CN108642159B

CN108642159B - Biochip detection system

Info

Publication number: CN108642159B
Application number: CN201810676781.4A
Authority: CN
Inventors: 朱滨; 徐建刚; 汪泽; 邢军芬
Original assignee: Shanghai Hongtan Biotechnology Co ltd
Current assignee: Shanghai Hongtan Biotechnology Co ltd
Priority date: 2018-06-27
Filing date: 2018-06-27
Publication date: 2022-07-01
Anticipated expiration: 2038-06-27
Also published as: CN108642159A

Abstract

The invention relates to the technical field of gene sequencing, and discloses a biochip detection system, which comprises: the PCR reaction device is used for amplifying the sample in the PCR tube; the hybridization device comprises a reaction cabin and a chip bearing platform which is provided with a biochip, so that the sample and the biochip are hybridized; the identification device detects the biochip processed by the hybridization device and obtains related gene information; and a conveying device for conveying the PCR tube to the PCR reaction device and conveying the amplified sample from the PCR reaction device to the hybridization device or conveying the hybridized biochip from the hybridization device to the recognition device. According to the invention, the conveying device is used for automatically conveying the PCR tube, the sample in the PCR tube and the hybridized biochip, so that the integration and systematization of the PCR reaction device, the hybridization device and the recognition device are realized, the mechanization and automation of biochip detection are realized, manual operation is reduced, the errors caused by manual operation can be reduced, and the detection efficiency of the biochip is improved.

Description

Biochip detection system

Technical Field

The invention relates to the technical field of gene detection, in particular to a biochip detection system.

Background

Biochips (also called DNA chips, gene chips) originate from crystallization by combining DNA hybridization probe technology with semiconductor industry technology, and mainly refer to a micro biochemical analysis system constructed on the surface of a solid-matrix chip by micromachining technology and microelectronic technology to realize accurate, rapid, and large-information-amount detection of cells, proteins, DNA, and other biological components. Briefly, biochips are prepared by placing a biological sample on a glass plate, a silicon wafer, a nylon membrane, etc., collecting signals with an instrument, and analyzing the data results with a computer.

The biochip has wide application, and can be used for detection of gene expression level, gene diagnosis, drug screening, individualized medical treatment, sequencing, bioinformatics research and the like. Specifically, the sequencing principle of the biochip is a hybridization sequencing method, i.e., a method for determining a nucleic acid sequence by hybridization with a group of nucleic acid probes of known sequence, in which probes of target nucleotides of known sequence are immobilized on the surface of a substrate. When the nucleic acid sequences with fluorescent labels are complementary matched with the nucleic acid probes at the corresponding positions on the biochip, a group of probe sequences with completely complementary sequences are obtained by determining the probe position with the strongest fluorescence intensity. The sequence of the target nucleic acid can be recombined according to the method. The sequencing of the biochip can analyze and determine gene sequences from blood or saliva, predict the possibility of suffering from various diseases, reasonably lock individual behavior characteristics and behaviors, and prevent and treat diseases in advance.

In the prior art, the use of the biochip mainly comprises the following steps: amplifying and marking, namely amplifying and amplifying a plurality of fragments of the sample by using methods such as PCR amplification or parallel solid phase cloning and the like, and marking by using biotin or fluorescence to obtain a marked sample; a hybridization reaction step, wherein target molecules in the marked sample are hybridized with probes on the biochip to generate a series of information; and signal detection and analysis, namely, using detection equipment to collect, process and analyze the fluorescence position and the fluorescence intensity of each reaction point on the biochip after hybridization reaction, and analyzing the image by using a chip scanner and related software to obtain related biological information.

In general, each step of the above biochip gene detection is an independent step, and each independent apparatus is used to perform the above steps individually, as described in detail in the PCR apparatus in reference 1, the spotting apparatus in reference 2, the hybridization apparatus in reference 3, the gene chip recognition apparatus in reference 4, and the like. The transfer of samples, biochips and the like among various devices requires manual operation and auxiliary execution, increases the cost and is easy to make mistakes; in addition, each above-mentioned equipment is independently and scattered and is placed, and occupation space is big, and the staff of being not convenient for carries out work systematically, greatly increased staff's working strength, the staff is because of the mistake appears in work easily because of excessive fatigue, biochip's detection efficiency is low. Therefore, there is a need for a detection system that can facilitate the systematic detection of biochips by the operator and improve the detection efficiency of biochips.

