U.S. patent application number 10/209819 was filed with the patent office on 2002-12-05 for apparatus for access to interstitial fluid, blood, or blood plasma components.
Invention is credited to Gowda, Ashok, McNichols, Roger.
Application Number | 20020183604 10/209819 |
Document ID | / |
Family ID | 24300921 |
Filed Date | 2002-12-05 |
United States Patent
Application |
20020183604 |
Kind Code |
A1 |
Gowda, Ashok ; et
al. |
December 5, 2002 |
Apparatus for access to interstitial fluid, blood, or blood plasma
components
Abstract
A transcutaneous implant having a stable biological seal at the
skin interface, obviating the need for puncturing the skin to
obtain fluid samples is described. The implant includes an advanced
filtration membrane to promote neovascularization which eliminates
mass transfer problems by promoting the development of capillary
networks with transcapillary mass transfer rates high enough to
insure rapid exchange of analyte between blood and the device.
Additionally the membrane provides a bioprotective layer which
prevents transport of proteins and cellular components into the
device.
Inventors: |
Gowda, Ashok; (College
Station, TX) ; McNichols, Roger; (Bryan, TX) |
Correspondence
Address: |
Neil Steinberg
Steinberg & Whitt
Suite 514
2672 Bayshore Parkway
Mountain View
CA
94043
US
|
Family ID: |
24300921 |
Appl. No.: |
10/209819 |
Filed: |
July 31, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10209819 |
Jul 31, 2002 |
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09575591 |
May 22, 2000 |
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6459917 |
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Current U.S.
Class: |
600/345 ;
604/93.01; 606/108 |
Current CPC
Class: |
A61B 5/150022 20130101;
A61B 5/686 20130101; A61B 5/150351 20130101; A61B 5/15142 20130101;
A61B 5/6865 20130101; A61B 5/6848 20130101; A61B 5/14546 20130101;
A61B 5/14865 20130101; A61M 2039/0261 20130101; A61B 5/150839
20130101; A61M 39/0247 20130101; A61M 2039/0276 20130101; A61B
5/14528 20130101; A61M 2039/0258 20130101 |
Class at
Publication: |
600/345 ;
604/93.01; 606/108 |
International
Class: |
A61M 031/00; A61M
037/00 |
Claims
What is claimed is:
1. An transcutaneous implant comprising: an access component to
provide a stable dermal interface; a central housing disposed
within the access component, the central housing having a first end
for external access and a second end; a first septum disposed
within the central housing; and a filtration membrane disposed at
the second end of the central housing to promote neovascularization
and transfer of analyte in bodily fluid into a reservoir formed by
the filtration membrane, the first septum and the central
housing.
2. The implant of claim 1 wherein the access component includes a
neck having a first end and a second end, and skirt that extends
outwardly from the second end of the neck to anchor the access
component in subcutaneous tissue.
3. The implant of claim 2 wherein the central housing is formed
integrally with the access component and is defined by an inner
surface of the neck.
4. The implant of claim 2 wherein the central housing extends
beneath the skirt of the access component and is adapted to be
secured to a wall of an arterio-venous shunt such that the
filtration membrane resides within the arterio-venous shunt.
5. The implant of claim 2 wherein the access component is covered
by a porous covering of material that encourages cell infiltration
and formation of subcutaneous tissue and collagen.
6. The implant of claim 5 wherein the porous covering of material
includes polyester velour.
7. The implant of claim 2 wherein the skirt and neck are integrally
formed of a flexible, biocompatible material.
8. The implant of claim 7 wherein the flexible biocompatible
material is a member of a group of materials that includes flexible
medical grade polyurethane, polymethyl methacrylate (PMMA),
polyethylene (PE), polyvinyl chloride (PVC), polycarbonate,
polypropylene (PP) polydimethyl siloxane (PDMS), ethylene glycol
dimethacrylate (EGDM), polytetrafluoroethylene PTFE), and
nylon.
9. The implant of claim 2 wherein the skirt includes holes in which
deposition of fibrous collagen after implantation helps to anchor
the access component.
10. The implant of claim 1 wherein the filtration membrane includes
a material that allows passive diffusion of the analyte in the
bodily fluid, but substantially prevents transport of cells and
larger proteins.
11. The implant of claim 1 wherein the filtration membrane includes
first material to promote neovascularization.
12. The implant of claim 11 wherein the first material includes
polyvinylidene fluoride (PVDF).
13. The implant of claim 11 wherein the filtration membrane further
includes a second material which allows passive diffusion of the
analyte in the bodily fluid, but substantially prevents transport
of cells and larger proteins.
14. The implant of claim 13 wherein the second material includes
polymerized polyethylene glycol (PEG).
15. The implant of claim 13 wherein the second material is
laminated on the first material to form a discrete two-layer
filtration membrane.
16. The implant of claim 13 wherein a portion of the second
material penetrates into the first material to form a partially
embedded two-layer filtration membrane.
17. The implant of claim 13 wherein the second material is
contained within a layer of the first material to form a fully
embedded two-layer filtration membrane.
