CN102530848A - Method for manufacturing mosquito-mouth-imitated hollow microneedle array - Google Patents

Abstract

The invention belongs to the field of micro-electro-mechanical systems (MEMS), and relates to a microneedle array which is manufactured by imitating a mosquito mouth, and is used for painless sample introduction. A method is characterized in that: a two-step and bi-directional deep reactive ion etching (DRIE) process is used for guaranteeing that the microneedles are completely etched, and the side walls of the microneedles have high smoothness; a silicon wafer is etched in a 40 percent KOH solution under the condition of heating in water bath at the temperature of 87 DEG C by an anisotropic wet etching process so as to obtain silicon microneedles of which the side walls are {411} crystal faces; and hollow silicon microneedles of which the height is 100 to 120 mu m, the diameters of needle holes are 10 to 25 mu m, and the centers of the needles holes are 5 to 10 mu m away from needle points are finally obtained. The method for manufacturing the microneedle array is simple, and easy to implement, low in cost and effectively solves the problems in a process for manufacturing out-of-plane hollow microneedles.

Description

A kind of preparation method of imitative mosquito mouth empty micropin array

Technical field

The present invention relates to a kind of preparation method of empty micropin array, particularly relate to a kind of microneedle array that is used for carrying out painless sample introduction that the mosquito mouth is made of simulating.

Background technology

In decades in the past, the micro-electro-mechanical systems micro-total analysis system of unifying has had very big development, particularly at medical science and medical field.At medical domain, the research of micropin has great importance for developing painless trace blood system.Micropin (Microneedles) refers generally to make through fine process; Size is at micron order; Diameter is the structure of needle-like at 30-80 μ m more than the length 100 μ m, material can be (Arrays of Hollow Out-of-Plane Microneedles for Drug Delivery [J] .Boris Stoeber.Journal of microelectromechanical systems such as silicon, polymer, metal; 2005,472-479).Micropin has widely at biomedical sector to be used, and for example is used for the biomedical measurement system, drug delivery system and microsampling analytical system etc.Micropin not only volume is small, and on performance, have conventional method incomparable characteristic-accurate, painless, efficient, convenient.This has greatly promoted Biomedical Development, makes the instrument in this field have more hommization.

As everyone knows, mosquito can have no under the situation of consciousness transdermal people and accomplishes sucking of blood.From seeing in appearance, the mosquito mouth is a long 3mm, external diameter 60 μ m, and the wheat head shape slim-lined construction of internal diameter 25 μ m, but this epitheca that just is evolved into by the mosquito lower lip is called beak.The design feature of mosquito mouth is in the lip groove at this beak back, to contain 6 elongated lancets that upper lip, a pair of maxilla, a pair of lower jaw and tongue specialization form (based on the research of the bionical coupling painless injection syringe needle of insect sucking mouth parts, Wang Jingchun, 2008).At present; Look like occasion in diabetic's the frequent blood samplings of needs such as blood sugar monitoring; Painless blood collecting technology is had very strong demand, therefore study the principle that mosquito is sucked blood, the structure of imitated mosquito mouthpart is also simulated its behavior of sucking blood; The skin that will be expected to develop painless Wicresoft is received and is risen blood sampling system, has great importance in the application aspect medical diagnosis on disease and the control for expanding the microfluidic analysis system.

Summary of the invention

The present invention simulates the mosquito mouth and combines MEMS (Micro-Electro-Mechanical System) technology to produce the microneedle array that is used for painless sample introduction, and a kind of preparation method of imitative mosquito mouth empty micropin array is provided.

Micropin in this microneedle array belongs to different plane hollow microneedle, and structure is similar with existing micropin, is made up of needle point, pin hole and substrate three parts, and needle point is used to puncture animal skin, and pin hole is used for the circulation of liquid, and substrate is a platform of making empty micropin array.

