CN217112075U

CN217112075U - Microfluidic biochip card for NanoSPR detection

Info

Publication number: CN217112075U
Application number: CN202123209766.5U
Authority: CN
Inventors: 黄丽萍; 刘钢; 王易
Original assignee: Liangzhun Shanghai Medical Devices Co ltd
Current assignee: Liangzhun Shanghai Medical Devices Co ltd
Priority date: 2021-12-20
Filing date: 2021-12-20
Publication date: 2022-08-02
Anticipated expiration: 2031-12-20

Abstract

The utility model discloses a micro-fluidic biological chip card for detecting NanoSPR, which belongs to the technical field of NanoSPR plasma resonance; the structure of the device comprises a bottom plate, wherein a flow channel is arranged on the bottom plate, a sample adding pool and a waste liquid pool are respectively arranged at two ends of the flow channel, and the depth of the sample adding pool is greater than that of the flow channel; a chip groove is arranged in the middle of the flow channel, and a biological chip is placed in the chip groove; the bottom plate is also provided with a through hole, and the position of the through hole corresponds to the chip groove; the surface sealing laminating of runner and waste liquid pond has hydrophilic membrane, the waste liquid pond is equipped with water absorbing material. The utility model provides a micro-fluidic biological chip card, which has simple structure and convenient sample adding, and does not need to additionally use an injector and a flow pump for sample adding; can be used for researching the interaction between biological molecules, detecting or controlling the quality of a specific antibody, disease mechanism, screening drugs, monitoring pharmacokinetics, fishing ligands, regulating immunity, identifying structure-function relationship, epitope and other fields.

Description

Microfluidic biochip card for NanoSPR detection

Technical Field

The utility model belongs to the technical field of the resonance of NanoSPR plasma, especially a micro-fluidic biological chip card for NanoSPR detects.

Background

Microfluidic Surface Plasmon Resonance (SPR) is commonly used in a variety of biochemical detection methods. The SPR technique does not require exogenous labeling of the sample and can also be used to measure biochemical reaction kinetics, thus obtaining affinity and thermodynamic parameters. The working detection principle of most of the SPR systems based on microfluidic flow cells currently in use is: the sample is transferred to the flow cell by an injection or pulling method by using an automatic sampler, reacts with a Microfluidic Chip (Microfluidic Chip) in the flow cell, and is then put into an instrument such as a microplate reader for detection.

For example, the chinese granted patent CN213875425U provides a biosensor cartridge and a biosensor device, in which one or more flow cells, a sensor chip and a sampler are integrated together to form an independent biosensor cartridge which can be conveniently detached and replaced, and the biosensor cartridge can be replaced after testing, thereby overcoming the problems of complex structure and the like of the existing biosensor analytical instrument based on surface plasmon resonance, improving the working efficiency and reducing the use cost. However, the analysis cartridge and the related devices also need to be matched with other devices and instruments such as a syringe, a flow pump and the like to realize the flow of the sample in the flow channel and the flow cell, so that the analysis cartridge and the related devices are inconvenient to carry and use; and the combined contact area of the sample liquid and the sensor chip is limited, which is not favorable for obtaining the detection accuracy and the sensitivity is limited.

Disclosure of Invention

In order to solve the problems of the prior art, the utility model provides a micro-fluidic biological chip card for nanoSPR detection, which is realized by the following technical scheme.

The microfluidic biochip card for detecting the NanoSPR comprises a bottom plate, wherein a flow channel is arranged on the bottom plate, a sample adding pool and a waste liquid pool are respectively arranged at two ends of the flow channel, and the depth of the sample adding pool is greater than that of the flow channel; a chip groove is arranged in the middle of the flow channel, and a biological chip is placed in the chip groove; the bottom plate is also provided with a through hole, and the position of the through hole corresponds to the chip groove; the surface sealing laminating of runner and waste liquid pond has hydrophilic membrane, the waste liquid pond is equipped with water absorbing material.

The application method of the microfluidic biochip card comprises the following steps: dropwise adding a sample or reagent liquid into the sample adding pool, allowing the liquid to flow into the flow channel and flow into the chip groove along the flow channel under the guiding action of the hydrophilic membrane and the capillary action of the flow channel, and contacting with the biochip and infiltrating the surface of the biochip to start reaction; the liquid continues to flow along the flow channel towards the waste liquid pool and is absorbed by the water absorbing material in the waste liquid pool.

