Micro-needle electroporation device

Abstract

The utility model belongs to the technical field of drug delivery, and particularly relates to a microneedle electroporation device. The microneedle electroporation device comprises a liquid inlet assembly, a liquid outlet assembly and a microneedle electroporation assembly, a liquid storage cavity is formed in the liquid storage assembly, and the liquid storage cavity communicates with the buffer cavity; the hollow microneedle array assembly comprises a substrate and a plurality of hollow microneedles embedded in the substrate, the substrate is arranged on the surface of the liquid storage cavity, the tip end of each hollow microneedle faces the side away from the substrate, a straight hole is formed in each hollow microneedle and communicates with the liquid storage cavity and the outer portion of the corresponding hollow microneedle, the diameter of the bottom of each hollow microneedle is 0.5-1.5 mm, and the height of each hollow microneedle is 1.5-2 mm; the diameter of the straight hole in the hollow microneedle is 140-180 microns; the interdigital electrode assembly is arranged on the side, where the hollow microneedles are arranged, of the surface of the substrate, and the interdigital electrode assembly comprises a positive electrode and a negative electrode which are arranged between the hollow microneedles in a crossed mode. According to the microneedle electroporation device, the transdermal transmission efficiency and the cell infection effect of drugs and / or vaccines are improved.

Description

Technical Field

[0001] The utility model belongs to the technical field of drug delivery, and specifically relates to a microneedle electroporation device. Background Art

[0002] Transdermal Drug Delivery System (TDDS) refers to a drug delivery system that delivers drugs through the skin into the systemic circulation to produce systemic or local therapeutic effects. It is widely used in clinical practice because of its safety and effectiveness. When a transdermal drug delivery system is used to deliver drugs, the drug passes through the stratum corneum of the skin to achieve a local therapeutic effect; or after passing through the stratum corneum, the drug continues to pass through the epidermis and dermis, and enters the systemic circulation through the capillaries to achieve systemic treatment.

[0003] Microneedles (MN) are a new type of physical penetration-promoting technology, consisting of multiple micron-sized tiny needle tips connected in an array on a base. Compared with muscle tissue, there are more active immune cells in the epidermis and dermis of the skin, especially antigen-presenting cells. Ordinary syringe needles penetrate the entire dermis to reach the subcutaneous tissue for vaccine injection, while microneedles can directly inject vaccines into the dermis due to their small size, which can achieve a more efficient and less side-effect immune effect. According to the type of microneedles and the method of drug delivery, it can be divided into: first pierce and then stick (solid microneedles), first pierce and then release (soluble microneedles, frozen microneedles), coating delivery (coated microneedles), and injection delivery (hollow microneedles, gel microneedles). However, due to the small size of microneedles, especially hollow microneedles, the mechanical strength of the microneedles will be reduced to a certain extent, affecting the penetration depth and durability; at the same time, the presence of cell membrane barriers also makes it difficult for drugs to enter the cells to exert their effects. Summary of the invention

[0004] The inventors of the utility model have discovered through extensive practice that the structural dimensions and penetration depth of the microneedles will cause certain damage to the epidermis and dermis of the skin, thereby affecting the delivery effect of drugs and / or vaccines. At the same time, due to the existence of the cell membrane barrier and its negative biological charge, electrostatic repulsion will also be generated on the delivered drugs and / or vaccines, affecting the drugs and / or vaccines from entering the cells to exert their effects.

[0005] The purpose of the utility model is to provide a microneedle electroporation device to address the problems of low transdermal drug delivery efficiency and poor cell transfection effect in existing microneedle devices. The device adopts hollow microneedles with specific structural dimensions and cooperates with interdigital electrodes to improve the transdermal delivery efficiency of drugs and / or vaccines and the cell infection effect.