Technical solution problem of the present invention adopts following technical scheme:

(1) photoetching for the first time: the layer of silicon dioxide of on silicon chip, growing; Then at the positive spin coating one deck of silicon chip photoresist, pin hole figure mask is placed on carries out ultraviolet exposure on the photoresist, use developing liquid developing; Obtain the pin hole figure, use etching machine engraving erosion oxide layer;

(2) the positive etching pin hole of silicon chip: adopt two step etching technics at the positive etching pin hole of silicon chip, etching depth is the half the of silicon wafer thickness;

(3) photoetching for the second time: carry out photoetching at the silicon chip back side and obtain the pin hole figure, and use etching machine engraving erosion silicon dioxide layer;

(4) silicon chip back-etching pin hole: adopt two step etching technics it to be carved fully and wear at silicon chip back-etching pin hole;

(5) photoetching for the third time: at the positive square mask pattern that uses the photoetching of needle point figure mask to obtain corroding needle point of silicon chip;

(6) wet etching: after photoetching is accomplished, removing oxide layer, remove photoresist then, put into 40%KOH solution wet etching, is 100 μ m up to the micropin height, stops corrosion, removes the residue oxide layer, obtains empty micropin array.

In sum, adopt dry etching and the wet etching this simpler method that combines among the present invention, produce the similar hollow different plane hollow microneedle of pinhole aperture and mosquito mouth, manufacture craft is simple, easy realization.When adopting the not only slippery of its sidewall of micropin that wet etching obtains to reduce sample introduction and the contact area of skin, thereby ease the pain sense.

Description of drawings

Fig. 1 is different plane hollow microneedle array sketch map.

Fig. 2 is a process flow diagram of making different plane hollow microneedle array.

Fig. 3 (a) makes the single empty micropin SEM figure that obtains with the present invention.

Fig. 3 (b) makes the microneedle array SEM figure that obtains with the present invention.

Among the figure: 1 needle point; 2 pin holes; 3 substrates; 4 silicon chips; 5 silicon dioxide layers; 6 photoresist layers; 7 pinhole mask versions; The pin hole that 8 dry etchings obtain; 9 residue oxide layers; 10 needle point mask; The micropin that 11 wet etchings obtain.

The specific embodiment

Be described in detail specific embodiment of the present invention below in conjunction with technical scheme and accompanying drawing.

Shown in Fig. 2 (a), after silicon chip 4 cleaned through standard cleaning liquid, put into oxidation furnace and carry out oxidation, and feed dried oxygen and wet oxygen in certain sequence, make the surface of silicon chip generate the fine and close silicon dioxide layer 5 of one deck, as substrate.Mask as the dry etching pin hole.Shown in Fig. 2 (b), spin coating one deck BP212 glue-line 6 on the silicon dioxide layer 5 in silicon chip 4 fronts.Shown in Fig. 2 (c), be placed on the BP212 glue-line 6 pinhole mask version 7 and aligning, adopt ultraviolet exposure technology, realize that the pin hole figure is to the transfer of BP212 glue-line 6 on the pinhole mask version 7.Shown in Fig. 2 (d), use developer solution that BP212 glue-line 6 is developed, obtain the pin hole figure, the silicon chip 4 that will have the pin hole figure is put into ICP etching machine etching silicon dioxide layer 5.Shown in Fig. 2 (e), use acetone soln to remove BP212 glue-line 6, silicon chip 4 is put into ICP etching machine once more adopt two step etching technics etchings, obtain pin hole 8, make etching depth reach 245 μ m.Shown in Fig. 2 (f), silicon chip 4 back sides are repeated as above technology (b)～(e), pin hole 5 is carved fully worn.Shown in Fig. 2 (g); The layer of silicon dioxide layer 5 that regrows in silicon chip 4 fronts, and spin coating one deck BP212 glue-line 6 are placed on needle point mask 10 on the BP212 glue-line 6 and aim at; Adopt ultraviolet exposure technology, realize that the needle point mask pattern is to the transfer of BP212 glue-line 6 on the needle point mask 10.Shown in Fig. 2 (h), use developer solution that BP212 glue-line 6 is developed, obtain the needle point mask pattern, use ICP etching machine engraving erosion silicon dioxide layer 5.Shown in Fig. 2 (i), after the use acetone soln is removed BP212 glue-line 6, silicon chip 4 is put into 40%KOH solution, carry out wet etching under 87 ℃ of conditions of constant temperature, be 100 μ m up to the micropin height, stop corrosion.Shown in Fig. 2 (j), remove residue silicon dioxide layer 9, the micropin 11 that wet etching obtains with HF solution.