The liquid in the microfluidic biochip card can flow mainly by means of the hydrophilic action of the hydrophilic membrane and the active driving action of the capillary action of the flow channel. The hydrophilic membrane can be made of common materials, for example, finished products (products of the company such as Desha/TESA) can be directly purchased, and the hydrophilic membrane is generally adhered to the bottom plate by using waterproof double-sided adhesive (such as 3M waterproof double-sided adhesive) so as to seal and isolate the flow channel and the chip groove from the outside; certainly, the hydrophilic film can be pasted by coating waterproof glue with low fluidity, but the surface of the hydrophilic film is smooth after pasting. The water-absorbing material can be common water-absorbing paper or sponge and other materials. In order to slow down the velocity of flow of liquid, set the degree of depth of application of sample pond to being greater than the degree of depth of runner, guarantee only add a quantitative liquid in the application of sample pond after, just can spill over the application of sample pond and slowly flow into in the runner.

Preferably, the bottom surface of the sample addition cell is a slope inclined toward the flow channel. As a first setting mode of the sample adding pool, the purpose of slowing down the flow speed of liquid can be met by utilizing the inclined plane.

Preferably, the sample adding pool comprises an overflow area and a sample adding area, the overflow area is communicated with the flow channel, the depth of the overflow area is the same as that of the flow channel, and the depth of the sample adding area is greater than that of the flow channel. As a second arrangement mode of the sample adding pool, a mode of arranging an overflow area in a step shape is adopted, liquid is added into the sample adding area, and the liquid overflows and then enters the overflow area and then flows into the flow channel.

Preferably, the sample adding pool is communicated with the flow channel through a connecting channel, and the bottom surface of the connecting channel is an inclined surface inclined towards the flow channel. The connecting channel is also arranged to prolong the flowing distance of the sample adding liquid and slow down the flow speed.

More preferably, the connecting channel has a smooth curve structure.

Preferably, the waste liquid pool is provided with a vent hole. The purpose of the vent hole is to ensure that liquid normally flows in the flow channel, so that air in the flow channel and the chip groove can be conveniently discharged.

Preferably, the flow channels are distributed on the bottom plate in a U shape. The flow channel is arranged in a U shape, so that the length of the flow channel is prolonged, the flowing time and the flowing speed of the liquid in the flow channel are increased, and the purpose of accommodating more liquid is realized.

Preferably, the flow channel comprises a main flow channel and 2 secondary flow channels, the 2 secondary flow channels are arranged on two sides of the main flow channel, and the chip groove is positioned on the main flow channel; the sample adding pool is positioned at one end of the main flow channel, 2 auxiliary flow channels are respectively connected at the other end of the main flow channel, and a waste liquid pool is arranged at the tail end of each auxiliary flow channel. The main runner and the 2 auxiliary runners form an M-shaped structure, the main runner is in the middle, and the 2 auxiliary runners are on two sides of the main runner. After the liquid flows into the main flow channel and reacts with the biochip, the waste liquid is divided into two paths along 2 secondary flow channels and flows into corresponding waste liquid pools.

Preferably, the inlet and the outlet of the chip groove connected with the flow channel are both in a horn structure. The chip groove and the runner are connected by an inlet and an outlet. The inflow port is arranged in a horn shape, so that the inflowing liquid can be spread out to infiltrate all areas of the biochip, and the liquid is prevented from flowing out of the chip groove only in the middle area of the biochip to affect the detection effect. The outflow port is arranged to be horn-shaped, so that dead angles can be reduced, air bubbles in the flow channel and the chip groove can be completely extruded, and the influence of the air bubbles on the refraction or reflection effect of light emitted by the probe is avoided.

Preferably, the bottom plate is of a sandwich structure, a water absorbing material is arranged in the sandwich structure, and the waste liquid pool is communicated with the water absorbing material. The water absorbing material (such as water absorbing paper) is arranged in the interlayer of the bottom plate, and the waste liquid pool is communicated with the water absorbing material, so that more waste liquid can be absorbed.

Compared with the prior art, the beneficial effects of the utility model are that: the microfluidic biochip card is simple in structure and convenient to sample, and a syringe and a flow pump are not required to be additionally used for sample adding; can be used for researching the interaction process between various biological molecules (such as polypeptide, protein, oligonucleotide, virus, bacteria and small molecule compound); specific antibody detection or quality control, disease mechanism and drug screening; the method belongs to the technical field of relevant pharmacokinetics real-time monitoring, ligand fishing, immunoregulation, structure-function relation, epitope identification and the like.