Reference 1: CN105039155A, a real-time fluorescent quantitative PCR instrument

Reference 2: CN103217324A, a biochip spotting instrument

Reference 3: CN102533525A full-automatic hybridization instrument

Reference 4: CN105590079A, method and equipment for continuously and automatically identifying and reading transmission signals of multiple biochips

Disclosure of Invention

The present invention is directed to the above-mentioned technical problems, and an object of the present invention is to provide a biochip detection system, which can facilitate the staff to systematically perform the steps of amplification, hybridization, detection, etc., thereby greatly reducing the working strength of the staff, reducing the manual operation errors, and improving the detection efficiency of the biochip.

The biochip detecting system of the invention comprises:

the PCR reaction device is used for amplifying the sample in the PCR tube;

the hybridization device comprises a reaction cabin and a chip bearing platform provided with a biochip, and is used for sucking a sample amplified by the PCR reaction device into the reaction cabin so as to perform hybridization between the sample and the biochip;

the identification device is used for identifying and analyzing the biochip processed by the hybridization device and obtaining related gene information;

and a conveying device for conveying the PCR tube filled with the biological sample to the PCR reaction device or conveying the amplified sample from the PCR reaction device to the hybridization device.

Compared with the prior art, the invention integrates the PCR reaction device, the hybridization device and the recognition device into a biochip detection system, and uses the conveying device to automatically convey the sample in the PCR tube, the sample in the PCR tube and the hybridized biochip, and realizes article transfer among the devices, thereby realizing integration and systematization of the PCR reaction device, the hybridization device and the recognition device, further realizing mechanization and automation of biochip detection, reducing manual operation and saving labor cost. In addition, the detection system reduces the working strength of workers, avoids the over-fatigue of the workers in the working process, thereby reducing the errors caused by manual operation and having high detection efficiency of the biochip.

Further, preferably, the transport device includes a carrier tray on which a hybridization reagent tube containing a hybridization buffer and the PCR tube containing the sample are placed, and a robot.

Through setting up the manipulator, can provide PCR pipe to PCR reaction unit mechanizedly, reduce manual work, reduce the cost of labor. Through setting up and bearing the tray, can change the position of hybridization reagent pipe and PCR pipe simultaneously, reduce the required operating procedure of detecting system, simplify the process.

In addition, preferably, the recognition device comprises a camera shooting mechanism and a data processing mechanism, and the camera shooting mechanism is arranged on the frame of the manipulator.

The information on the biochip after hybridization reaction is captured by the camera mechanism and transmitted to the data processing mechanism for processing, so that the relevant biological information is obtained. The identification device has simple structure and is convenient for operation.

Preferably, a first identification code is attached to the PCR tube containing the biological sample, a second identification code is attached to the biochip, and the first identification code and the second identification code are identified by the imaging mechanism.

The camera shooting mechanism is arranged to recognize the first identification code and the second identification code, so that the recognition device is simple and excellent in recognition effect. The camera shooting mechanism identifies the first identification code and the second identification code, so that whether the sample limited by the first identification code is matched with the biochip limited by the second identification code or not is conveniently compared, errors are reduced, and the detection efficiency of the biochip is improved.

Preferably, the PCR reaction apparatus includes an upper cover, a lower base, and a heating mechanism for heating a space formed between the upper cover and the lower base, the upper cover and the lower base being disposed to face each other in the vertical direction.

Through setting up heating mechanism, heat the space that forms between upper cover and the lower stage among the PCR reaction unit to the amplification environment to the sample that is located above-mentioned space heats, makes the sample in the PCR pipe can carry out the amplification. The PCR reaction device has simple structure and convenient operation.

Further, preferably, the biochip detecting system further comprises a cabinet, and the PCR reaction device, the hybridization device, the reading device and the conveying device are all arranged in the cabinet.

The PCR reaction device, the hybridization device and the reading device are uniformly arranged in a cabinet, so that the occupied space of each instrument is reduced to the maximum extent, the space is effectively utilized, and the system for detecting the biochip is convenient to carry out.

Preferably, the apparatus further comprises a control device communicatively connected to the PCR reaction device, the hybridization device, the reading device, and the transport device.

Through setting up controlling means control biochip detecting system's work, realize that biochip detects mechanization, the automation of whole process, need not artifical participation operation, very big reduction staff's working strength, reduce the misoperation, reduce the cost of labor, further improve biochip's detection efficiency.

Further, preferably, the camera mechanism includes a camera and a light source, and the camera and the light source are located on the same side with respect to the biochip.

The information on the biochip is shot by the camera, so that the identification device is simple and the identification effect is excellent. The light source is arranged and is positioned at the same side of the biochip with the camera, so that the camera is subjected to light supplementing treatment, the shooting definition of the camera is improved, and the information detection and analysis efficiency is improved.

