Automated biological sample detection device and detection method based on encoded liquid chip

Abstract

The application discloses an automatic biological sample detection device based on an encoding liquid phase chip and a detection method. The automatic biological sample detection device comprises a sample pretreatment area, a sample table, a sample detection area and a control unit. The sample pretreatment area comprises a sample adding unit and a first moving unit. The sample detection area comprises a sample detection unit and a second moving unit. The sample table is arranged between the sample pretreatment area and the sample detection area. The control unit is electrically connected with at least the first moving unit, the sample detection unit and the second moving unit. The automatic biological sample detection device provided by the application is compact in structure, convenient to install and low in manufacturing cost. When used, the automatic biological sample detection device can automatically perform sample pretreatment and sample detection, can reduce manual intervention, effectively improves detection efficiency and accuracy, reduces costs of manpower, reagents and the like in many aspects, is very suitable for popularization and use in practical application, and has a wide market prospect.

Description

TECHNICAL FIELD

[0001] The application relates to a biological sample detection device, in particular to an automatic biological sample detection device based on a coded liquid chip and a detection method, and belongs to the technical field of biochemical detection. BACKGROUND

[0002] Complex life activities are often the result of the synergistic effect of a group of biological molecules as core execution elements. The fingerprint left by numerous diseases at the molecular level is often determined by multiple biomarkers. With the advent of the era of precision medicine, high-sensitivity accurate quantification of multiple biomarkers in a large number of samples will increasingly become an indispensable mainstream analysis task in the fields of modern diagnostics, therapeutics, drug development, and translational medicine.

[0003] The coded liquid chip technology is a technology that uses classification coded microspheres suspended in a liquid phase as a reaction and signal detection carrier. It identifies the physical and chemical properties of the reaction carrier-microspheres, is a new type of biochip technology platform, and is widely used in genomics research, proteomics research, drug development, basic research, and clinical diagnosis. It has great application potential in the large-scale analysis of biological macromolecules such as nucleic acids and proteins.

[0004] Since the coded suspension chip technology is a new type of technology platform, there are still relatively few products based on the coded suspension chip technology. From the detection means, the existing detection products mainly have two types: the first type is a flow cytometry fluorescence product based on fluorescent microspheres, and the second type is an imaging product based on a two-dimensional code chip. Some automated instruments and equipment can adapt to flow cytometry fluorescence products, but there is still no automatic sample detection device and method that can fully match the imaging coded suspension chip, which has become a difficult problem to be solved in the field. SUMMARY

[0005] The main purpose of the present application is to provide an automatic biological sample detection device and method based on a coded liquid chip to overcome the deficiencies in the prior art.

[0006] To achieve the foregoing purposes of the application, the technical solutions adopted by the present application include:

[0007] One aspect of the present application provides an automatic biological sample detection device based on a coded liquid chip, which comprises:

[0008] A sample pretreatment area comprising a sample adding unit and a first moving unit connected to the sample adding unit, the first moving unit being used to drive the sample adding unit to perform a pipetting action to complete the pretreatment of the sample.

[0009] a sample detection area, comprising a sample detection unit and a second movement unit connected with the sample detection unit, the second movement unit being used to drive the sample detection unit to move, and the sample detection unit being used to detect a sample loaded on the sample plate;

[0010] a sample table, arranged between the sample pre-treatment area and the sample detection area, and used to at least carry the sample plate, the sample and the reagent container;

[0011] a control unit, electrically connected with at least the first movement unit, the sample detection unit and the second movement unit, and used to control at least the working state of the first movement unit, the sample detection unit and the second movement unit.

[0012] In an embodiment, the automatic biological sample detection device further comprises a body unit, and the sample pre-treatment area, the sample table and the sample detection area are sequentially arranged in the body unit from top to bottom.

[0013] In an embodiment, the first movement unit comprises a first Z-axis movement module, a second Z-axis movement module and a liquid operation module; the first Z-axis movement module is used to carry a sample adding unit, the first Z-axis movement module is connected with the second Z-axis movement module; the second Z-axis movement module is connected with the liquid operation module and is used to drive the liquid operation module to perform liquid operation; the first Z-axis movement module and the second Z-axis movement module are respectively used to drive the sample adding unit and the liquid operation module to move along the Z-axis of a three-dimensional coordinate system.

