U.S. patent application number 11/542974 was filed with the patent office on 2007-02-01 for hollow microneedle array.
Invention is credited to Jeb Flemming, David Ingersoll, Stanley H. Kravitz, Carrie Schmidt.
Application Number | 20070023386 11/542974 |
Document ID | / |
Family ID | 37301172 |
Filed Date | 2007-02-01 |
United States Patent
Application |
20070023386 |
Kind Code |
A1 |
Kravitz; Stanley H. ; et
al. |
February 1, 2007 |
Hollow microneedle array
Abstract
An inexpensive and rapid method for fabricating arrays of hollow
microneedles uses a photoetchable glass. Furthermore, the glass
hollow microneedle array can be used to form a negative mold for
replicating microneedles in biocompatible polymers or metals. These
microneedle arrays can be used to extract fluids from plants or
animals. Glucose transport through these hollow microneedles arrays
has been found to be orders of magnitude more rapid than natural
diffusion.
Inventors: |
Kravitz; Stanley H.;
(Placitas, NM) ; Ingersoll; David; (Albuquerque,
NM) ; Schmidt; Carrie; (Los Lunas, NM) ;
Flemming; Jeb; (SE Albuquerque, NM) |
Correspondence
Address: |
SANDIA CORPORATION
P O BOX 5800
MS-0161
ALBUQUERQUE
NM
87185-0161
US
|
Family ID: |
37301172 |
Appl. No.: |
11/542974 |
Filed: |
October 4, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10936360 |
Sep 8, 2004 |
7132054 |
|
|
11542974 |
Oct 4, 2006 |
|
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Current U.S.
Class: |
216/11 ;
216/2 |
Current CPC
Class: |
C03C 23/007 20130101;
C03C 23/002 20130101; B81C 1/00111 20130101; C03C 15/00 20130101;
C23F 1/00 20130101; A61M 2037/0053 20130101; A61M 37/0015 20130101;
B81B 2201/055 20130101 |
Class at
Publication: |
216/011 ;
216/002 |
International
Class: |
C23F 1/00 20060101
C23F001/00; B44C 1/22 20060101 B44C001/22 |
Goverment Interests
STATEMENT OF GOVERNMENT INTEREST
[0002] This invention was made with Government support under
contract no. DE-AC04-94AL85000 awarded by the U.S. Department of
Energy to Sandia Corporation. The Government has certain rights in
the invention.
Claims
1. A hollow microneedle array, comprising at least one hollow
microneedle comprising a photoetchable glass, wherein the at least
one hollow microneedle has a height, a bore with a cross-sectional
dimension, and a tip with a cross-sectional dimension.
2. The array of claim 1, wherein the photoetchable glass comprises
a lithium-aluminum-silicate glass containing silver and germanium
ions.
3. The array of claim 1, wherein the at least one hollow
microneedle is perpendicular to a photoetchable glass wafer.
4. The array of claim 1, wherein the height of the at least one
hollow microneedle is less than 1 millimeter.
5. The array of claim 1, wherein the bore of the at least one
hollow microneedle has a cross-sectional dimension of greater than
25 microns.
6. The array of claim 1, wherein the bore of the at least one
hollow microneedle has a cross-sectional dimension of greater than
100 microns.
7. The array of claim 1, wherein the bore is offset from the center
of the tip.
8. The array of claim 1, wherein the tip of the at least one hollow
microneedle has a cross-sectional dimension of greater than 100
microns.
9. The array of claim 1, wherein the tip of the at least one hollow
microneedle has a cross-sectional dimension of less than 300
microns.
10. A hollow microneedle array, comprising at least one hollow
microneedle comprising a polymer, wherein the at least one hollow
microneedle has a height, a bore with a cross-sectional dimension,
and a tip with a cross-sectional dimension.
11. The array of claim 10, wherein the polymer comprises a cast
polymer.
12. The array of claim 10, wherein the polymer comprises a hot
embossed polymer.
13. The array of claim 10, wherein the polymer comprises an
injection molded polymer.
14. The array of claim 10, wherein the height of the at least one
hollow microneedle is less than 1 millimeter.
15. The array of claim 10, wherein the bore of the at least one
hollow microneedle has a cross-sectional dimension of greater than
25 microns.
16. The array of claim 10, wherein the bore of the at least one
hollow microneedle has a cross-sectional dimension of greater than
100 microns.
17. The array of claim 10, wherein the bore is offset from the
center of the tip.
