Integrated System for Fully Automated Detection of Biochips

Abstract

This invention discloses an integrated system for fully automated biochip detection. The integrated system includes: an incubation fixture assembly and chip transfer unit, used at least for transferring the biochip, loading and unloading the incubation fixture, and encapsulating the biochip within the incubation fixture; a pipetting incubation unit, used at least for injecting the reagents required for detection into the incubation fixture and incubating the biochip; a pattern fixture assembly and chip retrieval unit, used at least for loading and unloading the pattern fixture, encapsulating the incubated biochip within the pattern fixture, and transferring the biochip; and a pattern detection unit, used at least for scanning and imaging detection of the incubated biochip. This invention enables automated chip encapsulation, scanning imaging, and, after detection and imaging, retrieval of the pattern fixture and the detected chip via a track-based transfer system, achieving fully automated biochip detection throughout the entire process.

Description

Technical Field

[0001] This invention relates in particular to an integrated system for fully automated detection of biochips, belonging to the field of biochip detection technology. Background Technology

[0002] Biochips have become important tools for life science research and medical diagnostics. Due to their advantages such as high throughput, parallelism, and low sample consumption, they are frequently used in medical diagnostics, genomics research, drug screening, and biomedical research. Biochips can be manufactured using semiconductor processes. High-density peptide chips synthesized on silicon wafers using semiconductor processes are characterized by small individual peptide sequence dots, typically 1 to 100 micrometers, preferably 5 to 20 micrometers; and high density, allowing for the in-situ synthesis of tens of thousands to hundreds of thousands of different peptide sequence dots at the bottom of a single well in a 96-well plate.

[0003] In the process of synthesizing chips using semiconductor technology, the chip area directly affects production costs. This means that chip manufacturing needs to make the most of the chip area to accommodate more probes with detection indicators per unit area, allowing for the analysis of more molecules or proteins in biological samples, thereby reducing the cost per indicator. In the detection process of biochips, the biochip is first loaded into a well plate fixture, then reacted, and the signal is collected and imaged using a microscope. The well plate holding the chip provides chip fixation and sealing during the detection process.

[0004] To achieve more efficient detection, more advanced optical systems are needed during imaging scanning to improve magnification and fluorescence collection efficiency. Because silicon wafers are opaque, they cannot be inspected from the back. Currently, in common 96-well plate detection systems, top-down inspection often faces the problem of insufficient working distance of high-magnification microscopes, resulting in unclear imaging. Especially near the well walls, surface tension causes the liquid surface to exhibit concave or convex curved shapes, severely affecting the chip's imaging quality and preventing full utilization of the bottom area of ​​individual wells for detecting more parameters. Therefore, the chip plate needs to be disassembled before using fluorescence objectives with higher numerical apertures for inspection. This step is usually done manually by inspectors using a screwdriver to disassemble the well plate fixture. Besides fixture loading and unloading, traditional biochip detection typically requires several manual steps, including chip pretreatment, reagent loading (sample and reagents required for the experiment), fixture transfer during the experimental process, and result detection and recording. These manual steps can reduce the accuracy and efficiency of detection and introduce multiple uncertainties due to operator error, sample contamination, and increased processing time. These uncertainties introduced by manual procedures not only make it impossible to fully reproduce the test process, but also make it impossible to analyze and trace the changes in experimental operations and the source of the problem when abnormal test results occur. Summary of the Invention

[0005] The main objective of this invention is to provide an integrated system for fully automated detection of biochips, thereby overcoming the shortcomings of the prior art.

[0006] To achieve the aforementioned objectives, the technical solution adopted by this invention includes:

[0007] This invention provides an integrated system for fully automated detection of biochips, comprising:

[0008] An incubation fixture assembly and chip transfer unit, used at least for transferring biochips, loading and unloading incubation fixtures, and encapsulating biochips in incubation fixtures;

[0009] A pipetting incubation unit, used at least for injecting reagents required for detection into an incubation fixture and for incubating the biochip;

[0010] A graphic fixture assembly and chip recycling unit is used for loading and unloading graphic fixtures, encapsulating incubated biochips in graphic fixtures, and transferring biochips.

[0011] The image detection unit is used at least for scanning and imaging detection of the incubated biochip.

[0012] In some more specific implementations, the incubation fixture assembly and chip transfer unit includes:

[0013] A chip loading module, used at least for conveying unprocessed biochips;

[0014] The incubation clamp loading and unloading module is used at least to transport the incubation clamp base and the incubation clamp cover to the incubation clamp assembly module, and to export the incubation clamp base and the incubation clamp cover disassembled from the incubation clamp assembly module.

[0015] The chip incubation input module runs along a first direction and is at least used to transport the incubation fixture base and / or the incubation fixture cap within the working area of ​​the incubation fixture assembly module, and to transport the incubation fixture containing the biochip assembled by the incubation fixture assembly module to the pipetting incubation unit.

