CN107199061B - Application method of multi-task full-automatic biochemical detection chip - Google Patents
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- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
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- 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
- G01N2035/00465—Separating and mixing arrangements
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Abstract
The invention discloses a multi-task full-automatic biochemical detection chip, which consists of a quantitative unit, a uniform mixing unit and a reaction unit. Removing blood cells and blood clots from the blood sample through the filter tank under the suction of the quantitative negative pressure pump, and allowing the plasma/serum passing through the filter tank to flow into the mixing tank under the drive of the quantitative negative pressure pump to be mixed with the reagent flowing from the reagent tank; the quantitative negative pressure pump and the quantitative booster pump which are arranged at the tail end of the microfluidic channel drive the mixed reagent in a reciprocating manner, so that the reagent is fully and uniformly mixed under the action of the micro-column array; under the drive of a quantitative negative pressure pump, the plasma/serum fully and uniformly mixed with the reagent respectively and quantitatively flows into each sample detection micro-tube, the mixed reagent quickly dissolves the detection reagent microspheres preset in the tube cavity, and the reaction process is started; and (3) under a specified temperature condition, after reacting for a certain time, detecting the absorbance value of each microtube by a photoelectric colorimetry, and calculating the concentration of the specific substance in the sample. Meanwhile, each biochemical detection item is provided with parallel quality control, so that the detection accuracy is improved.
Description
Technical Field
The invention relates to a medical examination device, in particular to a method for using a multi-task full-automatic biochemical detection chip.
Background
The biochemical analysis is to measure the concentration of specific chemical components in blood or other body fluids by adopting a photoelectric colorimetric principle, reflect the health condition of an organism, and is clinically used for assisting the diagnosis of diseases, the dynamic observation of disease evolution and the like. The substance to be detected is biochemically reacted to form another substance with specific absorption spectrum for different light sources such as ultraviolet light, visible light, infrared light or laser, and a spectrophotometer is adopted to detect the absorbance value so as to quantify the detected substance. With the development of science and technology, the spectrophotometer is basically replaced by an automatic high-flux biochemical analyzer at present, and the inspection efficiency is greatly improved. However, these instruments are generally bulky, expensive to purchase and maintain, require professional personnel to operate, and require a long time to complete a test, and therefore cannot be used for point-of-care testing (POCT), which requires rapid, on-site reporting, or even for home testing.
POCT is used for realizing rapid and convenient clinical field inspection, has the advantages of high detection real-time performance, low comprehensive cost, no dependence on professional equipment and the like, and is widely applied to the fields of clinical monitoring, inspection and quarantine, family health care and the like. The micro-fluidic chip technology integrates basic operation units such as sample preparation, separation, reaction, detection and the like in the processes of biological, chemical and medical analysis on a chip with a micron scale, automatically completes the whole analysis process, has the advantages of miniaturization, integration, automation, portability and the like, and is an important technical means for realizing POCT. The key links based on the microfluidic chip detection and analysis technology are the accurate quantification of microliter-scale samples and reaction reagents, the sufficient mixing of the microliter-scale samples and the reaction reagents before reaction, and the quality control problem of detection, and the three links directly influence the accuracy, controllability and result reliability of the microfluidic chip detection system. At present, a centrifugal method is generally adopted to carry out the quantification and the uniform mixing of microfluid, which needs external centrifugal equipment, and the separation and quantification of a sample, the quantification of a reagent, the uniform mixing and the like need multiple times of centrifugation, thereby increasing the complexity of a chip and the complexity of operation, and in addition, the whole chip is a communicated microtube and chamber system and can not be accessed to an independent quality control system.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides the full-automatic biochemical detection chip which can accurately quantify a sample and a reagent, fully mix a reaction system uniformly and simultaneously realize multi-task detection, has the advantages of high function integration, simple and convenient operation, small volume and low cost, and is suitable for POCT (point of care testing), pediatrics and emergency treatment in hospitals, particularly for household detection.
The invention adopts the following technical scheme for solving the technical problems:
the invention relates to a method for using a multi-task full-automatic biochemical detection chip, which is characterized in that: the chip consists of a quantitative unit, a uniform mixing unit and a reaction unit; in the quantitative unit, blood cells and blood clots are removed from the blood sample through the filter tank under the suction of the quantitative negative pressure pump, and the plasma/serum passing through the filter tank flows into the mixing tank under the drive of the quantitative negative pressure pump to be mixed with the reagent flowing from the reagent tank; the quantitative negative pressure pump and the quantitative booster pump which are arranged at the tail end of the microfluidic channel drive the mixed reagent in a reciprocating manner, so that the reagent is fully and uniformly mixed under the action of the micro-column array; under the drive of a quantitative negative pressure pump, the plasma/serum fully and uniformly mixed with the reagent respectively and quantitatively flows into each sample detection micro-tube, the mixed reagent quickly dissolves the detection reagent microspheres preset in the tube cavity, and the reaction process is started; and (3) under a specified temperature condition, after reacting for a certain time, detecting the absorbance value of each microtube by a photoelectric colorimetry, and calculating the concentration of the specific substance in the sample.