18. The array of claim 10, wherein the tip of the at least one
hollow microneedle has a cross-sectional dimension of greater than
100 microns.
19. The array of claim 10, wherein the tip of the at least one
hollow microneedle has a cross-sectional dimension of less than 300
microns.
20. A hollow microneedle array, comprising at least one hollow
microneedle comprising a metal, wherein the at least one hollow
microneedle has a height, a bore with a cross-sectional dimension,
and a tip with a cross-sectional dimension.
21. The array of claim 20, wherein the metal comprises an
electroplated metal.
22. The array of claim 20, wherein the metal comprises nickel,
copper, or gold.
23. The array of claim 20, wherein the height of the at least one
hollow microneedle is less than 1 millimeter.
24. The array of claim 20, wherein the bore of the at least one
hollow microneedle has a cross-sectional dimension of greater than
25 microns.
25. The array of claim 20, wherein the bore of the at least one
hollow microneedle has a cross-sectional dimension of greater than
100 microns.
26. The array of claim 20, wherein the bore is offset from the
center of the tip.
27. The array of claim 20, wherein the tip of the at least one
hollow microneedle has a cross-sectional dimension of greater than
100 microns.
28. The array of claim 20, wherein the tip of the at least one
hollow microneedle has a cross-sectional dimension of less than 300
microns.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. application Ser.
No. 10/936,360, filed Sep. 8, 2004, which is incorporated herein by
reference.
FIELD OF THE INVENTION
[0003] The present invention relates to hollow microneedle arrays
and, in particular, to hollow microneedle array comprising a
photoetchable glass, polymer, or metal.
BACKGROUND OF THE INVENTION
[0004] Hollow microneedle arrays are being developed for
transdermal drug delivery and the withdrawal of body fluids for
biomedical and other applications. The hollow microneedle array can
provide a minimally invasive means to transport relatively large
molecules into and out of the skin. Microneedles are desirable
because their small size and extremely sharp tip reduces insertion
pain and tissue trauma to the patient. The length of the
microneedles can be kept short enough to not penetrate to the pain
receptors in the inner layers of the skin. Furthermore, the bore of
the hollow microneedles can be large enough to provide a relatively
rapid rate of drug delivery or withdrawal of bodily fluid. For drug
delivery, the use of micron-size needle arrays increases skin
permeability due to the needle's penetration of the outer layer of
the skin, enabling the drugs to enter the body at therapeutically
useful rates. Likewise, hollow microneedle arrays may replace
painful hypodermic needles or syringes used for the sampling of
biological fluids (e.g., blood or interstitial fluid). For example,
for diabetics it is necessary to monitor and control blood sugar
levels during the course of a day. The most common approach to
monitor blood sugar is to stick the finger with a small needle and
measure sugar level in the blood drop that forms at the site of the
needle-stick. As a result, the patient may become sensitized to the
frequent, painful needle-sticks, perhaps to the point of avoidance,
and the sampling protocol is problematic. Microneedle arrays may
enable the diabetic to routinely sample blood sugar levels in a
pain-free manner.
[0005] With out-of-plane microneedles, the longitudinal axis of the
microneedles is perpendicular to the wafer. These microneedles are
typically short (e.g., less than a few hundred microns) and only
penetrate the outer barrier layers of the skin. Out-of-plane
needles can typically be made with a large density of needles per
chip. Therefore, two-dimensional arrays of microneedles have been
used to obtain adequate fluid flow at reasonable pumping rates.
See, e.g., P. Zhang et al., "Micromachined Needles for
Microbiological Sample and Drug Delivery System," Proc. Intl. Conf.
MEMS, NANO, and Smart Systems (ICMENS'03), Jul. 20-23, 2003, Banff,
Alberta, Canada. However, only microneedles with the correct
geometry and physical properties can be inserted into the skin. In
particular, the safety margin for needle breakage, or the ratio of
microneedle fracture force to skin insertion force, has been found
to be optimum for needles having a small tip radius and large wall
thickness. See M. R. Prausnitz, "Microneedles for transdermal drug
delivery," Advanced Druq Delivery Reviews 56, 581 (2004).
