阅读说明：本技术 一种多孔微针经皮递药及体液检测系统 (Porous microneedle transdermal drug delivery and body fluid detection system ) 是由 张武 林佳翰 林彦晓 尹舒琪 郭泽楷 董鹏才 胡裕鸿 于 2021-08-31 设计创作，主要内容包括：一种多孔微针经皮递药及体液检测系统,包括微针层、通道层和检测模块；微针层包括n组给药微针和m组检测微针,每组给药微针包括多个呈线性排布的多孔微针,每组检测微针包括多个呈线性排布的多孔微针；微针层中,每组给药微针与其他任意一组给药微针之间互不连通,每组给药微针与任意一组检测微针之间互不连通；通道层上设有n条条形的凹槽,凹槽的一端连接有药物入口,从而凹槽的内部形成传递药物的给药通道,药物入口经给药通道与给药微针连通,n组给药微针分别与n条凹槽一一对应；检测模块与检测微针连接,n≥2,m≥1。本发明具有独立的给药通道和检测通道,可连续给药,并实现给药与检测的诊疗一体化,属于经皮给药技术领域。(A porous microneedle transdermal drug delivery and body fluid detection system comprises a microneedle layer, a channel layer and a detection module; the microneedle layer comprises n groups of administration microneedles and m groups of detection microneedles, each group of administration microneedles comprises a plurality of linearly arranged porous microneedles, and each group of detection microneedles comprises a plurality of linearly arranged porous microneedles; in the microneedle layer, each group of drug delivery microneedles is not communicated with any other group of drug delivery microneedles, and each group of drug delivery microneedles is not communicated with any group of detection microneedles; the channel layer is provided with n strip-shaped grooves, one ends of the grooves are connected with drug inlets, so that drug delivery channels for delivering drugs are formed inside the grooves, the drug inlets are communicated with drug delivery micro-needles through the drug delivery channels, and the n groups of drug delivery micro-needles are respectively in one-to-one correspondence with the n grooves; the detection module is connected with the detection micro-needle, n is more than or equal to 2, and m is more than or equal to 1. The invention has independent drug delivery channel and detection channel, can continuously deliver drug, realizes the diagnosis and treatment integration of drug delivery and detection, and belongs to the technical field of transdermal drug delivery.)

1. A porous microneedle transdermal drug delivery and body fluid detection system is characterized in that: the micro-needle detection device comprises a micro-needle layer, a channel layer and a detection module;

the microneedle layer comprises n groups of administration microneedles and m groups of detection microneedles, each group of administration microneedles comprises a plurality of linearly arranged porous microneedles, and each group of detection microneedles comprises a plurality of linearly arranged porous microneedles;

in the microneedle layer, each group of drug delivery microneedles is not communicated with any other group of drug delivery microneedles, and each group of drug delivery microneedles is not communicated with any group of detection microneedles;

the channel layer is provided with n strip-shaped grooves, one ends of the grooves are connected with drug inlets, so that drug delivery channels for delivering drugs are formed inside the grooves, the drug inlets are communicated with drug delivery micro-needles through the drug delivery channels, and the n groups of drug delivery micro-needles are respectively in one-to-one correspondence with the n grooves;

the detection module is connected with the detection micro-needle, n is more than or equal to 2, and m is more than or equal to 1.

2. The system according to claim 1, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: the detection module comprises a detection electrode, the needle head of the porous microneedle is positioned on the front side of the microneedle layer, the detection electrode is attached to the back side of the microneedle layer, and the position of the detection electrode is matched with the position of the detection microneedle;

the groove is arranged on the front surface of the channel layer, the front surface of the channel layer faces to the back surface of the microneedle layer, and the opening position of the groove is adapted to the position of the drug delivery microneedle, so that the drug is permeated into the drug delivery microneedle from the opening of the groove.

3. The system according to claim 2, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: the gap layer is positioned between the microneedle layer and the channel layer, the detection electrode is fixed on the gap layer, n strip-shaped avoiding holes are formed in the gap layer, the positions of the avoiding holes are matched with the positions of the administration microneedles, and therefore the drugs in the grooves enter the administration microneedles through the avoiding holes.

