U.S. patent application number 14/675270 was filed with the patent office on 2018-12-27 for integrated surface stimulation device for wound therapy and infection control.
This patent application is currently assigned to The United States Government, as represented by the Department of Veterans Affairs. The applicant listed for this patent is Case Western Reserve University, The United States Government, as represented by the Department of Veterans Affairs, The United States Government, as represented by the Department of Veterans Affairs. Invention is credited to Kath M. Bogie, Steven L. Garverick, Daniel S. Howe, Christian A. Zorman.
Application Number | 20180369582 14/675270 |
Document ID | / |
Family ID | 57014997 |
Filed Date | 2018-12-27 |
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United States Patent
Application |
20180369582 |
Kind Code |
A9 |
Bogie; Kath M. ; et
al. |
December 27, 2018 |
Integrated Surface Stimulation Device for Wound Therapy and
Infection Control
Abstract
The present invention provides a thin and flexible device and
method of use thereof for wound treatment and infection control.
The integrated surface stimulation device may comprise a complete
wireless stimulation system in a disposable and/or reusable
flexible device for widespread use in multiple therapeutic
applications. The invention would be situated on the skin surface
of a patient and would be activated so as to reduce the overall
occurrence of infections and/or increase wound healing rates. As
provided, the device will comprise an integrated power supply and
pre-programmable stimulator/control system on a flexible polymeric
substrate layer with areas of stimulating electrodes, applied using
techniques such as those found in additive manufacturing processes.
The device is especially valuable in treating biofilm-based
infections.
Inventors: |
Bogie; Kath M.; (Shaker
Heights, OH) ; Garverick; Steven L.; (Cleveland
Heights, OH) ; Zorman; Christian A.; (Euclid, OH)
; Howe; Daniel S.; (San Diego, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The United States Government, as represented by the Department of
Veterans Affairs
Case Western Reserve University |
Washington
Cleveland |
DC
OH |
US
US |
|
|
Assignee: |
The United States Government, as
represented by the Department of Veterans Affairs
Washington
DC
Case Western Reserve University
Cleveland
OH
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20160287868 A1 |
October 6, 2016 |
|
|
Family ID: |
57014997 |
Appl. No.: |
14/675270 |
Filed: |
March 31, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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14363277 |
Jun 5, 2014 |
9320907 |
|
|
PCT/US2013/022139 |
Jan 18, 2013 |
|
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14675270 |
|
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|
61594105 |
Feb 2, 2012 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/0472 20130101;
B29K 2105/16 20130101; B29L 2031/753 20130101; B33Y 10/00 20141201;
B29K 2995/0005 20130101; B33Y 80/00 20141201; B29K 2079/08
20130101; B29C 64/135 20170801; B33Y 50/02 20141201; B29K 2505/14
20130101; A61N 1/0468 20130101; A61N 1/36031 20170801 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/04 20060101 A61N001/04; B29C 67/00 20060101
B29C067/00 |
Claims
1. A method for making electrode patterns in flexible substrates
for use with an Integrated Surface Stimulation Device (ISSD) for
wound therapy and infection control, the method comprising:
defining dimensions of a flexible substrate layer using at least
one STL (STereoLithography) file; defining topographical areas of
electrically conductive materials and electrically non-conductive
materials using said at least one STL (STereoLithography) file;
forming, through additive manufacturing techniques, a flexible
substrate layer having said dimensions, formed from the group
comprising polyimides, liquid crystal polymers, silicones, fabrics,
and thermoplastic polymers; and forming areas of electrically
conductive material and areas of electrically non-conductive
materials based upon said defining of topographical areas of
electrically conductive materials and electrically non-conductive
materials, wherein: said step of forming areas of electrically
conductive material and areas of electrically non-conductive
materials utilizing said additive manufacturing techniques and
executing concurrently with said forming of said flexible substrate
layer.
2. The method for making electrode patterns in flexible substrates
for use with an ISSD for wound therapy according to claim 1, the
method further comprising: imaging a patient wound, to include at
least wound dimensions and shape; and creating said at least one
STL (STereoLithography) file based upon said imaging,
3. The method for making electrode patterns in flexible substrates
for use with an ISSD for wound therapy according to claim 2, the
method further comprising: customizing said dimensions of a
flexible substrate layer and said topographical areas of
electrically conductive materials and electrically non-conductive
materials according to said imaging.
4. A method for using an ISSD for wound therapy and infection
control, the method comprising the following steps of: assessing a
wound and infection state; attaching an encapsulated power/control
module to said customized ISSD patch with electrodes and a flexible
substrate; applying a customized ISSD patch with electrodes and a
flexible substrate immediate to a wound location; setting ISSD
controls, including setting at least one of the following of a
power profile or at least one customized stimulation pattern;
initiating ES power and sequences on a resulting set up; and
monitoring wound and at least one of the following of battery
power, impedance, and temperature.
5. The method of using an ISSD for wound therapy and infection
control according to claim 4, the method further comprising:
formulating a customized electrode pattern according to said step
of assessing a wound type and infection state; fabricating said
customized electrode pattern by various techniques, including foil,
additive or 3-D printing techniques, or alternatively, by
traditional deposition techniques; and combining said customized
electrode pattern with selected flexible substrate as a resulting
patch for patient wound therapy.
6. The method of using an ISSD for wound therapy and infection
control according to claim 5, wherein said step of attaching an
encapsulated power/control module to said customized ISSD patch
with electrodes and a flexible substrate further comprises:
combining a customized disposable flexible substrate with a
re-usable sterilizable encapsulated power/control module.
7. The method of using an ISSD for wound therapy and infection
control according to claim 6, the method further comprising:
attaching a power source comprising a rechargeable battery with
capacity of at least 450 mA-h.
8. A method for simultaneous treatment and monitoring of wounds and
infections comprising the following steps of: electrically
connecting an encapsulated power module to said customized ISSD
patch; applying a customized ISSD patch with electrodes and a
flexible substrate immediate to a wound; establishing a wireless
communication connection for remote control between a control
module and said encapsulated power module; monitoring ongoing wound
and infection indicia over a course of time; establishing, based
upon said step of monitoring ongoing wound and infection indicia
over a course of time, a dynamic wound treatment ES profile for
execution over said course of time; and executing, over said course
of time, said dynamic wound treatment profile and said dynamic
infection control ES profile at said control module.
9. The method for simultaneous treatment and monitoring of wounds
and infections according to claim 8, wherein said steps of: (i)
monitoring ongoing wound and infection indicia over a course of
time; (ii) establishing a dynamic wound treatment ES profile for
execution; and (iii) establishing a dynamic infection control ES
profile for execution are all processed according to an open loop
program option or a closed loop option.
10. The method for simultaneous treatment and monitoring of wounds
and infections according to claim 9, wherein said step of
monitoring ongoing wound and infection indicia over a course of
time, and said step of executing said dynamic wound treatment ES
profile and said dynamic infection control ES profile are both
effectuated remotely through use of wireless communication.
11. A device for remote treatment of wound and infections
comprising: a customized ISSD patch with electrodes and a flexible
substrate; an encapsulated power module electrically attached to
said customized ISSD patch; and a control module having a wireless
communication module, said control module being in remote
communication with said encapsulated power module.
12. The device for remote treatment of wound and infections
according to claim 11, wherein: said flexible substrate is
disposable; and wherein said encapsulated power module is a
sterilizable encapsulation.
Description
[0001] This application claims priority to U.S. non-provisional
patent application Ser. No. 14/363,277, filed on Jun. 5, 2014,
which is a U.S. National Stage filing under 35 USC 371 of, and in
turn claims priority from, PCT Application No. PCT/US13/22139,
filed on Jan. 18, 2013, which in turn claims priority from U.S.
provisional Patent Application No. 61/594,105, filed on Feb. 2,
2012, the contents of which are each hereby incorporated by
reference in the entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to medical devices that
utilize electrical stimulation for surface-stimulated treatment of
infections and wounds in the human body. The present invention is a
patch, i.e. a thin, partially or fully flexible covering, which
incorporates a stimulation controller, wireless communication
device, miniaturized or wireless power, and a substrate with
customizable treatment electrodes.