[0016] The chip incubation output module runs along the second direction and is used at least within the working area of ​​the incubation fixture assembly module to transport the incubation fixture containing the biochip.

[0017] The incubation fixture assembly module is used at least to assemble the incubation fixture base and incubation fixture cover on the chip incubation input module into an incubation fixture, and to disassemble the incubation fixture on the chip incubation output module into an incubation fixture base and incubation fixture cover.

[0018] A portable water tank, at least for supporting the disassembled incubation fixture base and biochip;

[0019] A biochip output module, used at least to deliver the biochip to a graphic fixture assembly and chip recycling unit;

[0020] The first robotic arm is used to transfer at least one of the following between the chip loading module, the incubation fixture loading / unloading module, the chip incubation input module, the chip incubation output module, the incubation fixture assembly module, the mobile water tank, and the biochip output module: the incubation fixture base, the incubation fixture cap, the biochip, and the incubation fixture.

[0021] In some more specific implementations, the incubation fixture assembly module includes a first three-dimensional moving platform, a first gripping mechanism, and a first locking actuator. The first gripping mechanism and the locking actuator are disposed on the first three-dimensional moving platform and are capable of moving along at least one of the X-axis, Y-axis, and Z-axis of a three-dimensional coordinate system under the drive of the first three-dimensional moving platform. The first gripping mechanism is used to detachably grip the incubation fixture base and the incubation fixture cover. The first locking actuator is used to screw the locking sleeve on the incubation fixture cover so that the locking sleeve fixes and locks the incubation fixture cover to the incubation fixture base, or to disengage the locking sleeve from the incubation fixture base so that the incubation fixture cover is separated from the incubation fixture base.

[0022] In some more specific implementations, the incubation fixture assembly module further includes a pressure-holding mechanism, which is disposed on the three-dimensional moving platform and can be raised and lowered along the Z-axis of the three-dimensional coordinate system under the drive of the three-dimensional moving platform. The pressure-holding mechanism is at least used to press the incubation fixture cover and the incubation fixture base along the Z-axis.

[0023] In some more specific embodiments, the pipetting incubation unit includes:

[0024] A pipetting module, used at least for injecting reagents required for detection into the incubation fixture;

[0025] An incubation module, used at least for incubating biochips in reagents;

[0026] The second robotic arm is used at least to transfer the incubation fixture between the pipetting module and the incubation module.

[0027] Furthermore, the pipetting module includes a loading stage and a pipetting head, the transfer head being used to inject the reagents required for detection into the incubation fixture.

[0028] Furthermore, the incubation module includes an oscillating heater, which is used to provide at least the temperature and oscillation conditions required for the incubation of the biochip.

[0029] Furthermore, the incubation module also includes a capping mechanism, which is at least used to attach or detach a cap on the incubation fixture to encapsulate the reagent within the incubation fixture.

[0030] Furthermore, the incubation module also includes a cleaning mechanism, which is used at least to clean the incubated biochip, and the second robotic arm is capable of transferring the incubation fixture between the pipetting module, the incubation module, and the cleaning mechanism.

[0031] In some more specific implementations, the graphic fixture assembly and chip recycling unit includes:

[0032] A graphic fixture rotary platform is used at least for transporting graphic fixtures between a graphic fixture assembly and chip recycling unit and a graphic inspection unit.

[0033] A graphic fixture assembly module, used at least for loading and unloading graphic fixtures;

[0034] A third robotic arm is used at least to transfer the graphic fixture between the graphic fixture rotary platform and the graphic fixture assembly module.

[0035] In some more specific implementations, the graphic fixture assembly module includes a second three-dimensional moving platform, a second gripping mechanism, and a second locking actuator. The second gripping mechanism and the locking actuator are disposed on the second three-dimensional moving platform and are capable of moving along at least one of the X-axis, Y-axis, and Z-axis of a three-dimensional coordinate system under the drive of the second three-dimensional moving platform. The second gripping mechanism is used to detachably grip the graphic fixture base and the graphic fixture cover. The second locking actuator is used to screw the locking sleeve on the graphic fixture cover so that the locking sleeve fixes and locks the graphic fixture cover to the graphic fixture base, or to disengage the locking sleeve from the graphic fixture base so that the graphic fixture cover is separated from the graphic fixture base.

[0036] In some more specific implementations, the image detection unit includes an image detection mechanism and a fourth robotic arm. The image detection mechanism is used to perform scanning imaging detection on the biochip, and the fourth robotic arm is used to transfer the biochip between the image detection mechanism and the image fixture rotary platform.