[0006] Microneedle arrays have been fabricated by a number of
micromachining processes. Out-of-plane microneedles have typically
been fabricated using bulk micromachining or LIGA techniques (LIGA
is the German acronym for X-ray lithography, electrodeposition, and
molding). Therefore, most of these microneedles have been made of
silicon or metals. Silicon bulk micromachining has used either deep
reactive ion etching (DRIE) alone or in combination with KOH
etching to form the hollow microneedles. See H. J. G. E. Gardeniers
et al., "Silicon Micromachined Hollow Microneedles for Transdermal
Liquid Transport," J. Microelectromechanical Systems 12(6), 855
(2003) and P. Griss et al., "Side-Opened Out-of-Plane Microneedles
for Microfluidic Transdermal Liquid Transfer," J.
Microelectromechanical Systems 12(3), 296 (2003). However, these
fabrication processes are long and difficult and can result in
inconsistent wall slopes both in inside diameter and outside
diameter of the hollow microneedles. Furthermore, the expensive
capital equipment required is slow and not well-suited to eventual
mass production of microneedles. Finally, at the end of the
process, the silicon microneedles require oxidation so that only a
biocompatible silicon dioxide surface is in contact with biological
processes.
[0007] Therefore, a simple fabrication process using inexpensive
equipment, providing repeatable results, and directly producing
hollow microneedles in a biocompatible substrate is needed. The
present invention provides a method to fabricate hollow microneedle
arrays using a photoetchable glass wafer that solves these
problems.
SUMMARY OF THE INVENTION
[0008] The present invention is directed to a hollow microneedle
array, comprising at least one hollow microneedle, comprising a
photoetchable glass, a polymer, or a metal, wherein the at least
one hollow microneedle has a height, a bore with a cross-sectional
dimension, and a tip with a cross-sectional dimension. The height
of the hollow microneedle can be less than 1 millimeter, the bore
can have a cross-sectional dimension of greater than 25 microns,
and the tip can have a cross-sectional dimension of greater than
100 microns and less than 300 microns. The bore can be offset from
the center of the tip. The photoetchable glass can comprise a
lithium-aluminum-silicate glass containing silver and germanium
ions. The polymer can comprise a cast, hot embossed, or injection
molded polymer. The metal can comprise an electroplated metal, such
as nickel, copper, or gold.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The accompanying drawings, which are incorporated in and
form part of the specification, illustrate the present invention
and, together with the description, describe the invention. In the
drawings, like elements are referred to by like numbers.
[0010] FIGS. 1A-1E show a schematic illustration of a method to
fabricate a glass hollow microneedle array using a photoetchable
glass wafer.
[0011] FIG. 2 shows a bottomside view photograph of a heat-treated
image of a round bore and a circular patterned photoresist on the
topside of a transparent Foturan.RTM. glass wafer after a first
exposure to UV light.
[0012] FIG. 3 shows a topside view photograph of heat-treated
images of the regions between the microneedles and the round bores
of a glass microneedle array after a second exposure to UV
light.
[0013] FIG. 4 shows a scanning electron micrograph (SEM) of a
single glass hollow tapered microneedle.
[0014] FIG. 5 shows a SEM of a portion of a 4 by 11 rectangular
array of the glass hollow microneedles.
[0015] FIG. 6 shows a SEM of a glass hollow microneedle piercing a
100-micron-thickness sheet of aluminum foil.
[0016] FIGS. 7A-7E show a schematic illustration of a method to
fabricate a negative mold of a hollow microneedle array using a
photoetchable glass wafer.
[0017] FIG. 8 shows a graph of glucose extraction rates through
porcine skin with and without a hollow microneedle array.
DETAILED DESCRIPTION OF THE INVENTION
[0018] Photoetchable glasses have several advantages for the
fabrication of a wide variety of microsystems components.
High-aspect-ratio microstructures can be mass produced relatively
inexpensively with these glasses using conventional semiconductor
processing equipment. Glasses have high temperature stability, good
mechanical properties, are electrically insulating, and have better
chemical resistant than plastics and many metals. A particularly
attractive photoetchable glass is Foturan.RTM., made by Schott
Corporation and imported into the U.S. by Invenios Inc.