[0003] Open wounds can be difficult to treat. In particular,
chronic wounds, such as ischemic wounds and pressure ulcers, are a
major clinical challenge in the long-term care of people with
physical impairment and/or disability. Even in mild cases, special
care is required. Scientific studies show that electrical
stimulation quickens wound healing, reduces scar formation, and can
reduce discomfort therefrom. For example, galvanic treatment has
been known for many years as a means to deliver drugs and cosmetic
active agents into the skin for therapeutic purposes. Such
approaches are based on mechanisms such as iontophoresis and
electro-osmosis. A review of the literature reveals that galvanic
treatment is also valuable in the treatment of wounds and scars,
via several modes of action including accelerated cell
regeneration; tissue repair; accelerated cutaneous barrier recovery
(even with very low current); improved blood circulation; improved
respiration; and scar reduction. However, to date electrotherapy
protocol has been quite lacking especially for problematic wounds
such as pressure ulcers, and furthermore, its use in corollary
conditions, such as infections is essentially unknown.
[0004] To this end, there is a recognized need for an improved
integrated surface stimulation device (ISSD) that can be used in a
variety of mobile care settings, from the intensive care unit to
the patient's home. It would be highly advantageous for this ISSD
to employ electrical stimulation for wound treatment and/or
infection control, embodied on a thin and flexible substrate that
includes a self-contained power source and controller. Preferably,
such a system and device should be disposable and customizable for
particular types of wounds and infection associated therewith,
including the treatment protocol itself. Additional benefits may be
recognized when such a device may be fabricated according to novel
additive manufacturing techniques, and when provided with advanced
power sources, such as Lithium polymer batteries or the like that
provide sufficient power in order to deliver reliable stimulation
to a large wound for an extended period of time. Further benefits
can be realized when the novel application of the innovative
techniques and apparatus is used in order to effectively treat
infected wounds, especially those with biofilm colonies.
SUMMARY OF THE INVENTION
[0005] The present invention relates to a novel approach to
improving the management of infection and wound healing through the
use of an integrated surface stimulation device (ISSD). The ISSD
for wound management and infection control, according to the
present invention, is a wearable, flexible adhesive electrical
stimulation patch that is wireless, with the totality of the
component electronics and power source being wholly encapsulated
thereon in a thin, flat instantiation. In providing the above, the
invention utilizes advanced materials and fabrication techniques,
and is designed so as to have a simple, user-friendly communication
interface. More specifically, one embodiment of the invention
contains all the components of a single-channel, current-controlled
stimulation system within a lightweight, flexible,
independently-powered portable device utilizing a custom,
miniaturized (approximately 2-9 mm.sup.2) Application-Specific
Integrated Circuit (ASIC), also known as a custom IC. The ISSD uses
advanced materials and cutting-edge fabrication techniques to
provide sustained or intermittent application of Electrical
Stimulation (ES) combined with maintenance of a stable wound
healing environment. An optional software package with a graphical
user interface (GUI) may also be provided for use on a partner
device connected to the invented device, to be employed by a
medical professional.
[0006] The ISSD comprises a complete wireless stimulation system in
a disposable and/or reusable flexible device for widespread use in
multiple therapeutic applications. The invented device would be
situated on the skin surface of a patient and would be activated so
as to reduce the overall occurrence of infections and/or increase
wound healing rates. As manufactured, the device will comprise an
integrated power supply and pre-programmable stimulator/control
system mounted on the upper face of a flexible polymeric `backbone`
or substrate layer. The lower thee of the substrate layer will
comprise areas of stimulating electrodes, applied using thin film
deposition techniques such as sputtering, evaporation,
electroplating, and spray coating or foil deposition, Alternatively
the substrate layer may be constructed using additive manufacturing
techniques (one variant of which is known as 3D printing in some
applications), whereby interconnection means prepared thereon exist
for connection between components of circuitry and include vias
that are constructed and filled in a single process. The advantage
of additive manufacture of the substrate as disclosed herein is
that this approach would enable building the substrate in a single
process using multiple materials, thereby eliminating the need for
a mask (hereafter occasionally referred to as a "maskiess
fabrication" of the substrate with electrodes), and further to this
point, the same may be customized in a dramatically easier fashion
than if produced according to the other embodiments of
manufacturing as referenced above. Such maskless fabrication
techniques, vary, but in one illustrative embodiment, may comprise
additive manufacturing approaches such as selective laser melting,
where successive layers of material powder are exposed so as to be
melted or heated with a laser or ion beam, thereby hardening only
certain portions in order to produce the desired final structure.
Further to this, the equipment may be machines such as the
Envisiontec Bioplotter.TM., although many other machines may be
utilized as can be readily appreciated. The non-conductive
materials may be polyamide, silicone or other flexible polymeric
materials. The conductive materials may by silver particles in a
binder material, platinum particles in a binder material,
conductive inks or other conductive polymeric material. When
provided in accordance with the above, the device can then be
applied to the user with a medical grade pressure sensitive
adhesive coating provided on the lower face of the substrate
layer.
[0007] When provided as such, the invented system has features
which also make it advantageous for patients when compared with
conventional systems, in that it offers the advantage of electrical
stimulation for wound management and infection control, but does so
in a miniaturized, wholly self contained reusable wireless adhesive
patch-like device that can be worn on a patient's skin. To this
end, the present invention overcomes the aforementioned and other
disadvantages inherent in the prior art.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] With reference now to the drawings in detail, it is stressed
that the particulars shown, are by way of example and for the
purposes of illustrative discussion of embodiments of the present
invention, and are presented for providing what is believed to be
the most useful and readily understood description of the
principles and conceptual aspects of the invention. In this regard,
no attempt is made to show structural details in more detail than
is necessary for a fundamental understanding of the invention, the
description taken with the drawings making apparent to those
skilled in the art how the several forms of the invention may be
embodied in practice. Accordingly:
[0009] FIG. 1 is a photograph showing the physical appearance of an
incomplete prototype of a wound treatment device as applied to a
user, accordin to one embodiment of the invention;
[0010] FIG. 2 is a schematic representation of an exemplary cross
section of ISSD electrode-supporting substrate in accordance with
one embodiment of the invention;
[0011] FIG. 3 is an illustrative block diagram of flexible ISSD
circuitry 60 and related peripheral electronic components of the
device according to one embodiment of the invention;
[0012] FIG. 4 is schematic cross-sectional views illustrating an
exemplary fabrication sequence, reading in order from left to
right, with polyimide substrate used in the device in accordance
with one embodiment of the invention;
[0013] FIG. 5 is an electrical schematic diagram of one embodiment
of the device according to the invention; and
[0014] FIG. 6 is an operational flow diagram illustrating an
exempla reatme protocol utilized with one embodiment of the
invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] Before explaining at least one embodiment of the invention
in detail, it is to be understood that the invention is not limited
in this application to the details of construction and the
arrangement of the components set forth in the following
description or illustrated in the drawings. The invention is
applicable to other embodiments of being practiced or carried out
in various ways. Also, it is to be understood that the phraseology
and terminology employed herein is for the purpose of description
and should not be regarded as limiting.
