A microfluidic impedance-type biological online detection device

Abstract

The invention discloses a microfluidic impedance-type biological online detection device, which belongs to the technical field of microfluidic biological detection. The microfluidic impedance-type biological online detection device comprises a host, an impedance analyzer, a multiplexer and a detection body. The host is connected to the impedance analyzer, the impedance analyzer is connected to the multiplexer, and the multiplexer is connected to the detection body. The detection body comprises a microfluidic chip, a collecting plate and an anti-overflow plate which are sequentially distributed from top to bottom. An introduction tube and an outlet tube are fixedly connected to the upper end of the microfluidic chip, and a one-way valve is fixedly connected to the inside of the introduction tube and the outlet tube. The invention not only reduces the overflow during sample introduction through the arrangement of the collecting plate and the anti-overflow plate, but also facilitates the collection of overflowed and drawn sample reagents, reduces the difficulty of sample drawing, improves the sample drawing efficiency, reduces the contamination of the sample on the surface of the microfluidic chip, and improves the sample detection efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic biological detection, and more specifically, to a microfluidic impedance-type biological online detection device. Background Art

[0002] Microfluidics is a technology that integrates the basic operating units of sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a micrometer-scale chip to automatically complete the entire analysis process. Due to its huge potential in the fields of biology, chemistry, and medicine, it has developed into a new research field that intersects biology, chemistry, medicine, fluids, electronics, materials, and mechanics.

[0003] Microfluidic chips are the main platform for the realization of microfluidic technology. The main feature of the device is that its effective structure (channels, reaction chambers and other functional components) that contains fluids is micrometer-scale at least in one dimension. Due to the micrometer-scale structure, the fluid displays and produces special properties that are different from those at the macroscopic scale. Therefore, unique analytical performance is developed. Characteristics and development advantages of microfluidic chips: Microfluidic chips have the characteristics of controllable liquid flow, minimal consumption of samples and reagents, and analysis speed increased by ten or hundreds of times. It can analyze hundreds of samples simultaneously in a few minutes or even shorter time, and can realize the whole process of sample pretreatment and analysis online.

[0004] Electrical impedance tomography (EIT) is a visual detection technology that uses a series of electrodes on the surface of the object to detect the object to determine the conductivity or permittivity distribution of each position inside the target. EIT has been widely used in the field of biology due to its advantages such as no radiation source, non-invasive detection, fast detection speed and low cost. In biological detection, the visual detection technology of the position distribution of cells in flow can not only be used for real-time monitoring of cell manipulation applications, such as the detection of cell separation effects, but also can be used to verify the computational model of cell distribution in microfluidics.

[0005] Regarding the development of microfluidic technology, the current international research status innovation is mostly focused on separation and detection systems, and the research on many issues of how to introduce actual sample analysis on the chip, such as sample introduction, sample replacement, and extraction, is still very weak. When introducing or extracting biological sample reagents on the chip, the existing technology has a centimeter-level chip and a micron-level structure of the sample inlet. When introducing and extracting biological sample reagents, even if the operation is precise and accurate, there are still problems such as sample overflow and inconvenient collection, which not only seriously wastes sample reagents, but also causes chip contamination, affecting the detection process. Summary of the invention

[0006] 1. Technical issues to be solved

[0007] In view of the problems existing in the prior art, the purpose of the present invention is to provide a microfluidic impedance-type biological online detection device, which, through the setting of a collection plate and an anti-overflow plate, not only reduces the overflow during sample introduction, but also facilitates the collection of overflowed and drawn-out sample reagents, reduces the difficulty of sample drawing, improves the sample drawing efficiency, reduces the contamination of the sample on the surface of the microfluidic chip, and improves the sample detection efficiency.

[0008] 2. Technical solution

[0009] To solve the above problems, the present invention adopts the following technical solutions.