18. The implant of claim 13 wherein the filtration membrane further
includes a third material more rigid than at least one of the first
material and the second material to provide mechanical support to
the filtration membrane.
19. The implant of claim 11 wherein the first material has a pore
size ranging from 0.05 .mu.m to 40 .mu.m.
20. The implant of claim 1 wherein the first septum forms a
liquid-tight seal between the reservoir and a side of the first
septum nearest the first end of the central housing.
21. The implant of claim 20 wherein the first septum is formed of a
self-sealing material such that, after the first septum has been
penetrated by a fluid sampling/delivery device and the fluid
sampling/delivery device removed, the first septum self-seals to
re-establish the liquid-tight seal.
22. The implant of claim 21 wherein the first septum is formed from
a material that includes silicone rubber.
23. The implant of claim 1 wherein the central housing includes a
conduit disposed within the lumen of the central housing and
wherein the first septum is disposed within the conduit and the
filtration membrane is disposed at an end of the conduit adjacent
the second end of the central housing.
24. The implant of claim 23 wherein the conduit is formed
integrally with the central housing, the conduit being defined by
an inner surface of the central housing.
25. The implant of claim 23 wherein the conduit is formed of a
rigid biocompatible material.
26. The implant of claim 23 further comprising a cap disposed over
an end of the conduit adjacent the first end of the central
housing.
27. The implant of claim 23 further comprising a second septum
disposed within the conduit nearer the first end of the central
housing than the first septum, the first and second septa defining
a chamber within the conduit.
28. The implant of claim 23 further comprising a support member
disposed within the conduit to support the first septum, the first
septum being disposed within the conduit adjacent the support
member.
29. The implant of claim 1 further comprising a cap disposed over
the first end of the central housing.
30. The implant of claim 1 further comprising a second septum
disposed within the central housing nearer the first end than the
first septum, the first and second septa defining a chamber within
the central housing.
31. The implant of claim 30 wherein the second septum forms a
liquid-tight seal between the chamber and a side of the second
septum nearest the first end of the central housing.
32. The implant of claim 1 wherein the filtration membrane is
attached to the central housing using a medical grade adhesive.
33. The implant of claim 1 wherein the filtration membrane extends
outwardly to form a filtration surface area that exceeds an area of
a cross section of the second end of the central housing.
34. The implant of claim 1 further comprising a safety stop to
prevent a fluid sampling/delivery device from contacting the
filtration membrane.
35. The implant of claim 34 wherein the safety stop is disposed
within the reservoir, the safety stop including an aperture to
permit the analyte to pass between the reservoir and the fluid
sampling/delivery device.
36. The implant of claim 1 wherein the reservoir is lined with an
antibacterial coating.
37. The implant of claim 36 wherein the antibacterial coating
includes silver.
38. The implant of claim 1 wherein the first septum is removable
from the central housing to allow replacement thereof.
39. The implant of claim 1 further comprising a sampling stop
disposed at the first end of the central housing to limit the
insertion of a fluid sampling/delivery device such that the device
is prevented from contacting the filtration membrane.
40. The implant of claim 39 wherein the sampling stop includes a
stop wall adapted to engage a flange of the fluid sampling/delivery
device, the stop wall including an aperture to receive a narrower
portion of the fluid sampling/delivery device such that a tip of
the narrower portion of the fluid sampling/delivery device rests
within the reservoir when the flange of the fluid sampling/delivery
device engages the stop wall.
41. The implant of claim 39 wherein the sampling stop is removable
from the implant.
42. The implant of claim 1 wherein the central housing is adapted
to engage an analyte measurement device and fluid sampling device
such that the analyte in the reservoir is communicated to the
analyte measurement device via the fluid sampling device and
measured by the analyte measurement device while the analyte
measurement device and fluid sampling device are engaged by the
central housing.
43. A sensing system having a transcutaneous implant device
comprising: an electroenzymatic sensor; a transcutaneous implant
device, including: an access component to provide a stable dermal
interface; a central housing disposed within the access component,
the central housing having a first end for external access and a
second end; a first septum disposed within the central housing; and
a filtration membrane disposed at the second end of the central
housing to promote neovascularization and transfer of analyte in
bodily fluid into a reservoir formed by the filtration membrane,
the first septum and the central housing.
44. The sensing system of claim 43 wherein the electroenzymatic
sensor includes a chemical sensor disposed within the reservoir and
first and second terminals disposed adjacent the first end of the
central housing and coupled to the chemical sensor via respective
electrical conductors.
45. The sensing system of claim 43 wherein the electroenzymatic
sensor further includes a fluid withdrawal port to allow periodic
withdrawal of the analyte.
46. The sensing system of claim 43 wherein the electroenzymatic
sensor is removable.
47. The sensing system of claim 43 further comprising a display
device coupled adjacent the first end of the central housing, the
display device cooperating with the electroenzymatic sensor to
display a measure of the analyte.
48. The sensing system of claim 47 wherein the display device is a
wristwatch style device.
