U.S. patent application number 10/994105 was filed with the patent office on 2006-01-19 for microneedle array device and its fabrication method.
Invention is credited to Yu-Kon Chou, Shih-Chi Kuo.
Application Number | 20060015061 10/994105 |
Document ID | / |
Family ID | 35600412 |
Filed Date | 2006-01-19 |
United States Patent
Application |
20060015061 |
Kind Code |
A1 |
Kuo; Shih-Chi ; et
al. |
January 19, 2006 |
Microneedle array device and its fabrication method
Abstract
A microneedle array device and its fabrication method are
provided. The microneedle array device comprises a supporting pad
and plural of microneedles. Each microneedle has a top portion with
a via thereon, thereby the microfluid may flow in or out. The
intersection between the top portion and the inner tube of a
microneedle forms a convex needle structure, and is almost
perpendicular to the upper surface. For each microneedle, a hollow
closed tube is formed between the top portion and the supporting
pad. The fabrication method uses the substrates with high
transmittance and plural of convex area thereon as the upper and
lower caps, and applies a photolithography process to fabricate a
microneedle array mold. It then sputters or electroplates metal
material on the mold. The microneedle array is formed after having
taken off the mold. It is a simple fabrication process.
Inventors: |
Kuo; Shih-Chi; (Yangmei
Township, TW) ; Chou; Yu-Kon; (Sindian City,
TW) |
Correspondence
Address: |
SUPREME PATENT SERVICES
POST OFFICE BOX 2339
SARATOGA
CA
95070
US
|
Family ID: |
35600412 |
Appl. No.: |
10/994105 |
Filed: |
November 19, 2004 |
Current U.S.
Class: |
604/47 ;
604/173 |
Current CPC
Class: |
A61B 17/205 20130101;
A61M 2037/0053 20130101; Y10T 29/302 20150115; Y10T 29/49982
20150115; A61M 37/0015 20130101; Y10T 29/308 20150115; B81B
2201/055 20130101; B81C 1/00111 20130101; Y10T 29/304 20150115 |
Class at
Publication: |
604/047 ;
604/173 |
International
Class: |
A61B 17/20 20060101
A61B017/20 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 16, 2004 |
TW |
093121337 |
Claims
1. A microneedle array device having a monolithic structure,
comprising: a supporting pad having an upper surface; and a
plurality of microneedles, each microneedle having a slant or
concave curvy top portion, said top portion having a via for
microfluid to flow, a hollow closed tube being formed between said
top portion to said supporting pad, said top portion intersecting
with wall of said tube wall to form a convex needle structure, each
microneedle standing on said upper surface of said supporting pad,
and said microneedle being perpendicular to said upper surface of
said supporting pad.
2. The device as claimed in claim 1, wherein said tube wall of each
microneedle toruses to form an oval, circular or triangular
shape.
3. The device as claimed in claim 1, wherein said supporting pad
further comprises a bottom portion and at least a reservoir layer,
said reservoir layer is located above said bottom portion and below
said plurality of microneedles.
4. The device as claimed in claim 3, wherein said at least
reservoir layer is further divided into a plurality of reservoir
units, said reservoir units are separate from one another to
prevent microfluid stored in said reservoir units from flowing
among said reservoir units.
5. The device as claimed in claim 1, wherein said metal structure
is made of a metal selected from one of the Cu, Cr, Ni, Fe, Au, Pt,
Pd, stainless steel, and their alloy.
6. The device as claimed in claim 1, wherein the aperture of said
microneedle ranges from 10 um to 60 um.
7. The device as claimed in claim 1, wherein the circumference of
said microneedle ranges from 70 um to 250 um.
8. The device as claimed in claim 1, wherein the height of said
microneedle ranges from 100 um to 600 um.
9. A method of fabricating a microneedle array device, comprises
the steps of: (1) providing a substrate, and forming a plurality of
concave areas on a surface of said substrate; (2) coating a layer
of photo-sensitive material on top of said substrate, and coating a
layer of light transmission material on top of said photo-sensitive
material; (3) using a patterned mask for exposure and development
on said light transmission material to obtain a polymer hollow
microneedle array mold using said light transmission material as a
base; and (4) forming a microneedle array device using said polymer
hollow microneedle array mold.
