A sweat collection microfluidic patch based on micropump and preparation method thereof

Abstract

The application relates to a sweat collection microfluidic patch based on a micropump and a preparation method thereof, the sweat collection microfluidic patch comprising a micropump, a sweat absorption layer, a sweat microfluidic layer and a sealing layer, the sweat absorption layer, the sweat microfluidic layer and the sealing layer being stacked in sequence from bottom to top; wherein the sweat absorption layer is provided with a liquid inlet, the sweat microfluidic layer is provided with a liquid inlet area, the micropump transports sweat from the liquid inlet of the sweat absorption layer to the liquid inlet area of the sweat microfluidic layer; a plurality of collection areas are further arranged on the sweat microfluidic layer, the collection areas are connected through gradient burst valves, and one of the plurality of collection areas is connected with the liquid inlet area. The microfluidic module combined with the micropump can provide long-time time-series collection of sweat by using the programmable and accurate and stable active suction of the micropump.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of wearable microfluidic devices, in particular to a sweat collection microfluidic patch based on a micropump and a preparation method. BACKGROUND

[0002] In recent years, with the rapid development of biosensing technology and wearable devices, the demand for real-time and non-invasive health monitoring has gradually increased. Traditional biological analysis methods usually rely on the detection of blood samples, but the blood sampling process can cause physical discomfort and psychological stress to the subjects. Therefore, evaluating the exercise state and health condition by analyzing the fluctuation degree of relevant biochemical components in sweat has become a very promising alternative. Sweat, as an easily accessible body fluid, contains many biomarkers that can reflect the individual's health and physiological condition, such as electrolytes, hormones, proteins, and metabolites.

[0003] Although there are some initial commercial products and research prototypes, there are still many challenges and opportunities in the field of wearable sweat collection and sensing. When studying how to conveniently and accurately collect and detect the concentration of biological markers related to physical condition and certain diseases in sweat, there are often many problems. In 2017, the John Rogers group in the United States published a related paper in a journal, describing a time-series microfluidic sweat collection chip combined with a colorimetric detection method. This type of chip ignores several problems, which are listed as follows:

[0004] (1) The above-mentioned sweat collection chip can only rely on the pressure of natural sweat secretion of the body to drive the collection of sweat, and the adhesion of the collection layer to the skin is required to be high.

[0005] (2) Passive collection cannot be used for long-term continuous collection, and cannot fully realize the potential of sweat detection for body condition and disease prevention. For example, sweat collection and analysis in the context of military training or long-term training of professional athletes. SUMMARY

[0006] The present application aims to solve the above-mentioned problems by combining a microfluidic module with a micropump, using the programmable and accurate and stable active suction of the micropump to provide long-term time-series collection of sweat. Based on this, the present application provides a sweat collection microfluidic patch based on a micropump and a preparation method.

[0007] A sweat collection microfluidic patch based on a micropump, the sweat collection microfluidic patch comprising a micropump, a sweat absorption layer, a sweat microfluidic layer, and a sealing layer, the sweat absorption layer, the sweat microfluidic layer, and the sealing layer being stacked in order from bottom to top; wherein,

[0008] The sweat absorption layer is provided with a liquid inlet, and the sweat microfluidic layer is provided with a liquid inlet area. The micro-pump transports sweat from the liquid inlet of the sweat absorption layer to the liquid inlet area of the sweat microfluidic layer.

[0009] The sweat microfluidic layer is further provided with a plurality of collection areas, and the collection areas are connected by gradient burst valves. One of the plurality of collection areas is connected to the liquid inlet area.

[0010] In an alternative embodiment, the gradient burst valve includes a valve inlet and a plurality of valve outlets, each of which corresponds to a valve outlet channel. The plurality of valve outlets includes a first valve outlet and at least one second valve outlet. The valve outlet channel width of the first valve outlet is greater than that of the second valve outlet. Sweat selectively flows into the corresponding valve outlet channel from the first valve outlet or the second valve outlet.

[0011] In an alternative embodiment, each of the collection areas is provided with a plurality of collection bins. Adjacent two of the collection bins are connected by a flow channel. Each of the flow channels is provided with one or more flow outlets connected to the flow channel or the collection bin.

[0012] In an alternative embodiment, the liquid outlet of the collection bin is connected to the corresponding extraction chamber of each collection bin through a micro-channel.

[0013] In an alternative embodiment, each of the flow channels is further provided with a passive burst valve. The passive burst valve controls the flow of sweat to the flow channel or the collection bin.

[0014] In an alternative embodiment, the sweat collection microfluidic patch includes a plurality of sweat microfluidic layers. The plurality of sweat microfluidic layers are stacked and connected to each other.

[0015] The preparation method of the above-mentioned sweat collection microfluidic patch based on a micro-pump includes:

[0016] Preparation of a sweat absorption layer;

[0017] Preparation of a sweat microfluidic layer. A plurality of collection areas are formed on the sweat microfluidic layer. Each collection area includes a plurality of collection bins. The collection areas are connected by gradient burst valves. The collection bins are connected by flow channels.