[0037] Compared with the prior art, the advantages of the present invention include:

[0038] This invention provides an integrated system for fully automated detection of biochips. In the specific operation process, the operator loads the chip to be tested into the material box. Through the track of the incubation fixture assembly and chip transfer unit and the movement of the robot arm, the chip is loaded into the incubation fixture. The incubation fixture is locked, which improves the sealing performance and prevents leakage and contamination between samples.

[0039] This invention provides an integrated system for fully automated biochip detection. The chip is transported to a pattern fixture assembly and chip retrieval unit for automatic packaging under the movement of a track. After automatic scanning and imaging, the pattern fixture and the detected chip are retrieved through the transfer between tracks, realizing fully automated biochip detection throughout the process. Attached Figure Description

[0040] Figure 1a This is a schematic diagram of the overall structure of an integrated system for fully automated detection of biochips, provided in a typical embodiment of the present invention.

[0041] Figure 1b This is a schematic diagram of an integrated system for fully automated detection of biochips, provided in a typical embodiment of the present invention.

[0042] Figure 2 This is a schematic diagram of the overall structure of an integrated system for fully automated detection of biochips, provided in a typical embodiment of the present invention.

[0043] Figure 3 This is a schematic diagram of the overall structure of an integrated system for fully automated detection of biochips, provided in a typical embodiment of the present invention.

[0044] Figure 4 This is a schematic diagram of the structure of the incubation fixture assembly and chip transfer unit provided in a typical embodiment of the present invention;

[0045] Figure 5 This is a schematic diagram of the pipetting incubation unit provided in a typical embodiment of the present invention;

[0046] Figure 6 This is a schematic diagram of the graphic fixture assembly and chip recycling unit provided in a typical embodiment of the present invention;

[0047] Figure 7 This is a schematic diagram of the structure of the graphic detection unit provided in a typical embodiment of the present invention;

[0048] Figure 8 This is a flowchart of a fully automated detection method for biochips provided in a typical embodiment of the present invention. Detailed Implementation

[0049] In view of the shortcomings of the prior art, the inventors of this invention, through long-term research and extensive practice, have proposed the technical solution of this invention. The following will further explain and illustrate the technical solution, its implementation process, and principles in conjunction with the accompanying drawings and specific embodiments. Unless otherwise specified, the robotic arm, drive motor, three-dimensional moving platform, incubation fixture, graphic fixture, conveying module / mechanism, vibration heater, pipette head, graphic analyzer, controller, and related CNC programs mentioned in the embodiments of this invention are all known to those skilled in the art and can be obtained commercially. Therefore, their specific structures and equipment models are not specified here.

[0050] Please see Figure 1a and Figure 2 An integrated system for fully automated detection of biochips includes a pattern detection unit M1, a pattern fixture assembly and chip retrieval unit M2, an incubation fixture assembly and chip transfer unit M3, and a pipetting incubation unit M4. The biochip can be transferred between the pattern detection unit M1, the pattern fixture assembly and chip retrieval unit M2, the incubation fixture assembly and chip transfer unit M3, and the pipetting incubation unit M4, thereby completing the encapsulation of the biochip (including encapsulation in an incubation fixture and encapsulation in a pattern fixture), automated pipetting and incubation, scanning imaging detection, and retrieval after detection.

[0051] Specifically, the incubation fixture assembly and chip transfer unit M3 is used at least for transferring biochips, loading and unloading incubation fixtures, and encapsulating biochips in incubation fixtures. That is, the incubation fixture assembly and chip transfer unit M3 can perform the following functions: transporting / transferring biochips, transporting / transferring the incubation fixture base and incubation fixture cap required for encapsulating biochips, placing biochips between the incubation fixture base and the incubation fixture cap and fixing and encapsulating the incubation fixture base and the incubation fixture cap, transporting / transferring the incubation fixture with encapsulated biochips, disassembling the incubation fixture base and the incubation fixture cap, and outputting the encapsulated biochips, the disassembled incubation fixture base, and the incubation fixture cap to downstream process units or for storage.

[0052] Please refer to the following for details. Figure 1b , Figure 3 and Figure 4The arrows in the diagram indicate the direction of movement for the transferred biochips or carriers. Specifically, the incubation fixture assembly and chip transfer unit M3 includes a chip loading module 301, an incubation fixture loading / unloading module 302, a chip incubation input module 303, a chip incubation output module 304, an incubation fixture assembly module 305, a mobile water tank 306, a biochip output module 307, a first robotic arm 308, and a pressure holding mechanism 309. The first robotic arm 308 can operate between the chip loading module 301, the incubation fixture loading / unloading module 302, the chip incubation input module 303, the chip incubation output module 304, the incubation fixture assembly module 305, the mobile water tank 306, and the biochip output module 307.