10. The method as claimed in claim 9, wherein said substrate in
step (1) is made of silicon.
11. The method as claimed in claim 9, wherein said plurality of
concave areas on said substrate in step (1) are formed by an
etching technique.
12. The method as claimed in claim 11, wherein said etching
technique is anisotropic wet etching technique.
13. The method as claimed in claim 9, wherein said plurality of
concave areas on said substrate in step (1) are formed by X-ray
etching, ultra-violet etching, ion beam etching, or excimer laser
micromachining.
14. The method as claimed in claim 9, wherein said plurality of
concave areas on said substrate in step (1) are formed by micro
electro discharge machining technique.
15. The method as claimed in claim 9, wherein said photo-sensitive
material in said step (2) is SU-8 or JSR430N.
16. The method as claimed in claim 9, wherein said light
transmission material in said step (2) is PMMA or glass.
17. The method as claimed in claim 9, wherein said step (3) further
comprises a step of using a patterned mask to define the shape of
microneedles.
18. The method as claimed in claim 17, wherein patterned mask
comprises a plurality of pairs of closed curves, each said pair of
closed curves comprise a first closed curve and a second closed
curve, said first closed curve encompasses said second closed
curve, said second closed curve has a circumference smaller than
that of said first closed curve, and remaining areas are masked
except the area between said first and said second closed
curves.
19. The method as claimed in claim 17, wherein said step (3)
further comprises a step of forming at least a reservoir layer.
20. The method as claimed in claim 19, wherein the shape of each
said reservoir layer is defined by using a corresponding patterned
mask.
21. The method as claimed in claim 19, wherein the depth of each
said reservoir layer is controlled by adjusting exposure dosage of
light.
22. The method as claimed in claim 9, wherein said step (4) further
comprises the following sub-steps of: (4a) coating a metal layer on
outer surfaces of said polymer hollow microneedle array mold and
said light transmission material to form said microneedle array
device; and (4b) removing said polymer hollow microneedle array
mold from said microneedle array device.
23. The method as claimed in claim 22, wherein said coating of
metal or other material in said step (4a) is by electroplating,
electroless plating, evaporation, or sputtering.
24. The method as claimed in claim 22, wherein said metal is chosen
from one of the Cu, Cr, Ni, Fe, Au, Pt, Pd, stainless steel and
their alloys.
25. The method as claimed in claim 22, wherein said removing said
polymer hollow microneedle array mold in said step (4b) uses one of
oxygen removal, thermal removal, solvent removal, aqueous removal,
photo-degradation removal, and their combinations.
Description
FIELD OF THE INVENTION
[0001] The present invention generally relates to a microneedle
array structure, and more specifically to a microneedle array
device, and a method of forming the same.
BACKGROUND OF THE INVENTION
[0002] The current microneedle array may be made of silicon (Si
substrate), metal or polymer. The manufacturing methods of Si
substrate microneedle array can further be categorized as using wet
etching or dry etching. The manufacturing process of metal
microneedle array can further be categorized as using
electroplating or deposition. The manufacturing process of polymer
microneedle array can be further categorized as using molding or
photolithography.
[0003] Among the methods of microneedle array, the most widely
adopted is using Si substrate to fabricate the hollow needles or
mold. However, the fabrication process of using Si substrate is
more complicated, as disclosed in WO0217985, and requires many
steps of wet/dry etching and thin film deposition. As it takes a
longer time to fabricate, the yield rate is low and the cost is
high. U.S. Pat. No. 6,334,856 disclosed a method of fabricating a
microneedle array having flat needle tips and tapered tube, as
shown in FIG. 1. This type of design limits the width of the flow
channel and the flexibility of the needle. To fabricate the needle
higher than 100 um, the needle density must be restricted in
compromise for an appropriate size of aperture and strength of
needle structure. The restriction of low needle density further
causes the problem of insufficient sampling. In addition, the Si
substrate microneedles are brittle and break easily.