[0018] Providing a sealing layer, and stacking the sweat absorption layer, the sweat microfluidic layer and the sealing layer from bottom to top to form an integrated body.

[0019] In an alternative embodiment, the preparation of the sweat microfluidic layer further includes:

[0020] Creating micro- or nano-structures on a silicon wafer, forming a template, covering the template surface with a thin film made of anti-adhesion material;

[0021] Cleaning the substrate to be processed, removing surface contaminants and particles, coating the substrate with a thin film of material matching the micro- or nano-structures on the template (such as a photo-cured resin or a thermoplastic material);

[0022] According to the selected imprinting method (hot or UV imprinting), the substrate coated with the thin film is brought into contact and alignment with the template, and imprinting is performed at the appropriate pressure and temperature;

[0023] After complete curing, the template is separated from the substrate, and the substrate is cleaned of residual template residues and impurities, forming a sweat microfluidic layer. In an alternative embodiment, the preparation method further comprises:

[0024] Designing a three-dimensional model, 3D printing a mold;

[0025] Preparing uncured PDMS, vacuum treating the uncured PDMS;

[0026] Dropping the vacuum-treated PDMS into the mold and vacuum treating it;

[0027] Spinning the vacuum-treated PDMS on a glass flat plate;

[0028] Heating and curing the mold with the dropped PDMS and the glass flat plate, and surface treating the cured PDMS surface, respectively forming a sweat microfluidic layer and a sealing layer;

[0029] Embedding a colorimetric test paper (optional) in the sweat collection chamber of the sweat microfluidic layer;

[0030] The surface-treated sweat microfluidic layer and sealing layer are bonded, forming a sweat collection microfluidic patch.

[0031] In an alternative embodiment, the preparation of the sweat microfluidic layer further comprises:

[0032] Designing and drawing a two-dimensional graph of the layer where the microfluidic channel is located;

[0033] Cleaning the surface of the silicon wafer, and performing an oven drying treatment on the silicon wafer;

[0034] The oven-dried silicon wafer is spin-coated with photoresist;

[0035] The silicon wafer is subjected to a first baking and laser direct writing, and after the laser direct writing, a second baking is performed;

[0036] The silicon wafer after the second baking is developed, forming a soft lithography template;

[0037] PDMS reverse-molding the soft lithography template to obtain the sweat microfluidic layer.

[0038] In an alternative embodiment, the preparation method further comprises:

[0039] The integrated sweat microfluidic patch and micropump form a sweat collection device, which is worn on the hand or body.

[0040] In an alternative embodiment, a plurality of sweat microfluidic layers are prepared, and the plurality of sweat microfluidic layers are stacked on top of each other by connecting them.

[0041] In an alternative embodiment, the plurality of sweat microfluidic layers are processed into the same sweat collection microfluidic patch of the same material or multiple materials, increasing the sweat collection capacity of the sweat collection microfluidic patch.

[0042] The above-mentioned sweat collection microfluidic patch based on a micropump and the preparation method have the following advantages compared with the prior art:

[0043] 1. The gradient burst valve introduced in the present application can collect more times - more than the collection time of the prior art, and more times of sweat collection volume.

[0044] 2. The burst valve provided in the present application can avoid mixing of new and old sweat, and reduce the replacement frequency of the microfluidic patch in the same time.

[0045] 3. The programmable and controllable micropump introduced in the present application makes the output sweat pressure more stable, which is beneficial to the collection of sweat.

[0046] 4. The present application is combined with a large flux microfluidic platform, which can perform large-scale precise detection and better exploit the potential of sweat detection.

[0047] 5. The present application has stable sweat input pressure, can be designed in a multi-layer structure, greatly improves the use efficiency per unit area, and in addition, the present application can be expanded from a patch form to a waist bag, a backpack and other forms of sweat collection. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1 Fig. 1 is a structural schematic diagram of the sweat collection microfluidic patch based on a micropump of the present application;

[0049] Figure 2 Fig. 3 is a structural schematic diagram of the sweat microfluidic layer of the present application;

[0050] Figure 3 Fig. 5 is a structural schematic diagram of the gradient burst valve of the present application;

[0051] Figure 4 Structure diagram of the collection area of the present application;

[0052] Figure 5 Structure diagram of the microfluidic patch based on the micro-pump for collecting sweat of the present application;

[0053] Figure 6 Principle diagram of the burst valve of the present application;

[0054] Figure 7 Pressure transient characteristic diagram of the burst valve in the working state timing sequence of the present application. DETAILED DESCRIPTION

[0055] In order to make the purposes, technical solutions and advantages of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0056] The embodiments of the present application, examples of the embodiments are shown in the drawings, wherein the same or similar reference numerals represent the same or similar elements or elements having the same or similar functions throughout. The terms "first", "second", "third" and the like (if present) in the description and claims of the present application and the drawings are used to distinguish similar objects, and do not necessarily describe a particular order or sequence. It should be understood that the described objects can be interchanged under appropriate circumstances. In addition, the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusion. The direction terms mentioned in the present application, such as: up, down, left, right, front, back, inner, outer, side, etc. are only the direction of the drawings. The embodiments described below with reference to the drawings are exemplary and are only used to explain the present application, and cannot be understood as a limitation of the present application. In addition, the present application repeatedly refers to numbers and / or letters in different examples. Such repetition is for the purpose of simplification and clarity, and does not itself indicate the relationship between the various embodiments and / or arrangements discussed. In addition, the present application provides examples of various specific processes and materials, but those skilled in the art can realize the application of other processes and / or the use of other materials. Embodiment one

