CN108680759B - Multifunctional high-throughput automatic chromatography detector and application thereof - Google Patents

Multifunctional high-throughput automatic chromatography detector and application thereof Download PDF

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Publication number
CN108680759B
CN108680759B CN201711490591.5A CN201711490591A CN108680759B CN 108680759 B CN108680759 B CN 108680759B CN 201711490591 A CN201711490591 A CN 201711490591A CN 108680759 B CN108680759 B CN 108680759B
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chromatography
detector
chromatographic
component
shell
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CN108680759A (en
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王升启
肖瑞
荣振
吴凤池
王娈娈
张敏丽
王琼
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Academy of Military Medical Sciences AMMS of PLA
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Beijing Meiling Biotechnology Co ltd
Institute of Pharmacology and Toxicology of AMMS
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    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor

Abstract

The invention discloses a multifunctional high-flux automatic chromatography detector and application thereof in the technical field of biomedicine. The chromatography detector comprises a shell, a chromatography system, a mechanical system, a detection system and an analysis system; the chromatography system comprises a chromatography device and a chromatography component, wherein one or more channels are arranged on the side wall of the chromatography device, and the chromatography component is arranged in the channels; the mechanical system comprises a base, a motor, a photoelectric switch and a clamping groove, wherein the clamping groove is used for mounting the chromatography device, and the photoelectric switch is used for positioning the chromatography component; the detection system comprises a light source, a detector and a circuit board, and is used for capturing and detecting signals emitted by the chromatographic component; the analysis system comprises software and hardware equipment for installing the software, and is used for classifying, collecting, analyzing and storing data; the shell encapsulates the chromatography detector. The chromatographic detector can realize qualitative and quantitative detection of chromatographic results based on the principles of visible light, Raman, time-resolved fluorescence, chemiluminescence, up-conversion luminescence and the like.

Description

Multifunctional high-throughput automatic chromatography detector and application thereof
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to a multifunctional high-flux automatic chromatography detector and application thereof.
Background
Chromatography is a short term for chromatography, and a method for separating and measuring a multi-component mixture by using different separation media such as silica gel and a detection instrument according to different properties of each component is used. Taking the commonly used immunochromatography as an example, the principle is that a specific antibody is firstly fixed on a certain specific area of a nitrocellulose membrane, then a sample is dripped on one end of the membrane, the sample moves forwards along the membrane under the action of capillary, and when the sample moves to an area where the antibody is fixed, the corresponding antigen in the sample can be specifically combined with the antibody. In this case, if the analyte is stained with an immunological nanoparticle such as colloidal gold or an immunoenzyme, or a marker molecule having raman, chemiluminescence, up-conversion luminescence, and a time-resolved fluorescence signal is bound thereto, qualitative and quantitative measurement of the analyte can be achieved.
Since chromatographic detection methods are widely applied in a plurality of fields such as medical treatment, food, medicine, chemistry, judicial identification and the like, some chromatographic detection devices are also appeared in the market at present, but the devices can only detect the chromatographic result of one principle, for example, the devices can only read the result of a colloidal gold immunochromatographic test strip and can not respond to signals of Raman, time-resolved fluorescence, chemiluminescence, up-conversion luminescence and the like.
The invention patent with application number 201310045753X discloses a quantitative detection system and a detection method of a multi-channel test paper disc, the system consists of a multi-channel test paper disc, an optical system movement mechanism, a test paper disc bracket, a test paper disc movement mechanism, a signal amplification and filtering circuit, a control device, a data acquisition and processing device, wherein a signal detector adopts a photoelectric detector assembly, in order to acquire an output signal of the photoelectric detector assembly, a complex amplification and filtering circuit system is also needed, and the complexity of the whole system is increased. The invention patent with the application number of 2010105911120 discloses a quantitative detector for a color development signal of an immunochromatography detection test strip, which comprises a light source, a light-tight casing, a conversion lens, a slit, a light detector, a primary amplification circuit, an AD control circuit and a communication interface, and has the same problems as the invention patent with the application number of 201310045753X and also needs a complex circuit system.