[0004] The tip of the hollow microneedle in most prior arts is
designed as flat, except the design disclosed in WO0217985 (see
FIG. 2), which is a slant. This is because a slant tip is easier to
penetrate the human skin for micro-sampling than the flat tip, as
the human skin is flexible.
[0005] Kim et al. disclosed a method for fabricating metal
microneedle array in Journal of Micromechanics and Micro
engineering in 2004. They spread two layers of SU-8 on a glass
substrate and used a back exposure to separately bake the two
layers of SU-8. They also used reactive ion etching to obtain an
SU-8 pillar array structure, and then used sputtering,
electroplating, planarization and polishing to fabricate a tapered
metal hollow microneedle array, as shown in FIG. 3. However, the
method requires multiple layers of SU-8 to achieve the layered
effect and the high aspect ratio of the pillar is prone to slant or
twist. The fabrication process is difficult to maintain the
quality.
[0006] U.S. Pat. No. 6,663,820 disclosed another method of using
lithography and photolithography to fabricate polymer microneedle
array, as shown in FIG. 4. This method has the advantages of rapid
fabrication of micromold and microneedle, and low fabrication cost
of the material and process. However, the flat-tip microneedles are
still limited in the application. In addition, the polymer
microneedles of this method do not have microchannels or
reservoirs, and require additional fabrication process to attach
the microchannels and reservoirs, if necessary. It is, therefore,
difficult to have this method applied for mass production.
[0007] Numerous methods of fabricating microneedle array have been
proposed. Regardless of the material used, the object of the
microneedle array includes the capability to penetrate the human
skin for micro-injection or micro-sampling painlessly, easy to
fabricate, low in fabrication cost and safe to use.
SUMMARY OF THE INVENTION
[0008] The present invention has been made to overcome the
aforementioned drawback of conventional bonding methods of
fabricating microneedle array. The primary object of the present
invention is to provide a microneedle array device, including a
supporting pad and a plurality of microneedles. The supporting pad
has an upper surface. Each microneedle has a slant or concave top
portion with a via thereon, thereby the microfluid may flow in or
out. The intersection between the top portion and the inner tube of
a microneedle forms a convex needle structure. Each microneedle
stands on the upper surface of the supporting pad and is almost
perpendicular to the upper surface. A hollow closed tube is formed
between the top portion and the supporting pad.
[0009] The supporting pad further includes a bottom portion and at
least a layer of reservoir. The reservoir is located above the
bottom portion and below the microneedle. The reservoir can be
further divided, if necessary, into a plurality of reservoir units,
with reservoir units separated from one another to prevent the
microfluid flowing from one unit to another. The monolithic metal
structure of the present invention includes convex needle structure
formed by the intersection of the slant or concave top portion of
each microneedle and the inner tube of a microneedle. The main
feature of the present invention includes the safety of use and the
improvement of pain. Furthermore, the rigidity and the slant
uniformity of the microneedle with slant top portion are both
improved so that it is suitable for molding and mass
production.
[0010] Another object of the present invention is to provide a
method of fabricating a microneedle array device, including the
steps of: (1) providing a substrate, and forming a plurality of
concave areas on a surface of the substrate; (2) spreading a layer
of photo-sensitive material on the substrate and covering a layer
of light transmission material on top of the photo-sensitive
material; (3) using a patterned mask for exposing and lithography
of the light transmission material to obtain a polymer hollow
microneedle array mold based on the light transmission material;
and (4) using the polymer hollow microneedle array mold to form a
microneedle array device.
[0011] According to the present invention, there are several
techniques to be used in step (1) of forming a plurality of concave
areas, including etching, X-ray photo-etching, ultra-violet
etching, ion beam etching and excimer laser micromachining. Step
(4) of the method further includes the following substeps: (4a)
coating a layer of metal on the outer surface of the polymer hollow
microneedle array mold and the light transmission material to form
a microneedle array; and (4b) removing the polymer hollow
microneedle array mold from the microneedle array. In step (4), the
techniques for coating metal to the surface of the polymer hollow
microneedle array mold include electroplating, electroless plating,
evaporation, and sputtering. The metal used can be Cu, Cr, Ni, Fe,
Au, Pt, Pd, stainless steel and their alloys. The present invention
uses the coating of photo-sensitive polymer on the concave areas of
the substrate and covering with a light transmission material,
which is exposed to define an outline of the microneedle and using
lithography to obtain a polymer hollow microneedle array mold using
the high light transmission material as the base for further
fabrication of a metal microneedle array. The advantages of the
fabrication method of the present invention are simple process and
low in cost.