[0057] The present embodiment provides a microfluidic patch for collecting sweat based on a micro-pump, as shown in Figures 1-4As shown, the sweat collection microfluidic patch includes a micropump 10, a sweat absorption layer 20, a sweat microfluidic layer 30, and a sealing layer 40, the sweat absorption layer 20, the sweat microfluidic layer 30, and the sealing layer 40 are stacked in turn from bottom to top, and the micropump 10 is connected to the sweat absorption layer 20 and the sweat microfluidic layer 30. Among them,

[0058] The sweat absorption layer 20 covers the skin surface, and the sweat absorption layer 20 is provided with a liquid inlet 21. Preferably, the sweat absorption layer 20 covers two or more sweat gland outlets, and the sweat collected from the sweat gland outlets is provided to the micropump 10.

[0059] Further, the micropump 10 is a programmable micropump. The programmable and controllable micropump 10 makes the sweat pressure output to the sweat microfluidic layer 30 more stable, which is more conducive to the collection of sweat. After the sweat is absorbed by the sweat absorption layer 20 to the liquid inlet 21, the micropump 10 fills the sweat into the sweat microfluidic layer 30, and the micropump 10 can be programmed to stably deliver the sweat. The micropump 10 can also be provided with different sampling modes and programs to meet the collection needs of sweat under different conditions.

[0060] Preferably, the micropump 10 includes at least one microflow sub-pump, the microflow sub-pump includes a liquid containing cavity, at least one side wall of the liquid containing cavity is a piezoelectric ceramic sheet, the piezoelectric ceramic sheet vibrates to make the liquid containing cavity in a contraction or expansion state; when the liquid containing cavity is in an expansion state, a first one-way valve is opened, and a second one-way valve is closed, and liquid flows from the first one-way valve into the liquid containing cavity; when the liquid containing cavity is in a contraction state, the first one-way valve is closed, and the second one-way valve is opened, and the liquid in the liquid containing cavity flows out from the second one-way valve. For the specific structure of the micropump 10 of the present embodiment, please refer to the definition of patent CN201710923269.0, which will not be repeated here.

[0061] The sweat microfluidic layer 30 is provided with a liquid inlet area 31, and the micropump 10 has the ability to actively transport the sweat on the sweat absorption layer 20 to the sweat inlet of the sweat microfluidic layer 30.

[0062] Specifically, the micropump 10 transports the sweat from the liquid inlet of the sweat absorption layer 20 to the liquid inlet area of the sweat microfluidic layer 30.

[0063] The sweat microfluidic layer 30 is also provided with a plurality of collection areas 32, the collection areas 32 are connected through gradient burst valves 33, and one of the plurality of collection areas 32 is connected with the liquid inlet area 31.

[0064] The gradient burst valve 33 comprises a valve inlet 331 and a plurality of valve outlets 332, each of the valve outlets 332 is connected to a valve outlet channel 333, the plurality of valve outlets 332 comprises a first valve outlet 3321 and at least one second valve outlet 3322, the width of the valve outlet channel 333 corresponding to the first valve outlet 3321 is greater than the width of the valve outlet channel 333 corresponding to the second valve outlet 3322, thus, the sweat is selectively flowed into the valve outlet channel 333 from the first valve outlet 3321 or the second valve outlet 3322.

[0065] That is, the gradient burst valve 33 has a valve inlet and a plurality of valve outlets, among the plurality of valve outlets, one valve outlet has a more preferential sweat outflow capacity than other valve outlets, i.e. the optimal outlet. Since the width of the valve outlet channel corresponding to each valve outlet is not the same, one or more outlets other than the optimal outlet have the same width but lower sweat outflow capacity than the optimal outlet.

[0066] Preferably, the gradient burst valve 33 has a valve inlet 331 and four valve outlets 332, among the four valve outlets 3322, the first valve outlet 3321 connected to the collection area 32 is the optimal outlet. The remaining three are the second valve outlet 3322, the width of the valve outlet channel 333 corresponding to the first valve outlet 3321 is greater than the width of the valve outlet channel 333 corresponding to the second valve outlet 3322, and the sweat outflow capacity of the first valve outlet 3321 is higher than that of the second valve outlet 3322.

[0067] Preferably, the number of gradient burst valves 33 can be two or more, and the gradient burst valve 33 can determine the priority order of the sweat flow.

[0068] Each collection area 32 is provided with a plurality of collection bins 34, and adjacent two collection bins 34 are connected by a flow channel 35, each flow channel 35 is provided with one or more flow outlets 351, and the flow outlet 351 is connected to the flow channel 35 or the collection bin 34.

[0069] Preferably, the flow channel 35 is an arc-shaped channel.

