U.S. patent application number 11/995370 was filed with the patent office on 2008-09-04 for replaceable cartridge for allergy testing system.
Invention is credited to Jose Mir, Dennis Roland Zander.
Application Number | 20080214952 11/995370 |
Document ID | / |
Family ID | 37637827 |
Filed Date | 2008-09-04 |
United States Patent
Application |
20080214952 |
Kind Code |
A1 |
Mir; Jose ; et al. |
September 4, 2008 |
Replaceable Cartridge for Allergy Testing System
Abstract
A replaceable cartridge for use in a minimally invasive allergy
testing system includes a microneedle array; encapsulated
allergens, and packaging to hold the array in alignment with the
allergens. A method of manufacturing a replaceable cartridge is
disclosed. A formable layer is placed on a mold having cavities and
vacuum lines coupled to the cavities. Heat is applied to the
formable layer and a negative pressure is applied to the vacuum
lines to wrap the cavities with the formable layer. The wrapped
cavities are filled with allergens. The filled cavities are covered
with a plastic cover to form an encapsulated allergen assembly. A
removable seal is applied over the plastic cover. A microneedle
array having a substrate and at least one microneedle is formed. An
energy storage device is coupled to the substrate to form a
microneedle array assembly. The encapsulated allergen assembly is
coupled with the microneedle array assembly.
Inventors: |
Mir; Jose; (Rochester,
NY) ; Zander; Dennis Roland; (Penfield, NY) |
Correspondence
Address: |
JAECKLE FLEISCHMANN & MUGEL, LLP
190 Linden Oaks
ROCHESTER
NY
14625-2812
US
|
Family ID: |
37637827 |
Appl. No.: |
11/995370 |
Filed: |
July 11, 2006 |
PCT Filed: |
July 11, 2006 |
PCT NO: |
PCT/US06/26734 |
371 Date: |
January 11, 2008 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
60698202 |
Jul 11, 2005 |
|
|
|
Current U.S.
Class: |
600/556 ; 53/452;
604/47 |
Current CPC
Class: |
A61M 2037/0046 20130101;
A61M 37/0015 20130101; A61M 2037/003 20130101; A61B 5/0059
20130101; A61B 5/444 20130101; A61M 2037/0061 20130101; A61B 5/411
20130101 |
Class at
Publication: |
600/556 ; 604/47;
53/452 |
International
Class: |
A61M 37/00 20060101
A61M037/00; A61B 5/00 20060101 A61B005/00; B65B 43/00 20060101
B65B043/00 |
Claims
1. A replaceable cartridge for use in a minimally invasive allergy
testing system, comprising: a microneedle array; encapsulated
allergens; and packaging to hold the microneedle array in alignment
with the encapsulated allergens.
2. The replaceable cartridge of claim 1, further comprising: a
compressible stop coupled to the microneedle array and the
packaging.
3. The replaceable cartridge of claim 1, wherein the microneedle
array further comprises: a substrate; and at least one
microneedle.
4. The replaceable cartridge of claim 3, wherein the alignment
between the microneedle array and the encapsulated allergens is
such that: the at least one microneedle can not pierce the
encapsulated allergens; and the substrate can be pushed against the
encapsulated allergens by the minimally invasive allergy testing
system.
5. The replaceable cartridge of claim 3, wherein the alignment
between the microneedle array and the encapsulated allergens is
such that the at least one microneedle can pierce the encapsulated
allergens.
6. The replaceable cartridge of claim 3, wherein the at least one
microneedle further comprises a hollow needle.
7. The replaceable cartridge of claim 3, wherein the at least one
microneedle further comprises a grooved needle.
8. The replaceable cartridge of claim 3, wherein the at least one
microneedle further comprises a solid needle.
9. The replaceable cartridge of claim 3, wherein the at least one
microneedle further comprises a corrugated needle.
10. The replaceable cartridge of claim 1, wherein the microneedle
array comprises at least one needle of a first penetration depth
and at least one needle of a second penetration depth which is
different from the first penetration depth.
11. The replaceable cartridge of claim 1, wherein the microneedle
array comprises at least one needle with a cross-section that is
selected from the group consisting of: square, rectangular,
triangular, and circular.
12. The replaceable cartridge of claim 1, wherein the microneedle
array comprises at least one needle with a varying
cross-section.
13. The replaceable cartridge of claim 1, wherein the microneedle
array comprises a transparent material.
14. The replaceable cartridge of claim 1, wherein: the packaging
further comprises orifices; and the microneedle array further
comprises mesas which are aligned to slideably engage the
orifices.
15. The replaceable cartridge of claim 1, further comprising a
sealing layer for sealing the packaging to prevent contaminants
from reaching the microneedle array.
16. The replacement cartridge of claim 15, wherein the sealing
layer further comprises identifying marks.