Foturan.RTM. comprises a lithium-aluminum-silicate glass containing
traces of silver and germanium ions. When exposed to UV-light
within the absorption band of the metal ion dopants in the glass,
the germanium acts as a sensitizer, absorbing a photon and
stripping an electron that reduces neighboring silver ions to form
colloidal silver atoms. These silver colloids provide nucleation
sites for crystallization of the surrounding glass. If exposed to
UV light through a mask, only the exposed regions of the glass will
crystallize during subsequent heat treatment at a temperature
greater than the glass transformation temperature (e.g., greater
than 450.degree. C. in air for Foturan.RTM.). These nucleated
lithium metasilicate crystals typically have diameters of 1-10
microns. The crystalline phase is more soluble in hydrofluoric acid
(HF) than the unexposed vitreous, amorphous regions. In particular,
the crystalline regions are preferentially etched about 20 times
faster than the amorphous regions in 10% HF, enabling
microstructures with aspect ratios of about 20:1 to be formed when
the exposed regions are removed. Therefore, this process can
produce holes of greater than about 25 microns with a sidewall
slope of about 1-4.degree.. See T. R. Dietrich et al., "Fabrication
technologies for microsystems utilizing photoetchable glass,"
Microelectronic Engineering 30, 497 (1996), which is incorporated
herein by reference.
[0019] In FIGS. 1A-1E is shown a schematic illustration of a
preferred method to fabricate a hollow microneedle array,
comprising at least one hollow microneedle, using a photoetchable
glass wafer. The preferred method comprises exposing the
photoetchable glass wafer to ultraviolet light through a patterned
mask to define a latent image of a bore of at least one hollow
microneedle in the glass wafer; heating the glass wafer to a
temperature in excess of the glass transformation temperature to
transform the amorphous material in the latent image of the exposed
bore of the at least one microneedle to a crystalline material,
thereby providing an crystallized image of the bore of the at least
one microneedle in the glass wafer; exposing the glass wafer to
ultraviolet light through a patterned mask to define a latent image
of the regions between the at least one hollow microneedle; heating
the glass wafer to a temperature in excess of the glass
transformation temperature to transform the amorphous material in
the exposed latent image of the between regions to a crystalline
material, thereby providing a crystallized image of the between
regions in the glass wafer; and etching the glass wafer in an
etchant to remove the crystallized image regions, thereby providing
a glass hollow microneedle array comprising the at least one hollow
microneedle.
[0020] In FIG. 1A, a thick photoetchable glass wafer 11 is exposed
to deep UV light through a hard lithography mask 12 to define a
latent image 13 of the bore of the at least one hollow microneedle.
The photoetchable glass wafer 11 preferably comprises Foturan.RTM.
Microglass (Invenios, Inc). The wavelength of the UV light
preferably corresponds to the absorption band for the sensitizing
ion dopant dispersed in the glass. The energy density of the UV
light and the exposure time are preferably sufficient to expose the
latent image 13 through the thickness of the wafer 11. For
processing hollow microneedles, a deep UV light source (e.g.,
available from ABM Corp.) can be used and the intensity of the
light source at a wavelength of 240 nm can be about 16.5
mw/cm.sup.2. To define a latent image 13 of the bore through the
entire thickness of a 1 mm Foturan.RTM. wafer at this wavelength
and intensity, the exposure time can be about 4 hours. Using a more
intense light source can shorten the exposure time. The mask 12 can
be a fused silica photolithography mask, which blocks the deep UV
light in the unopen portions of the mask. The openings in the mask
preferably define at least one circular bore-hole, although other
cross-sections can also be used. The bores are preferable small
enough to provide a microneedle that easily penetrates the skin,
yet also large enough to enable adequate fluid flow. The diameter
of the circular bore-holes is preferably greater than 25 microns
and, more preferably, greater than 100 microns.
[0021] In FIG. 1B, the exposed Foturan.RTM. wafer 11 is heat
treated at a temperature greater than the glass transformation
temperature for a time duration sufficient to convert the exposed
amorphous latent image regions to the crystalline phase. The
exposed Foturan.RTM. glass wafer can be heat treated at 600.degree.
C. for 1 hour. This heat treatment converts the amorphous-phase
latent image regions to crystalline-phase image regions 14 that can
be etched later to form the through-hole bores 18 of the hollow
microneedles 19.
[0022] In FIG. 1C, when heat-treating is completed, a negative
acting photoresist (e.g., JSR Microposit) 15 is patterned onto the
front side of the Foturan.RTM. glass wafer using the darkened
crystalline image 14 as a reference. The photoresist mask 15 blocks
the areas that will form the walls of the hollow microneedles from
exposure to the deep-UV light. Therefore, the UV exposure defines a
latent image 16 of the region between the microneedles that are to
be removed by etching. If the tip is too small, the microneedle may
shear upon insertion into the skin. Furthermore, the wall thickness
of the body of the microneedle at the tip is preferably about 50
microns or greater. If the tip is too large, the microneedle will
not penetrate the skin. The photoresist pattern preferably provides
a circular microneedle, after etching, having a tip diameter of
greater than 100 microns and, preferably, less than 300 microns.
