POCT (Point of Care Testing) microfluidic detection chip carrying color coding microcarrier with photonic crystal structure

Abstract

The invention discloses a POCT (Point of Care Testing) microfluidic detection chip carrying a photonic crystal structure color coding microcarrier and a preparation method of the POCT microfluidic detection chip. The POCT chip comprises a high-definition and high-transparency cover glass used for packaging and visual detection and a chip main body used for placing the photonic crystal structure color coding microcarrier. And the liquid inlets on the chip main body are uniformly dispersed into the reaction chamber of the chip through the multi-stage flow channel. The reaction chamber comprises a plurality of limiting columns which can separate different microcarriers, so that each microcarrier can be in uniform contact with reaction liquid. After the microcarrier is placed on the chip main body in a random mode, the chip main body is packaged by cover glass and biological glue. Due to the fact that the whole chip is subjected to hydrophilic treatment, when an extremely small amount of to-be-detected sample is dropped into the liquid inlet, reaction liquid can rapidly infiltrate the interior of the whole chip and react with the coding microcarrier in the chip. And after incubation for half an hour, washing the residual sample with a buffer solution, and finally reading the result. According to the invention, trace unknown samples can be detected in a short time, and development of on-site rapid detection can be promoted.

Description

Technical fields:

[0001] This invention belongs to the field of point-of-care testing (POCT) in clinical medicine, specifically relating to a POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier and its preparation method. Background technology:

[0002] Biomarkers are widely used in disease detection. Their principle lies in the abnormal expression of certain biomarkers at the site of lesions in a patient's body. By defining the expression levels of these biomarkers, the occurrence of disease can be determined. However, there are many disease-related indicators, making it difficult to meet the needs of high-throughput clinical detection. With the development of technology, coded microcarriers have attracted the attention of researchers. Coded microcarriers are tools for multivariate analysis, containing different coding elements. Various bioprobes corresponding to different indicators are modified onto the surface of microcarriers with different coding information. By comparing the detection signal with the coding signal, high-throughput clinical detection can be achieved.

[0003] Microfluidics is a technology for precisely manipulating microfluidics, offering advantages such as portability, ease of use, and low sample consumption. Combining microfluidics with liquid biopsy technology can meet the clinical need for trace biomarker detection. However, POCT chips based on microfluidics can only detect single or a few indicators, failing to achieve high-throughput detection. Therefore, we designed a microfluidic chip as the main body, integrating coded microcarriers within the chip, to achieve high-throughput detection of disease-related trace biomarkers in clinical settings, demonstrating significant clinical value and development potential. Summary of the Invention:

[0004] The purpose of this invention is to address the shortcomings of existing technologies by developing a POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier, which can be used to achieve high-throughput detection of trace biomarkers related to diseases in clinical practice.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized by comprising a chip body, a packaged high-definition, high-transparency coverslip, and a photonic crystal microcarrier internally modified with different biological probes.

[0007] As a preferred embodiment, the chip body includes an inlet and an outlet, a dendritic multi-stage flow channel, and a reaction chamber. The coverslip and chip body are encapsulated with bio-adhesive to fabricate a POCT microfluidic detection chip carrying a photonic crystal structure color-coded microcarrier.

[0008] As a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the chip body is made of biocompatible resin and is prepared by a photopolymerization 3D printer. After the chip body is cured, it needs to be gently rinsed 3-5 times with anhydrous ethanol to remove any residual uncured resin on the surface, and then placed under a UV lamp for another 10 minutes to further cure, thereby enhancing the overall mechanical strength of the chip.

[0009] As a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the liquid inlet of the chip body is connected to a dendritic multi-stage flow channel, which can uniformly divide the liquid to be tested into multiple equal parts.

[0010] As a preferred embodiment, the POCT microfluidic detection chip equipped with photonic crystal structure color-coded microcarriers is characterized in that the reaction chamber includes multiple limiting pillars, which can separate different microcarriers. The tail ends of the multi-stage flow channels are all connected to the reaction chamber and directly opposite the first row of limiting pillars, which can further uniformly disperse the reaction liquid.

[0011] As a preferred embodiment, the POCT microfluidic detection chip equipped with photonic crystal structure color-coded microcarriers is characterized in that the limiting posts are arranged in a hexagonal pattern, and the internal cavity is slightly larger than a single coded microcarrier, allowing the microcarrier to move and rotate freely within the cavity, ensuring full contact with the reaction liquid. The height of the limiting posts is slightly lower than that of a single coded microcarrier, preventing two microcarriers from stacking together within a unit, ensuring that each unit has exactly one microcarrier.

[0012] As a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the last row of limiting posts faces the liquid outlet channel, which ultimately converges to the liquid outlet. The liquid inlet and outlet are of the same size and are symmetrically distributed at both ends of the chip body, and are connected to the reaction chamber through channels within the chip.