17. The replacement cartridge of claim 16, wherein the identifying
marks are selected from the group consisting of bar codes,
graphics, and alphanumeric characters.
18. The replacement cartridge of claim 17, wherein the identifying
marks are used for alignment by the minimally invasive allergy
testing system.
19. The replacement cartridge of claim 17, wherein the identifying
marks are used for identification of the allergens being
tested.
20. The replacement cartridge of claim 17, wherein the identifying
marks are used for identification of a patient.
21. A replaceable cartridge for use in a minimally invasive allergy
testing system, comprising: a re-usable microneedle array; at least
partially refillable encapsulated allergens; and packaging to hold
the re-usable microneedle array in alignment with the at least
partially refillable encapsulated allergens.
22. The replaceable cartridge of claim 21, wherein the re-usable
microneedle array comprises a washable microneedle array.
23. The replaceable cartridge of claim 21, wherein the at least
partially refillable encapsulated allergens comprise a sealing
layer which may be replaced by a replacement sealing layer, the
replacement sealing layer comprising an adhesive and measured
allergens coupled to the layer for alignment with the microneedle
array.
24. A replaceable cartridge for use in a minimally invasive allergy
testing system, comprising: a microneedle array for engagement with
a separate set of encapsulated allergens; and packaging to hold the
microneedle array in an alignment.
25. A replaceable cartridge for use in a minimally invasive allergy
testing system, comprising: refillable encapsulated allergens for
engagement with a separate microneedle array; and packaging to hold
the refillable encapsulated allergens in an alignment.
26. A method of manufacturing a replaceable cartridge for use in a
minimally invasive allergy testing system, comprising: placing a
formable layer on a mold having cavities and vacuum lines coupled
to the cavities; applying heat to the formable layer and applying a
negative pressure to the vacuum lines to wrap the cavities with the
formable layer; filling the wrapped cavities with allergens;
covering the filled cavities with a plastic cover to form an
encapsulated allergen assembly; applying a removable seal over the
plastic cover; forming a microneedle array having a substrate and
at least one microneedle; coupling an energy storage device to the
substrate to form a microneedle array assembly; and coupling the
encapsulated allergen assembly with the microneedle array
assembly.
27. The method of claim 26, wherein the formable layer comprises
PVDC.
28. The method of claim 26, wherein the microneedle array is formed
of glass, plastic, silicon, or metal.
29. The method of claim 26, wherein the energy storage device is
selected from the group consisting of an elastomer spring, an metal
spring, and a plastic spring.
30. A replaceable cartridge for use in a minimally invasive allergy
testing system formed by the process of claim 26.
Description
RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional patent
application No. 60/698,202 filed Jul. 11, 2005, the specification
of which is hereby officially incorporated by reference in its
entirety,
FIELD
[0002] The claimed invention generally relates to systems for
testing for medical conditions and, more particularly, to
replacement cartridges for allergy testing systems used to
determine a degree of reaction to one or more allergens by a
subject in a minimally invasive manner.
BACKGROUND
[0003] It is estimated that at least 50% of the population has some
form of allergy. Approximately 20 million patients are currently
tested for allergies using a number of techniques, for example,
skin prick test, intradermal test, blood test, and skin patch test.
Allergy test methods, such as the skin prick test are invasive and
manual, involving depositing drops of many allergens on a subject's
back, forearm, or other smooth body surface, labeling the region
for identification, and then pricking the region with a needle to
allow penetration of the allergy into the subject's body. The
intradermal test is even more invasive, involving injecting a small
amount of various allergens into the subject's skin. Due to the
nature of these processes, large areas of the subject's skin tend
to be affected.
[0004] Subjects undergoing these pin prick and intradermal tests
then wait a prescribed period of time to allow the allergens a
chance to react with their skin. Test regions must be large enough
to easily be identified and evaluated by the human eye or by
photographs which are then printed or enlarged. Although these
forms of allergy testing often cover a large area of a patient's
body, these manual determinations of allergic reaction provide the
medical practitioner with a snapshot in time which has been shown
to be useful in screening patients for allergic reactions.
[0005] Blood testing provides a highly invasive, yet possibly more
convenient method of allergy testing. Unfortunately, blood testing
does not surpass the sensitivity, specificity, and predictive value
of the skin test. Blood test results are often dependent upon the
laboratory which is performing the test. Blood testing for
allergies is also a more expensive option.
[0006] Therefore, there is a need for a minimally invasive allergy
testing system which does not need to cover large areas of a
patient's skin, which can be automated to a large extent, which can
be correlated to existing skin testing data, which offers more than
a snapshot in time of an allergic reaction, which is economical,
and which is easy to use and manufacture.
SUMMARY
[0007] A replaceable cartridge for use in a minimally invasive
allergy testing system is disclosed. The replaceable cartridge
includes a microneedle array; encapsulated allergens, and
[0008] packaging to hold the microneedle array in alignment with
the encapsulated allergens.