[0014] In an embodiment, the automatic biological sample detection device further comprises a third movement unit used to carry the sample table; the sample table comprises a sample plate placing module and a reagent placing module, the sample plate placing module is used to accommodate the sample plate, and the reagent placing module is used to accommodate the sample and the reagent container; the third movement unit comprises an X-axis movement module and a Y-axis movement module, and the X-axis movement module and the Y-axis movement module are respectively used to drive the sample table to move along the X-axis and the Y-axis of a three-dimensional coordinate system.

[0015] In an embodiment, the sample table further comprises a consumable placing module, and the consumable placing module is used to accommodate a consumable container.

[0016] In an embodiment, the sample detection unit comprises a fluorescent light source, an optical detection light path, an optical detection objective lens and an optical detection sensor; the second movement unit comprises a third Z-axis movement module; the third Z-axis movement module is used to carry the optical detection objective lens and drive the optical detection objective lens to move along the Z-axis of a three-dimensional coordinate system.

[0017] In an embodiment, the body unit has a frame structure prepared from a standard aluminum profile.

[0018] In one embodiment, the automated biological sample detection device further comprises an air purification module fixed on the body unit.

[0019] In one embodiment, the automated biological sample detection device further comprises a bright field illumination light source fixed on the body unit.

[0020] Another aspect of the present application provides an automated biological sample detection method based on coded liquid chip, comprising:

[0021] Providing the automated biological sample detection device based on coded liquid chip;

[0022] Adding sample into the sample and reagent container and placing on the sample stage, and setting sample plate on the sample stage;

[0023] Starting the automated biological sample detection device, moving the sample adding unit above the sample stage, and performing pipetting action to load the sample on the sample plate, completing sample pretreatment;

[0024] Then moving the sample detection unit to the position corresponding to the sample plate, and detecting the signal value of each sample on the sample plate until the detection is completed.

[0025] Compared with the prior art, the automated biological sample detection device based on coded liquid chip provided by the present application has compact structure, convenient installation and low manufacturing cost, and can automatically perform sample pretreatment and sample detection during use, which can reduce manual intervention, effectively improve detection efficiency and accuracy, reduce labor, reagent and other costs, and is very suitable for popularization and use in practical application, and has wide market prospect. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the present application, and those skilled in the art can obtain other drawings from the structures shown in these drawings without creative labor.

[0027] Figure 1 is a structural schematic diagram of an automated biological sample detection device based on coded liquid chip in an embodiment of the present application;

[0028] Figure 2 is a structural schematic diagram of a sample pretreatment unit in an embodiment of the present application;

[0029] Figure 3 This is a schematic diagram (top view) of a sample stage according to one embodiment of this application;

[0030] Figure 4 This is a schematic diagram of the structure of a biological detection unit according to an embodiment of this application;

[0031] Explanation of reference numerals in the attached drawings: 1-Body unit, 2-Sample pretreatment area, 3-Sample stage, 4-Sample detection area, 5-Sample dispensing unit, 6-First motion unit, 7-Sample and reagent container, 8-Consumable container, 9-Sample detection unit, 10-Second motion unit, 21-Z-axis motion module, 22-P-axis motion module, 23-Liquid operation module, 31-X-axis motion module, 32-Y-axis motion module, 33-Sample plate placement module, 34-Reagent placement module, 35-Consumable placement module, 40-Fluorescent light source, 41-Optical detection optical path, 42-Optical detection objective lens, 43-Optical detection sensor, 44-F-axis motion module. Detailed Implementation

[0032] The present application will be described in detail below through specific embodiments to facilitate a better understanding of the present application. However, the following embodiments do not limit the scope of the present application.

[0033] Please see Figures 1-3 As shown, this embodiment provides an automated biological sample detection device based on an coded liquid phase chip, which includes a body unit 1. The body unit 1 is divided into upper and lower spaces, wherein the upper space is set as a sample pretreatment area 2 and the lower space is set as a sample detection area 4. The upper and lower spaces can be separated by a sample stage 3.

[0034] Furthermore, the biological sample pretreatment area 2 is equipped with a sample application unit 5 and a first motion unit 6. The first motion unit 6 includes a first Z-axis motion module 21, a second Z-axis motion module 22, and a liquid operation module 23. Specifically, the first Z-axis motion module 21 carries the sample application unit 5 and is connected to the second Z-axis motion module 22. The second Z-axis motion module 22 is connected to the liquid operation module 23 and is used to coordinate with the liquid operation module 23 to perform liquid operations. The first Z-axis motion module 21 and the second Z-axis motion module 22 respectively drive the sample application unit 5 and the liquid operation module 23 to move along the Z-axis of a three-dimensional coordinate system; that is, the movement directions of the sample application unit 5 and the liquid operation module 23 are parallel.

