U.S. patent application number 16/398186 was filed with the patent office on 2019-10-24 for systems and methods for treatment of topical conditions.
The applicant listed for this patent is M.O.E. MEDICAL DEVICES LLC. Invention is credited to Gennady Friedman, Marc I. Zemel.
Application Number | 20190321091 16/398186 |
Document ID | / |
Family ID | 49775018 |
Filed Date | 2019-10-24 |
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United States Patent
Application |
20190321091 |
Kind Code |
A1 |
Zemel; Marc I. ; et
al. |
October 24, 2019 |
SYSTEMS AND METHODS FOR TREATMENT OF TOPICAL CONDITIONS
Abstract
The present disclosure provides a variety of systems, techniques
and machine readable programs for using plasmas and/or electric
fields alone, or in combination with other therapies, to treat
different tissue conditions as well as other conditions, such as
tumors, bacterial infections and the like.
Inventors: |
Zemel; Marc I.; (New
Rochelle, NY) ; Friedman; Gennady; (Richboro,
PA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
M.O.E. MEDICAL DEVICES LLC |
New Rochelle |
NY |
US |
|
|
Family ID: |
49775018 |
Appl. No.: |
16/398186 |
Filed: |
April 29, 2019 |
Related U.S. Patent Documents
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Application
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Filing Date |
Patent Number |
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14987529 |
Jan 4, 2016 |
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16398186 |
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13943012 |
Jul 16, 2013 |
9226790 |
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14987529 |
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PCT/US2012/031923 |
Apr 2, 2012 |
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13943012 |
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14215214 |
Mar 17, 2014 |
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14987529 |
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14215214 |
Mar 17, 2014 |
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14987529 |
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PCT/US12/55726 |
Sep 17, 2012 |
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14215214 |
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PCT/US12/31923 |
Apr 2, 2012 |
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PCT/US12/55726 |
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14584357 |
Dec 29, 2014 |
9351790 |
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14987529 |
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61584399 |
Jan 9, 2012 |
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61803775 |
Mar 20, 2013 |
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61803776 |
Mar 20, 2013 |
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61584399 |
Jan 9, 2012 |
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61535986 |
Sep 17, 2011 |
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61921304 |
Dec 27, 2013 |
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62119342 |
Feb 23, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 18/042 20130101;
A61N 2005/0659 20130101; H05H 1/2406 20130101; A61B 2018/00452
20130101; A61B 18/04 20130101; A61N 2005/0661 20130101; A61B
2018/122 20130101; A61N 5/0625 20130101; A61N 2005/0662 20130101;
A61B 2018/0016 20130101; A61B 2018/147 20130101; A61N 5/0624
20130101; A61B 2018/00119 20130101; A61B 2018/00321 20130101; A61B
18/08 20130101 |
International
Class: |
A61B 18/04 20060101
A61B018/04 |
Claims
1. A method of treating a topical condition, comprising: a)
providing an electrode adapted to be placed proximate an anatomical
region of interest having a topical condition; and b) applying an
electric field or plasma to the region of interest to treat the
topical condition, wherein applying the electric field or plasma
includes applying a pulsed voltage waveform to the electrode to
generate a plasma proximate the electrode, the pulsed voltage
waveform having pulses with durations between about 0.11 ns and 100
ns, and having a pulse repetition rate less than about 3,000
Hz.
2. The method of claim 1, wherein the power deposited by the plasma
on the anatomical region of interest is between about 1.0
milliwatts per square centimeter and about 10.0 watts per square
centimeter.
3. The method of claim 1, wherein the power deposited by the plasma
on the anatomical region of interest is between about 10.0
milliwatts per square centimeter and about 1.0 watts per square
centimeter.
4. The method of claim 1, wherein the anatomical region of interest
is exposed to the plasma for between about five seconds and about
fifteen minutes.
5. The method of claim 1, wherein the anatomical region of interest
is exposed to the plasma for between about thirty seconds and about
ten minutes.
6. The method of claim 1, wherein the anatomical region of interest
is exposed to the plasma for between about three minutes and about
seven minutes.
7. The method of claim 1, wherein the anatomical region of interest
is not wetted with a beneficial agent during the treatment.
8. The method of claim 1, wherein the anatomical region of interest
is wetted with a beneficial agent prior to applying plasma or an
electric field to the region of interest.
9. The method of claim 8, wherein the beneficial agent is
water.