Preferably, the carrier tray includes a tray body, a first groove portion for placing the hybridization reagent tube and a second groove portion for placing the PCR tube are formed in the tray body, and the carrier tray further includes a position limiting device for limiting the PCR tube so that the PCR tube does not separate from the tray body along with the needle fixed to the elevating arm.

Carry on spacingly to the PCR pipe through setting up stop device, when the pole needle that is fixed in the lift arm is taken out from the PCR pipe time, can avoid the pole needle to take the PCR pipe away from bearing the tray, need not the manual work and puts back the normal position with the PCR pipe to be favorable to improving biochip's detection efficiency.

Preferably, the chip carrier includes a frame and a platen located in the frame, the platen is provided with a plurality of carrier grooves for holding biochips, the chip carrier further includes an elastic member, two ends of the elastic member are respectively connected to the platen and the lower edge of the frame, and the platen can move up and down relative to the frame by the elastic member.

The chip bearing platform consists of a frame body and a bedplate which moves up and down in the frame body through an elastic piece, and the contact surface between the reaction cabin and the bedplate can be ensured to be closed all the time tightly in the process that the reaction cabin in the hybridization device moves towards the bedplate and is gradually pressed, so that the space formed between the reaction cabin and the bedplate is completely closed, the hybridization environment of a biochip in the reaction cabin is stable and closed, and the hybridization efficiency is high.

Drawings

FIG. 1 is a basic flow chart of a biochip measuring system according to an embodiment of the present invention;

FIG. 2 is a schematic view of the biochip detection system according to the embodiment of the present invention (for convenience, a part of the cabinet is hidden);

FIG. 3 is an enlarged view of a portion A of FIG. 2;

FIG. 4 is an overall schematic view of the robot;

FIG. 5 is a partial enlarged view of portion B of FIG. 2;

FIG. 6 is an overall schematic view of a carrying tray according to an embodiment of the present invention (for convenience, a portion of the frame is hidden);

FIG. 7 is an enlarged view of a portion D of FIG. 6;

FIG. 8 is a partial enlarged view of the portion C in FIG. 2

Fig. 9 is a bottom view of the camera.

Description of reference numerals:

1, a cabinet; 2-a control device; 3-PCR reaction device; 31-upper cover; 32-setting the platform; 4-a hybridization device; 41-chip carrier table; 41 a-frame; 41 b-a platen; 41 c-a carrying groove; 41 d-elastic member; 42-a reaction chamber; 43-bar needle; 44-a lifting arm; 5-a reading device; 51-an image pickup mechanism; 51 a-a camera; 51 b-a light source; 52-data processing means; 6-a conveying device; 61-a carrying tray; 61 a-a first slot portion; 61 b-a second slot; 62-a manipulator; 62 a-a flat plate portion; 62 b-a bifurcation; 62b 1-bifurcated leading end; 62b 2-arc-shaped portion; 62 c-a limit protruding strip; 62 d-a frame; a 62e-Z direction lead screw assembly; 62e 1-nut; 63-a limiting device; 63 a-limiting plate; 63 b-a detent; 63 c-perforation; 7-PCR tube; 71-a first identification code; 8-hybridization reagent tube; 9-a biochip; 91-second identification code.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings.

In the description of the present invention, it is to be understood that the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present invention and simplifying the description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention.

The invention provides a biochip detection system, which is shown in figures 1 and 2 and comprises a PCR reaction device 3, a hybridization device 4, a reading device 5 and a conveying device 6. Wherein: a PCR reaction device 3 for amplifying the sample in the PCR tube 7; a hybridization device 4 including a reaction chamber 42 and a chip carrier 41 on which the biochip 9 is placed, for sucking the sample amplified by the PCR reaction device 3 into the reaction chamber 42 to hybridize the sample with the biochip 9; a recognition device 5 for recognizing and analyzing the biochip 9 processed by the hybridization device 4 to obtain related gene information; and a transport unit 6 for transporting the PCR tube 7 containing the biological sample to the PCR reaction unit 3 and transporting the amplified sample from the PCR reaction unit 3 to the hybridization unit 4, or transporting the hybridized biochip 9 from the hybridization unit 4 to the reading unit 5.