[0070] Specifically, the flow channel 35 is a low-flow-resistance channel. The flow channel 35 can be provided with one or more inlets and at least two outlets, one or more of all the outlets have a higher flow priority, and the sweat is preferentially guided into the collection bin corresponding to the outlet, and then guided by the less preferred outlet to the low-flow-resistance channel of the next collection bin.

[0071] Preferably, the flow channel 35 has one inlet, and two flow outlets 351, one of which is connected to the corresponding collection bin 34, and the other is connected to the low-flow-resistance flow channel 35 of the next collection bin 34. The flow priority of the flow outlet 351 connected to the collection bin 34 is higher than that of the flow outlet 351 connected to the flow channel 35, so that the sweat is preferentially introduced into the corresponding collection bin, and then guided to the low-flow-resistance channel of the next collection bin.

[0072] The liquid outlet 341 of the collection bin 34 is connected to the corresponding extraction chamber 37 of each collection bin 34 through the micro channel 36.

[0073] Specifically, the collection bin 34 has one or more inlets, and one or more outlets connected to the extraction chamber 37 through the micro channel 36. Preferably, the collection bin 34 has one inlet and one outlet.

[0074] Each flow channel 35 is also provided with a passive burst valve 38, which controls the flow of sweat to the flow channel 35 or the collection bin 34.

[0075] Preferably, the number of collection bins 34 in each collection area 32 is the same or different. Preferably, a total of 16 sweat collection bins 34 are provided, and each four collection bins 34 form a collection area 32. The collection bins 34 in the collection area 32 are arranged in a tree shape, and the collection area 32 can also be a sweat collection tree. Two adjacent collection areas 32 are connected by a gradient burst valve 33, i.e. a total of 2 gradient burst valves 33. Since the collection bins 34 in the collection area 32 are provided with passive burst valves 38, the priority of the sweat flow in the collection area 32 is determined by the passive burst valves 38, so that the new and old sweat can be separated.

[0076] The collection bins 34 are connected by passive burst valves 38, and the collection areas 32 are connected by gradient burst valves 33. The gradient burst valve 33 can collect sweat for a longer time, which is multiple times longer than the prior art, and the volume of sweat collected is also multiple times larger. The passive burst valve 38 can avoid mixing of new and old sweat, and reduce the number of times of replacing the microfluidic patch in the same time.

[0077] Preferably, the channel connecting each gradient burst valve 33 and passive burst valve 38 is a capillary tube.

[0078] Further, the gradient burst valve 33 and the passive burst valve 38 of the present embodiment are both capillary burst valves, and the working principle of the capillary burst valve is as follows:

[0079] When the liquid flows uniformly in the capillary tube, it will be subjected to the adsorption force of the capillary tube wall, forming a curved liquid surface, i.e. a capillary pressure barrier.

[0080] When the divergence angle of the cross-section of the capillary tube suddenly expands, the gas-liquid phase interface contact line temporarily stops, the liquid surface curvature increases, resulting in the enhancement of the capillary pressure barrier, preventing the liquid from continuing to flow.

[0081] When the externally applied pressure or centrifugal force exceeds the capillary pressure barrier, the liquid surface will be broken, and the liquid will flow through the expanded cross-section, realizing the opening of the valve of the burst valve.

[0082] The size of the capillary pressure barrier depends on factors such as the surface tension of the liquid, the contact angle, the inner diameter of the capillary tube, and the angle of the cross-section expansion.

[0083] Specifically, the Young-Laplace equation is an algebraic equation that describes the capillary pressure difference on the interface between two stationary fluids, and its relationship with the capillary burst valve is:

[0084] The working principle of the capillary burst valve is to use the capillary pressure barrier to prevent the flow of liquid, and the size of the capillary pressure barrier can be calculated by the Young-Laplace equation.

[0085] The Young-Laplace equation shows that the capillary pressure barrier is related to factors such as the surface tension of the liquid, the contact angle, the inner diameter of the capillary tube, and the angle of the cross-section expansion.

[0086] The Young-Laplace equation can be used to predict the burst pressure of the capillary burst valve, thereby designing and optimizing the performance of the capillary burst valve.

[0087] Further, as shown in Figure 6 , preferably, in a square duct, β is the duct opening angle, the divergence angle. From the Young-Laplace equation, for a stationary but expanding interface, i.e. a bulging half-moon shaped gas-liquid interface as Figure 6 , and indicate the middle interface, there is

[0088]

[0089] where, is the width of the square duct, is the height of the duct. , is the minimum contact angle (critical advancing angle) of the liquid on this material.

[0090] For an interface that is about to move and expand to the extreme, that is, when the pressure difference inside and outside the interface is the largest,

[0091]

[0092] where, For the liquid to move from the narrow tube to the new width of the diffusion tube, i.e., as shown in Figure 6 The gas-liquid interface from the narrow tube to the diffusion tube part of the tube wall, the contact angle in the width direction becomes smaller, and the contact angle in the height direction, i.e., the outward direction perpendicular to the screen, does not change. Because the contact angle becomes smaller, the gas-liquid interface stops advancing and needs to expand to a sufficient angle to continue advancing. At this time, the contact angles of the four wall surfaces all reach the minimum contact angle (critical advancing angle) that can advance equally, .