4. The system according to claim 1, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: still include flow rate control module, flow rate control module includes fixed bed and first press the structure, the fixed bed is located the back on channel layer, it has first installation through-hole to open on the fixed bed, be equipped with first station on the recess, the opening of first installation through-hole is towards first station, first press the structure and pass first installation through-hole, first press the structure with adjustable be connected with first installation through-hole, the channel layer is made by flexible material, first press the structure from the back extrusion on channel layer or loosen the passageway of dosing.

5. The system according to claim 4, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: n is 3, the 3 grooves are respectively a middle groove and two side grooves, and the middle groove is positioned between the two side grooves;

a transverse groove is arranged between the side groove and the middle groove, and a connecting channel for communicating the middle groove and the side groove is formed in the transverse groove;

the intersection point of the lateral groove and the transverse groove is far away from the medicine inlet relative to the first station on the lateral groove, and the intersection point of the middle groove and the transverse groove is positioned between the medicine inlet and the first station on the middle groove;

the flow rate control module further comprises a second pressing structure, a second station is arranged on the transverse groove, a second mounting through hole is formed in the fixing layer, the opening of the second mounting through hole faces the second station, the second pressing structure penetrates through the second mounting through hole, the second pressing structure is connected with the second mounting through hole in an adjustable mode, and the second pressing structure extrudes or loosens the connecting channel from the back face of the channel layer.

6. The system according to claim 5, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: the first pressing structure and the second pressing structure are screws, and the screws are in threaded connection with the fixing layer.

7. The system according to claim 1, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: the material of the porous microneedle comprises polyglycidyl methacrylate.

8. The system according to claim 5, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: and m is 2, the detection microneedles and the administration microneedles are arranged at intervals, the number of the detection electrodes is two, and the two groups of detection electrodes respectively correspond to the two groups of detection microneedles.

9. The system according to claim 1, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: a curved groove is arranged between one end of the groove and the medicine inlet.

10. The system according to claim 3, wherein the porous microneedle transdermal delivery and body fluid testing system comprises: the channel layer and the gap layer are made of flexible PDMS.

Technical Field

The invention relates to the technical field of transdermal drug delivery, in particular to a porous microneedle transdermal drug delivery and body fluid detection system.

Background

Compared with the traditional invasive needle, the micro-needle transdermal drug delivery technology has the characteristic of minimally invasive painless, and is easy to develop a biological electronic integrated device for informatization detection. Compared with oral administration, transdermal administration has the clinical advantage of being more stable and safer. The length of the micro-needle structure is between 50 and 900 microns, and the micro-needle structure can penetrate through the stratum corneum of the skin to be in micro-contact with the dermis, but does not contact with blood vessels and nerves deep in the dermis, so that the problems of irritation pain to nerve endings, bleeding, inflammation and scabbing and the like are avoided, and the treatment compliance and the acceptability of patients are improved. The preparation of the micro-needle is based on the development requirements of simple processing, controllable release and high drug loading, various micron-scale needle arrays are prepared by a micro-nano processing technology, the early solid micro-needle is developed into the hollow micro-needle, and then the coating micro-needle, the soluble micro-needle, the swelling micro-needle and the porous micro-needle are developed by changing materials and processing technologies. The microneedle drugs are usually directly carried on a needle point or a substrate, and the technical requirements of high drug-loading capacity, controllable release, extraction function and other precise medical treatment are difficult to meet at the same time. In addition, microneedles are also used to extract subcutaneous body fluids for detection of components in the body fluids.