Compared with the prior art, the steps of amplification, hybridization and reading can be carried out in a centralized way in the biochip detection system, the occupied space of instruments and equipment used in related steps is reduced, workers do not need to switch positions in a large range to carry out auxiliary execution of different steps, the working intensity of the workers is greatly reduced, and the detection efficiency of the biochip 9 is improved. The conveying device 6 is used for automatically conveying the PCR tube 7 and samples in the PCR tube 7, and the integration and systematization of the PCR reaction device 3, the hybridization device 4 and the recognition device 5 are realized, so that the mechanization and automation of the detection of the biochip 9 are realized, the manual operation is reduced, and the labor cost is saved. In addition, the steps of amplification, hybridization and reading in the invention can be carried out in a centralized way in the biochip detection system, and workers can carry out the detection work of the biochip 9 systematically, thereby reducing the working strength, avoiding the error of the workers in the work due to over fatigue and further improving the detection efficiency of the biochip 9.

Referring to fig. 3 and 5, the transfer device 6 includes a carrier tray 61 and a robot 62, the carrier tray 61 carries thereon a hybridization reagent tube 8 containing a hybridization buffer and a PCR tube 7 containing a sample, and the robot 62 can transfer the PCR tube 7. By providing the manipulator 62, the PCR tube 7 can be mechanically supplied to the PCR reaction apparatus 3, and thus, the number of manual operations and the labor cost can be reduced. By providing the support tray 61, the positions of the hybridization reagent tubes 8 and the PCR tubes 7 can be changed simultaneously, thereby reducing the number of steps of the system and simplifying the process.

As shown in fig. 1 and 2, the reading device 5 includes a camera 51 and a data processing 52. The information on the biochip 9 after the hybridization reaction is collected by the camera 51, the fluorescence position and the fluorescence intensity of each reaction point on the biochip 9 are obtained, and the information is transmitted to the data processing 52. Specifically, the solution in the PCR tube 7 is amplified and carries a nucleic acid sequence with fluorescent label. The nucleic acid sequence is complementary matched with the nucleic acid probe at the corresponding position on the gene chip 9 in the hybridization device 4, and a group of probe sequences with completely complementary sequences is obtained. The data processing means 52 processes and analyzes the information to analyze the image, and thus biological information such as the presence or absence of a disease gene, a hereditary disease gene, an allergy gene, or the like can be obtained. The recognition device 5 has simple structure and is convenient for operation.

Referring to fig. 4 and 6, a first identification code 71 is attached to the PCR tube 7 containing the biological sample, a second identification code 91 is attached to the biochip 9, and the first identification code 71 and the second identification code 91 are identified by the imaging means 51. The imaging means 51 recognizes the first identification codes 71 before and after the PCR tubes 7 are supplied to the PCR reaction apparatus 3, respectively, and determines whether or not the PCR tubes 7 are the PCR tubes 7 to be set and whether or not misplacement occurs. When the error of the PCR tube 7 is identified, and the PCR tube 7 which is not to be placed is not identified, the error can be reported in time and the correct PCR tube 7 is replaced, so that the correctness of the PCR tube 7 is ensured, and the detection efficiency of the biochip 9 is improved. The camera means 51 recognizes the second identification code 91 before the sample is hybridized with the biochip 9 in the hybridization device 4, and compares whether the PCR tube 7 defined by the first identification code 71 matches with the biochip 9 defined by the second identification code 91. When the first identification code 71 and the second identification code 91 are detected to be not matched, an error is reported in time, the PCR tube or the biochip 9 is exchanged to ensure matching, errors are reduced, and therefore the detection efficiency of the biochip 9 is improved. The first identification code 71 and the second identification code 91 are two-dimensional codes in the present embodiment.

As shown in fig. 3 and 4, the manipulator 62 includes a flat plate portion 62a and a bifurcated portion 62b extending forward from the flat plate portion 62 a. The fork parts 62b form a holding space for holding an article (here, a PCR tube), and the position of the PCR tube 7 is changed by taking and placing the article. Preferably, the bifurcated portion 62b is a U-shaped member including two bifurcated forward ends 62b1 and an arcuate portion 62b2 connecting the two bifurcated forward ends 62b1, the U-shaped member being sized to mate with the PCR tube 7 to facilitate access by the robotic arm 62.

In particular, the opposing portions of the two branch ends 62b1 are roughened to increase the friction coefficient of the branch ends 62b1 and further increase the friction force applied to the PCR tube 7 at the branch ends 62b1, so that the PCR tube 7 is less likely to move left and right or slip downward at the branch portions 62b, and the robot 62 has a high gripping efficiency and a good transfer effect.