49. An apparatus for safely withdrawing bodily fluid from a
transcutaneous implant, the apparatus comprising: a projecting
portion adapted to extend through a septum of the transcutaneous
implant and into a collection reservoir of the implant; and a
flange adapted to engage a stop wall of the transcutaneous implant
such that the projecting portion of the apparatus is prevented from
contacting a filtration membrane of the transcutaneous implant.
50. The apparatus of claim 49 wherein the projecting portion
includes a non-coring needle.
51. The apparatus of claim 49 further comprising: a chamber; and an
aspirator to draw the bodily fluid from the collection reservoir
into the chamber.
52. The apparatus of claim 51 wherein the aspirator is a plunger
slideably disposed within the chamber and wherein the bodily fluid
is drawn from the collection reservoir into the chamber when the
plunger is slideably withdrawn from the chamber.
53. An apparatus for safely withdrawing bodily fluid from a
transcutaneous implant, the apparatus comprising: a chamber; an
aspirator operable to create suction pressure within the chamber;
and a projecting portion adapted to extend through a septum of the
transcutaneous implant and into a collection reservoir of the
transcutaneous implant, the projecting portion including a tip
having an aperture, and a passage extending between the chamber and
the aperture, the tip of the projecting portion being configured to
engage a safety stop disposed within the collection reservoir of
the transcutaneous implant such that tip of the aperture is
prevented from contacting a filtration membrane of the
transcutaneous implant and such that the aperture is unblocked and
able to receive the bodily fluid when the aspirator is operated to
create suction pressure within the chamber.
54. The apparatus of claim 53 wherein the projecting portion is
configured to prevent coring of the septum when extended there
through.
55. A septum for forming a liquid-tight seal within a lumen of a
transcutaneous implant, the septum comprising: an outer surface for
engaging the lumen of the transcutaneous implant; and a first
self-sealing aperture disposed within the outer surface.
56. The septum of claim 55 wherein the outer surface for engaging
the lumen of the transcutaneous implant includes threads to
screwably insert the septum into the lumen of the transcutaneous
implant.
57. The septum of claim 55 further comprising a second self-sealing
aperture disposed within the outer surface, the first and second
self-sealing apertures being positioned at respective ends of the
septum.
58. The septum of claim 55 wherein the septum further comprises a
stop surface to engage a stop wall of the lumen of the
transcutaneous implant to establish appropriate disposition of the
septum within the lumen.
Description
BACKGROUND OF THE INVENTION
[0001] The invention is directed to an apparatus for intradermal
implantation of a device to facilitate repeated, painless, safe,
and reliable access to interstitial fluid, blood, or blood plasma
for monitoring of blood borne or tissue analyte concentrations
including but not limited to glucose, cholesterol, lactate,
bilirubin, blood gases, ureas, creatinine, phosphates, myoglobin
and hormones or delivery of drugs or other injectable agents such
as chemotherapeutic agents, photosensitizing agents, hormones,
vaccines, or radiological or other contrast agents.
[0002] There is now a large body of evidence that intensive
management of blood sugars is an effective means to slow or even
prevent the progression of diabetic complications such as kidney
failure, heart disease, gangrene, and blindness. The design and
development of a simple apparatus for obtaining interstitial fluid,
blood or blood plasma samples without breaking the skin would be a
large advancement in trying to improve diabetic patient compliance
for monitoring blood glucose levels.
[0003] Maintaining blood glucose concentrations near normal levels
in diabetic patients can only be achieved with frequent blood
glucose monitoring so that appropriate actions can be taken, such
as insulin injections, or sugar ingestion. Unfortunately the
current methods of sensing are based on colorimetric or
electro-enzymatic approaches that require a blood or interstitial
fluid sample each time a reading is needed. Withdrawal of a blood
or interstitial fluid sample currently requires invasive methods of
penetrating the skin surface. These methods are both time-consuming
and painful and therefore there is a significant lack of compliance
among the diabetic population for monitoring their blood glucose
levels for the recommended five or more times daily.
[0004] Several research groups have focused efforts on methods for
minimally invasive withdrawal of (primarily) interstitial fluid
including the use of electrical current, suction, penetration,
microdialysis, and laser-assisted drilling of the stratum corneum.
While these techniques have shown some preliminary promise,
questions still remain as to the volume of fluid which can be
obtained, the repeatability of samples obtained, and the lack of
any significant improvement in skin trauma related to the sampling
methods. Additionally, the accuracy of glucose measurements on such
small samples of interstitial fluid will likely be highly sensitive
to contaminants from sweat or dirt on the surfaces being sampled
and requires development of new measurement technology appropriate
for such small or low concentration samples. Therefore, the ability
to directly withdraw interstitial fluid samples in an easy,
reliable and safe manner would be a significant advance in
minimally invasive sensing techniques.
[0005] Other groups are developing totally implantable sensors for
measurement of blood or interstitial fluid glucose concentration.
