CN119819392A - Two-sided microfluidic chip and preparation method thereof - Google Patents

Abstract

A two-sided microfluidic chip and a preparation method thereof, belonging to the field of sweat sensing. From bottom to top, it is divided into a skin-applying layer, a microfluidic channel layer, and a top layer; the microfluidic channel layer includes a main channel and multiple cavities, the main channel is surrounded by a semi-closed ring structure such as a circle or an ellipse with an opening, a cavity is provided in the central area as a liquid inlet, and the main channel is also connected to multiple cavities on the outside of the semi-closed ring structure in sequence, and an arrow-shaped "burst valve" is provided between any two adjacent sweat storage tanks; the arrow points in the same direction as the liquid flow direction. The inside of the chip becomes hydrophilic after being treated with chemical reagents, while the outside of the chip remains hydrophobic. The present invention introduces a "burst valve" structure and designs hydrophilicity at the same time to achieve sequential filling of liquid inside the chip. Under the influence of the burst pressure, the "burst valve" structure will hinder the flow of liquid in the flow channel until the previous flow channel and liquid storage tank are filled, thereby avoiding the mixing of samples in different time periods.

Description

Two-sided microfluidic chip and preparation method thereof

Technical Field

The invention relates to a double-sided (JANUS) microfluidic chip for sweat collection and a preparation method thereof, belonging to the field of sweat sensing.

Background

The microfluidic chip can be used in the sweat sensing field, sweat is collected and stored by a microfluidic technology, and physiological indexes in sweat are measured by electrochemical sensing or Raman detection and other methods, so that sweat sensing is realized. The sweat collection mode has remarkable advantages in the sweat sensing field, firstly, the required sample amount is small, the required sweat amount can be low to microliter or even nanoliter, and the chip is small in size, light in weight and convenient to integrate into wearable equipment.

The material of the commonly used microfluidic chip is Polydimethylsiloxane (PDMS), which is also called PDMS and has the advantages of good biocompatibility, thermal stability, flexibility and the like, and has great advantages in the sweat collecting field. However, as the PDMS material itself has a strong hydrophobicity, the liquid to be measured needs an external force to be pumped into the chip, which greatly reduces the collection efficiency, and the chip can not be wearable, and meanwhile, the liquid flows randomly inside the chip, so that the samples collected in different time periods can not be distinguished, and the problems limit the practicality of the microfluidic chip for sweat collection.

Disclosure of Invention

The invention aims to solve the technical problem of providing a microfluidic chip and a preparation method thereof, and solves the problem that liquid cannot flow into the chip independently due to the hydrophobicity of PMDS materials in the microfluidic chip applied to sweat collection and detection, and realizes sequential circulation of samples in the chip by using a blasting valve structure.

The micro-fluidic chip based on the PDMS material is divided into a skin attaching layer, a micro-flow channel layer and a top layer from bottom to top, wherein a micro-flow channel structure is arranged in the micro-flow channel layer and comprises a main flow channel and a plurality of cavities, the cavities are of an up-down through hole structure, the main flow channel is surrounded into a semi-closed loop structure with an opening, such as a round shape or an oval shape, the central area of the semi-closed loop structure is provided with a cavity serving as a liquid inlet, the main flow channel is sequentially connected and communicated with the cavities outside the semi-closed loop structure, the cavities outside the semi-closed loop structure form Chu Hanchi for storing sweat, the main flow channel between any two adjacent sweat storage tanks is provided with a blasting valve of an arrow-shaped structural channel, and the arrow direction is consistent with the flowing direction of liquid. The liquid inlet is connected and communicated with the starting end of the main flow channel, and the connection and the communication adopt micro-channel connection and communication.