[0016] At its broadest level, the present invention relates to a
medical device for treatment of wounds and/or infection(s)
comprising at least one electrically powered patch comprising ISSD
circuitry that includes interconnecting wires on a substrate layer;
at least one stimulation controller, the stimulation controller
being configured so as to provide variable stimulation patterns; at
least one configuration of electrodes attached to the substrate
layer and in electrical connectivity with the at least one
stimulation controller; at least one bi-directional wireless
communication link, the bi-directional wireless communication link
or module comprising at least one RF or infrared based interface;
at least one power source electrically coupled to at least one
configuration of electrodes and at least one stimulation
controller. The ISSD must also include means for encapsulating the
circuitry; and an adhesive means for attaching the substrate layer
to a treatment surface. The device is fabricated from thin and
flexible materials to enable at least those surfaces that contact a
patient skin to conform to the contour of the patient, and may be
processed with thick or thin film deposition techniques and/or
additive manufacturing techniques for application of the electrodes
and other circuitry components, and may also provide for the power
source to also feature a thin and flexible profile. By way of
illustration, one recitation of exemplary additive manufacturing
might include the following steps: 1) Load materials into
appropriate low and high temperature cartridges; 2) Adjust
temperature for each dispensing head to deliver appropriate
material flows; 3) Define dispense rate and pressure based on
materials characteristics; 4) Build up substrate in layers, with
materials changes in each layer such that the conductive material
is deposited in areas to form electrodes and vias defined by
pre-determined geometry and 5) Apply hydrogel over electrode
surfaces on lower face of substrate.
[0017] The principles and operation of powered treatment devices
according to the present invention may be better understood with
reference to the figures. The figures show exemplary embodiments of
the present invention and are not limiting.
[0018] FIG. 1 shows one embodiment of a powered treatment device 5
as a patch 5', including only the stimulation electrodes and
controller components of the ISSD circuitry 60, where the latter
has been fully implemented as an ASIC in order to reduce size and
improve flexibility of the device. FIG. 2 shows the schematic
cross-section of the supporting substrate, which is optionally made
of flexible materials. FIGS. 3 and 5 show two additional
embodiments of stimulation controller 20, one (FIG. 3) which
employs an ASIC (custom IC) to implement only the high-voltage,
sensing, and wireless communication modules 40 of stimulation
controller 20, and another (FIG. 5) in which off-the-shelf (OTS)
components have been used to implement these functions. In both
embodiments, stimulation controller 20 must be interconnected with
the electrodes 10 through interconnecting wires 17 (not
specifically depicted) and electrically connected with power source
or supply 50, all of which are carried by a disposable substrate
layer 15. Power supply 50 and stimulation controller 20 components
can be electrically connected or alternatively, bonded to the upper
face or side of substrate 15, or alternatively, power supply 50 and
stimulation controller 20 components can be reversibly bonded, that
is, they can be removed for reuse with a different substrate, by
use of releasable connective elements. Thin metallic conductive
electrodes and interconnects that are fabricated thereon. In
certain illustrative embodiments. three different polymeric
materials may be used to construct the flexible structures of the
substrate layer 15, specifically materials such as polyimides,
liquid crystal polymers, silicones, fabrics and thermoplastic
polymers.
[0019] Flexible stimulating electrode 10 regions can therefore be
microfabricated onto the lower face or side, which will be
secondarily coated and/or printed with a medical grade pressure
sensitive adhesive for attachment to the user. Because one key
design concept underlying inventive device 5 is forward compatible
upgradeability, it is provided with a flexible or adaptable
architecture that allows for the potential for functional expansion
such as multi-channel stimulation and biofeedback sensor
capability, which is provided as an alternate embodiment of the
present invention. The device comprises an integrated power supply
and pre-programmable stimulation controller 20 system electrically
and mechanically connected or otherwise mounted on the upper face
of a flexible polymeric `backbone` or substrate layer 15. The lower
face of substrate layer 15 comprises areas of stimulating
electrodes 10, applied using sputter coating techniques as
described hereafter and as illustratively shown in FIG. 4. The
device can be applied to the user with a medical grade pressure
sensitive adhesive coating 30. In most cases, it may be helpful to
have device 5 sterilized upon reuse or where not initially
sterilized prior to placement over an open wound area of a patient.
Many approaches may be used for this, and one illustrative
sterilization could involve using an ethylene oxide, which is a
low-temperature method that would allow device 5 to be fully
sterilized, but would not damage the on-board electronics. In one
embodiment, at least integrated power supply and pre-programmable
stimulation controller 20 system of device 5 is capable of being
sterilized, and to this end, may be fully encapsulated with a
polymer coating or the like in order to enclose the same from
moisture, and also, for protecting the electronic components
therein during sterilization by chemicals, etc., after use.
[0020] Accordingly, the above may be summarized in accordance with
one illustrative embodiment as a method for making electrode
patterns in flexible substrates for use with an ISSD for wound
therapy and infection control, as follows: (i) defining dimensions
of a flexible substrate layer 15 using at least one STL
(STereoLithography) file; (ii) defining topographical areas of
electrically conductive materials (e.g., stimulating electrode 10
regions and electrically non-conductive materials using at least
one STL; (iii) forming, through additive manufacturing techniques,
the flexible substrate layer 15 having the aforementioned
dimensions, formed from the group comprising polyimides, liquid
crystal polymers, silicones, fabrics, and thermoplastic polymers;
and (iv) forming areas of electrically conductive material
materials (stimulating electrode 10 regions) and areas of
electrically non-conductive materials based upon the defining of
topographical areas of electrically conductive materials
(stimulating electrode 10 regions) and electrically non-conductive
materials, such that the forming areas of electrically conductive
material (stimulating electrode 10 regions) and areas of
electrically non-conductive materials is done through the
aforementioned additive manufacturing techniques and is executed
concurrently with the forming of said flexible substrate layer 15.
The above is quite novel on various points, not the least of which
concerns the advantageous provision of concurrent formation of
flexible substrate layer 15 with electrically conductive material
materials (stimulating electrode 10 regions) and areas of
electrically non-conductive materials, a distinction which affords
savings of time, materials and expense in processing, and which
affords ease of production through portable additive manufacturing
machines such as 3-D printers and the like. In regards to the use
of STL file, the above method might further comprise imaging a
patient wound, by various visual means such as surface scanners,
photographic means, and/or visual and manual inspection, so as to
ascertain various wound indicia, at least wound dimensions and
shape. Once this resulting imaging has been created, the data
points therefrom are converted or created by use of image
processing software into at least one STL file. It is further noted
that the customizing of flexible substrate layer 15 and the
topographical layout or mask-like areas of electrically conductive
materials (stimulating electrode 10 regions) and electrically
non-conductive materials is done according to the imaging wherein
flexible substrate layer 15 will have a certain shape and
dimensions according to the shape and size of the wound and in
consideration of the natural or inherent shape of the affected body
part, while stimulating electrode 10 regions may have a certain
layout or electrode density based upon the size and shape of the
wound.
[0021] In a different embodiment however, the aforementioned
overall method may alternatively be partially summarized as
follows: (i) forming a flexible substrate layer 15 from the group
comprising polyimides, liquid crystal polymers, silicones, fabrics,
and thermoplastic polymers; (ii) using a pattern tool having an
embossing surface with embossments to present a relief pattern
complimentary to at least one desired relief pattern for a mask
layer; (iii) forming apertures in the mask layer; (iv) forming a
conductive material layer 10 on flexible substrate 15 based on the
relief pattern of the mask layer; and (v) electrically connecting
via the conductive material layer to output terminals of an ISSD
the through apertures.
[0022] The controller circuitry or stimulation controller 20
provides functions such as timing, intermittent operation, and
power monitoring, and combines with passive components, such as
resistors, capacitors, an inductor and connective wiring
(interconnecting wires 17, not specifically depicted), to produce
stimulating waveforms that are transmitted to inventive flexible
ISSD circuitry 60 which utilizes customized electrode 10 patterns
therein to ultimately deliver ES to a patient wound. In generating
the same, the duty factor of the high-voltage discharge pulses
produced using stimulation controller 20 will be proportionally
related to the average output power. The aforementioned passive
elements are usually separate components, and may, in one
embodiment, be mounted to a rigid circuit board (not depicted) and
can be connected by printed wiring (also not depicted). However, a
traditional rigid circuit board may not always meet design
requirements (such as specific types of required flexibility) that
may be required in some embodiments for stimulation controller 20.
In either case, all electronic components herein must be minimized
in quantity and size to maximize flexibility, as will be further
discussed below.