[0053] Specifically, the chip loading module 301 is used at least to transport unprocessed biochips to a designated location to await transfer to other functional modules; the incubation fixture loading / unloading module 302 is used at least to transport the incubation fixture base and incubation fixture cap to the incubation fixture assembly module 305, and to remove the incubation fixture base and incubation fixture cap disassembled from the incubation fixture assembly module 305; the chip incubation input module 303 runs along a first direction and is used at least to transport the incubation fixture base and / or incubation fixture cap within the working area of ​​the incubation fixture assembly module 305, and to transport the incubation fixture containing the biochip assembled by the incubation fixture assembly module 305 to the pipetting incubation unit M4; the chip incubation output module 304 runs along a second direction and is used at least to transport the incubation fixture containing the biochip within the working area of ​​the incubation fixture assembly module 305. A chip incubation fixture; an incubation fixture assembly module 305 is used at least to assemble the incubation fixture base and incubation fixture cap on the chip incubation input module 303 into an incubation fixture, and to disassemble the incubation fixture on the chip incubation output module 304 into an incubation fixture base and incubation fixture cap; a movable water tank 306 is used at least to carry and transfer the disassembled incubation fixture base and biochip; a biochip output module 307 is used at least to transport the biochip to the graphic fixture assembly and chip recycling unit M2; a first robotic arm 308 is used at least to transfer at least one of the incubation fixture base, incubation fixture cap, biochip, and incubation fixture between the chip loading module 301, the incubation fixture unloading module 302, the chip incubation input module 303, the chip incubation output module 304, the incubation fixture assembly module 305, the movable water tank 306, and the biochip output module 307.

[0054] Specifically, the chip loading module 301, the incubation fixture loading / unloading module 302, the chip incubation input module 303, the chip incubation output module 304, and the biochip output module 307 are all conveying mechanisms. These conveying mechanisms can be continuous conveying mechanisms of the chain or pulley type, or stepping conveying mechanisms driven by cylinders or motors. For example, the conveying mechanism may include a sprocket, a chain, and a carrier. The chain is mounted on the sprocket and can be driven by the sprocket. The carrier can be mounted on the chain and moves synchronously with the chain. For example, the conveying mechanism may also include a guide shaft and a carrier. The carrier is movably mounted on the guide shaft via a slider and can move along the guide shaft first under the drive of a motor or cylinder, thereby realizing the conveying of biochips or incubation fixtures, etc.

[0055] Specifically, the incubation fixture assembly module 305 includes a first three-dimensional moving platform, a first gripping mechanism, and a first locking actuator. The first gripping mechanism and the locking actuator are disposed on the first three-dimensional moving platform and can move along at least one of the X-axis, Y-axis, and Z-axis of a three-dimensional coordinate system under the drive of the first three-dimensional moving platform. The first gripping mechanism is used to detachably grip the incubation fixture base and the incubation fixture cover. The first locking actuator is used to screw the locking sleeve on the incubation fixture cover so that the locking sleeve fixes and locks the incubation fixture cover to the incubation fixture base, or to disengage the locking sleeve from the incubation fixture base so that the incubation fixture cover is separated from the incubation fixture base.

[0056] More specifically, the hatching clamp cover and the hatching clamp base are fixedly connected by a locking sleeve located on the hatching clamp cover and the hatching clamp base through a threaded connection. That is, the assembly, fixing or disassembly of the hatching clamp cover and the hatching clamp base is achieved by the first locking actuator performing a screwing action on the locking sleeve.

[0057] Specifically, it includes an incubation clamp base, an incubation clamp cover, and a locking sleeve. The incubation clamp base is provided with a receiving groove. The incubation clamp cover is detachably covered on the incubation clamp base along a first direction. The incubation clamp cover and the receiving groove enclose a receiving space for accommodating the biochip. The locking sleeve is used to connect the incubation clamp base and the incubation clamp cover to lock the incubation clamp base and the incubation clamp cover. The incubation clamp cover is also provided with multiple sample dispensing holes that penetrate the incubation clamp cover. The sample dispensing holes are connected to the receiving space, and the sample dispensing holes are used for dispensing samples.

[0058] More specifically, the pressure holding mechanism 309 is mainly used to assist the incubation fixture assembly module 305 in realizing the disassembly and assembly of the incubation fixture. More specifically, the pressure holding mechanism 309 is set on the three-dimensional moving platform and can move up and down along the Z-axis of the three-dimensional coordinate system under the drive of the three-dimensional moving platform. The pressure holding mechanism 309 can press the incubation fixture cover and the incubation fixture base along the Z-axis to keep the incubation fixture fixed when the first locking actuator performs a screwing action on the locking sleeve, thereby making the disassembly and assembly of the incubation fixture stable.