Drawings

FIG. 1 is a front view of a microfluidic biochip card;

FIG. 2 is a cross-sectional view of a microfluidic biochip card of a first preferred configuration;

FIG. 3 is a cross-sectional view of a microfluidic biochip card of a second preferred configuration;

FIG. 4 is a front view of a microfluidic biochip card of a third preferred configuration;

FIG. 5 is a front view of a microfluidic biochip card of a fourth preferred configuration;

FIG. 6 is a front view of a microfluidic biochip card of a fifth preferred configuration;

FIG. 7 is a front view of a flow channel and chip groove part of a microfluidic biochip card with a sixth preferred structure;

FIG. 8 is a cross-sectional view of a seventh preferred configuration of a microfluidic biochip card;

in the figure: 1. a base plate; 2. a flow channel; 201. a main flow channel; 202. a secondary flow passage; 3. a sample adding pool; 301. an overflow area; 302. a sample adding area; 4. a waste liquid tank; 5. a chip slot; 6. a biochip; 7. a through hole; 8. a hydrophilic membrane; 9. a connecting channel; 10. a vent hole; 11. absorbent paper.

Detailed Description

The technical solutions of the embodiments in this patent will be described clearly and completely with reference to the accompanying drawings, and it is obvious that the described embodiments are only some embodiments, not all embodiments, of this patent. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the patent without making creative efforts, shall fall within the protection scope of the patent.

In the description of this patent, it is noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", "top", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience in describing the patent and for simplicity in description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore, should not be construed as limiting the patent. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of this patent, it is noted that, unless expressly stated or limited otherwise, the terms "mounted," "connected," and "communicating" are to be construed broadly, e.g., as meaning fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. It is to be noted that all the figures are exemplary representations. The meaning of the above terms in this patent may be specifically understood by those of ordinary skill in the art.

The patent is described in further detail below by means of specific embodiments and with reference to the attached drawings.

As shown in fig. 1, the microfluidic biochip card for NanoSPR detection provided by the present invention comprises a bottom plate 1, a flow channel 2 is disposed on the bottom plate 1, a sample adding pool 3 and a waste liquid pool 4 are disposed at two ends of the flow channel 2, respectively, and the depth of the sample adding pool 3 is greater than that of the flow channel 2; a chip groove 5 is arranged in the middle of the flow channel 2, and a biochip 6 is placed in the chip groove 5; the bottom plate 1 is also provided with a through hole 7, and the position of the through hole 7 corresponds to the chip groove 5; the surface sealing laminating of runner 2 and waste liquid pond 4 has hydrophilic membrane 8, waste liquid pond 4 is equipped with water absorbing material.

As shown in FIG. 2, the bottom surface of the sample addition well 3 may be preferably provided as a slope inclined toward the flow channel 2. The flow rate of the liquid can be slowed down by the inclined surface.

As shown in fig. 3, as a preferable mode, the sample addition reservoir 3 includes an overflow area 301 and a sample addition area 302, the overflow area 301 is communicated with the flow channel 2, the depth of the overflow area 301 is the same as that of the flow channel 2, and the depth of the sample addition area 302 is greater than that of the flow channel 2. Liquid is added into the sample adding region by adopting a mode of arranging an overflow region in a step shape, and the liquid enters the overflow region after overflowing and then flows into the flow channel.

As shown in fig. 4, it is preferable that the sample addition reservoir 3 and the flow channel 2 communicate with each other through a connection channel 9, the connection channel 9 has a smooth curved structure, and a bottom surface of the connection channel 9 is an inclined surface inclined toward the flow channel 2. The connecting channel is also arranged to prolong the flowing distance of the sample adding liquid and slow down the flow speed.

As shown in fig. 5, the waste liquid tank 4 is preferably provided with a vent hole 10. The purpose of the vent hole is to ensure that liquid normally flows in the flow channel, so that air in the flow channel and the chip groove can be conveniently discharged. The flow channels are distributed on the bottom plate in a U shape. The flow channel is arranged in a U shape, so that the length of the flow channel is prolonged, the flowing time and the flowing speed of the liquid in the flow channel are increased, and the purpose of accommodating more liquid is realized.