[0006] In order to solve the above technical problems, the utility model adopts the following technical solutions:

[0007] The utility model provides a microneedle electroporation device, which comprises: a liquid inlet component, in which a buffer cavity is arranged; a liquid storage component, in which a liquid storage cavity is arranged, and the liquid storage cavity is communicated with the buffer cavity; a hollow microneedle array component, which comprises a substrate and a plurality of hollow microneedles embedded in the substrate, wherein the substrate is arranged on the surface of the liquid storage cavity, the tips of the hollow microneedles face a side away from the substrate, each of the hollow microneedles is provided with a straight hole, the straight hole communicates the liquid storage cavity and the outside of the hollow microneedle, the bottom diameter of the hollow microneedle is 0.5-1.5mm and the height is 1.5-2mm, and the diameter of the straight hole in the hollow microneedle is 140-180μm; an interdigitated electrode component, which is arranged on one side of the substrate surface where the hollow microneedle is arranged, and the interdigitated electrode component comprises a positive electrode and a negative electrode, and the two are cross-arranged between the hollow microneedles.

[0008] In some embodiments of the present application, the hollow microneedles are distributed at equal intervals, and the distance between two adjacent hollow microneedles is 0.5-1.5 mm.

[0009] In some embodiments of the present application, the positive electrode includes a first end, on which a plurality of first interdigital electrode strips are arranged side by side and at intervals, and two adjacent first interdigital electrode strips and the first end are arranged in a U-shape; the negative electrode includes a second end, on which a plurality of second interdigital electrode strips are arranged side by side and at intervals, and two adjacent second interdigital electrode strips and the second end are arranged in a U-shape; the first end and the second end are arranged in parallel; the first interdigital electrode strips and the second interdigital electrode strips are alternately arranged and extend toward each other's ends; the spacing between adjacent first interdigital electrode strips and second interdigital electrode strips is greater than the diameter of the hollow microneedle;

[0010] In some embodiments of the present application, the first interdigitated electrode strips and the second interdigitated electrode strips are arranged at equal intervals, and the hollow microneedles are evenly distributed in the space formed by the first interdigitated electrode strips and the second interdigitated electrode strips.

[0011] In some embodiments of the present application, the first interdigitated electrode strips and the second interdigitated electrode strips have the same width.

[0012] In some embodiments of the present application, the positive electrode is made of Cr / Au material; the negative electrode is made of Cr / Au material.

[0013] In some embodiments of the present application, the interdigitated electrode assembly further includes a pulse power supply, and the pulse power supply is respectively connected to the positive electrode and the negative electrode to generate electroporation.

[0014] In some embodiments of the present application, the hollow microneedles are made of resin.

[0015] In some embodiments of the present application, the surface of the hollow microneedle is metal-plated.

[0016] In some embodiments of the present application, the diameter of the straight hole is much smaller than the diameter of the maximum cross-sectional area of ​​the hollow microneedle.

[0017] In some embodiments of the present application, the thickness of the substrate is 0.1-0.5 mm.

[0018] The beneficial effects that can be achieved by the utility model compared with the prior art are as follows: the drugs and / or vaccines to be injected first enter the buffer cavity and then enter the liquid storage cavity; the hollow microneedle array penetrates the skin, partially or completely penetrates the stratum corneum to form a micro-sized channel, and the liquid in the liquid storage cavity enters the epidermis and dermis through the straight holes of the hollow microneedles; under the electroporation effect generated by the interdigitated electrode assembly, micropores are opened on the cell membrane barrier, and the drugs and / or vaccines enter the cell through the micropores on the cell membrane to play a role. Through the setting of the liquid storage cavity, the delivery amount of the microneedle electroporation device is large and stable, breaking through the limitation of the skin barrier on macromolecular drugs and improving the selectivity of the delivered drugs and / or vaccines. The hollow microneedle array assembly with a specific structure and size can ensure that the depth of penetration into the skin is appropriate with minimal damage to the epidermis and dermis of the skin. The microchannels created by the straight hole structure of the hollow microneedle are used to deliver drugs and / or vaccines to the epidermis and dermis. At the same time, under the electroporation action of the interdigitated electrode assembly, drugs and / or vaccines can accurately and efficiently enter the cells, and the drug absorption efficiency and intracellular transfection efficiency can be maximized and maintained stably in a short time.