[0012] The foregoing and other objects, features, aspects and
advantages of the present invention will become better understood
from a careful reading of a detailed description provided herein
below with appropriate reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 shows a conventional flat-top microneedle array made
of Si substrate.
[0014] FIG. 2 shows a conventional slant top microneedle array made
of Si substrate.
[0015] FIG. 3 shows a conventional flat-top microneedle array made
of metal.
[0016] FIG. 4 shows a conventional flat-top microneedle array made
of polymer.
[0017] FIG. 5A shows a cross-sectional view of the first embodiment
of a microneedle array device of the present invention.
[0018] FIG. 5B shows a schematic view of the concave top of a
microneedle of the present invention.
[0019] FIG. 5C shows a schematic view of the first embodiment of a
microneedle array device of the present invention.
[0020] FIGS. 6A and 6B show respective top views of the
microneedles having different inner tube shapes.
[0021] FIGS. 7A-7J show the fabrication method of the first
embodiment of a microneedle array device of the present
invention.
[0022] FIGS. 8A and 8B show respective top cross-sectional views of
the different shapes of concave areas of Si substrate of the
present invention.
[0023] FIG. 9A shows a cross-sectional view of the second
embodiment of a microneedle array device of the present
invention.
[0024] FIG. 9B shows a schematic view of the second embodiment of a
microneedle array device of the present invention.
[0025] FIG. 9C shows a top view of FIG. 9B.
[0026] FIG. 10A shows a cross-sectional view of the third
embodiment of a microneedle array device of the present
invention.
[0027] FIG. 10B shows a schematic view of the third embodiment of a
microneedle array device of the present invention.
[0028] FIG. 10C shows a top view of FIG. 10B.
[0029] FIGS. 11A-11K show the fabrication method of the second
embodiment of the present invention.
[0030] FIGS. 12A-12L show the fabrication method of the third
embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0031] FIG. 5A shows a cross-sectional view of a microneedle array
device 50 of the present invention. As shown in FIG. 5A,
microneedle array device 50 includes a supporting pad 51 and a
plurality of microneedles 52. Supporting pad 51 includes an upper
surface 511. For the purpose of safety and effective skin
penetration, the top portion of each microneedle 52 includes a
convex needle structure 521. The top portion of microneedle 52 can
be a slant 523 or a concave surface 523a, as shown in FIG. 5B. The
top portion of microneedle 52 intersects with tube wall 524 to form
convex needle structure 521. In addition, top portion 523 or 523a
includes a via 522, which allows the follow of a microfluid, for
example, a medicine to flow out or a blood to flow in. According to
the present invention, the microneedle array is a monolithic metal
structure with each microneedle 52 standing on and perpendicular to
the upper surface 511 of supporting pad 51, and a hollow closed
tube being formed between top portion 523 (523a) and supporting pad
51.
[0032] FIG. 5C shows a schematic view of the structure of
microneedle array device 50 of the present invention. The top
portion 523 of each microneedle 52 is a slant, and the
cross-section of tube wall 524 forms a closed oval, circular, or
triangular shape, as shown in FIG. 6A and FIG. 6B, respectively.
The metal for fabricating microneedle array can be Cu, Cr, Ni, Fe,
Au, Pt, Pd, stainless steel, or their alloys. The range of the
aperture of each microneedle is 10-70 um, the outer circumference
is 80-250 um, and the height is 100-600 um.