[0059] Understandably, the incubation fixture assembly module 305 is preferably located on the operating path of the chip incubation input module 303, the chip incubation output module 304, and the biochip output module 307, so as to directly realize the assembly and disassembly of the incubation fixture and the transfer of the fixture after assembly and disassembly. Specifically, when the incubation fixture assembly module 305 assembles the incubation fixture, the first robotic arm has already placed the biochip in the base of the incubation fixture, that is, the biochip is encapsulated at the same time when the incubation fixture is assembled.

[0060] Please refer to the following for details. Figure 3 and Figure 5 The pipetting incubation unit M4 is at least used to inject reagents required for detection into an incubation fixture containing a biochip and to incubate the biochip. Specifically, the pipetting incubation unit M4 includes: a pipetting module 401, an incubation module 402, a cleaning mechanism 403, and a second robotic arm 404. The pipetting module 401 is at least used to inject reagents required for detection into the incubation fixture; the incubation module 402 is at least used to incubate the biochip in the reagents; the cleaning mechanism 403 is at least used to clean the incubated biochip; and the second robotic arm 404 is at least used to transfer the incubation fixture (containing a biochip) between the pipetting module 401, the incubation module 402, and the cleaning mechanism 403.

[0061] Specifically, the pipetting module 401 includes a loading stage 4011 and a pipetting head 4012. The loading stage is used to place the incubation fixture so that the pipetting head 4012 can perform pipetting operations on the incubation fixture. The transfer head 4012 is used to inject the reagents required for testing into the incubation fixture.

[0062] Specifically, the incubation module 402 includes an oscillating heater, which is used to provide at least the temperature and oscillation conditions required for the incubation of the biochip.

[0063] Specifically, the incubation module 402 also includes a capping mechanism, which is used at least to attach and detach a cap on the incubation fixture to encapsulate the reagents within the incubation fixture.

[0064] Specifically, the second robotic arm 404 can transfer the incubation fixture between the pipetting module 401, the incubation module 402, and the cleaning mechanism 403. More specifically, the second robotic arm 404 can be a tracked robotic arm, etc.

[0065] Please refer to the following for details. Figure 3 and Figure 6 The graphic fixture assembly and chip recycling unit M2 includes a graphic fixture rotary platform 201, a graphic fixture assembly module 202, a chip unloading module 203, and a third robotic arm 204. The graphic fixture rotary platform 201 is used at least to transport graphic fixtures within the graphic fixture assembly and chip recycling unit M2 and between the graphic fixture assembly and chip recycling unit M2 and the graphic detection unit M1. The graphic fixture assembly module 202 is used at least to load and unload graphic fixtures. The chip unloading module 203 is used at least to export the biochip after scanning and imaging detection. The third robotic arm 204 is used at least to transfer graphic fixtures / biochips between the graphic fixture rotary platform 201, the graphic fixture assembly module 202, and the chip unloading module 203.

[0066] Specifically, the graphic fixture rotary platform 201 can be a circulating conveyor mechanism, such as a closed-loop conveyor belt. The graphic fixture assembly module 202 is set on the running trajectory of the graphic fixture rotary platform 201. The structure and function of the graphic fixture assembly module 202 are basically the same as those of the incubation fixture assembly module 305. The graphic fixture assembly module 202 mainly assembles the graphic fixture cover and the graphic fixture base on the graphic fixture rotary platform 201 to form a graphic fixture. It should be noted that before assembling the graphic fixture, the biochip has been placed on the graphic fixture base. After scanning and imaging detection, the graphic fixture cover and the graphic fixture base are disassembled and separated to remove the encapsulated biochip.

[0067] For example, the graphic fixture assembly module includes a second three-dimensional moving platform, a second gripping mechanism, and a second locking actuator. The second gripping mechanism and the locking actuator are disposed on the second three-dimensional moving platform and are capable of moving along at least one of the X-axis, Y-axis, and Z-axis of a three-dimensional coordinate system under the drive of the second three-dimensional moving platform. The second gripping mechanism is used to detachably grip the graphic fixture base and the graphic fixture cover. The second locking actuator is used to screw the locking sleeve on the graphic fixture cover so that the locking sleeve fixes and locks the graphic fixture cover to the graphic fixture base, or to disengage the locking sleeve from the graphic fixture base so that the graphic fixture cover is separated from the graphic fixture base.

[0068] It should be noted that the structure of this graphic fixture can be the same as that of the incubation fixture, and will not be described in detail here.

[0069] For details, please refer to Figure 3 and Figure 7 The image detection unit M1 includes an image detection mechanism 101, an image fixture storage rack 102, and a fourth robotic arm 103. The image detection mechanism 101 is used to perform scanning imaging detection on the biochip. The image fixture storage rack 102 is mainly used to temporarily place and store the image fixture to be detected (which contains the biochip). The fourth robotic arm is used to transfer the biochip between the image detection mechanism 101, the image fixture storage rack 102, and the image fixture rotary platform 201. Specifically, it includes grasping the image fixture on the image fixture rotary platform 201 or the image fixture storage rack 102 and placing it in the image detection mechanism 101; grasping the image fixture on the image fixture rotary platform 201 and placing it on the image fixture storage rack 102; and transferring the image fixture that has completed the detection in the image detection mechanism 101 to the image fixture rotary platform 201.

