US-20260126458-A1 - A METHOD FOR AUTOMATICALLY CONTROLLING A BIOCHIP AND AUTOMATIC CONTROL SYSTEM OF BIOCHIP

US20260126458A1US 20260126458 A1US20260126458 A1US 20260126458A1US-20260126458-A1

Abstract

The disclosure relates to a method for automatically controlling a biochip and an automatic control system, wherein the method comprises the operations of carrying a suction member through a pipette mechanism to suck a reagent, and carrying the suction member that has sucked the reagent through the pipette mechanism to add the reagent to the biochip, and also provides an automatic control system of a biochip using the method for automatically controlling a biochip. The method and system of a biochip may automatically schedule and control a plurality of biochips, so as to complete the labeling and capturing of biological information in tissues, and perform overall collection of the captured products, which meet the requirements of high utilization rate and high degree of automation for a biochip.

Inventors

FuTao HE
Wenwei Zhang
Xun Xu
Xiaojuan LEI
An Chen
Zhifeng QIU
Yan Hong
Zhiyuan WAN
MENGZHE SHEN
Ao Chen
Yuxiang Li

Assignees

BGI SHENZHEN

Dates

Publication Date: 20260507
Application Date: 20220930

Claims (20)

1 . A method for automatically controlling a biochip, comprising operation, the operation comprising: carrying a suction member by means of a pipette mechanism to suck a reagent; and carrying the suction member that has sucked the reagent by means of the pipette mechanism to add the reagent to the biochip.
2 . The method according to claim 1 , wherein the operation comprising at least one of following steps: incubation: the pipette mechanism carries the suction member to suck an incubation reagent, and the pipette mechanism carries the suction member that sucked the incubation reagent to add the incubation reagent to the biochip; tissue permeabilization: the pipette mechanism carries the suction member to suck a permeabilization reagent, and the pipette mechanism carries the suction member that has sucked the permeabilization reagent to add the permeabilization reagent to the biochip; reverse transcription: the pipette mechanism carries the suction member to suck a reverse transcription reagent, and the pipette mechanism carries the suction member that has sucked the reverse transcription reagent to add the reverse transcription reagent to the biochip; and tissue removal: the pipette mechanism carries the suction member to suck a tissue removal reagent, and the pipette mechanism carries the suction member that has sucked the tissue removal reagent to add the tissue removal reagent to the biochip.
3 . The method according to claim 2 , comprising at least one of: in each step of the operation, waste liquid is pumped by a waste liquid pumping mechanism; each step of the operation is automatically performed; and in each step of the operation, a current step and/or a current state are displayed to the user in real time.
4 . The method according to claim 2 , wherein after the tissue removal step, comprising at least one of following steps: nucleic acid release: the pipette mechanism carries the suction member to suck a nucleic acid release reagent, and the pipette mechanism carries the suction member that has sucked the nucleic acid release reagent to add the nucleic acid release reagent to the biochip to complete the nucleic acid release; and product collection: the pipette mechanism carries the suction member to suck the released nucleic acid and store the released nucleic acid.
5 . The method according to claim 4 , wherein a cleaning step is performed at least one of: between the incubation step and the tissue permeabilization step; between the tissue permeabilization step and the reverse transcription step; between the reverse transcription step and the tissue removal step; and between the tissue removal step and the nucleic acid release step.
6 . The method according to claim 5 , wherein the cleaning step comprises: the pipette mechanism carries the suction member to suck a cleaning reagent, and the pipette mechanism carries the suction member that has sucked the cleaning reagent to add the cleaning reagent to the biochip, and the waste liquid pumping mechanism pumps the cleaning waste liquid.
7 - 8 . (canceled)
9 . The method according to claim 1 , wherein before the operation, a plurality of biochips is arranged in a biochip kit, so that the information of the plurality of biochips is associated with the information of the biochip kit by scanning, and the permeabilization time of the plurality of biochips is input into the system; or the biochip on which a target is carried is provided with a customized size.
10 . (canceled)
11 . The method according to claim 9 , wherein the plurality of biochips is sequentially arranged in at least one row in the biochip kit.
12 . The method according to claim 11 , wherein if the plurality of biochips has the same permeabilization time: in the case that a plurality of biochips is arranged in one row, simultaneously pumping waste liquid of the permeabilization reagent, simultaneously adding the cleaning reagent, simultaneously pumping waste liquid of the cleaning agent, and simultaneously adding the reverse transcription reagent sequentially for the one row of biochips; and in the case that the plurality of biochips is arranged in two rows, pumping waste liquid of the permeabilization reagent and adding the cleaning reagent for the first row of biochips before pumping waste liquid of the permeabilization reagent and adding the cleaning reagent for the second row of biochips; then pumping waste liquid of the cleaning reagent and adding the reverse transcription reagent for the first row of biochips before pumping waste liquid of the cleaning reagent and adding the reverse transcription reagent for the second row of biochips.