Disclosure of Invention
The invention provides a multifunctional high-flux automatic chromatography detector and application thereof, aiming at the defects of the existing product. The specific technical scheme is as follows:
a multifunctional high-throughput automatic chromatography detector comprises a shell, a chromatography system, a mechanical system, a detection system and an analysis system; wherein the content of the first and second substances,
the chromatography system comprises a chromatography device and a chromatography component, wherein the chromatography device is a hollow pipeline, the side wall of the chromatography device is in a circular ring shape or a polyhedral shape, one or more channels are arranged on the side wall of the chromatography device along the length direction of the pipeline, and preferably, the number of the channels is 1, 2, 3, 4, 6, 8, 12 or 24; the chromatography component is arranged in the channel; the chromatography device is provided with a sample adding port;
the mechanical system comprises a base, a motor, a photoelectric switch and a clamping groove, wherein the motor is fixed on the base, the clamping groove is formed in the motor, the clamping groove is used for vertically and detachably mounting the chromatography device, the photoelectric switch is arranged on one side of the clamping groove, and the photoelectric switch is used for positioning the chromatography component in the channel;
the detection system comprises a light source, a detector and a circuit board, wherein the position of the detector corresponds to the chromatographic assembly and is used for capturing and detecting signals emitted by the chromatographic assembly;
the analysis system comprises software and hardware equipment for installing the software, and is used for classifying, collecting, analyzing and storing data;
the shell encapsulates the chromatography detector.
In the chromatographic detector, the chromatographic component is a chromatographic component for carrying out chromatography based on colloidal gold, Raman, time-resolved fluorescence, chemiluminescence or up-conversion luminescence principles; preferably, the chromatographic member is a chromatographic strip, and most preferably, the chromatographic member is an immunochromatographic strip.
In the above chromatographic detector, the number of the chromatographic devices is one or more, when the number of the chromatographic devices is multiple, the chromatographic devices are arranged in a circle or an array, and the detection system is located at the center of the plurality of chromatographic devices.
In the chromatographic detector, the base is arranged horizontally, vertically or obliquely, so that the chromatographic device is vertical, parallel or oblique to the horizontal plane.
In the chromatographic detector, when the chromatographic device is vertical to the horizontal plane, the sample addition port is arranged above the center of the pipeline of the chromatographic device; when the chromatography device is parallel to or inclined to the horizontal plane, the sample addition port is arranged at the upper end of the channel, preferably above the chromatography component.
In the chromatographic detector, the sample adding port is set in a manual, semi-automatic or full-automatic mode.
In the chromatographic detector, the hardware device for installing software is a computer or a mobile phone, and is installed in the shell or externally connected.
In the chromatography detector, the detector is selected from a visible light detector, a raman detector, a time-resolved fluorescence detector, a chemiluminescence detector, and an up-conversion photodetector.
In the chromatographic detector, the software comprises an initialization calibration module, a parameter setting module, a data acquisition and analysis module and a report output module.
In the chromatographic detector, the shell comprises a shell body, and the shell body is provided with a flip cover, a chromatographic system inlet, a power supply interface and a USB interface; the turnover cover corresponds to the chromatography system inlet, and the chromatography system inlet displays the chromatography device; the power interface and the USB interface are arranged on one side of the shell.
In the chromatographic detector, the detection system is positioned at one side of the chromatographic system and is fixed on the base; the detector is arranged below the flip cover.
In the chromatographic detector, the chromatographic detector further comprises a bar code scanner, and the software further comprises a bar code scanning module; the chromatography detector is powered by an external power supply or a built-in battery.
The chromatographic detector is applied to clinical diagnosis, inspection and quarantine, food safety detection, judicial identification and drug detection.
The invention has the beneficial effects that:
(1) the multifunctional high-flux automatic chromatographic detector can perform qualitative and quantitative detection on chromatographic results based on the principles of visible light, Raman, time-resolved fluorescence, chemiluminescence, up-conversion luminescence and the like, and realize real-time acquisition, classification, analysis, storage and transmission of data.