[0070] Specifically, the first and second robotic arms can be column-type or tracked robotic arms, while the third and fourth robotic arms must be suitable for industrial robots with multi-path and multi-dimensional motion.

[0071] Specifically, the integrated system for fully automated biochip detection also includes a control unit, which is connected to the pattern detection unit M1, the pattern fixture assembly and chip retrieval unit M2, the incubation fixture assembly and chip transfer unit M3, and the pipetting incubation unit M4, and is used to regulate the working status of the pattern detection unit M1, the pattern fixture assembly and chip retrieval unit M2, the incubation fixture assembly and chip transfer unit M3, and the pipetting incubation unit M4.

[0072] Please refer to the following for details. Figure 8 The fully automated detection process for biochips using the integrated system for fully automated biochip detection provided by this invention can include the following steps:

[0073] 1) The operator places the biochip to be tested and reagents into the designated container. The chip loading module 301 in the incubation fixture assembly and chip transfer unit M3 moves the container containing the biochip to the designated position, while the chip incubation input module 303 moves another carrier to the middle position.

[0074] The grippers of the incubation fixture assembly module 305 place the incubation fixture base onto the carrier, and the chip incubation input module 303 moves the incubation fixture base further to the feeding position;

[0075] The first robotic arm 308 picks up the biochip at the designated position and places it on the incubation fixture base. The chip incubation input module 303 moves the biochip and the incubation fixture base forward to the middle position.

[0076] The grippers of the incubation fixture assembly module 305 place the incubation fixture cover onto the incubation fixture base. After the incubation fixture cover is in place, the pressure holding mechanism 309 presses down. Under uniform pressure, the first locking mechanism of the incubation fixture assembly module 305 tightens the locking sleeve located on the incubation fixture cover, fixing and locking the incubation fixture cover and the incubation fixture base to form an incubation fixture. Then, it is moved into the downstream pipetting incubation unit M4 through the chip incubation input module 303.

[0077] 2) In the pipetting incubation unit M4, the second robotic arm 404 places the incubation fixture onto the loading stage 4011 of the pipetting module 401. The pipetting head 4012 adds the reagents required for each step of the test into the incubation fixture. After each sample addition, the second robotic arm 404 picks up the incubation fixture and places it into the vibration heater of the incubation module 402. The capping module of the incubation module 402 puts a cover on the incubation fixture to prevent the liquid in the incubation fixture from evaporating from the sample dispensing hole (which can be called the sample hole) and reduce cross-contamination between sample dispensing holes.

[0078] After the cover plate is installed, the system will run the vibration heater according to the preset temperature and oscillation parameters to ensure that the reaction between the biochip and the reagents takes place under the conditions required for detection.

[0079] The steps of adding reagents and vibration heating incubation will be repeated continuously until all reagents required for each detection step are added and incubated. According to the chip detection experiment requirements, when the plate washing procedure is required after the incubation is completed, the capping module first removes the capping plate, and the second robotic arm grabs the incubation fixture and places it in the cleaning mechanism 403 to clean the surface of the biochip.

[0080] 3) After cleaning, the second robot 404 of the pipetting incubation unit M4 transfers the incubation fixture to the loading table 4011. The first robot 308 of the incubation fixture assembly and chip transfer unit M3 transfers the incubation fixture to the chip incubation output module 304, and is transported to the unloading position by the chip incubation output module 304. At the unloading position, the incubation fixture assembly module 305 opens the locking sleeve on the incubation fixture, and the incubation fixture base and the incubation fixture cover separate. The fixture gripping mechanism of the incubation fixture assembly module 305 grips the incubation fixture cover onto the tray located in the incubation fixture unloading module 302, and then grips the incubation fixture base and chip and puts them into the moving water tank 306. The moving water tank 306 moves to the material picking station. The first robot 308 grips the biochip in the water tank and puts it into the material box of the biochip output module 307, and is transported by the biochip output module 307 to the station of the graphic fixture assembly and chip recycling unit M2.

[0081] 4) In the graphic fixture assembly and chip recycling unit M2, the third robot 204 transfers the biochips on the material box output module 307 containing biochips to the graphic fixture rotary platform 201. Under the conveying of the graphic fixture rotary platform 201, the material box containing biochips is moved to the loading position. The third robot 204 picks up the biochips and puts them into the graphic fixture base, and then puts the graphic fixture cover in place. The graphic fixture rotary platform 201 conveys the graphic fixture with the graphic fixture cover in place to the locking position.

