U.S. patent application number 16/130638 was filed with the patent office on 2019-05-02 for structural diffusion membranes for chemical sensors.
The applicant listed for this patent is Cardiac Pacemakers, Inc.. Invention is credited to Jack Gordon, Michael J. Kane, Yingbo Li.
Application Number | 20190125228 16/130638 |
Document ID | / |
Family ID | 66245288 |
Filed Date | 2019-05-02 |
United States Patent
Application |
20190125228 |
Kind Code |
A1 |
Kane; Michael J. ; et
al. |
May 2, 2019 |
STRUCTURAL DIFFUSION MEMBRANES FOR CHEMICAL SENSORS
Abstract
Embodiments herein relate to implantable chemical sensors for
detecting a physiological analyte and medical devices including the
same. In an embodiment, an implantable medical device is included.
The implantable medical device can include a chemical sensor
configured to detect an ion concentration in a bodily fluid. The
chemical sensor can include a sensing element. The sensing element
can include an outer barrier layer forming a top, a bottom, and
opposed sides of the sensing element and a structural reinforcing
element contacting the outer barrier layer. The top of the outer
barrier layer of the sensing element can include a polymeric matrix
permeable to analytes.
Inventors: |
Kane; Michael J.; (St. Paul,
MN) ; Li; Yingbo; (Shanghai, CN) ; Gordon;
Jack; (Minneapolis, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Cardiac Pacemakers, Inc. |
St. Paul |
MN |
US |
|
|
Family ID: |
66245288 |
Appl. No.: |
16/130638 |
Filed: |
September 13, 2018 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/1451 20130101;
A61B 5/14546 20130101; A61B 2562/162 20130101; A61B 5/1459
20130101; A61B 5/14735 20130101; A61B 5/1473 20130101 |
International
Class: |
A61B 5/145 20060101
A61B005/145; A61B 5/1459 20060101 A61B005/1459; A61B 5/1473
20060101 A61B005/1473 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 31, 2017 |
CN |
201711052948.1 |
Claims
1. An implantable medical device comprising: a chemical sensor
configured to detect an ion concentration in a bodily fluid, the
chemical sensor comprising: a sensing element, the sensing element
comprising an outer barrier layer forming a top, a bottom, and
opposed sides of the sensing element; a structural reinforcing
element contacting the outer barrier layer; the top of the outer
barrier layer comprising a polymeric matrix permeable to
analytes.
2. The implantable medical device of claim 1, wherein the
structural reinforcing element is disposed beneath, within, or on
top of the top of the outer barrier layer.
3. The implantable medical device of claim 1, the structural
reinforcing element comprising polyester, polyurethane,
polyethylene, polypropylene, nylon, sintered titanium, deep
reactive-ion etched silicon, sintered stainless steel, sintered
silica, liquid crystal, glass, borosilicate glass, or mixtures or
derivatives thereof.
4. The implantable medical device of claim 1, the structural
reinforcing element selected from the group comprising a woven
material, a non-woven material, electrospun material, and randomly
woven material.
5. The implantable medical device of claim 1, the structural
reinforcing element comprising one or more intramural struts
spanning a distance between the top and the bottom of the outer
barrier layer.
6. The implantable medical device of claim 5, the one or more
intramural struts comprising polyester, polyurethane, polyethylene,
polypropylene, nylon, sintered titanium, deep reactive-ion etched
silicon, sintered stainless steel, sintered silica, liquid crystal,
glass, borosilicate glass, or mixtures or derivatives thereof.
7. The implantable medical device of claim 1, the outer barrier
layer comprising polyHEMA, agarose, alginates, polyvinyl alcohol,
polyacrylate, collagen, PEG, gelatin, glass, borosilicate glass, or
mixtures or derivatives thereof.
8. The implantable medical device of claim 1, further comprising an
optical excitation assembly configured to illuminate the sensing
element; and an optical detection assembly configured to receive
light from the sensing element.
9. The implantable medical device of claim 1, the chemical sensor
having a diameter that is greater than 1.0 mm.
10. The implantable medical device of claim 1, the chemical sensor
configured to detect an ion selected from the group comprising of
potassium, sodium, chloride, calcium, magnesium, lithium, or
hydronium.
11. The implantable medical device of claim 1, the structural
reinforcing element comprising the shape of a rectangular column, a
cylinder, a conical shape, a frustoconical shape, a pyramid, a
frustopyramidal shape.
12. An implantable medical device comprising: a chemical sensor
configured to detect an ion concentration in a bodily fluid, the
chemical sensor comprising: a sensing element, the sensing element
comprising an outer barrier layer forming a top, a bottom, and
opposed sides of the sensing element; the outer barrier layer
defining an interior volume; a structural reinforcing element
disposed within the interior volume, wherein the structural
reinforcing element is porous.
13. The implantable medical device of claim 12, the structural
reinforcing element filling at least between 10% to 25% of the
interior volume.
14. The implantable medical device of claim 12, the structural
reinforcing element comprising polyester, polyurethane,
polyethylene, polypropylene, nylon, sintered titanium, deep
reactive-ion etched silicon, sintered stainless steel, sintered
silica, liquid crystal, glass, borosilicate glass, or mixtures or
derivatives thereof.
15. The implantable medical device of claim 12, the structural
reinforcing element comprising a borosilicate glass.
16. The implantable medical device of claim 12, the outer barrier
layer comprising polyHEMA, agarose, alginates, polyvinyl alcohol,
polyacrylate, collagen, PEG, gelatin, glass, borosilicate glass, or
mixtures or derivatives thereof.
17. The implantable medical device of claim 12, the outer barrier
layer comprising a silica-containing glass.
18. The implantable medical device of claim 12, a bottom of the
outer barrier layer comprising a glass interface plate for coupling
the sensing element to an optical excitation assembly and an
optical detection assembly.
19. The implantable medical device of claim 12, a top of the outer
barrier layer comprising polyHEMA.
20. The implantable medical device of claim 12, wherein the
structural reinforcing element is infused with one or more ion
selective sensors.
Description
[0001] This application claims the benefit of China Patent
Application No. 201711052948.1, filed Oct. 31, 2017, the content of
which is herein incorporated by reference in its entirety.
FIELD
[0002] Embodiments herein relate to implantable chemical sensors
for detecting a physiological analyte and medical devices including
the same.
BACKGROUND
[0003] Medical professionals frequently need to evaluate chemical
analyte concentrations of a patient when assessing the patient's
condition and/or diagnosing a problem. However, measuring
physiological concentrations of analytes, such as potassium amongst
others, generally requires drawing blood from the patient. Blood
draws are commonly done at a medical clinic or hospital and
therefore generally require the patient to physically visit a
medical facility. As a result, despite their significance,
physiological analyte concentrations are frequently measured only
sporadically.