[0010] A microfluidic impedance-type biological online detection device comprises a host, an impedance analyzer, a multiplexer and a detection body, wherein the host is connected to the impedance analyzer, the impedance analyzer is connected to the multiplexer, the multiplexer is connected to the detection body, the detection body comprises a microfluidic chip, a collection plate and an anti-overflow plate which are sequentially distributed from top to bottom, the upper end of the microfluidic chip is fixedly connected with an inlet pipe and an outlet pipe, the insides of the inlet pipe and the outlet pipe are fixedly connected with a one-way valve, an inlet and an outlet are provided on the collection plate, the inlet pipe matches the inlet, the outlet pipe matches the outlet, and the collection plate is A main absorption layer is fixedly connected to the upper end, and the main absorption layer is located on the outside of the outlet; an amplification tube is fixedly connected to the upper end of the anti-overflow plate, and the amplification tube is communicated with the introduction tube; a sealing film is fixedly connected to the inside of the amplification tube; a secondary absorption layer is fixedly connected to the upper end of the anti-overflow plate, and the secondary absorption layer is located on the outside of the amplification tube. The present invention not only reduces the overflow during sample introduction through the arrangement of the collection plate and the anti-overflow plate, but also facilitates the collection of overflowed and drawn-out sample reagents, reduces the difficulty of sample drawing, improves the sample drawing efficiency, reduces the contamination of the sample on the surface of the microfluidic chip, and improves the sample detection efficiency.

[0011] Furthermore, the lower ends of the collecting plate and the anti-overflow plate are fixedly connected with a mucous membrane, and the mucous membrane is made of a PET sticky film, and the connection and separation between the microfluidic chip and the collecting plate, and the collecting plate and the anti-overflow plate are achieved through the mucous membrane.

[0012] Furthermore, the main absorption layer and the secondary absorption layer both include a water-absorbing resin layer and a nano-absorption layer. The nano-absorption layer is located on the upper side of the water-absorbing resin layer. The nano-absorption layer is composed of a mixture of nano-zinc oxide and nano-silicon dioxide. The water-absorbing resin layer has a highly efficient absorption effect and is used to absorb liquid in the sample. The nano-absorption layer has a good adsorption effect and is used to absorb non-liquid substances in the sample.

[0013] Furthermore, a base is provided on the lower side of the detection body, a groove is provided on the upper end of the base, the microfluidic chip is fixedly connected inside the groove, and the base has a supporting and fixing function for the detection body, making it convenient to take and place the detection body.

[0014] Furthermore, the microfluidic chip is provided with a sample adding chamber, a pre-treatment chamber, a reaction chamber, a detection chamber and a storage chamber, so that the microfluidic chip can realize a series of processes such as reaction, separation and detection of sample reagents.

[0015] Furthermore, a microchannel is connected between the sample adding chamber, the pre-treatment chamber, the reaction chamber, the detection chamber and the storage chamber for the circulation of sample reagents between two adjacent chambers.

[0016] Furthermore, a microvalve is provided in the microchannel, and the flow of the sample reagent is controlled by opening and closing the microvalve.

[0017] Furthermore, the sample adding chamber is communicated with the introduction tube, and the storage chamber is communicated with the outlet tube.

[0018] A microfluidic impedance-type biological online detection device, and a method of using the device is as follows:

[0019] S1. A person skilled in the art uses wires to connect the host, the impedance analyzer, the multiplexer and the detection subject to each other to connect the detection circuits;

[0020] S2. Collect an appropriate amount of the biological sample reagent to be detected by using a syringe, then insert the needle into the amplification tube until the sealing film is pierced, the needle penetrates the sealing film and extends into the inner side of the amplification tube, and injects the biological sample reagent to be detected into the microfluidic chip;

[0021] S3. After the sample injection is completed, the needle is removed, and the anti-overflow plate contaminated with the biological sample reagent to be tested is torn off the collection plate, and then the sample is tested;

[0022] S4. After the detection is completed, the biological sample reagent flows out from the lead-out tube and is adsorbed on the main absorption layer. After all the biological sample reagents are led out, the collection plate is torn off the microfluidic chip to collect the biological sample reagents.

[0023] 3. Beneficial effects

[0024] Compared with the prior art, the advantages of the present invention are:

[0025] (1) This scheme not only reduces the overflow during sample introduction by setting up a collection plate and an anti-overflow plate, but also facilitates the collection of overflowed and drawn-out sample reagents, reduces the difficulty of sample drawing, improves the sample drawing efficiency, reduces the contamination of the sample on the surface of the microfluidic chip, and improves the sample detection efficiency.

[0026] (2) During the injection process, the sealing film 13 surrounds the outside of the needle and has the function of preventing the sample reagent from overflowing; part of the overflowed sample reagent flows to the secondary absorption layer 14 and is absorbed by the secondary absorption layer 14, so that the microfluidic chip 401 and the collection plate 402 are not easily contaminated and not easily affect the detection process; during the extraction process, the main absorption layer 11 absorbs the sample reagent, which can realize the convenient and rapid extraction of the sample reagent while also not easily causing contamination to the surface of the microfluidic chip 401, thereby improving the sample extraction and collection efficiency.