The skin-adhering layer is provided with a micro-pore array area which is transparent up and down and is used for transporting sweat, the micro-pore array area corresponds to the liquid inlet of the micro-flow channel layer up and down to form the liquid inlet of the chip together, a cavity at the tail end of the main flow channel is used as the liquid outlet at the same time, the top layer is used for sealing the chip, the top layer is provided with a plurality of micro-pore array areas, each micro-pore array area corresponds to the cavity area of the micro-flow channel layer, the micro-pores of the micro-pore array are used for balancing internal and external air pressure, the inside of the chip is changed into hydrophilcity after being treated by chemical reagents, the hydrophilcity of PDMS material is still kept outside the chip, and the change into hydrophilcity after being treated by the chemical reagents means that the PVA is adopted for treatment.

Further, the diameter of the skin layer micropore array area was 3mm, the micropore pitch in the micropore array was 200 μm, and the micropore diameter was 82.5 μm.

Further, the top layer is used for sealing the chip, the top layer is provided with a plurality of micropore array areas, each micropore array area corresponds to one cavity area on the outer side of the semi-closed loop structure of the cavity microfluidic channel layer and is used for balancing the micropore array of internal and external air pressure, the adjacent micropore distance of the micropore array of the top layer is 400 mu m, and the micropore diameter is 30 mu m.

Further, the width of the main flow channel is 200 mu m, an arrow-shaped 'explosion valve' structure exists in the main flow channel, and the arrow points to be consistent with the flowing direction of the liquid. The starting width of the arrow-shaped 'explosion valve' structure is 600 mu m, the tail width is consistent with the width of the main runner and is 200 mu m, and the included angles between the starting and tail ends and the main runner are 90 DEG and 135 DEG respectively.

Further, the thickness of the skin layer, the thickness of the inner flow channel layer and the thickness of the top layer are 200 mu m, and the diameter of the chip is 30mm, and the second method is realized by the steps of:

(1) Uniformly coating the mixed solution on a chip template and a cover plate template respectively, and thermally curing for 2 hours at 90 ℃;

respectively taking down the cured films from the two templates to respectively obtain a PDMS chip main body with a microfluidic channel structure and a skin layer, wherein the chip main body correspondingly comprises a top layer and a microfluidic channel layer;

(2) Preparing an air hole array by using power laser at all cavities except a liquid inlet on the top layer of the PDMS chip main body;

preparing a micropore array corresponding to the liquid inlet by using power laser at the position of the skin-adhering layer corresponding to the liquid inlet;

(3) Bonding the chip main body and the skin layer by an oxygen plasma treatment method to obtain a microfluidic chip;

(4) And hydrophilizing the interior of the microfluidic chip by a method of growing a PVA hydrophilic coating inside the chip, thereby forming a Janus structure.

Further, the step (2) of preparing the micropore array on the PDMS chip material by using laser specifically comprises the steps of focusing laser spots to a micron level by using a microscope, irradiating the surface of the PDMS material to prepare micropores, and realizing the preparation of the micropore array by using a displacement platform and control software;

The oxygen plasma bonding micro-fluidic chip in the step (3) is characterized in that a chip main body and a skin layer are sent into a cavity of a plasma etching machine, vacuum is pumped after sealing, the chip is processed for 120s, and the chip is quickly assembled after being taken out to form a firm chemical bond;

Further, after bonding, the PVA hydrophilic coating grows in the chip, and the chip is in a hydrophilic state in a short time due to oxygen plasma treatment, at the moment, PVA colloid aqueous solution is dripped into the chip from a liquid inlet, PVA solution residues on the outer side of the chip are cleaned, the PVA colloid aqueous solution is put into an oven for thermal curing, the hydrophilic coating is formed in the chip, and PDMS on the outer side of the chip is restored to a hydrophobic state, so that a hydrophilic structure on the inner side of the chip and a hydrophobic structure on the outer side of the chip are formed.

The application method of the microfluidic chip is characterized in that a skin-sticking layer is stuck to the surface of skin, sweat at a first moment enters from a liquid inlet and then is guided into a first sweat storage tank corresponding to a main flow channel, after the first sweat storage tank is full, sweat at a second moment enters into a corresponding second sweat storage tank, after the second sweat storage tank is full, sweat at a third moment enters into a corresponding third sweat storage tank, and the like until the last sweat storage tank is filled, namely a liquid outlet or enters into one sweat storage tank in the middle according to the requirement to stop, and due to the existence of a burst valve structure, sweat in the sweat storage tank cannot flow at will, so that mixing of samples at different time periods is avoided.