[0019] In some specific embodiments, the electric field intensity distribution between the microneedles and the electrodes can be adjusted by changing the parameters of the hollow microneedles and the interdigitated electrode assembly, thereby regulating the drug delivery efficiency. The microneedle electroporation device of the utility model has the advantages of high efficiency, significant drug efficacy and good controllability, providing technical support for the commercialization and clinical application of microneedles, and providing a guarantee for clinical diseases that require efficient absorption and continuous drug delivery in a short period of time. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The various objects, features and advantages of the present invention will become more apparent by considering the following detailed description of the preferred embodiments of the present invention in conjunction with the accompanying drawings. The accompanying drawings are only exemplary illustrations of the present invention and are not necessarily drawn to scale. In the accompanying drawings, the same reference numerals always represent the same or similar parts. Among them:

[0021] Figure 1 It is a three-dimensional diagram of a microneedle electroporation device according to an embodiment of the present invention.

[0022] Figure 2 yes Figure 1 Bottom view of .

[0023] Figure 3 yes Figure 1 Top view of the .

[0024] Figure 4 yes Figure 3 AA cross-section diagram.

[0025] Figure 5 It is a fluorescence imaging effect diagram after Luciferin mRNA is administered to mice using the microneedle electroporation device provided in Example 1 of the utility model and the traditional syringe respectively.

[0026] Figure 6 This is a fluorescence imaging effect diagram after the polypeptide model antigen OVA is administered to mice using the microneedle electroporation device provided in Example 1 of the utility model.

[0027] The reference numerals are explained as follows: 1. liquid inlet assembly; 11. buffer chamber; 12. first liquid inlet; 13. second liquid inlet; 2. liquid storage assembly; 21. liquid storage cover; 22. liquid storage chamber; 3. hollow microneedle array assembly; 31. substrate; 32. hollow microneedle; 33. straight hole; 4. interdigitated electrode assembly; 41. first end; 42. first interdigitated electrode strip; 43. second end; 44. second interdigitated electrode strip. DETAILED DESCRIPTION

[0028] Although the present invention can be easily embodied as embodiments of different forms, only some of the specific embodiments are shown in the drawings and described in detail in this specification. It should be understood that this description should be regarded as an exemplary description of the principles of the present invention and is not intended to limit the present invention to that described herein.

[0029] Thus, a feature indicated in this specification will be used to illustrate one of the features of an embodiment of the utility model, rather than implying that each embodiment of the utility model must have the described feature. In addition, it should be noted that this specification describes many features. Although some features can be combined together to illustrate possible system designs, these features can also be used in other combinations that are not explicitly described. Thus, unless otherwise stated, the described combinations are not intended to be limiting.

[0030] In the embodiments shown in the drawings, the indications of directions (such as up, down, left, right, front and back) used to explain the structure and movement of various elements of the utility model are not absolute but relative. These descriptions are appropriate when these elements are in the positions shown in the drawings. If the descriptions of the positions of these elements change, the indications of these directions also change accordingly.

[0031] See also Figures 1 to 4The microneedle electroporation device provided by an embodiment of the utility model comprises a liquid inlet component 1, a liquid storage component 2, a hollow microneedle array component 3 and an interdigitated electrode component 4, wherein a buffer cavity 11 is provided in the liquid inlet component 1; a liquid storage cavity 22 is provided in the liquid storage component 2, and the liquid storage cavity 22 is connected to the buffer cavity 11; the hollow microneedle array component 3 comprises a substrate 31 and a plurality of hollow microneedles 32 embedded in the substrate 31, wherein the substrate 31 is provided on the surface of the liquid storage cavity 22, and the tips of the hollow microneedles 32 face a direction away from the substrate 31. On the other side, each hollow microneedle 32 is provided with a straight hole 33, the straight hole 33 connects the liquid storage chamber 22 and the outside of the hollow microneedle 32, the bottom diameter of the hollow microneedle 32 is 0.5-1.5mm and the height is 1.5-2mm, and the diameter of the straight hole 33 in the hollow microneedle 32 is 140-180μm; the interdigitated electrode assembly 4 is arranged on one side of the surface of the substrate 31 where the hollow microneedle 32 is provided, and the interdigitated electrode assembly 4 includes a positive electrode and a negative electrode and the two are cross-arranged between the hollow microneedles 32.

