CN117405907A - Automatic biological sample detection device and detection method based on coded liquid phase chip - Google Patents
Automatic biological sample detection device and detection method based on coded liquid phase chip Download PDFInfo
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- 238000001514 detection method Methods 0.000 title claims abstract description 106
- 239000012472 biological sample Substances 0.000 title claims abstract description 43
- 239000007791 liquid phase Substances 0.000 title claims abstract description 22
- 239000000523 sample Substances 0.000 claims abstract description 166
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 22
- 239000007788 liquid Substances 0.000 claims description 22
- 230000003287 optical effect Effects 0.000 claims description 17
- 238000012360 testing method Methods 0.000 claims description 12
- 238000005286 illumination Methods 0.000 claims description 5
- 238000004887 air purification Methods 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00158—Elements containing microarrays, i.e. "biochip"
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00326—Analysers with modular structure
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The application discloses an automatic biological sample detection device and method based on an encoding liquid phase chip. The automated biological sample detection device comprises a sample pretreatment area, a sample stage, a sample detection area and a control unit. The sample pretreatment area comprises a sample adding unit and a first movement unit. The sample detection zone includes a sample detection unit and a second motion unit. The sample stage is disposed between the sample pretreatment area and the sample detection area. The control unit is electrically connected with at least the first motion unit, the sample detection unit and the second motion unit. The automatic biological sample detection device is compact in structure, convenient to install, low in manufacturing cost, capable of automatically performing sample pretreatment and sample detection during use, capable of reducing manual intervention, effectively improving detection efficiency and accuracy, reducing cost in multiple aspects such as manpower and reagents, and very suitable for popularization and use in actual application, and wide in market prospect.
Description
Technical Field
The application relates to a biological sample detection device, in particular to an automatic biological sample detection device and method based on a coded liquid phase chip, and belongs to the technical field of biochemical detection.
Background
Complex vital activities are often the result of a set of biomolecular interactions as a core actuator. Fingerprint marks left on the molecular level for many diseases are often determined by multiple biomarkers. Along with the advent of the precise medical era, high-sensitivity precise quantification of multiple biomarkers in a large number of specimens is becoming an indispensable mainstream analysis task in the fields of modern diagnostics, therapeutics, drug development, conversion medicine and the like.
The technology of the coded liquid phase chip is a technology for utilizing classified coded microspheres suspended in a liquid phase as a reaction and signal detection carrier, is identified by the physicochemical property of the reaction carrier-microspheres, is a novel biochip technology platform, has wide application in the aspects of genomics research, proteomics research, drug development, basic research, clinical diagnosis and the like at present, and has great application potential in large-scale analysis of biological macromolecules such as nucleic acid, protein and the like.
Because the coding suspension chip technology is a novel technical platform, products based on the coding suspension chip technology are few at present. From the detection means, the existing detection products mainly have two types: the first type is a flow type fluorescent product based on fluorescent microspheres, and the second type is an imaging product based on a two-dimensional code coding chip. There are some automated instruments and devices capable of adapting to flow fluorescent products, but there are no automated sample detection devices and methods capable of completely matching imaging encoded suspension chips, which has been a challenge in the art.
Disclosure of Invention
The main object of the present application is to provide an automated biological sample detection device and detection method based on an encoded liquid chip, so as to overcome the defects in the prior art.
In order to achieve the above object, the present application adopts the technical scheme that:
an aspect of the present application provides an automated biological sample testing device based on an encoded liquid phase chip comprising:
the sample pretreatment area comprises a sample adding unit and a first moving unit connected with the sample adding unit, wherein the first moving unit is used for driving the sample adding unit to execute liquid moving so as to complete pretreatment of a sample;
the sample detection area comprises a sample detection unit and a second motion unit connected with the sample detection unit, the second motion unit is used for driving the sample detection unit to move, and the sample detection unit is used for detecting a sample loaded on a sample plate;
the sample platform is arranged between the sample pretreatment area and the sample detection area and is at least used for bearing the sample plate, the sample and the reagent container;
and the control unit is electrically connected with at least the first motion unit, the sample detection unit and the second motion unit and is at least used for controlling the working states of the first motion unit, the sample detection unit and the second motion unit.
In one embodiment, the automated biological sample detection device further comprises a body unit, and the sample pretreatment area, the sample stage and the sample detection area are sequentially arranged in the body unit from top to bottom.