The porous micro-needle is chemically synthesized into a micro-needle array with certain porosity, and the drug is permeated into the skin through the micro-needle gap to complete drug delivery. In operation, the drug is pre-placed on the upper layer of the porous micro-needle for free permeation, so as to achieve the purpose of drug delivery. However, the existing technology adopting porous micro-needle for transdermal drug delivery has the following defects: 1. only a small amount of medicine can be loaded, and continuous administration cannot be realized; 2. the drug freely permeates through the pores, and the administration speed is difficult to control; 3. the independent control of the combined administration of a plurality of medicaments is difficult to realize due to the lack of a control system; 4. the micro-needle is communicated with the micro-needle in a porous way, so that the integration of drug delivery and body fluid detection is difficult to realize.

Disclosure of Invention

Aiming at the technical problems in the prior art, the invention aims to: provides a porous microneedle transdermal drug delivery and body fluid detection system which can realize diagnosis and treatment integration of drug delivery and body fluid detection.

In order to achieve the purpose, the invention adopts the following technical scheme: a porous microneedle transdermal drug delivery and body fluid detection system comprises a microneedle layer, a channel layer and a detection module; the microneedle layer comprises n groups of administration microneedles and m groups of detection microneedles, each group of administration microneedles comprises a plurality of linearly arranged porous microneedles, and each group of detection microneedles comprises a plurality of linearly arranged porous microneedles; in the microneedle layer, each group of drug delivery microneedles is not communicated with any other group of drug delivery microneedles, and each group of drug delivery microneedles is not communicated with any group of detection microneedles; the channel layer is provided with n strip-shaped grooves, one ends of the grooves are connected with drug inlets, so that drug delivery channels for delivering drugs are formed inside the grooves, the drug inlets are communicated with drug delivery micro-needles through the drug delivery channels, and the n groups of drug delivery micro-needles are respectively in one-to-one correspondence with the n grooves; the detection module is connected with the detection micro-needle, n is more than or equal to 2, and m is more than or equal to 1. After the structure is adopted, each medicine inlet is an independent inlet, so that medicines can be independently provided for each group of administration micro-needles through the medicine inlets and the grooves, the simultaneous conveying of different medicines is facilitated, and the simultaneous continuous medicine delivery of multiple medicines can be realized. Human tissue fluid can permeate into the detection module through the detection micro-needle to be detected, and diagnosis and treatment are integrated.

Preferably, the detection module comprises a detection electrode, the needle head of the porous microneedle is positioned on the front side of the microneedle layer, the detection electrode is attached to the back side of the microneedle layer, and the position of the detection electrode is adapted to the position of the detection microneedle; the groove is arranged on the front surface of the channel layer, the front surface of the channel layer faces to the back surface of the microneedle layer, and the opening position of the groove is adapted to the position of the drug delivery microneedle, so that the drug is permeated into the drug delivery microneedle from the opening of the groove.

Preferably, the system for transdermal drug delivery and body fluid detection of the porous microneedle further comprises a gap layer, the gap layer is located between the microneedle layer and the channel layer, the detection electrode is fixed on the gap layer, n strip-shaped avoiding holes are formed in the gap layer, the positions of the avoiding holes are matched with the positions of the drug delivery microneedle, and therefore drugs in the groove enter the drug delivery microneedle through the avoiding holes.

Preferably, the system for transdermal drug delivery and body fluid detection of the porous microneedle further comprises a flow rate control module, the flow rate control module comprises a fixed layer and a first pressing structure, the fixed layer is located on the back face of the channel layer, a first installation through hole is formed in the fixed layer, a first station is arranged on the groove, the opening of the first installation through hole faces the first station, the first pressing structure penetrates through the first installation through hole and is connected with the first installation through hole in an adjustable mode, the channel layer is made of a flexible material, and the first pressing structure extrudes or loosens the drug delivery channel from the back face of the channel layer. After adopting this kind of structure, because the channel layer is made by flexible deformable material, first press the structure from the bottom extrusion recess of recess, make the recess produce and warp to the break-make of the passageway of dosing in the steerable recess, and through the extrusion degree of adjustment first press the structure to the recess, and then the fluid resistance in the control recess, thereby adjust the speed of dosing.