(2) The chromatography device of the functional high-flux automatic chromatography detector adopts a hollow cylinder or polyhedron structure, the number of channels can be increased only by thickening the cylinder or polyhedron, the device can be conveniently expanded into various channels such as 6, 12, 24 and the like, and compared with a disc-shaped structure, the device has small volume and is convenient to carry; the bottom of the chromatography device is detachably connected with the clamping groove, so that the chromatography devices of different channels can be conveniently clamped into the clamping groove and detached. The sample adding of the chromatography system adopts a manual, semi-automatic or full-automatic mode, and particularly, the full-automatic mode can realize the full-automatic operation of the whole instrument system.
(3) The chromatographic detector can obviously improve the detection efficiency, sensitivity and accuracy, and is suitable for detecting one or more indexes of a sample and one or more indexes of a plurality of samples. Has wide market prospect in the fields of clinical diagnosis, inspection and quarantine, food safety detection, judicial appraisal, drug detection and the like.
Brief description of the drawings
FIG. 1 is a vertical assembly view of the multifunctional high-throughput automated chromatography detector of the present invention;
FIG. 2 is a tilted assembly diagram of the multifunctional high-throughput automated analytical instrument according to the present invention;
FIG. 3 is a horizontal assembly diagram of the multifunctional high-throughput automated chromatography detector of the present invention shown in FIG. 1;
FIG. 4 is a horizontal assembly view of the multifunctional high-throughput automated chromatography detector of the present invention shown in FIG. 2;
FIG. 5 is a schematic illustration of an array structure chromatography system according to the present invention;
FIG. 6 is a housing diagram of a multifunctional high-throughput automated chromatography detector based on visible light detection according to embodiment 2 of the present invention;
FIG. 7 is a back view of a multifunctional high-throughput automated chromatography detector based on visible light detection according to embodiment 2 of the present invention;
wherein, 1-channel; 2-a card slot; 3-a photoelectric switch; 4-a motor; 5-a base; 6-a detector; 7-a sample addition port; 8-a chromatographic component; 9-built-in computer; 10-a housing; 11-a flip cover; 12-chromatography system inlet; 13-a power interface; 14-USB interface, 15-chromatography device.
Modes for carrying out the invention
The technical solution in the embodiments of the present invention is further described below with reference to the drawings in the embodiments of the present invention.
Example 1: multifunctional high-throughput automatic chromatography detector
A multifunctional high-throughput automatic chromatography detector is shown in figure 1, and comprises a shell, a chromatography system, a mechanical system, a detection system and an analysis system; wherein the content of the first and second substances,
the chromatography system comprises a chromatography device 15 and a chromatography component 8, wherein the chromatography device 15 is a hollow pipeline, the side wall of the chromatography device is a circular ring, and in another embodiment, the side wall of the chromatography device is polyhedral; 4 channels 1 are arranged on the side wall of the pipeline along the length direction of the pipeline, and in another embodiment, the number of the channels 1 is 1, 2, 4, 8, 12 or 24; a chromatography component 8 is arranged in each channel 1; the chromatography device 15 is provided with a sample addition port 7.
The mechanical system comprises a base 5, a motor 4, a photoelectric switch 3 and a clamping groove 2, wherein the motor 4 is fixed on the base 5, the clamping groove 2 is arranged on the motor 4, the clamping groove 2 is used for vertically and detachably mounting the chromatography device 15, and the chromatography device 15 can be fixed in the clamping groove 2 through an adaptive structure; a photoelectric switch 3 is arranged on one side of the clamping groove 2, and the photoelectric switch 3 is used for selecting or positioning a chromatography component 8 in the channel 1; the mechanical system controls switching between the objects to be tested.
The base 5 is horizontally arranged, so that the chromatographic device 15 is vertical to the horizontal plane; the sample addition port 7 is disposed above the center of the channel of the chromatography device 15.
In another embodiment, the base 5 is vertically or obliquely arranged, such that the chromatographic device 15 is parallel or inclined to the horizontal, as shown in FIGS. 2-4; the sample adding port 7 is arranged at the upper end of the channel 1 and is arranged above the chromatographic component 8.