[0082] When the graphic fixture assembly module 202 is in operation, the graphic fixture base and the graphic fixture cover of the graphic fixture are fixedly combined, and the biochip is encapsulated in the graphic fixture.

[0083] Subsequently, the graphic fixture is moved to the picking position of the graphic detection unit M1, and the fourth robot arm 103 grabs the graphic fixture and puts it into the graphic detection mechanism (e.g., graphic analyzer) 101, and puts the remaining graphic fixtures containing the images to be imaged and containing the biochip into the graphic fixture storage rack 102.

[0084] After completing the automatic imaging scan of all biochips, the graphic fixture rotary platform 201 transports the graphic fixture to the unlocking position of the graphic fixture assembly and chip recycling unit M2. At the unlocking position, the graphic fixture assembly module 202 releases the locking sleeve of the graphic fixture.

[0085] The disassembled graphic fixture is transported by the graphic fixture rotary platform 201 to the unloading position of the graphic fixture assembly and chip recycling unit M2. The third robot arm 204 picks up the top cover of the graphic fixture, puts the analyzed biochip into the unloading box, and then the operator retrieves the chip from the box. The chip testing steps are all completed.

[0086] Example

[0087] An example of chip quality testing using an integrated system for fully automated biochip testing provided by this invention.

[0088] Operating procedures:

[0089] 1) Load the chip into the incubation fixture and wait for sample addition;

[0090] 2) Add buffer solution (usually PBST) to the sample well of the incubation fixture, shake to mix, and incubate at 57°C for 20-60 minutes to allow the buffer solution to fully wet the chip surface.

[0091] 3) Add blocking solution (usually a protein-based reagent), shake to mix, and incubate at 37°C for 15-60 minutes to reduce background interference.

[0092] 4) Add the primary antibody, shake to mix, and incubate at 37°C for 60 minutes. After incubation, wash the plate.

[0093] 5) Add the secondary antibody, shake to mix, and incubate at 37°C for 60 minutes. After incubation, wash the plate.

[0094] 6) The chip is removed from the incubation fixture and transferred to the graphics fixture, ready for automated imaging.

[0095] 7) Scan and image, then retrieve the scanned chip.

[0096] This invention provides an integrated system for fully automated detection of biochips. In the specific operation process, the operator loads the chip to be tested into the material box. Through the track of the incubation fixture assembly and chip transfer unit and the movement of the robot arm, the chip is loaded into the incubation fixture. The incubation fixture is locked, which improves the sealing performance and prevents leakage and contamination between samples.

[0097] This invention provides an integrated system for fully automated detection of biochips. It achieves automatic liquid addition and pipetting through a pipetting and incubation unit, provides suitable experimental conditions for chip incubation through an incubation module, so that the primary antibody can fully bind to the chip peptides, and the secondary antibody can then bind to the primary antibody on the chip, amplifying the fluorescence signal value. Finally, it can automatically wash away excess unbound reagents on the chip surface.

[0098] This invention provides an integrated system for fully automated biochip detection. The chip is transported to a pattern fixture assembly and chip retrieval unit for automatic packaging under the movement of a track. After automatic scanning and imaging, the pattern fixture and the detected chip are retrieved through the transfer between tracks, realizing fully automated biochip detection throughout the process.

[0099] It should be understood that the above embodiments are merely illustrative of the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. An integrated system for fully automated detection of biochips, characterized in that, include: An incubation fixture assembly and chip transfer unit, used at least for transferring biochips, loading and unloading incubation fixtures, and encapsulating biochips in incubation fixtures; A pipetting incubation unit, used at least for injecting reagents required for detection into an incubation fixture and for incubating the biochip; A graphic fixture assembly and chip recycling unit is used for loading and unloading graphic fixtures, encapsulating incubated biochips in graphic fixtures, and transferring biochips. The image detection unit is used at least for scanning and imaging detection of the incubated biochip. The image detection unit includes an image detection mechanism, a fourth robotic arm, and an image fixture storage rack. The image detection mechanism is used for scanning and imaging detection of the biochip. The image fixture storage rack is used for temporarily placing and storing the image fixture to be detected. The fourth robotic arm is used for transferring the biochip between the image detection mechanism, the image fixture storage rack, and the image fixture rotary platform. The incubation fixture assembly and chip transfer unit includes: A chip loading module, used at least for conveying unprocessed biochips; The incubation clamp loading and unloading module is used at least to transport the incubation clamp base and the incubation clamp cover to the incubation clamp assembly module, and to export the incubation clamp base and the incubation clamp cover disassembled from the incubation clamp assembly module. The chip incubation input module runs along a first direction and is at least used to transport the incubation fixture base and / or the incubation fixture cap within the working area of ​​the incubation fixture assembly module, and to transport the incubation fixture containing the biochip assembled by the incubation fixture assembly module to the pipetting incubation unit. The chip incubation output module runs along the second direction and is used at least within the working area of ​​the incubation fixture assembly module to transport the incubation fixture containing the biochip. The incubation fixture assembly module is used at least to assemble the incubation fixture base and incubation fixture cover on the chip incubation input module into an incubation fixture, and to disassemble the incubation fixture on the chip incubation output module into an incubation fixture base and incubation fixture cover. A portable water tank, at least for supporting the disassembled incubation fixture base and biochip; A biochip output module, used at least to deliver the biochip to a graphic fixture assembly and chip recycling unit; The first robotic arm is used to transfer at least one of the following between the chip loading module, the incubation fixture loading / unloading module, the chip incubation input module, the chip incubation output module, the incubation fixture assembly module, the mobile water tank, and the biochip output module: the incubation fixture base, the incubation fixture cap, the biochip, and the incubation fixture.