[0004] Implanted chemical sensors offer the promise of being able
to gather data on analyte concentrations in real time even while a
patient is away from a medical treatment facility. For example,
implanted chemical sensors can measure analyte concentrations from
the interstitial fluid as the analyte passes through a soft
hydrophilic diffusion membrane and into a chemical sensor. The
measurements can occur continuously or semi-continuously providing
a far richer data set for a medical professional to evaluate.
SUMMARY
[0005] Embodiments herein relate to implantable chemical sensors
for detecting a physiological analyte and medical devices including
the same. In a first aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, an implantable medical device is included. The implantable
medical device can include a chemical sensor configured to detect
an ion concentration in a bodily fluid. The chemical sensor can
include a sensing element. The sensing element can include an outer
barrier layer forming a top, a bottom, and opposed sides of the
sensing element and a structural reinforcing element contacting the
outer barrier layer. The top of the outer barrier layer of the
sensing element can include a polymeric matrix permeable to
analytes.
[0006] In a second aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can be disposed beneath,
within, or on top of the top of the outer barrier layer.
[0007] In a third aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can be formed of
polyester, polyurethane, polyethylene, polypropylene, nylon,
sintered titanium, deep reactive-ion etched silicon, sintered
stainless steel, sintered silica, liquid crystal, glass,
borosilicate glass, or mixtures or derivatives thereof.
[0008] In a fourth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can be formed of a woven
material.
[0009] In a fifth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can include one or more
intramural struts spanning a distance between the top and the
bottom of the outer barrier layer.
[0010] In a sixth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, the one or more intramural struts can be formed of
polyester, polyurethane, polyethylene, polypropylene, nylon,
sintered titanium, deep reactive-ion etched silicon, sintered
stainless steel, sintered silica, liquid crystal, glass,
borosilicate glass, or mixtures or derivatives thereof.
[0011] In a seventh aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, an outer barrier layer can be formed of polyHEMA, agarose,
alginates, polyvinyl alcohol, polyacrylate, collagen, PEG, gelatin,
glass, borosilicate glass, or mixtures or derivatives thereof.
[0012] In an eighth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, the implantable medical device can include an optical
excitation assembly configured to illuminate the sensing element;
and an optical detection assembly configured to receive light from
the sensing element.
[0013] In a ninth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a chemical sensor can have a diameter that is greater than
1.0 mm.
[0014] In a tenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a chemical sensor can be configured to detect an ion
selected from the group consisting of potassium, sodium, chloride,
calcium, magnesium, lithium, or hydronium.
[0015] In an eleventh aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, an implantable medical device is included. The implantable
medical device can include a chemical sensor configured to detect
an ion concentration in a bodily fluid. The chemical sensor can
include a sensing element. The sensing element can include an outer
barrier layer forming a top, a bottom, and opposed sides of the
sensing element, where the outer barrier layer defines an interior
volume. The sensing element can also include a structural
reinforcing element disposed within the interior volume, where the
structural reinforcing element is porous.
[0016] In a twelfth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can fill at least between
10% to 25% of the interior volume.
[0017] In a thirteenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can be formed of a
polyester, polyurethane, polyethylene, polypropylene, nylon,
sintered titanium, deep reactive-ion etched silicon, sintered
stainless steel, sintered silica, liquid crystal, glass,
borosilicate glass, or mixtures or derivatives thereof.
[0018] In a fourteenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can be formed of a
borosilicate glass.
[0019] In a fifteenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, an outer barrier layer can be formed of polyHEMA, agarose,
alginates, polyvinyl alcohol, polyacrylate, collagen, PEG, gelatin,
glass, borosilicate glass, or mixtures or derivatives thereof.
[0020] In a sixteenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, an outer barrier layer can be formed of a glass.
[0021] In a seventeenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, an outer barrier layer can be formed of a borosilicate
glass.
[0022] In an eighteenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, the bottom of an outer barrier layer can include a glass
interface plate for coupling the sensing element to an optical
excitation assembly and an optical detection assembly.
[0023] In a nineteenth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, the top of the outer barrier layer can be formed of
polyHEMA.
[0024] In a twentieth aspect, in addition to one or more of the
preceding or following aspects, or in the alternative to some
aspects, a structural reinforcing element can be infused with one
or more ion selective sensors.
[0025] This summary is an overview of some of the teachings of the
present application and is not intended to be an exclusive or
exhaustive treatment of the present subject matter. Further details
are found in the detailed description and appended claims. Other
aspects will be apparent to persons skilled in the art upon reading
and understanding the following detailed description and viewing
the drawings that form a part thereof, each of which is not to be
taken in a limiting sense. The scope herein is defined by the
appended claims and their legal equivalents.
BRIEF DESCRIPTION OF THE FIGURES
[0026] Aspects may be more completely understood in connection with
the following drawings, in which:
[0027] FIG. 1 is a schematic top view of an implantable medical
device in accordance with the embodiments herein.
[0028] FIG. 2 is a cross-sectional view of a chemical sensor taken
along line 2-2' of FIG. 1.
[0029] FIG. 3 is a schematic plan view of a structural reinforcing
element in accordance with various embodiments herein.
[0030] FIG. 4 is a schematic plan view of a structural reinforcing
element in accordance with various embodiments herein.
[0031] FIG. 5 is a cross-sectional view of a chemical sensor in
accordance with additional embodiments herein.
[0032] FIG. 6 is a cross-sectional view of a chemical sensor in
accordance with additional embodiments herein.
[0033] FIG. 7 is a cross-sectional view of a chemical sensor in
accordance with additional embodiments herein.
[0034] FIG. 8 is a cross-sectional view of a chemical sensor in
accordance with additional embodiments herein.
[0035] FIG. 9 is a schematic top view of an implantable medical
device in accordance with additional embodiments herein.
[0036] FIG. 10 is a schematic cross-sectional view of a sensing
element in accordance with additional embodiments herein.
[0037] FIG. 11 is a schematic cross-sectional view of an
implantable medical device in accordance with various embodiments
herein.
[0038] FIG. 12 is a schematic diagram of components of an
implantable medical device in accordance with various embodiments
herein.
[0039] While embodiments are susceptible to various modifications
and alternative forms, specifics thereof have been shown by way of
example and drawings, and will be described in detail. It should be
understood, however, that the scope herein is not limited to the
particular embodiments described. On the contrary, the intention is
to cover modifications, equivalents, and alternatives falling
within the spirit and scope herein.
DETAILED DESCRIPTION
[0040] Implanted chemical sensors offer the promise of being able
to gather data on analyte concentrations in real time even while a
patient is away from a medical treatment facility.