The detection system comprises a light source, a detector 6 and a circuit board, wherein the position of the detector 6 corresponds to the chromatographic assembly 8 and is used for capturing and detecting signals emitted by the chromatographic assembly 8.
The analysis system comprises software and hardware equipment for installing the software, and is used for classifying, collecting, analyzing and storing data.
The shell encapsulates the chromatography detector. The shell comprises a shell body 10, wherein the shell body 10 is provided with a flip cover 11, a chromatography system inlet 12, a power supply interface 13 and a USB interface 14; the flip cover 11 corresponds to the chromatography system inlet 12, and the chromatography system inlet 12 displays the chromatography device 15; the power interface 13 and the USB interface 14 are arranged on one side of the shell; the chromatography detector is powered by an external power supply.
In this embodiment, the chromatography device 15 is a single device, and the chromatography component 8 is an immunochromatographic test strip.
In another embodiment, the chromatographic devices 15 are in plurality, arranged in a circle or array, and the detection system is located at the center of the plurality of chromatographic devices, as shown in FIG. 5.
The sample addition port 7 is arranged manually, and in another embodiment, the sample addition port 7 is arranged in a semi-automatic or full-automatic mode. The hardware device for installing software is a computer and is installed in the shell, and in another embodiment, the hardware device for installing software is a mobile phone.
The detector 6 is a micro optical camera detection device.
The software comprises an initialization calibration module, a bar code scanning module, a parameter setting module, a data acquisition and analysis module and a report output module.
In the chromatographic detector, the detection system is positioned at one side of the chromatographic system and is fixed on the base 5; the detector 6 is disposed below the flip 11.
In another embodiment, the detector 6 can be a visible, Raman, fluorescence, or upconversion luminescence detector, among others, depending on the type of the chromatographic assembly 8.
The multifunctional high-flux automatic chromatography detector comprises the following operation steps:
(1) putting the immunochromatography component into a chromatography device, and putting the chromatography device into a clamping groove;
(2) starting an instrument power supply, connecting a computer through a USB interface, and starting a matched software system;
(3) the photoelectric switch automatically detects and corrects the zero position of the immunochromatographic component;
(4) adding a sample from a sample addition port;
(5) waiting for 10 min;
(6) starting an image acquisition function of a detector (a miniature optical camera), and automatically acquiring an immunochromatography result; and automatically analyzing and interpreting image information of the immunochromatography, and printing an interpretation result.
Example 2: multifunctional high-throughput automatic chromatography detector
The difference between this embodiment and embodiment 1 is that the chromatography component 8 is a raman signal immunochromatographic test strip, the chromatography device has 4 channels, and the detector 6 is a raman spectrometer.
The multifunctional high-throughput automated chromatography detector has the operation steps different from those of the embodiment 1, in which the step (7) is as follows: starting a detection function of the Raman spectrometer, setting parameters of the Raman spectrometer, such as laser power, integration time and the like, on a mobile phone or a computer through execution software, and carrying out point-by-point detection on the immunochromatography result based on the enhanced Raman; automatically analyzing and interpreting the detection result of the enhanced Raman immunochromatography, and printing the interpretation result.
Example 3: detection of Procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) in a single sample
Materials: CRP, PCT, IL6 colloidal gold chromatography system; the multifunctional high-throughput automatic chromatography detector similar to that described in embodiment 1 of the invention is adopted, except that the chromatography device is provided with three channels; one sample of human serum (supplied by the hospital laboratory, Beijing 301).