Preferably, n is 3, and the 3 grooves are respectively a middle groove and two side grooves, and the middle groove is located between the two side grooves; a transverse groove is arranged between the side groove and the middle groove, and a connecting channel for communicating the middle groove and the side groove is formed in the transverse groove; the intersection point of the lateral groove and the transverse groove is far away from the medicine inlet relative to the first station on the lateral groove, and the intersection point of the middle groove and the transverse groove is positioned between the medicine inlet and the first station on the middle groove; the flow rate control module further comprises a second pressing structure, a second station is arranged on the transverse groove, a second mounting through hole is formed in the fixing layer, the opening of the second mounting through hole faces the second station, the second pressing structure penetrates through the second mounting through hole, the second pressing structure is connected with the second mounting through hole in an adjustable mode, and the second pressing structure extrudes or loosens the connecting channel from the back face of the channel layer. After the structure is adopted, the first pressing structure and the second pressing structure can control independent administration or mixed administration of the administration channels, and control the administration proportion and the administration speed of the mixed administration.

Preferably, the first pressing structure and the second pressing structure are screws, and the screws are in threaded connection with the fixing layer. After adopting this kind of structure, can conveniently control the extrusion degree to dosing passageway and connecting channel through rotatory screw.

Preferably, the material of the porous microneedle comprises polyglycidyl methacrylate. The substrate structure for fixing the porous micro-needles is made of the poly glycidyl methacrylate, so that the micro-needles in each row are not communicated with each other, and the independence of each group of administration micro-needles and detection micro-needles is ensured.

Preferably, m is 2, the detection microneedles and the administration microneedles are arranged at intervals, the number of the detection electrodes is two, and the two groups of detection electrodes correspond to the two groups of detection microneedles respectively.

Preferably, a curved groove is provided between one end of the groove and the drug inlet. After adopting this kind of structure, the effect that the curved groove is used for buffering liquid velocity of flow for the medicine can be comparatively accurate control.

Preferably, the channel layer and the gap layer are made of flexible PDMS.

In summary, the present invention has the following advantages:

the porous micro-needle is adopted for medicine permeation, the porosity of the micro-needle can be adjusted through processes such as chemical reaction and the like, the medicine-loading rate is increased, and the micro-needle has the characteristics of minimally invasive and painless property.

The porous micro-needle is independently partitioned, so that the channels for drug delivery and body fluid detection in the micro-fluidic system are independent, and the diagnosis and treatment integration of drug delivery and body fluid detection is realized.

The drug delivery system with three drug delivery channels and two connecting channels is adopted, each channel is provided with an independent mechanical switch, the drug delivery speed can be controlled, each channel can be independently controlled, the separately controlled combined drug delivery function is realized, and the continuous and adjustable drug delivery is realized.

Drawings

Fig. 1 is a perspective view of a porous microneedle transdermal drug delivery and body fluid detection system.

Figure 2 is a perspective view of another angle of a system for transdermal drug delivery and body fluid testing of porous microneedles.

Fig. 3 is an exploded view of a porous microneedle transdermal drug delivery and body fluid detection system.

Fig. 4 is a perspective view of the channel layer.

Fig. 5 is a perspective view of a microneedle layer.

FIG. 6 is a perspective view of a rectangular parallelepiped sleeve.

Fig. 7 is a perspective view of a flow rate control module.

Fig. 8 is a flow chart for the preparation of a microneedle layer.

Fig. 9 is a diagram of the fabrication of a substrate structure.

FIG. 10 is an assembly view of a microneedle layer, a channel layer, and a gap layer.

Wherein, 1 is a microneedle layer, 2 is a gap layer, 3 is a channel layer, 4 is a flow velocity control module, and 5 is a detection module.

11 is a drug administration microneedle, and 12 is a detection microneedle.

31 is a middle groove, 32 is a side groove, 33 is a transverse groove, 34 is a curved groove, and 35 is a drug inlet.

Reference numeral 41 denotes a fixing layer, 42 denotes a first pressing structure, 43 denotes a second pressing structure, 44 denotes a first mounting through hole, and 45 denotes a second mounting through hole.