[0041] Highly-porous soft hydrophilic polymers are ideal materials
for use with implanted chemical sensors because of their ability to
permit the rapid transport of large amounts of analytes across
sensor walls and thus contribute to rapid response times for
sensors built using the same. However, many such materials lack
desirable levels of structural integrity. Such materials are
generally soft and flexible which can lead to challenges when
designing sensor elements, especially as the sensors get larger. In
particular, the use of such materials in a chemical sensor can
resulting in undesirable deformation and/or structural failure and
interference at the optical interface of the chemical sensor, which
can lead to diminished response and/or loss of function of the
chemical sensor.
[0042] Embodiments herein, however, can include structural
reinforcing elements that can provide structural integrity to soft
hydrophilic diffusion membranes of chemical sensors. Thus, by
including structural reinforcing elements, chemical sensors made
using soft hydrophilic materials can maintain their structural
integrity over the lifetime of the sensor.
[0043] Referring now to FIG. 1, an implantable medical device (IMD)
100 is shown in accordance with the embodiments herein. The IMD 100
can include an implantable housing 102 and a header 104 coupled to
the implantable housing 102. Various materials can be used.
However, in some embodiments, the housing 102 can be formed of a
material such as a metal, ceramic, a polymer, or a composite. The
header 104 can be formed of various materials, but in some
embodiments the header 104 can be formed of a transparent or
translucent polymer such as an epoxy material. In some embodiments
the header 104 can be hollow. In other embodiments the header 104
can be filled with components and/or structural materials such as
epoxy or another material such that it is non-hollow.
[0044] The IMD 100 can also include a chemical sensor 106 coupled
to the implantable housing 102. Chemical sensor 106 can be
configured to detect an ion concentration of a bodily fluid when
implanted in the body. In some embodiments, the chemical sensor 106
can be configured to detect an ion selected from the group
consisting of potassium, sodium, chloride, calcium, magnesium,
lithium, hydronium, hydrogen phosphate, bicarbonate, and the like.
Bodily fluids can include blood, interstitial fluid, serum, lymph,
serous fluid, cerebrospinal fluid, and the like. In some
embodiments chemical sensor 106 can be configured to detect one or
more of an electrolyte, a protein, a sugar, a hormone, a peptide,
an amino acid, and a metabolic product. However, many other
analytes are also contemplated herein.
[0045] It will be appreciated that chemical sensor 106 can be
positioned at any location along IMD 100, including a location
along the implantable housing 102 and a location along the header
104. The IMD 100 can take on various dimensions. In a particular
embodiment herein it can be approximately 2 to 3 inches in length,
0.4 to 0.6 inches wide, and 0.15 to 0.35 inches thick. However, in
some embodiments, the IMD 100 can be about 0.25, 0.5, 1.0, 2.0,
3.0, 4.0, or 5.0 inches in length. In some embodiments the length
can be in a range wherein any of the foregoing lengths can serve as
the upper or lower bound of the range, provided that the upper
bound is greater than the lower bound. In some embodiments, the IMD
100 can be about 0.25, 0.5, 0.75, 1.0, or 2.0 inches in width. In
some embodiments the length can be in a range wherein any of the
foregoing widths can serve as the upper or lower bound of the
range, provided that the upper bound is greater than the lower
bound. In some embodiments, the IMD 100 can be about 0.10, 0.25,
0.50, 0.75 or 1.0 inches thick. In some embodiments the thickness
can be in a range wherein any of the foregoing thicknesses can
serve as the upper or lower bound of the range, provided that the
upper bound is greater than the lower bound.
[0046] In some embodiments, the chemical sensor 106 can be in the
shape of a circle. The diameter of the chemical sensor 106 can be
about 0.5 mm, 0.75 mm, 1.0 mm, 1.5 mm, 1.75 mm, 2.0 mm, 2.5 mm,
2.75 mm, 3.0 mm, 3.25 mm, 3.5 mm, 3.75 mm, 4.0 mm, 4.5 mm, or 5.0
mm. In some embodiments the diameter can be in a range wherein any
of the foregoing diameters can serve as the upper or lower bound of
the range, provided that the upper bound is greater than the lower
bound. In some embodiments, the diameter of the chemical sensor 106
is greater than or equal to 1.5 mm. Though chemical sensor 106 is
depicted in FIG. 1 in the shape of a circle, it will be appreciated
that chemical sensor 106 can assume a variety of shapes, including
but not limited to a square, a rectangle, a triangle, a trapezoid,
an oval, and the like. It will also be appreciated that IMD 100 can
include one or more chemical sensors that measure the same, or
different analytes. In some embodiments, one or more chemical
sensors can be arranged as an array in a variety of shapes, such
as, for example, a grid, a circle, a mosaic, a geometric patter, or
the like.
[0047] The height (depth) of the chemical sensor 106 can be about
0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.75 mm, 1.0 mm, 1.5 mm,
1.75 mm, 2.0 mm, 2.5 mm, 2.75 mm, 3.0 mm, 3.25 mm, 3.5 mm, 3.75 mm,
4.0 mm, 4.5 mm, or 5.0 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In
some embodiments the height of the chemical sensor 106 can be in a
range wherein any of the foregoing distances can serve as the upper
or lower bound of the range, provided that the upper bound is
greater than the lower bound.
[0048] Referring now to FIG. 2, a cross-sectional view of chemical
sensor 106 along line 2-2' of FIG. 1 is shown. Chemical sensor 106
can include, but not be limited to, sensing element 202, optical
excitation assembly 218, and optical detection assembly 220. FIG. 3
shows an optical chemical sensor. However, in other embodiments the
chemical sensor can be a potentiometric chemical sensor.
[0049] The sensing element 202 can include an outer barrier layer
204 formed, in full or in part, from a permeable material, such as
an ion permeable polymeric matrix material, and the like. Exemplary
materials for the outer barrier layer 204 are described in greater
detail below. Outer barrier layer 204 can form a top 205, a bottom
210, and opposed sides 206 and 208 to surround an interior volume
222 of sensing element 202. Bottom 210 and opposed sides 206 and
208 of outer barrier layer 204 will be discussed in more detail
below in reference to FIGS. 3-5. Briefly, however, they can be
formed of the same material as the top 205, or they can be formed
from a different material. In some embodiments, at least the top
205 of outer barrier layer 204 can be permeable to sodium ions,
potassium ions, hydronium ions, creatinine, urea, and the like.
Outer barrier layer 204 can also include an active agent disposed
therein including, but not limited to anti-inflammatory agents,
angiogenic agents, and the like. Exemplary active agents are
described in greater detail below.
[0050] It will be appreciated, however, that bottom 210 may or may
not be a discrete layer. For example, in some embodiments, bottom
210 and a transparent member 216 within a recessed pan 214 of the
implantable housing 102 may be combined with different material or
combined as one layer with same type of material.