Referring to FIG. 4, further, the upper surface of the branch part 62b is inclined downward toward the stopper protrusion 62c, and the PCR tube 7 at the branch part 62b has a gravitational component inclined downward toward the stopper protrusion 62 c. When the hand 62 forks the PCR tube 7 into the bifurcated tip 62b1, the PCR tube 7 can be placed at any position of the bifurcated tip 62b1, and the precision of gripping the PCR tube 7 by the hand 62 is low. During the process of lifting and transferring the PCR tube 7, the PCR tube 7 is moved in the direction of the stopper projection 62c by the gravity component in the inclined downward direction, and is stopped and stopped by the stopper projection 62c, and the PCR tube 7 is held at the same position as the branched front end 62b 1. Regardless of the initial position of the PCR tube 7 on the manipulator 62, it will eventually slide to the same position of the manipulator 62, and the control system can control the manipulator 62 to precisely drop the object.

Referring to fig. 4, the manipulator 62 further includes a frame 62d, the frame 62d is driven by a two-axis linkage mechanism, and the two-axis linkage mechanism drives the frame 62d to transmit in the X direction and the Y direction. The two-axis linkage mechanism comprises an X-direction lead screw component and a Y-direction lead screw component, the Y-direction lead screw component is fixed on a nut of the X-direction lead screw component, and the rack 62d is fixed on the nut of the Y-direction lead screw component. The rack 62d is provided with a Z-direction screw assembly 62e, and the robot is fixed to a nut of the Z-direction screw assembly 62 e. (wherein, the structure and the working principle of the screw assembly are the prior art, and are not described herein again. The driving mechanism is set to be a two-axis linkage mechanism, the rack 62d is independently driven to move in the X direction and the Y direction, and the Z-direction lead screw assembly 62e is matched to work, so that the mechanical arm 62 and the camera 51a are driven to move in three dimensions, and the driving mechanism is good in driving precision and high in efficiency.

In another embodiment, the driving mechanism may be provided to include a three-axis linkage mechanism, and the driving mechanism drives the three-dimensional motion of the frame 62d and further drives the three-dimensional motion of the robot arm and the camera 51a, and thus the driving mechanism has high driving accuracy and high efficiency.

In the biochip detecting system, the robot 62 is required to be used a plurality of times to transfer the PCR tubes 7, the camera 51a is also required to be used a plurality of times to capture the first identification code 71, the second identification code 91 and the information on the biochip 9, and in the step of capturing the first identification code 71 and the second identification code 91 by the camera 51a, the camera 51a and the robot 62 have overlap in stroke. In order to simplify the internal structure of the biochip detecting system, particularly, referring to fig. 4, the camera 51a is located on the frame 62d of the robot arm 62, and in the present embodiment, the camera 51a is fixedly disposed on the flat plate portion 62a of the robot arm 62 and movably connected to the frame 62 d. The camera 51a is fixed to the flat plate portion 62a of the manipulator 62, so that the manipulator 62 and the camera 51a are integrated, the positions of the manipulator 62 and the camera 51a can be changed synchronously, the operation steps of the manipulator 62 and the camera 51a can be simplified, and the detection efficiency of the biochip 9 can be improved.

Referring to fig. 3, the PCR reaction apparatus 3 includes an upper cover 31, a lower stage 32 and a heating mechanism for heating a space formed between the upper cover 31 and the lower stage 32, wherein the upper cover 31 and the lower stage 32 are disposed opposite to each other, and the heating mechanism includes a heating sheet in the present embodiment, and the heating sheet is disposed in the upper cover 31 and the lower stage 32 (the heating sheet is disposed in the upper cover 31 and the lower stage 32 as the heating mechanism, and the structure and the operation principle thereof are the prior art, and are not shown in the figure for simplicity). When the upper cover 31 and the lower base 32 are closed, a space is formed between the upper cover and the lower base for placing the PCR tube 7. The heating means heats the space to heat the amplification environment of the sample in the space, and thereby the sample in the PCR tube 7 is amplified. The PCR reaction device 3 has simple structure and convenient operation. Particularly, the heating plates are respectively arranged in the upper cover 31 and the lower table 32, and heat the sample in the space up and down simultaneously, so that the heating is uniform, the amplification environment of the sample is stable, and the amplification efficiency is high.

Referring to FIG. 2, the biochip measuring system further includes a cabinet 1, and the PCR reaction device 3, the hybridization device 4, the reading device 5, and the transportation device 6 are disposed in the cabinet 1. Set up PCR reaction unit 3, hybridization device 4 and recognition device 5 in rack 1 in unison, effectively utilize the space, make things convenient for biochip 9 to detect work and go on systematically. In addition, the cabinet 1 can also avoid the entering of impurities such as dust, and the PCR tube 7 device, the hybridization device 4, the recognition device 5 and the conveying device 6 in the cabinet 1 are protected from being interfered by external impurities.