[0009] Another replaceable cartridge for use in a minimally
invasive allergy testing system is disclosed. The replaceable
cartridge includes a re-usable microneedle array, at least
partially refillable encapsulated allergens, and packaging to hold
the re-usable microneedle array in alignment with the at least
partially refillable encapsulated allergens.
[0010] Another replaceable cartridge for use in a minimally
invasive allergy testing system is disclosed. The replaceable
cartridge includes a microneedle array for engagement with a
separate set of encapsulated allergens, and packaging to hold the
microneedle array in an alignment.
[0011] Another replaceable cartridge for use in a minimally
invasive allergy testing system is disclosed. The replaceable
cartridge includes refillable encapsulated allergens for engagement
with a separate microneedle array; and packaging to hold the
refillable encapsulated allergens in an alignment.
[0012] A method of manufacturing a replaceable cartridge for use in
a minimally invasive allergy testing system is also disclosed. A
formable layer is placed on a mold having cavities and vacuum lines
coupled to the cavities. Heat is applied to the formable layer and
a negative pressure is applied to the vacuum lines to wrap the
cavities with the formable layer. The wrapped cavities are filled
with allergens. The filled cavities are covered with a plastic
cover to form an encapsulated allergen assembly. A removable seal
is applied over the plastic cover. A microneedle array having a
substrate and at least one microneedle is formed. An energy storage
device is coupled to the substrate to form a microneedle array
assembly. The encapsulated allergen assembly is coupled with the
microneedle array assembly.
[0013] The claimed invention is compatible with a system and method
to minimize the invasiveness of allergy testing, degree and area of
reaction, testing time, general discomfort, and risk of infection.
Another advantage of the claimed invention is that it enables a
much smaller test area footprint when compared to prior testing
devices. The much smaller footprint also simplifies and expedites
the allergy testing process for a medical staff. The claimed
invention is compatible with micro-fluidic technology, and
therefore much smaller quantities of allergens may be dispensed,
reducing the severity of the reaction for a patient, and possibly
reducing the cost for the testing. The allergen dispensing process
may also be automated in some embodiments, allowing for automated
and quantified allergy reactivity data readout, thereby reducing
uncertainty and subjectivity. A further advantage possible with
automated embodiments is the ability to capture continuous or
nearly continuous visual images of an allergy test site. This
allows scientist and medical personnel the chance to study the time
rate of change for certain allergic reactions, and better
understand a patient's reaction and sensitivity. Overall, the
minimally invasive allergy testing system enables a relatively fast
allergy test cycle time, lowers the cost of such testing, and
significantly reduces the chance for errors.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIGS. 1-2E schematically illustrate embodiments of an
allergy testing system.
[0015] FIGS. 3A & 3B to FIGS. 8A & 8B schematically
illustrate side views (A) and top views (B), respectively, of
embodiments of microneedles for use in an allergy testing
system.
[0016] FIG. 9 schematically illustrates a side view of a corrugated
microneedle embodiment for use in an allergy testing system.
[0017] FIG. 10A schematically illustrates an exploded perspective
view of an embodiment of an allergy testing system.
[0018] FIG. 10B schematically illustrates an assembled,
cross-sectional view of the allergy testing system embodiment of
FIG. 10A.
[0019] FIG. 11A schematically illustrates an exploded perspective
view of an embodiment of an allergy testing system.
[0020] FIG. 11B schematically illustrates an assembled,
cross-sectional view of the allergy testing system embodiment of
FIG. 11A.
[0021] FIGS. 12A-12C schematically illustrate one possible method
of applying allergens to a subject using an embodiment of an
allergy testing system.
[0022] FIGS. 12D1-12D4 schematically illustrate different
embodiments of gathering and analyzing allergy test data after the
allergens have been applied by the allergy testing system in FIGS.
12A-12C.
[0023] FIG. 13 schematically illustrates an embodiment of an
allergy testing system.
[0024] FIGS. 14A-14P schematically illustrate an embodiment of a
process for manufacturing a replaceable allergen cartridge for use
in an allergy testing system.
[0025] FIGS. 15A and 15B schematically illustrate an embodiment of
a process for allergy testing using the replaceable allergen
cartridge of FIG. 14P.
DETAILED DESCRIPTION
[0026] FIG. 1 schematically illustrates an embodiment of a
minimally invasive allergy testing system 20. The minimally
invasive allergy testing system 20 has a microneedle array 22 which
is coupled to an array of encapsulated allergens 24. The
microneedle array 22 has at least one microneedle, and preferably a
plurality of microneedles which may be spaced in a linear array, a
two-dimensional array, or any other spacing desired. The
microneedles 22 may have a height of about 50-300 microns and a
diameter of about 10-80 microns in order to penetrate a subject's
skin, although other embodiments may have other dimensions. (Skin
not illustrated in this view.) The microneedle array may be
manufactured out of a number of different substances, for example,
silicon, glass, metal, quartz, or plastic. Due to its attractive
micromachining properties, silicon may be anisotropically etched
using chemical and reactive ion etching processes to fabricate the
microneedles, although other materials and manufacturing processes
can be used.
