Microfluidic structure for high viscosity liquid immunoassays

Abstract

A microchannel structure for high-viscosity liquid immunoreaction includes a microchannel with an inlet at one end and an outlet at the other end. Several tortuous turbulence structures are spaced apart along the flow direction on both the bottom and top surfaces of the microchannel. The height of each tortuous turbulence structure increases sequentially along the flow direction. Each tortuous turbulence structure includes several interconnected baffles, each baffle tilted towards the substrate where the inlet is located, and each baffle forming an angle of 25°–60° with either the bottom or top surface of the microchannel. Several secondary baffles are spaced apart on the sides of each tortuous turbulence structure. The unequal angles of the baffles on the bottom and top surfaces of the microchannel create an asymmetric turbulence structure, breaking the symmetrical flow field, enhancing local vortices, and the secondary baffles forming turbulence branches, increasing the fluid contact area and improving the diffusion efficiency of the high-viscosity fluid.

Description

Technical Field

[0001] This invention relates to the field of physics, and more particularly to microfluidic technology for immune responses to high-viscosity liquids (such as leukocyte collection fluid, high-concentration cell suspensions, etc.), and especially to a microchannel structure for immune responses to high-viscosity liquids. Background Technology

[0002] Microfluidics is the science and technology involved in systems that use microchannels (tens to hundreds of micrometers in size) to process or manipulate tiny fluids (volumes ranging from nanoliters to picoliters). It encompasses chemistry, fluid physics, microelectronics, new materials, biology, and biomedical engineering. In practical applications, microfluidics integrates basic operational units of biological, chemical, and medical analysis processes—such as sample preparation, reaction, separation, and detection—onto a chip of just a few square centimeters, automating the entire analytical process. Its fundamental characteristic and greatest advantage lies in the flexible combination and large-scale integration of multiple unit technologies on a controllable micro-platform.

[0003] In existing technologies, traditional fishbone-shaped microchannel designs are designed for low-viscosity fluids (such as aqueous solutions), and their mixing efficiency depends on laminar diffusion. However, they are not effective in mixing high-viscosity liquids during immune reactions. High-viscosity fluids have high resistance and slow flow rates, which leads to a significant decrease in mixing efficiency and makes them prone to clogging within the microchannels. In particular, during immune reactions, the aggregation or non-specific adsorption of biomolecules (such as antibodies and antigens) further exacerbates the non-uniformity of flow. Summary of the Invention

[0004] The purpose of this invention is to provide a microchannel structure for immune reactions of high-viscosity liquids, thereby solving the technical problem of low mixing efficiency of existing microchannel structures in immune reactions of high-viscosity liquids.

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

[0006] A microfluidic structure for high-viscosity liquid immunoassay includes a substrate with microchannels disposed therein. One end of each microchannel has an inlet, and the other end has an outlet. On the bottom and top surfaces of the microchannel, between the inlet and outlet, several tortuous flow-disrupting structures are spaced apart along the flow direction. These tortuous flow-disrupting structures extend in a tortuous manner from the front to the rear of the microchannel, with their heights increasing sequentially along the flow direction. Any one of the tortuous flow-disrupting structures... Each of the zigzag turbulence structures includes several turbulence plates connected end to end. Each turbulence plate is inclined toward the substrate where the liquid inlet is located. Each turbulence plate forms an inclination angle of 25°-60° with the bottom or top surface of the microchannel. The inclination angle of the turbulence plate on the bottom surface of the microchannel is greater than or less than the inclination angle of the turbulence plate on the top surface of the microchannel. Each of the zigzag turbulence structures has several secondary turbulence plates spaced apart on its side. The length direction of the secondary turbulence plates is parallel to the flow direction of the microchannel.

[0007] Furthermore, the tilt angle of the spoiler is 35°-50°.

[0008] Furthermore, the tilt angle of the baffle plate on the bottom surface of the microchannel is 45°, and the tilt angle of the baffle plate on the top surface of the microchannel is 30°.

[0009] Furthermore, the ratio of the length of the secondary spoiler to the length of the main spoiler is in the range of 1 / 5 to 1 / 3.

[0010] Furthermore, the height of the tortuous turbulence structure near the inlet of the microchannel is 10 μm, and the height of the tortuous turbulence structure near the outlet of the microchannel is 25 μm.

[0011] Furthermore, the inner wall of the microchannel is provided with alternating hydrophilic and hydrophobic layers.

