U.S. patent application number 16/882182 was filed with the patent office on 2020-11-12 for implantable sensor apparatus and methods.
The applicant listed for this patent is GLYSENS INCORPORATED. Invention is credited to Robert ENGLER, Joseph LUCISANO, Jonathan WILENSKY.
Application Number | 20200352480 16/882182 |
Document ID | / |
Family ID | 1000004978042 |
Filed Date | 2020-11-12 |
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United States Patent
Application |
20200352480 |
Kind Code |
A1 |
LUCISANO; Joseph ; et
al. |
November 12, 2020 |
IMPLANTABLE SENSOR APPARATUS AND METHODS
Abstract
Implantable sensor apparatus and methods of implantation. In one
embodiment, a fully implantable, biocompatible sensor is disposed
within a cavity or pocket formed within a living being, such that
the sensor remains in a desired orientation and placement so as to
enhance the performance of the sensor, and mitigate the effects of
one or more factors potentially deleterious to the operation of the
sensor and the host being. In one implementation, the sensor
comprises an implantable biocompatible oxygen-based glucose sensor
which is implanted deep within the being's torso tissue proximate
the extant fascia, and oriented such that an active detector aspect
of the device faces away from the being's skin surface. In one
variant, the deep placement, orientation, and construction of the
sensor itself cooperate to enhance the performance of the sensor,
especially over extended periods of time, with little need for
external calibration.
Inventors: |
LUCISANO; Joseph; (San
Diego, CA) ; WILENSKY; Jonathan; (San Diego, CA)
; ENGLER; Robert; (Del Mar, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
GLYSENS INCORPORATED |
San Diego |
CA |
US |
|
|
Family ID: |
1000004978042 |
Appl. No.: |
16/882182 |
Filed: |
May 22, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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14982346 |
Dec 29, 2015 |
10660550 |
|
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16882182 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/0015 20130101;
A61B 5/0031 20130101; A61M 5/14 20130101; A61B 17/32093 20130101;
A61B 5/14542 20130101; A61M 5/1723 20130101; A61B 5/0004 20130101;
A61B 5/72 20130101; A61B 5/14503 20130101; A61B 5/14532 20130101;
A61M 2230/005 20130101; A61M 2210/1021 20130101; A61M 2230/201
20130101 |
International
Class: |
A61B 5/145 20060101
A61B005/145; A61M 5/172 20060101 A61M005/172; A61B 17/3209 20060101
A61B017/3209; A61B 5/00 20060101 A61B005/00 |
Goverment Interests
GRANT INFORMATION
[0001] This invention was made in part with government support
under NIH Grant No. DK-77254. The United States government has
certain rights in this invention.
Claims
1.-28. (canceled)
29. A method of providing treatment to a living being, the living
being having a first sensor apparatus implanted at least partly
within a cavity formed in a tissue of the living being, the method
comprising: identifying an extant incision location on the living
being, the extant incision having been previously used for
implantation of the first sensor apparatus within the cavity;
forming an incision at least partly at the extant incision location
to explant the first sensor apparatus from the living being;
disposing a second sensor apparatus at least partly within the
cavity so that the second sensor apparatus is situated in a desired
position and orientation relative to at least one anatomical
feature of the living being; closing off at least the formed
incision so that the second sensor apparatus is substantially
contained and operable within the living being; and utilizing the
second sensor apparatus to monitor the at least one physiological
parameter associated with the living being for a period of
time.
30.-31. (canceled)
32. The method of claim 29, wherein the utilizing the second sensor
apparatus to monitor the at least one physiological parameter
associated with the living being for a period of time comprises
utilizing at least one oxygen-based glucose sensing element of the
second sensor apparatus to monitor the at least one physiological
parameter.
33. The method of claim 32, wherein the utilizing the at least one
oxygen-based glucose sensing element comprises substantially
mitigating a foreign body response of the tissue to the second
sensor apparatus by obviating peroxide-based substances contacting
the tissue.
34. The method of claim 29, wherein: the second sensor apparatus
comprises at least one round side and at least one flat side
opposite the round side; and the disposing a second sensor
apparatus at least partly within the cavity comprises inserting the
second sensor apparatus into the incision via the at least one
round side of the second sensor apparatus.
35. The method of claim 34, wherein: the forming an incision
comprises forming a transverse incision; and the situating the
second sensor apparatus comprises situating the second sensor
apparatus such that the second sensor apparatus is vertically
oriented with respect to transverse incision.
36. The method of claim 29, wherein the forming the incision
comprises forming the incision on a lower abdomen of the living
entity, the formed incision disposed lateral to a midline of the
living being, and inferior to a umbilicus and superior to an
inguinal ligament of the living being.
37. The method of claim 29, wherein: an external portion of a
sensor region of the first sensor element and an external portion
of a sensor region of the second sensor element are substantially
identical; and the disposing the second sensor apparatus at least
partly within the cavity comprises disposing the second sensor
apparatus within the cavity within which the first sensor apparatus
was previously disposed such that the external portion of the
second sensor element is disposed within one or more features
formed in the tissue by the external portion of the first sensor
element while implanted.
38. The method of claim 37, wherein the forming the incision at
least at the extant incision location and the disposing the second
sensor apparatus within the cavity within which the first sensor
apparatus was previously disposed, cooperate to reduce a propensity
for thickening of a fibrous encapsulation of the second sensor
apparatus by the living being.
39. The method of claim 29, wherein the disposing the second sensor
apparatus comprises situating the second sensor apparatus proximate
to a subcutaneous fascial layer of the tissue of the living being,
with a sensing portion of the second sensor apparatus facing the
subcutaneous fascial layer.
40. The method of claim 39, wherein the utilizing the second sensor
apparatus to monitor the at least one physiological parameter
associated with the living being for a period of time comprises
causing the sensing region to maintain contact with tissue
proximate the subcutaneous facial layer for the period of time.
41. A method of providing treatment to a living being, comprising:
forming an incision within abdominal tissue of the living being so
as to access a fascial layer of the living being, the fascial layer
disposed within the abdomen of the living being; forming a pocket a
prescribed depth within the abdomen and proximate the fascial
layer, the pocket formed to at least partly receive a blood glucose
sensor apparatus; disposing the blood glucose sensor at least
partly within the pocket such that an active sensor face or portion
of the sensor apparatus faces the fascial layer; and activating the
blood glucose sensor to be operable within the living being; and
closing at least a portion of the incision; wherein the forming a
pocket at a prescribed depth within the abdomen and proximate the
fascial layer and the disposing of the blood glucose sensor at
least partly within the pocket, provides insensitivity of the blood
glucose sensor to one or more topically or locally administered
therapeutic agents.
42. The method of claim 41, further comprising: injecting the one
or more topically or locally administered therapeutic agents at a
site at least proximate to the incision; and operating the blood
glucose sensor to obtain at least data relating to a blood glucose
level of the living being.
43. The method of claim 30, wherein the forming the pocket at a
prescribed depth within the abdomen comprises separating adipose
tissue from the fascial layer, such that little or no tissue
removal occurs, in order to minimize tissue and blood vessel
trauma.
44. The method of claim 30, wherein the forming the pocket at a
prescribed depth within the abdomen comprises forming the pocket at
a depth selected to eliminate a salient visible protrusion of the
abdomen proximate the formed incision.
45. The method of claim 30, wherein the forming the pocket at a
prescribed depth within the abdomen comprises forming the pocket at
a depth selected to place a sensing region of the blood glucose
sensor proximate a region of high solute availability within the
tissue.
46. The method of claim 30, wherein the forming the pocket at a
prescribed depth within the abdomen comprises forming the pocket at
a depth selected to expose the blood glucose sensor to a prescribed
level of blood oxygen so as to enhance an operating range of the
blood glucose sensor.
47. A method of providing treatment to a living being, comprising:
evaluating first data relating at least a depth of implantation of
a blood glucose sensor within a living being to a level of
experienced foreign body response (FBR); based at least on the
first data, identifying a target location for implantation of the
blood glucose sensor, the target location including a target depth;
forming an incision within abdominal tissue of the living being so
as to access a fascial layer of the living being, the fascial layer
disposed at or proximate to the target depth; forming a pocket
proximate the fascial layer to at least partly receive a blood
glucose sensor apparatus; disposing the blood glucose sensor at
least partly within the pocket; activating the blood glucose sensor
to be operable within the living being; and closing at least a
portion of the incision.
48. The method of claim 47, wherein the identifying the target
location for implantation extends the operational lifetime of the
blood glucose sensor within the living being relative to an
operational lifetime obtained from implantation of the blood
glucose sensor at another depth, the another depth having a greater
level of FBR associated therewith as compared to a level of FBR at
the target depth.
49. The method of claim 47, wherein the identifying the target
location for implantation comprises identifying a location that
provides substantial insensitivity of the blood glucose sensor to
ingested or locally injected therapeutic agents.
50. The method of claim 47, wherein the evaluating first data
relating at least a depth of implantation of a blood glucose sensor
within a living being to a level of experienced foreign body
response (FBR) comprises evaluating data relating to a level of
encapsulation of an implanted sensor obtained after explant thereof
for at least one living being.