The microfluidic chip and the preparation method thereof have the advantages that the microfluidic chip can be applied to collection and detection of human sweat. The hydrophilic difference of the inner side and the outer side of the micropore array at the liquid inlet of the chip is obtained by a method of growing the PVA hydrophilic coating, and the two-sided difference generates a unidirectional conduction effect of liquid, namely the liquid spontaneously moves from the hydrophobic outer side to the hydrophilic inner side of the micropore array, and the liquid is prevented from overflowing to the hydrophobic outer side under the action of no external force, so that the collection efficiency of the microfluidic chip on body surface sweat is effectively improved;

in addition, the invention introduces a burst valve structure on the basis of the conventional microfluidic technology, and realizes sequential filling of liquid in the chip by burst pressure. Under the influence of burst pressure, the burst valve structure can obstruct the liquid circulation in the flow channel until the previous flow channel and the liquid storage tanks are completely filled, so that collected sweat is sequentially filled into each liquid storage tank, and the mixing of samples in different time periods is avoided.

Drawings

The invention will be further described with reference to examples of embodiments with reference to the accompanying drawings.

Fig. 1 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention.

Fig. 2 is a schematic structural diagram of a microfluidic channel according to an embodiment of the present invention.

FIG. 3 is a flowchart illustrating steps performed in accordance with an embodiment of the present invention.

Fig. 4 is an effect display diagram of a Janus structure in an embodiment of the present invention.

Fig. 5 is a view showing the effect of the "burst valve" structure in the embodiment of the present invention.

Detailed Description

Referring to fig. 1 and 2, the microfluidic chip of the invention is formed by bonding three layers of films made of PDMS, and the structure comprises a skin layer, a microfluidic channel layer and a top layer from bottom to top, wherein the diameter of the chip is 30mm, the thicknesses of the skin layer, the inner channel layer and the top layer are all 200 μm, the inside of the chip becomes hydrophilic after being treated by chemical reagents, and the outside of the chip still keeps the hydrophobicity of the PDMS; the central area of the skin-sticking layer is provided with a micropore array area for sweat transportation, the diameter of the area is 3mm, the distance between micropore arrays is 200 mu m, the diameter of micropores is 82.5 mu m, a microchannel structure is arranged in the microchannel layer, the microchannel structure comprises a main channel and a plurality of cavities connected with the main channel, the cavities in the central area and the micropore arrays of the skin-sticking layer form a liquid inlet of a chip together, the rest cavities serve as Chu Hanchi for sweat storage, the cavities at the tail ends of the channels serve as liquid outlets at the same time, the width of the main channel is 200 mu m, an arrow-shaped explosion valve structure is arranged in the main channel, the arrow points are consistent with the flowing direction of liquid, the initial width of the arrow-shaped explosion valve structure is 600 mu m, the tail width is consistent with the width of the main channel, the included angles between the initial and the tail ends of the main channel are 90 DEG and 135 DEG respectively, the top layer is used for sealing the chip, the micropore arrays for balancing the air pressure inside and outside the micropore arrays are 400 mu m, and the micropore array is 30 mu m.

As shown in fig. 3, the preparation method of the microfluidic chip of the present invention specifically includes the following steps:

Preparing PDMS gel, coating the PDMS gel on a mold, and thermally curing to obtain a micro-fluidic chip main body (a micro-fluidic channel layer and a top layer) and a skin-adhering layer;

preparing a micropore array for balancing internal and external air pressure at each cavity of the chip main body by utilizing a laser processing method;

preparing a micropore array for sweat transportation by using a laser processing method in the central area of the skin-contacting layer;

bonding the chip main body and the skin layer by an oxygen plasma treatment method to obtain a microfluidic chip;

And hydrophilizing the interior of the microfluidic chip by a method of growing a PVA hydrophilic coating inside the chip, thereby forming a Janus structure.