[0027] The encapsulated allergens 24 have a corresponding set of
allergens associated with the microneedles in the microneedle array
22. The microneedle array 22 and the encapsulated allergens 24 may
be held in alignment with each other by a package 26. The minimally
invasive allergy testing system 20 also has an activation system 28
which may be directly or indirectly coupled to the microneedle
array 22 and/or the encapsulated allergens 24. The activation
system 28 causes a skin of a test subject to be pricked, while
releasing corresponding encapsulated allergens 24 into contact with
the appropriate test prick.
[0028] There is a great degree of flexibility in configuring the
activation system 28. In some embodiments, the activation system 28
can be a mechanical plunger or other mechanical system, which is
pressed by a medical professional, or even the test subject
themselves. In other embodiments, the activation system 28 can be a
spring-loaded release which allows a predictable force to be
applied to the microneedle array 22 as it pricks the subject's
skin. Further embodiments of an allergy testing system 20 may have
an activation system which is an electro-mechanical system, such as
a solenoid, motor, or a micromechanical actuator.
[0029] The microneedle array 22, the encapsulated allergens 24,
and/or the activation system 28 may be separate components of the
allergy testing system 20. In the embodiment illustrated in FIG. 1,
the microneedle array 22 and the encapsulated allergens 24 are
removably packaged from the activation system 28. This removability
allows for designs and embodiments with simple replacement of the
microneedles and encapsulated allergens which are typically only
used once.
[0030] FIG. 2A illustrates another embodiment of an allergy testing
system 30. This allergy testing system 30 has the microneedle array
22 directly coupled to the activation system 28. The microneedle
array 22 may still be removably coupled to the activation system 28
in some embodiments. For simplicity, the microneedle array 22 is
schematically illustrated in this and other embodiments as only
having a single needle 32. It should be understood that any number
of microneedles 32 may be present on the microneedle array 22,
depending on size of the microneedle array 22 and the number of
allergy test sites desired. The needles 32 of the microneedle array
22 are positioned to contact the encapsulated allergens 24 as the
activation system 28 is engaged. In the orientation of FIG. 2A, the
activation system 28 will engage downwards 34 to push the
microneedles 32 of the microneedle array 22 through the
corresponding encapsulated allergen sites, and then on into a
subject's skin 36. In this embodiment, the microneedles 32 are
wetted with the allergens before the skin 36 is pierced.
[0031] FIG. 2B schematically illustrates an allergy testing system
38 which is similar to the allergy testing system of FIG. 2A, with
the addition of at least one hollow microneedle 40 in the
microneedle array 22. In this embodiment, when the hollow
microneedle 40 pierces the encapsulated allergens 24, the allergens
may be drawn into the hollow portion of the microneedle 40, which
may then deposit the allergens deeper within the subject's skin 36
after the microneedle pierces the skin 36. The allergens will also
coat the outside of the microneedle 40, similar to the embodiment
of FIG. 2A.
[0032] FIG. 2C schematically illustrates another embodiment of a
minimally invasive allergy testing system 42. This allergy testing
system 42 has the microneedle array 22 indirectly coupled to the
activation system 28. The microneedle array 22 may still be
removably coupled to the activation system 28 in some embodiments.
The needles 44 of the microneedle array 22 are hollowed-through and
the side of the microneedle array 22 opposite the hollowed
microneedle 44 is arranged to contact the encapsulated allergens 24
when the activation system 28 is engaged. In the orientation of
FIG. 2C, the activation system 28 will engage downwards 34 to push
encapsulated allergens 24 through the corresponding hollowed
microneedle 44, and then on into a subject's skin 36.
[0033] FIG. 2D schematically illustrates another embodiment of a
minimally invasive allergy testing system 46. Similar to the
embodiment of FIG. 2C, this allergy testing system 46 has the
microneedle array 22 indirectly coupled to the activation system
28. The microneedle array 22 may still be removably coupled to the
activation system 28 in some embodiments. The microneedles 48 in
this embodiment are not hollow microneedles. Instead, when the
activation system 28 is engaged (downwards in the orientation of
FIG. 2D), the activation system 28 will squeeze the encapsulated
allergens 24 through a groove or channel 50 near the microneedle
array 22. The activation system 28 indirectly pushes the
microneedle array 22 into contact with the subject 36 before,
after, or while the allergens arrive at the prick location. The
timing of the arrival of the allergens may be controlled by several
parameters, including, for example, changing the viscosity of the
allergens, building in a desired flow resistance in the allergen
channel 50, and/or, choosing the strength of the allergen
encapsulation to allow for a quick or a slow release of the
allergens.