[0051] The outer barrier layer 204 can include a structural
reinforcing element 212 disposed within, on or under the outer
surface of the outer barrier layer 204. For example, the structural
reinforcing element 212 can be disposed within, on top of, or
beneath the outer barrier layer 204. In some embodiments, the
structural reinforcing element 212 can be disposed within, on or
under the exterior surface of opposed sides 206 and 208. In yet
other embodiments, structural reinforcing element 212 can be
disposed within, on or under the outer surface of bottom 210 of the
outer barrier layer 204. In still other embodiments, the structural
reinforcing element 212 can be disposed within, on or under the
outer surface of the entire outer barrier layer 204. The structural
reinforcing element will be further discussed in reference to FIGS.
3-5 below. It will be appreciated that the structural reinforcing
elements embodied herein can take on many shapes and forms in
accordance with additional embodiments herein.
[0052] The structural reinforcing elements can come in various
shapes and sizes. In some embodiments, the structural reinforcing
elements can be columnar, pyramidal, frustopyramidal, conical,
frustoconical, cylindrical, rectangular, and the like. In some
embodiments, the base of the structural reinforcing element can
have a greater width than the top of the structural reinforcing
element. In some embodiments, the top of the structural reinforcing
element can have a greater width than the bottom of the structural
reinforcing element. In some embodiments, the top and the bottom of
the structural reinforcing element can have the same width. The
height of the structural reinforcing elements can be about 0.1 mm,
0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.75 mm, 1.0 mm, 1.5 mm, 1.75 mm,
2.0 mm, 2.5 mm, 2.75 mm, 3.0 mm, 3.25 mm, 3.5 mm, 3.75 mm, 4.0 mm,
4.5 mm, or 5.0 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some
embodiments the height of the structural reinforcing elements can
be in a range wherein any of the foregoing diameters can serve as
the upper or lower bound of the range, provided that the upper
bound is greater than the lower bound.
[0053] The structural reinforcing elements can be positioned in
various places within the sensing element. In some embodiments,
there can be multiple structural reinforcing elements and they can
be spaced out across the sensing element (such as spaced out across
the width of the chemical sensor along X and/or Y axes, wherein the
depth of the chemical sensor would be the Z axis). In some
embodiments, multiple structural reinforcing elements can be evenly
spaced out. In some embodiments, multiple structural reinforcing
elements can spaced from each other, but with a bias toward the
middle of the diameter of the chemical sensor, such that a central
portion (such as a central 50% of the overall diameter) has a
higher density of structural reinforcing elements.
[0054] Materials suitable for forming the structural reinforcing
elements discussed herein can include, but not be limited to,
porous rigid polymers, porous rigid ceramics, polyester,
polyurethane, polyethylene, polypropylene, nylon, sintered
titanium, deep reactive-ion etched silicon, sintered stainless
steel, sintered silica, liquid crystal, glass, silica-containing
glass, borosilicate glass such as but not limited to VYCOR.RTM., or
mixtures or derivatives thereof. Structural reinforcing elements
will be discussed in more detail below.
[0055] The implantable housing 102 can include a recessed pan 214
into which the sensing element 202 fits. In some embodiments, the
top of the recessed pan 214 can be substantially flush with the top
of the sensing element 202.
[0056] In some embodiments, implantable housing 102 can define an
aperture occluded by a transparent member 216. The transparent
member 216 can be a glass (including but not limited to
borosilicate glasses), a polymer or other transparent material. The
aperture can be disposed at the bottom of the recessed pan 214. The
aperture can provide an interface allowing for optical
communication between sensing element 202 and the optical
excitation 218 and optical detection 220 assemblies. In some
embodiments, the bottom 210 of the outer barrier layer 204 can be
combined with the transparent member 216. Bottom 210 and
transparent member 216 may be combined with different material or
combined as one layer with same type of material.
[0057] It will be appreciated that outer barrier layer 204, or
portions thereof such as the bottom 210, can be made from a
transparent polymer matrix material to allow for optical
communication between the sensing element 202 and optical
excitation 218 and optical detection 220 assemblies.
[0058] The optical excitation assembly 218 can be configured to
illuminate the sensing element 202. Optical excitation assembly 218
can include a light source such as a light emitting diode (LED),
vertical-cavity surface-emitting lasers (VCSELs),
electroluminescent (EL) devices, and the like. Optical detection
assembly 220 can include a component selected from the group
consisting of a photodiode, a phototransistor, a charge-coupled
device (CCD), a junction field effect transistor (JFET) optical
sensor, a complementary metal-oxide semiconductor (CMOS) optical
sensor, an integrated photo detector integrated circuit, a light to
voltage converter, and the like. Optical excitation 218 and optical
detection 220 assemblies are discussed in further detail below.
[0059] Referring now to FIG. 3, a schematic plan view is shown of a
structural reinforcing element 212 in accordance with various
embodiments herein. The structural reinforcing element 212 can take
on many different shapes including but not limited to a square, a
rectangle, a triangle, a trapezoid, an oval, and the like.
[0060] In the view of FIG. 3, the structural reinforcing element
212 is solid, but porous. However, it will be appreciated that in
some embodiments, the structural reinforcing element 212 can be
formed of a non-porous material. Further, in some embodiments, the
structural reinforcing element can include one or more apertures
disposed therein. Referring now to FIG. 4 a schematic plan view is
shown of a structural reinforcing element 212 in accordance with
various embodiments herein. As can be seen, the structural
reinforcing element 212 includes apertures 402.
[0061] Referring now to FIGS. 5-7, sensing element 202 is shown in
accordance with various embodiments herein. As discussed above with
reference to FIG. 2, sensing element 202 can include an outer
barrier layer 204. Outer barrier layer 204 can form a top 205, a
bottom 210, and opposed sides 206 and 208 to surround an interior
volume 222 of sensing element 202. Outer barrier layer 204 can also
include a structural reinforcing element 212.
[0062] For example, FIG. 5 shows a sensing element 202 having an
outer barrier layer 204, the outer barrier layer including a top
205, a bottom 210, and opposing sides 206 and 208, the entirety of
which can be formed from a material permeable to sodium ions,
potassium ions, and hydronium ions, and the like. Materials
suitable for use in the outer barrier layer 204 are discussed
further below.
[0063] The sensing element 202 can include one or more intramural
struts 306 spanning a distance between the top 205 and the bottom
210 of the outer barrier layer 204. The one or more intramural
struts 506 can include a structural reinforcing element 212
disposed within, on or under the outer surface of the intramural
struts 506. Materials suitable for forming the structural
reinforcing element 212 of the one or more intramural struts 506
can include, but not be limited to rigid porous polymers, rigid
porous ceramics, polyester, polyurethane, polyethylene,
polypropylene, nylon, sintered titanium, deep reactive-ion etched
silicon, sintered stainless steel, sintered silica, liquid crystal,
glass, borosilicate glass, or mixtures or derivatives thereof.