51. The method of claim 47, wherein the blood glucose sensor
comprises a plurality of sensor elements, and the method further
comprises executing, after said activating, at least one computer
program operative to execute on the blood glucose sensor, the at
least one computer program causing: (i) evaluating of data from
each of the individual sensor elements over a period of time for
one or more effects of foreign body response; and (ii) based at
least on the evaluating, causing compensation for the one or more
effects.
Description
COPYRIGHT
[0002] A portion of the disclosure of this patent document contains
material that is subject to copyright protection. The copyright
owner has no objection to the facsimile reproduction by anyone of
the patent document or the patent disclosure, as it appears in the
Patent and Trademark Office patent files or records, but otherwise
reserves all copyright rights whatsoever.
1. TECHNICAL FIELD
[0003] The disclosure relates generally to the field of sensors,
therapy devices, implants, and other devices which can be used
consistent with human beings or other living entities, and in one
exemplary aspect to methods and apparatus enabling implantation of
such sensors and/or electronic devices for, e.g., monitoring of one
or more physiological parameters.
2. DESCRIPTION OF RELATED TECHNOLOGY
[0004] Implantable electronics is a rapidly expanding discipline
within the medical arts. Owing in part to great advances in
electronics and wireless technology integration, miniaturization,
and performance, sensors or other types of electronics or
implantable devices (e.g., therapy agent delivery devices or
materials, implants, and the like) which once were beyond the realm
of reasonable use in vivo on a living subject can now be surgically
implanted within such subjects with minimal effect on the recipient
subject, and in fact many inherent benefits.
[0005] One particular area of note relates to blood glucose
monitoring for subjects, including those with so-called "type 1" or
"type 2" diabetes. As is well known, regulation of blood glucose is
impaired in people with diabetes by: (1) the inability of the
pancreas to adequately produce the glucose-regulating hormone
insulin; (2) the insensitivity of various tissues that use insulin
to take up glucose; or (3) a combination of both of these
phenomena. To correct this disregulation requires blood glucose
monitoring.
[0006] Currently, glucose monitoring in the diabetic population is
based largely on collecting blood by "fingersticking" and
determining its glucose concentration by conventional assay. This
procedure has several disadvantages, including: (1) the discomfort
associated with fingersticking, which should be performed
repeatedly each day; (2) the near impossibility of sufficiently
frequent sampling (some blood glucose excursions require sampling
every 20 minutes, or more frequently, to accurately treat); and (3)
the requirement that the user initiate blood collection, which
precludes warning strategies that rely on automatic early
detection. Using the extant fingersticking procedure, the frequent
sampling regimen that would be most medically beneficial cannot be
realistically expected of even the most committed patients, and
automatic sampling, which would be especially useful during periods
of sleep, is not available.
[0007] Implantable glucose sensors have long been considered as an
alternative to intermittent monitoring of blood glucose levels by
the fingerstick method of sample collection. These devices may be
partially implanted, where certain components reside within the
body but are physically connected to additional components external
to the body via one or more percutaneous elements. Partially
implanted sensors (discussed in greater detail below) are not
viable for long-term use, particularly due to the undesirability of
having an essentially open wound on the body for an extended
period, and all of the attendant problems associated therewith
(including greater risk of infection, the body's natural response
to attempt to expel the percutaneous or "through the skin" portion
of the implant, etc.).
[0008] Implantable sensor devices may alternatively be fully
implanted, where all components of the system reside within the
body, and there are no percutaneous elements. The operability of
one such fully implanted sensor has been demonstrated as a central
venous implant in dogs (Armour et al., Diabetes, 39:1519 1526
(1990), incorporated herein by reference in its entirety). Although
this sensor provided recording of blood glucose, which is most
advantageous for clinical applications, the described implantation
at a central venous site poses several risks and drawbacks,
including risk of blood clot formation and vascular wall damage. An
alternative that does not present such risks to the user is to
implant the sensor in a "solid" tissue site and to relate the
resulting signal to blood glucose concentration.
[0009] Typical sensors implanted in solid tissue sites measure the
concentration of solutes, such as glucose, in the blood perfusing
the microcirculation in the vicinity of the sensor. Glucose
diffuses from nearby capillaries to the sensor surface. Because
such diffusion occurs effectively only over very small distances,
the sensor responds to the substrate supply only from nearby blood
vessels. Conversely, solutes that are generated in the locality of
the sensor may be transported away from the sensor's immediate
vicinity by the local microvasculature. In either case, the local
microcirculation may influence the sensor's response.
[0010] One problem that has confronted previous attempts to implant
sensors in solid tissue is that the pattern of blood vessels in the
vicinity of the sensor may be highly variable, and may change with
time in response to the implantation procedure and the presence of
an implant. In some cases, microscopic blood vessels may be close
to the sensing element, resulting in substantial diffusive flux and
clear, strong signals. In other cases, blood vessels are more
distant and sensors may appear not to function, to function weakly,
or to function only with substantial delays.
[0011] Further complicating the spatial inhomogeneity of the
microvasculature are the phenomena of vasomotion and variations in
regional blood flow. Vasomotion describes the unsynchronized
stop-start blood flow cycles that are observed in individual
capillaries in living tissue. This phenomenon is characterized by
spatial asynchrony--some capillaries have flow while immediate
neighbors do not. Vasomotion does not occur continuously or
frequently and may be most common when the tissue is otherwise at
rest. But, when it occurs, the frequency often can be on the order
of 2 to 4 cycles per minute, with flow interruption in individual
capillaries ranging from partial to complete.
[0012] Regional blood flow is also affected by posture and the
position of the body, such-that localized surface pressure on a
blood vessel may occlude it completely, albeit temporarily. The
occurrence of such complete occlusion is not predictable.
[0013] Traditionally, such "solid tissue" sensors (including the
aforementioned glucose sensors) are implanted within the living
subject at a generally superficial layer or level of the tissue
e.g., at a prescribed superficial depth below the skin; see, e.g.,
Gough et al., Science Translational Medicine, 28 Jul. 2010: Vol. 2,
Issue 42, pp. 42ra53, wherein individual sensor telemetry units
were implanted in subcutaneous tissue sites in 20-kg anesthetized
Yucatan minipigs by making an incision 5 cm long and 0.5 to 1 cm
deep, retracting the skin, and exposing the dermal layers. A pocket
was created between the subdermal fat and underlying muscle with
blunt dissection. The implants were placed in this pocket with the
sensor surface facing inward away from the skin. The foregoing
superficial implantation technique is used to ostensibly (i)
mitigate tissue trauma resulting from the surgical implantation
procedure, and (ii) mitigate interference from interposed solid
tissue to the propagation of electromagnetic radiation (e.g.,
wireless transmissions to and from the implant). Specifically,
historically larger implants require a larger volume within the
solid tissue of the recipient, and hence placing the larger implant
further down into the layers of tissue, etc. residing below the
epidermis requires a larger incision, possibly including through
various blood vessels and other features which may extend the
host's surgical recovery time, and possibly requiring removal of
some solid tissue to accommodate the volume of the implant.
[0014] Moreover, the extraction or "explant" process (i.e., removal
of the sensor after expiration of its useful lifetime, or for other
reasons) can become more difficult and traumatic to the tissue the
deeper the implant is located; such trauma is especially
exacerbated if there is a significant foreign body response (FBR)
which may cause tissue to responsively grow around the implant over
time (e.g., fibrous encapsulation or similar processes), due to
inter alia, the presence of certain compounds such as peroxides or
electrical potential/current generated by the sensor. In effect,
the size of the implanted device combined with the encapsulating
tissue (which may be of a more fibrous and less resilient nature
than the neighboring undisturbed tissue) increases over time,
thereby making explant that much more difficult and traumatic to
the host. In fact, many prior art fully implantable sensors
actually encourage FBR to, inter alia, attempt to enhance tissue
and blood vessel contact with the implanted sensor's sensing
element (e.g., membrane), thereby further exacerbating difficulties
with the subsequent explant, and potentially causing deleterious
changes in sensor performance due to the changing relationship
between the patient's tissue and the sensor.
[0015] However, restriction of the implantation of such sensors to
more superficial locations within the solid tissue as in the prior
art carries with it several drawbacks, including inter alia (i)
reduced performance of or interference with the sensor due to,
e.g., injection or introduction of various substances proximate to
the epidermis, (ii) aesthetic considerations such as a visibly and
tactilely detectable "bulge" of the sensor through the host's skin;
(iii) susceptibility of the sensor and its components to
deleterious external influences such as ballistic or other
impingement, electromagnetic interference, etc.; and (iv) an
increased propensity for the sensor to erode through the skin
surface, leading to infection and a need to explant the device.
[0016] Prior art partially implantable sensors (e.g., those which
include a percutaneous connection element and components worn
external to the living being, such as the device 100 shown in FIG.
