Micro-fluidic chip based on reflector light path and preparation method of micro-fluidic chip

Abstract

The invention relates to a micro-fluidic chip based on a reflector light path and a preparation method of the micro-fluidic chip. The reflector light path comprises an incident optical fiber channel, an emergent optical fiber channel and a liquid drop flow channel, a first reflecting mirror runner and a second reflecting mirror runner are arranged on the two sides of the liquid drop runner, liquid metal is poured into the first reflecting mirror runner and the second reflecting mirror runner respectively, and then the liquid metal is cooled and solidified to form a first reflecting mirror and a second reflecting mirror. By utilizing a light path formed by multiple reflections, the effective absorption light path is increased, and the detection sensitivity and accuracy are improved; and the liquid drop flow channel is not bent, so that the liquid drops are not damaged, and the compatible liquid drop size range is wide.

Description

Technical Field

[0001] The present invention belongs to the technical field of microfluidics, and particularly relates to a microfluidic chip based on a mirror optical path and a preparation method thereof. Background Art

[0002] Microfluidic technology is a technology for manipulating tiny volumes of liquid in a chip channel at the micron scale. Using this technology, microdroplets with highly monodisperse, highly controllable size and structure can be produced. These microdroplets have been widely used in fields such as drug delivery, biological templates, cell culture, and microreactors. When microdroplets are used in applications such as cell culture and microreactors, optical detection (fluorescence / scattered light / absorbance, etc.) of each microdroplet is usually required to distinguish its contents, so as to prepare for subsequent selection or statistics.

[0003] Taking absorbance detection, one of the most widely used analysis methods at present, as an example, it can be used to monitor the growth density of bacteria / cells, enzyme activity detection, quantitative monitoring of biological macromolecules, etc. In a traditional absorbance detection system, a standard liquid sample cell with a 10-mm optical path is usually used, and the amount of the liquid to be measured is generally more than 2 mL. In recent years, to address the problem of micro-detection, there have also been spectrophotometers with ultra-micro sample cells on the market, which can directly perform photometric analysis on micro-liter samples. The photometric cells of most micro-spectrophotometers are generally composed of two glass or quartz planes with a certain gap. The liquid is squeezed by the two planes to form a thin layer or a micro-cylinder with a specific thickness. Two mutually aligned optical fibers are installed behind the two glass planes to analyze the absorption spectrum of the liquid. However, the common feature of the above methods is that the light-receiving area of the sample cells used is much larger than the light source spot. The droplets in microfluidics usually have diameters ranging from dozens to hundreds of micrometers, making it difficult to achieve the above characteristics, and it also poses higher requirements for the optical path: (1) reducing stray light interference; (2) high sensitivity; (3) absolute alignment of the light source, receiver, and in-chip optical path. According to the BEER law, the absorbance signal of a substance is proportional to the concentration of the compound and the length of the optical path. Therefore, increasing the effective absorption optical path is the key to improving sensitivity. One idea is to introduce a capillary liquid core waveguide. However, there will be a certain dead volume at the interface after the capillary detection cell is integrated with the microfluidic chip, which will affect the accurate measurement of the next sample, and the capillary liquid core waveguide is expensive; another idea, such as Chinese Patent CN102539361B, uses optical fibers to introduce and export optical signals into and out of the microfluidic chip, and uses a Z-shaped channel to flatten the droplet, allowing the optical path to pass through the flattened droplet, so as to achieve highly sensitive detection of the absorbance of micro-droplets. However, the droplet is very easy to break when flowing through the narrow Z-shaped channel, and the increase in the optical path is limited. There is also an idea of a multi-reflection microfluidic chip absorbance sensor. The sensor includes a group of micro-machined mirrors, a micro-lens for collimating light, an incident optical fiber, an output optical fiber, and a micro-channel, etc. The incident light is reflected by the micro-machined mirrors and passes through the detection channel multiple times, and finally is collected by the output optical fiber. The absorbance of the solution is detected by measuring the change in the light intensity output by the output optical fiber. Although this scheme realizes highly sensitive absorbance detection, the processing of the mirrors is difficult and requires high-precision lithography equipment.

[0004] Therefore, researching a method for fabricating an on-chip mirror for micro-droplet optical sensing with low cost, high stability, easy processing, and wide application range is of great significance for the development of research in fields such as life science, environmental monitoring, and food safety. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a microfluidic chip based on a mirror optical path and its preparation method to achieve highly sensitive detection of the absorbance of micro-droplets in the microfluidic chip.

[0006] The present invention provides a microfluidic chip based on a mirror optical path. The mirror optical path includes an incident optical fiber channel, an exit optical fiber channel, and a droplet flow channel. On both sides of the droplet flow channel, there are a first mirror flow channel and a second mirror flow channel. Liquid metal is poured into the first mirror flow channel and the second mirror flow channel respectively, and then cooled and solidified to form a first mirror and a second mirror.