[0034] FIG. 2E is a further embodiment of an allergy testing system
52. This embodiment is similar in design and operation to the
embodiment of FIG. 2A, with the addition of a sheet 54 to cover the
orifice 56 where the allergen will be applied by the microneedle
32. The sheet 54 may be a thin sealing film employed over at least
a portion of the orifices and a surface of the package 26 to serve
as a sterile layer between the subject's skin 36 and the
encapsulated allergens 24 and/or the microneedle array 22. The
sealing film 54 may be removed before use or left behind on the
patient's skin 36. If left behind on the patient's skin, the
sealing film 54 may have a human readable code or a machine
readable code, such as a barcode, or other identification marks 58.
These identifying marks can be used for orientation in the analysis
stage to be discussed later in this specification. The identifying
marks can also identify the various allergens being used in one or
more locations. The identifying marks may be pre-imaged on the
sealing film 54, or they may be marked onto the film 54 with a
microneedle 32 when the allergy test is performed. In some
embodiments, the sealing film 54 may be transparent for ease in
seeing the allergy test sites.
[0035] The microneedles in the microneedle array 22 may have a
variety of geometries. FIGS. 3A and 3B schematically illustrate an
embodiment of a microneedle 60 with a substantially square or
rectangular cross-section in a side view and a corresponding top
view, respectively.
[0036] FIGS. 4A and 4B schematically illustrate an embodiment of a
microneedle 62 with a substantially circular cross-section in a
side view and a corresponding top view, respectively. The
microneedle embodiment shown in FIG. 4A illustrates another
variation possible with microneedle design. The microneedle 62 has
a wedged top. Although other embodiments are not shown wedged, they
could be modified in further embodiments to have a wedge-shaped
top.
[0037] FIGS. 5A and 5B schematically illustrate an embodiment of a
microneedle 64 with a substantially triangular cross-section in a
side view and a corresponding top view, respectively.
[0038] FIGS. 6A and 6B schematically illustrate an embodiment of a
microneedle 66 with a substantially square or rectangular
cross-section in a side view and a corresponding top view,
respectively. This microneedle, however, is a hollow microneedle,
having a channel formed within the needle for the passage of
allergens.
[0039] FIGS. 7A and 7B schematically illustrate an embodiment of a
microneedle 68 with a substantially square or rectangular
cross-section in a side view and a corresponding top view,
respectively. This microneedle, however, is a grooved microneedle,
having a channel formed on the side of the needle for the passage
of allergens.
[0040] FIGS. 8A and 8B schematically illustrate an embodiment of a
microneedle 70 with a changing cross-sectional area that tapers to
a point.
[0041] Any of the features of the microneedles in the embodiments
of FIGS. 3A-8B may be combined with one another, and
cross-sectional shapes may be varied. For example, a microneedle
could be both hollowed and grooved at the same time. As mentioned
before, the microneedles may have a height of about 50-300 microns
and a diameter of about 10-80 microns in order to penetrate a
subject's skin, although other embodiments may have other
dimensions. (Skin not illustrated in this view.) The microneedle
array may be manufactured out of a number of different substances,
for example, silicon, glass, metal, or plastic. Due to its
attractive micromachining properties, silicon may be
anisotropically etched using chemical and reactive ion etching
processes to fabricate the microneedles, although other materials
and manufacturing processes can be used.
[0042] A further embodiment of a microneedle 72 is schematically
illustrated in FIG. 9. In this embodiment, the microneedle is
corrugated around a generally pointed microneedle structure.
Corrugated needle designs like this one may facilitate the entry
and exit of the microneedle from the test subject 36 with a reduced
amount of force. The corrugations may also provide channels for the
allergens to enter a puncture site.
[0043] Referring to FIGS. 10A and 10B, another embodiment of a
minimally invasive allergy testing system 74 is schematically
illustrated in an exploded perspective view and an assembled side
cross-sectional view, respectively. The allergy testing system
includes a microneedle substrate 76 that supports an array of
hollow microneedles 78 with integral mesas 80. The mesas 80 are not
absolutely necessary, but in some embodiments, they can provide
stability for the microneedles 78 as the microneedles are engaged.
(This will be explained in more detail later.) A linear array of
microneedles having mesas are illustrated in this embodiment, but
other embodiments may have other numbers and types of components in
other shapes and configurations. The substrate 76, microneedles 78,
and mesas 80 may be manufactured from a number of different
materials, such as silicon, glass, metal, or plastic. The
microsystem allergy testing device 74 also includes a package
assembly 82 which houses the substrate 76, microneedles 78, and
mesas 80 such that the top surface of substrate 76 rests against a
compressible stop 84 along an inner surface of the package 82. The
compressible stop 84 may be permanently compressible, or may be an
energy storage device such as a spring. The microneedles 78 are
mounted for movement within the package 82 from a position where
the upper tips of the microneedles 78 lie within orifices 86, such
that they do not protrude significantly outside of the package
assembly, to a position protruding outside of the package assembly
82.