[0012] Compared with existing technologies, the effects of this invention are positive and significant. Inclining the baffle towards the inlet is more effective for vortex formation than tilting it towards the outlet. The unequal inclination angles of the baffles on the bottom and top surfaces of the microchannel create an asymmetric turbulence structure, breaking the symmetrical flow field, enhancing local vortices, and forming secondary baffle branches to increase the fluid contact area and improve the diffusion efficiency of high-viscosity fluids. Simultaneously, the tortuous height gradient of the turbulence structure reduces initial flow resistance at the inlet, preventing a sharp increase in pressure drop, and enhances shear disturbance at the outlet, compensating for the decrease in mixing efficiency caused by increased viscosity. This achieves efficient mixing of low Reynolds number (Re<1) fluids under high viscosity conditions, making it suitable for high-viscosity (5mPa·s-200mPa·s) liquid environments, improving mixing efficiency while reducing the risk of clogging and extending device lifespan. Attached Figure Description

[0013] Figure 1 This is a top view of the bottom surface of a microchannel structure for high-viscosity liquid immune reactions according to the present invention.

[0014] Figure 2 This is a three-dimensional schematic diagram of the bottom surface of a microchannel structure for high-viscosity liquid immune reactions according to the present invention. Detailed Implementation

[0015] The present invention will be further described below with reference to embodiments, but the present invention is not limited to these embodiments. Any similar variations of the present invention should be included within the scope of protection of the present invention. The use of directions such as up, down, front, back, left, right, center, inside, and outside in the present invention is only for the convenience of clear description and is not intended to limit the technical solution of the present invention.

[0016] like Figures 1-2 As shown, this invention provides a microchannel structure for high-viscosity liquid immunoreaction, including a substrate, in which microchannels are disposed. An inlet 1 is located at the left end of the microchannel, and an outlet 2 is located at the right end. On the bottom and top surfaces of the microchannel, between the inlet 1 and the outlet 2, several tortuous flow-disrupting structures 3 are spaced apart along the flow direction. The tortuous flow-disrupting structures 3 extend from the front side of the microchannel to the rear side in a tortuous manner, and the height of the tortuous flow-disrupting structures 3 increases sequentially along the flow direction of the microchannel. Any one of the tortuous flow-disrupting structures... Each of the tortuous flow-disrupting structures 3 includes several flow-disrupting plates 4 connected end to end. Each flow-disrupting plate 4 is inclined towards the substrate side where the liquid inlet 1 is located. Each flow-disrupting plate 4 forms an inclination angle of 25°-60° with the bottom or top surface of the microchannel. The inclination angle of the flow-disrupting plate 4 on the bottom surface of the microchannel is greater than or less than the inclination angle of the flow-disrupting plate 4 on the top surface of the microchannel. Each of the tortuous flow-disrupting structures 3 has several secondary flow-disrupting plates 5 spaced apart on its side. The length direction of the secondary flow-disrupting plates 5 is parallel to the flow direction of the microchannel.

[0017] Working principle:

[0018] The baffle 4 is tilted towards the substrate side where the inlet 1 is located, and towards the substrate side where the outlet 2 is located, resulting in better vortex formation. The inclination angles of the baffles 4 on the bottom and top surfaces of the microchannel are not equal, forming an asymmetric baffle structure, breaking the symmetrical flow field, enhancing local vortices, and the secondary baffle 5 forms baffle branches, increasing the fluid contact area and improving the diffusion efficiency of high-viscosity fluids. At the same time, the height gradient of the tortuous baffle structure 3 is set to reduce the initial flow resistance at the inlet 1 and avoid a sharp increase in pressure drop, and to enhance shear disturbance at the outlet 2 to compensate for the decrease in mixing efficiency caused by the increase in viscosity. Thus, it can achieve efficient mixing of low Reynolds number (Re<1) fluids under high viscosity conditions, and is suitable for high viscosity (5mPa·s-200mPa·s) liquid environments, improving mixing efficiency while reducing the risk of clogging and extending device life.

[0019] Furthermore, the tilt angle of the spoiler 4 is 35°-50°.

[0020] Furthermore, the tilt angle of the baffle 4 on the bottom surface of the microchannel is 45°, and the tilt angle of the baffle 4 on the top surface of the microchannel is 30°.