Referring to FIG. 1, the biochip detecting system further includes a control device 2, and the control device 2 is communicatively connected to the PCR reaction device 3, the hybridization device 4, the reading device 5 and the transportation device 6. Through the work of controller control PCR reaction unit 3, hybridization device 4, recognition device 5 and conveyor 6, realize mechanization, the automation of 9 testing processes of biochip, need not artifical participation operation, very big reduction staff's working strength, reduce manual operation error, reduce the cost of labor, further improve 9 biochip's detection efficiency. The cabinet 1 is provided with a display for displaying control options or detection results (the working principle of the display is the prior art, so the display is not shown in the figure). Of course, a separate controller may be provided outside the cabinet 1, and a display may be provided on the controller to control the execution of the above method.

Referring to FIG. 9, the imaging mechanism 51 includes a camera 51a, and the camera 51a and the light source 51b are located on the same side with respect to the biochip 9. By setting the camera 51a to take the information on the biochip 9, the taking device is simple, the taking effect is excellent, and the signal detection and analysis steps are facilitated. In the actual shooting process, sometimes the definition of the shot image information is influenced due to insufficient light, the light source 4b is arranged on the periphery of the camera 4a to supplement light to the biochip 7, the shooting precision of the camera 4a is improved, and the signal detection and analysis efficiency is improved. Meanwhile, the light source 51b and the camera 51a are positioned on the same side of the biochip 9, and the same-direction illumination and shooting are performed, so that the forward photography is performed, the imaging is clear, the distortion degree is small, and the information acquisition efficiency is improved. In this embodiment, referring to fig. 7, the light source 51b is a plurality of beads surrounding the casing of the camera 51a, so as to realize uniform supplementary lighting. Of course, the light source 4b may be a single LED lamp disposed near the camera 4a, and is not limited to the form of a lamp bead as long as supplementary lighting can be achieved.

Referring to FIG. 8, the carrier tray 61 includes a tray body in which a first groove 61a for placing the hybridization reagent tube 8 and a second groove 61b for placing the PCR tube 7 are formed. In particular, the first groove portion 61a has a semicircular shape at one end and a rectangular shape at the other end in a plan view, and is fitted to the hybridization reagent tube 8 having a semicircular shape at one end and a rectangular shape at the other end in a plan view. When the hybridization reagent tube 8 is set, the first groove portion 61a automatically recognizes the setting direction of the hybridization reagent tube 8, and the setting efficiency of the hybridization reagent tube 8 is improved. In another embodiment, the first groove 61a and the second groove 61b may have other shapes that are adapted to the outer shapes of the hybridization reagent tube 5b and the PCR tube 5, respectively.

Referring to fig. 8, the supporting tray 61 further includes a limiting device 63, and the limiting device 63 limits the position of the PCR tube 7, so that the PCR tube 7 cannot be separated from the tray body along with the rod pins 43 fixed to the lifting arm 44. The limiting device 63 comprises a limiting plate 63a, a clamping piece 63b is further arranged on the tray body, the limiting plate 63a can be clamped and fixed with the clamping piece 63b, and the limiting plate 63a is fixedly arranged on the shell of the hybridization device 4. The needle 43 in the hybridization device 4 is fixed to the lifting arm 44, the needle 43 can move up and down under the driving of the lifting arm 44, and the stopper plate 63a is provided with a through hole 63c for the needle 43 to pass through. Carry out spacingly to PCR pipe 7 through setting up stop device 63, when the pole needle 43 is taken out from PCR pipe 7, the card is decided 63b and is fixed with limiting plate 63a block, fixed limiting plate 63a is with PCR pipe 7 card dress, prevent PCR pipe 7's rising trend, thereby can avoid pole needle 43 to take PCR pipe 7 away from bearing tray 61, need not the manual work and put back the normal position with PCR pipe 7, thereby be favorable to improving biochip 9's detection efficiency.

Referring to fig. 6, the chip carrier 41 includes a frame 41a and a platen 41b located in the frame 41a, the platen 41b is opened with a plurality of carrier slots 41c for holding the biochips 9, the chip carrier 41 further includes an elastic member 41d, two ends of which are respectively connected to the lower edges of the platen 41b and the frame 41a, and the platen 41b can move up and down relative to the frame 41a by the elastic member 41 d. The chip carrier 41 is composed of a frame 41a and a platen 41b which moves up and down in the frame 41a through an elastic member 41d, and the reaction chamber 42 in the hybridization device 4 can ensure that the contact surface between the reaction chamber 42 and the platen 41b is always tightly closed in the process of moving toward the platen 41b and gradually pressing, so that the space formed between the reaction chamber 42 and the platen 41b is completely sealed, the hybridization environment of the biochip 9 therein is stably sealed, and the hybridization efficiency is high.