Normally, however, when a foreign body such as a medical implant is
introduced into a host, the natural tendency of the surrounding
tissue is to degrade or extrude the implant. If the host cannot
eliminate the foreign body, a chronic inflammatory reaction results
and the object is encapsulated in fibrous tissue with foreign body
giant cells residing at the tissue-material interface. This capsule
poses a difficult problem in the development of implanted sensing
or sampling devices. In the case of interstitial fluid sampling,
the fibrous capsule presents a mass transfer barrier and therefore
limits the concentration of analyte reaching the collection site.
Also, encapsulated implants may exhibit a significant lag time in
the response to changes in blood glucose concentration. The ability
of the capsule to limit mass transfer has been demonstrated in
several studies (see, for example, Wood et al., Assessment of a
Model for Measuring Drug Diffusion Through Implant-Generated
Fibrous Capsule Membranes, Biomaterials. 16:957-9, (1995)).
SUMMARY OF THE INVENTION
[0006] The present invention is directed to a method and apparatus
for analyte detection which substantially overcomes one or more of
the problems due to the limitations and disadvantages of the
related art. More specifically, the present invention is directed
to a transcutaneous implant, methods for implanting and using the
transcutaneous implant and fluid withdrawal/delivery implements and
replaceable components for use with the transcutaneous implant. In
one embodiment, the transcutaneous implant includes an access
component to provide a stable dermal interface, a central housing
disposed within the access component, a septum disposed within the
central housing, and a filtration membrane disposed at a distal end
of the central housing to promote mass transfer of analyte in
bodily fluid into a reservoir formed by the filtration membrane,
the septum and the central housing.
[0007] These and other features and advantages of the present
invention will be apparent from the accompanying drawings and from
the detailed description and claims that follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The present invention is illustrated by way of example, and
not by way of limitation, in the figures of the accompanying
drawings and in which like reference numerals refer to similar
elements and in which:
[0009] FIG. 1A is an elevational perspective side view of the
implantable access port in accordance with the present
invention;
[0010] FIG. 1B is an elevational cross-section of the implantable
access port shown in FIG. 1A;
[0011] FIG. 1C is an elevational perspective side view of the
transcutaneous access component according to one embodiment of the
present invention;
[0012] FIG. 1D is an elevational perspective side view of the
advanced filtration membrane component of the present
invention;
[0013] FIG. 1E is an elevational perspective side view of the
housing component which contains safety valves and reservoir of the
present invention;
[0014] FIG. 2A is an elevational cross-section of another
embodiment of a port for access to the blood space in accordance
with the present invention;
[0015] FIG. 2B is an elevational cross section of another
embodiment of the access port that includes a specially shaped
filtration membrane to enhance mass transfer;
[0016] FIG. 2C is an elevational side view of another embodiment of
the access port in which a safety stop is included within the
collection chamber to prevent damage to the filtration membrane and
the collection chamber is coated with an antibacterial agent;
[0017] FIG. 2D is a cross-sectional view of an another embodiment
the of the access port of the present invention;
[0018] FIG. 2E is a cross-sectional view of yet another embodiment
the of the access port of the present invention;
[0019] FIG. 2F is a cross-sectional view of an another embodiment
the of the access port of the present invention;
[0020] FIG. 3A illustrates a side view of the access port of the
present invention which has been implanted;
[0021] FIG. 3B illustrates a side view of the access port of the
present invention which has been implanted and is in use with a
device for collection or delivery of fluid;
[0022] FIG. 4A illustrates a side view of an implanted access port
according to an embodiment that includes an external sampling
stop;
[0023] FIG. 4B illustrates insertion of a sampling device that
includes a needle into the implanted access port of FIG. 4A;
[0024] FIG. 5A illustrates a side view of an implanted access port
used in conjunction with an external analyte measurement
device;
[0025] FIG. 5B illustrates a side view of an implanted access port
according to an embodiment that includes a replaceable
electro-enzymatic sensor;
[0026] FIG. 5C illustrates a close up side view of the replaceable
sensor included in the implanted access port of FIG. 5B; and
[0027] FIG. 5D illustrates the implantable access port and
replaceable electroenzymatic sensor of FIG. 5B used in conjunction
with a wristwatch style measurement device.
DETAILED DESCRIPTION
[0028] The invention disclosed herein eliminates many of the
problems associated with prior art methods for fluid withdrawal. In
one embodiment, a transcutaneous implant is provided, obviating the
need for puncturing the skin to obtain fluid samples. The implant
promotes a stable biological seal at the skin interface and
prevents capsule formation and exit site infection. The implant
includes an advanced filtration membrane that eliminates the mass
transfer problem by promoting capillary networks with
transcapillary mass transfer rates high enough to insure rapid
exchange of analyte between blood and the device. There are several
strategies for promoting this neovascularization, including
prevascularization, the release of angiogenic factors, and
microarchitecture-driven neovascularization.