In one embodiment, the first motion unit comprises a first Z-axis motion module, a second Z-axis motion module, and a liquid handling module; the first Z-axis movement module is used for bearing the sample loading unit and 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 for driving the liquid operation module to execute liquid operation; the first Z-axis movement module and the second Z-axis movement module are respectively used for driving the sample adding unit and the liquid operation module to move along the Z axis of a three-dimensional coordinate system.
In one embodiment, the automated biological sample detection device further comprises a third motion unit for carrying the sample stage; the sample platform comprises a sample plate placing module and a reagent placing module, wherein the sample plate placing module is used for accommodating the sample plate, and the reagent placing module is used for accommodating 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 for driving the sample stage to move along the X axis and the Y axis of a three-dimensional coordinate system.
In one embodiment, the sample stage further comprises a consumable placement module for receiving a consumable container.
In one 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 motion unit comprises a third Z-axis motion module; the third Z-axis movement module is used for bearing the optical detection objective lens and driving the optical detection objective lens to move along a Z axis of a three-dimensional coordinate system.
In one embodiment, the fuselage cell has a frame structure that is made from standard aluminum profiles.
In one embodiment, the automated biological sample detection device further comprises an air purification module secured to the fuselage cell.
In one embodiment, the automated biological sample testing device further comprises a brightfield illumination source secured to the airframe unit.
Another aspect of the present application provides an automated biological sample detection method based on an encoded liquid phase chip, comprising:
providing the automatic biological sample detection device based on the coded liquid phase chip;
adding a sample into the sample and reagent container, placing the sample on a sample table, and arranging a sample plate on the sample table;
starting the automatic biological sample detection device, moving a sample adding unit to the position above the sample table, and executing a moving liquid to load the sample onto the sample plate so as to finish pretreatment of the sample;
and then, the sample detection unit is moved to a position corresponding to the sample plate, and the signal value of each sample on the sample plate is detected until the detection is completed.
Compared with the prior art, the automatic biological sample detection device based on the coded liquid phase chip has the advantages of compact structure, convenience in installation and low manufacturing cost, can automatically perform sample pretreatment and sample detection during use, can reduce manual intervention, effectively improve detection efficiency and accuracy, reduces various costs of manpower, reagents and the like, and is very suitable for popularization and use in practical application, and has wide market prospect.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following description will simply refer to the drawings that are used in the description of the embodiments or the prior art. It is evident that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained from the structures shown in these drawings without inventive effort for a person of ordinary skill in the art.
FIG. 1 is a schematic diagram of an automated biological sample testing device based on an encoded liquid phase chip according to an embodiment of the present application;
FIG. 2 is a schematic diagram of a sample pretreatment unit according to an embodiment of the present application;
FIG. 3 is a schematic view (top view) of a sample stage according to an embodiment of the present disclosure;
FIG. 4 is a schematic diagram of a biological detection unit according to an embodiment of the present application;
reference numerals illustrate: 1-fuselage unit, 2-sample pretreatment area, 3-sample platform, 4-sample detection area, 5-sample adding 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 light path, 42-optical detection objective, 43-optical detection sensor, 44-F axis motion module.
Detailed Description
The present application is described in detail and in detail by way of specific examples below to facilitate a better understanding of the present application, but the following examples do not limit the scope of the present application.
Referring to fig. 1-3, the present embodiment provides an automated biological sample detection device based on an encoded liquid phase chip, which includes a body unit 1, wherein the body unit 1 is internally divided into an upper space and a lower space, the upper space is configured as a sample pretreatment area 2, the lower space is configured as a sample detection area 4, and the upper space and the lower space can be separated by a sample stage 3.
Further, a sample adding unit 5 and a first moving unit 6 are disposed in the biological sample pretreatment area 2. The first movement unit 6 includes a first Z-axis movement module 21, a second Z-axis movement module 22, and a liquid operation module 23. Specifically, the first Z-axis motion module 21 is configured to carry the sample loading unit 5, and is connected to the second Z-axis motion module 22. The second Z-axis movement module 22 is connected to the liquid handling module 23 and is adapted to perform a liquid handling in cooperation with the liquid handling module 23. The first Z-axis movement module 21 and the second Z-axis movement module 22 are respectively used for driving the sample loading unit 5 and the liquid handling module 23 to move along the Z-axis of a three-dimensional coordinate system, that is, the movement directions of the sample loading unit 5 and the liquid handling module 23 are parallel.
