverse transcription reagent is sucked up by the pipetting mechanism (302), and then the reverse transcription reagent is added to the biochip (7) by the pipetting mechanism (302), and after the reverse transcription is completed, the waste liquid is sucked away by the waste liquid sucking mechanism (304); Tissue removal: The tissue removal reagent is sucked by the pipetting mechanism (302), and then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the tissue removal reagent to add the tissue removal reagent to the biochip (7), and after the tissue removal is completed, the waste liquid is sucked away by the waste liquid extraction mechanism (304); Nucleic acid release: The nucleic acid release reagent is sucked by the pipetting mechanism (302), and then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the nucleic acid release reagent to add the nucleic acid release reagent to the biochip (7) to complete the nucleic acid release; Product collection: The released nucleic acid is sucked up by the pipetting mechanism (302) and the released nucleic acid is stored. The automated control method of the automated control system of a biochip according to claim 32, wherein cleaning is performed between the blocking step and the antibody incubation step and/or cleaning is performed between the antibody incubation step and the drying step and/or cleaning is performed between the drying step and the tissue permeabilization step and/or cleaning is performed between the tissue permeabilization step and the reverse transcription step and/or cleaning is performed between the reverse transcription step and the tissue removal step and/or cleaning is performed between the tissue removal step and the nucleic acid release step. According to the automated control method of the automated control system of the biochip according to claim 33, the cleaning step comprises: sucking the cleaning reagent through the pipetting mechanism (302), then the pipetting mechanism (302) carries the pipette tip (3021) that has sucked the cleaning reagent to add the cleaning reagent to the biochip (7), and then the waste liquid is sucked away by the waste liquid extraction component (3041).

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