Microfluidic Detection Strip Chip and Preparation and Method Thereof
20230234047 · 2023-07-27
Inventors
Cpc classification
B01L2200/16
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/069
PERFORMING OPERATIONS; TRANSPORTING
B01L3/5023
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A microfluidic detection strip chip for multiple indicator detection of microsample and method thereof are disclosed. The microfluidic detection strip chip includes a substrate, a plurality of microfluidic pipes, and a plurality of reagent blocks, the microfluidic pipes and the reagent blocks arranged in a lattice are arranged on the substrate for detection of enzyme, chemistry, protein, polypeptide, amino acid, nucleic acid, and exocrine components in samples. The microfluidic pipes and reagent blocks are made using micro processing technology, and the reagent blocks are printed to the lattice array grooves constructed by the substrate and microfluidic pipes, thus realizing an analysis and detection effect of multiple indicators of microsample.
Claims
1. A microfluidic detection strip chip for multiple indicator detection of micro sample, including: a substrate configured to carry the microfluidic detection strip chip and participate in forming a groove, a microfluidic pipe configured to control a flow speed and direction of liquid sample or reagents and participate in forming the groove, the microfluidic pipe is bonded to a surface of the substrate, and a plurality of reagent blocks configured to adsorb the liquid sample or reagents and perform chromogenic reaction, the reagent block is arranged in the groove.
2. The microfluidic detection strip chip according to claim 1, wherein the microfluidic pipe comprises two independent pipeline systems configured to detect two different types of indicators.
3. The microfluidic detection strip chip according to claim 2, wherein the microfluidic pipe comprises three or more independent pipeline systems configured to detect three or more different types of indicators.
4. The microfluidic detection strip chip according to claim 3, wherein the microfluidic pipe comprises a first port, a capillary network and a second port, the first port is connected with the capillary network, the capillary network is connected with the second port, the capillary network and a substrate form a groove, and the groove is connected with the capillary network through the second port.
5. The microfluidic detection strip chip according to claim 4, wherein the microfluidic pipe further comprises a sample adding component configured to add sample or reagents, the sample adding component is connected with the first port.
6. The microfluidic detection strip chip according to claim 5, wherein the sample adding component comprises a sample hole, the sample hole comprises a first interface configure to connect a syringe for filling sample.
7. The microfluidic detection strip chip according to claim 6, wherein the sample adding component further comprises an extension tube, the extension tube is connected with the first interface and a first port configured to increase a convenience of filling sample.
8. The microfluidic detection strip chip according to claim 7, wherein the sample adding component further comprises a reagent hole, the reagent hole comprises a second interface and a second extension tube, the second extension tube is connected to the second interface and the first port configured to connect a syringe for adding reagents.
9. The microfluidic detection strip chip according to claim 8, wherein the sample adding component further comprises an elastic fluid reservoir configured to store liquid sample or reagents, and slowly and continuously inject the liquid sample or reagents into a capillary network through a first port.
10. The microfluidic detection strip chip according to claim 9, wherein the elastic fluid reservoir comprises an injection kettle, a capsule body and a valve, the injection kettle is connected with the capsule body configured to connect a syringe needle, and the capsule body is pluggable connected with a first port through the valve.
11. The microfluidic detection strip chip according to claim 4, wherein the second port comprises a first stage second port, a second stage second port and a last stage second port, the first stage second port has a smallest opening configured to connect a groove close to a first port, and the last stage second port has a largest opening configured to connect the groove far from the first port.
12. The microfluidic detection strip chip according to claim 4, wherein the microfluidic pipe further comprise a plurality of micro valves configured to control a flow direction of liquid sample or reagents.
13. The microfluidic detection strip chip according to claim 1, wherein a plurality of grooves is arranged in a lattice to accommodate a plurality of reagent blocks.
14. The microfluidic detection strip chip according to claim 13, wherein the reagent block comprises a reaction part configured to provide a chromogenic reaction between a sample and a reagent.
15. The microfluidic detection strip chip according to claim 14, wherein the reagent block further comprises a waste liquid absorption part configured to adsorb sample or reagents.
16. The microfluidic detection strip chip according to claim 15, wherein the reagent block further comprises a filter membrane part, the filter membrane part is arranged between a reaction part and a second port configured to filter a large particle component in a sample.
17. The microfluidic detection strip chip according to claim 16, wherein the reagent block is arranged in a groove close to a first port to detect indicator with large target molecular weight.
18. The microfluidic detection strip chip according to claim 17, wherein the reagent block is arranged in the groove far from the first port to detect indicator with small target molecular weight.
19. A method of a microfluidic detection strip chip, comprising: selecting a microfluidic detection strip chip; filling a sample; filling a reagent; controlling a reaction condition; and scanning to obtain a result.
20. The method of a microfluidic detection strip chip according to claim 19, wherein the step of filling a sample comprising: connecting a sample adding component to the microfluidic detection strip chip, suctioning the sample with a syringe, connecting the syringe with an interface, and injecting the sample into the microfluidic detection strip chip.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] In order to more clearly explain the technical solution of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained from these drawings without any creative effort.