[0093] The micro-pump-based advantage of the present application is that the flow rate of sweat can be adjusted according to different use scenarios, and corresponding sweat collection can be performed according to different sweat patterns. Before the breakthrough of the first burst valve, the pressure accumulates as shown in Figure 7 When the breakthrough pressure is reached, the pressure will drop partially when the sweat is filled, and when the sweat collection bin is completely filled, the liquid continues to advance to the micro-pipe. At this time, the pressure needs to continue to accumulate to be slightly higher than the previous maximum pressure accumulation, and enter the micro-pipe to perform the next sweat filling cycle.

[0094] The collection method of the sweat collection microfluidic patch based on the micro-pump of the present embodiment is as follows:

[0095] After the sweat is absorbed by the sweat absorption layer 20 of the sweat collection microfluidic patch, it is filled and collected into the sweat microfluidic layer 30 by the micro-pump 10. In the sweat microfluidic layer 30, the sweat first encounters a sweat priority determination structure, i.e., a passive burst valve 38. The sweat preferentially fills the sweat collection bin 34 with a small breakthrough pressure, and then the pressure increases. The newly generated sweat advances to the side arc-shaped flow channel 35, and then fills the sweat collection bin 34 again, and then advances to the next sweat collection bin 34 through the arc-shaped flow channel 35, until the sweat collection area 32 is filled. After filling the sweat collection area 32, the next sweat priority determination structure, i.e., the gradient burst valve 33, is encountered. After the gradient burst valve 33 is determined, the sweat preferentially flows to the sweat collection area 32 with a low breakthrough pressure. The filling process of the sweat collection area 32 is as described above. After filling the entire collection area 32, the pressure continues to increase, and the other valve outlet of the gradient burst valve 33 begins to flow out of the sweat and enters the next gradient burst valve 33. Then, the third sweat collection area 32 is preferentially filled, and then the fourth sweat collection area is filled after the pressure increases. Until the sweat collection bin of all the sweat collection areas is filled.

[0096] The present embodiment is suitable for sweat collection and analysis in a motion state.

[0097] Embodiment Two

[0098] The present embodiment provides a sweat collection microfluidic patch based on a micro-pump, as shown in Figure 5As shown, the sweat collection microfluidic patch includes a micropump 10, a sweat absorption layer 20, a sweat microfluidic layer 30, and a sealing layer 40, the sweat absorption layer 20, the sweat microfluidic layer 30, and the sealing layer 40 are stacked in order from bottom to top, and the micropump 10 is connected to the sweat absorption layer 20 and the sweat microfluidic layer 30. Among them, the sweat collection microfluidic patch includes a plurality of sweat microfluidic layers 30, the plurality of sweat microfluidic layers 30 are stacked, and each of the sweat microfluidic layers 30 are connected to each other.

[0099] In the sweat collection microfluidic patch of the embodiment, because the thickness of the sweat microfluidic layer 30 is very thin, the stacking design can be performed without increasing the thickness and weight too much, and without causing additional burden to the user. After the sweat fills the first sweat microfluidic layer 30, the sweat will fill the next sweat microfluidic layer 30 in turn, until all the collection reservoirs 34 of the sweat microfluidic layers 30 are filled.

[0100] The embodiment is suitable for sweat collection in extreme cases, greatly increases the time length of collecting sweat and the capacity of collecting sweat, and has great potential for component analysis for heatstroke prevention and heatstroke prevention. For example, after collecting the sweat of a mountaineer, the movement pattern analysis is performed to obtain information to warn the mountaineer to pay attention to his body state and avoid some dangers.

[0101] In addition, the embodiment also provides a preparation method of the sweat collection microfluidic patch based on the micropump, the preparation method further includes preparing a plurality of sweat microfluidic layers 30, and connecting and combining the plurality of sweat microfluidic layers 30 so that the plurality of sweat microfluidic layers 30 are stacked. The plurality of sweat microfluidic layers 30 are processed into the same medium, i.e., the same sweat collection microfluidic patch, thereby increasing the sweat collection capacity of the sweat collection microfluidic patch.

[0102] Specifically, the plurality of sweat microfluidic layers 30 are connected and combined so that the plurality of sweat microfluidic layers 30 can be stacked, thereby increasing the capacity of the time sequence collection of the sweat sample.

[0103] Preferably, the plurality of sweat microfluidic layers 30 are processed into the same sweat collection microfluidic patch of the same material or multiple materials, thereby increasing the sweat collection capacity of the sweat collection microfluidic patch.

[0104] The present application provides a long-time time-series collection of sweat by using the programmable and accurate active suction of a micro-pump, in-situ colorimetric detection of biochemical molecules such as blood sugar, lactic acid and some disease-related characteristic molecule concentrations in sweat, or non-instantaneous long-time and large-volume sweat accurate detection on a micro-fluidic platform, which can effectively play a role in personal physical condition understanding, sports state monitoring and even some disease prevention. The sweat detection can fully exert the great potential in personal physiological state monitoring and disease prevention, and can provide strong and stable technical support for researchers studying sweat and human-related metabolism.