As shown in Figure 2, process flow steps is following:

(a) with silicon chip 4 as substrate, to its clean, two-sided oxidation, generate the fine and close silicon dioxide layer 5 of one deck on its surface, as the mask of dry etching pin hole;

(b) spin coating one deck BP212 glue-line 6 on the silicon dioxide layer 5 in silicon chip 4 fronts;

(c) be placed on the BP212 glue-line 6 pinhole mask version 7 and aligning, adopt ultraviolet exposure technology, realize that the pin hole figure is to the transfer of BP212 glue-line 6 on the pinhole mask version 7;

(d) use developer solution that BP212 glue-line 6 is developed, obtain the pin hole figure, the silicon chip 4 that will have the pin hole figure is put into ICP etching machine etching silicon dioxide layer 5;

(e) use acetone soln to remove BP212 glue-line 6, silicon chip 4 is put into ICP etching machine once more adopt two step etching technics etching pin holes 8, make etching depth reach 245 μ m;

(f) silicon chip 4 back sides are repeated as above technology (b)～(e), pin hole 5 is carved fully worn;

(g) the layer of silicon dioxide layer 5 that regrows in silicon chip 4 fronts; And spin coating one deck BP212 glue-line 6; Be placed on the BP212 glue-line 6 needle point mask 10 and aligning, adopt ultraviolet exposure technology, realize that the needle point mask pattern is to the transfer of BP212 glue-line 6 on the needle point mask 10;

(h) use developer solution that BP212 glue-line 6 is developed, obtain the needle point mask pattern, use ICP etching machine engraving erosion silicon dioxide layer 5;

(i) after the use acetone soln is removed BP212 glue-line 6, silicon chip 4 being put into 40%KOH solution, carry out wet etching under 87 ℃ of conditions of constant temperature, is 100 μ m up to the micropin height, stops corrosion;

(j) remove residue silicon dioxide layer 9, the micropin 11 that wet etching obtains with HF solution.

Empty micropin array through above-mentioned technology is made is as shown in Figure 3.

Claims (1)

1. the manufacture craft of an imitative mosquito mouth empty micropin array is characterized in that following steps:

(1) photoetching for the first time: the layer of silicon dioxide of on silicon chip, growing; Then at the positive spin coating one deck of silicon chip photoresist, pin hole figure mask is placed on carries out ultraviolet exposure on the photoresist, use developing liquid developing; Obtain the pin hole figure, use etching machine engraving erosion oxide layer;

(2) the positive etching pin hole of silicon chip: adopt two step etching technics at the positive etching pin hole of silicon chip, etching depth is the half the of silicon wafer thickness;

(3) photoetching for the second time: carry out photoetching at the silicon chip back side and obtain the pin hole figure, and use etching machine engraving erosion silicon dioxide layer;

(4) silicon chip back-etching pin hole: adopt two step etching technics it to be carved fully and wear at silicon chip back-etching pin hole;

(5) photoetching for the third time: at the positive square mask pattern that uses the photoetching of needle point figure mask to obtain corroding needle point of silicon chip;

(6) wet etching: after photoetching is accomplished, removing oxide layer, remove photoresist then, put into 40%KOH solution wet etching, is 100 μ m up to the micropin height, stops corrosion, removes the residue oxide layer, obtains empty micropin array.

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