[0041] In addition, the attached drawings are only schematic diagrams of the application and are not necessarily drawn to scale. The same reference numerals in the figures represent the same or similar parts, and therefore repeated description of them will be omitted. Some block diagrams shown in the figures are functional entities, which do not necessarily correspond to physically or logically independent entities. These functional entities can be implemented in one or more hardware modules or component combinations.
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[0069] The drawings, described above, are provided for purposes of illustration, and not of limitation, of the aspects and features of various examples of embodiments of the invention described herein. The drawings are not intended to limit the scope of the claimed invention in any aspect. For simplicity and clarity of illustration, elements shown in the drawings have not necessarily been drawn to scale and the dimensions of some of the elements may be exaggerated relative to other elements for clarity.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0070] In order to make the purpose, technical solution and advantages of the application more clearly, the application is further described in detail below in combination with embodiments. It should be understood that the specific embodiments described herein are only used to explain the application, not to limit the application.
[0071] It should be noted that the up, down, left, right, far, near, front, back, positive and negative directions in this embodiment are only relative concepts to each other or refer to the normal use state of the product, and should not be considered as restrictive.
[0072] Referring to
[0073] As shown in
[0074] As shown in
[0075] As shown in
[0076] As shown in
[0077] In addition, the second port 22 can comprise a first stage second port 221, a second stage second port 222, a third stage second port 223, and a last stage second port 224. Among them, an opening size of the first stage second port 221 is the smallest, which is set near the first port 24, when a syringe injects liquid samples or reagents through the capillary network 21 and the second port 22 into the groove 23, the liquid samples or reagents can flow into the groove 23 at a slowest speed. The opening sizes of the second stage second port 222 and the third stage second port 223 can gradually increase, which can be set in a middle area of the capillary network 21, when the syringe pushes liquid samples or reagents through the capillary network 21 and the second port 22 to enter the space of the groove 23, and the liquid samples or reagents can flow into the groove 23 at an increased speed accordingly. The opening size of the last stage second port 224 is the largest, which is set in an area far from the first port 24, when the syringe pushes liquid samples or reagents through the capillary network 21 and the second port 22 to enter the space of the groove 23, the liquid samples or reagents can flow into the groove 23 at a faster speed. Thus, through different opening sizes of the second port 22, the liquid sample or reagent injected by the syringe can almost synchronously flow from the first port 24 into the capillary network 21 and into the groove 23. It should be noted that the second port 22 can also be set with a forth or more stages as required.
[0078] In addition, the interface 25 and the first port 24 can be set at a lower end of the capillary network 21, or at an upper end of the capillary network 21, or at a left end, or at a right end, or at any area between the capillary network 21. Accordingly, a position of the first stage second port 221, the second stage second port 222, the third stage second port 223, and the last stage second port 224 need to be changed.
[0079] It can be understood that when it is need to fill a liquid sample or reagent to the groove 23 through the capillary network 21 and the second port 22 at a fastest speed, a position of the groove 23 can be set in an area closest to the first port 24, and a larger pipe diameter of the capillary network 21 and a largest opening of the second port 22 can be made. On the contrary, when it is need to fill a liquid sample or reagent to the groove 23 through the capillary network 21 and the second port 22 at a slowest speed, the position of the groove 23 can be set in the area farthest from the first port 24, and a smaller pipe diameter of the capillary network 21 and a smallest opening of the second port 22 can be made.
[0080] As shown in
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[0087] As shown in
[0088] In addition, as shown in
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[0090] It should be noted that the lattice arranged grooves 23 of the microfluidic detection strip chip in the preferred embodiment of the present invention can be divided into a plurality of areas according to a distance between the groove 23 and the first port 24. Similarly, the reagent blocks 3 can be divided into a plurality of categories based on a target molecular weight of indicators detected by the reagent blocks 3. If the molecular weight of the indicator detected by the reagent block 3 is large, the reagent block 3 can be set in the groove 23 in the area near the first port 24. On the contrary, if the molecular weight of the indicator detected by reagent block 3 is small, the reagent block 3 can be set in the groove 23 in the area far from the first port 24. Thus, depending on a laminar flow effect of the microfluidic pipe 2, different target molecules in liquid samples can enter into different types of the reagent blocks 3 almost at the same time, reducing a detection time, provide detection efficiency.
[0091] It should be noted that an amount of liquid sample or reagent required for the microfluidic strip chip in the preferred embodiment of the present invention can be accurately designed and obtained by actual testing, so as to provide a reference for users.
[0092] It should be noted that the reagent blocks 3 of the microfluidic strip chip in the preferred embodiment of the present invention can also be divided into a plurality of categories according to different principles of chromogenic reaction. The reagent blocks 3 with same or similar principle can be set in a same area, and a same set of microfluidic pipes 2 can be set in the area to facilitate users to fill liquid samples or reagents.
[0093] Referring to
[0094] S110: Design a microfluidic detection strip chip, including a microfluidic pipe, a substrate, and a plurality of reagent blocks.