[0105] Embodiment three

[0106] The present embodiment provides a sweat collection device integrating the sweat collection micro-fluidic patch of the above-mentioned embodiments, which is worn on the hand or body.

[0107] Since the overall thickness of the sweat collection micro-fluidic patch is very thin, the wearable sweat collection micro-fluidic patch can be changed into a wearable waist bag or backpack and the like, which is more conducive to sweat collection and user use.

[0108] Embodiment four

[0109] The present embodiment provides a preparation method of a sweat collection micro-fluidic patch, which comprises the following steps:

[0110] S100, preparing a sweat absorption layer. The sweat absorption layer 20 is prepared, which covers the skin surface, and the liquid inlet 21 is arranged on the sweat absorption layer 20.

[0111] S200, preparing a sweat micro-fluidic layer 30, a plurality of collection zones 32 are formed on the sweat micro-fluidic layer 30, each collection zone 32 comprises a plurality of collection bins 34, the collection zones 32 are connected through gradient burst valves 33, and the collection bins 34 are connected through flow channels 35. The sweat micro-fluidic layer 30 is further provided with a liquid inlet zone 31, a micro-channel 36, an extraction chamber 37 and a passive burst valve 38, the passive burst valve 38 is arranged in the flow channel 35, and the micro-channel 36 communicates with the extraction chamber 37.

[0112] S300, providing a sealing layer 40, the sweat absorption layer 20, the sweat micro-fluidic layer 30 and the sealing layer 40 are sequentially stacked from bottom to top to be integrated, cooperating with the micro-pump 10, to obtain a sweat collection micro-fluidic patch.

[0113] The preparation of the sweat micro-fluidic layer 30 comprises the following steps:

[0114] S210, preparing a template. Create micro- or nano-structures on a silicon wafer to form a template, and cover the template surface with a thin film of anti-adhesion material.

[0115] Preferably, S211, fabricating the template. Create micro- or nano-structures on a silicon wafer to form a template using electron beam lithography, ion beam sculpting, or laser drawing, etc. S212, coating the template. Cover the template surface obtained in step S212 with a thin film of anti-adhesion material, preferably, the anti-adhesion material can be a polymer similar to Teflon, for example.

[0116] S220, cleaning the substrate to be processed to remove surface contaminants and particles, and coating the substrate with a thin film of material matching the micro- or nano-structures on the template, to complete the preparation of the substrate. Preferably, S221, cleaning the substrate. Clean the substrate to be processed to remove surface contaminants and particles. S222, coating the substrate. Coat the cleaned substrate with a thin film of material matching the micro- or nano-structures on the template, preferably, the thin film material can be a polymer, for example.

[0117] S230, place the template and the substrate coated with the thin film together in contact, apply uniform pressure, and apply heat during the embossing process, to emboss the template and the substrate, to complete the embossing process of the template and the substrate.

[0118] Preferably, S231, template and substrate in contact. Place the substrate coated with the thin film material obtained in step S222 and the template obtained in step S212 together, so that their surfaces are in contact with each other. S232, apply pressure. Apply pressure to the template and the substrate after contact. Preferably, use a press or embossing equipment to apply uniform pressure; S233, apply heat, to complete hot embossing. Apply heat during the embossing process in step S232 to increase the flowability of the material and the bonding between the template and the substrate. Preferably, use hot embossing to cure the uncured PDMS to form the sweat microfluidic layer 30.

[0119] S240, separate the template from the substrate, clean the remaining template residues and impurities on the substrate, to form the sweat microfluidic layer.

[0120] Preferably, S241, separation. Separate the template from the substrate. Preferably, use mechanical force or chemical treatment to achieve separation of the template and the substrate. S242, cleaning. Clean the remaining template residues and impurities to ensure the purity of the resulting structure, to obtain the sweat microfluidic layer.

[0121] Further, in an alternative embodiment, the method of preparing a sweat collection microfluidic patch further comprises:

[0122] S10, design a three-dimensional model, and make a mold by 3D printing the three-dimensional model. Preferably, a design drawing software such as Soildworks software is used to draw a 3D model that meets the design, and then a 3D printer is used to print the designed 3D model to complete the mold making.

[0123] S20, prepare the uncured PDMS, and vacuum treat the uncured PDMS. Preferably, the uncured PDMS is obtained by mixing the PDMS and its matching curing agent at a ratio of 10:1, and the uncured PDMS is placed in a vacuum pump for vacuum treatment to remove bubbles in the PDMS.

[0124] S30, drop the vacuum treated PDMS into the mold, and vacuum treat it. Preferably, the uncured PDMS treated by the first vacuum treatment in step S20 is poured into the printed mold obtained in step S10, and then the second vacuum treatment is performed again to remove bubbles in the PDMS.

[0125] S40, drop and spin coat the vacuum treated PDMS on a glass flat plate. Preferably, the uncured PDMS obtained in step S20 is dropped on a glass flat plate and spin coated by a spin coater to obtain a 0.5mm thick PDMS thin layer as a surface sealing layer 40.