[0023] Depending on the desired effect and system requirements, one
may employ one of three possible illustrative embodiments, wherein
the stimulation controller 20 comprises either: (i) two ICs (an IC
microcontroller coupled with an ASIC stimulator); or (ii) a single
IC (e,g., an IC microcontroller coupled with an OTS discrete
stimulator); or (iii) a full-function IC, i.e. an ASIC that
includes both stimulator and microcontroller functions, each of
which is preferably miniaturized.
[0024] The ASIC embodiment may be either partially or completely
based on an ASIC that may include all circuit functions required
for actuation and sensing of the ISSD, as well as communication to
the external computing device, such as a laptop computer, smart
phone or the like, as contrasted with the discrete stimulator
mentioned above which provides for these components separately. In
either case, a high-voltage transistor may be required as part of a
boost converter that provides the approximately 100-V level
required for electrical stimulation in some circumstances. In one
embodiment, all boost converter circuitry, excluding the
aforementioned high-voltage inductor, diode, and storage capacitor
components, could potentially be integrated onto the ASIC. Analog
preamplifiers and analog-to-digital converter for sensing of
electrode current and other biological signals of interest can also
be fully integrated. Wireless communication circuits that comprise
the wireless communications module 40 (discussed hereafter) can
also be fully integrated, except for the infra-red (IR) photo
diodes based embodiment required by the illustrative IrDA channel
when used in a rigid circuit board-based embodiment. Because
IR-based connectivity approaches require line-of-sight to a given
partner device, in one illustrative embodiment, wireless
communications can employ alternative wireless communication
approaches such as the Bluetooth.RTM. Low Energy (version 4)
standard, or other RF approaches for wireless communications module
40. The inventive flexible ISSD circuitry 60 may then comprise at
least: (i) a stimulation controller 20 mounted on a circuit board
which is in turn mounted on substrate layer 15, wherein the
stimulation controller 20 has different embodiments, either two ICs
(an IC microcontroller coupled with an ASIC stimulator); or a
single IC (e.g., an IC microcontroller coupled with an OTS discrete
stimulator); or a full-function ASIC that provides both
microcontroller and stimulator functions, as discussed herein);
(ii) a bi-directional wireless communications module 40 which
includes connectivity to an IR interface (photodiode pair) or an RF
interface required for wireless communication; (iii) a high-voltage
boost converter circuit in electrical connectivity with stimulation
controller 20, said high-voltage boost converter circuit comprising
an appropriate high-voltage inductor/diode/storage capacitor as
required by stimulation controller 20, said high-voltage boost
converter circuit being charged to the aforementioned high-voltage
level; (iv) power source 50 connected to the circuit board upon
which stimulation board 20 is mounted; (v) stimulating electrodes
10 connected an interconnection means to the circuit board upon
which stimulation board 20 is mounted; and (vi) the interconnecting
means, wherein the interconnection means is provided for
electrically connecting at least stimulating electrodes 10 with
stimulation controller 20, the interconnection means illustratively
including at least one or more components chosen from the group
comprising: interconnecting wires 17 (not specifically depicted);
thin film deposited structures; or thin film platinum interconnect
structures in combination with a bonding, wherein the bonding is
chosen from the group comprising wire bonding or flip chip bonding.
In contrast to the full-function ASIC embodiment, the two-IC
embodiment offers a separate high-voltage stimulator ASIC and
microcontroller in order to permit straight-forward firmware
upgrades and to minimize the cost of the ISSD, given that
inexpensive OTS microcontrollers can be employed. This embodiment
provides for the function of the stimulator to be preserved in the
case where the microcontroller requires upgrading. The stimulator
may be implemented using any preferred technology independent of
the microcontroller and furthermore, may include sensory circuits
such as for monitoring movement or other vital statistics in a
user. In any case, the above ISSD circuitry can be encapsulated via
an encapsulation means that protects the same from moisture and the
like, all of which, when mounted on substrate layer 15, can be
adhered to the skin of a user through the adhesive means described
herein.
[0025] Regardless of the particular embodiment of stimulation
controller 20, ISSD circuitry 60 may employ an aforementioned
high-voltage boost converter circuit with a step-up loop that
includes the aforementioned high-voltage transistor, and a storage
capacitor that is rated for an illustrative maximum 100V, at an
illustrative 100-nF capacity in order to maximize the voltage
aspects of the overall system, and for increasing the
(interchangeable) battery life of power source 50. In both the
two-IC embodiment and the full-function ASIC embodiment, the
step-up capacitor may be provisioned to be physically separate, off
chip, but in electrical connectivity therewith. In the particular
case of the two-IC embodiment, both ICs can be obtained in die form
and can be 1) flip-chip bonded directly to metal traces on the
flexible substrate, then sealed with protective coating, or 2) wire
bonded to the lead frame of a standard surface-mount IC package
that would then be hermetically sealed. The former is potentially
smaller and more flexible, while the latter is simpler to
manufacture and potentially more robust. Where an embodiment is
desired that includes customized rather than OTS ICs, a custom IC
(ASIC) could be fabricated using an illustrative 0.7-micron
high-voltage CMOS foundry process provided by ON Semiconductor
(available from ON Semiconductor of Phoenix, Ariz.), via the MOSIS
service of Marina del Rey, Calif. Thereafter, it is noted that in
the present invention, variable stimulation patterns are provided
to accommodate different types of wounds and the changing treatment
thereof over time. To this end, software can be pre-programmed on
the microcontroller of a two-IC embodiment, or on the ASIC of a
full-function ASIC embodiment. The various parameters that may be
considered when providing such software within device 5 might, in
one embodiment, be effected through usage of the below
considerations set forth in Table 1, below.
TABLE-US-00001 TABLE 1 Specifications for conformable flexible
integrated surface stimulation device (ISSD) Variable Relevance
Criteria Safety Prolonged contact with skin Substrate materials
must be requires neither the materials biocompatible &
stimulation may be employed nor the stimulation charge-balanced.
delivered will cause tissue damage Reliability In order to be
effective, ES Stimulation is ideally delivered must be delivered as
consistently over an illustrative 7 day programmed. lifetime of the
device. Sterilization Devices in contact with open May use
illustrative ethylene oxide wounds must be initially sterile
sterilization to achieve sterility while to minimize infection.
maintaining electrical functionality. System configuration Flexible
Chronic wounds occur on many Conform to an arc equal in radius to a
parts of the body. circumference of any rounded body parts. Size
Device must be suitable for Overall footprint will vary to fit
target clinical use in a variety of wound. wound locations.
Electrode layout Stimulating electrodes deliver Electrodes to be
located at the wound therapeutic ES to the wound. margins and can
be patterned based on wound size and shape. Low-profile & Not
interfere with overlying Maximum height less than 3 mm in one
lightweight bedclothes or cause high illustrative embodiment.
Maximum pressure if accidentally lain on. weight less than 15 g in
one illustrative embodiment. System function Wound occlusion A
moist microenvironment Maintenance of adherence to skin for up
provides optimal wound to 7 days with full wound occlusion. healing
User-friendly interface Clinical acceptance requires Includes a
customizable design for an ease-of-use. intuitive GUI for selection
and control of stimulation patterns. Programmable Optimal
stimulation variables Stimulation pulse variables making up for ES
therapy can be defined. the respective profile(s) may be based
Stimulation profiles can be on data from prior clinical studies,
applied intermittently or illustratively described as: continuous,
for duty cycles Range Increment from 5 min/day to 24 h/day. Pulse
width 0-200 .mu.s 5 .mu.s Amplitude 0-20 mA 0.5 mA Frequency 0-20
Hz 1 Hz Power supply Independent power supply, Battery-powered,
capable of up to 7 capable of 7 days use is days continuous use.
Battery will last required for un-tethered system. longer with
intermittent use.