[0033] FIGS. 7A-7J shows the fabrication method of the first
embodiment of the present invention. First, a substrate is
provided, which including a plurality of concave areas on the
surface. According to the present invention, there are several
techniques for forming a plurality of concave areas, including
etching, X-ray photo-etching, ultra-violet etching, ion beam
etching and excimer laser micromaching. The present embodiment uses
an anisotropic wet etching for explanation.
[0034] As shown in FIG. 7A, a single crystal silicon with a
grainorientation [1,0,0] is used as a substrate 700, and a
protective layer 702 is deposited on the surface. Protective layer
702 can be made of Si.sub.3N.sub.4. The wet etching areas 705 are
defined, as shown in FIG. 7B, followed by wet etching. The solution
commonly used in silicon anisotropic wet etching includes potassium
hydroxide (KOH) and Tetra-methyl-ammonium hydroxide (TMAH). After
etching the silicon, a plurality of concave areas 710 are formed.
Each concave area 710 has two slants 711, as shown in FIG. 7C.
Slant 711 defines a slant top 523 of each microneedle. The shape of
the plurality of concave areas can vary in accordance with the
fabrication process, for example, a V-shape 710a or U-shape 710b,
as shown in FIG. 8A and FIG. 8B, respectively. In other words, a
U-shaped concave area 710 defines a concave curvy top portion 523a
of a microneedle.
[0035] Before the coating of photo-sensitive material 720, a
sacrificial layer or mold release layer 715 is coated on top of
substrate 700 for the subsequent mold release, as shown in FIG. 7D.
The commonly used material for the sacrificial or mold release
layer includes Su-8, Al, Au, silicon rubber and Teflon.
[0036] The next step is to spread a photo-sensitive material 720 on
top of sacrificial layer 715, and a light transmission material 730
on top of photo-sensitive material layer 720, as shown in FIG. 7E.
Photo-sensitive material 720 used in the present invention is SU-8,
a negative photo-resist developed by Microlithography Chemical
Corporation (USA), or JSR 430N, a positive or negative photo-resist
developed by Japanese Synthetic Rubber (Japan). Light transmission
material can be either glass or PMMA.
[0037] The next step is exposure and lithography to obtain a
polymer hollow microneedle array mold 760 using light transmission
material 730 as a base. As shown in FIG. 7F, a patterned mask 750
defining the shape of tube wall 524 and via 522 of microneedle 52
is used before the exposure. The shapes can be either oval,
circular 524a, or triangular 524b, as shown in FIG. 5C, FIG. 6A,
and FIG. 6B, respectively. If SU-8 negative photo-resist is used as
photo-sensitive material 720, the bond forms at a later stage of
the exposure to light and stays during the development. The
un-exposed part is dissolved. After the mold release, a polymer
hollow microneedle array mold 760 having a plurality of polymer
microneedles is obtained for subsequent metal plating, as shown in
FIG. 7G. Because the present invention directly applies
photo-sensitive material 720 on the slant of concave areas 710 on
substrate or the concave curvy top, the top portion 761 of polymer
microneedle 765 is also slant or concave curvy surface. Microneedle
765 has a via 762 reaching light transmission material 730.
[0038] Finally, polymer hollow microneedle array mold 760 is used
to form a microneedle array device 50, as shown in FIG. 7J. The
forming of a microneedle array device step further includes the
following two substeps: (a) coating a metal layer 780 on the outer
surfaces of polymer hollow microneedle array mold 760 and light
transmission material layer 730 to form a microneedle array device
50, and (b) removing polymer hollow microneedle molde 760 from
microneedle array device 50.
[0039] Similarly, before the coating of metal layer 780 in sub-step
(a), a sacrifical layer or mold release layer 770 is deposited on
the outer surfaces of polymer hollow microneedle array mold 760 and
light transmission material layer 730, and a starting layer 771
(FIG. 7H) is electroplated to electro-cast. The material for
sacrificial layer 770 includes either Cu, Al, or Au. The material
for starting layer 771 is any metal.
[0040] In sub-step (a), the electroplating, electroless plating,
evaporation and sputtering is used to plate metal layer 780 on the
upper surface (FIG. 7I) of strating layer 771. The metal for
plating metal layer 780 may include Cu, Cr, Ni, Fe, Au, Pt, Pd,
stainless steel, and their alloys.