The reference numeral 6 denotes a microneedle cone mold, 61 denotes a PGMA polymer liquid, 7 denotes a microneedle substrate mold, and 71 denotes a microneedle substrate structure.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings and detailed description.

Example one

As shown in fig. 1 to 7, a system for transdermal drug delivery and body fluid detection of porous microneedles comprises a microneedle layer 1, a channel layer 3 and a detection module 5; the microneedle layer comprises n groups of administration microneedles 11 and m groups of detection microneedles 12, each group of administration microneedles comprises a plurality of linearly arranged porous microneedles, and each group of detection microneedles comprises a plurality of linearly arranged porous microneedles; in the microneedle layer, each group of drug delivery microneedles is not communicated with any other group of drug delivery microneedles, and each group of drug delivery microneedles is not communicated with any group of detection microneedles; n strip-shaped grooves are formed in the channel layer, one ends of the grooves are connected with drug inlets 35, so that drug delivery channels for delivering drugs are formed in the grooves, the drug inlets are communicated with drug delivery micro-needles through the drug delivery channels, and the n groups of drug delivery micro-needles are respectively in one-to-one correspondence with the n grooves; the detection module is connected with the detection micro-needle, n is more than or equal to 2, and m is more than or equal to 1.

The detection module comprises a detection electrode, the needle head of the porous microneedle is positioned on the front side of the microneedle layer, the detection electrode is attached to the back side of the microneedle layer, and the position of the detection electrode is matched with the position of the detection microneedle; the groove is arranged on the front surface of the channel layer, the front surface of the channel layer faces to the back surface of the microneedle layer, and the opening position of the groove is adapted to the position of the drug delivery microneedle, so that the drug is permeated into the drug delivery microneedle from the opening of the groove.

The porous microneedle transdermal drug delivery and body fluid detection system further comprises a gap layer, the gap layer is located between the microneedle layer and the channel layer, the detection electrode is fixed on the gap layer, n strip-shaped avoiding holes are formed in the gap layer, the positions of the avoiding holes are matched with the positions of the drug delivery microneedles, and therefore drugs in the grooves enter the drug delivery microneedles through the avoiding holes.

The overall size of the gap layer is 5x14mm, the size of three independent channels is 350un x5000 μm, the thickness is 100 μm, the detection electrode is a three-electrode system, the width of the three electrodes is 250 μm, the width of each electrode is 80 μm, the thickness is 20 μm, the length of the left and right electrodes in the three electrodes is 6.1mm, the length of the middle electrode is 6.3mm, and the electrode tip is in a rectangle of 100x200 μm.

The utility model provides a porous micropin percutaneous medicine delivery and body fluid detection system still includes flow rate control module, flow rate control module includes fixed layer 41 and first press the structure 42, the fixed layer is located the back on passageway layer, it has first installation through-hole 44 to open on the fixed layer, be equipped with first station on the recess, the opening of first installation through-hole is towards first station, first press the structure and pass first installation through-hole, first press the structure and be connected with adjustable first installation through-hole, the passageway layer is made by flexible material, first press the structure from the back extrusion on passageway layer or loosen the passageway of dosing.

In the flow velocity control module, the fixed layer is positioned on a cuboid sleeve, the size of an internal cavity of the cuboid sleeve is 1.75x3.5x5mm, wherein 1.75mm is the height, and the cuboid sleeve is sleeved outside the channel layer and the gap layer.

n is 3, the 3 grooves are respectively a middle groove 31 and two side grooves 32, and the middle groove is positioned between the two side grooves; a transverse groove 33 is arranged between the side groove and the middle groove, and a connecting channel for communicating the middle groove and the side groove is formed in the transverse groove; the intersection point of the lateral groove and the transverse groove is far away from the medicine inlet relative to the first station on the lateral groove, and the intersection point of the middle groove and the transverse groove is positioned between the medicine inlet and the first station on the middle groove; the flow rate control module further comprises a second pressing structure 43, a second station is arranged on the transverse groove, a second mounting through hole 45 is formed in the fixing layer, the opening of the second mounting through hole faces the second station, the second pressing structure penetrates through the second mounting through hole, the second pressing structure is connected with the second mounting through hole in an adjustable mode, and the second pressing structure extrudes or loosens the connecting channel from the back face of the channel layer.