[0007] Preferably, the material of the microfluidic chip includes, but is not limited to, transparent materials such as polydimethylsiloxane (PDMS), polycarbonate (PC), polystyrene (PS), polymethyl methacrylate (PMMA), cycloolefin polymer (COP), and cycloolefin copolymer (COC).

[0008] Preferably, the first mirror flow channel or the second mirror flow channel includes at least one inlet.

[0009] Preferably, when only an inlet is provided in the first mirror flow channel or the second mirror flow channel, the microfluidic chip needs to be evacuated in advance. By using the porous air permeability of the microfluidic chip material, the liquid metal is sucked in and fills the mirror flow channel, and the side wall of the mirror flow channel serves as the mirror.

[0010] Preferably, when the first mirror flow channel or the second mirror flow channel includes an inlet and an outlet, the liquid metal is pressed in from the inlet and pressed out from the outlet.

[0011] Preferably, an incident optical fiber exhaust channel is provided on one side of the incident optical fiber channel, and an exit optical fiber exhaust channel is provided on one side of the exit optical fiber channel, which facilitates the insertion of the optical fiber into the optical fiber channel.

[0012] The present invention provides a preparation method of the above-mentioned microfluidic chip based on a mirror optical path, including the following steps:

[0013] (1) Design the flow channels of the microfluidic chip, and plan the droplet optical detection area, including the droplet flow channel, the incident optical fiber channel, the exit optical fiber channel, the optical fiber exhaust channel, the shape and position of the mirror. Among them, the mirror needs to set the mirror flow channel in an area that does not affect the optical path.

[0014] (2) Process the mold, cast the mold, punch holes, and bond according to the conventional method of the microfluidic chip.

[0015] (3) Place the microfluidic chip on a heating table, pour liquid metal into the mirror flow channel, and fill the planned area of the mirror.

[0016] (4) Cool down, the liquid metal solidifies, the side wall of the mirror flow channel serves as the mirror, and by using the flat side wall of the mirror flow channel, the mirror surface of the mirror is also very flat and smooth.

[0017] (5) Insert the incident optical fiber into the incident optical fiber channel and the outgoing optical fiber into the outgoing optical fiber channel, and the mirror optical path of the microfluidic chip is completed.

[0018] Preferably, the size of the droplet flow channel is related to the droplet size, generally 0.2 to 0.8 times the diameter of the droplet to be measured.

[0019] Preferably, the height of the droplet flow channel is 10 to 300 micrometers and the width is 10 to 300 micrometers.

[0020] More preferably, the height of the droplet flow channel is 125 micrometers and the width is 100 micrometers.

[0021] Preferably, the droplet flow channel flattens the droplet so that the droplet covers the optical path, and smaller-sized droplets can be accommodated by shortening the distance between the incident optical fiber and the outgoing optical fiber or the width of the droplet flow channel.

[0022] Preferably, the liquid metal is a low-melting-point metal, including tin-bismuth alloy, gallium-indium-tin alloy, etc.

[0023] Preferably, the mirror flow channel of the second mirror has the function of shielding stray light.

[0024] The present invention also provides an application of the above-mentioned microfluidic chip based on the mirror optical path in micro-droplet optical sensing.

[0025] Beneficial effects

[0026] (1) The present invention utilizes the optical path formed by multiple reflections, increases the effective absorption optical path, improves the detection sensitivity and accuracy; and the droplet flow channel has no bends, the droplet is not damaged, and a wide range of droplet sizes can be accommodated.

[0027] (2) The present invention can adjust the optical fiber angle and mirror layout as needed, further increase the number of reflections and the optical path, and adjust flexibly.

[0028] (3) In the present invention, the mirror preparation process is simple, the cost is low, and the stability is high. Description of the Drawings

[0029] Figure 1 It is a schematic diagram of the flow channel design of the mirror optical path of the microfluidic chip in Embodiment 1 of the present invention.

[0030] Figure 2 It is a working schematic diagram of the mirror optical path of the microfluidic chip in Embodiment 1 of the present invention.

[0031] Figure 3 It is the absorbance light intensity signal of the microfluidic chip based on the mirror optical path in Embodiment 1 of the present invention for detecting droplets of different concentrations of methylene blue.

[0032] Reference numerals: 1 - incident optical fiber channel, 2 - incident optical fiber exhaust channel, 3 - exit optical fiber channel, 4 - exit optical fiber exhaust channel, 5 - first mirror channel, 6 - first mirror, 7 - second mirror channel, 8 - second mirror, 9 - droplet channel. Detailed implementation mode

[0033] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0034] Embodiment

[0035] This embodiment provides a microfluidic chip based on a mirror optical path, and its structure is as Figure 1 shown, including an incident optical fiber channel 1, an exit optical fiber channel 3, and a droplet channel 9; on both sides of the droplet channel 9, there are a first mirror channel 5 and a second mirror channel 7. Liquid metal is poured into the first mirror channel 5 and the second mirror channel 7 respectively, and then cooled and solidified to form a first mirror 6 and a second mirror 8; on one side of the incident optical fiber channel 1, there is an incident optical fiber exhaust channel 2, and on one side of the exit optical fiber channel 3, there is an exit optical fiber exhaust channel 4.