[0035] Furthermore, the sample detection area 4 is provided with a sample detection unit 9 and a second motion unit 10. The sample detection unit 9 can employ a fluorescence detection instrument commonly used in the art, which generally includes a fluorescence light source 40, an optical detection optical path 41, an optical detection objective lens 42, and an optical detection sensor 43, etc. The corresponding detection principle can be found in ZL201210329727.5, ZL201710897270.0, ZL201710243958.7, etc. The second motion unit 10 includes a third Z-axis motion module 44 for supporting the optical detection objective lens 42, which can drive the optical detection objective lens 42 to move along the Z-axis of the three-dimensional coordinate system.

[0036] Furthermore, the sample stage 3 may include a sample plate placement module 33, a reagent placement module 34, and a consumable placement module 35, etc., and the sample stage 3 is supported by a third motion unit. The sample plate placement module 33, reagent placement module 34, and consumable placement module 35 are respectively used to hold the sample plate, sample and reagent containers 7, and consumable containers 8. There may be one or more sample and reagent containers 7, preferably multiple, and they are respectively used to hold the initial sample and various biochemical reagents (e.g., coded liquid phase chips) for processing the initial sample. There may also be one or more consumable containers 8, preferably multiple, and they are respectively used to hold various consumables required for detection, such as pipette tips, sample tubes, etc., and are not limited thereto. The sample plate may be a multi-well plate, used to hold the initial sample, the pretreated sample, blank control sample, etc., and is not limited thereto. The third motion unit includes an X-axis motion module 31 and a Y-axis motion module 32, which are respectively used to drive the sample stage 3 to move along the X-axis and Y-axis of the three-dimensional coordinate system.

[0037] Furthermore, the automated biological sample detection device of this embodiment also includes a control unit 11, which is electrically connected to the first Z-axis motion module 21, the second Z-axis motion module 22, the third Z-axis motion module 44, the X-axis motion module 33, the Y-axis motion module 34, and the optical detection sensor 43, and is used at least to control the operating state of these components. The control unit 11 can be a PLC, MCU, or PC, and is not limited to these. The optical detection sensor 43 can be a CCD or other photoelectric detection equipment.

[0038] Furthermore, the body unit 1 can be made of standard aluminum profiles and has a frame structure. The first Z-axis motion module 21, X-axis motion module 33, sample detection unit 9, etc., can all be fixed to the body unit 1.

[0039] In this embodiment, the first Z-axis motion module 21, the second Z-axis motion module 22, the third Z-axis motion module 44, the X-axis motion module 33, and the Y-axis motion module 34 can be driven by pneumatic, hydraulic, or electric devices, such as linear motors or pneumatic telescopic rods, and are not limited thereto.

[0040] Furthermore, the automated biological sample detection device of this embodiment also includes an air purification module 12, which is fixed to the main unit 1. The air purification module 12 can be an FFU-type air purifier or other types of air purification components commonly used in the art.

[0041] Furthermore, the automated biological sample detection device of this embodiment also includes a bright field illumination source 13, which is fixed on the upper body unit 1 and is used to cooperate with the sample detection unit 9 to realize bright field imaging detection of the sample.

[0042] Furthermore, the automated biological sample detection device of this embodiment may also include a housing, which covers the body unit 1, and a display screen is installed on the surface of the housing. The display screen can be connected to the sample detection unit 9 and the control unit to intuitively display the detection spectrum of the sample.

[0043] The automated biological sample detection device of this embodiment can be used to detect various types of biological and biochemical samples. For example, a method for detecting biological samples using the automated biological sample detection device includes:

[0044] The biological sample is added to the sample and reagent container 7 and then placed on the sample stage 3, which also has a sample plate pre-placed on it.

[0045] When the automated biological sample detection device is started, the sample loading unit 5 will automatically move above the sample stage 3 and continuously or intermittently perform pipetting actions to load the sample or a mixture of sample and coded liquid phase chip and blank control sample onto the sample plate to complete the sample pretreatment.