In order to prevent a person from being scratched by sharp corners of the frame 41a when the person passes through the frame 41a or the frame 41a from being scratched by other devices when the person moves, the corners of the frame 41a are rounded. The platen 41b is provided with a plurality of bearing grooves 41c, and the plurality of bearing grooves 41c are divided into two rows on average.

Referring to fig. 7, a sleeve 41e is coaxially inserted into the elastic member 41d, and for the purpose of enhancing stability, the outer diameter of the sleeve 41e near the upper edge of the frame 41a is smaller than that of the sleeve 41e near the lower edge of the frame 41 a. The bottom end of the bundle 41e is connected to the lower edge of the frame 41a, and the platen 41b can slide up and down along the top end of the bundle 41 e. At this time, the sleeve 41e limits the stretching direction of the elastic member 41d to be vertical up and down, so that the bedplate 41b accurately moves up and down in the frame 41a along the vertical direction, the bedplate 41b is prevented from being inclined, the stress on the bedplate 41b is balanced, the placing is stable, and the closed hybridization of the biochip 9 is facilitated. The hybridization environment of the biochip 9 is stable and closed, and the hybridization efficiency is high.

In this embodiment, the elastic member 41d is a spring, but in other embodiments, the elastic member 41d may be an elastic rubber block or an elastic piece.

The biochip 9 to which the present detection system is applied includes, but is not limited to, gene chips, protein chips, and tissue chips.

In particular, the amplification, hybridization, and detection in the present invention may be performed sequentially or individually.

The following detailed description of the specific embodiments and advantages of the present invention:

the first identification code 71 and the second identification code 91 are respectively pasted on the PCR tube 7 and the biochip 9 which are filled with the biological samples.

The steps of placing the PCR tube 7 and the hybridization reagent tube 8 on the carrier tray 61 and attaching the first identification code 5a and the second identification code 7a and the steps of placing the PCR tube 5, the hybridization reagent tube 5b and the biochip 7 may be reversed, and preferably, the first identification code 5a and the second identification code 7a are attached first.

The carrier tray 61 and the chip carrier 41 are pushed into the cabinet.

The camera 51a captures information of the first identification code 71 on the PCR tube 7, and transmits the captured information to the controller, and the controller identifies whether the PCR tube 7 is placed at a correct position and in a correct direction for the PCR tube to be amplified.

When the PCR tube 7 is not the PCR tube 7 to be placed, a warning sound is given or an abnormality is displayed on the display, so that a worker is reminded to place the PCR tube 7 again.

The controller controls the operation of the robot 62, and the robot 62 supplies the PCR tube 7 to the PCR reaction apparatus 3, and the PCR reaction apparatus 3 amplifies the sample supplied to the PCR reaction apparatus 3.

After the amplification is completed, the controller controls the operation of the robot 62, and the robot 62 returns the PCR tube 7 to the carrier tray 61.

The tray 61 of the PCR tube 7 carrying the amplified sample is pushed to the hybridization device 4, and the stopper 63a is engaged and fixed by the engaging member 63 b. The lifting arm 44 of the hybridization device 4 drives the needle 43 to move downwards and insert into the PCR tube 7, the bidirectional peristaltic pump of the hybridization device 4 works in a bidirectional way repeatedly for many times, and the liquid inlet capillary tube sucks or adds liquid in the PCR tube 7 repeatedly for many times for sample introduction.

After the sample introduction is finished, the lifting arm 44 drives the needle 43 to move upwards and draw out of the PCR tube 7. The fixed stopper plate 63a stops the PCR tube 7 to prevent the PCR tube 7 from rising, thereby preventing the probe pin 43 from taking the PCR tube 7 off the carrier tray 61.

The camera 51a captures the information of the second identification code 91 on the biochip 9, and transmits the captured information to the controller, and the controller identifies whether the biochip 9 is matched with the PCR tube 7 or not, and whether the biochip 7 is matched with the PCR tube 5 or not.

When the biochip 9 is not matched with the PCR tube 7, a warning tone is given or an abnormality is displayed on a display, thereby reminding a worker to replace the biochip 9.

During the reaction chamber 42 moves toward the chip carrier 41 and gradually presses the platen 41b, the elastic member 41d is compressed downward to have an upward restoring force. The upward restoring force of the elastic member 41d causes the platen 41b and the two opposing surfaces of the reaction chamber 42 to always abut against each other over the entire surface thereof during the pressing process, and the reaction chamber 42 and the platen 41b are completely sealed. The biochip 9 is hybridized in the space between the reaction chamber 42 and the chip carrier 41.