The whole size of the channel layer is 5 multiplied by 14mm, the height is 650 mu m, three grooves are arranged in parallel, the length of each groove is 9400 mu m, the width of each groove is 350 mu m, the depth of each groove is 50 mu m, a medicine inlet is a circular through hole with the radius of 330 mu m, the distance between one end of each groove and the medicine inlet is 350 mu m, a curved groove comprises circular arc sections which are alternately connected and respectively have the radii of 225 mu m and 75 mu m, the width of each curved groove is 150 mu m, the distance from one end to the other end of each curved groove is 350 mu m, the length of a transverse groove is 2000 mu m, the width of each groove is 200 mu m, and the depth of each groove is 50 mu m.

The first pressing structure and the second pressing structure are screws, and the screws are in threaded connection with the fixing layer. The length of the screw is 1mm, the outer diameter of the threaded rod is 0.6mm, and the outer diameter of the head of the screw is 0.8mm.

The material of the porous microneedle comprises polyglycidyl methacrylate.

And m is 2, the detection microneedles and the administration microneedles are arranged at intervals, the number of the detection electrodes is two, and the two groups of detection electrodes respectively correspond to the two groups of detection microneedles. Enzymatic reaction detection of detection electrode based on glucose oxidase (GOx)The blood glucose concentration is measured, and the blood glucose concentration measuring instrument consists of a reference electrode (Ag/AgCl), a counter electrode (Pt) and a working electrode (Pt + GOx). Glucose in tissue fluid is catalyzed by GOx to generate gluconic acid and hydrogen peroxide. At a certain potential, metal Pt is coupled with H₂O₂Catalytically decompose and form an electric current for measuring the blood glucose concentration in the interstitial fluid.

A curved groove 34 is provided between one end of the recess and the drug inlet.

The channel layer and the gap layer are made of flexible PDMS.

The whole size of the microneedle layer is 5mm multiplied by 5mm, five rows of porous microneedles are arranged, each row of porous microneedles is formed by arranging 10 porous microneedles, and the gap between every two adjacent rows of porous microneedles is 1000 microns, wherein the 1 st, 3 rd and 5 th rows of porous microneedles are administration microneedles and are connected with an administration channel for delivering drugs, and the 2 nd and 4 th rows of porous microneedles are detection microneedles for extracting tissue fluid and are connected with detection electrodes. Each porous microneedle is conical with the height of 350 mu m and the bottom surface diameter of 250 mu m, and the porous microneedles are arranged on a substrate structure which is 400 mu m thick.

As shown in fig. 8, a process for preparing a microneedle layer is performed by aligning and pressing a microneedle substrate structure 71 with a microneedle conical mold 6, pouring PGMA polymer liquid 61 containing a certain proportion of porogen stock solution, vacuumizing for 1 hour at room temperature, irradiating for 1 hour under 365nm ultraviolet light for photocuring, and then grinding the surface of the structure, so that the microneedle structure with the porogen is independently distributed on the microneedle substrate structure without the porogen. And peeling off the device, putting the device into a mixed solution of methanol and water with the volume ratio of 1:1, and soaking for 4 hours to dissolve the pore-forming material, thereby obtaining the porous microneedle device which is independent and not communicated with each other, namely the microneedle layer.

The microneedle conical die can be manufactured by machining a conical hole in a polyacrylic acid thin plate through a mechanical method and then performing secondary reverse molding through flexible Polydimethylsiloxane (PDMS). The microneedle base mold 7 is fabricated in the same manner.

As shown in fig. 9, after obtaining the microneedle substrate mold, pouring and photocuring the mixture of the monomer stock solution without the porogen and the photoinitiator in the microneedle substrate mold to form a microneedle substrate structure, and then peeling off the microneedle substrate structure for use.