10. The method of claim 8, wherein the beneficial agent includes at
least one material selected from the group consisting of organic
materials, gaseous materials, gelatinous materials, liquid
materials amino acids, saline, deionized water, and phosphate
buffered saline.
11. The method of claim 1, wherein the topical condition includes
onychomycosis.
12. The method of claim 1, wherein the topical condition includes
psoriasis.
13. The method of claim 1, wherein the topical condition includes
an infection.
14. The method of claim 1, wherein the topical condition includes
vitiligo.
15. The method of claim 1, wherein at least one of reactive oxygen
species and reactive nitrogen species are delivered to the region
of interest.
16. The method of claim 1, further comprising applying a
sensitizing material to the region of interest prior to application
of plasma to the region of interest.
17. The method of claim 1, further comprising applying a blocking
material to tissue proximate the region of interest to protect the
tissue from plasma.
18. The method of claim 1, wherein the electric field has a
strength between about 3,000V/mm and 20,000 V/mm.
19. The method of claim 18, wherein the electric field does not
result in substantial formation of plasma in the anatomical region
of interest.
20. The method of claim 19, wherein the electric field results in
no detectable plasma formation in or on the anatomical region of
interest.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is a continuation-in-part of U.S.
patent application Ser. No. 14/987,529, filed Jan. 4, 2016, which
in turn is a continuation of U.S. patent application Ser. No.
13/943,012, filed Jul. 16, 2013, which in turn is a continuation of
International Patent Application No. PCT/US2012/031923, filed Apr.
2, 2012, which in turn claims the benefit of priority of U.S.
Provisional Patent Application Ser. No. 61/584,399, filed Jan. 9,
2012.
[0002] This patent application is a continuation-in-part of U.S.
patent application Ser. No. 14/987,529, filed Jan. 4, 2016, which
in turn is a continuation-in-part of U.S. patent application Ser.
No. 14/215,214, filed Mar. 17, 2014, which in turn claims the
benefit of priority of U.S. Provisional Patent Application Ser. No.
61/803,775, filed Mar. 20, 2013 and U.S. Provisional Patent
Application Ser. No. 61/803,776, filed Mar. 20, 2013.
[0003] This patent application is a continuation-in-part of U.S.
patent application Ser. No. 14/987,529, filed Jan. 4, 2016, which
in turn is a continuation-in-part of U.S. patent application Ser.
No. 14/215,214, filed Mar. 17, 2014, which in turn is a
continuation of and claims the benefit of priority of International
Patent Application No. PCT/US12/55726, filed Sep. 17, 2012, which
in turn claims the benefit of priority of International Patent
Application No. PCT/US12/31923, filed Apr. 2, 2012, U.S.
Provisional Patent Application Ser. No. 61/584,399, filed Jan. 9,
2012, and, U.S. Provisional Patent Application Ser. No. 61/535,986,
filed Sep. 17, 2011.
[0004] This patent application is a continuation-in-part of U.S.
patent application Ser. No. 14/987,529, filed Jan. 4, 2016, which
in turn is a continuation in part of U.S. patent application Ser.
No. 14/584,357, filed Dec. 29, 2014, which in turn claims the
benefit of priority of U.S. Provisional Patent Application Ser. No.
61/921,304, filed Dec. 27, 2013.
[0005] This patent application is a continuation-in-part of U.S.
patent application Ser. No. 14/987,529, filed Jan. 4, 2016, which
in turn claims the benefit of priority of U.S. Provisional Patent
Application Ser. No. 62/119,342, filed Feb. 23, 2015. The
disclosure of each of the aforementioned patent applications is
incorporated by reference herein in its entirety for any purpose
whatsoever.
BACKGROUND
Field of the Disclosure
[0006] The present disclosure relates to methods and systems for
treating onychomycosis and other pathogenic infections of the nail.
Particularly, the present disclosure is directed to the treatment
of onychomycosis and other pathogenic infections of the nail in a
manner that is assisted and/or enhanced by use of plasma and/or the
application of strong electric fields.
Description of Related Art
[0007] Onychomycosis is a particularly difficult condition to treat
due to the fact that the fungus often lives underneath or within
the nail. The nail is mainly comprised of hard keratin, which makes
it difficult to penetrate. A variety of techniques are known in the
art for treating onychomycosis. These include topical drugs,
systemic drugs, electrical heating, light-based heating, and
ultraviolet light. Each of these treatments suffers from one or
more shortcomings as described below:
[0008] 1. Topical Drugs--are effective at killing the underlying
fungal infection (such as T. rubrum), but have difficulty
penetrating the nail. Common examples include ciclopirox,
amorolfine, and terbinafine. Dosing cycles are also long--they can
run from 6 to 18 months.