13 . The method according to claim 11 , wherein if the plurality of biochips does not have the same permeabilization time and the plurality of biochips are arranged sequentially in an ascending order according to the permeabilization time, in the case that the plurality of biochips are arranged in one row, pumping waste liquid of the permeabilization reagent, adding the cleaning reagent, pumping waste liquid of the cleaning reagent, adding the reverse transcription reagent sequentially for the plurality of biochips according to a temporal sequence of completion of the permeabilization time; in the case that the plurality of biochips are arranged in two rows, and the two rows of biochips do not have the same permeabilization time therebetween, pumping waste liquid of the permeabilization reagent, adding the cleaning reagent, pumping waste liquid of the cleaning agent, and adding the reverse transcription reagent sequentially for biochips in the first row of biochips according to a temporal sequence of completion of the permeabilization time before pumping waste liquid of the permeabilization reagent, adding the cleaning reagent, pumping waste liquid of the cleaning agent, and adding the reverse transcription reagent sequentially for biochips in the second row of biochips according to a temporal sequence of completion of the permeabilization time; and in the case that the plurality of biochips are arranged in two rows, if the two rows of biochips have the same permeabilization time therebetween, first pumping waste liquid of the permeabilization reagent, adding the cleaning reagent, pumping waste liquid of the cleaning agent and adding the reverse transcription reagent sequentially for other biochips than the biochips having the same time among the first row of biochips according to a temporal sequence of completion of the permeabilization time; after pumping waste liquid of the permeabilization reagent and adding the cleaning reagent for the biochips having the same time among the first row of biochips, pumping waste liquid of the permeabilization reagent and adding the cleaning reagent for the biochips having the same time among the second row of biochips; after pumping waste liquid of the cleaning agent and adding the reverse transcription reagent for the biochips having the same time among the first row of biochips, pumping waste liquid of the cleaning agent and adding the reverse transcription reagent for the biochips having the same time among the second row of biochips; then pumping waste liquid of the permeabilization reagent, adding the cleaning reagent, pumping waste liquid of the cleaning agent and adding the reverse transcription reagent sequentially for other biochips among the second row of biochips according to a temporal sequence of completion of the permeabilization time.
14 . The method according to claim comprising a waste liquid pumping step, the waste liquid pumping step comprising: in the case that the plurality of biochips are arranged in one row, moving the waste liquid pumping mechanism above the biochip kit, starting a pump of the waste liquid pumping mechanism to first pump the waste liquid at a higher position in the biochip kit and then pump the waste liquid at a lower position in the biochip kit through a waste liquid pumping member, raising the waste liquid pumping member along a Z axis and closing the pump, and moving the waste liquid pumping mechanism to a cleaning region for cleaning; and in the case that the plurality of biochips are arranged in two rows, pumping the waste liquid reacted by the first row of biochips before pumping the waste liquid reacted by the second row of biochips, wherein the pumping step is the same as the pumping step when the plurality of biochips are arranged in one row.
15 . The method according to claim 9 , wherein after inputting the permeabilization time of each biochip, the system scans the information of the biochip kit and the information of the biochip in the biochip kit to determine whether the position of the biochip in the biochip kit, the number of the biochip and the information of the biochip are matched with the information in the system; if no matched, remind the user; if matched, determine the states of the existing biochip kits in the system: if some of the existing biochip kit are not in the reverse transcription step or the nucleic acid release step, remind the user that it is still necessary to wait for a duration of X before transferring the biochip kit to the reaction region to perform the operation; and if all the existing biochip kits are in the reverse transcription step or the nucleic acid release step, determine whether there is a vacancy in the reaction region; if there is no vacancy, remind the user that it is still necessary to wait for a duration of Y before transferring the biochip kit to the reaction region; and if there is a vacancy, transfer the biochip kit to the reaction region to perform the operation.
16 . The method according to claim 10 , wherein between the step of placing the biochip in the biochip kit and the operation, the biochip kit is transferred to the reaction region by a gripper mechanism to perform the operation, and the gripper mechanism and the pipette mechanism work independently of each other.
17 . The method according to claim 16 , wherein in each step of the operation, neither the gripper mechanism nor the pipette mechanism contacts the biochip; or covering a sealing cover and/or a temperature control cover and opening a sealing cover and/or a temperature control cover are performed on the biochip kit by the gripper mechanism.
18 . (canceled)
19 . The method according to claim 4 , comprising at least one of: in the product collection step, the biochip kit is first transferred to a slanted region by the gripper mechanism, and product collection is conducted in the slanted region; and in the product collection step, the pipette mechanism carries a suction member to suck a reagent, the pipette mechanism carries the suction member that has sucked the reagent to flush the biochip in the biochip kit, and the pipette mechanism carries the suction member to perform product collection.
20 . (canceled)
21 . The method according to claim 1 , comprising a step of retrieving a suction member by the pipette mechanism before the operation, the step comprising: determining whether a current column in a suction member container satisfies the conditions for retrieving a suction member, in the case that the number and position satisfy the conditions, the pipette mechanism moves above the row of suction members and drops along the height direction, and at the same time the row of suction members are retrieved; if the current column does not satisfy the conditions for retrieving a suction member, a next column is polled until polling of the suction member container is completed, and polling of the next suction member container begins until polling of all the suction member containers is completed; and if there is still not a column that satisfies the conditions for retrieving a suction member, the user is reminded to replenish a suction member.