[0064] In some embodiments, the intramural struts 306 can have a
larger size or diameter on the side that contacts the bottom 210 in
comparison to the size of the intramural struts that contacts the
top 205. However, the reverse may also be true, such as shown in
FIG. 6 described below. In some embodiments, the intramural struts
306 can be circular, oval, square, or polygonal in cross-section.
The length of the struts can depend on the size of the sensing
element, but in some embodiments can be 0.1 mm, 0.2 mm, 0.3 mm, 0.4
mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 2 mm, 3 mm, 4 mm,
5 mm, 7 mm, 9 mm, 11 mm, 13 mm, 15 mm, 20 mm, or 30 mm; or can fall
within a range between any of the foregoing distances. The number
of struts can vary. The number of struts used can be 1, 2, 3, 4, 5,
7, 9, 11, 13, 15, 20, 25, 30, 40, 50, 60, 80, 100 or more. In some
embodiments, the number of struts can fall within a range between
any of the foregoing.
[0065] The sensing element(s) 202 embodied herein can include an
interior volume 222 and can also include disposed therein various
indicator beads for detecting an ion concentration of a bodily
fluid when implanted in the body. For example, FIG. 5 shows a first
indicator bead 502 and a second indicator bead 504. The first and
second indicator beads 502 and 504 can include a polymeric support
material and one or more ion selective sensors as described more
fully below. Physiological analytes such as potassium ion, sodium
ion, hydronium ion, and the like, can diffuse through the top 205
of the outer barrier layer 204, and where present, the structural
reinforcing element 212, and onto and/or into first and second
indicator beads 502 and 504 where they can bind with the ion
selective sensors to produce a fluorimetric or colorimetric
response.
[0066] In some embodiments, the first indicator beads 502 can be
segregated to one side of the interior volume 222, with or without
an interior divider. In some embodiments, the second indicator
beads 504 can be segregated to a different side of the interior
volume than the first indicator beads 502. In some embodiments, the
first indicator beads 502 and second indicator beads 504 can be
designed to detect the same analyte. In some embodiments, the first
indicator beads 502 and second indicator beads 504 can be designed
to detect the different analytes. In some embodiments the first
indicator beads 502 and the second indicator beads 504 can be
separated out by having two individual outer barrier layers 204.
For example, instead of a single outer barrier layer 204, there can
be two discrete outer barrier layers 204 with each surrounding a
separate set of indicator beads. In various embodiments, the two
sets of beads can be spaced out by a certain distance, such as at
least about 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 5, 10 or 15
millimeters and less than 100, 70, 50, 40, 30, or 20
millimeters.
[0067] Beyond diffusion through the top 205, in some embodiments
additional diffusion of physiological analytes is also possible
through bottom 210, opposing sides 206 and 208, and, where present,
the structural reinforcing element 212.
[0068] While FIG. 5 shows discrete indicator beads, it will be
appreciated that the indicator components can also exist in other
forms such as a single larger combined mass, an infusion, or the
like, as will be discussed with respect to FIGS. 7 and 8.
[0069] In some embodiments, the sensing element(s) 202 embodied
herein can include an aqueous solution 508 disposed within the
interior volume 222. In some embodiments, the aqueous solution 508
can include potassium ions at a concentration of about 3.0 to about
6.0 mmol/L. In some embodiments, the aqueous solution 508 can
include potassium ions at a concentration of about 1.0, 2.0, 3.0,
4.0, 5.0, 6.0, 7.0, or 8.0 mmol/L. In some embodiments, the
concentration of potassium ions in the aqueous solution 508 can be
in a range between any of the foregoing multiples provided that the
upper bound of the range is greater than the lower bound of the
range. In some embodiments, the aqueous solution 508 can surround
the exterior of sensing element 202 during packaging and prior to
use, as discussed below in reference to FIG. 10.
[0070] In FIGS. 5 and 6, sensing element 202 is shown having an
outer barrier layer 204, the outer barrier layer including a top
205, a bottom 210, and opposing sides 206 and 208, the entirety of
which can be formed from a polymeric matrix permeable to sodium
ions, potassium ions, and hydronium ions, and the like. Permeable
materials suitable for use in the outer barrier layer 204 are
discussed further below.
[0071] FIG. 5 shows a structural reinforcing element 212 disposed
within the interior volume 222 of sensing element 202. In the
embodiment shown in FIG. 6, the structural reinforcing element 212
can be created from a porous material. In some embodiments, the
structural reinforcing element 212 can fill at least 5%, 10%, 15%,
20%, 25%, 30%, 40%, or 50% of the interior volume 222 of sensing
element 202. It will be appreciated that the structural reinforcing
element 212 can fill an interior volume falling within a range,
wherein any of the forgoing percentages can serve as the lower or
upper bound of the range, provided that the lower bound of the
range is a value less than the upper bound of the range. In some
embodiments, the structural reinforcing element 212 disposed within
interior volume 222 can be infused with one or more ion selective
sensors, which are described more fully below.
[0072] FIG. 6 shows a structural reinforcing element 212 disposed
within the interior volume 222 of sensing element 202. In the
embodiment shown in FIG. 6, the structural reinforcing element 212
can be created from a porous material. In some embodiments, the
structural reinforcing element 212 can fill at least 5%, 10%, 15%,
20%, 25%, 30%, 40%, or 50% of the interior volume 222 of sensing
element 202. In some embodiments, the structural reinforcing
element 212 disposed within interior volume 222 can be infused with
one or more ion selective sensors, which are described more fully
below. The structural reinforcing element 212 can include one or
more intramural struts 506.
[0073] It will be appreciated that some portions of the outer
barrier layer 204 can be formed of a different material, while in
other embodiments the entire outer barrier layer 204 can be formed
of the same material. FIG. 7, shows a sensing element 202 having an
outer barrier layer 204 where the top 205, and opposing sides 206
and 208 are formed from the same material that is permeable to
sodium ions, potassium ions, and hydronium ions, and the like. The
bottom 210 is shown having a different material composition. It
will be appreciated that bottom 210 of outer barrier layer 204 can
be formed of a transparent material to couple the sensing element
202 to the optical excitation 218 and optical detection 220
assemblies. Coupling the sensing element 202 to the optical
excitation 218 and optical detection 220 assemblies can facilitate
optical communication between the two structures.