As shown in fig. 6, as a preferable mode, the runner 2 includes a

main runner

201 and 2 sub-runners 202, the 2 sub-runners 202 are provided on both sides of the main runner 201, and the chip tray 5 is located in the middle of the main runner 201; the sample adding reservoir 3 is located at one end of the main flow channel 201, the 2 auxiliary flow channels 202 are respectively connected to the other end of the main flow channel 201, and the waste liquid reservoir 4 is arranged at the tail end of the auxiliary flow channel 202. The main runner and the 2 auxiliary runners form an M-shaped structure, the main runner is in the middle, and the 2 auxiliary runners are on two sides of the main runner. After the liquid flows into the main flow channel and reacts with the biochip, the waste liquid is divided into two paths along the 2 secondary flow channels and flows into the corresponding waste liquid pool.

As shown in fig. 7, the inlet and outlet of the chip groove 5 connected to the flow channel 2 are preferably in a trumpet shape. The chip groove and the runner are connected by an inlet and an outlet. The inflow port is arranged in a horn shape, so that inflow liquid can be spread out to infiltrate all areas of the biochip, and the phenomenon that the liquid flows out of the chip groove only when infiltrating the middle area of the biochip to affect the detection effect is avoided. The outflow port is arranged to be horn-shaped, so that dead angles can be reduced, air bubbles in the flow channel and the chip groove can be completely extruded, and the influence of the air bubbles on the refraction or reflection effect of light emitted by the probe is avoided.

As shown in fig. 8, as a preferable mode, the bottom plate 1 is a sandwich structure, and a water absorbent paper 11 is arranged in the sandwich structure, and the waste liquid tank 4 is communicated with the water absorbent paper 11. The water absorption paper is arranged in the interlayer of the bottom plate, and the waste liquid pool is communicated with the water absorption paper, so that more waste liquid can be absorbed.

The above embodiments describe the implementation of the present invention in detail, however, the present invention is not limited to the specific details of the above embodiments. Within the scope of the claims and the technical idea of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

Claims

1. The microfluidic biochip card for detecting the NanoSPR is characterized by comprising a bottom plate, wherein a flow channel is arranged on the bottom plate, a sample adding pool and a waste liquid pool are respectively arranged at two ends of the flow channel, and the depth of the sample adding pool is greater than that of the flow channel; a chip groove is arranged in the middle of the flow channel, and a biological chip is placed in the chip groove; the bottom plate is also provided with a through hole, and the position of the through hole corresponds to the chip groove; the surface sealing laminating of runner and waste liquid pond has hydrophilic membrane, the waste liquid pond is equipped with water absorbing material.

2. The microfluidic biochip card for NanoSPR detection according to claim 1, wherein the bottom surface of the sample application reservoir is a sloped surface inclined toward the flow channel.

3. The microfluidic biochip card for NanoSPR detection according to claim 1, wherein the sample application reservoir comprises an overflow region and a sample application region, the overflow region is in communication with the flow channel, the overflow region has the same depth as the flow channel, and the sample application region has a depth greater than the depth of the flow channel.

4. The microfluidic biochip card for NanoSPR detection according to claim 1, wherein the sample application reservoir is in communication with the flow channel via a connecting channel, and the bottom surface of the connecting channel is an inclined surface inclined toward the flow channel.

5. Microfluidic biochip card for NanoSPR detection according to claim 4, wherein the connecting channels are smoothly curved structures.

6. A microfluidic biochip card for NanoSPR detection according to claim 1, wherein the waste reservoir is provided with a vent.

7. The microfluidic biochip card for NanoSPR detection according to claim 1, wherein the flow channels are distributed in a U-shape on the base plate.

8. The microfluidic biochip card for NanoSPR detection according to claim 1, wherein the flow channel comprises a main flow channel and 2 secondary flow channels, the 2 secondary flow channels are disposed at two sides of the main flow channel, and the chip slot is located on the main flow channel; the sample adding pool is positioned at one end of the main flow channel, 2 auxiliary flow channels are respectively connected at the other end of the main flow channel, and a waste liquid pool is arranged at the tail end of each auxiliary flow channel.

9. The microfluidic biochip card for NanoSPR detection according to claim 1, wherein the inlet and outlet of the chip slot connected to the flow channel are both of a horn structure.

10. A microfluidic biochip card for NanoSPR detection according to any of claims 1-9, wherein the base plate is a sandwich structure, and a water absorbent material is disposed within the sandwich structure, and the waste reservoir is in communication with the water absorbent material.