1), suffer from many disabilities, including without limitation (i)
reduced wearer "body image" (i.e., the wearer is self-conscious of
the apparatus on the exterior of their skin, such as when swimming,
at the beach, etc.); (ii) discomfort for the wearer, including
interference with clothing, "bulkiness"; (iii) pain due the device
probe or sensor penetrating the skin to a subcutaneous location;
(iv) increased risk of infection due to sensor penetration (e.g.,
"open" wound); and (v) susceptibility to damage or loss due to
mechanical shock, acceleration, frictional forces on the user's
skin (such as when swimming), loss of adhesion to the skin, or the
like. Hence, such external sensing devices similarly are not
optimized for monitoring of e.g., blood glucose, let alone for use
for extended periods.
[0017] As such, there is a compelling need for a sensor designed to
enable greater flexibility of implantation location and depth
(including depths that avoid the foregoing disabilities and
drawbacks associated with prior art implantable devices), as well
as techniques for implanting the sensor in an optimized location
and orientation so as to enhance its performance and
longevity/viability within the recipient. Ideally, such apparatus
and techniques would overcome the disabilities associated with each
of the prior art fully implantable and partially implantable
paradigms discussed above.
SUMMARY
[0018] The present disclosure satisfies the foregoing needs by
providing, inter alia, improved methods and apparatus for
implantation of a sensing or other electronic device within a
living subject.
[0019] In one aspect, a miniaturized fully implantable sensor is
disclosed. In one embodiment, the sensor comprises a plurality of
oxygen-based glucose sensing elements disposed on a sensing region
thereof, and is fabricated from biocompatible materials and uses
biocompatible processes for sensing which advantageously mitigate
or eliminate physiological responses from the host (e.g., FBR), and
also dynamically accommodate any FBR which does occur
algorithmically within the device. In one particular
implementation, the miniaturized size, optimized shape, and
biocompatibility of the sensor apparatus enable, inter alia, deeper
and less traumatic implantation within the host's solid tissue (and
subsequent extraction), thereby providing all of the benefits of an
implantable sensor without the attendant disabilities of both prior
art fully implantable and partially implantable devices and
associated techniques.
[0020] In another aspect, a method of implantation of an electronic
device such as a sensor is disclosed. In one embodiment, the method
includes surgically implanting the sensor at a prescribed location
(e.g., proximate to a fascial layer of the solid tissue of the
host), as well as in a prescribed orientation so as to optimize one
or more performance aspects of the sensor.
[0021] In another aspect, a method of enhancing the performance of
an implantable electronic device is disclosed. In one embodiment,
the device comprises a glucose sensor, and the method includes
implanting the device within a host's solid tissue such that a
sensing portion of the device is disposed so as to avoid or
mitigate the effects of one or more sources of signal interference
or degradation.
[0022] In yet a further aspect, methods of enabling and testing an
implantable electronic device (e.g., the aforementioned sensor
apparatus) are disclosed.
[0023] In a further aspect, methods of providing treatment to a
living subject are disclosed.
[0024] In yet another aspect, a method of implanting a sensor
apparatus in a living entity is disclosed. In one embodiment, the
method includes obtaining a sensor; forming a cavity within a
portion of tissue of the living entity, at least a portion of the
cavity disposed proximate a subcutaneous fascial layer of the
living entity; activating the sensor apparatus so that it can at
least sense at least one physiological parameter, and transmit data
wirelessly; disposing the sensor apparatus at least partly within
the cavity so that the sensing region of the sensor apparatus is
(i) situated immediately proximate the subcutaneous fascial layer
and in direct contact with tissue proximate the subcutaneous
fascial layer, and (ii) oriented with the sensing region
substantially facing the subcutaneous fascial layer; and closing
off the formed cavity such that the implanted sensor apparatus is
substantially contained within, and operable to transmit the data
wirelessly, within the living entity.
[0025] In one implementation, the sensor apparatus includes a power
supply, a plurality of sensing elements disposed substantially
within a sensing region of the sensor apparatus, signal processing
apparatus in data communication with the plurality of sensing
elements, and a wireless interface in data communication with the
signal processing apparatus, the sensing apparatus configured for
monitoring of at least one physiological parameter indicative of a
glucose level within the living entity.
[0026] In another embodiment, the sensor is configured for
monitoring of at least one physiological parameter, and the method
includes: forming a cavity within a portion of tissue of the living
entity; disposing the sensor at least partly within the cavity so
that the sensor is situated in a desired position relative to at
least one anatomical feature of the living entity; and closing off
the formed cavity such that the implanted sensor is substantially
contained and operable within the living entity.
[0027] In a further aspect, a method of providing therapy to a
living being is disclosed. In one embodiment, the method includes:
incising a portion of an abdomen of the living being; forming a
cavity within a portion of the solid tissue of the living being
accessible via the incising; disposing a sensor apparatus at least
partly within the cavity so that the sensor apparatus is situated
in a desired position and orientation relative to at least one
anatomical feature of the living being; closing off the formed
cavity such that the implanted sensor apparatus is substantially
contained and operable within the living being; receiving wireless
communications from the sensor apparatus; and injecting at least
one therapy agent at a site on the abdomen at least proximate the
incised portion.
[0028] In one implementation, the disposition of the sensor
apparatus in the desired position and orientation cooperate to
mitigate one or more deleterious effects on operation of the sensor
apparatus resulting from the injecting of the therapy agent.
[0029] In yet another aspect, a method of providing treatment to a
living being is disclosed. In one embodiment, the method includes:
incising a portion of an abdomen of the living being; forming a
cavity within a portion of the solid tissue of the living being
accessible via the incising; disposing a first sensor apparatus at
least partly within the cavity so that the first sensor apparatus
is situated in a desired position and orientation relative to at
least one anatomical feature of the living being; closing off the
formed cavity such that the first sensor apparatus is substantially
contained and operable within the living being; utilizing the first
sensor apparatus to monitor at least one physiological parameter
associated with the living being for a first period of time;
subsequently re-incising the portion of the abdomen to explant the
first sensor apparatus from the living being; disposing a second
sensor apparatus at least partly within a cavity so that the second
sensor apparatus is situated in a desired position and orientation
relative to at least one anatomical feature of the living being;
closing off the cavity so that the second sensor apparatus is
substantially contained and operable within the living being; and
utilizing the second sensor apparatus to monitor the at least one
physiological parameter associated with the living being for a
second period of time.
[0030] In another embodiment, the living being has a first sensor
apparatus implanted at least partly within a cavity formed in the
solid tissue of the living being, and the method includes:
identifying an extant incision location on the living being, the
extant incision having been previously used for implantation of the
first sensor apparatus within the cavity; re-incising at least the
extant incision location to explant the first sensor apparatus from
the living being; disposing a second sensor apparatus at least
partly within a cavity so that the second sensor apparatus is
situated in a desired position and orientation relative to at least
one anatomical feature of the living being; closing off the cavity
so that the second sensor apparatus is substantially contained and
operable within the living being; and utilizing the second sensor
apparatus to monitor the at least one physiological parameter
associated with the living being for a period of time.
[0031] In an additional aspect, sensor apparatus configured for
implantation within tissue of a living being is disclosed. In one
embodiment, the sensor apparatus includes: a substantially
biocompatible housing; at least one sensing element disposed at
least partly on an outer surface of the housing and configured such
that the sensing element can sense at least one solute when placed
in contact with at least a portion of the tissue; signal processing
apparatus in signal communication with the at least one sensing
element and configured to process signals generated by the at least
one sensing element. In one implementation, the sensor apparatus is
configured to be implanted within the tissue such that the sensor
apparatus is disposed proximate a fascial or musculature layer of
the living being, and operate with the at least one sensing element
also proximate the fascial or musculature layer.
[0032] Other features and advantages of the present disclosure will
immediately be recognized by persons of ordinary skill in the art
with reference to the attached drawings and detailed description of
exemplary embodiments as given below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] FIG. 1 is an illustration of a typical prior art external
sensor apparatus (partially implantable glucose monitor), including
typical placement on the abdomen of the host.
[0034] FIG. 2 is a front perspective view of one exemplary
embodiment of a fully implantable sensor apparatus according to the
present disclosure.
[0035] FIGS. 2A-2C are top, bottom, and side elevation views,
respectively, of the exemplary sensor apparatus of FIG. 2.
[0036] FIG. 3 is a generalized logical flow diagram illustrating an
exemplary embodiment of a method of electronic device implantation
in accordance with the present disclosure.
[0037] FIG. 3A is a generalized logical flow diagram illustrating
an exemplary embodiment of a method of preparing a sensor apparatus
for implantation in accordance with the present disclosure.
[0038] FIG. 3B is a generalized logical flow diagram illustrating
an exemplary embodiment of a method of therapy device or material
implantation in accordance with the present disclosure.
[0039] FIG. 3C is a rear perspective view of an exemplary
embodiment of the sensor apparatus, including one or more
attachment or anchoring apparatus.
[0040] FIG. 4 is perspective cross-sectional view of abdominal
"solid tissue" of a typical human being, showing the various
components and layers thereof, including fascial layers.
