CN116175697A - A preparation method of low-cost blasting valve-controlled microfluidic patch made by laser cutting - Google Patents

Abstract

The invention discloses a preparation method of a low-cost burst valve control microfluidic patch manufactured by laser cutting, which comprises the following steps of drawing, and drawing a designed model in a laser cutting system; cutting a transparent PI film with the thickness of 50 mu m by adopting a laser cutting system to prepare a ventilation layer with a first capillary blast valve; cutting the single-layer double-sided adhesive tape into a preset shape by using a laser cutting technology, repeating the cutting process for three times to form a sweat stream layer with enough height; the prepared color marks are placed in four microchambers of the sweat stream layer, the color marks in the microchambers have sensitive color reaction to glucose with different concentrations, and by comparing the R value in the RGB color model with the R value in the standard model, the concentration of the glucose in sweat can be seen to have higher sensitivity in the range of 0.1 mM-1 mM, and the color marks have better anti-interference performance to alcohol, urea, chloride and lactic acid possibly existing in sweat.

Description

A preparation method of low-cost blasting valve-controlled microfluidic patch made by laser cutting

technical field

The invention relates to the field of microfluidic patch, in particular to a method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting.

Background technique

There are also a large number of biomarkers in human sweat, such as glucose, lactic acid, urea, sodium, potassium, protein, etc. Many studies have found that the concentration of biomarkers in sweat is highly correlated with the concentration of biomarkers in blood. Compared with blood sampling, sweat collection is more convenient and non-invasive, and it is expected to be an ideal method for health information monitoring, especially for diabetic patients who need daily sampling. It is hoped that sweat sensing will be introduced into home medicine to realize early warning and diagnosis of diseases. Recently, many methods for collecting sweat have been proposed to obtain meaningful information about the physiological state of the body. Among them, microfluidic chips integrated with microsensors are ideal platforms for personal health status monitoring based on sweat analysis, where sweat can be collected, stored, and analyzed in situ. When the body heat rises or the ambient temperature rises, the sweat glands will naturally secrete sweat, and the osmotic pressure between the plasma and the epidermis will push the secreted sweat to the surface of the skin and enter the analysis area of the microfluidic chip. However, there is unavoidable mixing between the measured sweat and the sweat to be measured on the skin surface, which greatly affects the accuracy of the biomarker measurement due to the deformation of the biomarker over time. To avoid this problem, a sequential acquisition strategy based on microfluidic patches is proposed, with the assistance of multifunctional valves, to achieve precise control of sweat acquisition, storage, in situ detection, and outflow through well-designed pathways.

Here we describe a method to direct flow in these types of skin-mounted microfluidic devices through a set of carefully designed capillary burst valves (CBVs), which direct sweat flow to fill microreservoirs in a sequential fashion, thereby providing precise sampling. ability. The team used a valve technology that directs the flow of sweat from an inlet location to a series of isolated reservoirs in a defined sequence. A team reported a microfluidic system using soft lithography to cast microchannels, reservoirs, valves, and other components from low-modulus elastomers. However, these delicate microchannels and valves integrated in microfluidic patches are usually fabricated through silicon molds using soft lithography, and the entire production process relies on resource-intensive laboratories and high-cost facilities.

Accordingly, the present invention proposes a flexible microfluidic patch manufacturing method with ingenious design and simple preparation, which is convenient for sweat collection and sensing of diabetic patients who have sampling needs every day.

Contents of the invention

In order to overcome the above-mentioned defects in the prior art, the present invention provides a low-cost blasting valve-controlled microfluidic patch preparation method made by laser cutting, which captures and stores sweat in chronological order, avoiding the sweat being tested and the sweat being tested. The mixing of sweat, in addition, can detect the concentration of glucose in sweat in a chronological order, which provides the possibility to monitor blood sugar elevation in time. The color markers in the microchambers have sensitive color reactions to different concentrations of glucose. By comparing the RGB color model It can be seen that the glucose concentration in sweat has higher sensitivity in the range of 0.1mM to 1mM, and has better resistance to alcohol, urea, chloride and lactic acid that may exist in sweat. interfere with performance.

Technical solutions

A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting, comprising the following steps:

1) Drawing, draw the designed model in the laser cutting system;

2) A laser cutting system is used to cut a transparent PI film with a thickness of 50 μm to prepare a ventilation layer with a first capillary burst valve;

3) Cut the single-layer double-sided tape into a predetermined shape with laser cutting technology, and repeat it three times to form a high enough sweat layer;

4) Put the pre-prepared color markers into the four microchambers of the sweat layer, wrap them with a transparent PI film, and open a hole of 1mm in the middle;

5) The prepared ventilation layer is pasted on the sweat layer;

6) Encapsulate with BOPP film on one side as the top layer and bottom layer;

7) Finally, the microfluidic patch is easily pasted on the skin through the double-sided adhesive tape with 5mm large holes, that is, the adhesive layer.