The application method of the multitask full-automatic biochemical detection chip is also characterized in that:
the chip surface around the blood specimen sample inlet has the property of sample affinity, and the opening position of the sample inlet pipeline is low, so that all samples are ensured to be sucked away;
the blood cell filtering device is a microarray structure with gradually reduced spacing in the range of 100-1 mu m, negative pressure in a fluid channel provided by a quantitative negative pressure pump promotes a blood sample to pass through a filtering pool, blood cells and blood clots are removed, and plasma or serum is obtained;
adding anticoagulant substances such as heparin, sodium citrate, EDTA and the like into the blood cell filtering pool to prevent the entering blood specimen from coagulating, and filtering to obtain a plasma sample; or increasing the roughness of the inner surface of the blood cell filter tank to promote the blood specimen to be coagulated, and obtaining serum after removing blood clots through negative pressure suction filtration;
the quantification of the plasma/serum sample is realized by a quantitative negative pressure pump, under the suction of the quantitative negative pressure pump, the quantitative plasma/serum sample flows into a sample mixing pool, is fully and uniformly mixed by a micro-column array in the mixing pool, and is fully and uniformly mixed with the reagent under the reciprocating action of the quantitative negative pressure pump and a quantitative booster pump;
the detection unit is used for detecting that the number of the microtubes is 1 or more according to the requirements of a detection task, reagent microspheres corresponding to detection items are preset in a tube cavity, a mixed reagent flows into the microtubes and then quickly dissolves the reagent microspheres, and a reaction process is started; under the condition of specified temperature, after reacting for a certain time, detecting the absorbance value of each microtube by a photoelectric colorimetry, and calculating the concentration of a specific substance in a sample;
in order to ensure the accuracy of the detection result of the sample, each sample detection micro-tube is provided with a corresponding quality control detection micro-tube, a quality control reagent flows into the quality control detection micro-tube and then quickly dissolves the reagent microspheres, a reaction process is started, the reaction conditions and the detection conditions are the same as those of the sample detection micro-tube, and the concentration of a quality control product is calculated through the absorbance value.
Compared with the prior art, the invention has the technical effects that:
1. the invention adopts the microfluidic technology, integrates the separation and quantification of the sample, the sufficient and uniform mixing of the sample and the detection reagent and the reaction of a plurality of biochemical detection items on one chip, has the advantages of high integration level, small volume and low cost, and can be operated by non-professional personnel;
2. according to the invention, the blood cells and blood clots in the blood specimen are removed, and the quantitative negative pressure pump provides filtering power through the micro-column array which is arranged from large to small in the middle distance of the filtering pool, so that the interference of various blood cells and blood clots in the blood specimen is effectively removed;
3. the filtered plasma/serum sample is sucked into the mixing pool through the negative pressure of the quantitative negative pressure pump and is quantitatively added into the reaction reagent, so that the quantification is accurate and the operation is simpler and more convenient than that of the traditional centrifugal microfluid quantification mode;
4. the plasma/serum and the reagent which are quantitatively absorbed flow in a micro-column array arranged in the mixing pool at the same time, so that the plasma/serum and the reagent in the mixing pool are fully mixed;
5. each sample detection micro-tube on each chip completes one biochemical detection, the detection of a plurality of biochemical projects can be completed by expanding the number of the detection micro-tubes, independent quality control detection micro-tubes corresponding to the detection micro-tubes are arranged on the chip simultaneously, the reaction conditions and the detection conditions are consistent with those of the sample detection micro-tubes, and the accuracy of the sample detection result is ensured by comparing the quality control results.
Drawings
FIG. 1 is a schematic diagram of a multi-task full-automatic biochemical detection chip according to the present invention;
reference numbers in the figures: the device comprises a biochemical detection chip 1, a filter tank 2, a filter micro-column array 3, a micro-valve 4, a mixing tank 5, a mixing micro-column array 6, a quantitative booster pump 7a, a quantitative negative pressure pump 7b, a quantitative hemostix 8, a quality control tank 10, a reagent tank 11, a quality control reaction micro-tube 12 and a sample reaction micro-tube 13.