[0041] FIG. 5 is side cross-sectional view of an exemplary sensor
apparatus implanted within a cavity or pocket formed in the tissue
of FIG. 4, and proximate to the muscular fascia thereof.
[0042] FIG. 6 is a generalized logical flow diagram illustrating an
exemplary embodiment of a method of surgical implantation utilizing
a common implantation site and incision, in accordance with the
present disclosure.
[0043] FIG. 7 herein is a plot of "proximity index" vs. average
sensor O.sub.2 level at 12 weeks (implanted duration) obtained
during clinical trials by the Assignee hereof using an exemplary
sensor device.
[0044] All Figures.COPYRGT. Copyright 2015 GlySens Incorporated.
All rights reserved.
DETAILED DESCRIPTION
[0045] Reference is now made to the drawings, wherein like numerals
refer to like parts throughout.
Detailed Description of Exemplary Embodiments
[0046] Exemplary embodiments of the present disclosure are now
described in detail. While these embodiments are primarily
discussed in the context of a fully implantable glucose sensor,
such as those exemplary embodiments described herein, and/or those
set forth in U.S. Pat. No. 7,894,870 to Lucisano et al. issued Feb.
22, 2011 and entitled "Hermetic implantable sensor"; U.S. Patent
Application Publication No. 20110137142 to Lucisano et al.
published Jun. 9, 2011 and entitled "Hermetic Implantable Sensor";
U.S. Pat. No. 8,763,245 to Lucisano et al. issued Jul. 1, 2014 and
entitled "Hermetic feedthrough assembly for ceramic body"; U.S.
Patent Application Publication No. 20140309510 to Lucisano et al.
published Oct. 16, 2014 and entitled "Hermetic Feedthrough Assembly
for Ceramic Body"; U.S. Pat. No. 7,248,912 to Gough, et al. issued
Jul. 24, 2007 and entitled "Tissue implantable sensors for
measurement of blood solutes"; and U.S. Pat. No. 7,871,456 to Gough
et al. issued Jan. 18, 2011 and entitled "Membranes with controlled
permeability to polar and apolar molecules in solution and methods
of making same," each of the foregoing incorporated herein by
reference in its entirety, it will be recognized by those of
ordinary skill that the present disclosure is not so limited. In
fact, the various aspects of the disclosure are useful with, inter
alia, other types of implantable sensors and/or electronic
devices.
[0047] Further, while the following embodiments describe specific
implementations of e.g., oxygen-based multi-sensor element devices,
and specific protocols and locations for implantation (e.g.,
proximate the waistline on a human abdomen), those of ordinary
skill in the related arts will readily appreciate that such
descriptions are purely illustrative, and in fact the methods and
apparatus described herein can be used consistent with, and without
limitation: (i) other implantation locations; (ii) living beings
other than humans; (iii) other types or configurations of sensors
(e.g., peroxide-based glucose sensors, or sensors other than
glucose sensors, such as e.g., for other analytes such as lactose);
and/or (iv) devices intended to deliver substances to the body
(e.g. implanted drug pumps, drug-eluting solid materials, and
encapsulated cell-based implants, etc.); and/or other devices
(e.g., non-sensors and non-substance delivery devices).
[0048] As used herein, the terms "health care provider" and
"clinician" refer without limitation to providers of health care
services such as surgical procedures, diagnosis, monitoring,
administration of pharmacological agents, counseling, etc., and
include for instance physicians, nurses, medical assistants,
technicians, and can even include the user/patient themselves (such
as where the patient self-administers, self-monitors, etc.).
[0049] As used herein, the terms "orient," "orientation," and
"position" refer, without limitation, to any spatial disposition of
a device and/or any of its components relative to another object or
being, and in no way connote an absolute frame of reference.
[0050] Likewise, as used herein, the terms "top," "bottom," "side,"
"up," "down," and the like merely connote, without limitation, a
relative position or geometry of one component to another, and in
no way connote an absolute frame of reference or any required
orientation. For example, a "top" portion of a component may
actually reside below a "bottom" portion when the component is
mounted to another device or object.
Overview
[0051] In one exemplary aspect, the present disclosure provides a
methodology wherein a fully implantable, biocompatible sensor is
disposed within a cavity or pocket formed within a living being
(e.g., the frontal portion of a human, more specifically the
abdomen, proximate the waistline), such that the sensor remains in
a desired orientation and placement after the cavity or pocket is
closed, so as to enhance the performance of the sensor (e.g., from
an accuracy perspective), and also mitigate the effects of one or
more factors potentially deleterious to the operation of the sensor
and to the host being (e.g., human). The foregoing features enhance
the robustness of the sensor, and ostensibly extend the time period
over which the sensor may remain implanted and continue to provide
useful data and signals.
[0052] In one implementation, the sensor comprises a somewhat
planar biocompatible oxygen-based glucose sensor with multiple
(e.g., 8) individual sensor elements disposed in a common sensing
region on one side of the somewhat planar housing, which is
implanted deep within the being's torso subcutaneous tissue
proximate the extant abdominal muscle fascia, and optionally
oriented so that the sensing region faces away from the being's
skin surface (i.e., the plane of the sensor is substantially
parallel to the fascia and the epidermis/dermis, with the sensing
region facing inward toward the musculature under the fascia).
[0053] In one variant, the deep placement, orientation, and
construction of the exemplary glucose sensor itself cooperate to
enhance the performance of the sensor, especially over extended
periods of time, with little or no external calibration.
[0054] Due in large part to the miniaturization and integration of
the sensor, the foregoing implantation technique can advantageously
be performed on an outpatient basis by a clinician using only local
anesthetic. Recovery time from the procedure is minimal, and
current implementations of the sensor apparatus have demonstrated
longevity in vivo well in excess of one year.
Exemplary Implantable Sensor
[0055] Referring now to FIGS. 2-2C, one exemplary embodiment of a
sensor apparatus useful with various aspects of the present
disclosure is shown and described.
[0056] As shown in FIGS. 2-2C, the exemplary sensor apparatus 200
comprises a somewhat planar housing structure 202 with a sensing
region 204 disposed on one side thereof (i.e., a top face 202a). As
will be discussed in greater detail infra, the exemplary
substantially planar shape of the housing 202 provides mechanical
stability for the sensor apparatus 200 after implantation, thereby
helping to preserve the orientation of the apparatus 200 (e.g.,
with sensing region 204 facing away from the epidermis and toward
the proximate fascial layer), resisting rotation around its
longitudinal axis 208, and translation, or rotation about its
transverse axis 210, which might otherwise be caused by e.g.,
normal patient ambulation or motion, sudden accelerations or
decelerations (due to e.g., automobile accidents, operation of
high-performance vehicles such as aircraft), or other events or
conditions. Notwithstanding, the present disclosure contemplates
sensor apparatus of shapes and/or sizes other than that of the
exemplary apparatus 200, including use of means to maintain the
desired orientation and position such as e.g., protruding tabs,
"anchoring" the sensor apparatus to surrounding physiological
structures such as the fascial layer by means of sutures or the
like, and so forth.
[0057] It is also appreciated that depending on the type of sensor
apparatus used, undesired movement (translation, rotation) of the
sensor apparatus can be inhibited through physiological interaction
of the sensor apparatus with the host subject at the site of
implantation. For example, clinical trials of the exemplary
apparatus 200 by the Assignee hereof indicate that some degree of
tissue "contouring" with at least the sensing region 204 occurs
over the duration of a typical implantation, due to inter alia
normal biological processes within the host. In effect, the host's
tissue closely contacts and develops contours directly reflective
of the shape of the sensing region 204, thereby indirectly
providing enhanced mechanical coupling (and attendant resistance to
movement).
[0058] The exemplary sensor apparatus of FIGS. 2-2C further
includes a plurality of individual sensor elements 206 with their
active surfaces disposed substantially within the sensing region
204 on the top face 202a of the apparatus housing. In the exemplary
embodiment (i.e., an oxygen-based glucose sensor), the eight (8)
sensing elements 206 are grouped into four pairs, one element of
each pair an active sensor, and the other a reference (oxygen)
sensor. Exemplary implementations of the sensing elements and their
supporting circuitry and components are described in, inter alia,
U.S. Pat. No. 7,248,912, previously incorporated herein. It will be
appreciated, however, that the type and operation of the sensor
apparatus may vary; i.e., other types of sensor elements/sensor
apparatus, configurations, and signal processing techniques thereof
may be used consistent with the various aspects of the present
disclosure, including, for example, signal processing techniques
based on various combinations of signals from individual elements
in the otherwise spatially-defined sensing elements pairs.
