TW200416867A - Method of fabrication for hollow microneedle array - Google Patents

Abstract

Methods for manufacturing microneedle array, with simplified procedures and a lower material cost, are provided to fabricate microneedles each having an end with inclined plane. Because of the sharp end can easily intrude into an organism, the microneedle array is favorable for applications in drug dispensing and sampling. The fabrication procedure starts from wet-etching a silicon base to form an indent with ramp geometry area. Using the indent as a mold, the microneedle array can be produced by varies ways such as metal plating, exposing/developing, and micro processing.

Description

200416867 V. Description of the invention (l) The technical field to which the invention belongs "In particular, ΐ 明 ί: A method for manufacturing a kind of microneedle (mlcroneedle), especially a kind of hollow microneedle array with a slanted tip ) 的 制造 方法。 Manufacturing method. [Prior technology] Recognized r i empty microneedle array (h〇U〇w microneedle array) Lu Yu blood collection system, micro sampling and 荜 y) widely used materials can be divided into semiconductor materials ^ /, professional students or Type by material s T ¥ body material 枓, southern molecular material and metal. In the field of semiconductor material manufacturing, in the relevant patents, it is said that before the related patents, extension wnno + head array evening + silicon wafer as a circle _65 and other cases 5, surface 17 9 8 5, etching in the thin film deposition step, Eryi Guang due to ^ Long so that the production capacity is not so impressive :: The manufacturing process is complicated and takes a long time. "The cost cannot be reduced, and the road to mass production is difficult. In addition, part of the process system # φ US6334856, the width of the flow channel ° is a conical needle, as in the previous case, the inner diameter and the strong root of the structure are gradually taken to the end. Shrinking and increasing the density of the array 'causes: Insufficient ::: This = ten, can not be applied, due to the gradual shrinking of the pipe diameter, high driving power of the injection of fun, or thorium, which is relatively high: resistance increase Large, so the root end must be raised to the more common flat-head micro-preparation costs. Invasion of flexible biological tissues, relatively, ^, 'because of the lack of sharpness, it is not easy, otherwise there will be a marginal "situation. Structural strength, [Summary of the invention]

200416867 V. Description of the invention (2) The technical problems to be solved in this creation, the appearance and structural strength of Yushan Cheng are limited by the two-narrow narrow needle array manufacturing process: It is too complicated to achieve the quantity; Existing column manufacturers; After the microneedle array provided by the present invention, this method-oblique circle = bevel-shaped recessed area 'random shadow or micromachining, is used to produce micro: ;; The # 4 ^ 'head array achieved by the present invention, this microneedle does not: can be used to make microneedles into biological tissues in a simple process, but also can be used as Af and bevel-shaped, with acute angles and easy to invade [Implementation] T as Turn the mold to copy the microneedle array of other materials. : ': On the microneedles provided by Ming (such as Shixi wafer, acrylic or light = f is mainly on the substrate in advance, and subsequent follow-up = use the bevel geometry of this recessed area as the shape and right M: I metal, exposure, development, or micromachining, etc. Six, micro-needle arrays with beveled ends are made in a temple. To make one, metal-plated micro-needle arrays, please refer to "Figure 1A" to "When nu θ is provided in the preferred embodiment, the first step of the invention" is completed in the first step of the present invention: The manufacturing method of the step-by-step pin and pin array is firstly performed on a Shixi wafer by 1 1 〇 (Such as Niu Niu (Sl3N4n 0 "layout of the protective layer on the upper and lower surfaces" laying photoresist as shown in Figure 1A "" ", said, slashed the area and etched the protective layer