[0074] However, in some embodiments, the bottom can be formed from
a different material than the outer barrier layer. Referring now to
FIG. 8, another cross-sectional view of a chemical sensor is shown
in accordance with some embodiments. In some embodiments, the
bottom 210 can be formed from a glass, such as a borosilicate
glass. In some embodiments, the bottom 210 can be formed from
transparent polymeric materials. In some embodiments, bottom 210
can be fused to an implantable housing at the interface with a
transparent member, as discussed above.
[0075] Referring now to FIG. 9, an implantable medical device 900
is shown in accordance with the embodiments herein. Implantable
medical device 900 can include an implantable housing 102 coupled
to a header 104. The chemical sensor 106 is shown coupled to the
header 104. It will be appreciated that more than one chemical
sensor can be included in the header 104 of medical device 900.
[0076] In some embodiments, it may be desirable to ship the
chemical sensor and/or medical device with the sensor pre-wetted
(e.g., bathed in an aqueous solution). Referring now to FIG. 10, an
embodiment of chemical sensor 106 is shown having a seal 1002 over
the top 205 of sensing element 202. Seal 1002 can provide a tight
seal between the external environment and the chemical sensor 106
when packaged. For example, seal 1002 can provide an effective
barrier to keep aqueous solution 308 within recessed pan 214 such
that the sensing element 202 can be constantly bathed in aqueous
solution 308 prior to implant.
[0077] In some embodiments, the aqueous solution 308 present in
recessed pan 214 can also include potassium ions at a concentration
of about 3.0 to about 6.0 mmol/L. In some embodiments, the aqueous
solution 308 can include potassium ions at a concentration of about
1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, or 8.0 mmol/L. In some
embodiments, the concentration of potassium ions in the aqueous
solution 308 can be in a range between any of the foregoing amounts
provided that the upper bound of the range is greater than the
lower bound of the range.
[0078] Seal 1002 can be removed from the chemical sensor 106 by a
medical professional just prior to implantation. In some
embodiments, seal 1002 can be non-porous to the passage of aqueous
solutions. In some embodiments, seal 1002 can be made from a
polymer such as polyethylene terephthalate (PET),
polytetrafluoroethylene (PTFE), polyethylene, polystyrene, and the
like. In some embodiments, the seal 1002 can be made from a foil,
such as a metal foil. In some embodiments, the seal 1002 can be
made from a radiopaque material.
[0079] Referring now to FIG. 11, a schematic cross-sectional view
of IMD 100 is shown in accordance with various embodiments herein.
The IMD 100 can include implantable housing 102. The implantable
housing 102 of IMD 100 can include various materials such as
metals, polymers, ceramics, and the like. In some embodiments, the
implantable housing 102 can be a single integrated unit. In other
embodiments, the implantable housing 102 can include implantable
housing 102 and epoxy header 104, as discussed above. In some
embodiments, the implantable housing 102, or one or more portions
thereof, can be formed of titanium. In some embodiments, one or
more segments of the implantable housing 102 can be hermetically
sealed.
[0080] Implantable housing 102 can define an interior volume 804
that in some embodiments is hermetically sealed off from the area
1106 outside of IMD 100. The IMD 100 can include circuitry 1108.
Circuitry 1108 can include various components, such as components
1110, 1112, 1114, 1116, 1118, and 1120. In some embodiments, these
components can be integrated and in other embodiments these
components can be separate. In some embodiments, the components can
include one or more of a microprocessor, memory circuitry (such as
random access memory (RAM) and/or read only memory (ROM)), recorder
circuitry, telemetry circuitry, chemical sensor interface
circuitry, power supply circuitry (which can include one or more
batteries), normalization circuitry, chemical sensor control
circuitry, and the like. In some embodiments recorder circuitry can
record the data produced by the chemical sensor and record time
stamps regarding the same. In some embodiments, the circuitry can
be hardwired to execute various functions, while in other
embodiments the circuitry can be implemented as instructions
executing on a microprocessor or other computation device.
[0081] A telemetry interface 1122 can be provided for communicating
with external devices such as a programmer, a home-based unit,
and/or a mobile unit (e.g., a cellular phone, portable computer,
etc.). In some embodiments telemetry interface 1122 can be provided
for communicating with implanted devices such as a therapy delivery
device (e.g. a pacemaker, cardioverter-defibrillator) or
monitoring-only device (e.g. an implantable loop recorder). In some
embodiments, the circuitry can be implemented remotely, via either
near-field, far-field, conducted, intra-body or extracorporeal
communication, from instructions executing on any of the external
or the implanted devices, etc. In some embodiments, the telemetry
interface 1122 can be located within implantable housing 102. In
some embodiments, the telemetry interface 1122 can be located in
header 104.
[0082] The optical excitation 218 and optical detection 220
assemblies of the chemical sensor 106 can be in electrical
communication with the circuitry 1108 within the interior volume
1104. In some embodiments, the control circuitry 1108 is configured
to selectively activate the optical excitation 218 and optical
detection 220 assemblies of the chemical sensor 106.
[0083] Referring now to FIG. 12, a schematic diagram of components
of IMD 100 in accordance with various embodiments herein. It will
be appreciated that some embodiments can include additional
elements beyond those shown in FIG. 12. In addition, some
embodiments may lack some elements shown in FIG. 12. IMD 100 can
gather information through one or more sensing channels. A
microprocessor 1202 can communicate with a memory 1204 via a
bidirectional data bus. The memory 1204 can include read only
memory (ROM) or random access memory (RAM) for program storage and
RAM for data storage, or any combination thereof. The implantable
medical device can also include one or more chemical sensors 106
and one or more chemical sensor channel interfaces 1206 which can
communicate with a port of microprocessor 1202. The chemical sensor
channel interface 1206 can include various components such as
analog-to-digital converters for digitizing signal inputs, sensing
amplifiers, registers which can be written to by the control
circuitry in order to adjust the gain and threshold values for the
sensing amplifiers, source drivers, modulators, demodulators,
multiplexers, and the like. A telemetry interface 1122 is also
provided for communicating with external devices such as a
programmer, a home-based unit, and/or a mobile unit (e.g., a
cellular phone, portable computer, etc.), implanted devices such as
a pacemaker, cardioverter-defibrillator, loop recorder, and the
like.
Outer Barrier Layer
[0084] As referenced above, the outer barrier layer of the sensing
element can be formed of a permeable material. In some embodiments,
the outer barrier layer can be formed from an ion-permeable
polymeric matrix material. Suitable polymers for use as the
ion-permeable polymeric matrix material can include, but are not
limited to polymers forming a hydrogel. Hydrogels herein can
include homopolymeric hydrogels, copolymeric hydrogels, and
multipolymer interpenetrating polymeric hydrogels. Hydrogels herein
can specifically include nonionic hydrogels.