[0026] As mentioned above, the central core of present device 5 is
comprised of a flexible polymeric biomaterial insulating substrate
(substrate layer 15) on which the flexible power supply 50 and
rigid stimulation controller 20 will be attached along with the
thin metallic electrodes and interconnects that are fabricated
thereon. In certain illustrative embodiments, three different
polymeric materials may be used to construct the flexible
structures of the substrate layer 15, specifically materials such
as polyimides, liquid crystal polymers, and thermoplastic polymers.
In one particular embodiment, a combination of thick polyimide
foils and thin film resins may be used for producing substrate
layer 15 in order to meet the requirements for the device to be
durable for longer periods in different environments, such as those
encountered where use is needed for say, one week of continuous use
in moist environments. One illustrative example of production of
this variant of substrate layer 15 within the overall context of
the present invention may be seen in FIG. 4, which details an
exemplary process sequence for fabricating a flexible polyimide
ISSD substrate. Substrate layer 15 may optionally be manufactured
from any polytner material that is suitable for flexible
electronics and biomedical uses according to a process that
utilizes patterning that creates via structures thereon between the
aforementioned circuit components through use of a micromachining
step, or any suitable material which can accommodate the powered
treatment device components, Suitable materials include, but are
not limited to woven material, non-woven material, polymers, or a
combination thereof, and, in the case of woven materials might
alternatively include the usage of smart fabrics which employ
conductive traces on or within the fabric whether purely woven,
knitted, sewn, couched, or whether provided as e-broidery and/or
printed structures. Nevertheless, in one illustrative embodiment,
substrate layer 15 may alternatively be made from liquid crystal
polymers, polyimides, vinyl materials or polyester. Optionally,
substrate layer 15 can be made up of a plurality of materials,
which can be stacked or connected in a co-planar way by any
suitable attachment means. In some embodiments, base layer
substrate 15 is made up of one continuous piece of material.
Substrate layer 15 may readily facilitate attachment of the overall
device 5 to a desired body area. Attachment mechanisms may include
but are not limited to medical grade adhesives, adhesive strips,
suction cups and/or any combinations thereof. It has also been
found that lower cost medical grade pressure sensitive adhesives
such as Dermabond.RTM. (2-octyl cyanoacrylate, marketed under the
aforementioned trademark by Johnson & Johnson of New Brunswick,
N.J.) can be used, in one embodiment, to attach substrate layer 15
to intact skin. On removal, this type of medical grade pressure
sensitive adhesive preferentially adheres to the substrate
material, thus causing no skin damage, and can remain strongly
adherent after many hours or days.
[0027] In one embodiment, the present invention provides flexible
ISSD circuitry 60 to be situated on substrate layer 15 that is
processed from LCP for component side isolation, or as depicted in
FIG. 4, is alternatively processed from an illustrative
spin-castable polyimide material that utilizes patterning processes
in order to create via structures between the circuit components of
flexible ISSD circuitry 60. One exemplary approach utilizes a
micromachining step, such as a KOH-based wet chemical etching step,
in order to create the via structures depicted in FIGS. 2 and 4.
Such an etchant is effective in removing polyimide, and the use of
etchant-resistant materials such as platinum for electrodes 10 and
illustratively, chromium for the metallic etch mask can offer good
resistance to the etchant. Alternatively, plasma etching, laser
micromachining or other material removal techniques can be utilized
to realize the same structures, but in either case, successful
fabrication of the flexible ISSD circuitry 60 is critically
dependent on the fabrication of effective interconnect structures
that fill the microfabricated vias. Simultaneous electroplating on
both the sidewalls and the bottom surface of the vias enables
complete filling within an illustrative current thickness range of
say, 10 microns. Alternative electroplating options may be afforded
under ultrasonic conditions or with the use of `filler` materials.
Following fabrication of substrate layer 15 and interconnects
thereon, the discrete components thereof can be mounted at
designated locations on the (illustrative polyimide) substrate
layer 15 using a conventional electronics packaging adhesive.
Electrical connections that may comprise a part of an
interconnection means or in one embodiment, interconnecting wires
17, between the discrete components and the thin film platinum
interconnect structures may, in one illustrative embodiment, be
made by wire bonding. Flip chip bonding can also be used to make
secure electrical connections. The electrical connections can be
mechanically secured, electrically isolated and environmentally
protected by a third polyimide film of roughly the same thickness
as the discrete components (0.5 mm) so as to ensure complete
coverage of the wire bonds. It can be locally applied so as to not
interfere with the global flexibility of the substrate. After
localized polyimide encapsulation, the polyimide substrates can be
removed from their silicon wafer pairs by a mild acetone soak or
other appropriate methodology as known in the art.
[0028] In an additional embodiment (not specifically depicted), the
present invention provides a method of production of device 5 and
details of which, in terms of the illustrative materials and
fabrication, are discussed henceforth. The central core of the
device 5 is a flexible electrode-supporting substrate 15 comprised
of a Liquid Crystalline Polymer circuit material (LCP) sheet with
an 18 .mu.m copper cladding layer on one of its surfaces, not
necessarily depicted in FIG. 4, but which is nevertheless roughly
similar to the fabrication sequences of which are illustratively
described in one embodiment as seen in FIG. 4. In one embodiment,
the structures of electrodes 10 are fabricated on the non-copper
clad user-applied side of the insulating substrate 15 by
photolithographic patterning, platinum thin film sputtering, and
lift-off patterning. Electrodes 10 can be made of any suitable
material, such as zinc, copper, manganese dioxide, iron, magnesium,
silicon, sodium, silver, silver/silver chloride, carbon, graphite,
platinum, nickel, gold, lithium or a combination thereof.
Optionally, electrodes 10 can be made by any suitable technique. In
some embodiments, electrode is made by a suitable printing
technique. Electrodes 12 can be disposed in any suitable way on
substrate 15 in spaced relation to power source 50 and electrically
connected to power source 50 in any suitable way, or as described
herein. Vias for vertical electrical interconnects between the two
sides are then formed through the LCP by laser micromachining or
plasma etching from the copper-clad component side to the back of
the platinum electrodes. Platinum is sputter deposited on the
sidcwalls of the vias prior to electroplating to form a vertical
interconnect between the bio side electrodes and the stimulation
circuitry on the component side, as depicted in FIG. 2 and FIG. 4.
Lateral interconnect structures are then fabricated by lithographic
patterning and copper etching. The upper surface of the substrate
15 can be composed of a flexible or partially flexible barrier
material (optionally part of the aforementioned encapsulation
means) that provides a safe interface with the patient's
environment, yet protects the electrical components from direct
exposure to moisture, especially for the sensitive and delicate
microprocessor chips and electrical interconnects. This packaging
or encapsulation means must not impede the flexibility of the
substrate, be impervious to impurity diffusion, be mechanically
durable and be electrically insulating. Paulen.RTM. is one
embodiment for this application since it meets the design
requirements and has been found to be a suitable candidate coating
material for implanted medical devices. The lower side of substrate
15, which is intended to be applied to the skin of a patient, is
secondarily coated with a medical grade pressure sensitive adhesive
for attachment to the user, as part of the aforementioned adhesive
means. The metalized surfaces on the component side are passivated
by the application of a vapor deposited Parylene.RTM. film and/or
spin-castable polymer. Windows into the passivation layer can be
formed by laser micromachining or plasma etching to facilitate
electrical connection with discrete components, and can provide
patterning in varying layouts as may be required for customized
electrode patterns in specific applications involving particular
(size/type) wound remediation and the like. In order to meet the
need for customization, the above offers an aspect of provision for
modularity wherein the electronic components of ISSD circuitry 60
can be mounted on a second LCP sheet that serves as the substrate
for the reusable electronic components. Interconnect structures are
fabricated on this LCP sheet using the methods described above.
Therewith, further connections between the electronic components
and the interconnect structures, including the interconnection
means, can also be made by wire bonding or flip chip bonding. The
reusable component substrate can then mounted on the
electrode-supporting substrate using a conventional packaging
adhesive. The reusable component substrate is mechanically secured,
electrically isolated and environmentally protected by an
encapsulating means of polymer film of roughly the same thickness
as the discrete components (0.5 mm) so as to ensure complete
coverage of wire bonds. The upper surface of substrate 15 of device
5 is thus composed of a flexible barrier material that provides a
safe interface with the patient's environment in such a way that
protects the electrical components but does not impede flexibility.
