Polymer material micro-fluidic chip for biochemical color development detection

Abstract

The invention provides a micro-fluidic chip for biochemical color development detection. The invention provides a micro-fluidic chip for biochemical color development detection and a manufacturing method of the micro-fluidic chip, aiming at the problems of relatively weak mixing efficiency, single application scene and relatively tedious manufacturing of a common micro-fluidic chip. The chip is provided with a flow channel, and the flow channel comprises a liquid inlet part and a liquid mixing part; the liquid inlet part comprises two liquid inlet sections, and liquid to be detected and a reagent are respectively introduced into the two liquid inlet sections; the liquid mixing part comprises a drainage section, a turbulent flow section and a mixed flow section, and liquid is led into the mixed flow section and the conflux channel through the drainage section to be mixed. The micro-fluidic chip can be conveniently and effectively produced by using a COC material, adopting a production method of producing a thin sheet by injection molding and adopting photoresist bonding.

Description

Technical Field

[0001] The present invention relates to the field of biochemical detection, and in particular to a microfluidic chip for biochemical colorimetric detection and a manufacturing method thereof. Background Art

[0002] Nowadays, most microfluidic chips are made of glass, which has good biocompatibility and excellent optical properties. However, the bonding of the chip requires the bonding surface to have high flatness and surface affinity, and requires strict surface cleaning, which makes the chip manufacturing process complicated and time-consuming. However, many polymer materials such as PDMS, PP, PMMA, etc. have low chip manufacturing costs and fast processing speeds, and have been widely studied in the application of microfluidic chips.

[0003] In actual biochemical testing, tedious and complex laboratory steps are often required for qualitative analysis, which is not suitable for emergency situations. Microfluidic chip technology is like a fish in water in these emergency situations. Microfluidic chips have many functions, and most biochemical detection microfluidic chips include microfluidic mixing functions. However, the flow channel size of the current microfluidic chips with microfluidic mixing functions is usually in the micron level. It is different from macroscopic fluid mixing that produces turbulence by changing the spatial structure. Because the Re of the flowing fluid in the microscale is very small, the formation of turbulence is curbed, and the two fluids are not easy to mix. There have been some improvements to this problem, such as the Y-channel microfluidic chip that squeezes the two fluids into the mixing channel to enhance the convection effect and thus enhance the mixing effect, and the serpentine channel microfluidic chip, by adding multiple arc channels in the mixing channel, thereby enhancing the convection effect when the liquid is mixed. Although these improvements have achieved some results, the mixing effect is still not enough. Summary of the invention

[0004] One purpose of the present invention is to solve the problem in the prior art that the mixing uniformity and mixing efficiency of microfluidic chips are low, resulting in poor detection effect. The microfluidic chip of the present invention improves the flow mixing efficiency by changing the flow channel structure and thus changing the flow characteristic parameters, thereby improving the problem of poor mixing detection effect of microfluidic chips on the market today.

[0005] Another object of the present invention is to provide a method for manufacturing a microfluidic chip for liquid mixing. The chip manufacturing method of the present invention is convenient and fast to achieve large-scale mass production;

[0006] The technical solution adopted by the present invention to achieve the first technical purpose is: an observation thin area and a flow channel are provided on the chip, and the flow channel includes two liquid inlet parts and a plurality of liquid mixing parts;

[0007] The liquid inlet portion includes two liquid inlet sections for respectively introducing two types of fluids;

[0008] The width and depth of the flow channel of the liquid mixing part are 1.0 mm and 0.5 mm respectively, and the cross section of the flow channel is a "thin and tall" rectangle. There is a grid-type structure in the drainage channel, which is a parallelogram with a width and length of 0.5 and 1.15 mm, and is recessed at the bottom of the flow channel;

[0009] The liquid mixing part includes an upper liquid mixing part and a lower liquid mixing part, wherein the upper liquid mixing part and the lower liquid mixing part include a drainage channel, a mixing channel, and a converging channel, wherein the outlet of the drainage channel of the upper liquid mixing part is connected to the inlet of the mixing channel of the upper liquid mixing part, the outlet of the mixing channel of the upper liquid mixing part is connected to the inlet of the drainage channel of the lower liquid mixing part, and the converging channel is located at the bottom of the mixing channel groove;

[0010] The liquid mixing section is composed of two upper liquid mixing sections and two lower liquid mixing sections connected in sequence.