2. The integrated system for fully automated detection of biochips according to claim 1, characterized in that: The incubation fixture assembly module includes a first three-dimensional moving platform, a first gripping mechanism, and a first locking actuator. The first gripping mechanism and the first locking actuator are disposed on the first three-dimensional moving platform and can move along at least one of the X-axis, Y-axis, and Z-axis of a three-dimensional coordinate system under the drive of the first three-dimensional moving platform. The first gripping mechanism is used to detachably grip the incubation fixture base and the incubation fixture cover. The first locking actuator is used to screw the locking sleeve on the incubation fixture cover so that the locking sleeve fixes and locks the incubation fixture cover to the incubation fixture base, or to disengage the locking sleeve from the incubation fixture base so that the incubation fixture cover is separated from the incubation fixture base.

3. The integrated system for fully automated detection of biochips according to claim 2, characterized in that: The incubation fixture assembly module also includes a pressure holding mechanism, which is disposed on the three-dimensional moving platform and can be raised and lowered along the Z-axis of the three-dimensional coordinate system under the drive of the three-dimensional moving platform. The pressure holding mechanism is at least used to press the incubation fixture cover and the incubation fixture base along the Z-axis.

4. The integrated system for fully automated detection of biochips according to claim 1, characterized in that: The pipetting incubation unit includes: A pipetting module, used at least for injecting reagents required for detection into the incubation fixture; An incubation module, used at least for incubating biochips in reagents; The second robotic arm is used at least to transfer the incubation fixture between the pipetting module and the incubation module.

5. The integrated system for fully automated detection of biochips according to claim 4, characterized in that: The pipetting module includes a loading stage and a pipetting head, the pipetting head being used to inject the reagents required for testing into the incubation fixture.

6. The integrated system for fully automated detection of biochips according to claim 4, characterized in that: The incubation module includes an oscillating heater, which is used to provide at least the temperature and oscillation conditions required for the incubation of the biochip.

7. The integrated system for fully automated detection of biochips according to claim 6, characterized in that: The incubation module also includes a capping mechanism, which is at least used to attach or detach a cap on the incubation fixture to encapsulate the reagent within the incubation fixture.

8. The integrated system for fully automated detection of biochips according to claim 7, characterized in that: The incubation module also includes a cleaning mechanism, which is used at least to clean the incubated biochip. Furthermore, the second robotic arm is capable of transferring the incubation fixture between the pipetting module, the incubation module, and the cleaning mechanism.

9. The integrated system for fully automated detection of biochips according to claim 4, characterized in that, The graphic fixture assembly and chip recycling unit includes: A graphic fixture rotary platform is used at least for transporting graphic fixtures between a graphic fixture assembly and chip recycling unit and a graphic inspection unit. A graphic fixture assembly module, used at least for loading and unloading graphic fixtures; A third robotic arm is used at least to transfer the graphic fixture between the graphic fixture rotary platform and the graphic fixture assembly module.

10. The integrated system for fully automated detection of biochips according to claim 9, characterized in that: The graphic fixture assembly module includes a second three-dimensional moving platform, a second gripping mechanism, and a second locking actuator. The second gripping mechanism and the second locking actuator are disposed on the second three-dimensional moving platform and can move along at least one of the X-axis, Y-axis, and Z-axis of a three-dimensional coordinate system under the drive of the second three-dimensional moving platform. The second gripping mechanism is used to detachably grip the graphic fixture base and the graphic fixture cover. The second locking actuator is used to screw the locking sleeve on the graphic fixture cover so that the locking sleeve fixes and locks the graphic fixture cover to the graphic fixture base, or to disengage the locking sleeve from the graphic fixture base so that the graphic fixture cover is separated from the graphic fixture base.

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