[0126] S50, heat and cure the mold with dropped PDMS and the glass flat plate with surface sealing layer, and perform surface treatment on the cured PDMS surface to form a sweat microfluidic layer and a surface sealing layer, respectively. Preferably, the mold with uncured PDMS of step S30 and the glass flat plate with surface sealing layer of step S40 are placed in a 65° oven for curing for two hours to make them solidify. Then, the cured PDMS is placed in a plasma surface cleaner for surface treatment for ninety seconds. Finally, a sweat microfluidic layer and a surface sealing layer are formed, respectively.

[0127] As an optional step, S60, embed a colorimetric test paper in the sweat collection reservoir 34 of the sweat microfluidic layer 30. Preferably, the colorimetric test paper is embedded in the sweat collection reservoir 34 of the sweat microfluidic layer 30.

[0128] S70, adhere the surface treated sweat microfluidic layer 30 and the surface sealing layer 40 to form a sweat collection microfluidic patch. Preferably, the PDMS (sweat microfluidic layer 30 and surface sealing layer 40) obtained through steps S60 and S70 is adhered to further obtain a complete sweat collection microfluidic patch.

[0129] In addition, the sweat collection microfluidic patch can be connected to a watchband of a device integrated with the micropump 10, and tied tightly at the wrist to perform exercise and open the device for long-term sweat collection.

[0130] Further, in an alternative embodiment, the method for preparing the sweat collection microfluidic patch further comprises using a soft lithography preparation method.

[0131] S1, design a two-dimensional model, and make a two-dimensional graph of the layer where the microfluidic channel is located. Draw the designed two-dimensional graph using L-Edit software.

[0132] S2, clean the surface of the silicon wafer and perform drying treatment on the silicon wafer. Clean the surface of the silicon wafer, use plasma cleaning for 100 seconds, and then perform 170°C drying on the silicon wafer, which lasts for ten minutes.

[0133] S3, spin coating of photoresist on the dried silicon wafer. Spin coating of SU8 photoresist on the dried silicon wafer to obtain a 100-micron-thick SU8 gel on the surface of the silicon wafer.

[0134] S4, first baking of the silicon wafer, laser direct writing with the two-dimensional graph, and second baking after laser direct writing. Perform baking-laser direct writing-baking treatment on the silicon wafer.

[0135] S5, develop the silicon wafer after the second baking to form a soft lithography template. Develop the silicon wafer after laser direct writing to obtain a soft lithography template.

[0136] S6, PDMS reverse molding of the soft lithography template to obtain a sweat microfluidic layer. Perform PDMS reverse molding on the soft lithography template obtained in step S5 to obtain a sweat microfluidic layer 30 consistent with the pre-design.

[0137] After step S6, the sweat absorption layer 20, the sweat microfluidic layer 30, and the sealing layer 40 can be integrated with the micropump 10 to make a sweat collection device, connected to a watchband, tightened at the wrist, and moved to open the device for long-term sweat collection, or can be worn on the arm or body for sweat collection.

[0138] The specific structure of the sweat collection microfluidic patch can be referred to the above definition of the sweat collection microfluidic patch, which will not be repeated here.

[0139] It should be understood that although the steps are shown in sequence, these steps are not necessarily executed in sequence. Unless otherwise specified herein, the execution of these steps is not strictly limited in sequence, and these steps can be executed in other sequences. Moreover, at least part of the steps can include multiple sub-steps or multiple stages, which are not necessarily executed at the same time, but can be executed at different times, and the execution sequence of these sub-steps or stages is not necessarily sequential, but can be executed in rotation or alternation with at least part of other steps or sub-steps or stages of other steps.

[0140] The sweat collection microfluidic patch and the preparation method thereof introduce the gradient burst valve to be able to collect for a longer time, multiple times the collection time of the prior art, and multiple sweat collection volumes; the burst valve is arranged to be able to avoid mixing of new and old sweat, and to reduce the replacement frequency of the microfluidic patch in the same time; the programmable controllable micropump is introduced to make the output sweat pressure more stable, which is conducive to the collection of sweat; the microfluidic patch can be combined with a large-flux microfluidic platform to perform large-scale accurate detection and better play the potential of sweat detection; due to the stable sweat input pressure, a multi-layer structure can be designed to greatly improve the use efficiency per unit area, and the patch form can be expanded to a waist bag and a backpack for sweat collection.

[0141] The technical features of the above embodiments can be combined in any manner. To make the description concise, all possible combinations of the technical features in the above embodiments are not described, but as long as the combinations of the technical features do not contradict, they should be considered as falling within the scope of the present disclosure.

[0142] The above embodiments only express several implementation manners of the present application, and the description is relatively specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be pointed out that, for those skilled in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A microfluidic patch for sweat collection based on a micropump, characterized in that, The sweat-collecting microfluidic patch includes a micropump, a sweat-absorbing layer, a sweat microfluidic layer, and a sealing layer, which are stacked sequentially from bottom to top; wherein... The sweat absorption layer is provided with a liquid inlet, the sweat microfluidic layer is provided with a liquid inlet area, and the micro pump transports sweat from the liquid inlet of the sweat absorption layer to the liquid inlet area of ​​the sweat microfluidic layer. The sweat microfluidic layer is further provided with multiple collection areas, which are connected by gradient burst valves. One of the collection areas is connected to the liquid inlet area. The gradient burst valve includes a valve inlet and multiple valve outlets. Each valve outlet is connected to a valve outlet channel. The multiple valve outlets include a first valve outlet and at least one second valve outlet. The width of the valve outlet channel of the first valve outlet is greater than the width of the valve outlet channel of the second valve outlet. Sweat selectively flows into the corresponding valve outlet channel from the first valve outlet or the second valve outlet.