Page 7 V. Description of the invention (3) The area to be wet-etched after 1 1 0 is obtained, and the partial silicon wafer exposed in s 1 1 1 is further treated as a circle for wet-etched area 1 0 0 during wet etching. Wet etching, because the silicon crystal has the characteristics of a chamfered concave area x 0 in etching, and the protective layer 110 that can be formed on the bottom side is also a micro-view / second king c picture, and then the area 1 1 2; Then, for example, "the first D type" means that the initial metal layer 1 2 0 (such as chromium, nickel θ, etc.) is to be dry-etched, and a shadowing technology is applied on the top surface of the broken wafer 100, such as "1 E m ^, Called, etc.) 'Then use the micro material 1 3 0 again, and form a number of plating ^ 丄 2 0 lay a photosensitive metal layer 1 2 0, this plating area 丄 3 d 1 way out of the local starting gold and then, On the plating area 13 is a tubular hollow area; the plating metal (such as copper, " nickel 箄, etc.) is the starting metal layer 1 2 0 on 1 4 0. And forming a metal microneedle-like starting metal; the characteristics of the ΓΠ column will correspond to the bevel-like surface, as shown in the end of the metal microneedle 14o. Figure 1 G: 」Needle 1 4 Ω · Printed β material 1 3 〇 Expose a hollow metal U needle 1 4 0, and then take out a silicon wafer through a metal microneedle 1 4 〇 perforation 丄 〇 2 ◦ Carved, formed, in the above system 5, the definition of the area to be dry etched 1 1 2 is not limited to wet etching: Ke, basically as long as it is performed before dry etching 'and' plating Metal technology can optionally be electroplated, electroless platlng, vapor deposition or sputtering

S to putter mg), etc., so the starting metal layer 丄 20 is not absolutely necessary, and the metal material can also be selected from nickel, iron, gold, platinum, palladium, each

Page 8 200416867 V. Description of the invention (4) Type alloy or non-recorded steel. In addition, it is not necessary to use Shi Xijing's surface-shaped recessed area, and to form an inclined basin on the substrate as a substrate. Special features can also be dry etching, or f "radiation: i light Polymer materials, such as resistance, etc. = limited to the above-mentioned id: the substrate of the planar recessed area ", and not, / 卞-system step ordering. And the density of the AL array forming a micro-needle array is too small, and it is said that,,, by controlling the distance to be wet: 2: the second is to define the distance between the two areas to be wet ... See, and the money to be wet chart " The second 22 A 0 of this creation is shown in the second to the second F. 2nd process of the wet etching area ":" I "Figure 2B" defines A2 "or the length of the remaining wet ^: the length of the inner warp … Different distances B 2, β 2! 〇, 2 3 〇 are shown as "2F graph". P & Arrays of different densities can be created: Beyond microneedles, they can also be manufactured. Please refer to "Mother"; "= ^ = Example of micro-needle made of other materials is to first have metal micro-needle 7 = ^, the third comparison of this creation: depositing a release layer 3 2 0 (such as Teflon; To: Wafer 300 Table 10 and Shixi Wafer 300, will be high ^ :: f metal microneedle:… along the metal micro pin. Press, wait to heat = thin; microneedle 3 40. Therefore, gold Erbei's mold is released after cooling, and one mold is mass-produced for manufacturing other materials ::; micro: 200416867 V. Description of Invention (5) According to different materials, the demoulding method can use heating, cooling, and interface coating. This method uses layers, solvents, and direct demolding. 贰. Exposing and developing microneedle arrays in addition to the metal microneedle and polymer microneedle manufactured by the above-mentioned plating technology, it also uses silicon wafers with bevel-like recesses. The microneedle body can also be made by exposure molding. Please refer to Fig. 4A to Fig. 4 (b). The execution steps of the fourth preferred embodiment of the present invention are: 4 A. Deposit on the surface of silicon wafer 401 Etching protective layer 4 0 2; 4 Β. Laying photoresist exposure and development to define the area to be etched, and etching protection After the layer 402, the area to be wet etched is 403; 4 C. The non-isotropic etching (wet etch) silicon wafer 401 is obtained with the recessed area 404 with a bevel geometry; (Such as black photoresist) After 405, lay a sacrificial layer such as gold (or a release layer such as Teflon) 4 0 6; 4 Ε. Then lay a photosensitive material 4 7 and perform the first exposure to obtain the first exposure. Area 4 0 8; 4 F. Perform a second exposure to obtain a micro-needle-shaped second exposure area 4 0 9; 4 G. Remove the sacrificial layer 4 6 (or directly remove the film) to obtain a substrate 4 with a bevel geometry 1 0; 4 II. Substrate 4 1 0 Microneedle array 4 2 0 is obtained after development. In the above steps, the non-reflective layer 4 5 is mainly used to avoid overexposure due to different exposure depth when the photosensitive material is exposed. The layer 4 0 5 sacrificial layer 4 6 (or release layer) can be changed in order of laying; moreover, it can also be demolded and then exposed and developed. In addition, laying more than one layer of photosensitive material can be used to change the needle through