[0011] The above technical solution is specifically as follows: when the two types of fluids in laminar flow flow through the drainage channel, they will flow in the inner and outer channels respectively. Due to the action of centrifugal force, the inner fluid will move to the outer channel, and the liquid will gather more in the outer channel, so that the liquid in the inner channel and the liquid in the outer channel will be squeezed and centrifugally mixed. When flowing through the mixed flow channel, since the speeds of the inner and outer fluids are not consistent, the speed of the outer fluid is faster than that of the inner fluid, and the outer fluid gathers at the micro-convexity first, and the outer fluid is hindered by the flow channel wall at the connection of the micro-convexity (the design here is to change the Peclet number Pe when the fluid is mixed and the inner and outer flow channels The flow velocity and flow direction of the inner fluid) changes the direction and speed of the fluid, and when the inner fluid flows into the micro-convexity, it is squeezed by the outer fluid and accumulates to a certain extent in the upper part of the micro-convexity, while the outer fluid flows into the flow converging channel and the flow mixing channel under the squeeze of the flow channel wall at the micro-convexity and the inner fluid in the upper part of the micro-convexity. The function of the flow converging channel is to squeeze and centrifugally mix the fluids squeezed into the flow converging channel from both sides, and the inner fluid in the upper part of the micro-convexity will flow out from the outlet of the flow mixing channel under the traction of the outer fluid after accumulating to a certain extent, thereby promoting the mixing of the fluids on both sides of the flow mixing channel.

[0012] The observation thin area is a small concave area located on the cover plate, and its thickness is smaller than that of the cover plate. The biochemical color development test results can be viewed through the observation thin area to reduce the interference of the cover plate thickness on the results;

[0013] The above technical solution is specifically that after the liquid to be tested is mixed in the liquid mixing part, the liquid to be tested flows into the detection pool, and the detection result is viewed through the observation thin area of ​​the cover plate, or an optical fiber or other detection equipment is externally connected to the observation thin area. The thickness of the observation thin area is smaller than that of the cover plate, which can effectively reduce the influence of irrelevant factors on the results.

[0014] The manufacturing method comprises the following steps: 1) manufacturing a set of one-mold two-cavity molds, and setting molding spaces for the cover plate and the flow channel layer in the set of molds, wherein the two cavities are the molding cavities for the cover plate and the flow channel layer, respectively, and using COC material for injection molding. The good optical properties of the material can accurately feedback the detection results in real time. 2) firstly cleaning each thin slice in an ultrasonic cleaning machine for 150 seconds, and drying it in a vacuum drying oven at 70°C for 30 minutes, and then using cyclopentanone to dilute the SU-8 photoresist in a certain proportion, and coating it on the contact surface between the cover plate and the flow channel layer, using a mask plate with a flow channel shape pattern for shielding, and using 365nm ultraviolet light to irradiate and cure the SU-8, and obtain a microfluidic chip for biochemical color development detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A three-dimensional diagram of the chip of the present application;

[0016] Figure 2 This is a schematic diagram of the structure of the flow channel of the chip of this application;

[0017] Figure 3 This is a schematic diagram of the enlarged structure of the liquid mixing channel of the chip of the present application;

[0018] Figure 4 This is a schematic diagram of the core structure of the chip of this application;

[0019] Description of reference numerals: 1 cover plate, 2 flow channel layer, 3 liquid inlet hole, 4 liquid outlet hole, 5 observation thin area, 6 flow channel;

[0020] 7 liquid inlet flow channel, 8 liquid mixing part, 9 detection tank;

[0021] 10 drainage channel, 11 grid structure, 12 upper liquid mixing portion, 13 flow converging channel, 14 lower liquid mixing portion; Specific implementation plan

[0022] The following is a further explanation in conjunction with the accompanying drawings. In order to avoid confusion or blurring the focus of this application, some specific details will be omitted in the description. Based on the embodiments of the present invention, all other implementation methods obtained by ordinary technicians in this field without making any creative work are within the scope of protection of the present invention.