Medical grade silicone can also be used to encapsulate the
electronic components in order to further ensure biocompatibility,
electrical compatibility as an encapsulating material for
microelectronics, and for ease of overall application.
[0029] In terms of power supply, device 5 provides for varying
approaches to power source 50, which typically requires provision
of a requisite voltage that is necessary to generate stimulating
waveforms. Power source 50 may comprise single-use batteries,
however discharge characteristics must be repeatable to ensure
reliable delivery of pre-programmed stimulation patterns. A flat
power discharge profile that will provide consistent power for
longer periods (e.g., approximately 7 days or so) of stimulation is
desirable, although the inventive electronics design also allows
for a somewhat sloped discharge profile. Therefore, any battery
chemistry can be used. The battery must be thin, small, durable and
strong. Power supply or source 50 can be modified in 1.5-V
increments as necessary, but generally will be either 1.5 V or 3.0
V. To this end, power source 50 is ideally thin and flexible as
specifically described below in one illustrative embodiment, but it
can nevertheless be of any suitable size and shape that can
accommodate the aforementioned requirements. In one embodiment, the
power source 50 is depicted as a single electrochemical cell.
However, power source 50 need not be limited to one cell, but may
include a plurality of connected electrochemical cells, galvanic
cells, batteries, with/without electronics configured to regulate
the electrical potential (voltage) to the level required by the
particular body area of the subject. In some embodiments, the
current and or voltage supplied by the power source is fixed and
cannot be adjusted by a user, although stimulation controller 20
can provide for any direct stimulation capability. The thickness of
the illustrative electrochemical cell or power supply 50 may be in
the range of about 4-20 mm thick. By way of example, a suitable
electrochemical cell may be a button or watch battery, such as a
lithium coin battery providing approximately 40 mA-hr at 3V, may be
utilized. However, this may in some cases prove too heavy and
bulky, and as such in alternative embodiments, power supply 50 may
be provided in a 1.5-V cell with step-up circuitry, with total
battery current consumption for a nominal stimulation pattern of
.about.1 mA, thereby giving a battery life of say, 240 hours with a
15% stimulation duty cycle, or may also be provided as a thin cell
applied using a suitable printing technique. Recent developments in
battery technology have led to the development of very low profile,
flexible `ribbon` batteries, such as PowerPaper.TM. batteries
(available from Graphic Solutions, Chicago, Ill.), which are
ultra-thin (<1 mm thick) flexible batteries that can be directly
printed onto a variety of surfaces. The cathode and anode layers of
these illustrative batteries arc fabricated from proprietary
ink-like materials, thereby creating a 1.5-V battery that is thin
and flexible and does not require bulky casing or encapsulation. In
addition, the materials used in this illustrative battery, zinc and
manganese dioxide, are classified by the Federal Drug
Administration (FDA) as environmentally friendly, non-hazardous and
may be disposed of without restriction. These types of batteries
are capable of providing up to 1 mA continuous current. However,
these ribbon type batteries often do not provide adequate power for
longer periods, and may be useful for more temporary applications
Terminals for connection thereto may be located in any desired
location to connect to the specific cell employed and may acquire
any suitable shape and size, depending on the specific
application.
[0030] In one alternative embodiment, stimulation controller 20 may
include a reusable stimulator PCB (35.times.20 mm) capable of
producing pulses up 21 mA in amplitude and 250 .mu.s in duration,
powered from a single 450 mAhr rechargeable Lithium Polymer battery
such as the PowerStream GM043436-PCB to power the device. The
benefit of such a exemplary battery is that it provides sufficient
power to deliver reliable stimulation to a large wound for an
extended period of time (for example, up to seven days) and can be
recharged for use with a different substrate on the same patient.
As can be appreciated, this represents a significant advance in
terms of overall performance.
[0031] The invented device may be provisioned as a single-channel,
single-pattern stimulator device, which would require a system
control switch (not specifically depicted) to switch the operating
state of device 5 between one of two states, off and on. However
alternative embodiments of the device will also include the
potential for multiple stimulation patterns and feedback to the
clinician or technician through stimulation controller 20, which as
discussed above, offers the capability for more sophisticated
control, interrogation and feedback options. In providing such
features, bi-directional wireless communication module 40 may
further include an RF or an infrared communication link and
protocol (such as an IrDA-based infrared communication link and
protocol) that allows the ISSD to communicate via multiple channels
with outside partner devices (not depicted) such as computers,
smart phones, tablets, lap tops, etc., so as to allow system
control and retrieval of sensor data without a physical connection
to device 5. In such an illustrative embodiment, the selected
communication protocol might allow up to 256 units to be used in
the same vicinity. If based on illustrative IrDA-type optical
components, it is noted that the inherently narrow transmission
focus thereof (approximately a 30 degree cone) can mitigate
potential communications issues emanating from inventive device 5,
because selection of a given partner device requires pointing the
partner device at the inventive device 5 being programmed at any
given time. Communication software can further be utilized for
modifying stimulation parameters in stimulation controller 20 and
for displaying stimulation waveform graphs on the partner device.
To this end software to allow system control and retrieval of
sensor data (e.g., outside control adjustment and feedback upload)
using the link might be provided in accordance with the
illustrative steps 610-670 as outlined in FIG. 6. Sensor data and
other status parameters can be uploaded to the partner device and
displayed to facilitate any necessary adjustments. Afterwards, any
(bio) data provided from the sensors (electrodes 10) can be
uploaded to the partner device for further analysis offline, if
desired by a given medical professional. To this end, the
aforementioned optional software package may also be provided with
a graphical user interface (GUI) for use on a partner device
connected to the inventive device, as employed by a medical
professional.
[0032] When provided in accordance with the above, treatment device
5, including all device components, has an overall thin and
flexible profile, which may suit the contour of a body area of a
subject. Treatment device 5 may therefore be of any size, color and
shape suitable for application to a desired body area. In some
embodiments, the thickness of device 5 may limited to 10 mm to
ensure flexibility, but may be thicker in other applications. The
thickness of device 5 may also be dependent upon the type of
material used and the flexibility of that material. In some
embodiments device 5 may be partially and/or completely disposable.
To this end, in some embodiments substrate layer 15 may be
disposable, while the ISSD circuitry 60 may be reusable (modular,
and therefore easily switched to anew replacement substrate layer
15), or alternatively, the whole device 5 may be deemed disposable,
Regardless of which embodiment is chosen, device 5 must be stable
over a wide range of temperatures and humidity levels, and may be
used over all body areas of a patient or user, and to this end, may
be designed or customized to fit any area of the body and to have
any desirable size, according to the area to be treated. By way of
further note, electrodes 10 can also be customized in terms of
overall number, size, and distribution on substrate layer 15. The
customization of electrodes is often less important when the
application usage of device 5 is for pain treatments (which are
better customized through the use of amplitude variations and the
like for varied pain states). In the ease of wound and/or infection
treatment, however, it is often important to be able to vary the
aforementioned design parameters in order to adequately treat
different types and sizes of wounds or states of infection, as well
as underlying presenting basis (e.g., whether planktonic or biofilm
in nature).
[0033] The device of the present invention can therefore be a fully
integrated device or can be part of a kit with removable components
so that the covering, battery source, etc. may be replaced as
needed. The device may also be removed from the body area at the
end of treatment time. Time of treatment can vary, and accordingly,
the device in some embodiments can be removed from contact with the
body area after a time period which can be predetermined, upon
expiration of a timer, or which can be determined according to the
desired treatment and/or until no more improvement can be seen. The
treatment can optionally be a one-time treatment, or can be
repeated in suitable time intervals any suitable number of times.