[0032] Through the above structural design, the drug and / or vaccine to be injected first enters the buffer chamber 11, and then enters the liquid storage chamber 22; the hollow microneedle array 3 penetrates the skin, partially or completely penetrates the stratum corneum to form a micro-sized channel, and the liquid in the liquid storage chamber 22 enters the epidermis and dermis through the straight hole 33 of the hollow microneedle 32; under the electroporation effect generated by the interdigitated electrode assembly 4, micropores are opened on the cell membrane barrier, and the drug and / or vaccine enters the cell through the micropores on the cell membrane to play a role. Through the setting of the liquid storage chamber 22, the delivery amount of the microneedle electroporation device is large and stable, which can meet the needs of continuous administration of a large amount of drugs at a time, and improve the selectivity of the delivered drugs and / or vaccines. The hollow microneedle array assembly 3 with a specific structure and size can ensure that the depth of penetration into the skin is appropriate and causes little damage to the epidermis and dermis of the skin. The straight hole 33 structure of the hollow microneedle 32 is used to generate a microchannel to deliver drugs and / or vaccines to the epidermis and dermis. At the same time, under the electroporation action of the interdigitated electrode assembly 4, the drugs and / or vaccines can be accurately and efficiently introduced into the cells, and the drug absorption efficiency and the intracellular transfection efficiency can be maximized and maintained stable in a short time.

[0033] In this embodiment, the number of hollow microneedles 32 is 16, and the arrangement is 4×4. In other embodiments, the number of hollow microneedles 32 may also be 4 (2×2), 9 (3×3), 25 (5×5) or other values, and the number may be adjusted according to actual needs. In the present utility model, the number of hollow microneedles 32 is not specifically limited. When the number of hollow microneedles 32 is 16, a 4×4 array arrangement is presented in the interdigitated electrode assembly, and the transdermal delivery efficiency and cell infection effect of drugs and / or vaccines are better.

[0034] The liquid inlet assembly 1 is further provided with a first liquid inlet 12 and a second liquid inlet 13 which are interconnected through the buffer chamber 11. The first liquid inlet 12 is used to input medicine and / or vaccine, and the second liquid inlet 13 is used to output medicine and / or vaccine. In this embodiment, the first liquid inlet 12 and the second liquid inlet 13 are both circular.

[0035] The liquid inlet assembly 1 is matched and connected with the front end of the syringe through the first liquid inlet 12. In this embodiment, the first liquid inlet 12 is circular, and the front end of the syringe can be matched and connected with the first liquid inlet 12 through a silicone tube. In other embodiments, the first liquid inlet 12 can also be other shapes, as long as it can be matched and connected with the front end of the syringe.

[0036] See also Figure 2 , the hollow microneedles 32 are evenly spaced, and the distance between two adjacent hollow microneedles 32 is 0.5-1.5 mm. The distance between the hollow microneedles refers to the distance between the central axes of the hollow microneedles minus the bottom diameter. The evenly spaced hollow microneedles 32 can better synergize with the interdigital electrode assembly 4, so that the electric field strength generated by the interdigital electrode assembly 4 is evenly distributed, which is beneficial to improving the delivery effect of drugs and / or vaccines.

[0037] See also Figure 2 The positive electrode includes a first end 41, on which a plurality of first interdigitated electrode strips 42 are arranged side by side and at intervals, and two adjacent first interdigitated electrode strips 42 and the first end 41 are arranged in a U-shape. The negative electrode includes a second end 43, on which a plurality of second interdigitated electrode strips 44 are arranged side by side and at intervals, and two adjacent second interdigitated electrode strips 44 and the second end 43 are arranged in a U-shape. The first end 41 and the second end 43 are arranged in parallel, and the first interdigitated electrode strips 42 and the second interdigitated electrode strips 44 are arranged alternately and extend toward each other's ends, and the spacing between adjacent first interdigitated electrode strips 42 and second interdigitated electrode strips 44 is greater than the diameter of the hollow microneedles 32. The number of the first interdigitated electrode strips 42 and the second interdigitated electrode strips 44 can be adaptively adjusted according to the number and arrangement of the hollow microneedles 32. The spacing between adjacent first interdigitated electrode strips 42 and second interdigitated electrode strips 44 is greater than the diameter of the microneedle in the same plane. This arrangement is to enable the interdigitated electrode assembly 4 and the hollow microneedle 32 to be staggered, thereby facilitating the synergistic effect of the transmission effect of the hollow microneedle array assembly 3 and the electroporation effect of the interdigitated electrode assembly 4, thereby improving the delivery efficiency of drugs and / or vaccines into cells.