Description

TECHNICAL FIELD The present disclosure relates to the field of automatic operation of a biochip, in particular to a method for automatically controlling a biochip and an automatic control system thereof. BACKGROUND Spatial transcriptomics is to measure a total mRNA of a complete tissue section, combine the spatial information of the total mRNA with the morphological content, and draw the positions where all gene expressions occur, so as to obtain a complex and complete gene expression map of a biological process. Microscopy and sequencing technology may be combined to obtain gene expression data while preserving the spatial location information of samples to a maximum extent, which provides important information for the relationship between cell function, phenotype and location in tissue microenvironment. Spatial transcriptomics technology obtains a spatial position and the corresponding gene expression information, and performs analysis on the spatial transcriptomics data so that it may be known which signal transduction pathways activate some cells. Scientists may select genes of interest through the data generated by spatial transcriptomics technology, and display their spatially resolved expressions on an original tissue section. Since all mRNAs are captured, it is possible to select any number of genes in the form of any combination so as to view and analyze together, but no longer limited to viewing only a single gene. These research processes are all required to transform the information in biological tissues into detectable forms through biochemical reactions, which involve multiple reagents and usually require cumbersome manual operations therein to repeat multiple rounds or multiple steps of biochemical reactions with different principles. The inventors have found that, space research technology is mainly based on microfluidic chip, laser microdissection, targeted multiple staining, capture biochip with oligonucleotide chain modification and the like. 10X Genomics mainly provides a manual operation based solution, and supporting instrument solutions are provided: BondRX immunohistochemical staining instrument based on Leica of Nano String Company and laser capture dissection for multiple staining and imaging performed on GeoMx platform; multiple staining and in-situ imaging based on PhenoCycler-Fusion of Akoya Company. The above, which are all based on semi-automatic biochemical operation, microscopy and sequencing, based on full-automatic microscope and manual biochemical operation, or based on full-automatic multiple staining and microscopy of a single biochip, are difficult to incorporate the aspects of high degree of automation of biochemical reaction, high spatial resolution, large sample processing flux and wide capture range. Further, the inventors have found that, the supporting instruments of spatial omics mainly focus on multiple staining, or post-staining imaging, or a combination thereof. These instruments which may only handle standard biochips with a length-width of 25 mm*75 mm, are not compatible with the application of biochips with other sizes. For other planar biochips, it cannot be adapted as well. At the same time, only a target region of interest may be selected to collect a target object so that it is difficult to collect all the products on a large scale. For example, it is not possible to perform the function of overall product collection for a flat biochip with a centimeter level length-width. In addition, the inventors have found that, the solution containing collecting samples to perform mixed sequencing which needs manual time-consumption to select a target region of interest (ROI), may only be performed at a low flux, rather than performing high-flux processing of a biochip. The instruments found by the inventors generally require that the target biochip or the biochip needs an additional region for sealing and/or clamping, which cannot incorporate a high utilization rate and a minimized reagent consumption of a biochip at the same time. Halfway intervention by personnel is required. SUMMARY In order to achieve the above-described object, the present disclosure provides a method for automatically controlling a biochip, comprising an operation, the operation comprising: carrying a suction member by means of a pipette mechanism to suck a reagent, and carrying the suction member that has sucked the reagent by means of the pipette mechanism to add the reagent to the biochip. In some embodiments, the operation includes at least one of following steps: incubation: the pipette mechanism carries the suction member to suck an incubation reagent, and the pipette mechanism carries the suction member that has sucked the incubation reagent to add the incubation reagent to the biochip;tissue permeabilization: the pipette mechanism carries the suction member to suck a permeabilization reagent, and the pipette mechanism carries the suction member that has sucked the permeabilization r