[0027] (3) The lower ends of the collection plate and the anti-overflow plate are fixedly connected with a mucous membrane, which is made of a PET sticky film. The microfluidic chip and the collection plate, and the collection plate and the anti-overflow plate are connected and separated by the mucous membrane.

[0028] (4) Both the main absorption layer and the secondary absorption layer include a water-absorbing resin layer and a nano-absorption layer. The nano-absorption layer is located on the upper side of the water-absorbing resin layer. The nano-absorption layer is composed of a mixture of nano-zinc oxide and nano-silicon dioxide. The water-absorbing resin layer has a high absorption effect and is used to absorb the liquid in the sample. The nano-absorption layer has a good absorption effect and is used to absorb the non-liquid substances in the sample.

[0029] (5) A base is provided at the lower side of the detection body, and a groove is provided at the upper end of the base. The microfluidic chip is fixedly connected inside the groove. The base has a supporting and fixing function for the detection body, making it convenient to take and place the detection body.

[0030] (6) The interior of the microfluidic chip is equipped with a sample loading chamber, a pretreatment chamber, a reaction chamber, a detection chamber, and a storage chamber, so that the microfluidic chip can realize a series of processes such as reaction, separation, and detection of sample reagents.

[0031] (7) A microfluidic channel is connected between the sample adding chamber, the pre-treatment chamber, the reaction chamber, the detection chamber and the storage chamber to circulate the sample reagent between two adjacent chambers.

[0032] (8) A microvalve is provided in the microchannel, and the flow of sample reagent is controlled by opening and closing the microvalve. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 It is the connection principle diagram of the present invention;

[0034] Figure 2 A three-dimensional diagram of the detection subject of the present invention;

[0035] Figure 3 An exploded diagram of the detection body of the present invention;

[0036] Figure 4 is a three-dimensional diagram of the microfluidic chip of the present invention;

[0037] Figure 5is a three-dimensional diagram of a collecting plate of the present invention;

[0038] Figure 6 A three-dimensional diagram of the anti-overflow plate of the present invention;

[0039] Figure 7 for Figure 6 The structural diagram at A in the middle;

[0040] Figure 8 It is a schematic diagram of the structure of the main absorption layer and the secondary absorption layer of the present invention;

[0041] Fig. 9 Schematic diagram of the internal structure of the microfluidic chip of the present invention.

[0042] Description of the numbers in the figure:

[0043] 1 host, 2 impedance analyzer, 3 multiplexer, 4 detection body, 401 microfluidic chip, 402 collection plate, 403 anti-overflow plate, 5 bottom support, 501 groove, 6 introduction tube, 7 lead-out tube, 8 one-way valve, 9 inlet, 10 outlet, 11 main absorption layer, 12 amplification tube, 13 sealing film, 14 secondary absorption layer, 15 mucous membrane, 16 sample addition chamber, 17 pretreatment chamber, 18 reaction chamber, 19 detection chamber, 20 storage chamber, 21 microchannel, 22 microvalve. DETAILED DESCRIPTION

[0044] The following will combine the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all the embodiments. All other embodiments obtained by ordinary technicians in this field without creative work based on the embodiments of the present invention belong to the scope of protection of the present invention.

[0045] In the description of the present invention, it should be noted that the terms "upper", "lower", "inner", "outer", "top / bottom" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific position, be constructed and operated in a specific position, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance.

[0046] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "provided with", "mounted / connected", "connected", etc. should be understood in a broad sense. For example, "connected" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0047] Embodiment 1:

[0048] See also Figure 1 A microfluidic impedance-type biological online detection device includes a host 1, an impedance analyzer 2, a multiplexer 3 and a detection body 4. The host 1 is connected to the impedance analyzer 2, the impedance analyzer 2 is connected to the multiplexer 3, and the multiplexer 3 is connected to the detection body 4. The host 1 is a manual operation platform, the impedance analyzer 2 is used to observe and record the detection process, the multiplexer 3 is used to control the required excitation electrodes and detection electrodes, and a bottom bracket 5 is provided on the lower side of the detection body 4. A groove 501 is opened at the upper end of the bottom bracket 5. The microfluidic chip 401 is fixedly connected to the inside of the groove 501. The bottom bracket 5 has a supporting and fixing effect on the detection body 4, which is convenient for taking and placing the detection body 4.