[0095] First of all, determine a detection item category, indictors and performance index of the microfluidic detection test strip chip to meet user needs.
[0096] With an assistant of design software, a circuit diagram of the microfluidic pipe can be drawn. The circuit diagram of the microfluidic pipe at least includes one capillary network, a plurality of first ports, a plurality of grooves, a plurality of second ports, and at least one interfaces, and can also include at least one extension tube, one or more filters, and one or more elastic fluid reservoirs.
[0097] Among them, a plurality of groove areas can be divided according to a distance between the groove and the first port. Similarly, a plurality of groove areas containing different reagent blocks can be divided according to a molecular weight of the indicator detected by the reagent block. Then the reagent block layout scheme can be determined. In addition, the reagent blocks can also be divided into a plurality of categories according to different principles of chromogenic reaction. The reagent blocks with same or similar principles of chromogenic reaction can be set in the same groove area, and the same set of microfluidic pipes can be set in the same area to facilitate users to fill liquid samples or reagents.
[0098] According to the circuit diagram of the microfluidic pipe, a substrate can be designed.
[0099] Then an amount of liquid sample or reagent required for microfluidic detection strip chip can be measured so as to provide a reference for users.
[0100] S120. Fabricate the microfluidic pipe by micro machining process. Generally, polymer materials or silicon based materials can be selected, injection molding technology, etching technology and/or 3D printing technology can be used, and 3D modeling can be conducted according to the circuit diagram of the microfluidic pipe designed in step S110 to produce the microfluidic pipe.
[0101] S130: Make the reagent blocks by micro machining process. The reagent block can be usually a disk-shaped dry test paper block or semi dry test paper block or gel block or one or more micro chambers to form a detection unit. The types of reagent blocks can comprise a dry chemical detection reagent block, an immunological detection reagent block and a chip reagent block.
[0102] S140: Bond the microfluidic pipe to the substrate to form a lattice grooves on the substrate with a capillary network. The microfluidic pipe made in step S120 can be combined with the substrate by bonding or thermal bonding. One substrate can combine one or more microfluidic pipes on one side, and one substrate can also combine two or more microfluidic pipes on the front and back. It can be understood that if 3D printing technology is used to make microfluidic pipes, 3D printing technology can be used to make microfluidic pipes and substrate complexes.
[0103] S150: Print the reagent blocks to the lattice grooves on the substrate which can be implemented using a prior art (patent publication No. CN112362648A). It should be noted that a semi dry reagent block, gel reagent block or liquid reagent block can be covered with a micro cover plate or film.
[0104] S160: Install a plurality of components, including an interface, an extension tube, a valve, an elastic fluid reservoir and/or a filter screen, print identification codes in a blank area of the substrate, make a complete microfluidic detection strip chip, and put it into a packaging box.
[0105] As shown in
[0106] S210: Select a microfluidic detection strip chip. According to a sample type and detection purpose, the microfluidic detection strip chip or a combination of several microfluidic detection strip chips can be selected.
[0107] S220: Add samples. A process of adding samples can include a plurality of steps as fellow: (a) connect a sample adding component to the microfluidic detection strip chip, such as an interface, an extension tube, an filter screen, an elastic fluid reservoir, (b) absorb liquid samples with a syringe, (c) connect the syringe with the interface, and (d) push the syringe to add samples into the microfluidic detection strip chip. If the sample is a solid or semi-solid material, such as dry or molded feces, dried blood or urine residue, it can be needed to dissolve the solid or semi-solid material with normal saline or pure water, and then use the syringe to suck the sample, connect the interface, and fill the sample into the microfluidic detection strip chip. It should be noted that a minimum amount of liquid sample should be needed according to the microfluidic detection strip chip, so as to ensure that each reagent block of the microfluidic detection strip chip can be fully soaked. If the amount of liquid sample is not insufficient, and then the liquid sample can be diluted in an appropriate proportion to reach the minimum amount marked on the microfluidic detection strip chip.
[0108] S230: Add reagents. According to an instruction for the microfluidic detection strip chip, before or after adding samples, absorb a certain amount of a reagent or a plurality of reagents or a combination of a plurality of reagents with a syringe, connect the interface of the microfluidic detection strip chip, and add the reagents.
[0109] S240: Control a chromogenic reaction condition. According to the instructions of the microfluidic detection strip chip, provide a suitable temperature and humidity environment, remove a micro cover plate or film covering the reagent block, and leave an appropriate reaction time.
[0110] S250: Scan and obtain a result. After the chromogenic reaction in step S240 completed, scan the microfluidic detection strip chip with a vision sensor under an appropriate light condition to obtain a chromogenic reaction data of each reagent block, and then obtain a detection result of multiple indicators in the sample with an algorithm.
[0111] The above description is only an example of the application, and does not limit the technical scope of the application. Therefore, any minor modification, equivalent change and modification of the above embodiments according to the technical essence of the application still fall within the scope of the technical solution of the application. Professionals should be aware that professionals can use different methods to achieve the described functions for each specific application, but such implementation should not be considered beyond the scope of this application.