[0013] As a preferred embodiment, the POCT microfluidic detection chip equipped with photonic crystal structure color-coded microcarriers is characterized in that the coded microcarriers are randomly distributed within the limiting pillars and are distinguished by the structural color coding within the microcarriers. The photonic crystal structure color-coded microcarriers are synthesized from silica nanoparticles of different particle sizes. Different biological probes are modified on the surface of the photonic crystal microcarriers with different structural color codes, enabling them to respond to different biomarkers.

[0014] As a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that both the chip body and the microcarrier need to be sealed with bovine serum albumin (BSA), which not only improves the overall wettability of the POCT microfluidic detection chip, but also prevents non-specific adsorption during the detection process.

[0015] As a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the chip is sealed with a high-definition, high-transparency cover glass, the length of which is equal to the distance from the end of the inlet to the beginning of the outlet, and the width of which is equal to the width of the chip body. The high-definition, high-transparency cover glass is not treated; instead, a thin layer of bio-adhesive is brushed onto the surface of the chip body to prevent excessive adhesive from clogging the channels. After the chip is encapsulated, the structure color-coded microcarrier can still be clearly seen through the cover glass.

[0016] As a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that when an extremely small amount of the sample to be tested is dropped into the inlet, the reaction solution rapidly wets the entire hydrophilic chip and the internal structure color-coded microcarrier, and then reacts with it. The detection chip requires a half-hour incubation period, followed by rinsing with buffer solution to remove any remaining sample, and finally, the results are read. Attached image description:

[0017] Figure 1 ; Schematic diagram of a POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier.

[0018] Figure 2 ; Schematic diagram of the main structure of the POCT microfluidic detection chip.

[0019] Figure 3 ; Magnified schematic diagram of the reaction chamber of the detection chip.

[0020] Figure 4 A physical image of the POCT microfluidic detection chip.

[0021] In the diagram, 1. Chip body; 2. High-definition, high-transparency cover glass; 3. Photonic crystal microcarrier; 4. Liquid inlet; 5. Liquid outlet; 6. Dendritic multi-stage flow channel; 7. Reaction chamber; 8. Limiting column; Detailed implementation method:

[0022] The above-described solution will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. All equivalent transformations or modifications made according to the spirit and essence of the invention should be covered within the protection scope of the invention. Implementation conditions not specified in the embodiments are generally conditions found in conventional experiments.

[0023] A POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized by comprising a chip main body 1, a high-definition, high-transparency cover glass 2, and a photonic crystal microcarrier 3 internally modified with different biological probes.

[0024] In this embodiment, the chip body 1 includes an inlet 4 and an outlet 5, a dendritic multi-stage flow channel 6, and a reaction chamber 7. A cover glass slide 2 and the chip body 1 are encapsulated with bio-adhesive to prepare a POCT microfluidic detection chip carrying a photonic crystal structure color-coded microcarrier.

[0025] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the chip body 1 is made of biocompatible resin and is prepared by a photopolymerization 3D printer.

[0026] Furthermore, after the chip body 1 has been cured, it needs to be gently rinsed 3 to 5 times with anhydrous ethanol to remove the uncured resin residue on the surface, and then placed under a UV lamp for another 10 minutes to enhance the overall mechanical strength of the chip.

[0027] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the liquid inlet 4 of the chip body is connected to the dendritic multi-stage flow channel 6, which can uniformly divide the liquid to be tested into multiple equal parts.

[0028] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the reaction chamber 7 includes multiple limiting pillars 8, which can separate different microcarriers.

[0029] Furthermore, the tail ends of the multi-stage flow channels are all connected to the reaction chamber and are directly opposite the first row of limiting columns, which can further disperse the reaction liquid evenly.

[0030] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the limiting posts are arranged in a hexagonal shape, and the cavity inside is just slightly larger than a single coding microcarrier. The microcarrier can move and rotate freely inside the cavity, so that it can fully contact the reaction liquid.

[0031] Furthermore, the height of the limiting post 8 is slightly lower than that of a single coding microcarrier to avoid two microcarriers stacking together within the unit, ensuring that each unit has one and only one microcarrier.

[0032] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the last row of limiting posts is directly opposite the liquid outlet channel, and the liquid outlet channel eventually converges to the liquid outlet 5.

[0033] Furthermore, the liquid inlet 4 and liquid outlet 5 are of the same size and are symmetrically distributed at both ends of the chip body, and are connected to the reaction chamber through channels inside the chip.

[0034] In the embodiment, the POCT microfluidic detection chip equipped with photonic crystal structure color coding microcarrier is characterized in that the coding microcarrier is randomly distributed within the limiting post 8, and is distinguished by the structure color coding inside the microcarrier.

[0035] Furthermore, the aforementioned photonic crystal structure color-coded microcarriers are synthesized using silica nanoparticles of different particle sizes. The surfaces of these photonic crystal microcarriers with different structure color codes are modified with different biological probes, enabling them to respond to various biomarkers.