[0049] See also Figure 3 The detection body 4 includes a microfluidic chip 401, a collection plate 402 and an anti-overflow plate 403, which are arranged in sequence from top to bottom. Figure 4 The upper end of the microfluidic chip 401 is fixedly connected with an inlet tube 6 and an outlet tube 7, and the inside of the inlet tube 6 and the outlet tube 7 are fixedly connected with a one-way valve 8. The flow direction of the one-way valve 8 in the inlet tube 6 is from outside to inside, and the flow direction of the one-way valve 8 in the outlet tube 7 is from inside to outside.

[0050] See also Figure 5 The collecting plate 402 is provided with an inlet 9 and an outlet 10, the inlet pipe 6 matches the inlet 9, the outlet pipe 7 matches the outlet 10, the upper end of the collecting plate 402 is fixedly connected with a main absorption layer 11, and the main absorption layer 11 is located outside the outlet 10, please refer to Figure 6 and Figure 7 The upper end of the anti-overflow plate 403 is fixedly connected with the amplification tube 12, the amplification tube 12 is communicated with the introduction tube 6, the inside of the amplification tube 12 is fixedly connected with the sealing film 13, the upper end of the anti-overflow plate 403 is fixedly connected with the secondary absorption layer 14, and the secondary absorption layer 14 is located on the outside of the amplification tube 12.

[0051] See also Figure 8The main absorption layer 11 and the secondary absorption layer 14 both include a water-absorbing resin layer and a nano-absorption layer. The nano-absorption layer is located on the upper side of the water-absorbing resin layer. The nano-absorption layer is composed of a mixture of nano-zinc oxide and nano-silicon dioxide. The water-absorbing resin layer has a high absorption effect and is used to absorb the liquid in the sample. The nano-absorption layer has a good absorption effect and is used to absorb the non-liquid substances in the sample.

[0052] See also Figure 7 The lower ends of the collecting plate 402 and the anti-overflow plate 403 are fixedly connected with a mucous membrane 15, and the mucous membrane 15 is made of a PET sticky film. The connection and separation between the microfluidic chip 401 and the collecting plate 402, and the collecting plate 402 and the anti-overflow plate 403 are achieved through the mucous membrane 15.

[0053] See also Fig. 9 The microfluidic chip 401 is provided with a sample adding chamber 16, a pretreatment chamber 17, a reaction chamber 18, a detection chamber 19 and a storage chamber 20, so that the microfluidic chip 401 can realize a series of processes such as reaction, separation and detection of sample reagents. The sample adding chamber 16 is communicated with the introduction tube 6, and the storage chamber 20 is communicated with the outlet tube 7. A microchannel 21 is connected between the sample adding chamber 16, the pretreatment chamber 17, the reaction chamber 18, the detection chamber 19 and the storage chamber 20. The microchannel 21 is used for the circulation of sample reagents between two adjacent chambers. A microvalve 22 is provided in the microchannel 21, and the flow of the sample reagent is controlled by opening and closing the microvalve 22.

[0054] A microfluidic impedance-type biological online detection device, and a method of using the device is as follows:

[0055] S1. A person skilled in the art uses a wire to connect the host 1, the impedance analyzer 2, the multiplexer 3 and the detection subject 4 to each other, thereby connecting the detection circuit;

[0056] S2. Collect an appropriate amount of the biological sample reagent to be detected by a syringe, then insert the needle into the amplification tube 12 until the sealing film 13 is pierced, and the needle penetrates the sealing film 13 and extends into the inner side of the amplification tube 12, and injects the biological sample reagent to be detected into the microfluidic chip 401;

[0057] S3, after the sample injection is completed, the needle is removed, and the anti-overflow plate 403 contaminated with the biological sample reagent to be detected is torn off from the collection plate 402, and then the sample is tested;

[0058] S4. After the detection is completed, the biological sample reagent flows out from the outlet tube 7 and is adsorbed on the main absorption layer 11. After all the biological sample reagents are drawn out, the collection plate 402 is torn off the microfluidic chip 401 to collect the biological sample reagents.

[0059] During the injection process, the sealing film 13 surrounds the outside of the needle and has the function of preventing the sample reagent from overflowing; part of the overflowed sample reagent flows to the secondary absorption layer 14 and is absorbed by the secondary absorption layer 14, so that the microfluidic chip 401 and the collection plate 402 are not easily contaminated and not easily affect the detection process; during the extraction process, the main absorption layer 11 absorbs the sample reagent, while achieving convenient and rapid extraction of the sample reagent, it is also not easy to cause pollution to the surface of the microfluidic chip 401, thereby improving the sample extraction and collection efficiency.