2. The microfluidic patch for sweat collection based on a micropump according to claim 1, characterized in that, Each collection area is provided with multiple collection bins, and two adjacent collection bins are connected by a flow channel. Each flow channel is provided with one or more flow outlets, and the flow outlets are connected to the flow channel or the collection bins.

3. The microfluidic patch for sweat collection based on a micropump according to claim 2, characterized in that, The outlet of the collection chamber is connected to the extraction chamber corresponding to each collection chamber through a microchannel.

4. The microfluidic patch for sweat collection based on a micropump according to claim 2, characterized in that, Each of the aforementioned circulation channels is also equipped with a passive burst valve, which controls the flow of sweat to the circulation channel or collection chamber.

5. The microfluidic patch for sweat collection based on a micropump according to claim 1, characterized in that, The sweat collection microfluidic patch includes multiple sweat microfluidic layers, which are stacked and interconnected.

6. The method for preparing a microfluidic patch for sweat collection based on a micropump according to any one of claims 1-5, characterized in that, The preparation method includes: Prepare a sweat-absorbing layer; A sweat microfluidic layer is prepared, and multiple collection areas are formed on the sweat microfluidic layer. Each collection area includes multiple collection chambers. The collection areas are connected by gradient burst valves, and the collection chambers are connected by flow channels. A sealing layer is provided, which is made by stacking the sweat absorption layer, the sweat microfluidic layer and the sealing layer from bottom to top into one piece.

7. The method for preparing a microfluidic patch for sweat collection based on a micropump according to claim 6, characterized in that, The preparation of the sweat microfluidic layer further includes: Micron or nanostructures are created on a silicon wafer to form a template, and a thin film is covered on the surface of the template, the film being an anti-adhesion material. Clean the substrate to be processed, remove surface contaminants and particles, and coat the substrate with a thin film material that matches the micron or nanostructure on the template. Depending on the selected imprinting method, the substrate coated with the film is brought into contact with and aligned with the template, and imprinting is performed under appropriate pressure and temperature. The imprinting method is either thermal imprinting or ultraviolet imprinting. After complete curing, the template is separated from the substrate, and any remaining template residue and impurities on the substrate are cleaned to form a sweat microfluidic layer.

8. The method for preparing a microfluidic patch for sweat collection based on a micropump according to claim 6, characterized in that, The preparation method further includes: Design a 3D model, and then create a mold by 3D printing the 3D model. Prepare uncured PDMS and perform vacuum treatment on the uncured PDMS; Vacuum-treated PDMS is dropped into the mold and then subjected to vacuum treatment. The vacuum-treated PDMS was drop-coated onto a glass plate. The mold and the glass plate on which PDMS was dropped are heated and cured. The surface of the cured PDMS is then surface-treated to form a sweat microfluidic layer and a sealing layer, respectively. The surface-treated sweat microfluidic layer and the sealing layer are bonded together to form a sweat-collecting microfluidic patch.

9. The method for preparing a microfluidic patch for sweat collection based on a micropump according to claim 8, characterized in that, Use Dragon Skin or Ecoflex materials instead of PDMS.

10. The method for preparing a microfluidic patch for sweat collection based on a micropump according to claim 6, characterized in that, The preparation of the sweat microfluidic layer further includes: Design and draw a two-dimensional graphic of the layer containing the microfluidic channel; Clean the surface of the silicon wafer and then dry it. The dried silicon wafer is then spin-coated with photoresist. The silicon wafer undergoes a first baking process, the two-dimensional pattern is imported and laser direct writing is performed, and a second baking process is performed after the laser direct writing. The silicon wafer that has undergone secondary baking is developed to form a soft photolithography template; The soft photolithography template is molded using PDMS to obtain the sweat microfluidic layer.

11. The method for preparing a micropump-based sweat collection microfluidic patch according to any one of claims 6-10, characterized in that, The preparation method further includes: A sweat collection device is formed by integrating a sweat microfluidic patch and a micropump, which is worn on the hand or body.

12. The method for preparing a microfluidic patch for sweat collection based on a micropump according to any one of claims 6-10, characterized in that, Multiple sweat microfluidic layers are prepared, and the multiple sweat microfluidic layers are connected and combined, and the multiple sweat microfluidic layers are stacked one on top of the other.

13. The method for preparing a microfluidic patch for sweat collection based on a micropump according to claim 12, characterized in that, The multiple sweat microfluidic layers are processed into the same sweat collecting microfluidic patch made of the same material or multiple materials, thereby increasing the sweat collecting capacity of the sweat collecting microfluidic patch.

Images