Other microneedle tip cross-sections and dimensions can be used.
The photoresist mask 15 can be patterned so that the bore 18 is
offset from the tip of the microneedle 19, thereby reducing
clogging of the bore which can occur when the fluid outlet is at
the tip of the needle. The photoresist-masked glass wafer 11 is
then exposed again to the deep-UV light for a sufficient period of
time to define the height of the microneedles. For example, for
400-500 micron tall microneedles in Foturan.RTM., the second
exposure can be 35 minutes using the UV light source described
above.
[0023] In FIG. 1D, the exposed glass wafer 11 can be cleaned of the
photoresist and heat treated to crystallize the latent image 16
defined by the second exposure. Heat treatment of the twice-exposed
Foturan.RTM. for an additional 1 hour at 600.degree. C. will form
crystallized image regions 17 between the microneedles, in addition
to the previously formed crystallized images 14 of the bores. The
surface of the wafer can be lapped.
[0024] In FIG. 1E, the glass wafer 11 is etched to remove the
crystallized image regions 14 to form the bores 18 and to remove
the crystallized image regions 17 to form the spacings between the
hollow microneedles 19. The backside of the wafer can be covered
with photoresist (not shown) to prevent etching of the wafer
backside. The Foturan.RTM. glass wafer can be etched for 40 minutes
in unbuffered 10:1 HF solution. The crystalline material
preferentially etches 20:1 times faster then the vitreous material
in a 10:1 HF solution, using an ultrasonic bath. Since the wet
chemical etch is anisotropic, an array of hollow microneedles 10
with sloped sidewalls and a small tip radius is formed, as is
preferred for penetration of the skin. The etching time can be
adjusted to obtain the desired microneedle height and
cross-sectional dimensions.
[0025] Alternatively, both UV exposures can be done sequentially to
define the latent images of the regions between the microneedles
and the bores, followed by a single heat treatment, albeit while
sacrificing mask alignment accuracy. For example, a first exposure
of the regions between the microneedles can produce enough
darkening by itself (apparently due to the formation of isolated
silver atoms) to enable alignment of the bore mask to the faintly
darkened latent image 16 of the between regions. Following a second
exposure to define the latent image 13 of the bores, the exposed
wafer can be heat treated to crystallize both latent images 16 and
13 simultaneously to form crystallized images of both the between
regions 17 and the bores 14. The crystallized images can then be
etched to form the glass hollow microneedle array. Alternatively,
the bores can be defined in a first exposure and the between region
mask aligned to the darkened latent image of the bores for a second
exposure of the between regions, followed by a single heat
treatment.
[0026] In FIG. 2 is shown a bottomside view photograph of a
dark-shaded, crystallized image 14 of a circular bore and a
circular patterned photoresist 15 on the topside of a transparent
Foturan.RTM. glass wafer after a first exposure to UV light and a
first heat treatment, but before the second exposure, according to
the preferred method shown in FIGS. 1A and 1B.
[0027] In FIG. 3 is shown a topside view photograph of the
dark-shaded, crystallized image 17 the spacings between the
outsides of the microneedles in an array, in addition to the
previously formed dark-shaded crystallized images 14 of the
circular bores, after a second exposure to UV light and a second
heat treatment, but before etching, according to the preferred
method shown in FIGS. 1A to 1D. The light-shaded regions
surrounding each dark-shaded bore corresponds to the unexposed
vitreous regions underneath the patterned photoresist 15 in FIG. 2.
The center-to-center spacing of the light-shaded vitreous regions
is about 1 mm. Each light-shaded vitreous region has a diameter of
about 350 microns, before etching. The diameter of each exposed,
dark-shaded bore region is about 50 microns, before etching. The
bores are offset from the center of the microneedle tip by about 50
microns.
[0028] In FIG. 4 is shown a scanning electron micrograph (SEM) of a
single glass hollow microneedle 19, after etching. The microneedle
is about 400-500 micrometers tall with through-holes 18 that are 1
mm deep. The outside diameter of the tapered microneedle 19 at the
base is about 350 microns and about 200 microns at the tip. The
diameter of the offset bore 18 at the microneedle tip is about 200
microns.