[0044] An encapsulated set of allergens 88 associated with each
hollow microneedle 78, is sandwiched between the substrate 76 and
the plunger 90. The plunger 90 may be activated by an activation
system (not shown), such as manual pressure, mechanical systems,
electromechanical systems, piezoelectric, or a micromechanical
actuator. Pressure applied to the plunger 90 causes the release of
substrate 76 from resting stop 84 as well as the flow of allergens
88 through the channels associated with one of the hollow
microneedles 78 positioned adjacent each encapsulated allergen.
Motion of substrate 76 causes each of the microneedles 78 to
protrude out of the package assembly 82 through the orifices 86
towards the patient's skin (not shown in this figure, but in this
embodiment, the test subject would be above the allergy testing
system 74 as oriented.) When the plunger is depressed far enough,
the microneedles 78 pierce the patient's skin while mesas 80 fit
into orifices 86 in package 82 to help increase travel and
positional stability of the microneedles 78.
[0045] This embodiment also optionally has a thin sealing film 92
employed over a surface of the package assembly 82 to serve as a
sterile layer between the subject's skin and the microneedles 78.
Sealing film 92 may be removed before use or left behind on the
patient's skin along with human readable, barcode, or other
identifying marks 94. Such identifying marks have been discussed
above with regard to previous embodiments.
[0046] Referring to FIGS. 11A and 11B, another embodiment of a
minimally invasive allergy testing system 96 is schematically
illustrated in an exploded perspective view and an assembled side
cross-sectional view, respectively. The allergy testing device 96
illustrated in FIGS. 11A and 11B is similar in structure and
operation to the allergy testing device 74 embodied in FIGS. 10A
and 10B, except as described herein. In the embodiment of FIGS. 11A
and 11B, solid microneedles 98 are used along with encapsulated
allergens 100 that are located in the path between the microneedles
98 and the patient's skin (again, the skin is not illustrated in
this embodiment, but the test subject would be above the allergy
testing system 96 in the orientation illustrated.) As the plunger
90 is activated, microneedles 98 puncture the encapsulated
allergens 100, releasing the allergens, and continue to move
outward until they also penetrate the subject skin. After the
patient's skin is pricked by the microneedles 98, the allergen is
then free to penetrate.
[0047] FIGS. 12A-12C schematically illustrate one possible method
of applying allergens to a subject using an embodiment of an
allergy testing system. In a first step, FIG. 12A, the minimally
invasive allergy testing system 102 is placed in contact with a
subject's skin 36. Since this embodiment of an allergy testing
system 102 has a sealing layer 92, that is the portion of the test
system initially in contact with the skin 36. In other systems, the
portion initially in contact with the skin 36 might be the package
assembly 82. In FIG. 12A, the microneedle array is in a resting
position. In a second step, FIG. 12B, the plunger 90 is activated,
in the orientation of FIG. 12B, in a downward direction, causing
the substrate 76 to compress the compressible stop 84. This causes
the microneedles 98 to puncture the encapsulated allergens 100, the
sealing layer 92, and then the skin 36. In FIG. 12B, the
microneedle array 98 is in an penetrating position. If the
compressible stop 84 is an energy storage device, such as a memory
foam or a spring, then in a further step, FIG. 12C, the
compressible stop 84 retracts the substrate 76 and therefore lifts
the microneedles 98 from the skin 36 and substantially back into
the resting position. The encapsulated allergens 100 are allowed to
enter the puncture holes in the optional sealing layer 92 and the
holes in the skin 36. The various possible needle shapes and
geometries have been discussed earlier, and the microneedle shapes
illustrated in this example are not intended to be limiting.
Furthermore, microneedles of differing lengths on the same
substrate 76 may be used. A benefit of providing different length
microneedles may be to allow different allergens to reach a
targeted skin depth, or to test the same allergen at different
depths for studied comparisons.
[0048] FIGS. 12D1-12D4 schematically illustrate different
embodiments of gathering and analyzing allergy test data after the
allergens have been applied by the allergy testing system in FIGS.
12A-12C. FIG. 12D1 schematically illustrates a test subject's skin
36 which has been pricked and injected with allergens 100 by the
microneedles 98 of a minimally invasive allergy testing system 102.
In the embodiment of FIG. 12D1, the sealing layer 92 has been
removed, prior to manual viewing of the test results. Here, a
schematic human eye 104 is looking for a reaction 106 to a
particular allergen. While the allergy test results may be
evaluated using a manual approach such as this, other methods may
make it easier to distinguish results given the close spacings
between allergy test points possible with microneedles. If the
sealing layer 92 is left in place, as in FIG. 12D2, patient
information, test identification, and allergen identification may
be aided by markings on the sealing layer as left behind on the
skin 36.