Page 10 200416867

It can be integrated with a microfluidic channel to form a detailed blood collection and delivery system. The detailed description is as follows. Please refer to Figures 5A to 5G. The execution steps are: 5 A · Etching and depositing 5 0 1 to obtain a missing layer with a bevel geometry. 5 0 5, sacrificial layer (or release layer) light material 5 0 7 for the first exposure 5C. For the second exposure; 5d · lay a second layer of photosensitive material 5 1 0, a non-reflective layer 5 1 1. The fourth exposure of the laying line; 5F · Removal of the substrate to the substrate 5 2 with a bevel geometry yields a microneedle array 5 3 〇. Among them, the non-reflective layer and the sacrificial layer can be replaced or different according to different structural requirements and processes. The substrate can be made with positive or negative photoresistance. Therefore, 'using similar processes and materials' to form different sizes of flow channel groups. The control of the tube diameter will make the application layer of the needle be a flow channel connection network (the distance of flow channel 5 and the size of the area, which can be controlled using the above method) The microneedle can be formed, and then various bevel combinations can be produced. The silicon wafer recessed area 5 0 4 of the protective layer 5 2 of the fifth preferred embodiment of the present invention is laid with non-reflective 5 06 and 5B. Layer photosensitivity to obtain the first exposure area 508; laying a non-reflective layer 509, and performing a third exposure; 5 E. then lay a second layer of photosensitive material 512, enter the layer 506 (or directly remove the film), get; 5 G · Substrate 5 2 0 After development, the release layer can be adjusted in sequence and omitted, and the second exposure is more robust; In addition, the photosensitive material can also be stacked and stacked in more than one layer (flow channel 5 a , 5 b), different faces are wider; or as the storage area and 3) ', define the density of the beveled needles between the etched areas. Various beveled needles on the bevel substrate, such as single bevel

Page 11 200416867 V. Explanation of the invention (7) (such as "Figure 6" A) The slope of the formula (such as "the second double slope (such as the factory Figure 7" B, C, etc.). A) or other formal parameters For micro-machining, please refer to Six Best Practices for Depositing a Protective Layer to Etch a Silicon Wafer 8 D · Laying a sacrificial plastic material 6 6 0 7 and arranging (defining a plastic material in the flow using laser processing for injection molding. The above limits the present invention Proven in manufacturing microneedle arrays "Figure 8A" to "Figure 8η" using the techniques of the present invention, the execution steps are as follows: 8 ^ The present invention disclosed in No. 602; 8B. Definition is waiting = Mengjing The surface of the circle 601 is obtained with a slope of 4 = the engraved area 603; 8C. The animal layer 605 (or the release layer ^ may ^ the recessed area 604; 〇6) is stamped to form a slope 8F ·, 8G. With = In addition to the sacrificial layer 6 0 5 (or Ί 才 = 是 热 = or ^, 崎, and obtained the substrate description, it is only the preferred embodiment of the present invention " the scope of Ming Guan Shi; anyone familiar with this technique Patents = equal changes and modifications made, all should be covered