[0023] The liquid to be detected and the reagent enter the flow channel (6) of the flow channel layer (2) from the flow channel through the two liquid inlet holes (3), flow through the liquid inlet flow channel, and flow into the drainage channel (10) of the mixing part (8). When passing through the grid structure (11), the two-phase liquid will be affected by the stagnation effect of the grid structure, which promotes the initial mixing of the two liquids, so that when the two types of fluids in laminar flow flow through the drainage channel, they will flow in the inner and outer channels respectively. Due to the effect of centrifugal force, the inner side fluid will move to the lower mixing part (14), and the liquid will gather more in the upper mixing part (12), so that the liquid in the inner channel and the liquid in the outer channel will be squeezed and centrifuged and mixed, and the outer fluid will be affected by the micro-flow. The obstruction of the flow channel wall at the convex connection causes the direction and speed of the fluid to change. When the inner fluid flows into the micro-convex part, it is squeezed by the outer fluid and accumulates to a certain extent in the upper part of the micro-convex part. The outer fluid will flow into the flow converging channel (13) and the flow mixing channel (15) under the squeezing of the flow channel wall at the micro-convex part and the inner fluid in the upper part of the micro-convex part. The function of the flow converging channel is to squeeze and centrifugally mix the fluids squeezed into the flow converging channel from both sides. After accumulating to a certain extent, the inner fluid in the upper part of the micro-convex part will flow out from the outlet of the flow mixing channel (15) under the traction of the outer fluid, thereby promoting the mixing of the fluids on both sides of the flow mixing channel.

[0024] After the liquid is uniformly mixed and reacted in the mixing section, it flows into the detection pool (9) at the tail of the microfluidic chip. The experimental results can be observed from the outside of the chip, and a large portion of the liquid will remain in the detection pool. The detection results can be observed through the observation thin curve (5) of the cover plate, and then the waste liquid flows out from the liquid outlet (4).

[0025] Make a set of one-mold two-cavity molds, the core of which is as follows Figure 4 As shown, the mold is provided with molding spaces for the cover plate and the runner layer respectively, and the two cavities are molding cavities for the cover plate and the runner layer respectively. The cover plate and the runner layer sheet can be obtained by one-time injection molding. COC material is used for injection molding. The good optical properties of this material can accurately feedback the detection results in real time.

[0026] First, each thin slice was cleaned in an ultrasonic cleaner for 150 seconds and dried in a vacuum drying oven at 70°C for 30 minutes. Then, SU-8 photoresist was diluted with cyclopentanone in a certain proportion and coated on the contact surface between the cover plate and the flow channel layer. A mask plate with a flow channel shape pattern was used for masking, and 365nm ultraviolet light was used to irradiate and cure SU-8 to obtain a microfluidic chip for biochemical colorimetric detection.