[0060] The present invention not only reduces the overflow during sample introduction by setting up the collection plate 402 and the anti-overflow plate 403, but also facilitates the collection of overflowed and drawn-out sample reagents, reduces the difficulty of sample drawing, improves the sample drawing efficiency, reduces the contamination of the sample on the surface of the microfluidic chip 401, and improves the sample detection efficiency.

[0061] The above is only a preferred specific implementation manner of the present invention; but the protection scope of the present invention is not limited thereto; any technician familiar with the technical field within the technical scope disclosed by the present invention; any equivalent replacement or change based on the technical solution and improved concept of the present invention shall be covered by the protection scope of the present invention.

Claims

1. A microfluidic impedance-type biological online detection device, comprising a host (1), an impedance analyzer (2), a multiplexer (3) and a detection body (4), wherein the host (1) is connected to the impedance analyzer (2), the impedance analyzer (2) is connected to the multiplexer (3), and the multiplexer (3) is connected to the detection body (4), characterized in that: The detection body (4) comprises a microfluidic chip (401), a collection plate (402) and an anti-overflow plate (403) which are arranged in sequence from top to bottom. The upper end of the microfluidic chip (401) is fixedly connected with an inlet pipe (6) and an outlet pipe (7). The insides of the inlet pipe (6) and the outlet pipe (7) are fixedly connected with a one-way valve (8). The collection plate (402) is provided with an inlet (9) and an outlet (10). The inlet pipe (6) matches the inlet (9), and the outlet pipe (7) matches the outlet (10). ), the upper end of the collecting plate (402) is fixedly connected to a main absorption layer (11), the main absorption layer (11) is located on the outside of the outlet (10), the upper end of the anti-overflow plate (403) is fixedly connected to an amplification tube (12), the amplification tube (12) is communicated with the introduction tube (6), the interior of the amplification tube (12) is fixedly connected to a sealing film (13), the upper end of the anti-overflow plate (403) is fixedly connected to a secondary absorption layer (14), the secondary absorption layer (14) is located on the outside of the amplification tube (12); The lower ends of the collecting plate (402) and the anti-overflow plate (403) are fixedly connected with a mucous membrane (15), the mucous membrane (15) is made of a PET sticky film, the main absorption layer (11) and the secondary absorption layer (14) both include a water-absorbing resin layer and a nano-absorption layer, the nano-absorption layer is located on the upper side of the water-absorbing resin layer, and the nano-absorption layer is formed by a mixture of nano-zinc oxide and nano-silicon dioxide; The method for using the above-mentioned microfluidic impedance-type biological online detection device is as follows: S1. A person skilled in the art uses wires to connect the host (1), the impedance analyzer (2), the multiplexer (3) and the detection subject (4) to each other, thereby connecting the detection circuits; S2. Collect an appropriate amount of the biological sample reagent to be detected by using a syringe, then insert the needle into the amplification tube (12) until the sealing film (13) is pierced, and the needle penetrates the sealing film (13) and extends into the inner side of the amplification tube (12), and injects the biological sample reagent to be detected into the microfluidic chip (401); S3. After the sample injection is completed, the needle is removed, and the anti-overflow plate (403) contaminated with the biological sample reagent to be tested is torn off from the collection plate (402), and then the sample is tested; S4. After the detection is completed, the biological sample reagent flows out from the outlet tube (7) and is adsorbed on the main absorption layer (11). After all the biological sample reagents are drawn out, the collection plate (402) is torn off the microfluidic chip (401) to collect the biological sample reagents.

2. A microfluidic impedance-based biological online detection device according to claim 1, characterized in that: A base (5) is provided on the lower side of the detection body (4), a groove (501) is provided on the upper end of the base (5), and the microfluidic chip (401) is fixedly connected inside the groove (501).

3. The microfluidic impedance-based biological online detection device according to claim 1, characterized in that: The microfluidic chip (401) is provided with a sample addition chamber (16), a pre-treatment chamber (17), a reaction chamber (18), a detection chamber (19) and a storage chamber (20) inside.

4. The microfluidic impedance-based biological online detection device according to claim 3, characterized in that: A microfluidic channel (21) is connected between the sample adding chamber (16), the pre-treatment chamber (17), the reaction chamber (18), the detection chamber (19) and the storage chamber (20).

5. The microfluidic impedance-based biological online detection device according to claim 4, characterized in that: A microvalve (22) is provided in the microchannel (21).

6. The microfluidic impedance-based biological online detection device according to claim 3, characterized in that: The sample adding chamber (16) is in communication with the introduction tube (6), and the storage chamber (20) is in communication with the outlet tube (7).

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