Page 12 200416867 The diagram is a brief description of diagrams 1 A to 1 Η The diagram is the manufacturing flow of the first preferred embodiment of the present invention: Process diagrams 2 A to 2 F diagrams are the first of the present invention. The manufacturing flowchart of the embodiment 5 Figures 3A to 3C are the manufacturing flowchart of the preferred embodiment of the present invention. Figures 4A to 4C are the fourth preferred embodiment of the present invention. Manufacturing flow chart 1 Figures 5A to 5G are manufacturing flowcharts of the fifth preferred embodiment of the present invention. Figures 6 and 7 are the shapes of the bevel-shaped recessed areas of the present invention and various microneedle shapes can be obtained. Figures from Zhao and Figure 8A to Figure 8 are the manufacturing flowchart of the sixth preferred embodiment of the present invention. [Illustration of Symbols] 1 0 0 Silicon wafer 1 0 1 Notched area 1 0 2 Perforation 1 1 〇 Protective layer 1 1 1 To be wet etched 1 1 2 To be dried 4k engraved area 1 2 0 Starting metal layer 1 3 〇 Photosensitive material 1 3 1 Bell area 1 4 〇 Metal microneedle 2 1 0 ik engraved area 2 2 0% k engraved area 2 3 〇 engraved area 3 0 0 silicon wafer 3 1 〇 gold. Belongs to microneedle 3 2 0 release layer 3 3 0 埶 y, ',' Plastic film 3 4 0 microneedle

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200416867

Brief description of the figure 4 0 1 Silicon wafer 4 0 2 Protective layer 4 0 3 Ik etched area 4 0 4 Notch area 4 0 5 Non-reflective layer 4 0 6 Sacrificial layer 4 0 7 Photosensitive material 4 〇8 — Exposure Area 4 0 9 Second exposure area 4 1 0 Substrate 4 2 0 Microneedle array 5 0 1 Silicon wafer 5 0 2 Protective layer 5 0 4 Notch area 5 0 5 Non-reflective layer 5 0 6 Sacrificial layer 5 0 7 Photosensitive material 5 0 8th-exposure area 5 0 9 Non-reflective layer 5 1 0 Photosensitive material 5 1 1 Non-reflective layer 5 1 2 Photosensitive material 5 2 〇Substrate 5 3 〇Microneedle array 5 a ^ 5 b, 5 C Channel 6 〇1 Silicon wafer 6 0 2 Protective layer 6 0 3 Area to be wet-etched 6 〇4 Notched area 6 〇5 Sacrificial layer 6 〇6 Plastic material 6 〇7 Substrate 6 1 〇Microneedle array 6 a , 6b runner

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Claims (1)