[0085] In some embodiments, hydrogels herein can be prepared from
polymerization of various monomers or macromers including one or
more of poly 2-hydroxyethyl methacrylate (polyHEMA),
2-hydroxypropyl methacrylate (HPMA), acrylamide, acrylic acid,
N-isopropylacrylamide (NIPAm), methoxyl polyethylene glycol
monoacrylate (PEGMA), and the like. In some embodiments, polymers
can include, but are not limited to polyhydroxyethyl methacrylate
(HEMA), cellulose, polyvinyl alcohol, polyacrylate, dextran,
polyacrylamides, polyhydroxyalkyl acrylates, polyvinyl
pyrrolidones, and mixtures and copolymers thereof. In some
embodiments, suitable polymers for use with the ion-permeable
polymeric matrix described herein include those that are
transparent.
[0086] In yet other embodiments, the outer barrier layer can be
formed from porous materials such as, agarose, alginates, collagen,
polyethylene glycol (PEG), gelatin, glass, borosilicate glass, or
mixtures or derivatives thereof. In some embodiments, the outer
barrier layer is formed from glass. In some embodiments, the outer
barrier layer is formed from borosilicate glass.
Structural Reinforcing Element
[0087] As discussed above, the outer barrier layer of the sensing
element can include a structural reinforcing element disposed
within the outer barrier layer. In other embodiments, the
structural reinforcing element can be disposed on the outer or
inner surfaces of the outer barrier layer. In some embodiments, the
structural reinforcing element can be formed from an ion-permeable
material. In other embodiments, the structural reinforcing element
can be formed form a non-permeable material.
[0088] Materials suitable for use with the structural reinforcing
elements herein can include polyesters, such as polyethylene
terephthalate (e.g., Dacron.RTM.); polyurethanes, including but not
limited to Tecothane.RTM. aromatic polyether-based thermoplastic
polyurethanes (TPUs); polyethylene; polypropylene; nylon; silk;
polymethylmethacrylate (PMMA); sintered titanium; deep reactive-ion
etched silicon; sintered stainless steel; sintered silica; liquid
crystal; alumina; ceramic; glass; borosilicate glass; and the
like.
[0089] In some embodiments, the structural reinforcing element can
exhibit a stiffness greater than the material of the outer barrier.
In some embodiments, the structural reinforcing element can be
about 10, 20, 30, 40, 50, 60, 80, 100, 150, 200, 300, 400, 500,
600, 700, 800, 900, 1000, 1500, 2000, or 2500 percent stiffer than
the outer barrier layer material. In some embodiments, the
structural reinforcing element can greater than 3000 percent
stiffer than the outer barrier layer material.
[0090] In some embodiments, the structural reinforcing element can
exhibit rigidity greater than the material of the outer barrier. In
some embodiments, the structural reinforcing element can be about
10, 20, 30, 40, 50, 60, 80, 100, 150, 200, 300, 400, 500, 600, 700,
800, 900, 1000, 1500, 2000, or 2500 percent more rigid than the
outer barrier layer material.
[0091] In some embodiments, the structural reinforcing element can
exhibit greater tensile strength than the material of the outer
barrier. In some embodiments, the structural reinforcing element
can exhibit about 10, 20, 30, 40, 50, 60, 80, 100, 150, 200, 300,
400, 500, 600, 700, 800, 900, 1000, 1500, 2000, or 2500 percent
more tensile strength than the outer barrier layer material.
[0092] In some embodiments, the structural reinforcing element can
include a woven material. In some embodiments, the structural
reinforcing element can include a woven material made from an
ion-permeable polymeric material. In some embodiments, the
structural reinforcing element can include a woven material made
from a non-permeable material. In some embodiments, the woven
material can include a uniform weave pattern of fibers throughout
the entirety of the structural reinforcing element. In other
embodiments, the woven material can include a non-uniform weave
pattern of fibers throughout the entirety of the structural
reinforcing element. In some embodiments, the woven material can
include oriented weave patterns. In other embodiments, the
structural reinforcing element can include a non-woven material
having a non-uniform weave pattern of fibers throughout the
entirety of the structural reinforcing element. An example of a
non-woven material is Tyvek.RTM., which is made from high-density
polyethylene fibers. In some embodiments, the structural
reinforcing element can include an electrospun polymeric material.
In some embodiments, the electrospun polymeric material can include
a randomly woven polymeric material.
[0093] In yet other embodiments, the structural reinforcing element
can be formed into a one-piece molded unit that can be infused with
one or more ion selective sensors.
Ion Selective Sensors
[0094] In accordance with the embodiments herein, sensing elements
202 can include one or more ion selective sensors included within
one or more types of indicator beads, or infused within the
structural reinforcing elements as described herein. Ion selective
sensors may either rely on surface phenomena or on concentration
changes inside the bulk of a phase. Ion selective sensors can
include optical sensors, including both non-carrier optical sensors
and carrier-based optical sensors, and ion-selective electrodes
(ISEs). In some embodiments, the ion selective sensor is
fluorimetric, and can include a complexing moiety and a fluorescing
moiety. Fluorimetric ion selective sensors can exhibit differential
fluorescent intensity based upon the complexing of an analyte to a
complexing moiety. In some embodiments, the ion selective sensor
can be colorimetric, and can include a complexing moiety and a
colorimetric moiety. Colorimetric ion selective sensors can exhibit
differential light absorbance based upon the complexing of an
analyte to a complexing moiety.
[0095] In some embodiments, the ion selective sensor comprises a
non-carrier or carrier-based fluorescent or colorimetric ionophoric
composition that comprises a complexing moiety for reversibly
binding an ion to be analyzed, and a fluorescing or colorimetric
moiety that changes its optical properties as the complexing agent
binds or releases the ion. The complexing agents of the invention
can optionally be appended with one or more organic substituents
chosen to confer desired properties useful in formulating the ion
sensing composition. By way of example, the substituents can be
selected to stabilize the complexing agent with respect to leaching
into the solution to be sensed, for example, by incorporating a
hydrophobic or polymeric tail or by providing a means for covalent
attachment of the complexing agent to a polymer support within the
ion selective sensor.
[0096] In some embodiments, the sensing element can include ion
selective sensors such as an ionophore or a fluoroionophore.
Suitable ionophores for use with the embodiments herein can
include, but not be limited to, sodium specific ionophores,
potassium specific ionophores, calcium specific ionophores,
magnesium specific ionophores, and lithium specific ionophores.
Suitable fluoroionophores for use with the embodiments herein can
include, but not be limited to, lithium specific fluoroionophores,
sodium specific fluoroionophores, and potassium specific
fluoroionophores.
[0097] Exemplary ion selective sensors and methods for their use
are disclosed in commonly assigned U.S. Pat. No. 7,809,441, the
contents of which is herein incorporated by reference in its
entirety.