[0036] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that both the chip body and the microcarrier need to be sealed with bovine serum albumin (BSA), which not only improves the overall wettability of the POCT microfluidic detection chip, but also prevents non-specific adsorption during the detection process.

[0037] In the embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that the chip is sealed with a high-definition, high-transparency cover glass, the length of which is equal to the distance from the tail end of the inlet to the head end of the outlet, and the width of which is equal to the width of the chip body.

[0038] Furthermore, the high-definition, high-transparency cover glass is not treated; instead, a thin layer of bio-adhesive is brushed onto the surface of the chip body to prevent excessive adhesive from clogging the channels.

[0039] Furthermore, after the chip is packaged, the structure color-coded microcarrier can still be clearly seen through the cover glass.

[0040] In the embodiments, as a preferred embodiment, the POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier is characterized in that when an extremely small amount of the sample to be tested is dropped into the inlet, the reaction solution will rapidly wet the entire hydrophilic chip and the internal structure color-coded microcarrier, and then react with it.

[0041] Furthermore, the detection chip needs to be incubated for half an hour, then the residual sample is rinsed with buffer solution before the results are read.

[0042] The above are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principle of the present invention should be considered within the scope of protection of the present invention.

Claims

1. A POCT microfluidic detection chip equipped with a photonic crystal structure color-coded microcarrier, characterized in that... It includes a chip body, a packaged high-definition, high-transparency cover glass, and an internally integrated photonic crystal microcarrier modified with different biological probes. The chip body includes an inlet and an outlet, a dendritic multi-stage flow channel, and a reaction chamber. A POCT microfluidic detection chip carrying a photonic crystal structure color-coded microcarrier is fabricated by encapsulating the coverslip and the chip body with bio-adhesive.

2. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier as described in claim 1, characterized in that... The chip body is made of biocompatible resin and is prepared using a photopolymerization 3D printer. After the chip body is cured, it needs to be gently rinsed 3 to 5 times with anhydrous ethanol to remove the uncured resin residue on the surface, and then placed under a UV lamp for another 10 minutes to enhance the overall mechanical strength of the chip.

3. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier as described in claim 1, characterized in that... The liquid inlet of the chip body is connected to a dendritic multi-stage flow channel, which can evenly divide the liquid to be tested into multiple equal parts.

4. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier as described in claim 1, characterized in that... The reaction chamber contains multiple limiting columns that can separate different microcarriers. The tail ends of the multi-stage flow channels are all connected to the reaction chamber and are directly opposite the first row of limiting columns, which can further disperse the reaction liquid evenly.

5. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier as described in claim 1, characterized in that... The limiting posts are arranged in a hexagonal shape, and the cavity inside is slightly larger than a single coded microcarrier. The microcarrier can move and rotate freely inside the cavity, allowing it to fully contact the reaction liquid. The height of the limiting post is slightly lower than that of a single coding microcarrier to avoid two microcarriers stacking together in the unit, so that each unit has one and only one microcarrier.

6. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier as described in claim 1, characterized in that... The last row of limiting posts is directly opposite the liquid outlet channel, which eventually converges at the liquid outlet. The inlet and outlet are the same size and are symmetrically distributed at both ends of the chip body, and are connected to the reaction chamber through channels inside the chip.

7. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier according to claim 1, characterized in that... The coded microcarriers are randomly distributed within the limiting post and are distinguished by the structural color coding inside the microcarriers. The aforementioned photonic crystal structure-color encoded microcarriers are synthesized using silica nanoparticles of varying sizes. Different biological probes are modified onto the surface of these photonic crystal microcarriers with different structure-color codes, enabling them to respond to various biomarkers.

8. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier according to claim 1, characterized in that... Both the chip body and the microcarrier need to be sealed with bovine serum albumin (BSA), which not only improves the overall wettability of the POCT microfluidic detection chip, but also prevents non-specific adsorption during the detection process.

9. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier according to claim 1, characterized in that... The chip is sealed with a high-definition, high-transparency cover glass, the length of which is equal to the distance from the end of the inlet to the beginning of the outlet, and the width of which is equal to the width of the chip body. The high-definition, high-transparency cover glass is left untreated; instead, a thin layer of bio-adhesive is brushed onto the surface of the chip body to prevent excessive adhesive from clogging the channels. After the chip is packaged, the structure color-coded microcarriers can still be clearly seen through the cover glass.

10. The POCT microfluidic detection chip with photonic crystal structure color-coded microcarrier according to claim 1, characterized in that... When an extremely small amount of the test sample is dropped into the inlet, the reaction solution rapidly wets the entire hydrophilic chip and its internal structure-color encoded microcarriers, and then reacts with them. The detection chip requires a 30-minute incubation period, followed by rinsing with buffer solution to remove any remaining sample, and finally, the results are read.

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