Further, the thickness of the polyimide film is 0.75 mm, and the cutting parameters of the ultraviolet laser are set as follows: scanning speed 100 mm/s, pulse frequency 20 kHz, pulse width 0.5 μs, and the focal length is fixed on the upper surface of the polyimide film , the coverage position is three first capillary blast valves in each group, a total of four groups, the angle at the entrance is 105°, and the entrance of the channel is a rectangular microchannel with a width of 250 μm and a height of 50 μm.

Further, the angle at the entrance of the second capillary burst valve is 180 degrees, the entrance of the second capillary burst valve is a curved microchannel with a width of 500 μm and a height of 450 μm, and the diameter of the microchamber is 3 mm. The diameter of the sweat layer is 30mm.

Further, the color mark is formed by air-drying the surface of the dust-free paper after soaking it in the GOD-POD solution at 4°C for three hours in the dark. The color mark has a sensitive color reaction to different concentrations of glucose. By comparing RGB The color model is the R value in the standard color and the R value of the standard model. It can be seen that the glucose concentration in the sweat has a high sensitivity in the range of 0.1mM to 1mM, and it is sensitive to alcohol, urea, and chloride that may exist in the sweat. And lactic acid have good anti-interference performance.

Further, from top to bottom, the microfluidic patch is a top layer, a ventilation layer, a sweat layer, a bottom layer, and an adhesive layer.

Further, the upper side of the top layer is provided with a standard color card for color comparison, and four directions of the ventilating layer are provided with a color card for balancing the pressure between the microchamber and the outside world and ensuring that the liquid flows in. The air in the microchamber can be smoothly removed, and the liquid is blocked in the microchamber without leaking out. Four microchambers are arranged on the sweat layer, and capillary tubes are connected between the microchambers. The capillary channels between the microchambers are all provided with a second capillary burst valve with adjustable burst pressure for sequential collection of sweat, and an inlet hole is provided at the center of the sweat layer.

Further, the lower side of the inlet hole is provided with a small hole at the center of the bottom layer, and the lower side of the small hole is provided with a large hole at the center of the adhesive layer for collecting sweat.

Further, colored markers for color reaction are placed in the microchamber.

Beneficial effect

Compared with the prior art, the present invention has the following beneficial effects:

1. The materials involved in the production are polyimide film and 3M double-sided tape. These materials are cheap and can effectively reduce production costs;

2. Two different capillary burst valves are designed, which realize the sequential collection of sweat through the capillary burst valve, which is conducive to testing the sweat composition in different time periods; through the operation of different types of capillary burst valves, the microfluidic patch has The ability to collect, store and detect sweat in chronological order;

3. Select the colorimetric method to detect the concentration of glucose in sweat through enzyme-based reagents, which can efficiently and selectively detect the concentration of glucose in sweat;

4. Detecting the concentration of glucose in sweat in time order provides the possibility to monitor the rise of blood sugar in time. The color markers in the microchamber have a sensitive color reaction to different concentrations of glucose. By comparing the R value in the RGB color model with the From the R value of the standard model, it can be seen that the concentration of glucose in sweat has high sensitivity in the range of 0.1mM to 1mM, and has good anti-interference performance to alcohol, urea, chloride and lactic acid that may exist in sweat. It shows that the microfluidic patch has application potential in the fields of human sweat management and physiological information monitoring.

Description of drawings

Fig. 1 is the structural explosion diagram of the microfluidic patch in the present invention;

Fig. 2 is the perspiration layer design drawing (a) of the second capillary blasting valve and the transom layer design drawing (b) of the first capillary blasting valve;

Figure 3 is a schematic diagram of the side view (a) and front view (b) of the second capillary burst valve when the liquid is immobilized in the microchannel, as the contact angle increases from θ _A to θ _A+β , the liquid flows to the second Schematic diagram (c) of the inlet of the capillary burst valve;

Fig. 4 is the design idea of the first capillary blasting valve;

Figure 5 is a schematic diagram of the entire platform for liquid collection in chronological order (a), and the time when liquid is filled into each microchamber (b).

reference sign

Standard color card 1, top layer 2, ventilation layer 3, first capillary burst valve 4, micro chamber 5, second capillary burst valve 6, sweat layer 7, small hole 8, large hole 9, adhesive layer 10, bottom layer 11 , Color marking 12, capillary 13, inlet hole 14.