After the hybridization reaction is finished, the camera 51a collects the biological information on the biochip 9, obtains the fluorescence position and the fluorescence intensity of each reaction point on the biochip 9, and transmits the information to the data processing mechanism 52. The data processing means 52 processes and analyzes the conditions of each reaction site on the biochip 7 after the hybridization reaction, analyzes the image, and converts the fluorescence into data, thereby obtaining the biological information.

It is obvious to those skilled in the art that the respective steps of the above-described control method can be deleted or adjusted in order as necessary within the scope of the technical idea of the present invention.

It will be appreciated by those of ordinary skill in the art that in the embodiments described above, numerous technical details are set forth in order to provide a better understanding of the present application. However, the technical solutions claimed in the claims of the present application can be basically implemented without these technical details and various changes and modifications based on the above-described embodiments. Accordingly, in actual practice, various changes in form and detail may be made to the above-described embodiments without departing from the spirit and scope of the invention.

Claims

1. A biochip detection system, comprising:

the PCR reaction device is used for amplifying the biological sample in the PCR tube;

the hybridization device comprises a reaction cabin and a chip bearing platform for placing a biochip, wherein a sample amplified by the PCR reaction device is sucked into the reaction cabin to be hybridized with the biochip, the chip bearing platform comprises a frame body and a bedplate positioned in the frame body, a plurality of bearing grooves for placing the biochip are formed in the bedplate, the chip bearing platform also comprises an elastic piece, two ends of the elastic piece are respectively connected to the bedplate and the lower edge of the frame body, and the bedplate can move up and down relative to the frame body by utilizing the elastic piece;

the identification and reading device is used for identifying and analyzing the biochip processed by the hybridization device and obtaining related gene information, and the identification and reading device further comprises a data processing mechanism;

a transport device for transporting the PCR tube containing the biological sample to the PCR reaction device or transporting the amplified sample from the PCR reaction device to the hybridization device; the conveying device comprises a bearing tray and a manipulator, wherein the bearing tray is loaded with a hybridization reagent tube with a built-in hybridization buffer solution and the PCR tube with a built-in biological sample;

the bearing tray comprises a tray body, a first groove part for placing the hybridization reagent tube and a second groove part for placing the PCR tube are formed on the tray body, the bearing tray also comprises a limiting device for limiting the PCR tube, so that the PCR tube cannot be separated from the tray body along with a rod needle fixed on a lifting arm, and the lifting arm is the lifting arm of the hybridization device;

the manipulator comprises a flat plate part and a bifurcate part extending forwards from the flat plate part, a clamping space for clamping articles is formed by the bifurcate part, a limiting protruding strip is arranged at the front end of the bifurcate part, and the upper surface of the bifurcate part inclines downwards towards the direction of the limiting protruding strip;

a first identification code is pasted on the PCR tube with the biological sample, a second identification code is pasted on the biochip, and the first identification code and the second identification code are identified by a camera shooting mechanism of the identification device;

the camera shooting mechanism is arranged on a rack of the manipulator, the rack is driven to act through a two-axis linkage mechanism, the two-axis linkage mechanism drives the rack to transmit in the X direction and the Y direction, the two-axis linkage mechanism comprises an X-direction lead screw component and a Y-direction lead screw component, the Y-direction lead screw component is fixed on a nut of the X-direction lead screw component, the rack is fixed on a nut of the Y-direction lead screw component, a Z-direction lead screw component is arranged on the rack, and the manipulator is fixed on a nut of the Z-direction lead screw component;

the camera shooting mechanism respectively identifies the first identification codes before and after the PCR tube is provided to the PCR reaction device so as to judge whether the PCR tube is the PCR tube to be placed or not and whether misplacement occurs or not, and the camera shooting mechanism identifies the second identification code before the amplified sample is hybridized with the biochip in the hybridization device and compares whether the PCR tube limited by the first identification code is matched with the biochip limited by the second identification code or not;

the biochip detection system also comprises a cabinet, wherein the PCR reaction device, the hybridization device, the reading device and the conveying device are all arranged in the cabinet.

2. The system of claim 1, wherein the PCR reaction apparatus comprises an upper cover, a lower plate and a heating mechanism for heating a space formed between the upper cover and the lower plate.

3. The biochip detection system according to claim 1, further comprising a control device communicatively connected to the PCR reaction device, the hybridization device, the reading device, and the transport device.

4. The biochip detection system according to claim 1, wherein the camera mechanism comprises a camera and a light source, the camera and the light source being located on the same side with respect to the biochip.