The monomer stock solution was prepared by mixing Glycidyl Methacrylate GMA (Glycidyl Methacrylate,10 ml; 73.3mmol,1equiv.), a crosslinking agent Trimethylolpropane trimethacrylate TRIM (Trimethylolpropane trimethacrylate, 6.18 ml; 19.4mmol, 0.26equiv.), and a crosslinking agent Triethylene glycol Dimethacrylate TEGDMA (Triethylene glycol Dimethacrylate,15.7 ml; 57.6mmol,0.79equiv.), and stored at-15 ℃.

The porogen stock solution was formed by mixing Polyethylene Glycol (PEG) powder (Polyethylene Glycol, Mw ═ 10kDa, 20g) with 2-Methoxyethanol (2-methoxyethanel, 100g) at 50 ℃.

Rapidly heating the monomer stock solution to room temperature by using 37 ℃ water bath, uniformly mixing the monomer stock solution with the pore-foaming agent stock solution according to a certain proportion, uniformly stirring, and adding 0.10g of photoinitiator Irgacure 184 to form poly glycidyl methacrylate PGMA (polyglycidyl methacrylate) polymer liquid for injection into a PDMS mold for photocuring. And (3) peeling off the cured material, and then putting the cured material into ethylene glycol to dissolve and remove the pore-forming agent in the cured material to form PGMA polymer solid containing a porous structure.

When the microneedle layer is prepared, the porosity of the microneedles can be adjusted by changing the proportion of the pore-forming agent in the material.

The channel layer is made of flexible PDMS, and the channel layer is obtained through the steps of SU8 glue homogenizing, exposure, development, PDMS curing, PDMS peeling and the like.

The material of the gap layer adopts flexible PDMS, the preparation method of the gap layer is similar to the preparation of the channel layer, and the preparation method of the electrode comprises the following steps: firstly, forming a titanium (Ti) electrode structure with the thickness of 30nm and a platinum (Pt) electrode structure with the thickness of 150nm on the gap layer by magnetron sputtering and photoetching. And then respectively dripping and coating Ag/AgCl and GOx on the counter electrode and the working electrode through a mask layer and curing to form a three-electrode structure.

After the gap layer, the channel layer and the microneedle layer are all prepared, a multilayer bonding integration process is carried out, as shown in fig. 10, the gap layer, the channel layer and the microneedle layer are assembled in a bonding mode, and after the assembly is finished, the flow rate control module is installed.

During the use, paste the front on the human skin with the micropin layer, press the structure with two seconds and screw, make it extrude the connecting channel completely, the connecting channel is broken off, and at this moment, three delivery channel independently administrates medicine, and the medicine entry passes through the hose connection medicine, carries the medicine to in the micropin of dosing continuously to in permeating into the human body through the micropin of dosing, different medicines can be independently carried to three medicine entry, also can carry same kind of medicine.

Example two

Loosen two second pressing structures, make the connecting channel intercommunication, the first pressing structure that corresponds middle recess is screwed, make middle recess break off at its first station department, two other first pressing structures loosen, carry first medicine toward the medicine entry on two lateral part recesses, carry second medicine toward the medicine entry of middle recess, at this moment, second medicine mixes with first medicine through two connecting channel respectively, permeate into the human body through porous micropin again, thereby realize mixing and dosing, at this in-process, the extrusion degree of two first pressing structures of accessible control and two second pressing structures, the mixing proportion and the rate of dosing of control two kinds of medicines.

The embodiment is not described in the first embodiment.

EXAMPLE III

The two first pressing structures corresponding to the two side grooves are screwed tightly, so that the two side grooves are extruded at a first station and the channel is disconnected, the first pressing structure and the two second pressing structures corresponding to the middle groove are loosened, medicine is conveyed to the medicine inlet of the middle groove, and the medicine can flow to the two side grooves through the connecting channel, so that the single-inlet three-channel medicine feeding function is realized.

The embodiment is not described in the first embodiment.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.