[0049] FIG. 12D3 schematically illustrates an embodiment of an
allergy analysis system 108 which can optionally be used in place
of or in conjunction with manual evaluation methods. The allergy
analysis system 108 includes a module 110 with imaging optics 112.
The imaging optics 112 focuses images of the tested skin area on an
image sensor 114. The image sensor 114 is coupled to an image
analyzer or processor 116. The image analyzer 116 can analyze the
captured images for color, shape, dimension, and location in the
test field. Based on this analysis and correlation with what
allergen was tested in which location, the analyzer 116 determines
reactivity data for each allergen. The reactivity data, as well as
the captured images may be stored, displayed, transmitted, and/or
printed by the analyzer 116. Optionally, the analyzer may output
this data to another processor for storage, display, further
analysis, transmission, and/or printing. In the embodiment of FIG.
12D3, the analyzer 116 is directly coupled to the allergy analysis
system 108. In other embodiments, the analyzer 116 may be remotely
coupled to the analysis system 108 via a wireless or cabled
link.
[0050] The image analyzer 116 may comprise a central processing
unit (CPU) or processor and a memory which are coupled together by
a bus or other link, although other numbers and types of components
in other configurations and other types of systems, such as an
application specific integrated circuit (ASIC) could be used. The
processor may execute a program of stored instructions for one or
more aspects of the claimed invention, including the method for
determining a degree of reaction to one or more allergens as
described and illustrated herein. The memory stores these
programmed instructions for execution by the processor. A variety
of different types of memory storage devices, such as random access
memory (RAM) or a read only memory (ROM) in the system or a floppy
disk, hard disk, CD ROM, or other computer readable medium which is
read from and/or written to by a magnetic, optical, or other
reading and/or writing system that is coupled to the processor, can
be used for the memory to store these programmed instructions.
[0051] In the example of FIG. 12D3, the skin puncture site 118
shows a positive allergy reaction 106, while skin puncture sites
120, 122 show negative allergy reactions. The imaging module 110
should be placed in alignment with the original allergy testing
device 102 (from FIGS. 12A-12C) such that the imaging optics 112
creates images of test sites 118, 120, and 122. These test sites
118, 120, 122 are associated with each allergen in correlated
locations on image sensor 114. Image patterns associated with each
allergen, as imaged by sensor 114, are captured and transmitted to
image analyzer 116 for analysis as described above in order to
identify color, shape, dimension, allergic reaction, and/or a time
rate of change of the allergic response. The determination of a
time rate of change in the allergic response may be a great benefit
to medical professionals who often do not have the time to manually
observe a reaction on a continuous or substantially continuous
basis that would let them see how allergic reactions vary over
time.
[0052] In other embodiments of an allergy testing system which have
an allergy imaging analysis system 108, it may be important to
determine topographic information when assessing reactivity to an
allergen. In such embodiments, an extra set of imaging optics and
an extra image sensor may be displaced laterally from the other
optical system to obtain stereoscopic, parallax information about a
given test location. Parallax information may in turn be used to
calculate topographic profiles of test regions.
[0053] FIG. 12D4 schematically illustrates an embodiment of a
minimally invasive allergy testing system 124 with an integrated
imaging and analysis module 110. The microneedle array 126 and
plunger 128 operate in similar fashion to the corresponding
elements in FIG. 12A, except as described herein. In this
embodiment, the array of microneedles 126 and plunger 128 are made
of glass or some other transparent material, such as transparent
hard plastic, such that imaging module 110 may image the tested
regions with the needles in-situ, or even slightly or completely
retracted. Preferably, the width of the microneedles 130 relative
to their spacing should be fine enough to allow enough imaging area
for an adequate diagnosis of the allergic reaction.
[0054] FIG. 13 schematically illustrates a further embodiment of a
minimally invasive allergy testing system 132. The allergy testing
system 132 is coupled to a band 134 which may be wrapped around a
portion of a person's body. In this example, the part of the body
illustrated is an arm 136. Of course, it would be apparent to those
skilled in the art that attachment band 134 could be compatible
with or modified to attach to other portions of the body.