[0041] In sub-step (b), the technique for removing polymer hollow
microneedle array mold 760 from microneedle array device 50 is to
remove sacrificial layer 770 deposited on the outer surfaces of
polymer hollow microneedle array mold 760 and light transmission
material layer 730. The technique includes oxygen plasma removal,
thermal removal, solvent removal, aqueous removal or
photo-degradation removal.
[0042] FIG. 9A and FIG. 10A show the second and the third
embodiments of a microneedle array device of the present invention,
respectively.
[0043] FIG. 9A is similar to the structure shown in FIG. 5A. The
difference lies in microneedle array device 90 in FIG. 9A has a
reservoir layer 91 below a plurality of microneedles 52 and above
bottom portion 92. Reservoir layer 91 is for storing or mixing the
medicine or collecting blood sample. As shown in FIG. 9B and FIG.
9C, reservoir 91 may be further divided into a plurality of
reservoir unit 93. Reservoir units 93 are separate from one another
to block the flow of microfluid. They may be used for blood
analysis.
[0044] Similarly, microneedle array device 100 in FIG. 10A has two
reservoir layers 101 below a plurality of microneedles 52 and above
bottom portion 102. Reservoir layer 91 is for storing or mixing the
medicine or collecting blood sample. As shown in FIG. 10B and FIG.
10C, reservoir layers 101 may be further divided into a plurality
of reservoir unit 103. Reservoir units 103 are separate from one
another to block the flow of microfluid.
[0045] FIGS. 11A-11K show the fabrication method of the second
embodiment of the present invention.
[0046] The fabrication method of the second embodiment is similar
to that of first embodiment. The only difference is in the exposure
and development step. Because the second embodiment has a reservoir
layer 91 in the structure, the second embodiment requires an
additional exposure than the first embodiment. During the second
exposure, a corresponding patterned mask 750a is used to define
reservoir layer 91 and the shape of reservoir units 93 within. By
adjusting the exposure dosage to control the depth "a" of the
reservoir layer, the result of this step is to obtain a polymer
hollow microneedle array mold 160. The remaining steps of the
fabrication are identical to those in FIG. 7A-7J.
[0047] FIGS. 12A-12L show the fabrication method of the third
embodiment of the present invention.
[0048] The fabrication method of the third embodiment is also
similar to that of first embodiment The only difference is still in
the exposure and development step. Similarly, because the third
embodiment has two more reservoir layers 101 in the structure, the
third embodiment requires two additional exposures than the first
embodiment. During the second and third exposures, a corresponding
patterned mask 750a, 750b is used to define, respectively, each
reservoir layer 101 and the shape of reservoir units 103 within. By
adjusting the exposure dosage to control the depths "a" and "b" of
the reservoir layers, the result of this step is to obtain a
polymer hollow microneedle array mold 260. Therefore, according to
the present invention, the first exposure is to form the shape and
the structure of the microneedles, and the second and subsequent
exposures are for forming the shape and the structure of the
reservoir layer. The remaining steps of the fabrication are
identical to those in FIG. 7A-7J.
[0049] In summary, compared to the other molding techniques, the
present invention directly applies photo-sensitive polymer on the
concave areas of the substrate to form a polymer hollow microneedle
array mold having slants and concave curvy surface. Then, the
polymer hollow microneedle array mold is used with the evaporation
and electroplating techniques to fabricate metal microneedle array
device. This method greatly reduces the complexity of the
fabrication and the cost of the material. The metal microneedle
array electroplated on the polymer hollow microneedle array mold
has a good rigidity and slant uniformity, and is suitable for mass
production. The present invention may be widely used in blood
sampling, micro-sampling and medication injection systems.
[0050] Although the present invention has been described with
reference to the preferred embodiments, it will be understood that
the invention is not limited to the details described thereof.
Various substitutions and modifications have been suggested in the
foregoing description, and others will occur to those of ordinary
skill in the art. Therefore, all such substitutions and
modifications are intended to be embraced within the scope of the
invention as defined in the appended claims.
* * * * *