[0038] See also Figure 2, the first interdigitated electrode strips 42 and the second interdigitated electrode strips 44 are arranged at equal intervals, and the hollow microneedles 32 are evenly distributed in the space formed by the first interdigitated electrode strips 42 and the second interdigitated electrode strips 44. The first interdigitated electrode strips 42 and the second interdigitated electrode strips 44 arranged at equal intervals can better form a cross arrangement with the hollow microneedles 32, which is conducive to improving the synergistic effect of the two, so that the delivered drugs and / or vaccines can efficiently and accurately enter the cells to play a role.

[0039] See also Figure 2 The width of the first interdigitated electrode strip 42 is the same as that of the second interdigitated electrode strip 44. The purpose of this arrangement is to ensure that the interdigitated electrode assembly 4 can generate a uniform electric field strength, better play the role of electroporation, better deliver drugs and / or vaccines into cells, and improve delivery efficiency.

[0040] In this embodiment, the positive electrode is made of Cr / Au material, the thickness of Cr is 25-35nm, and the thickness of Au is 150-250nm; the negative electrode is made of Cr / Au material, the thickness of Cr is 25-35nm, and the thickness of Au is 150-250nm. Specifically, the positive electrode and the negative electrode of the interdigital electrode assembly 4 can be plated on the side of the substrate 31 where the hollow microneedle 32 is provided by the magnetron sputtering process through the electrode mask design. The specific material and thickness enable the interdigital electrode assembly 4 to produce electroporation in the epidermis and dermis without causing discomfort and damage to the skin surface.

[0041] The interdigitated electrode assembly 4 also includes a pulse power supply (not shown in the figure), which is connected to the positive electrode and the negative electrode respectively to produce an electroporation effect. First, the drug and / or vaccine is delivered to the epidermis and dermis through the straight hole 33 of the hollow microneedle 32, and then the pulse power supply is turned on to produce an electroporation effect, opening micropores on the cell membrane, so that the drug and / or vaccine delivered to the epidermis and dermis can enter the cell through the micropores to play a role; it can also be delivered through the hollow microneedle 32 while the pulse power supply is also turned on, so that the drug and / or vaccine delivered to the epidermis and dermis can enter the cell immediately through the electroporation effect. Compared with the former, this method can further improve the efficiency of drug and / or vaccine delivery.

[0042] The parameter settings of the pulse power supply can be: voltage 30-90V, pulse width 15-25ms, pulse number 10-20, pulse interval 1-2sec. By adjusting the pulse power supply parameter settings, the electric field intensity generated by the interdigitated electrode assembly 4 can be regulated, thereby regulating the electroporation effect, that is, the delivery efficiency and effect can be regulated in this way.

[0043] See also Figure 2, the hollow microneedle 32 is made of resin, and the surface of the hollow microneedle 32 has a metal coating. Now the hollow microneedle 32 is made of resin and has a metal coating on the surface, which can enhance the mechanical strength of the hollow microneedle 32 and thus improve durability.

[0044] See also Figure 2 The diameter of the straight hole 33 is much smaller than the diameter of the maximum cross-sectional area of ​​the hollow microneedle 32. The purpose of this arrangement is: first, it is easier to control the speed of drug administration; second, through the effect of the microchannel generated by the straight hole 33 in the hollow microneedle 32, it is easier to deliver the drug and / or vaccine to the designated location, and enter the cell through the micropores generated on the cell membrane by electroporation to exert its effect.

[0045] In this embodiment, the hollow microneedle 32 is conical, and the straight hole 33 is cylindrical. In other embodiments, the hollow microneedle 32 may be pyramidal, and the straight hole 33 may be prismatic.

[0046] See also Figure 1 and Figure 4 The thickness of the substrate 31 is 0.1-0.5 mm. The substrate 31 with a specific thickness can better fix the hollow microneedles 32.