[0029] Certain microporous materials allow blood vessels to grow
and be maintained at the tissue-material interface and in some
cases within the pores of the material. However this is not true
for all porous polymer membranes, even those with similar
porosities and chemistries. What influences the host response is
not necessarily the chemistry of the material, but the
microstructure of individual features within the material onto
which host cells can attach. Materials that are microporous but
contain large planar features promote an avascular host response
while the same material lacking these planar features and having a
more fibrous structure promote neovascularization at the
tissue-material interface. Thus, in embodiments of the present
invention, microporous polymers having a fibrous structure are
integrated into the implanted transport membrane to reduce fibrosis
and enhance neovascularization.
[0030] An embodiment of the present invention is illustrated in
FIGS. 1A-1E. As shown in FIG. 1A, an implantable access port (IAP)
1 includes three main components. First, the device includes an
access component 5 for providing a stable dermal interface for the
transcutaneous implant. Second, the device uses an advanced
filtration membrane 10 engineered to promote improved mass transfer
between analytes in the blood and those collected by the device.
Finally, a central housing 15 with septa 20 that form self-sealing
apertures and a reservoir 25 for storage of fluid prior to
collection is provided. Annular support members 19 are affixed to
the central housing 15 (or formed integrally with the central
housing) to support and position the septa 20.
[0031] Using needles, capillary tubes or other aspirating device,
interstitial fluid, blood or blood plasma can be sampled from the
access port 1 in a painless fashion since the skin at the exit site
is effectively removed. Practice of this device by a diabetic
patient would allow the patient to monitor blood glucose levels
more frequently and maintain approximately normal 24-hour
blood-glucose profiles thereby reducing complications related to
the disease.
[0032] The preferred embodiment of this invention is described
below. Alternate embodiments are listed as well. The design of the
IAP is based on providing a stable interface for the implant at an
externally located site and incorporating a suitable membrane for
long-term biocompatibility and filtration performance.
[0033] Access Component
[0034] The access component 5 shown in FIG. 1C includes a flat,
disc-shaped skirt 30 having a central opening 35 and an array of
through holes 40 distributed around the discshaped skirt 30.
Extending out from one side of the skirt 30 in registration with
the opening is an integral tubular neck 45 whose lumen 50 is in
registration with the opening of the skirt 35. The access component
5, including the skirt 30 and neck 45, is preferably formed of a
flexible, thermally stable, biocompatible material such as flexible
medical grade polyurethane, polymethyl methacrylate (PMMA),
polyethylene (PE), polyvinyl chloride (PVC), polycarbonate,
polypropylene (PP) polydimethyl siloxane (PDMS), ethylene glycol
dimethacrylate (EGDM), polytetrafluoroethylene PTFE), nylon or the
like.
[0035] Preferably, the entire body of the skirt 30 and neck 45 is
covered by a porous covering or bed 55 of material such as
polyester velour (U.S. Catheter and Instrumentation Company of
Glenfalls, N.Y. Part # 600k61121). In one embodiment, the thickness
of the covering 55 preferably may range from 0.01 mm to 1.5 mm, and
even more preferably is about 0.1 mm. The covering encourages cell
infiltration and the formation of subcutaneous tissue and collagen.
The overall design of the access component 5 may be as set forth in
U.S. Pat. No. 5,662,616, which is hereby incorporated herein by
reference.
[0036] In the present invention, the skirt 30 preferably has a
diameter ranging from 0.2 to 4.0 cm, even more preferably about 2.5
cm. The thickness of the skirt 30 preferably may range from 0.05 to
about 0.5 cm, and even more preferably is about 0.2 cm. The central
opening of the skirt and lumen 35 of the neck preferably may range
from 0.1 to 3.0 cm in diameter, and even more preferably are about
0.7 cm. The outer diameter of the neck 45 preferably may range from
0.25 to 2.0 cm, and even more preferably is about 1.0 cm. The
height of the entire access component 5 preferably ranges from
about 0.25 to about 2.5 cm, and even more preferably is about 1.0
cm.
[0037] Advanced Filtration Membrane
[0038] FIG. 1D illustrates the advanced filtration membrane 10
according to one embodiment. The membrane 10 is designed to allow
for passive diffusion of analytes in interstitial fluid (ISF) while
preventing transport of cells and larger proteins. The filtration
membrane 10 is preferably constructed from a polyvinylidene
fluoride (PVDF) membrane 60, although other materials may be used
including, but not limited to, cellulose acetate, mixed esters of
cellulose, polysulfone, polyester, polypropylene, cellulose
nitrate, polycarbonate, nylon (charged and uncharged),
polyethylene, and vinyl acetate ethylene copolymers. The PVDF
membrane 60 is used to promote microachitecture-driven
neovascularization 62. To prevent cells from entering the
collection reservoir 25, the surface of the PVDF membrane 60
adjacent the reservoir 25 is laminated with an ultrafiltration
membrane 65 consisting of any biocompatible material with pore
sizes of less than 1.0 .mu.m. Preferably, the ultrafiltration
membrane is constructed using a hydrogel of photopolymerized
polyethylene glycol (PEG). The molecular weight of the PEG membrane
may range in size from 100 Da to 50 Kda or more preferably 575 Da.