The operation steps are as follows:
(1) preparing CRP, PCT and IL6 colloidal gold immunochromatographic test strips, respectively loading the colloidal gold immunochromatographic test strips into different channels of a chromatography device, and loading the chromatography device into a clamping groove;
the preparation method of the CRP, PCT and IL6 colloidal gold immunochromatographic test strip comprises the following steps: preparing a gold combined pad by using a monoclonal mouse anti-human CRP detection antibody electrostatically adsorbed and modified by colloidal gold; spraying monoclonal mouse anti-human CRP capture antibody and secondary antibody onto corresponding detection area and control area of reaction membrane for coating; sticking a reaction film, a gold combination pad, a sample pad and a water absorption pad on a PVC back lining to obtain a test paper board, and cutting the test paper board into strips to obtain the CRP colloidal gold immunochromatographic test strip; the preparation method of the PCT and IL6 colloidal gold immunochromatographic test strip is the same as that of the test strip;
(2) starting an instrument power supply, connecting the ipad through a USB interface, and starting a matched software system;
(3) the photoelectric switch automatically detects and corrects the zero position of the immunochromatographic component;
(4) starting a bar code scanner, and scanning a bar code of a sample to be detected;
(5) adding a sample from a sample addition port;
(6) waiting for 10 min;
(7) starting the image acquisition function of the micro optical camera, automatically scanning signals, automatically analyzing and interpreting image information of immunochromatography, and printing an interpretation result.
The experimental results are as follows: the sample was positive for PCT, CRP, and IL-6. The experimental result is consistent with the detection result of Beijing 301 hospital.
Example 4: detection of creatine kinase-isozyme (CK-MB), Fatty Acid Binding Protein (FABP), cardiac troponin I (CTnI), myoglobin (MyO) in multiple samples
Materials: CK-MB, FABP, CTnI, MyO Raman chromatography systems; the multifunctional high-throughput automatic chromatography detector similar to that described in embodiment 2 of the invention is adopted, and is characterized in that the chromatography device is provided with 8 channels, and the base is arranged obliquely; two human serum samples (supplied by the Beijing 301 Hospital laboratory).
The operation steps are as follows:
(1) preparing CK-MB, FABP, CTnI and MyO Raman signal immunochromatographic test strips, respectively loading 2 Raman signal immunochromatographic test strips of different types into a channel of a chromatography device, and loading the chromatography device into a clamping groove;
the preparation method of the CK-MB, FABP, CTnI and MyO Raman signal immunochromatography test strip comprises the following steps: adsorbing a Raman reporter molecule DTNB by colloidal gold, and then covalently modifying a monoclonal mouse anti-human CK-MB detection antibody to prepare a gold binding pad; taking a nitrocellulose membrane as a reaction membrane, and spraying a monoclonal mouse anti-human CK-MB capture antibody and a secondary antibody onto a corresponding detection area and a control area on the reaction membrane for coating; sticking a reaction film, a gold combination pad, a sample pad and a water absorption pad on a PVC back lining to obtain a test paper board, and cutting the test paper board into strips to obtain the CK-MB Raman signal immunochromatographic test strip; the preparation method of the immunochromatographic test strip for FABP, CTnI and Myo Raman signals is the same as that of the test strip;
(2) starting an instrument power supply, connecting the ipad through a USB interface, and starting a matched software system;
(3) the photoelectric switch automatically detects and corrects the zero position of the immunochromatographic component;
(4) starting a bar code scanner, and scanning a bar code of a sample to be detected;
(5) adding a sample from a sample addition port;
(6) waiting for 10 min;
(7) starting a detection function of the Raman spectrometer, and carrying out point-by-point detection on the immunochromatography result based on the enhanced Raman; automatically analyzing and interpreting the detection result of the enhanced Raman immunochromatography, and printing the interpretation result.
The experimental results are as follows: in sample 1, FABP was positive, and the remaining three were negative and not detected. CK-MB, FABP, CTnI, MyO were all positive in sample 2. The experimental results of the sample 1 and the sample 2 are consistent with the results of the Beijing 301 hospital.
The structure and the application of the multifunctional high-flux automatic chromatography detector provided by the embodiment of the invention are described in detail, and the detector can be used for quantitative or semi-quantitative automatic analysis of a sample by using detection means such as visible light, chemiluminescence, time-resolved fluorescence, up-conversion luminescence, Raman and the like, and realizes automatic identification, analysis, storage and transmission of data. The target object detected by the chromatographic detector can be biomacromolecules, micromolecular compounds, cell and subcellular components such as protein, nucleic acid, sugar and the like, and can be used in the fields of clinical diagnosis, inspection and quarantine, food safety detection, judicial identification, medicine, drug detection and the like.