[0047] In this example, see Figure 4 The liquid storage component also includes a liquid storage cap 21, and the liquid storage cap 21 and the base 3 in the liquid inlet component 1 and the hollow microneedle array component 3 are sealed to form a liquid storage chamber 22. The liquid storage chamber 22 is used to store the drugs and / or vaccines to be injected, so that the delivery amount of the microneedle electroporation device is larger and more stable, and it is also applicable to most macromolecular drugs, breaking through the limitation of the skin barrier on the types of macromolecular drugs and improving the selectivity of drug delivery. In another embodiment, the microneedle electroporation device is formed in an integrated manner using 3D printing combined with magnetron sputtering metal and other technologies, which simplifies the preparation process.

[0048] The beneficial effects that can be achieved by using the microneedle electroporation device provided by the utility model are specifically described below through examples.

[0049] Example 1

[0050] Please refer to Figures 1 to 4The microneedle electroporation device comprises a liquid inlet component 1, a liquid storage component 2, a hollow microneedle array component 3 and an interdigitated electrode component 4, wherein a buffer cavity 11 is provided in the liquid inlet component 1; a liquid storage cavity 22 is provided in the liquid storage component 2, and the liquid storage cavity 22 is connected to the buffer cavity 11; the hollow microneedle array component 3 comprises a substrate 31 and 16 hollow microneedles 32 uniformly arranged in a 4×4 pattern and embedded in the substrate 31, wherein the substrate 31 is provided on the surface of the liquid storage cavity 22, and the tips of the hollow microneedles 32 face away from the substrate. On one side of the bottom 31, each hollow microneedle 32 is provided with a straight hole 33, and the straight hole 33 connects the liquid storage chamber 22 and the outside of the hollow microneedle 32. The hollow microneedle 32 is conical, with a bottom diameter of 1 mm and a height of 1.8 mm. The straight hole 33 is cylindrical, with a diameter of 160 μm; the interdigitated electrode assembly 4 is arranged on one side of the surface of the substrate 31 where the hollow microneedle 32 is provided, and the interdigitated electrode assembly 4 includes a positive electrode and a negative electrode, and the two are cross-arranged between the hollow microneedles 32.

[0051] Application Example 1

[0052] This application example uses the microneedle electroporation device provided in Example 1 to administer naked luciferase (Luciferin) mRNA to mice: the thigh area of ​​7-week-old mice is depilated the day before the operation, the mice are fixed during the operation, the microneedle electroporation device loaded with mRNA drugs is pressed tightly on the skin of the mouse thigh part, the thumb is pressed for 2 minutes, and the pulse power supply is turned on for electroporation (parameter settings: voltage is 90V, duration is 20ms, number of pulses is 20, pulse interval is 1sec), until the liquid in the liquid storage chamber 22 is exhausted, the pulse power supply is turned off, and the administration is completed. The piercing effect of the microneedle electroporation device is 100%, and after the end of the administration, the trace gradually disappears over time, which shows that the microneedle electroporation device not only has a good piercing effect but also has minimal damage to the mouse skin.

[0053] 4 hours after the end of the administration, the small animal in vivo fluorescence imaging was performed. The specific test method and steps are as follows: 4 hours after the electroporation of Luciferin mRNA, 100 to 200 μL of D-luciferin substrate was injected into each mouse intraperitoneally, and the mice were anesthetized by gas. In vivo fluorescence imaging was performed using the small animal optical 3D in vivo imaging system (IVIS-Spectrum), which can quantitatively observe the transfection efficiency of Luciferin mRNA in mice. The results are shown in Figure 2. Figure 5 As shown, compared with the fluorescence intensity displayed by intramuscular injection using a traditional syringe, the fluorescence intensity displayed by injecting Luciferin mRNA using the microneedle electroporation device of Example 1 is lower, indicating that the microneedle electroporation device has a higher in vivo transfection efficiency of Luciferin mRNA and has the advantages of painless, minimally invasive large-area transfection.