Optical Excitation and Detection Assemblies
[0098] In some embodiments, the optical excitation assembly 218 can
include solid state light sources such as GaAs, GaAlAs, GaAlAsP,
GaAlP, GaAsP, GaP, GaN, InGaAlP, InGaN, ZnSe, or SiC light emitting
diodes or laser diodes that excite the sensing element(s) 202 at or
near the wavelength of maximum absorption for a time sufficient to
emit a return signal. However, it will be understood that in some
embodiments the wavelength of maximum absorption/reflection varies
as a function of concentration in the colorimetric sensor.
[0099] In some embodiments, the optical excitation assembly 218 can
include other light emitting components including incandescent
components. In some embodiments, the optical excitation assembly
218 can include a waveguide. The optical excitation assembly 218
can also include one or more bandpass filters, high pass filter,
low pass filter, antireflection elements, and/or focusing
optics.
[0100] In some embodiments, the optical excitation assembly 218 can
include a plurality of LEDs with bandpass filters, each of the
LED-filter combinations emitting at a different center frequency.
According to various embodiments, the LEDs can operate at different
center-frequencies, sequentially turning on and off during a
measurement, illuminating the sensing element 202. As multiple
different center-frequency measurements are made sequentially, a
single unfiltered detector can be used in some embodiments.
However, in some embodiments, a polychromatic source can be used
with multiple detectors that are each bandpass filtered to a
particular center frequency.
[0101] The sensing element 202 can include one or more types of
indicator beads having embedded therein various types of ion
selective sensors, described below. Physiological analytes of
interest can diffuse into and out of the sensing element 202 and
bind with an ion selective sensor to result in a fluorimetric or
colorimetric response. Reference analytes can similarly diffuse
into and out of the sensing element 202 and serve as a control
sample. Exemplary ion selective sensors are described more fully
below.
[0102] The optical detection assembly 220 can be configured to
receive light from the sensing element 202. In an embodiment, the
optical detection assembly 220 can include a component to receive
light. By way of example, in some embodiments, the optical
detection assembly 220 can include a charge-coupled device (CCD).
In other embodiments, the optical detection assembly 220 can
include a photodiode, a junction field effect transistor (JFET)
type optical sensor, or a complementary metal-oxide semiconductor
(CMOS) type optical sensor. In some embodiments, the optical
detection assembly 220 can include an array of optical sensing
components. In some embodiments, the optical detection assembly 220
can include a waveguide. The optical detection assembly 220 can
also include one or more bandpass filters and/or focusing optics.
In some embodiments, the optical detection assembly 220 can include
one or more photodiode detectors, each with an optical bandpass
filter tuned to a specific wavelength range.
[0103] The optical excitation and detection assemblies, 218 and
220, respectively, can be integrated using bifurcated fiber-optics
that direct excitation light from a light source to one or more
sensing elements 202, or simultaneously to sensing element(s) 202
and a reference channel. Return fibers can direct emission signals
from the sensing element(s) 202 and the reference channels to one
or more optical detection assemblies 220 for analysis by a
processor, such as a microprocessor. In some embodiments, the
optical excitation and detection assemblies are integrated using a
beam-splitter assembly and focusing optical lenses that direct
excitation light from a light source to the sensing element and
direct emitted or reflected light from the sensing element to an
optical detector for analysis by a processor.
Active Agents
[0104] Various embodiments herein can include an active agent
disposed within the outer barrier layer. The active agent can be
any drug or bioactive agent which can serve as a useful
therapeutic, prophylactic, or even diagnostic agent when released
into the patient. Exemplary bioactive agents include, but are not
limited to, the following: an anti-inflammatory;
anti-proliferative; anti-arrhythmic; anti-migratory;
anti-neoplastic; antibiotic; anti-restenotic; anti-coagulation;
anti-infectives; anti-oxidants; anti-macrophagic agents (e.g.,
bisphosphonates); anti-clotting (e.g., heparin, coumadin, aspirin);
anti-thrombogenic; immunosuppressive agents; an agent that promotes
healing; steroids (e.g., a glucocorticosteroid)); and combinations
thereof.
[0105] Suitable active agents for use with the embodiments herein
can specifically include, but are not limited to anti-inflammatory
agents. In some embodiments, suitable anti-inflammatory agents can
include steroids generally and, in specific, corticosteroids. In
some embodiments, the anti-inflammatory agent can include
ketorolac, dexamethasone, hydrocortisone, prednisolone,
methylprednisolone, indomethacin, diclofenac, ketoprofen,
piroxicam, metamizol magnesium and the like. In some embodiments,
anti-inflammatory agents can be configured to be eluted shortly
after implantation of the device.
[0106] In some embodiments, suitable active agents can also include
angiogenic agents, to promote the in-growth of capillaries. In some
embodiments, angiogenic agents can be configured to be eluted at a
later time (e.g., following elution of an anti-inflammatory at an
earlier point in time) to promote the ingrowth of capillaries to
the chemical sensor.
[0107] In some embodiments, suitable angiogenic agents can include
growth factors such as vascular endothelial growth factor (VEGF),
fibroblast growth factor (FGF), platelet-derived growth factor
(PDGF), and the like. In some embodiments, the additional active
agents can include immobilized heparin to prevent blot clot
formation.
[0108] Active agents herein can be in various forms including in a
solution, as a suspension, as a particulate, or the like.
[0109] The embodiments described herein are not intended to be
exhaustive or to limit the invention to the precise forms disclosed
in the following detailed description. Rather, the embodiments are
chosen and described so that others skilled in the art can
appreciate and understand the principles and practices. Aspects
have been described with reference to various specific and
preferred embodiments and techniques. However, it should be
understood that many variations and modifications may be made while
remaining within the spirit and scope herein.
[0110] It should be noted that, as used in this specification and
the appended claims, the singular forms "a," "an," and "the"
include plural referents unless the content clearly dictates
otherwise. Thus, for example, reference to a composition containing
"a compound" includes a mixture of two or more compounds. It should
also be noted that the term "or" is generally employed in its sense
including "and/or" unless the content clearly dictates
otherwise.
[0111] It should also be noted that, as used in this specification
and the appended claims, the phrase "configured" describes a
system, apparatus, or other structure that is constructed or
configured to perform a particular task or adopt a particular
configuration to. The phrase "configured" can be used
interchangeably with other similar phrases such as arranged and
configured, constructed and arranged, constructed, manufactured and
arranged, and the like.
[0112] All publications and patent applications in this
specification are indicative of the level of ordinary skill in the
art to which this invention pertains. All publications and patent
applications are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated by reference. Nothing
herein is to be construed as an admission that the inventors are
not entitled to antedate any publication and/or patent, including
any publication and/or patent cited herein.
* * * * *