[0059] The exemplary sensor apparatus of FIGS. 2-2C also includes a
plurality (three in this instance) of tabs or anchor apparatus 213
disposed substantially peripheral on the apparatus housing. As
discussed in greater detail below with respect to FIGS. 3 and 3C,
these anchor apparatus provide the implanting surgeon with the
opportunity to anchor the apparatus to the anatomy of the living
subject, so as to frustrate translation and/or rotation of the
sensor apparatus 200 within the subject immediately after
implantation but before any body response (e.g., FBR) of the
subject has a chance to immobilize (such as via encapsulation) the
sensor apparatus. In the illustrated embodiment, the tabs or anchor
apparatus 213 each comprise a substantially closed loop through
which the surgeon may optionally run a dissolvable suture or other
such mechanism so as to effect the aforementioned anchoring. The
closed loop may be formed e.g., at time of formation of the
apparatus housing (e.g., when the housing is formed, molded,
forged, or otherwise fashioned), or can be applied thereafter
(e.g., via welding or brazing or adhesion of a wire loop or the
like to the housing). It will be also appreciated that other
configurations, numbers, and/or anchoring mechanisms may be used
consistent with the present disclosure, as discussed in greater
detail infra.
[0060] Various other construction details of the exemplary sensor
apparatus 200 are described in U.S. Pat. No. 7,894,870 to Lucisano
et al. issued Feb. 22, 2011 and entitled "Hermetic implantable
sensor"; U.S. Patent Application Publication No. 20110137142 to
Lucisano et al. published Jun. 9, 2011 and entitled "Hermetic
Implantable Sensor"; U.S. Pat. No. 8,763,245 to Lucisano et al.
issued Jul. 1, 2014 and entitled "Hermetic feedthrough assembly for
ceramic body"; U.S. Patent Application Publication No. 20140309510
to Lucisano et al. published Oct. 16, 2014 and entitled "Hermetic
Feedthrough Assembly for Ceramic Body"; U.S. Pat. No. 7,248,912 to
Gough, et al. issued Jul. 24, 2007 and entitled "Tissue implantable
sensors for measurement of blood solutes"; and U.S. Pat. No.
7,871,456 to Gough et al. issued Jan. 18, 2011 and entitled
"Membranes with controlled permeability to polar and apolar
molecules in solution and methods of making same", each of the
foregoing incorporated herein by reference in its entirety.
[0061] As noted above, one embodiment of the sensor apparatus 200
is configured for so-called "deep" implantation within the solid
tissue of the subject (e.g., low on the frontal abdominal region),
approximately at the level of the deep/muscle fascial layer. As is
known, a fascia is a band or sheet of connective tissue fibers,
primarily collagen, disposed beneath the skin, and which functions
to attach, stabilize, enclose, and separate muscles and other
internal organs. Fasciae are classified according to their distinct
layers as in superficial fascia, deep (or muscle) fascia, visceral
and parietal fascia, and by their functions and anatomical
location. Like ligaments, aponeuroses, and tendons, fasciae are
made up of fibrous connective tissue containing closely packed
bundles of collagen fibers oriented in a wavy pattern substantially
parallel to a direction of pull. The collagen fibers are produced
by the fibroblasts located within the fascia. Fasciae are
accordingly flexible structures able to resist great unidirectional
tensile forces.
[0062] As will be described subsequently herein, exemplary
disposition of the sensor apparatus 200 at the deep muscular
fascial level provides several benefits both from the perspective
of the user (patient) and the clinician (e.g., surgeon).
Methods for Implantation
[0063] Referring now to FIG. 3, methods of implantation of one or
more sensors, and treatment of a living being, are described in
detail.
[0064] As shown in FIG. 3, one exemplary embodiment of a method 300
of implantation of a sensor is disclosed. At step 302, the patient
(e.g., human being) is evaluated for: (i) the propriety of use of
the implantable sensor (e.g., whether contraindications or other
factors make the use of the particular sensor impractical or
undesirable); (ii) the best or desired implantation site (which, as
discussed elsewhere herein, may or may not be a previously utilized
site); and (iii) any other factors which the heath care provider
should consider, such as recent other surgeries, recent ingestion
of pharmacological agents, and the like.
[0065] At step 304, the patient is prepared for surgery (whether
traditional, laparoscopic, or otherwise). Such preparation may
include for example placement in a surgical environment (e.g.,
operating or treatment room), disinfecting the surface of the skin
at and proximate to the incision site, (such as using Betadine.RTM.
or similar topical microbicide), administration of pharmaceuticals
or other agents for, e.g., anesthetization of the implantation area
via local anesthetic, sedation of the patient via various sedating
agents, anesthetization of the patient (generally) via a general
anesthetic, administration of a prophylactic dose of an antibiotic
compound, or the like.
[0066] The incision site(s) may also be marked on the patient at
this point. In one variant, the incision site, as well as the
desired extent of the pocket to be formed (discussed below) may be
marked to aid the surgeon during the implantation procedure. A
typical incision length for the sensor apparatus of FIG. 2 is on
the order of 2.5 cm, although greater and lesser lengths are
contemplated by the present disclosure depending on, e.g., the
actual size and shape of the implanted device, particular
anatomical features or considerations relating to the patient,
etc.
[0067] At step 306, the sensor is prepared for surgical
implantation in the patient. In one embodiment, the exemplary
sensor apparatus 200 of FIG. 2 herein is utilized, although as
previously discussed, any number of types and/or configurations of
sensors may be used consistent with the method 300. In the case of
the sensor apparatus 200 of FIG. 2, the sensor includes a sensing
region 204 disposed on one side of the substantially planar sensor
apparatus housing, through which all glucose monitoring is
conducted when the sensor apparatus is in vivo. The sensor
apparatus 200 is (i) removed from its packing/shipping container,
preserving its sterility after removal and before implantation,
(ii) powered up, and (iii) functionally tested so as to assure its
operability in certain regards.
[0068] FIG. 3A illustrates one exemplary methodology for carrying
out step 306 of the method 300. As shown in FIG. 3A, the sensor
apparatus is first removed from its storage/packing container as
noted above (step 315). Next, the power supply of the apparatus is
enabled, such as by inserting or enabling electrical contact with a
battery of the apparatus (step 317). Where the power supply of the
apparatus requires energizing by an outside electrical field (e.g.
where power is to be delivered to the device by inductive
coupling), an appropriate external apparatus is utilized.
[0069] Next, per step 319, the desired configuration for the
particular application (e.g., analyte monitoring selection,
wireless interface parameters, sensing/data transmission frequency,
etc. for a given patient) may be determined (as applicable). It is
noted that while the exemplary methods of FIGS. 3-3A illustrate
determination of such a configuration, the present disclosure
contemplates any number of other options, including utilizing a
fully pre-programmed sensor apparatus (e.g., with no required or
possible user configuration), so as to inter alia, simplify the
preparation and implantation of the apparatus, and avoid any
potential programming or configuration errors, thereby obviating at
least step 319.
[0070] Per step 321, a communication channel is established between
the signal processing/microcontroller architecture of the sensor
apparatus and an external device, such as via a wireless "command"
channel and protocol. Similarly, a wired (e.g., micro-USB) form
factor can be used along with a serialized bus protocol such as VC,
PCIe, etc. While wireless communication with the sensor apparatus
may be desired for many cases, the wired implementation may also be
constructed such that the physical interface is shielded after
completion, internal to the sensor apparatus, or otherwise adapted
so as to preclude any ingress of biological matter into the
apparatus housing, or conversely any egress of substances from
inside the device housing into the surrounding tissue of the
patient.
[0071] A properly configured external device (e.g., tablet
computer, smartphone, desktop/laptop, flash drive, etc.) can be
used to transmit commands to the sensor apparatus once the channel
is established, according to the prescribed command protocol.
[0072] Per step 323, the command channel established in step 321 is
utilized to configure the sensor apparatus, which may include
"flashing" the non-volatile storage within the device with new
firmware, configuring one or more user-selectable parameters or
options, and the like.
[0073] Per step 325, the configured device is then tested to assure
proper programming/functionality prior to implantation (although
some testing can be accomplished after implantation, as described
elsewhere herein).
[0074] Note that in one embodiment, the sensor is entirely
pre-programmed, and is configured to transmit "raw" data signals
off-sensor to a receiver (the latter enabling subsequent processing
of the raw data signals). However, in certain other embodiments,
the sensor apparatus can optionally be configured with a plurality
of capabilities such that a user (e.g., health care provider) can
selectively enable or disable features for the current
patient/application, thereby in effect customizing the sensor
apparatus for the application. For instance, in one variant, the
sensor apparatus might include algorithms or signal processing
applicable to a particular operational context (e.g., sensing of
multiple ones of certain analytes), but which are not appropriate
for the current application or patient due to their physiology,
age, type of medical condition/diabetes, etc. Similarly, electronic
design factors may form a basis for the selective configurability,
such as e.g., where the sensor apparatus is fitted with multiple
wireless air interface types and/or frequency bands,
modulation/coding schemes (MCS), etc., all of which may not be
needed after implantation. For instance, in one option, due to
extant interference by virtue of the patient's job, residence
location, prevailing environment, etc., certain wireless
frequencies (e.g., different frequencies within the ISM band) or
types of interfaces (e.g., OFDM versus direct sequence versus
narrowband/FDMA) may be more desirable than others, and hence can
be selected at time of implantation (subject to regulatory
restrictions and requirements), with non-selected options shut off
or put to sleep so as to conserve electrical power within the
implanted device after implantation, thereby extending its
viability in vivo. In this regard, the clinician can optionally be
given a menu of choices in terms of device configuration from which
to select so as to readily optimize the implantation for that given
patient, without having to employ a single-function or particular
device configuration which may or may not be available to the
clinician at that particular surgical location and/or point in
time.