(Sigma Chemical). In one embodiment, the laminated filtration
membranes 10 are formed by spin coating aqueous hydrogel precursor
solutions on the inside of the PVDF membrane 60 (e.g., a precursor
solution consisting of 23% PEG-dacrylate and 0.1%
2,2'-dimethoxy-2Dipheny- lacetophenone (Sigma Chemical Part #
24650-42-8), a UV-activated free radical polymerization agent). The
high viscosity of the solution and surface tension between the PVDF
membrane and the precursor solution does not allow significant
solution penetration into the pores of the PVDF membrane and
therefore does not inhibit neovascularization. The coated PVDF
membrane 60, is then illuminated by UV light (e.g., 365 nm, 20
mW/cm.sup.2) at a distance of approximately 1 cm until complete
polymerization has taken place (typically two to ten seconds or
less). The filtration membrane 10 is then attached to the housing
15 using a medical grade adhesive (e.g., an epoxy such as Loctite #
4981).
[0039] In one embodiment, the PVDF membrane 60 has a pore size
ranging from 0.05 .mu.m to 40 .mu.m, preferably about 5 .mu.m. The
thickness of the filtration membrane 10 preferably may range from
10 .mu.m to 500 .mu.m, and even more preferably is about 100 .mu.m.
The diameter of the filtration membrane 10 preferably ranges from
0.1 to 3.0 cm in diameter, and even more preferably is about 0.7
cm.
[0040] In short, the filtration membrane is designed to promote
neovascularization on the tissue interfacing side while preventing
cellular passage with a bioprotective layer on the device side. As
mentioned above, PEG is preferable but many materials with pore
sizes too small for cells to pass through may be used. In addition,
as mentioned above, photopolymerized PEG is suitable but other
techniques of polymerization of the PEG are acceptable, for
example, thermal or chemical methods may be used to initiate
polymerization of the PEG.
[0041] Implant Housing
[0042] As depicted in FIG. 1E, the central housing 15 includes a
conduit 70 with septa 20 contained within the conduit 70. The
distal end of the conduit 75 is sealed with the filtration membrane
10. The portion of the conduit between the top of the filtration
membrane 10 and the bottom of the lower septum 20 form the
collection reservoir 25. The top of the conduit 70 contains a cap
80 to prevent debris and contaminants from entering the conduit 70
when the implant 1 is not in use. Although the cap depicted in FIG.
1E is a hinged, spring-loaded cap, numerous other cap designs may
be used including, without limitation, a removable, snap-on or
screw on cap.
[0043] The conduit 70 is preferably formed of stainless steel
tubing or other rigid biocompatible material. Alternatively, the
conduit may be formed integrally with the housing unit 15, being
defined by the lumen thereof. The outer diameter of the housing
element 15 may range from 0.1 to 2.0 cm, and is preferably about
0.7 cm. The lumen diameter of the housing element 15 may range from
0.125 to 1.775 cm, and is preferably about 0.5 cm. Each of the
septum 20 is preferably constructed of a elastic, self-sealing
biocompatible material, more preferably silicone rubber and is
sized to fit snugly within the lumen of the conduit, thus providing
a liquid-tight seal between the collection reservoir 25 and the
upper portion of the conduit. The thickness of the individual
septum 20 preferably may range from 0.05 to 1.0 cm and more
preferably is about 0.3 cm. The distance between the bottom of the
lower septum 20 and the filtration membrane 10 defines the depth of
the collection reservoir 25 and preferably may range from 0.05 cm
to 2.0 cm and more preferably is about 0.2 cm. The resulting volume
of the collection reservoir 25 may range from 0.6 .mu.l to 5.0 ml
and more preferably is about 40 .mu.l.
[0044] FIG. 2A illustrates an alternative embodiment of an
implantable access port designed to be used for filtration of blood
components. The implant includes a transcutaneous access component
85 with a central housing component 90 connected to an
arterio-venous shunt 95. The distal end of the housing component
100 is secured to the wall of the arterio-venous shunt such that an
appropriate filtration membrane 103 resides within the lumen of the
arterio-venous shunt 105. Blood flowing through the arterio-venous
shunt 95 is thereby filtered by the filtration membrane 103 and
fluid is subsequently collected through the housing 90.
[0045] FIG. 2B illustrates a further embodiment of an implantable
access port described above modified such that the filtration
membrane 110 is shaped to increase the surface area and hence mass
transport between the tissue space and collection reservoir of
analytes in interstitial fluid, blood, or blood plasma.
[0046] FIG. 2C illustrates a further embodiment of the collection
reservoir in which a safety stop 115 is incorporated to prevent the
aspirating device such as needles or capillary tubes from damaging
the filtration membrane and a coating of silver 120 is used to
prevent bacterial accumulation in the collected fluid. As shown in
FIG. 2C, the safety stop includes apertures along its circumference
to permit analyte to pass in either direction between the reservoir
and the aspirating device (or an agent delivery device).