Detailed Description
Referring to fig. 1, the multi-task full-automatic biochemical detection chip in this embodiment is composed of a quantification unit, a mixing unit and a reaction unit; inserting a quantitative blood collector 8 with a quantitative blood sample into an inlet of a biochemical detection chip 1, opening micro valves 4a and 4d and a quantitative negative pressure pump 7b to enable the blood sample to flow into a filter tank 2, enabling the blood sample to flow through a filter micro-column array 3 under the action of the quantitative negative pressure pump 7b, enabling cells and blood clots in the blood sample to be blocked by the filter micro-column array 3, enabling the blood plasma/serum to flow into a mixing tank 5, then closing the micro valve 4a, enabling the quantitative negative pressure pump 7b to continue working, opening a micro valve 4c to enable a reagent in a reagent tank 11 to flow into the left side of the mixing tank 5, opening the micro valve 4a to enable the quantitative negative pressure pump 7b to drive the blood plasma/serum and the reagent to reach the right side of the mixing tank through a mixing micro-column array 6, and then closing the micro valve 4d and the quantitative negative pressure pump 7 b; the microvalves 4b and 4a and the quantitative booster pump 7a are opened, and the plasma/serum and the reagent are driven to pass through the mixing micro-column array 6 to reach the leftmost side of the mixing pool; repeating the two processes to make the mixed solution of the blood plasma/blood serum and the reagent flow in the mixed micro-column array in a reciprocating way to achieve full and uniform mixing; opening the micro valve 4a, sequentially opening the micro valves 4j, 4i and 4h and the quantitative negative pressure pump 7b, enabling the uniformly mixed plasma/serum and reagent mixed liquid to quantitatively flow into the sample reaction micro tubes 13c, 13b and 13a, rapidly dissolving the detection reagent microspheres preset in the reaction micro tubes, and closing the micro valves 4a, 4j, 4i and 4 h; then, the micro valves 4e, 4f and 4g are opened in sequence, the quantitative decompression pump 7b is kept opened, so that the quality control liquid in the quality control pool 10 sequentially and quantitatively flows into the quality control release pipes 12a, 12b and 12c, the detection reagent microspheres preset in the quality control reaction pipes are rapidly dissolved, and then all the micro valves and the micro pumps are closed; under the condition of specified temperature, after reacting for a certain time, detecting the absorbance value of each microtube by a photoelectric colorimetry, and calculating the concentration of the specific substance in the sample and the quality control product.
In specific implementation, the corresponding structural arrangement includes:
as shown in fig. 1, the chip surface around the quantitative blood collector 8 has hydrophilicity, and the opening position of the sample introduction pipeline is low, so as to ensure that all blood samples are sucked away;
as shown in fig. 1, a filtering micro-column array 3 is arranged in a blood cell filtering pool 2 to remove blood cells and blood clots;
as shown in fig. 1, the number of the sample reaction microtubes is 1 or more, each sample detection microtube completes a biochemical detection, and an independent quality control detection microtube corresponding to the detection microtube is provided, the reaction conditions and the detection conditions are consistent with those of the sample detection microtubes, and the accuracy of the sample detection results is ensured by comparing the quality control results.
The above-mentioned embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements made to the technical solution of the present invention by those skilled in the art without departing from the spirit of the present invention shall fall within the protection scope defined by the claims of the present invention.
Claims (4)
1. A method for using a multi-task full-automatic biochemical detection chip is characterized by comprising the following steps: the chip consists of a quantitative unit, a uniform mixing unit and a reaction unit;
the quantitative unit comprises a biochemical detection chip (1), a filter tank (2), a filter micro-column array (3), a micro valve (4), a mixing tank (5), a mixing micro-column array (6), a quantitative booster pump (7 a), a quantitative negative pressure pump (7 b), a quantitative blood collector (8), a quality control tank (10), a reagent tank (11), a quality control reaction micro-tube (12) and a sample reaction micro-tube (13);
a quantitative blood collector (8) with a quantitative blood sample is inserted into the inlet of the biochemical detection chip (1), the micro valves (4 a, 4 d) and the quantitative negative pressure pump (7 b) are opened to make the blood sample flow into the filter tank (2), under the action of a quantitative negative pressure pump (7 b), a blood sample flows through a filtering micro-column array (3), cells and blood clots in the blood sample are blocked by the filtering micro-column array (3), plasma/serum flows into a mixing pool (5), then a micro valve (4 a) is closed, the quantitative negative pressure pump (7 b) continues to work, the micro valve (4 c) is opened, a reagent in a reagent pool (11) flows into the left side of the mixing pool (5), the micro valve (4 a) is opened, the quantitative negative pressure pump (7 b) drives the plasma/serum and the reagent to pass through the mixing micro-column array (6) and reach the right side of the mixing pool, and then the micro valve (4 d) and the quantitative negative pressure pump (7 b) are closed; opening the micro valves (4 b), (4 a) and the quantitative booster pump (7 a), and driving the plasma/serum and the reagent to pass through the mixing micro-column array (6) to the leftmost side of the mixing pool; repeating the two processes to make the mixed solution of the blood plasma/blood serum and the reagent flow in the mixed micro-column array in a reciprocating way to achieve full and uniform mixing; opening a micro valve (4 a), sequentially opening the micro valves (4 j, 4i, 4 h) and a quantitative negative pressure pump (7 b), enabling the uniformly mixed blood plasma/serum and reagent mixed liquid to quantitatively flow into a sample reaction micro tube (13 c, 13b, 13 a), rapidly dissolving a detection reagent microsphere preset in the reaction micro tube, and closing the micro valves (4 a, 4j, 4i, 4 h); then, the micro valves (4 e, 4f and 4 g) are opened in sequence, the quantitative decompression pump (7 b) is kept opened, so that the quality control liquid in the quality control pool (10) flows into the quality control release pipes (12 a, 12b and 12 c) in sequence and quantitatively, the detection reagent microspheres preset in the quality control reaction pipes are dissolved rapidly, and then all the micro valves and the micro pumps are closed; under the condition of specified temperature, after reacting for a certain time, detecting the absorbance value of each microtube by a photoelectric colorimetry, and calculating the concentration of the specific substance in the sample and the quality control product.