Claims (10)

1. The multifunctional high-throughput automatic chromatography detector is characterized by comprising a shell, a chromatography system, a mechanical system, a detection system and an analysis system; wherein the content of the first and second substances,
the chromatography system comprises a chromatography device and a chromatography component, wherein the chromatography device is a hollow pipeline, the side wall of the chromatography device is in a circular or polyhedral shape, one or more channels along the length direction of the pipeline are arranged on the side wall of the chromatography device, and the chromatography component is arranged in the channels; the chromatography device is provided with a sample adding port;
the mechanical system comprises a base, a motor, a photoelectric switch and a clamping groove, wherein the motor is fixed on the base, and the clamping groove is formed in the motor; the clamping groove is used for vertically and detachably mounting the chromatography device, one side of the clamping groove is provided with a photoelectric switch, and the photoelectric switch is used for positioning the chromatography component in the channel;
the detection system comprises a light source, a detector and a circuit board; the position of the detector corresponds to the chromatographic assembly and is used for capturing and detecting signals emitted by the chromatographic assembly;
the analysis system comprises software and hardware equipment for installing the software, and is used for classifying, collecting, analyzing and storing data;
the shell encapsulates the chromatographic detector;
the chromatography component is used for performing chromatography based on the principles of chromatography, colloidal gold, Raman, time-resolved fluorescence, chemiluminescence or up-conversion luminescence;
the base is arranged horizontally, vertically or obliquely, so that the chromatography device is vertical, parallel or oblique to the horizontal plane;
the sample adding port is set in a manual, semi-automatic or full-automatic mode;
when the chromatography device is vertical to the horizontal plane, the sample adding port is arranged above the center of the pipeline of the chromatography device; and when the chromatography device is parallel to or inclined to the horizontal plane, the sample adding port is arranged at the upper end of the channel.
2. The chromatographic detector of claim 1, wherein the chromatographic assembly is a chromatographic strip.
3. The chromatography detector according to claim 1 or 2, wherein the number of the chromatography devices is one or more, and when the number of the chromatography devices is plural, the chromatography devices are arranged in a circle or an array, and the detection system is located at the center of the plurality of the chromatography devices.
4. The chromatography detector of claim 1, wherein the sample port is disposed above the chromatography component.
5. The chromatographic detector of claim 1, wherein the detector is selected from a visible light detector, a Raman detector, a time-resolved fluorescence detector, a chemiluminescence detector, or an up-conversion photodetector.
6. The chromatographic detector of claim 1, wherein the software comprises an initialization calibration module, a parameter setting module, a data acquisition and analysis module, and a report output module; the hardware equipment for installing the software is a computer or a mobile phone and is arranged in the shell or externally connected.
7. The chromatography detector of claim 1, wherein the housing comprises a shell, and the shell is provided with a flip, a chromatography system inlet, a power supply interface and a USB interface; the turnover cover corresponds to the chromatography system inlet, and the chromatography system inlet displays the chromatography device; the power interface and the USB interface are arranged on one side of the shell.
8. The chromatography detector of claim 7, wherein the detection system is located on one side of the chromatography system, the detection system being secured to the base; the detector is arranged below the flip cover.
9. The chromatographic detector of claim 1, wherein the chromatographic detector further comprises a barcode scanner, and the software further comprises a barcode scanning module; the chromatography detector is powered by an external power supply or a built-in battery.
10. Use of the chromatographic detector according to claim 1 for quarantine inspection, food safety inspection, judicial identification or drug testing.
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CN109752372A (en) * 2019-01-17 2019-05-14 上海大学 A kind of sea Cymag on-line measuring device
CN110057808A (en) * 2019-05-27 2019-07-26 中国人民解放军军事科学院军事医学研究院 Sample swivel mount and Raman spectrum detector
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