Preferably, the aspirating or delivery device having a side opening
to the fluid intake or exhaust port to avoid blockage when the tip
of the aspirating or delivery device contacts the bottom of the
safety stop. In an alternative embodiment, apertures smaller than
the tip of the aspirating or agent delivery device may be
distributed throughout the surface of the safety stop, permitting a
fluid intake or exhaust port to be located anywhere on the
aspirating or agent delivery device, including on the bottom of its
tip.
[0047] FIG. 2D is a cross-section of the implantable access port
shown in FIG. 1A demonstrating alternative configurations for
layers contained in the advanced filtration membrane 10. The
advanced filtration membrane 10 may be composed of a discrete
twolayer filtration membrane 140. In this configuration the PVDF
membrane 60 is coated with a discrete layer of PEG membrane 65.
Alternatively the advanced filtration membrane 10 may be composed
of a partially embedded 2-layer filtration membrane 141 in which
the PEG ultrafiltration membrane 65 partially penetrates a small
distance into the PVDF membrane 60. In another alternative, the
advanced filtration membrane 10 may be composed of a fully embedded
2-layer filtration membrane 142. In this configuration the full
thickness of the PEG ultrafiltration membrane 65 is contained
within a thickness of the PVDF membrane 60. In yet another
alternative, the advanced filtration membrane 10 may be composed of
a three layer filtration membrane 143. In this configuration a
membrane support screen 64 is included to provide additional
support to the filtration membrane 10. The membrane support screen
may consist of any semi-rigid or rigid material but is preferably
made using a stainless steel screen.
[0048] FIG. 2E is a cross-section of the implantable access port
shown in FIG. 1A demonstrating alternative configurations for the
housing 15 in which a replaceable septa insert 130 is incorporated.
In this embodiment, the septa 20 are contained within a replaceable
insert 130. The replaceable insert 130 may contain a threaded wall
135 such that once the septa 20 become worn to the point that they
no longer self-seal, the user may unscrew the insert 130 and
replace it with a new one. The new septa insert 130 is screwed into
the threaded wall of the housing until it abuts a stop wall 131,
thus allowing the inert 130 to be properly disposed within the
lumen of the housing 15 (or conduit as shown in FIG. 1E). Other
mechanisms for securing the replaceable insert may also be used
including, without limitation, friction holds, mechanical catches
and the like.
[0049] FIG. 2F is a cross-section of the housing 15 in which only a
single self-sealing septum 20 is used. Any of the alternative
embodiments may contain a single self-sealing septum 20 as opposed
to the two-septum configuration as shown in FIG. 1B.
[0050] Turning to the operation of the preferred embodiment of the
present invention, referring to FIG. 3A, the access port 1 is
implanted so that the skirt 30 of the access component 5 is
anchored in the subcutaneous tissue 200 and the neck 45 of the
access component 5 penetrates the dermal 205 and epidermal layer
210 of the skin. After implantation, fibrous collagen begins to
deposit in the holes 40 in the skirt 30 to help anchor the access
component 5. The velour covering 55 provides a porous,
fibrous-structure bed to encourage the growth of tissue and
collagen around the skirt 30 to provide a biological seal with the
epidermal cells which migrate and invaginate along the neck 50
until they reach the covering.
[0051] The housing component 15, which is fixed within the access
component 5, provides for collection of fluid from the body without
requiring breaking the skin barrier. The filtration membrane 10
attached to the housing 15 allows passage of interstitial fluid,
blood, or blood plasma while preventing larger cells and proteins
from entering the collection reservoir 25. The fluid filtered by
the membrane and stored in the collection reservoir becomes the
sample for analyte measurement using any applicable small volume
sensor.
[0052] In the preferred embodiment, as shown in FIG. 3B, the access
port 1 is designed to be used in conjunction with a sampling device
215. The sampling device 215 may be a needle or catheter, but is
preferably a specially designed capillary tube 220 with an integral
stop 225 such that it can not be introduced far enough to damage
the filtration membrane 10. The sampling device 215 is passed
through the self-sealing septa such that the distal end of the
sampling device 230 is positioned within the collection reservoir
25 but does not come in contact with the filtration membrane 10.
Fluid is drawn within a collection chamber of the sampling device
215 by capillary action or aspirating the proximal end of the
sampling device 215 (e.g., by slideably withdrawing a plunger from
the chamber of the sampling device 215).
[0053] Alternatively the implantable access port described herein
may be used to deliver agents into the body. Such agents might
include, but are not limited to, drugs, hormones, chemotherapeutic
agents, photosensitizing agents, vaccines, radiological, or
contrast agents. In operation, the agent to be administered would
be placed within the collection reservoir 25 (now being used as a
delivery reservoir) and the membrane 10 would be designed to allow
passage of the agent into the subcutaneous fluid or blood space. Of
particular interest, is the operation of the implantable access
port to deliver insulin or for use in combination with insulin
pumps.