Detailed ways

In order to better illustrate and set forth the content of the present invention, the following will be expanded and described in conjunction with the accompanying drawings and implementation examples:

As shown in Figures 1-5, the present invention discloses a method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting, which includes the following steps:

1) Drawing, draw the designed model in the laser cutting system;

2) A laser cutting system is used to cut a transparent PI film with a thickness of 50 μm to prepare a ventilation layer with a first capillary burst valve;

3) Cut the single-layer double-sided tape into a predetermined shape with laser cutting technology, and repeat it three times to form a high enough sweat layer;

4) Put the pre-prepared color markers into the four microchambers of the sweat layer, wrap them with a transparent PI film, and open a hole of 1mm in the middle;

5) The prepared ventilation layer is pasted on the sweat layer;

6) Encapsulate with BOPP film on one side as the top layer and bottom layer;

7) Finally, the microfluidic patch is easily pasted on the skin through the double-sided adhesive tape with 5mm large holes, that is, the adhesive layer.

Further, the thickness of the polyimide film is 0.75 mm, and the cutting parameters of the ultraviolet laser are set as follows: scanning speed 100 mm/s, pulse frequency 20 kHz, pulse width 0.5 μs, and the focal length is fixed on the upper surface of the polyimide film , the coverage position is three first capillary blast valves 4 in each group, a total of four groups, the angle at the entrance is 105°, and the entrance of the channel is a rectangular microchannel with a width of 250 μm and a height of 50 μm.

Further, the angle at the entrance of the second capillary burst valve 6 is 180 degrees, the entrance of the second capillary burst valve 6 is a curved microchannel with a width of 500 μm and a height of 450 μm, and the diameter of the microchamber 5 is 3 mm , the diameter of the sweat flow layer 7 is 30mm.

Further, the colored mark 12 is formed by air-drying the surface of the dust-free paper after being soaked in GOD-POD solution at 4°C in the dark for three hours. The colored mark 12 has a sensitive color reaction to different concentrations of glucose. Comparing the RGB color model, that is, the R value in the standard color 1 with the R value of the standard model, it can be seen that the concentration of glucose in sweat has a high sensitivity in the range of 0.1mM to 1mM, and it is sensitive to alcohol, urea and other substances that may exist in sweat. , chloride and lactic acid have good anti-interference performance.

Further, the microfluidic patch is top layer 2 , ventilation layer 3 , sweat layer 7 , bottom layer 11 , and adhesive layer 10 from top to bottom.

Further, the upper side of the top layer 2 is provided with a standard color card 1 for color comparison, and the four directions of the ventilation layer 3 are provided with four directions for balancing the pressure between the microchamber 5 and the outside world, ensuring that the liquid When the air in the microchamber 5 flows in, the air in the microchamber 5 can be smoothly removed, and the liquid is blocked in the microchamber 5 and does not leak out. Three first capillary burst valves 4, and the sweat layer 7 is provided with four microchambers 5. The microchambers 5 are communicated with capillary channels 13, and the capillary channels 13 between the microchambers 5 are provided with second capillary burst valves 6 with adjustable burst pressure for sequential collection of sweat. An inlet hole 14 is arranged at the center of the sweat flow layer 7 .

Further, the lower side of the inlet hole 14 is provided with a small hole 8 at the center of the bottom layer 11, and the lower side of the small hole 8 is provided with a large hole at the center of the adhesive layer 10 for collecting sweat 9.

Further, a color mark 12 for color reaction is placed in the microchamber 5 .

Specifically, the entire microfluidic patch has four microchambers 5 for sweat storage, and two different types of second capillary burst valves 6 and first capillary burst valves 4 are respectively designed on the sweat layer and the ventilation layer, To realize timing acquisition, the second capillary burst valve 6 provides the first-stage burst pressure (BP), which sequentially controls the flow and collection of liquid in the four microchambers 5, and the second-stage burst pressure is provided by the first capillary burst valve 4, Its function is to balance the pressure between the microchamber 5 and the outside world, to ensure that when the liquid flows in, the air in the microchamber 5 can move out smoothly, and the liquid is blocked in the microchamber 5 and will not leak out. When the secreted sweat enters from the large hole 9 In the microfluidic patch, the capillary channel 13 can transfer the sweat on the skin surface to the microchamber 5 parallel to the first capillary burst valve 4 and release the air;

The flow sequence of sweat is: enter from the large hole 9, then pass through the small hole 8, the inlet hole 14, and then flow into the microchamber 5 on the right. After the microchamber 5 on the right is full, it will flow clockwise Follow the capillary 13 to flow;

When the liquid is still in the capillary 13, the additional pressure generated by the difference between the inner and outer curved liquid levels satisfies the Young equation (Fig. 3)