Use of the present invention can facilitate temporary alleviation
and elimination of the above conditions. Duration of effect can
therefore be affected by time and frequency of application,
stimulation pattern variables, type and amount of current used, and
severity of condition. In one embodiment, the device is a dermal
patch configured for home use. In other embodiments, the device can
be applied in a supervised environment. To this point, treatment
according to the present inventions may be beneficial in all body
areas. Being thin, flexible and versatile in shape and form, the
devices of the present invention can be designed to fit any area of
the body and to have any desirable size, according to the area
having the disorder.
Novel Electrotherapy for Acute Infected Wounds as a Method for
Inhibiting Planktonic and Bacterial Activity.
[0034] It is understood that wound infection delays healing and
increases mortality. Increasingly, antibiotics are showing reduced
efficacy in the face of multi-resistant bacteria. The increasing
prevalence of multi-resistant bacteria indicates that novel
approaches to infection control are needed as both alternative and
adjunctive therapies to standard antibiotic regimes. Such
infections are particularly challenging when biofilms are involved
given that biofilms have protective coatings made up of
polysaccharides and other components that shield the given bacteria
colony in the biofilm from treatment. Hence, there is a clinical
need for an intervention that can reduce incident infection, clear
existing infection and accelerate healing, especially when a
patient has an infection that exhibit biofilm colonies. The novel
use of Electrical Stimulation (ES) as disclosed herein has the
potential to address this clinical challenge by reducing incident
infection, clearing existing infection and accelerating
healing.
[0035] Both planktonic and biofilm bacterial wound infections can
be positively impacted by the novel use of ES to improve healing
rates in both acute and chronic wounds can be effectively treated.
The novel system and methods relating to ES treatment as disclosed
herein increases local metabolic activity of cells and tissue
oxygenation (flesh healing), disrupts existing biofilm colonies,
and even inhibits biofilm formation from the outset. Additionally,
the novel system and methods relating to ES also reduces acute
wound infection by bactericidal effects on many strains relevant
for complications of acute traumatic wounds. These effects may be
due to electrolysis products or to increases in bacterial membrane
permeability. Sustained ES application in accordance with the
present invention is bactericidal when applied to infected but
unwounded skin, and additionally, increases blood flow and
capillary density in compromised wounds, thereby speeding up
healing rates thereof. The resulting efficacy of the present
invention appears to vary with stimulation profile, which in at
least one illustrative case, is that the primary ES factor being
current density, thereby implying that the bactericidal effect is
electrochemically mediated. Low-intensity electric fields (e.g.,
those having a field strength of 1.5 to 20 V/cm and current
densities of 15 pA/cm.sup.2 to 2.1 mA/cm.sup.2) can combat the
inherent resistance of biofilm bacteria to biocides and
antibiotics. Biofilm infections are a well known for being
difficult to eradicate, especially when compared with planktonic
cell of the same species of bacteria. The novel application of
electrochemically mediated treatment with the inventive device
offers a bioelectric effect that reduces the concentrations of the
antibacterial agents needed to kill biofilm bacteria when compared
with those needed to kill planktonic cells of the same species. The
electric field from the novel ES device and method can aid the
disruption or penetration of the antibacterial agents through the
protective polysaccharide and other coatings that shield the
biofilm. This penetration is, in one illustration, accomplished by
a form of electrophoresis that may augment the electrochemical
generation of resulting surface agents that enhance the efficacy of
given antibacterial.
[0036] In accomplishing the above, the present invention therefore
provides for a method for using an ISSD for wound therapy as well
as for infection control, including for difficult infections like
biofilm based infections. To this end, in one illustrative
embodiment, the method might comprising the following steps of: (i)
assessing a wound and/or infection state; (ii) applying a
customized ISSD patch with electrodes 10 and a flexible substrate
15 immediate to a wound location; (iii) attaching an encapsulated
power/control module 20 to said customized ISSD patch with
electrodes and the flexible substrate 15; (iv) setting ISSD
controls, including setting at least one of the following of a
power profile or at least one customized stimulation pattern; (v)
initiating ES power and sequences on a resulting set up; and (vi)
monitoring wound and at least one of the following of battery
power, impedance, and temperature. Additionally, the inventive
method may further comprise: (vii) formulating a customized
electrode 10 pattern according to the step of assessing a wound
type and infection state; (viii) fabricating said customized
electrode 10 pattern by various techniques, including foil,
additive or 3-D printing techniques, or alternatively, by
traditional deposition techniques; and (ix) combining said
customized electrode 10 pattern with selected flexible substrate 15
as a resulting patch 5' for patient wound therapy. Also the method
may additionally include: (x) attaching an encapsulated
power/control module 20 to customized ISSD patch 5' with electrodes
10 and a flexible substrate 15, and additionally; (xi) combining a
customized disposable flexible substrate 15 with a re-usable,
sterilizable encapsulated power/control module 20. What is
specifically meant by encapsulated power module 20 being
sterilizable or having a sterilizable encapsulation is that it is
encapsulated in a plastic or other type of complete encapsulation
that can seal off the electronics therein from the harmful effects
of water or chemicals that may be used in the course of
sterilization at a level that can kill microorganisms. Separately,
it is noted that optional provision is contemplated for attaching a
power source 50 comprising a rechargeable battery (power supply 50)
with capacity of at least 450 mA-h.
[0037] In applying the above inventive method in a clinical
setting, one illustrative approach calls for the novel approach of
providing treatment and monitoring of wounds and infections
concurrently or at same time. Thus, one employing this novel
approach might be able to simultaneously or concurrently treat and
monitor wounds and infections through the following steps of: (i)
applying a customized ISSD patch 5' with electrodes 10 and a
flexible substrate 15 immediate to a wound of a patient; (ii)
electrically connecting an encapsulated power and control module 20
to customized ISSD patch 5'; (iii) establishing a wireless
communication connection for remote control between a control
module 40 and encapsulated power and control module 20; (iv)
monitoring ongoing wound and infection indicia over a course of
time ; (v) establishing, based upon the preceding step of
monitoring ongoing wound and infection indicia over a course of
time, a dynamic (e.g., potentially revisable depending on changes
to identified wound and infection indicia) wound treatment ES
profile for execution over said course of time; (vi) establishing,
monitoring ongoing wound and infection indicia over a course of
time, a dynamic infection control ES profile for execution over the
course of time; and (vii) executing, over the course of time, said
dynamic wound treatment ES profile and the dynamic infection
control ES profile at the control module. Additionally, the method
may further include processing steps (iv)-(vi) through an open loop
program option or a closed loop option. An open loop program option
may be further described in one embodiment as: In the open-loop
embodiment the medical professional will receive a report of the
wound/infection status transmitted from the ISSD. The medical
professional will be able to alter the ES profile remotely to
maintain optimal treatment. In the closed-loop embodiment, the
medical professional will receive a report of the wound/infection
status transmitted from the ISSD and the ISSD will adjust the ES
profile in real time based on the wound indicia being
monitored.
[0038] In the above, it is noted that the wound and infection
indicia may include particulars such as wound temperature, wound
impedance, and wound pH. Monitoring such particulars is
advantageous inasmuch as it has now been found that impedance
decreases over time where a wound is healing and/or where infection
presence is decreasing, and similarly, temperature exhibits similar
paradigms of decrease. Additionally, the step of monitoring while
treating is further advantageous in that all wound healing (and
infection resolution) goes through different stages over time, and
consequently, it has now been found that the inventive approach of
utilizing treatment factors such as pulse width, pulse interval,
and interpulse amplitude variables is to be pursued in a dynamic
fashion, whereby the same are increased or decreased over time
increments and over the overall course of time in response to the
respective stage of healing or infection resolution. Similarly, the
monitored presence of say, just an infection without wound presence
normally entails utilization of different treatment factors, such
as a relatively lower current than that which is normally employed
compared to wound healing. Also similarly, monitoring for biofilms
as opposed to planktonic infections may alter the treatment
factors, just as monitoring for an acute infection turning into a
chronic infection, because a chronic infection (unlike acute) may
normally imply wound treatment factors in addition to purely
infection treatment factors. Hence, the infection state as
monitored can drive the electrical pattern and any accompanying
customization therewith.