[0036] In this embodiment, the preparation method of the above-mentioned microfluidic chip based on a mirror optical path includes the following steps:

[0037] (1) Design the microfluidic chip channels, and plan the droplet optical detection area, including the incident optical fiber channel 1, the incident optical fiber exhaust channel 2, the exit optical fiber channel 3, the exit optical fiber exhaust channel 4, the first mirror channel 5, the first mirror 6, the second mirror channel 7, the second mirror 8, and the droplet channel 9; the first mirror channel 5 is provided with an inlet and an outlet, and the second mirror channel 7 is only provided with an outlet; the height of the droplet channel 9 is 125 microns and the width is 100 microns;

[0038] (2) Process the mold, cast the mold, punch holes, and bond according to the conventional method of the microfluidic chip;

[0039] (3) Place the microfluidic chip on a heating table, pour liquid metal into the mirror channels, and fill the mirror planning area;

[0040] (4) Cool down, the liquid metal solidifies, and the side walls of the mirror channels serve as mirrors. Moreover, by using the flat side walls of the mirror channels, the mirror surfaces of the mirrors are also very flat and smooth;

[0041] (5) Insert the incident optical fiber into the incident optical fiber channel 1 and the output optical fiber into the output optical fiber channel 3, and the mirror optical path of the microfluidic chip is completed, as Figure 2 shown.

[0042] When the height of the droplet flow channel is 125 μm, the width is 100 μm, and the droplet diameter is 230 μm, the above-prepared microfluidic chip based on the mirror optical path detects the concentration of methylene blue solution by absorbance, and its resolution can be as low as 1 μM, as Figure 3 shown.

Claims

1. A microfluidic chip based on a reflector optical path, characterized in that: The reflector optical path includes an incident optical fiber channel, an output optical fiber channel, and a droplet flow channel; a first reflector flow channel and a second reflector flow channel are provided on both sides of the droplet flow channel, and liquid metal is poured into the first reflector flow channel and the second reflector flow channel respectively, and then cooled and solidified to form the first reflector and the second reflector.

2. The microfluidic chip according to claim 1, characterized in that: The material of the microfluidic chip is a transparent material, including one of polydimethylsiloxane PDMS, polycarbonate PC, polystyrene PS, polymethyl methacrylate PMMA, cycloolefin polymer COP or cycloolefin copolymer COC.

3. The microfluidic chip according to claim 1, characterized in that: The first reflector flow channel or the second reflector flow channel includes at least one inlet.

4. The microfluidic chip according to claim 3, characterized in that: When the first reflector channel or the second reflector channel is provided with only an inlet, the microfluidic chip needs to be evacuated, and then the liquid metal is sucked in and fills the reflector channel, and the side wall of the reflector channel acts as a reflector.

5. The microfluidic chip according to claim 3, characterized in that: When the first reflector flow channel or the second reflector flow channel is provided with an outlet, the liquid metal is pressed in from the inlet and pressed out from the outlet.

6. The microfluidic chip according to claim 1, characterized in that: An incident optical fiber exhaust channel is provided on one side of the incident optical fiber channel, and an exit optical fiber exhaust channel is provided on one side of the exit optical fiber channel.

7. A method for preparing a microfluidic chip based on a reflector optical path, comprising the following steps: (1) Design the flow channel of the microfluidic chip and plan the droplet optical detection area, including the droplet flow channel, incident optical fiber channel, output optical fiber channel and optical fiber exhaust channel, and the shape and position of the reflector. The reflector flow channel needs to be set in an area that does not affect the optical path; (2) Processing molds, mold turning, drilling, and bonding according to conventional methods for microfluidic chips; (3) placing the microfluidic chip on a heating platform, pouring liquid metal into the reflector flow channel, and filling the reflector planning area; (4) Cooling down, the liquid metal solidifies, and the side wall of the reflector channel acts as a reflector; (5) Insert the incident optical fiber into the incident optical fiber channel and insert the output optical fiber into the output optical fiber channel, and the reflector optical path of the microfluidic chip is completed.

8. The preparation method according to claim 7, characterized in that: The droplet flow channel has a height of 10 to 300 microns and a width of 10 to 300 microns.

9. The preparation method according to claim 7, characterized in that: The droplet flow channel flattens the droplet so that the droplet covers the optical path, and is compatible with droplets of smaller size by shortening the distance between the incident optical fiber and the output optical fiber or the width of the droplet flow channel.

10. Application of the microfluidic chip based on reflector optical path as claimed in claim 1 in micro-droplet optical sensing.

Images