[0021] Furthermore, the ratio of the length of the secondary spoiler 5 to the length of the spoiler 4 is in the range of 1 / 5 to 1 / 3.

[0022] Furthermore, the height of the tortuous turbulence structure 3 near the inlet 1 of the microchannel is 10 μm, and the height of the tortuous turbulence structure 3 near the outlet 2 of the microchannel is 25 μm.

[0023] Furthermore, the inner wall of the microchannel is provided with alternating hydrophilic and hydrophobic layers, which can reduce the adsorption of biomolecules and prevent clogging. Implementation method: Polyethylene glycol is locally modified on a PDMS (polydimethylsiloxane) substrate, with PDMS as the hydrophobic layer and polyethylene glycol as the hydrophilic layer.

[0024] Specifically, the specific structures and principles of the hydrophilic layer, hydrophobic layer, PDMS (polydimethylsiloxane), and polyethylene glycol in this invention, as well as other aspects not described in detail, all adopt well-known solutions in the prior art, which are already understood by those skilled in the art and will not be elaborated here.

[0025] Example 1: Microchannel for CRP detection in blood.

[0026] Processing technology:

[0027] The mold was fabricated on the silicon wafer using SU-8 photoresist. The asymmetric tilt angle of the spoiler 4 was 40° at the top and 55° at the bottom. The secondary spoiler 5 had a length of 50 μm and a height gradient of 10 μm → 20 μm.

[0028] The inner wall is modified with a polyethylene glycol (PEG) coating by PDMS molding bonding.

[0029] Performance testing:

[0030] Fluorescently labeled antibodies were injected into whole blood samples (viscosity ~8 mPa·s), and the mixing homogeneity was observed using a confocal microscope.

[0031] The results showed that, compared with existing technologies, the mixing efficiency was improved by 62%, and the coefficient of variation (CV) of the detection signal was reduced from 15% to 6%.

[0032] Example 2: Formation of immune complexes in polymer solutions.

[0033] Application scenario: Detection of IgG antigen in polymer solutions.

[0034] Parameter optimization: The bump height gradient was adjusted from 15μm to 25μm to adapt to PEG solutions with a viscosity of 50mPa·s.

[0035] Results: Reaction time was reduced by 40%, and nonspecific adsorption was reduced by 30%.

Claims

1. A microfluidic structure for immunoreaction with high-viscosity liquids, characterized in that, The system includes a substrate with microchannels. One end of each microchannel has an inlet, and the other end has an outlet. On both the bottom and top surfaces of the microchannels, between the inlet and outlet, several zigzag turbulence structures are spaced apart along the flow direction. These zigzag turbulence structures extend from the front to the rear of the microchannel in a zigzag pattern, with their heights increasing sequentially along the flow direction. Each zigzag turbulence structure includes several interconnected baffles. Each baffle is inclined towards the substrate side where the inlet is located, and each baffle forms an angle of 25°-60° with either the bottom or top surface of the microchannel. The angle of inclination of the baffles on the bottom surface of the microchannel is greater or less than the angle of inclination of the baffles on the top surface of the microchannel. Each of the tortuous flow-disrupting structures has several secondary flow-disrupting plates spaced apart on its side. The secondary flow-disrupting plates are located on the side of the tortuous flow-disrupting structure facing the liquid inlet, and the length direction of the secondary flow-disrupting plates is parallel to the flow direction of the microchannel.

2. The microfluidic structure for high-viscosity liquid immune reactions according to claim 1, characterized in that: The tilt angle of the spoiler is 35°-50°.

3. The microfluidic structure for high-viscosity liquid immune reactions according to claim 1, characterized in that: The tilt angle of the baffle plate on the bottom surface of the microchannel is 45°, and the tilt angle of the baffle plate on the top surface of the microchannel is 30°.

4. The microfluidic structure for high-viscosity liquid immune reactions according to claim 1, characterized in that: The ratio of the length of the secondary spoiler to the length of the main spoiler is in the range of 1 / 5 to 1 / 3.

5. A microfluidic structure for high-viscosity liquid immune reactions according to claim 1, characterized in that: The height of the tortuous turbulence structure near the inlet of the microchannel is 10 μm, and the height of the tortuous turbulence structure near the outlet of the microchannel is 25 μm.

6. A microfluidic structure for high-viscosity liquid immune reactions according to claim 1, characterized in that: The inner wall of the microchannel is provided with alternating hydrophilic and hydrophobic layers.

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