2. The method of claim 1, wherein the surface of the chip around the quantitative blood collector (8) is hydrophilic, and the opening of the sample inlet channel is low to ensure that all blood samples are sucked away.
3. The method of claim 1, wherein the hemocyte filtration pool (2) contains a micro-column array (3) for removing blood cells and blood clots.
4. The method as claimed in claim 1, wherein the number of the sample reaction micro-tubes is 1 or more, each sample detection micro-tube performs a biochemical detection, and an independent quality control detection micro-tube corresponding to the detection micro-tube is provided, the reaction conditions and the detection conditions are the same as those of the sample detection micro-tubes, and the accuracy of the sample detection results is ensured by comparing the quality control results.
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| CN107807104A (en) * | 2017-11-28 | 2018-03-16 | 苏州市苏测检测技术有限公司 | Heavy metal component rapid detection system in food |
| CN108704677B (en) * | 2018-04-27 | 2024-05-28 | 广州万孚生物技术股份有限公司 | Microfluidic chip and analytical instrument comprising same |
| CN108519373B (en) * | 2018-04-27 | 2024-03-15 | 广州万孚生物技术股份有限公司 | Chemiluminescence micro-fluidic chip and analysis instrument comprising same |
| KR102401909B1 (en) * | 2018-08-30 | 2022-05-24 | 주식회사 엘지화학 | A high-speed screening analysis system for reaction optimization |
| CN108795729B (en) * | 2018-09-28 | 2019-02-05 | 湖南乐准智芯生物科技有限公司 | A kind of biochip and its micro liquid sampling structure |
| GB201819417D0 (en) * | 2018-11-29 | 2019-01-16 | Quantumdx Group Ltd | Vacuum-assisted drying of filters in microfluidic systems |
| CN111948409B (en) * | 2019-05-15 | 2024-05-14 | 深圳市理邦精密仪器股份有限公司 | Microfluidic test card, test card assembly, device and control method |
| CN110124760B (en) * | 2019-05-15 | 2021-12-21 | 无锡壹闪生物科技有限公司 | Micro-flow postposition quantitative device and micro-flow control chip |
| CN110102355B (en) * | 2019-05-23 | 2021-04-27 | 江苏集萃智能传感技术研究所有限公司 | Microfluidic immunoassay chip and system |
| CN111530515A (en) * | 2020-05-08 | 2020-08-14 | 北京森美希克玛生物科技有限公司 | Micro-fluidic chip |
| CN112505027B (en) * | 2020-11-15 | 2021-11-26 | 厦门波耐模型设计有限责任公司 | Detection method, device and system of integrated detection test paper |
| CN113649096A (en) * | 2021-09-16 | 2021-11-16 | 苏州集微光电有限公司 | Exosome separation micro-fluidic chip and preparation method thereof |
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| WO2003025547A1 (en) * | 2001-09-21 | 2003-03-27 | Biomedlab Corporation | Method and device for screening analytes using surface plasmon resonance |
| CN105195243A (en) * | 2015-10-26 | 2015-12-30 | 深圳华迈兴微医疗科技有限公司 | Magnetic particulate chemiluminescent micro-fluidic chip for quantitatively detecting myohemoglobin |
| CN106053859A (en) * | 2016-08-02 | 2016-10-26 | 杭州霆科生物科技有限公司 | Centrifugal type glycosylated hemoglobin detection micro-fluidic chip |
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