Further, a sample detection unit 9 and a second movement unit 10 are disposed in the sample detection area 4. The sample detection unit 9 may adopt a fluorescence detection instrument commonly used in the art, which generally includes a fluorescence light source 40, an optical detection light path 41, an optical detection objective 42, an optical detection sensor 43, and the like, and the corresponding detection principles may refer to ZL201210329727.5, ZL201710897270.0, ZL201710243958.7, and the like. The second movement unit 10 comprises a third Z-axis movement module 44 for carrying the optical detection objective 42, etc., which third Z-axis movement module 44 can drive the optical detection objective 42 along the Z-axis of the three-dimensional coordinate system.
Further, the sample stage 3 may include a sample plate placement module 33, a reagent placement module 34, a consumable placement module 35, etc., and the sample stage 3 is carried by a third movement unit. The sample plate placing module 33, the reagent placing module 34, and the consumable material placing module 35 are respectively used for accommodating a sample plate, a sample, a reagent container 7, and a consumable material container 8. The sample and reagent containers 7 may be one or more, preferably a plurality, and are used for holding the initial sample, various biochemical reagents (e.g., coded liquid chips) for processing the initial sample, and the like, respectively. The consumable container 8 may also be one or more, preferably a plurality, and is used to accommodate various types of consumables required for performing the test, such as a pipette head, a sample tube, and the like, without being limited thereto. The sample plate may be provided with a multi-well plate for accommodating a preliminary sample, a pre-treated sample, a blank sample, etc., and is not limited thereto. The third movement unit comprises an X-axis movement module 31 and a Y-axis movement module 32, and the X-axis movement module 31 and the Y-axis movement module 32 are respectively used for driving the sample stage 3 to move along the X-axis and the Y-axis of the three-dimensional coordinate system.
Further, the automated biological sample testing device of the present embodiment further includes a control unit 11, where the control unit 11 is electrically connected to the first Z-axis movement module 21, the second Z-axis movement module 22, the third Z-axis movement module 44, the X-axis movement module 33, the Y-axis movement module 34, the optical detection sensor 43, and the like, respectively, and is at least used for controlling the working states of these components. The control unit 11 may employ a PLC, an MCU, a PC, or the like, and is not limited thereto. The optical detection sensor 43 may employ a CCD or the like or other photodetection device.
Further, the fuselage cell 1 may be made of standard aluminum profiles and have a frame structure. Wherein the first Z-axis movement module 21, the X-axis movement module 33, the sample detection unit 9, etc. may be fixed to the body unit 1.
The first Z-axis movement module 21, the second Z-axis movement module 22, the third Z-axis movement module 44, the X-axis movement module 33, the Y-axis movement module 34, and the like in the present embodiment may employ a pneumatic driving device, a hydraulic driving device, an electric driving device, and the like, such as a linear motor, a pneumatic telescopic rod, and the like, without being limited thereto.
Further, the automated biological sample testing device of the present embodiment further includes an air cleaning module 12, and the air cleaning module 12 is fixed to the body unit 1. The air cleaning module 12 may employ an FFU type air cleaner or other type of air cleaning assembly commonly used in the art.
Further, the automated biological sample detection device of the present embodiment further includes a bright field illumination light source 13, where the bright field illumination light source 13 is fixed on the upper layer machine body unit 1, and is used to cooperate with the sample detection unit 9 to implement bright field imaging detection on the sample.
Furthermore, the automated biological sample detection device of this embodiment may further include a housing, where the housing covers the body unit 1, and a display screen is mounted on a surface of the housing, where the display screen may be connected to the sample detection unit 9 and the control unit, and is configured to visually display a detection spectrum of the sample.
The automatic biological sample detection device of the embodiment can be used for detecting various types of biological and biochemical samples. For example, a method of detecting a biological sample using the automated biological sample detection device comprises:
adding a biological sample into a sample and reagent container 7, and then placing the biological sample on a sample table 3, wherein a sample plate is also placed on the sample table 3 in advance;
starting the automatic biological sample detection device, automatically moving the sample adding unit 5 to the position above the sample table 3, continuously or intermittently executing liquid moving, loading a sample or a mixture of the sample and the coded liquid phase chip, a blank reference sample and the like onto a sample plate, and completing pretreatment of the sample;
and then the sample detection unit 9 can automatically move to the position below the sample table corresponding to the sample plate without human intervention, and the signal values of the samples on the sample plate are detected one by one until the detection is completed.
In the implementation process of the detection method, except that the sample, the reagent and the like are placed and the final sample collection needs manual operation, other steps are automatically completed by the automatic biological sample detection device, so that the detection efficiency and accuracy are effectively improved, and the labor and reagent cost are reduced.