Here _PA is the pressure from the inner curved liquid level, _PO is the pressure from the outer curved liquid level, σ is the surface tension coefficient, θ _A and θ _V represent the contact angle of the liquid with the side wall and the upper and lower walls, respectively, W and h are the width and height of the capillary channel 13, respectively, when the liquid flows to the second capillary burst valve 6, the width of the capillary channel 13 suddenly expands, and the three-phase contact line of the liquid stops immediately until the contact angle increases from _θA to _θA+β (Fig. 3), the liquid could pass through the second capillary burst valve 6, and the burst pressure (BP) of the liquid at the inlet is

Therefore, the pressure of the liquid flow at the second capillary burst valve 6 increases, which can achieve the expectation of different branches and diversions. In addition, because the height and width of the first capillary burst valve 4 are significantly smaller than the second capillary burst valve 6 (Fig. 2), the former BP is much larger than the latter, which makes sweat burst in the second capillary burst valve 6 and proceed to the next microchamber 5 instead of leaking out from the first capillary burst valve 4 .

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the technical solutions of the present invention have been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that it still The technical solutions described in the foregoing embodiments can be modified, or some of the technical features can be replaced equivalently; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (8)

1. A low-cost blasting valve-controlled microfluidic patch preparation method made by laser cutting, characterized in that, comprising the steps: ①Drawing, draw the designed model in the laser cutting system; ②A laser cutting system is used to cut the transparent PI film with a thickness of 50 μm to prepare the ventilation layer with the first capillary burst valve; ③Using laser cutting technology to cut the single-layer double-sided tape into a predetermined shape, repeat three times to form a high enough sweat layer; ④Put the pre-prepared color markers into the four microchambers of the sweat layer, wrap them with a transparent PI film, and open the bottom layer with 5mm holes; ⑤ The prepared ventilation layer is pasted on the sweat layer; ⑥ Use single-sided BOPP film as the top layer and bottom layer for packaging; ⑦ Finally, the microfluidic patch is easily pasted on the skin through the double-sided adhesive tape with 5mm large holes, that is, the adhesive layer. 2. A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 1, wherein the thickness of the polyimide film is 0.75mm, and the cutting parameters of the ultraviolet laser are set It is: scanning speed 100mm/s, pulse frequency 20kHz, pulse width 0.5μs, the focal length is fixed on the upper surface of the polyimide film, and the covering position is three first capillary blasting valves (4) in each group, a total of four groups, The angle at the entrance is 105°, and the entrance of the channel is a rectangular microchannel with a width of 250 μm and a height of 50 μm. 3. A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 2, wherein the angle at the entrance of the second capillary blasting valve (6) is 180 degrees , the entrance of the second capillary burst valve (6) is a curved microchannel with a width of 500 μm and a height of 450 μm, the diameter of the microchamber (5) is 3 mm, and the diameter of the sweat layer (7) is 30 mm. 4. A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 3, wherein the color mark (12) is a dust-free paper in a GOD-POD solution at 4°C After three hours of immersion in the dark, the surface is air-dried and formed. The color mark (12) has a sensitive color reaction to different concentrations of glucose. By comparing the RGB color model, that is, the R value in the standard color 1 and the standard model It can be seen that the concentration of glucose in sweat has high sensitivity in the range of 0.1mM to 1mM, and has good anti-interference performance to alcohol, urea, chloride and lactic acid that may exist in sweat. 5. A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 4, wherein the microfluidic patch is top layer (2), top layer (2), Ventilation layer (3), sweat flow layer (7), bottom layer (11), adhesive layer (10). 6. A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 5, characterized in that, the upper side of the top layer (2) is provided with a standard color for color comparison card (1), four directions of front, rear, left, and right sides of the ventilation layer (3) are provided to balance the pressure between the microchamber (5) and the outside world, and ensure the air energy in the microchamber (5) when the liquid flows in. three first capillary burst valves (4) that are smoothly removed and the liquid is blocked in the microchamber (5) without leaking out; the sweat layer (7) is provided with four microchambers (5), so Capillary ducts (13) are communicated between the microchambers (5), and the second capillary ducts (13) between the microchambers (5) are provided with adjustable burst pressure for the sequential collection of sweat. For the burst valve (6), an inlet hole (14) is arranged at the center of the sweat layer (7). 7. A method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 6, wherein the lower side of the inlet hole (14) is provided with a bottom layer (11 ) in the center of the small hole (8), the underside of the small hole (8) is provided with a large hole (9) located in the center of the adhesive layer (10) for collecting sweat. 8. the method for preparing a low-cost blasting valve-controlled microfluidic patch made by laser cutting according to claim 7, is characterized in that, in the microchamber (5), a colored mark ( 12).

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