[0075] Moreover, the aforementioned optional configuration of the
device can be accomplished when the device is in vivo, such as
after a trial period. For example, in one variant, the implantation
"lifetime" of the sensor apparatus may be extended (assuming
suitable physiological monitoring performance continues) by
selectively shutting down or powering off various features,
functions or components of the implanted sensor, reprogramming
(e.g., download of new firmware which further optimizes operation,
etc.), such as via wireless command to the signal
processor/microcontroller of the device. Hence, what was ostensibly
a 12-month implantation period may be extended by selective in vivo
reconfiguration of the device in order to optimize power
consumption. As is well known, digital processors and wireless
baseband processors each may employ multiple different power planes
and "sleep" states which progressively reduce power consumption by
the device, depending on the operation demands on the device. If it
is determined that, e.g., the frequency of calculations or sensor
samplings can be reduced later in the life of a given
implementation (such as where the host becomes more familiar with
his/her own monitoring, response to certain ingested foods or
liquids, etc.), it may be that the "tempo" of operation of the
sensor apparatus can be reduced, providing attendant power
consumption reduction. For instance, in the context of the
exemplary sensor apparatus 200 of FIG. 2, the sensor apparatus
includes multiple (4) sets of sensing and reference sensing
elements, which are in one implementation adapted to dynamically
compensate for e.g., FBR or other so-called "confounding factors"
occurring proximate the sensing elements (see, inter alia, U.S.
Pat. No. 7,248,912 previously incorporated herein, for a discussion
of various such factors), thereby maintaining the accuracy of the
device as a whole. Accordingly, as sensing elements or sets thereof
become inoperative or unreliable, these elements/sets can be
selectively removed from the signal processing logic and
deactivated, thereby conserving electrical power, and ostensibly
extending the implantation lifetime of the sensor apparatus in that
given patient.
[0076] Using the foregoing approach of a reconfigurable sensor
apparatus, the cost and inventory burden associated with the
sensors is reduced, since in effect a "one size fits all" device
can be stocked for use across a wide variety of potential
applications. It will be appreciated, however, that the various
aspects of the disclosure can be practiced with equal success using
unique or heterogeneous sensor apparatus or electronic devices
across different patients, including for instance having variations
in size or shape (e.g., adult and juvenile sizes), sensing
capability/configuration (multiple analytes for certain types of
patients, a single analyte for others), communications and/or data
processing capabilities, etc.).
[0077] It will be appreciated that while the aforementioned
embodiment of the methodology powers up and checks the
functionality of the device (and optionally enables/disables
features of the sensor) prior to implantation, one or more of these
procedures can be performed when the device is in vivo (including
after the surgical implantation procedure is complete) if desired.
For example, in one such variant, the sensor is powered up prior to
implantation (since a power circuit or battery malfunction
generally cannot be rectified after implantation), yet is not
"configured" for operation and tested until it is disposed at its
target implantation location deep within the patient's tissue. This
approach can advantageously be utilized to, inter alia, both (i)
test the sensor in the actual environment which it will be
subsequently used (as opposed to merely in "open air" or its
sterile shipping/packing environment, each of which may not allow
the tests with appropriate sensory input signals as compared to
being in vivo with the sensor active sensing region 204 in contact
with the patient's tissue) and (ii) obtain representative signal
inputs (e.g., from the sensor's sensing array) and outputs (e.g.,
wireless signals of insufficient strength may be attenuated by the
patient's tissue, such attenuation which could not be accurately
assessed before the sensor was placed beneath the tissue).
[0078] Testing performed on the sensor apparatus may include for
example: (i) battery voltage or current checks; (ii) wireless
interface checks such as transmission of test data or actual sensed
data; (iii) functional command checks, such as where a command is
wirelessly transmitted to the device in order to cause the sensor
apparatus to perform a function, reconfigure itself, transmit data,
etc.
[0079] Referring again to FIG. 3, at step 308 of the method 300,
the patient is surgically incised at the target location (e.g., in
the lower abdomen, lateral to the midline, inferior to the
umbilicus and superior to the inguinal ligament, and a cavity
formed below the skin and extending to the fascia underlying the
target location. In one variant, the user's superficial (scarpal)
fascia is incised, and the adipose tissue 405 immediately proximate
the deeper fascial membrane 402 (i.e., anterior abdominal fascia;
see FIGS. 4 and 5) is merely separated from the fascial membrane so
as to form the desired cavity or pocket 502, with little or no
tissue removal from the patient. Such separation is preferably
performed using "blunt" techniques (i.e., without cutting per se),
to minimize tissue and blood vessel trauma, and also mitigate
prospective FBR (which may be exacerbated from cutting versus blunt
formation), but may also be performed using an instrument such as a
scalpel or surgical scissors if needed or desired for other
reasons. In an alternate variant, the surgeon may remove a small
amount of fat cells or tissue in the region in order to accommodate
the volume of the sensor apparatus. In yet another variant, a
specialized "pocket forming" surgical tool may be inserted into the
location where the pocket is desired, and then removed to create a
suitable pocket.
[0080] In one exemplary embodiment of the method 300, the pocket is
formed in a substantially vertical direction relative to the
(substantially transverse) incision; i.e., the incision is formed
low on the patient's abdomen, and the pocket is formed internally
with a longitudinal axis thereof pointing roughly towards the
patient's head or upper abdomen.
[0081] As noted supra, the target implantation site is in one
implementation chosen to be in the patient's lower abdomen, lateral
to the midline, inferior to the umbilicus and superior to the
inguinal ligament. While other sites may be used consistent with
the present disclosure, this site often has significant advantages
associated therewith, both for the implanting surgeon and the
patient. Specifically, in obese individuals (or even those merely
with a significant amount of fat around their midsection),
implantation is typically less traumatic and invasive at the
aforementioned target location, since the thickness of the fatty
tissue layer in such individuals declines rapidly as a function of
proximity to the groin area. Hence, less damage to the patient's
tissue and blood vessels occurs when performing implantation in
this region.
[0082] Moreover, in combination with the aforementioned formation
of the cavity in a generally "vertical" direction upward from the
incision, such incision location advantageously affords the surgeon
the ability to implant the sensor apparatus 200 deeply within the
patient's abdomen (with all of the attendant benefits thereof), yet
with minimal tissue and blood vessel trauma.
[0083] It is also appreciated that from an aesthetic perspective,
placement of the incision low on the patient's abdomen can be
highly desirable, so as to put the resulting scar out of normal
view (e.g., below the "bikini line" or such).
[0084] Once the cavity or pocket 502 (FIG. 5) is formed, the sensor
apparatus 200 is implanted within the cavity/pocket in the
direction 500 shown, so that the sensing region 204 is both
proximate the target fascial layer and oriented in the desired
direction (step 310). As discussed supra, the somewhat planar shape
of the sensor housing 202 helps to maintain the desired sensor
orientation and placement; accordingly, the sensor apparatus 200 in
the present embodiment of the method 300 is inserted into the
cavity 502 with the "flat" sides substantially parallel to the
plane of the fascial layer 402, musculature 404, superficial fascia
406, superficial fatty tissue layer 407, and epidermis 408, as
shown in FIG. 5. In one variant, the sensor apparatus 200 is
oriented "round side up", such that the rounded end 211 (see FIG.
2) is inserted into the formed pocket first, thereby aiding in
placement with minimal friction and effort.
[0085] Per step 312 of the method 300, the sensor apparatus 200 can
optionally be affixed or "anchored" to the patient's anatomy so as
to, inter alia, preclude the sensor apparatus from moving or
dislocating within the patient after implantation (and potentially
affecting the operation of the sensor apparatus, such as by changes
or failure of the tissue coupling to the sensing elements of the
apparatus). In one such variant, sutures are used in conjunction
with one or more anchor points or tabs 213 formed or disposed on
the outer surfaces of the sensor apparatus 200 (see FIGS. 2 and
3C), such that the sensor apparatus can be sutured to the patient's
underlying fascia (e.g., anterior abdominal fascia) or other
anatomical feature(s) within or proximate to the formed pocket in
the desired location and orientation. In one variant, dissolvable
sutures of the type well known in the medical arts are used for
such purpose, thereby enabling the sensor apparatus to be secured
within the patient until FBR and/or other natural body processes
perform this function. Use of the dissolvable sutures provides,
inter alia, for easier subsequent explant, since the sutures will
have completely dissolved by time of explant (e.g., a year or 18
months from implantation), thereby obviating having to surgically
sever and remove them. Notwithstanding, it will be appreciated that
non-dissolvable sutures (and/or other anchoring or securing means,
such as e.g., (polyester velour) fabric patches or tabs, or the
like) may be used consistent with the present disclosure as
desired.