[0029] In FIG. 5 is shown an SEM of a portion of a 4 by 11
rectangular array 10 of the glass hollow microneedles. The
center-to-center spacing between adjacent microneedles is about 1.0
mm.
[0030] In FIG. 6 is shown an SEM of a glass hollow microneedle
piercing a 100-micron-thickness sheet of aluminum foil. The foil
piercing demonstrates the inherent strength of the Foturan.RTM.
glass microneedles.
[0031] An even less expensive method of fabricating the
microneedles is to replicate them using a negative mold made from
the original glass hollow microneedle array structure. A negative
mold can be made by depositing a mold material onto the glass
hollow microneedle array. For example, a negative mold of
Foturan.RTM. microneedles can be made by electroplating a metal
(e.g., nickel, copper, or gold) onto a sputtered seed layer
deposited on the Foturan.RTM. microneedles. After the negative
plated mold is created and released from the glass array; a liquid
polymer, such as Zeonor 1020R, can be cast into the mold. After the
Zeonor 1020R is cooled and solidified, the polymeric hollow
microneedle array can be easily peeled off the plated negative mold
and the mold can be re-used. Other plastics that can be hot
embossed or injection molded, such as polycarbonate, can also be
used.
[0032] Alternatively, a negative mold can be made directly of the
photoetchable glass, as shown in FIGS. 7A-7E. In FIG. 7A, a
photoetchable glass wafer 21 is exposed to the deep UV light
through a lithography mask 22 to define a latent image 23 of the
regions between the microneedles to a depth partially through the
thickness of the wafer 21. In FIG. 7B, the exposed wafer is
heat-treated to convert the amorphous-phase latent image regions 23
to crystalline-phase image regions 24. In FIG. 7C, a photoresist 25
is patterned onto the front side of the once heat-treated glass
wafer using the darkened crystalline image regions 24 as a
reference. The photoresist 25 can be patterned to block the areas
that will form the bores and regions between the microneedles. The
UV exposure can be sufficient to define a latent image 26 of the
wall regions of the microneedles to a depth that is greater than
the first exposure. In FIG. 7D, the exposed wafer can be heat
treated a second time to crystallize the latent image 26 from the
second exposure and provide crystallized images 27 of the wall
regions of the microneedles. In FIG. 7E, the crystallized image
regions 24 and 27 of the glass wafer can be etched to provide a
glass negative mold 20. A structural material can then be molded
into the negative mold. For example, a polymer can be cast or
injection molded, or a metal can be electroplated, into the
negative mold. The negative mold can be removed to provide a
microneedle array of the structural material. The posts 28 of the
negative mold 20 thereby provide the hollow bores and the recessed
regions 29 of the negative mold provide the walls of the
microneedles.
[0033] Alternatively, as described previously, both exposures can
be done sequentially to define the latent images of the regions
between the microneedles 23 and the wall regions 26. The
twice-exposed wafer can then be heat treated to crystallize both
latent images 23 and 26 simultaneously to form crystallized images
of both the in-between regions 24 and the wall regions 27. The
crystallized images can then be etched to form the glass negative
mold.
[0034] Extraction studies of the Foturan.RTM. microneedles for
glucose harvesting were made. For these studies, porcine skin was
used as a human skin surrogate. The skin was soaked in a deionized
water bath for 4 hours to fully saturate the material. Tests were
conducted using a Franz diffusion cell. A Franz diffusion cell has
fluid on both sides of the porcine skin. Therefore, this method
provides a better representation of diffusion through living tissue
than having air on one side.
[0035] In FIG. 8 is shown a graph of glucose extraction rates
through porcine skin with and without the glass microneedle array
shown in FIG. 5. The flux of glucose transport across the porcine
skin, for the negative control, using a 21 mM glucose donor
solution, was 0.0012 mM/min/cm.sup.2. The flux of glucose transport
across the porcine skin, using a 21 mM glucose donor solution, with
the microneedles inserted, was 0.609 mM/min/cm.sup.2, 500 times
greater then the transport without the microneedles in place.
Because the open area of the microneedle array is much smaller than
the open area of the bare skin, a small change in concentration
produces a large change in flux across the microneedle array.
[0036] The present invention has been described as a hollow
microneedle array comprising a photoetchable glass, polymer, or
metal. It will be understood that the above description is merely
illustrative of the applications of the principles of the present
invention, the scope of which is to be determined by the claims
viewed in light of the specification. Other variants and
modifications of the invention will be apparent to those of skill
in the art.
* * * * *