[0054] The implantable access port described herein may be
implanted anywhere on the body having a soft tissue layer
sufficiently thick to accommodate the protrusion of the access port
into the subdermal space. Preferably the implant is placed on the
wrist or arm area for easy patient access and may include a device
or implement to cover the port such as a wrist watch interface or
skin colored bandage to improve patient acceptance of the aesthetic
qualities of the device. Further, for durability, the access port
is preferably placed somewhere on the body which is not subject to
a lot of exposure or contact such as the abdomen.
[0055] As seen from the foregoing, the implantable access port
provides a method for withdrawal of body fluids without requiring
breach of the skin barrier. The implantable access port also
provides for filtration of interstitial fluid, blood, or blood
plasma resulting in a sample of fluid containing an analyte of
interest. Because of its porosity and fibrous structure, the access
port forms an infection-free, transcutaneous implant having a
biological seal around the device. Therefore, the implant is
suitable for long term use. Since the implant resides in the plane
between the subcutaneous and dermal layers of tissue, subsequent
removal is simple if necessary. Additionally, the access port has
relatively few components and may be easily manufactured with
common, readily available materials. Once implanted, the withdrawal
of fluid from the body can be performed in a painless and reliable
manner.
[0056] FIG. 4A illustrates a side view of an embodiment of an
implanted access port which includes an external sampling stop 235
for providing safe access to the interstitial fluid without
damaging the filtration membrane 10. As shown in FIG. 4B, the
external sampling stop 235 permits a needle 217 to be used with the
sampling device 215 in a safe manner. The sampling device 215 is
inserted into the external sampling stop 235 until a flange at the
forward end of the sampling device abuts a stop wall 237. As the
sampling device 215 is inserted into the sampling stop 235, the
needle 217 extends through an aperture in the stop wall 237, passes
through the self-sealing septa 20 and comes to rest with the tip
located just within the reservoir 25. The needle is preferably a
non-coring needle (Part No. 7165, Popper & Sons, Inc., New Hyde
Park, N.Y.) to prevent coring of the self-sealing septa 20. The
sampling stop 235 can be custom designed according to the needle
217 and sampling device 210 used. In one embodiment, the sampling
stop is removable, for example by unplugging or unscrewing from the
implant 1, thus permitting sampling stops having various profiles
and receptacle shapes to be used interchangeably. In an alternative
embodiment, the sampling stop 235 forms part of the implant and is
capped by an end cap as discussed above (see, for example, FIG. 1E,
element 80).
[0057] FIG. 5A illustrates a side view of the implanted access port
used in conjunction with an external analyte measurement device. In
this embodiment an external analyte measurement device 240 is
interfaced with the sampling device 215. This configuration allows
for interstitial fluid withdrawn from the device and containing the
analyte of interest to be directly communicated to an external
analyte measurement device 240.
[0058] FIG. 5B illustrates a side view of an implanted access port
that incorporates a replaceable electro-enzymatic sensor 245. In
one embodiment, the sensor chemistry 260 is contained with the
electroenzymatic sensor 245 and is placed within the reservoir 25
containing the interstitial fluid. Such a sensor chemistry is
described in detail by Quinn et al. (Photo-crosslinked copolymers
of 2 hydroxyethyl methacrylate, poly(ethylene glycol)
tetra-acrylate and ethylene dimethacrylate for improving
biocompatibility of biosensors), the entire content of which is
hereby incorporated by reference. In the embodiment shown in FIG.
5B, a working electrode terminal 250 and a reference electrode
terminal 255 are incorporated on the replaceable sensor 245 such
that they are located outside the access port 1 with electrical
conductors that are connected with the sensor chemistry 260. By
this arrangement, an external analyte measurement device 240 may be
interfaced with the replaceable sensor 245 to provide a measurement
of the analyte of interest. FIG. 5C illustrates a close up side
view of the replaceable sensor 245. The sensor 245 may also contain
a fluid withdrawal port 252 that would allow the user to withdraw
interstitial fluid periodically in order to calibrate the
electroenzymatic sensor 245. Alternatively, the sensor 245 can be
removed from the access port 1 and calibrated in known
standards.
[0059] FIG. 5D illustrates the implantable access port and
replaceable electroenzymatic sensor of FIG. 5B used in conjunction
with a wristwatch style measurement display device. In this
embodiment, a wristwatch style analyte measurement display device
265 may be continuously worn over the access port 1 and replaceable
sensor 245 to display continuous measurement of the analyte of
interest. Numerous other styles and configurations of measurement
display devices may be worn over the access port in alternative
embodiments.
[0060] While the present invention has been described with
reference to illustrative embodiments that include specific
details, such embodiments and details should not be construed as
limiting the scope of the invention. For example, though numerous
preferences for shapes, materials, sizes and configurations have
been described, other shapes, materials, sizes and configurations
may be used without departing from the spirit and scope of the
present invention. Those having ordinary skill in the art and
access to the teachings provided herein will recognize additional
modifications, applications, and embodiments within the scope the
invention described herein and additional fields in which the
invention would be of significant utility without undue
experimentation. Thus the scope of the invention should be
determined by the appended claims and their legal equivalents,
rather than by the examples given.
* * * * *