200416867 VI. Scope of patent application1. A method for manufacturing a microneedle array, including the following steps: depositing a protective layer on the surface of a stone wafer; defining a plurality of areas to be wet-etched; A plurality of recessed areas, and a subsequent processing is performed using the recessed areas to obtain a microneedle array 歹 lj. 2. The method of manufacturing a microneedle array as described in item 1 of the scope of patent application, wherein the subsequent processing is selected from one of a group combination of electroplating, exposure development, and micromachining. 3. The microneedle array manufacturing method as described in item 1 of the scope of the patent application, wherein the silicon wafer is replaced with an acrylic material (PMMA), and the notched region with a bevel geometry is obtained by laser processing. 4. According to the method for manufacturing a microneedle array as described in item 1 of the scope of the patent application, wherein the silicon wafer is replaced with a photoresist material, and the recessed area with a bevel geometry is obtained by oblique exposure development. 5. The method for manufacturing a microneedle array as described in item 1 of the scope of the patent application, wherein the end surface of any microneedle in the microneedle array is partially or entirely inclined. 6. The microneedle array manufacturing method according to item 1 of the scope of patent application, wherein the subsequent processing further includes the following steps; a photosensitive material is laid on the Shi Xi wafer in a lithography (Π thogr aphy) manner, and a Notched forged area; a metal plated on the plated area to form a plurality of metal microneedles Page 15 200416867 VI. Patent application head; and 7 8 9 〇 2 remove the photosensitive material to expose the hollow metal microneedle; dry the needle to rub the machine to obtain a plurality of perforations through the metal micro as in the scope of patent application No. 6 The microneedle array system & wherein the bevel-shaped recessed area is formed by an advanced method, which is a step of layering on the silicon wafer, and the "": the starting metal layer of starting gold. ^ Plating person is exposed in the microneedle array as described in item 6 of the scope of the patent application. The method of plating the metal is selected from the group consisting of electroless platlng, vapor deposition (sputtering) ) In one of the group combinations—.n) or splashing the microneedle as described in item 6 of the scope of the patent application, wherein the metal is selected from copper, chromium, nickel, iron, eight & methods, pure metals and their alloys The method of micro-needle described in the terms of group platinum and palladium of stainless steel, processing, ef g and group of lithography: Vi Ϊ I: I Item 6: the method of manufacturing the micro-needle array, Jiayu G a U has the metal microneedles with the steps of manufacturing multiple microneedles. Μ 夕 曰 ® as the manufacturer of the microneedle array described in the item% of the patent application. Page 16 200416867 VI. Patent application method, in which the method of manufacturing the microneedles is: 'Micro hot press forming group combination 12 of which are selected from micro injection molding and' as described in item 1 of the patent application range. One of the subsequent processes further includes: a head array manufacturing method, laying a non-reflective layer and a sacrificial layer instead of laying a photosensitive material; " reading on a silicon wafer; performing exposure to expose an exposed area of the photosensitive material; v The sacrifice layer was removed in the shape of a needle array, and a substrate was developed by developing the substrate to obtain a surface geometry; as described in the scope of patent application, item 3 of the patent = head array. In the method, two of the photosensitive materials are laid: ten: the array manufacturer sacrifices the layer, and then the substrate is obtained; after f, the light is removed first as described in the patent application scope i 仃 * Light and development. Method, in which the sacrificial layer array is manufactured * ΐ 申 = ;;; according to the microneedle two-car train manufacturing steps described in the item, the material is exposed and the flow channel is connected :::: the inner diameter is changed, or it is included; The manufacturing method of the microneedle array according to the first item, the r β subsequent processing further includes the following laying-sacrifice layer on the silicon wafer; pressing with a plastic material; and removing. The sacrificial layer ′ obtains a substrate with a bevel geometry; 3 4 5 6 7 page 17 200416867 6. Patent application scope Perform a micro-processing 8 .Γ1T scope item κ: = microneedle array. The method, /, the sacrificial layer is replaced by the manufacturing method of the spin-pin master array. The method is one in which the plastic material is selected: a group combination of 2 needle array manufacturing materials. …, The solid materials and thermoplastic materials are described in the scope of claim 17 of the microneedle '/, the plastic material is used for rhinoceros, the array manufacturing step of the plastic material injection molding step, the steps are Replaced by the method described in item 27 of the scope of the patent application, wherein the micro-machining treatment is selected from one of the group consisting of ~ Shishuo array manufacturing squares. A method for manufacturing a microneedle array by field shooting and etching, including wet etching on a surface with a protective layer: ν privacy · a bevel-shaped recessed area; a wafer to form the silicon by lithography On the wafer, a recessed plated area is formed on the head. H belongs to the M area. The metal microneedles are removed and the photosensitive material is removed to expose the metal microneedles. Dry rice engraving the Shixi wafer to obtain a plurality of perforations through the metal micro. The microneedle array manufacturer 1R 4 4 7 as described in the patent application scope No. 22 was