[0086] It is also noted that while the exemplary sensor apparatus
embodiment (e.g., as shown in FIGS. 2 and 3C) has three (3) anchor
points or tabs 213 (i.e., one on the front "rounded" portion as
shown in FIG. 2, and two on the rear "squared" portion as shown in
FIG. 3C), more or less may be used. While the present disclosure
contemplates use of no anchoring means (e.g., allowing the sensor
apparatus 200 to "float" within the pocket, the latter which is
closed or otherwise configured so as to maintain the desired
placement of the sensor apparatus after implantation), or a single
anchor (e.g., a single suture or other means with a single tab 213
on one side or end of the sensor apparatus, so as to at least
partly constrain the sensor within the pocket 502), two (2) or more
anchors, ideally spaced apart at some distance from each other
relative to a characteristic dimension of the sensor apparatus, is
considered optimal in many cases so as to frustrate potential
"flipping" of the sensor apparatus within the pocket, especially
when the pocket is not completely or partly closed off (e.g.,
before the normal FBR has had an opportunity to establish
encapsulation) after implantation; this approach is especially
useful in highly active individuals where, by nature of aggressive
or jarring physical motion (such as mountain bike riding, playing
contact sports, gymnastics, etc.), such undesired movement of the
sensor apparatus within the pocket is more likely to occur.
[0087] Lastly, per step 314 of the method 300, the surgical
incision (and optionally the cavity itself) are closed, and
post-surgical treatment is applied to the patient. In one variant,
the surgical incision is closed (e.g., via suturing, surgical tape
or adhesive, and/or surgical staples) such that scarpal fascia and
skin (lower inverted layer and higher layer) are closed, yet the
formed pocket 502 is not affirmatively closed off (e.g., sutured),
so as to reduce trauma to the patient and ostensibly facilitate
later explant. Alternatively, the pocket 502 may be partly or fully
closed off, such as via the aforementioned suturing or other means
(e.g., dissolvable surgical tape or patch). Providing such "deep"
as well as surface layer wound closures may be helpful in aiding
healing and avoiding subsequent compromise of the closed wound,
especially in individuals where their particular anatomy and
anticipated activity profile might otherwise place undue stress on
a single-layer closure.
[0088] The exemplary "deep implantation" approach of the present
disclosure provides, inter alia, reduced sensitivity to or
possibility of interference from injections or biological processes
which may occur at or near the dermis/epidermis, and further
provides some degree of enhanced "mechanical" shielding or
ballistic protection for the potentially more delicate sensing
region by virtue of both (i) the layer of tissue, etc. interposed
between the sensor and the patient's epidermis, and (ii) the
orientation of the sensing region away from any external forces
which may impinge on the patient's abdomen, such as a missed
baseball or football catch, steering wheel in an automobile
accident, or the like. Additionally, the present disclosure
contemplates the implantation of a biocompatible shield, which may
be a rigid ceramic or the like plate or cup-shaped element, or may
comprise a compliant material such as silicone rubber, which can be
disposed immediately proximate the sensor apparatus or at a tissue
layer closer to the epidermis, and which can provide additional
ballistic or impingement protection for the sensor apparatus when
implanted, such as for patients who engage in contact sports,
military, or law enforcement activities, or the like.
[0089] Further, implantation of the sensor apparatus at a greater
subcutaneous depth (i.e., proximate the muscular fascia) reduces or
even eliminates any visible protrusion of the subject's abdomen,
thereby making the sensor apparatus effectively invisible to the
external observer.
[0090] Further, implantation of the sensor directly proximate a
muscle fascia layer enhances the availability of solutes to the
sensor, as the sensor is closer to the rich vascular bed associated
with the underlying muscle. This enhanced solute availability
advantageously supports increased solute flux to the sensor and
thereby increased magnitudes of sensor signals and signal-to-noise
ratios, enhancing sensor accuracy and performance. Shallow
implantation further may result in reduced or insufficient access
to blood oxygen levels, thereby reducing the effective range of the
device in measuring blood glucose; conversely, the "deep"
implantation described herein affords enhanced access to oxygen,
and accordingly extends the dynamic range of the device, which
results in, inter alia, enhanced operational flexibility (including
enhanced time before explant is required).
[0091] Further, deeper implantation sites are associated with more
stable, less fluctuating temperatures, which is of advantage for
sensor types that possess temperature dependency.
[0092] Further, deeper implantation reduces risks for erosion of
the sensor through the skin, the risk for which would otherwise be
exacerbated by proximity of the sensor to the epidermis and
exposure to external mechanical forces.
[0093] It will also be appreciated that in the exemplary embodiment
of the sensor apparatus (FIG. 2, et seq), the sensing elements are
disposed substantially on an opposite face or side from the
(internal) radio frequency transmitter/transceiver antenna (not
shown), such that emissions from the latter (such as via primary or
ancillary lobes of the radiation pattern used for signal
transmission) are substantially directed outward from the patient
and away from the sensing elements (and supporting electronics
within the sensor housing, such as an analog "front end" circuit
used to receive signals from the sensing elements in one
implementation), thereby mitigating electromagnetic noise or
interference (EMI) in the sensing circuitry from antenna
emissions.
[0094] Selection of the exemplary location near the muscular
fascial layer 402 advantageously also requires only minimal
surgical intervention (e.g., outpatient procedure or the like
performed by a general surgeon or similar clinician versus a
specialist), since the fascial layer in the exemplary embodiment is
not penetrated or incised. Accordingly, only a small incision is
necessary (e.g., approximately one to one-and-one-half inches long
based on the current implementation of the sensor apparatus), and
the entire procedure generally can be completed in less than 15
minutes.
[0095] Moreover, it is contemplated by the inventors hereof that
the degree or level of FBR within the patient may be directly or
indirectly related to the depth of implantation of a given implant
(e.g., sensor), such that implantation of such a device at one
depth may result in a differing type and/or magnitude of FBR than
would occur for the same device implanted at a different depth in
the same patient at the same location. Accordingly, the present
disclosure contemplates, in one embodiment, use of such
relationship as a factor in considering a depth of surgical
implantation. For instance, in the case where anecdotal or other
data indicates that FBR is reduced or ameliorated in severity or
type as depth of implantation increases, such information may be
used in selecting a target location and depth for the sensor
apparatus or other implanted device. As noted above, prior art
approaches to implantation generally consider only "shallow"
implantation and/or implantation so as to maintain a prescribed
relationship to the patient's external (dermal) layers.
[0096] It will also be appreciated that while the foregoing
methodology is described substantially in terms of use of a deep or
musculature fascial layer, a more superficial fascial or other
layer may in certain cases be used (so as to minimize trauma and
recovery time of the subject by not incising or cutting through the
superficial fascial layer, while simultaneously providing good
sensor performance and the other benefits described herein).
[0097] For example, it is contemplated that further miniaturization
of the sensor apparatus will occur over time (e.g., as electronics,
power sources, etc. are further integrated and reduced in size),
such that a smaller incision and smaller/shallower "pocket" can be
used for implantation.
[0098] Additionally, the present disclosure contemplates other
potential implantation sites, including for example those yet
deeper within the patient's anatomy than the exemplary embodiments
previously described. For instance, it may be desirable in certain
cases to incise through the deeper anterior abdominal fascia
referenced above and form the pocket 502 within tissue on the
interior side thereof, such as in the case of patients with friable
skin structures, or where further protection of the implantable
device is desired, or where perfusion of the tissue layers
otherwise accessible to the device in the previously described
exemplary embodiments is inadequate. In such cases, the preferred
orientation of the device would be such that its active face (i.e.
the face that required access to perfused tissue) would be adjacent
to the fascia layer on which the device was being located. For
instance, in one such variant of the implantation method, the
sensor apparatus 200 of FIG. 2 is disposed at the previously
discussed implantation site and with sensor-face outward (i.e.,
facing the muscular fascia, but from the interior side), and radio
frequency energy is transmitted substantially through the subject
toward their back (and thereby maintaining a high level of "noise"
isolation between the RF interface and the electronics of the
sensor elements). In another configuration of the sensor 200
adapted for such instances, the radio frequency transceiver/antenna
may be configured to transmit RF energy through the same sensor
apparatus housing face as the sensor; e.g., with reduced RF power
so as to mitigate any possible noise or interference issues with
the disposition of the RF transceiver/antenna on or under the same
face of the apparatus housing as the sensor elements. Various other
configurations will be appreciated by those of ordinary skill given
the present disclosure.
[0099] It is also envisaged that as circuit integration is
increased, and component sizes (e.g., lithium or other batteries)
decrease, and further improvements are made, the sensor may
increasingly be appreciably miniaturized, such that successively
smaller and smaller incisions are required for implantation of the
sensor apparatus over time. Laparoscopic implantation, or even a
coarse "injection" delivery by trocar are also feasible methods of
implantation with appropriate adaptation, such adaptation being
well within the skill of an ordinary artisan in the medical or
surgical arts when given the present disclosure.