[0046] Then, without human intervention, the sample detection unit 9 will automatically move to the position below the sample stage corresponding to the sample plate, and detect the signal value of each sample on the sample plate one by one until the detection is completed.

[0047] During the implementation of this detection method, apart from the manual operation required for sample and reagent placement and final sample collection, all other steps are automatically completed by the automated biological sample detection device, thereby effectively improving detection efficiency and accuracy and reducing labor and reagent costs.

[0048] The specific embodiments of this application have been described in detail above, but they are merely examples, and this application is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions to this application are within the scope of this application. Therefore, all equivalent changes and modifications made without departing from the spirit and scope of this application should be covered within the scope of this application.

Claims

1. An automated biological sample detection device based on an coded liquid phase chip, characterized in that... include: Fuselage unit (1); The sample pretreatment area (2) includes a sample loading unit (5) and a first motion unit (6) connected to the sample loading unit (5). The first motion unit (6) is used to drive the sample loading unit (5) to perform a pipetting action to complete the sample pretreatment. The first motion unit (6) includes a first Z-axis motion module (21), a second Z-axis motion module (22), and a liquid operation module (23). The first Z-axis motion module (21) is used to support the sample loading unit (5). The first Z-axis motion module (21) is connected to the second Z-axis motion module (22), and the second Z-axis motion module (22) is connected to the liquid operation module (23). The first Z-axis motion module (21) and the second Z-axis motion module (22) are respectively used to drive the sample loading unit (5) and the liquid operation module (23) to move along the Z-axis of a three-dimensional coordinate system. The sample detection area (4) includes a sample detection unit (9) and a second motion unit (10) connected to the sample detection unit (9). The second motion unit (10) is used to drive the sample detection unit (9) to move. The sample detection unit (9) is used to detect the sample loaded on the sample plate. The sample detection unit (9) includes a fluorescent light source (40), an optical detection optical path (41), an optical detection objective (42), and an optical detection sensor (43). The second motion unit (10) includes a third Z-axis motion module (44). The third Z-axis motion module (44) is used to carry the optical detection objective (42) and to drive the optical detection objective (42) to move along the Z-axis of a three-dimensional coordinate system. The sample stage (3) and the third motion unit for supporting the sample stage (3) are arranged in the body unit (1) from top to bottom. The sample pretreatment area (2), the sample stage (3) and the sample detection area (4) are arranged in sequence from top to bottom. The sample stage (3) is arranged between the sample pretreatment area (2) and the sample detection area (4). The sample stage (3) includes a sample plate placement module (33) and a reagent placement module (34). The sample plate placement module (33) is used to hold the sample plate, and the reagent placement module (34) is used to hold the sample and the reagent container (7). The third motion unit includes an X-axis motion module (31) and a Y-axis motion module (32). The X-axis motion module (31) and the Y-axis motion module (32) are used to drive the sample stage (3) to move along the X-axis and Y-axis of a three-dimensional coordinate system, respectively. The control unit (11) is electrically connected to at least the first motion unit (6), the sample detection unit (9) and the second motion unit (10), and is used to control the working state of the first motion unit (6), the sample detection unit (9) and the second motion unit (10).

2. The automated biological sample detection device based on an encoded liquid phase chip according to claim 1, characterized in that: The sample stage (3) also includes a consumable placement module (35) for accommodating a consumable container (8).

3. The automated biological sample detection device based on an coded liquid phase chip according to claim 1, characterized in that: The fuselage unit (1) has a frame structure made of standard aluminum profiles.

4. The automated biological sample detection device based on an encoded liquid phase chip according to claim 1, characterized in that... It also includes an air purification module (12), which is fixed on the body unit (1).

5. The automated biological sample detection device based on an encoded liquid phase chip according to claim 1, characterized in that... It also includes a bright field lighting source (13), which is fixed on the fuselage unit (1).

6. An automated biological sample detection method based on an coded liquid phase chip, characterized in that... include: An automated biological sample detection device based on an coded liquid phase chip, as described in any one of claims 1-5, is provided; Add the sample to the sample and reagent container (7) and place it on the sample stage (3), and set the sample plate on the sample stage (3); Start the automated biological sample detection device, move the sample loading unit (5) above the sample stage (3) and perform a pipetting action to load the sample onto the sample plate to complete the sample pretreatment; Then the sample detection unit (9) is moved to the position corresponding to the sample plate and the signal value of each sample on the sample plate is detected until the detection is completed.

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