Claims

1. A microfluidic chip for biochemical colorimetric detection, characterized in that: The chip comprises a cover plate (1) and a flow channel layer (2) which are arranged in sequence from top to bottom, and the layers are connected and fixed up and down by an adhesive; The cover plate (1) is provided with a liquid inlet hole (3), an observation thin area (5) and a liquid outlet hole (4); the observation thin area is a relatively thin area on the cover plate and is arranged opposite to the detection pool (9); (the thin area is arranged here to reduce the influence of the thickness of the cover plate on the biochemical colorimetric detection result) the flow channel layer (2) is provided with a liquid inlet part (7), a liquid mixing part (8) and a detection pool (9) which are connected in sequence, the liquid inlet part (2) is connected to the liquid inlet hole (3), and the detection pool (9) is connected to the liquid outlet hole (4); the liquid inlet part (2) includes a liquid inlet flow channel; the liquid mixing part includes an upper liquid mixing part (12 ) and a lower liquid mixing portion (14) and a flow converging channel (13), the upper liquid mixing portion and the lower liquid mixing portion having the same structure and being arranged in a mirror image, the upper liquid mixing portion (14) comprising a drainage channel (10) and a flow mixing channel (15), a grid structure (11) being designed in the drainage channel (10), the drainage channel (10) being connected to the flow mixing channel (15), the flow mixing channel (15) being connected to the next drainage channel, the flow converging channel flowing through the upper liquid mixing portion and the lower liquid mixing portion and connecting the two drainage channels; the upper portion of the detection pool (9) corresponds to the lower surface of the observation thin area (5) of the cover plate (1).

2. A microfluidic chip for biochemical colorimetric detection according to claim 1, characterized in that: The drainage channel is arc-shaped and is divided into inner and outer channels; a micro-convex connection is provided in the mixing channel so that the fluid can be mixed evenly in the mixing channel.

3. A microfluidic chip for biochemical colorimetric detection according to claim 1, characterized in that: A grid structure is designed in the drainage channel, and the structure is used to promote liquid mixing.

4. A microfluidic chip for biochemical colorimetric detection according to claim 1, characterized in that: The liquid mixing part has a converging channel, which runs from the upper drainage channel to the next drainage channel. The converging channel is characterized by a flat rectangular cross-section, which is curved as a whole and arranged in parallel with the liquid mixing part as a whole.

5. A microfluidic chip for biochemical colorimetric detection according to claim 1, characterized in that: The liquid mixing part is composed of an upper liquid mixing part and a lower liquid mixing part, and the structural features of the two are mirror-symmetrical, and the outlet of the upper liquid mixing part is connected to the inlet of the lower liquid mixing part.

6. A microfluidic chip for biochemical colorimetric detection according to claim 1 or 4, characterized in that: The thickness of the cover plate is 1.0 mm, and the thickness of the flow channel layer is 2.0 mm. There are 2 liquid inlets, 1 observation thin area and 1 liquid outlet on the cover plate. The aperture of the liquid inlet is 1.0 mm, the diameter and depth of the observation thin area are 1.6 mm and 0.5 mm respectively, and the aperture of the liquid outlet is 1.0 mm; the width and depth of the liquid inlet flow channel are 1.2 mm and 0.5 mm respectively, the width and depth of the flow channel of the liquid mixing part are 1.0 mm and 0.5 mm respectively, and the aperture of the detection pool is 1.0 mm.

7. A microfluidic chip for biochemical colorimetric detection according to claim 1 or 5, characterized in that: The observation thin area arranged on the cover plate has a thickness smaller than that of the cover plate, and the biochemical color development test result can be viewed through the observation thin area, thereby reducing the interference of the cover plate thickness on the result.

8. A microfluidic chip for biochemical colorimetric detection according to claim 1, characterized in that: The production method comprises the following steps: 1) Make a set of one-mold two-cavity molds, and set the molding spaces of the cover plate and the runner layer in the mold respectively. The two cavities are the molding cavities of the cover plate and the runner layer respectively. Use COC (cyclic olefin copolymer) material for injection molding. The good optical properties of this material can accurately feedback the test results in real time. 2) Each thin slice was first cleaned in an ultrasonic cleaner for 150 seconds and dried in a vacuum drying oven at 70°C for 30 minutes. Then, SU-8 was coated on the contact surface between the cover plate and the flow channel layer, and 365nm ultraviolet light was used to irradiate and cure SU-8 to obtain a microfluidic chip for biochemical colorimetric detection.

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