[0039] it is further noted that the aforementioned method for
simultaneous treatment and monitoring of wounds and infections may
provide that the step of monitoring ongoing wound and infection
indicia over a course of time, as well as the step of executing the
dynamic wound treatment ES profile and the dynamic infection
control ES profile may both be effectuated remotely through use of
wireless communication, such as bi-directional wireless module(s)
40 as depicted in FIG. 1. In some cases, control module 20 has
wireless communication module 40 encapsulated therewith.
[0040] Illustratively, the following particulars were observed in
one exemplary usage of the inventive system and apparatus for
treating wound infections:
EXAMPLE 1
Electrical Stimulation (ES) Promotes the Healing of Ischemic
Wounds
[0041] Approach: The effects of varying clinically relevant ES
variables were evaluated using a modified version of the Gould F344
rat ischemic wound model. Stimulation was delivered using the novel
lightweight integrated, single-channel, current-controlled ISSD as
further disclosed herein. Customized ES patterns in accordance with
the novel approach disclosed herein were utilized, which, in this
illustration, included stepwise variation, indicating the effects
of five (5) different stimulation paradigms within an appropriate
current density range to be studied. These five (5) different
illustrative stimulation paradigms included: Pattern 1: pulse
amplitude 4 mA, pulse width 100 .mu.s, interpulse interval 50 ms;
Pattern 2: pulse amplitude 2 mA, pulse width 100 .mu.s, interpulse
interval 50 ms; Pattern 3: pulse amplitude 6 mA, pulse width 100
.mu.s, interpulse interval 50 ms; Pattern 4: pulse amplitude 4 mA,
pulse width 150 .mu.s, interpulse interval 50 ms; and Pattern 5:
pulse amplitude 4 mA, pulse width 100 .mu.s, interpulse interval 40
ms. Within each of the aforementioned five (5) respective groups,
8-10 animals were treated for 28 days or until the ischemic wounds
were healed, and additionally, 5 animals were treated for just 12
days. Eight (8) rats received sham devices as a control. A
quantitative multivariable outcomes assessment procedure was used
to evaluate the effects of ES.
[0042] Results: Ischemic wounds treated with a decreased interpulse
interval (IPI) had the highest rate of complete wound closure at
three (3) weeks. Wounds treated with decreased pulse amplitude (PA)
had a lower proportion of closed wounds than sham (control)
ischemic wounds and showed sustained inflammation with a lack of
wound contraction.
Results According to Specific Illustrations of Exemplary
Stimulation Variable Settings:
[0043] Acute infected wounds: ES was delivered by the ISSD with a
10% duty cycle for up to 28 days or until all treatment wounds
appeared to be fully healed. The median values selected for
proof-of concept testing were pulse amplitude 11 mA, pulse width
110 .mu.s, pulse frequency 17 Hz. By 21 days post-injury, ES
treated infected wounds were 84% smaller than untreated control
wounds.
[0044] Chronic wounds: Optimal stimulator parameters will vary
depending on wound type and extent, but benefits have been seen for
a wide range of parameters. The optimal treatment parameters for
delivery of effective ES for chronic wound therapy are therefore
guided by the underlying physiological effects. In pre-clinical
testing, ES delivered by the ISSD with a 10% duty cycle with pulse
amplitude 4 mA, pulse width 100 .mu.s, interpulse interval 40 ms
had the highest rate of complete wound closure at 3 weeks.
[0045] Conclusion: The systematic study of innovatively varying ES
paradigms using the novel ISSD provides insight into the
advantageous use of ES in ischemic wound healing. This conclusion
is based upon the following findings. Specifically, clinically
appropriate ES can more than double the proportion of ischemic
wounds closed by three (3) weeks in this model. Ninety percent
(90%) of wounds treated with a decreased IPI healed by twenty-one
(21) days compared with only twenty-nine percent (29%) of ischemic
wounds treated with decreased PA, which appears to inhibit
healing.
[0046] It is further noted that, in the above example (as well as
for other illustrations of the novel method) the innovative ISSD
undergirded much of the advantageous results. Specifically, the
innovative delivery of power has superior reliability, and is able
to deliver ES over an extended period of time that heretofore has
not been realized. Thus, the innovations of: customized electrodes,
customized pulse, customized width, intermittent v. continuous
pulsing, etc as disclosed herein are indeed novel, and furthermore,
the actual use of ES in both acute and chronic wounds (especially
in combating troublesome biofilms) is heretofore unknown.
[0047] The above approach can be employed in human (in vivo)
applications in order to speed up healing of both chronic and acute
wounds, as well as for reducing infections of both planktonic and
biofilm types, especially in topical rather than systemic
applications. In doing so, one illustrative method might include
some or all of the following exemplary steps: 1) Assess wound type
and/or infection type; 2) Formulate customized electrode pattern by
considering, for example wound size; 3) Fabricate customized
electrode pattern by various techniques, including additive or 3-D
printing techniques, or alternatively, by traditional deposition
techniques, combine with selected flexible substrate as resulting
patch for patient wound; 4) Apply patch immediate to wound
location, attach ISSD controls; 5) Set power profile or customized
profile in accordance with particulars described elsewhere herein;
6) Initiate ES power and sequences on resulting set up; 7) Monitor
battery power, impedance, and temperature. Thereafter, if the
measure impedance increases over time from a base impedance as
measured, then that means that the target wound is healing. Also,
operators should monitor the measured temperature at the wound
site, as this factor is typically related to infection level, such
that elevated temperature indicates infection activity overall,
although it is to be noted that this normally is more indicative of
planktonic infections which are often more biologically active,
rather than biofilm based infections which tend to be more stable;
8) Retain patch with ES treatment on for a specified period of
time. In one exemplary usage where the system is complimentary to
antibiotic use, one illustrative period of use is for approximately
seven (7) days. Note that this treatment period may vary, in
accordance with wound type, patient history, electrode
customization and ES pattern profiles and current density chosen by
the medical provider.
[0048] Of additional note, is the understanding that in some
embodiments, one may dispense with steps 2 and 3 in cases where the
customized electrode pattern has already been fabricated off site
and combined with the flexible substrate for use as part of a
readily accessible stockpile or pre-configured customized patches
that are suitable for a specific wound types. Such provision would
eliminate the need to have fabrication equipment on site. In such
cases, the stock customized patches could be respectively produced
in mass according to shape and size (depending on the areas of body
being treated) and for type of wound (e.g., a more electrodes or a
higher density of electrodes in a given electrode pattern might be
used for wounds such as chronic wounds, or for acute traumatic or
surgical wounds, and the like).
[0049] It is noted that the aforementioned can be applied to more
than just the actual flesh of human patients undergoing the
innovative ES treatment with the novel apparatus. Specifically, the
novel method and apparatus can also be adapted in an alternate
embodiment, to medical device surface treatments, such as for oral
biofilms, mouth guards, orthodontics, tracheostomy tubes,
endotracheal tubes, indwelling catheters as well as other classes
of catheter, and in general other medical devices that are
susceptible to infections, especially those caused by biofilm
buildup. In adapting to the same, an exemplary approach might be as
follows: to provide a tracheostomy tube with integrated conductive
regions which can be used to deliver bactericidal stimulation, a
flexible lining for a mouth guard bath with integrated electrodes
that can be activated to deliver bactericidal stimulation while the
fixture is being cleaned.
[0050] One skilled in the art can appreciate from the foregoing
description that the broad techniques of the embodiments of the
present invention can be implemented in a variety of forms.
Therefore, while the embodiments of this invention have been
described in connection with particular examples thereof, the true
scope of the embodiments of the invention should not be so limited
since other modifications will become apparent to the skilled
practitioner upon a study of the drawings, specification, and
following claims.
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