[0100] As previously noted, the "deep" implantation technique of
the present disclosure can also be utilized not only for other
types of sensors, but also for apparatus and/or materials other
than sensors, including for example devices intended to deliver
substances to the body (e.g. implanted drug pumps, drug-eluting
solid materials, and encapsulated cell-based implants, etc.),
and/or other devices for which implantation may be desired. FIG. 3B
shows an exemplary embodiment of a method of implantation of such
non-sensor apparatus. As shown in FIG. 3B, one exemplary embodiment
of a method 350 of implantation of e.g., a non-sensor apparatus,
such as a therapy apparatus or implant, is disclosed. At step 352,
the patient (e.g., human being) is evaluated for: (i) the propriety
of use of the implantable apparatus; (ii) the best or desired
implantation site (which, as discussed elsewhere herein, may or may
not be a previously utilized site); and (iii) any other factors
which the heath care provider should consider, such as recent other
surgeries, recent ingestion of pharmacological agents, and the
like.
[0101] At step 354, the patient is prepared for surgery (whether
traditional, laparoscopic, or otherwise), as discussed previously
herein. The incision site(s) may also be marked on the patient at
this point.
[0102] At step 356, the sensor is prepared for surgical
implantation in the patient. In one embodiment, the exemplary
therapy apparatus or implant is (i) removed from its
packing/shipping container, preserving its sterility after removal
and before implantation, (ii) powered up (if applicable), and (iii)
functionally tested so as to assure its operability in certain
regards, as applicable.
[0103] At step 358 of the method 350, the patient is surgically
incised at the target location, and a cavity formed below the skin
and extending to the fascia underlying the target location. In one
variant, the user's superficial (scarpal) fascia is incised, and
the adipose tissue 405 immediately proximate the deeper fascial
membrane 402 (i.e., anterior abdominal fascia; see FIGS. 4 and 5)
is merely separated from the fascial membrane so as to form the
desired cavity or pocket 502, with little or no tissue removal from
the patient. In an alternate variant, the surgeon may remove a
small amount of fat cells or tissue in the region in order to
accommodate the volume of the therapy apparatus or implant. In yet
another variant, a specialized "pocket forming" surgical tool may
be inserted into the location where the pocket is desired, and then
removed to create a suitable pocket.
[0104] As noted supra, the target implantation site is in one
implementation chosen to be in the patient's lower abdomen, lateral
to the midline, inferior to the umbilicus and superior to the
inguinal ligament. While other sites may be used consistent with
the present disclosure, this site often has significant advantages
associated therewith, both for the implanting surgeon and the
patient; e.g., less damage to the patient's tissue and blood
vessels occurs when performing implantation in this region.
[0105] Once the cavity or pocket 502 (FIG. 5) is formed, the
therapy apparatus or implant is implanted within the cavity/pocket
per step 360.
[0106] Per step 362 of the method 350, the therapy apparatus or
implant can optionally be affixed or "anchored" to the patient's
anatomy so as to, inter alia, preclude the apparatus or implant
from moving or dislocating within the patient after implantation
(and potentially affecting the operation thereof).
[0107] Lastly, per step 364 of the method 350, the surgical
incision (and optionally the cavity itself) are closed, and
post-surgical treatment is applied to the patient.
"Re-use" of Surgical Sites
[0108] The present disclosure further contemplates that (i) the
same implantation site and/or incision used for sensor implantation
can be used for successive implantations of sensors and/or other
apparatus, (ii) a different implantation site and/or incision can
be used for such successive implantations (e.g., access to the same
fascial-proximate region may occur via the same or different
incision, and access to a different fascial-proximate region may
occur via the same or different incision), and (iii) a pre-existing
or prior incision from an unrelated procedure (e.g., appendectomy,
cesarean section, etc.) may be "repurposed" for implantation,
thereby mitigating aesthetic concerns relating to the creation of
new scars. Hence, a healthcare provider is advantageously given a
range of options dependent upon the application; e.g., particular
patient desires, complications, changes since the last
implantation, etc.
[0109] As shown in FIG. 6, the foregoing "re-use" methodology for
implantation 600 first identifies the site of the prior
implantation and incision at step 602. At step 604, the patient is
prepared for surgery. As noted above, such surgery (and
preparation) is advantageously minimal, typically on an outpatient
basis with local anesthetic.
[0110] At step 606, the new sensor to be implanted is unpackaged
and readied for implantation, as described supra. At step 608, the
prior incision is re-incised (either wholly or in part), and the
extant cavity formed within the tissue re-opened such that the
implanted sensor apparatus can be removed (step 610).
[0111] Per step 612, the "new" sensor apparatus 200 is disposed
within the cavity and tested as appropriate, in the desired
position and orientation as previously described. Note that
depending on the degree of FBR encountered (e.g., contouring of the
tissue proximate the sensor elements 206, etc.), it may be
desirable to locate the sensing region 204 in a slightly different
location, such as in areas where no contouring or "imprint" has
occurred. Conversely, there are situations where it may be
desirable to utilize the already contoured portion of the tissue
(i.e., mimic placement of the prior sensor apparatus as closely as
possible).
[0112] Finally, per step 614, the incision (and optionally the
cavity itself as desired) is closed (e.g., sutured or adhered using
e.g., an adhesive bandage, surgical staples, or tissue adhesive),
with the patient receiving post-surgery treatment and processing
for discharge as required.
[0113] It will be recognized that the term "new sensor apparatus"
in the preceding discussion is not limited to a distinct physical
device. For example, the procedure of FIG. 6 may be modified such
that the existing (implanted) device is merely provisioned for use
again within the same patient (e.g., by changing out the battery,
other renewable component, or the like). It is recognized that to
the degree that a patient's body has already "assimilated" the
sensor in terms of FBR or other biological processes, there may be
advantages to re-use of the sensor apparatus (or parts thereof) in
that same patient in terms of, e.g., reduction of tissue trauma in
explanation (such as where the exemplary battery or the like can be
replaced without a full explant of the sensor apparatus), or where
reduced levels of FBR are anticipated by leaving the already
implanted device in vivo. These considerations should be weighed,
however, against other factors such as degradation or loss of one
or more sensor element pairs due to e.g., FBR occurring prior to
the explant procedure.
Anecdotal Performance
[0114] Human clinical trials conducted by the Assignee hereof
authorized by the U.S. Food and Drug Association (FDA) to date
indicate superior performance of the foregoing techniques and
apparatus, including notably (i) the ability of the sensor
apparatus to remain implanted for extended periods without
deleterious foreign body response to the sensor from the host which
impairs the operation of the sensor, (ii) general insensitivity to
ingested or locally injected substances which might otherwise
interfere with the performance of the device (e.g., acetaminophen,
insulin injections, etc.) and (iii) the ability of the sensor
apparatus to provide a stable output for extended (e.g., multiple
week) intervals. These advantages are due at least in part by
virtue of the selected target location being deep(er) within the
abdominal subcutaneous tissue of the patient (e.g., proximate the
fascia), and the orientation of the sensing region of the apparatus
200 away from possible sources of interference or degradation.
[0115] FIG. 7 herein is a plot of "proximity index" vs. average
sensor O.sub.2 level at 12 weeks (implanted duration), which
illustrates exemplary anecdotal data obtained by the Assignee
hereof during trials of a generally comparable sensing device and
using, inter alia, ultrasound techniques. Specifically, the data of
FIG. 7 demonstrates the aforementioned stability of output for
extended periods, which is in part afforded by the sensor device's
access to the blood supply by virtue of its "deep" placement. Each
point on the graph of FIG. 7 represents the average of the output
from the four (4) oxygen reference electrodes on a given implanted
device. The "proximity index" metric of FIG. 7 provides an
indication of the distance between the sensing area aspect of the
implanted device and the underlying muscle layer. Any positive
value of the index indicates physical separation (i.e., lack of
intimate contact between the sensing area and the target tissue
such as the muscle fascia). Conversely, any negative index value
indicates close contact between the sensing area and the muscle
fascia. Hence, as can be seen in FIG. 7, excellent physical contact
of the sensing area of the device and the muscle fascia was
maintained.
[0116] It will be recognized that while certain embodiments of the
present disclosure are described in terms of a specific sequence of
steps of a method, these descriptions are only illustrative of the
broader methods described herein, and may be modified as required
by the particular application. Certain steps may be rendered
unnecessary or optional under certain circumstances. Additionally,
certain steps or functionality may be added to the disclosed
embodiments, or the order of performance of two or more steps
permuted. All such variations are considered to be encompassed
within the disclosure and claimed herein.
[0117] While the above detailed description has shown, described,
and pointed out novel features as applied to various embodiments,
it will be understood that various omissions, substitutions, and
changes in the form and details of the device or process
illustrated may be made by those skilled in the art without
departing from principles described herein. The foregoing
description is of the best mode presently contemplated. This
description is in no way meant to be limiting, but rather should be
taken as illustrative of the general principles described herein.
The scope of the disclosure should be determined with reference to
the claims.
* * * * *