Attachment band 134 need not circle completely around and back to
itself, although preferred embodiments may have Velcro.RTM.
attachments which wrap around the body and then connect to
themselves. The purpose of the attachment band 134 is to hold a
test frame 138 in substantially the same position during a
minimally invasive allergy test. The test frame 138 defines an
opening in the band 134 through which the skin may be accessed. The
test frame 138 also has a first alignment coupling, such as a hinge
140 onto which a package 142 containing a microneedle array and
encapsulated allergens may be placed for aligned engagement with
the skin in the test frame 138. The test frame 138 has a second
alignment coupling, such as a hinge 144 onto which an allergy
imaging system 146 may be placed for aligned engagement with the
skin in the test frame 138. In some embodiments, the allergen and
microneedle package 142 will be engaged with the test frame at
different times from the imaging system 146. In other embodiments,
such as the transparent embodiments, both the allergen and
microneedle package 142 and the imaging system 146 may be engaged
at the same time. In various embodiments, the alignment coupling
does not have to be a hinged connection. It may, instead, be a
temporary guide for the manual placement of an otherwise loose
portion of the testing system, such as the allergen package, or the
imaging system. In the embodiment of FIG. 13, the analyzer 148 is
illustrated as being remotely coupled to the imaging system 146.
This remote link may be a physical wire or a radio frequency (RF)
or optical wireless link.
[0055] All of the minimally invasive allergy testing systems
embodied herein, and their equivalents, are intended to be used
with replaceable cartridges having the microneedle array and the
encapsulated allergens. FIGS. 14A-14P schematically illustrate an
embodiment of a process for manufacturing a replaceable allergen
cartridge for use in an allergy testing system.
[0056] The process begins, FIG. 14A, with a mold 150, having
cavities 152 and vacuum lines 154 coupled to each cavity. Next,
FIG. 14B, a formable layer 156 is placed on top of the mold 150. An
example of a material which may be used for the formable layer 156
is polyvinylidene chloride (PVDC). Next, FIG. 14C, heat 158 is
applied to the PVDC 156, while a negative pressure 160 is applied
to the vacuum lines 154 from the back side of the mold 150. This
causes the PVDC 156 to fill the mold cavities 152. A top view of
the PVDC 156 coating the mold 150 may be seen in FIG. 14D.
[0057] Next, FIG. 14E, allergens 162 are filled into the
PVDC-wrapped cavities. The array of allergens do not have to be the
same, but may be any combination of unique allergens and/or
repeats. A plastic cover 164, such as the one shown in a top view
in FIG. 14F may then be applied, FIG. 14G, to the top of the array
of allergens 162. FIG. 14H illustrates the assembly package of FIG.
14G in a side view. Next, FIG. 14J, a removable seal 166 is applied
to the top of the package. The mold 150 can then be removed,
leaving the encapsulated allergens 168 as illustrated in FIG.
14K.
[0058] In a parallel, preceding, or subsequent step, FIG. 14L, a
microneedle array 170 is formed out of silicone, glass, plastic,
quartz, or metal. Suitable methods of microneedle construction have
been discussed above. Next, FIG. 14M, elastomer springs 172 are
coupled to the substrate of the microneedle array 170. FIGS. 14L
and 14M show the microneedle array 170 in a top view. FIG. 14N
shows the microneedle array 170 and the elastomer springs 172 in a
side view. The elastomer springs in this embodiment are just one
type of energy storage device which may be coupled to the
microneedle array 170. Other embodiments may have energy storage
devices which include metal springs and plastic springs.
[0059] Next, the allergen array assembly 168 from FIG. 14K and the
microneedle array assembly from FIG. 14N are coupled together as in
FIG. 14P to form a replaceable allergen cartridge 174. The coupling
of the two sections may be accomplished with adhesives, shrink
wrapping, or packaging.
[0060] FIGS. 15A and 15B schematically illustrate an embodiment of
a process for allergy testing using the replaceable allergen
cartridge 174 of FIG. 14P. FIG. 15A illustrates the replaceable
cartridge 174 in contact with skin 36 after peeling away the
removable seal 166. Previous discussions have covered the
activation systems and imaging systems which may be used with the
microneedle array and encapsulated allergen components of the
replaceable cartridge. For simplicity, and to avoid duplication,
those other elements are not shown here. Instead, FIG. 15B
illustrates how the encapsulated allergens in this embodiment of a
replaceable allergen cartridge may be compressed into the puncture
area 176 of the microneedles.
[0061] Although the descriptions and figures of the embodiments
described above show single needle arrays or one dimensional array
systems, the claimed invention is easily extendible to two
dimensions.
[0062] Having thus described several embodiments of the claimed
invention, it will be rather apparent to those skilled in the art
that the foregoing detailed disclosure is intended to be presented
by way of example only, and is not limiting. Various alterations,
improvements, and modifications will occur and are intended to
those skilled in the art, though not expressly stated herein. These
alterations, improvements, and modifications are intended to be
suggested hereby, and are within the spirit and the scope of the
claimed invention. Additionally, the recited order of the
processing elements or sequences, or the use of numbers, letters,
or other designations therefore, is not intended to limit the
claimed processes to any order except as may be specified in the
claims. Accordingly, the claimed invention is limited only by the
following claims and equivalents thereto.
* * * * *