The preparation of the micropore array on the PDMS material by laser comprises focusing laser spots to a micron level by using a microscope, irradiating the surface of the PDMS material to prepare micropores, and realizing the preparation of the micropore array by using a displacement platform and control software;

the oxygen plasma bonding micro-fluidic chip is characterized in that a chip main body and a cover plate are sent into a cavity of a plasma etching machine, vacuum is pumped after sealing, and the micro-fluidic chip is processed for 60 seconds, and two sample films are taken out and then are quickly assembled to form a firm chemical bond;

After bonding is completed, the chip is in a hydrophilic state in a short time due to oxygen plasma treatment, at the moment, PVA solution is led into the chip, PVA solution residue outside the chip is cleaned, the PVA solution is put into an oven for thermal curing, the hydrophilic coating is formed inside the chip, and PDMS outside the chip is restored to a hydrophobic state, so that a hydrophilic structure inside the chip and a hydrophobic structure outside the chip are formed;

The effect of the Janus structure on the droplets on the hydrophilic side, the hydrophobic side, is shown in FIG. 4, where the droplets on the hydrophilic side cannot pass through the Janus microporous membrane, while the droplets on the hydrophobic side can pass through the microporous membrane quickly.

The effect of the microfluidic chip is shown in fig. 5, liquid spontaneously flows into the chip due to the Janus structure, and as shown in fig. S1 and S2, before filling the cavity before the explosion valve, the liquid cannot pass through the explosion valve, and after the previous cavity is filled, the liquid flows through the explosion valve and enters the next cavity, and the process is circulated until the whole chip is filled.

Claims (9)