[0054] Application Example 2

[0055] This application example uses the microneedle electroporation device provided in Example 1 to administer the polypeptide model antigen OVA to mice: the thighs of 7-week-old mice were depilated the day before the operation, and the mice were fixed during the operation. Microneedles loaded with 10μg, 20μg, and 30μg of drugs were pressed tightly on the thighs of the mice, respectively. The microneedles were removed after 3 minutes, and the pulse power supply parameters were set as follows: voltage of 90V, duration of 20ms, number of pulses of 20, pulse interval of 1sec, until the liquid in the liquid storage chamber 22 was exhausted, the pulse power supply was turned off, and the administration was completed. 30 minutes after the end of the administration, the small animal in vivo fluorescence imaging was performed, and the results were as follows: Figure 6 As shown, it can be seen that with the increase of the dosage, the fluorescence intensity and fluorescence area of ​​the mice increase accordingly, which not only proves the delivery effect of the microneedle device on large molecule protein drugs, but also shows that the microneedle device can break through the limitation of low dosage of solid microneedles and smear microneedles, and can achieve controllable dosage according to specific applications.

[0056] Although the utility model has been described with reference to several typical embodiments, it should be understood that the terms used are illustrative and exemplary, rather than restrictive. Since the utility model can be implemented in a variety of forms without departing from the spirit or essence of the utility model, it should be understood that the above-mentioned embodiments are not limited to any of the aforementioned details, but should be widely interpreted within the spirit and scope defined by the attached claims, so all changes and modifications falling within the scope of the claims or their equivalents should be covered by the attached claims.

Claims

1. A microneedle electroporation device, characterized in that: include: A liquid inlet assembly, wherein a buffer chamber is provided; A liquid storage component, wherein a liquid storage cavity is provided therein, and the liquid storage cavity is communicated with the buffer cavity; A hollow microneedle array assembly, comprising a substrate and a plurality of hollow microneedles embedded in the substrate, wherein the substrate is disposed on the surface of the liquid storage cavity, the tips of the hollow microneedles face the side away from the substrate, each of the hollow microneedles is provided with a straight hole, the straight hole connects the liquid storage cavity and the outside of the hollow microneedle, the bottom diameter of the hollow microneedle is 0.5-1.5 mm and the height is 1.5-2 mm, and the diameter of the straight hole in the hollow microneedle is 140-180 μm; The interdigitated electrode assembly is arranged on the side of the substrate surface where the hollow microneedles are arranged. The interdigitated electrode assembly includes a positive electrode and a negative electrode which are cross-arranged between the hollow microneedles.

2. The microneedle electroporation device according to claim 1, characterized in that: The hollow microneedles are distributed at equal intervals, and the distance between two adjacent hollow microneedles is 0.5-1.5 mm.

3. The microneedle electroporation device according to claim 1 or 2, characterized in that: The positive electrode comprises a first end portion, on which a plurality of first interdigitated electrode strips are arranged side by side and at intervals, and two adjacent first interdigitated electrode strips and the first end portion are arranged in a U shape; The negative electrode comprises a second end portion, on which a plurality of second interdigital electrode strips are arranged side by side and at intervals, and two adjacent second interdigital electrode strips and the second end portion are arranged in a U shape; The first end and the second end are arranged in parallel, the first interdigitated electrode strips and the second interdigitated electrode strips are arranged alternately and extend toward each other's ends; the spacing between adjacent first interdigitated electrode strips and second interdigitated electrode strips is greater than the diameter of the hollow microneedle.

4. The microneedle electroporation device according to claim 3, characterized in that: The first interdigital electrode strips and the second interdigital electrode strips are arranged at equal intervals, and the hollow microneedles are evenly distributed in the space formed by the first interdigital electrode strips and the second interdigital electrode strips.

5. The microneedle electroporation device according to claim 3, characterized in that: The first interdigital electrode strips and the second interdigital electrode strips have the same width.

6. The microneedle electroporation device according to claim 1 or 2, characterized in that: The positive electrode is made of Cr / Au material; the negative electrode is made of Cr / Au material.

7. The microneedle electroporation device according to claim 1 or 2, characterized in that: The interdigital electrode assembly further comprises a pulse power supply, which is respectively connected to the positive electrode and the negative electrode to produce an electroporation effect.

8. The microneedle electroporation device according to claim 1 or 2, characterized in that: The hollow microneedle is made of resin; and the surface of the hollow microneedle is coated with a metal layer.

9. The microneedle electroporation device according to claim 1 or 2, characterized in that: The diameter of the straight hole is much smaller than the diameter of the maximum cross-sectional area of ​​the hollow microneedle.

10. The microneedle electroporation device according to claim 1 or 2, characterized in that: The thickness of the substrate is 0.1-0.5 mm.

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