replaced with an acrylic material (PMMA). The notch area of the bevel geometry. The square circle of the microneedle array manufacturing item described in item 22 is replaced with a photoresist material, and the lack of bevel geometry is obtained through the development of the light. The end surface of the microneedle array manufacturing microneedle item described in item 22 is part or all. Layers on wafers with beveled recesses 2-22. Item 2 of the 2nd metal formula 1 ati ng) After the microneedle array manufacturing method is formed, a deposition step is performed first, and the plating area is exposed. The manufacturing method of the microneedle array is selected from the group consisting of electric ore and non-electric bond steaming. Forging (deposition) or sputtering the microneedle array manufacturing method, chromium, nickel, iron, gold, platinum rust steel group combination of the method 'wherein the silicon crystal and through laser processing as in the patent application method'wherein Silicon crystal processing or tilting exposed areas. Such as the patent application method, where the metal is shaped. For example, the scope of patent application method, where the starting metal layer of the bevel is on the part of the stone evening, such as the scope of patent application method, where electroless p plating (sputter i ng) is applied. The pure metal of palladium and its group combination, the second item 2 is selected from copper alloy and no. 9) The method for manufacturing a microneedle array as described in the second patent application item No. 22, wherein the photosensitive material is removed and the Perforation _ group combination of laser processing, etching and lithography 0〇416867 Six of the scope of the patent application, such as the 22 method of the scope of patent application, which further includes manufacturing a plurality of microneedles = metal microneedles using the microneedle array manufacturing method as a mold. Steps ^ and。 of the scope of patent application. Method, in which the microneedles are manufactured, and the prostitute needle array manufacturing method, Shijiao ”is micro-injected into inflammation. 4 methods, in which the microneedles are manufactured by the micro-needle micro-hot-pressing group combination. The microneedle array manufacturing method is gone. Wet #carved one surface with the second right: it includes the following steps: a bevel-shaped recessed area; a silicon wafer with 5 layers is laid with a non-reflective layer and a photosensitive material; s on the silicon wafer; perform exposure to make the photosensitive area / one of the exposure area; "form a micro-needle array shirt to remove the sacrificial layer to get a star; develop the substrate to obtain _ micro-needle: 口 何 之Bottom * method, in which the Shixi wafer system is replaced by Jin Mi Gan reading, ft + μ 4 Dinggu 4 acrylic material (PMMA), obtained obliquely by injection processing. For example, the scope of application for patent 3 2 The method of "#", in which the Shi Xi wafer system array is manufactured by a radiation processing method or an oblique exposure development method, and passes through the sunken area. The defect of the bevel geometry of the service tool is obtained by the way. As described in item 32 of the patent application scope, the manufacturer of the microneedle array is # 20, page 20, 200416867, and the patent scope is ^ 丄. All are beveled. The τ song's knowledge is A 6 as described in the No. 32 item of Shen Qing's patent scope. The micro- # method is described below, in which the needle array is used to make a ^ sacrificial layer, and then the obtained substrate is exposed and mixed. After the steps of manufacturing the light and display of the microneedle array, the first step is to replace the sacrifice layer in the microneedle array manufacturing square tool with a demolding genus. • tu: The micro-needle two method described in item 32 of the scope 'which further includes repeatedly laying the photosensitivity "::: t step, so that the flow channel of the micro-needle array has internal 禋:: ^ is a storage area or a first-level channel The use of connection network " Another 5'-manufacturing method includes the steps of: etching a surface with a bevel-like recessed area with a protective layer; day 5], laying a sacrificial layer in the shape of the silicon On the wafer; compression molding with a plastic material; removing the sacrificial layer to obtain a substrate with a micro-machining process to get the second place. ::! The microneedle array stacking method described in item 40, wherein the silicon wafer system is replaced with a single press: 歹 j 衣 & square and obtained by laser processing ^ ^ force material (pmma) & The recessed area with bevel geometry, the 7 exposed 8 work, 40% 4 200416867 6. Patent application scope 4 2 · If the patent application scope No. 40 method, where the silicon wafer is replaced by two = needle master Array manufacturing process or oblique exposure development method to obtain I-Zia transmission through the concave area. (2) What is the lack of the inclined plane? The microneedle production method described in item 40 of the patent application scope, wherein any or all of the microneedle arrays are inclined plane. " Fifth, the details are partly described in the micro-method described in item 40 of the patent application scope, wherein the sacrificial layer is replaced with a release layer car.] The clothing party is as described in item 40 of the patent application scope. In the microneedle array manufacturing method, the plastic material is one selected from the group consisting of thermosetting materials. Kelvin thermoplastic material The microneedle array manufacturing method described in the patent application scope No. 40, wherein the plastic material is subjected to the step of compression molding, and the plastic material is injection-molded in a few steps. It is replaced with the microneedle array manufacturing method as described in the patent application No. 40, wherein the micro-processing is selected from one of a group combination of laser processing and etching. 4 4 4 4 5 4 6 4 7