1. A two-sided microfluidic chip based on PDMS material, characterized in that it is divided into a skin-applying layer, a microfluidic channel layer, and a top layer from bottom to top; a microfluidic channel structure exists in the microfluidic channel layer, which includes: a main channel, a plurality of cavities, and the cavities are hole structures that are transparent from top to bottom; the main channel is surrounded by a semi-closed ring structure such as a circle or an ellipse with an opening, wherein a cavity is provided in the central area of the semi-closed ring structure as a liquid inlet, and the main channel is also connected and communicated with multiple cavities outside the semi-closed ring structure in sequence, and the multiple cavities outside the semi-closed ring structure constitute a sweat storage pool for storing sweat, and an arrow-shaped structural channel "burst valve" is provided on the main channel between any two adjacent sweat storage pools; the arrow points in the same direction as the liquid flow direction; the liquid inlet is connected and communicated with the starting end of the main channel, and the connection is connected and communicated by a microchannel connection; A microporous array area that is transparent from top to bottom is provided in the center of the skin-applying layer. The micropores are used to transport sweat. The microporous array area corresponds to the liquid inlet of the microfluidic channel layer from top to bottom, and together they constitute the liquid inlet of the chip; the cavity at the end of the main channel also serves as the liquid outlet; the top layer is used to seal the chip, and the top layer is provided with a plurality of microporous array areas, each of which corresponds to the area of the cavity of the aforementioned microfluidic channel layer, and the micropores of the microporous array are used to balance the internal and external air pressures; the inside of the chip becomes hydrophilic after being treated with chemical reagents, while the outside of the chip still maintains the hydrophobicity of the PDMS material. 2. A two-sided microfluidic chip based on PDMS material according to claim 1, characterized in that the chemical reagent treatment to become hydrophilic refers to the use of PVA treatment to become hydrophilic. 3. A two-sided microfluidic chip based on PDMS material according to claim 1, characterized in that the diameter of the micropore array area of the skin-attaching layer is 3 mm, the micropore spacing in the micropore array is 200 μm, and the micropore diameter is 82.5 μm; the top layer is used to seal the chip, and the top layer is provided with multiple micropore array areas, each micropore array area corresponds to a cavity area outside the semi-closed ring structure of the cavity microfluidic channel layer, and the micropore array is used to balance the internal and external air pressures. The spacing between adjacent micropores of the micropore array in the top layer is 400 μm, and the micropore diameter is 30 μm. 4. A two-sided microfluidic chip based on PDMS material according to claim 1, characterized in that the width of the main channel is 200 μm, and there is an arrow-shaped "burst valve" structure in the main channel, and the arrow points in the same direction as the liquid flow; the starting width of the arrow-shaped "burst valve" structure is 600 μm, and the ending width is consistent with the width of the main channel, both of which are 200 μm. 5. A two-sided microfluidic chip based on PDMS material according to claim 1, characterized in that the angles between the start and the end of the main channel are 90° and 135° respectively. 6. A two-sided microfluidic chip based on PDMS material according to claim 1, characterized in that the thickness of the skin-applying layer, the internal flow channel layer, and the top layer are all 200 μm, and the chip diameter is 30 mm. 7. A method for preparing a two-sided microfluidic chip based on PDMS material according to any one of claims 1 to 6, characterized in that it specifically comprises the following steps: (1) stirring the PDMS precursor and the crosslinking agent for 30 min; applying the mixed solution evenly on the chip template and the cover template, respectively, and thermally curing at 90° C. for 2 h; The cured films are removed from the two templates respectively to obtain a PDMS chip body with a microfluidic channel structure and a skin-attaching layer, wherein the chip body correspondingly includes a top layer and a microfluidic channel layer; (2) using a high-power laser to prepare an array of air holes in all cavities except the liquid inlet on the top layer of the PDMS chip body; At a position of the skin-applying layer corresponding to the liquid inlet, a micropore array corresponding to the liquid inlet is prepared by using a high-power laser; (3) bonding the chip body and the skin-attaching layer by oxygen plasma treatment to obtain a microfluidic chip; (4) The interior of the microfluidic chip is hydrophilized by growing a PVA hydrophilic coating inside the chip, thereby forming a Janus structure. 8. The method according to claim 7, characterized in that step (2) preparing the microwell array on the PDMS chip material by using a laser comprises: focusing the laser spot to a micrometer level using a microscope, and irradiating the laser spot on the surface of the PDMS material to prepare the microwells, and using a displacement platform and control software to realize the preparation of the microwell array; The step (3) of bonding the microfluidic chip with oxygen plasma is specifically as follows: the chip body and the skin-attaching layer are placed in the chamber of a plasma etcher, and vacuumized after sealing, and processed for 120 seconds, and then quickly assembled after being taken out to form a strong chemical bond; The step (4) of growing a PVA hydrophilic coating inside the chip is specifically as follows: after bonding is completed, the chip is in a hydrophilic state for a short period of time due to oxygen plasma treatment, at which time a PVA colloidal aqueous solution is dripped into the chip from the liquid inlet, and the PVA solution residue on the outside of the chip is cleaned off. After being placed in an oven for thermal curing, a hydrophilic coating is formed inside the chip, and at the same time, the PDMS outside the chip returns to a hydrophobic state, thereby forming a two-sided structure in which the inside of the chip is hydrophilic and the outside of the chip is hydrophobic. 9. A method for using a two-sided microfluidic chip based on PDMS material as described in any one of claims 1-6, characterized in that the skin-attaching layer is attached to the skin surface, sweat at the first moment enters from the liquid inlet and is then introduced into a first sweat storage pool corresponding to the main channel, when the first sweat storage pool is full, the sweat enters the corresponding second sweat storage pool at the second moment, when the second sweat storage pool is full, the sweat enters the corresponding third sweat storage pool at the third moment, and so on until the last sweat storage pool, i.e., the liquid outlet, is filled or the sweat enters a certain sweat storage pool in the middle as needed and stops; due to the existence of the "bursting valve" structure, the sweat in the sweat storage pool cannot flow arbitrarily, thereby avoiding the mixing of samples in different time periods.