The specific embodiments of the present application have been described in detail above, but they are merely examples, and the present application is not limited to the specific embodiments described above. Any equivalent modifications and substitutions for this application will be within the scope of this application to those skilled in the art. Accordingly, equivalent changes and modifications are intended to be included within the scope of the present application without departing from the spirit and scope thereof.
Claims (10)
1. An automated biological sample testing device based on an encoded liquid phase chip, comprising:
the sample pretreatment area (2) comprises a sample adding unit (5) and a first moving unit (6) connected with the sample adding unit (5), wherein the first moving unit (6) is used for driving the sample adding unit (5) to perform a liquid moving action so as to finish pretreatment of a sample;
a sample detection zone (4) comprising a sample detection unit (9) and a second movement unit (10) connected with the sample detection unit (9), wherein the second movement unit (10) is used for driving the sample detection unit (9) to move, and the sample detection unit (9) is used for detecting a sample loaded on a sample plate;
a sample stage (3) arranged between the sample pretreatment area (2) and the sample detection area (4) and at least used for bearing the sample plate and the sample and reagent container (7);
the control unit (11) is electrically connected with at least the first motion unit (6), the sample detection unit (9) and the second motion unit (10) and is at least used for controlling the working states 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 the coded liquid phase chip according to claim 1, further comprising a body unit (1), wherein the sample pretreatment area (2), the sample stage (3) and the sample detection area (4) are sequentially arranged in the body unit (1) from top to bottom.
3. The automated biological sample testing device of claim 1, wherein the device is further configured to: the first movement unit (6) comprises a first Z-axis movement module (21), a second Z-axis movement module (22) and a liquid operation module (23); the first Z-axis movement module (21) is used for bearing the sample adding unit (5), the first Z-axis movement module (21) is connected with the second Z-axis movement module (22), and the second Z-axis movement module (22) is connected with the liquid operation module (23); the first Z-axis movement module (21) and the second Z-axis movement module (22) are respectively used for driving the sample adding unit (5) and the liquid operation module (23) to move along the Z axis of a three-dimensional coordinate system.
4. Automated biological sample detection device based on coded liquid phase chip according to claim 1, characterized in that it further comprises a third movement unit for carrying the sample stage (3); the sample stage (3) comprises a sample plate placing module (33) and a reagent placing module (34), wherein the sample plate placing module (33) is used for accommodating the sample plate, and the reagent placing module (34) is used for accommodating the sample and the reagent container (7); the third movement unit comprises an X-axis movement module (31) and a Y-axis movement module (32), and the X-axis movement module (31) and the Y-axis movement module (32) are respectively used for driving the sample stage (3) to move along the X axis and the Y axis of a three-dimensional coordinate system.
5. The automated biological sample testing device based on an encoded liquid phase chip of claim 4, wherein: the sample stage (3) further comprises a consumable placement module (35), and the consumable placement module (35) is used for accommodating a consumable container (8).
6. The automated biological sample testing device of claim 1, wherein the device is further configured to: the sample detection unit (9) comprises a fluorescent light source (40), an optical detection light path (41), an optical detection objective lens (42) and an optical detection sensor (43); the second motion unit (10) comprises a third Z-axis motion module (44); the third Z-axis movement module (44) is used for carrying the optical detection objective lens (42) and driving the optical detection objective lens (42) to move along the Z axis of a three-dimensional coordinate system.
7. The automated biological sample testing device based on an encoded liquid phase chip of claim 2, wherein: the fuselage cell (1) has a frame structure made of standard aluminum profiles.
8. The automated biological sample detection device based on coded liquid phase chips according to claim 2, further comprising an air purification module (12), said air purification module (12) being fixed on said fuselage cell (1).
9. The automated biological sample testing device based on coded liquid phase chips according to claim 2, further comprising a bright field illumination source (13), said bright field illumination source (13) being fixed to said fuselage cell (1).
10. An automated biological sample detection method based on an encoded liquid phase chip is characterized by comprising the following steps:
providing an automated biological sample detection device based on an encoded liquid phase chip according to any one of claims 1-9;
adding a sample into a sample and reagent container (7), placing the sample on a sample table (3), and arranging a sample plate on the sample table (3);
starting the automatic biological sample detection device, enabling a sample adding unit (5) to move above the sample table (3), and executing liquid moving so as to load the sample onto the sample plate, so as to finish pretreatment of the sample;
and then, moving a sample detection unit (9) to a position corresponding to the sample plate, and detecting signal values of each sample on the sample plate until detection is completed.
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