[0009] 2. Systemic drugs--can also be effective at killing the
underlying fungal infection, but have several potential side
effects (such as liver failure) and require relatively long dosing
cycles (daily pills up to 6 months). Common examples include
terbinafine and itraconazole.
[0010] 3. Electrical and light-based heating--various approaches
have been attempted. However, most involve attempting to provide
the heat required to kill the pathogen while preserving the
underlying tissue. These attempts have proved difficult to
implement in practice. Examples include Nomir Medical Technologies
and PathoLase.
[0011] 4. Ultraviolet Light--Keraderm, a startup company, has
attempted to use UVC (light ranging from 200 to 280 nm) using a
xenon flash lamp to kill the underlying infection. The nail will
transmit some amount of UVC, but the exposure levels can be
significant (120 mJ/cm.sup.2) and some dermatologists have
expressed concern about causing skin cancer in the underlying nail
bed, which would be quite difficult to treat.
[0012] The present disclosure presents improvements on the state of
the art as set forth hereinbelow.
SUMMARY OF THE DISCLOSURE
[0013] The purpose and advantages of the present disclosure will be
set forth in and become apparent from the description that follows.
Additional advantages of the disclosed embodiments will be realized
and attained by the methods and systems particularly pointed out in
the written description hereof, as well as from the appended
drawings.
[0014] To achieve these and other advantages and in accordance with
the purpose of the disclosure, as embodied herein, the disclosure
includes a variety of nail treatment methods that have been
developed using the application of plasma and/or the application of
electric fields. The infected nail and nail bed are porous
structures. The pores are primarily created by the pathogenic
micro-organisms that consume the nail (keratin) and nail bed
material, creating microchannels similar to how earthworms burrow
through soil. In many of the embodiments described herein, a high
electric field is created within the nail and nail bed. When the
electric field exceeds the air/gas breakdown field, plasma will be
created within the pores of the nail bed and nail. Applicant also
believes that the application of a high electric field in and of
itself is of significant therapeutic benefit. The plasma within
pores of the nail and nail bed can be sustained in the same way as
the plasma in dielectric barrier discharges by pulsing or otherwise
time varying the electric field. The electric field and the plasma
created within the pores of the nail bed and the nail are two of
the key agents that kill or slow down the growth of the infecting
micro-organisms directly or indirectly by generating various
chemically active species within micro-organism bodies and in the
medium surrounding them. The direct effect of electric field on
micro-organisms can include the effect of electroporation.
Electroporation can inactivate (kill or slow the growth) of various
micro-organisms including bacteria and fungi. Plasma can also
affect micro-organism directly through the presence of charges,
plasma generated electric field or through short penetration UV
radiation generated in plasma. Estimated treatment time during
which electric field and/or plasma within the nail and the nail bed
occurs is preferably at least a tenth of a second and preferably no
more than 1 hour, and in any desired time increment therebetween in
increments of minutes, seconds or fractions of a second (e.g., 0.1,
0.01, 0.01, 0.001 seconds), as desired.
[0015] An electric field that may or may not (as desired) cause
generation of plasma within the pores of the nail and nail bed can,
in turn, be created by a multitude of different embodiments by
applying high voltage to the surface of the nail. In order to apply
the high voltage to the surface of the nail, the following
techniques can be used. For example, a highly polarizable material
can be positioned between one or more high voltage electrodes and
the nail surface. This highly polarizable material can be
polarizable fluid like water, gel, thin film of electrically
conducting paint or epoxy, or even ionized gas (plasma). In some
embodiments, the polarizable material will cover the surface of the
nail in a conformal fashion in order to create the electric field
within the nail and the nail bed uniformly under the surface of the
nail. In other embodiments, the polarizable material may cover a
portion of the entire nail. The polarizable material may also cover
one nail or multiple nails simultaneously.
[0016] In the embodiments where plasma is employed as the highly
polarizable material covering the entire nail surface or its
portion, this plasma can be formed proximate to the outer surface
of the nail in a variety of ways. For example, this plasma can
include a corona discharge plasma, a dielectric barrier discharge
plasma, plasma "jets" of various kinds where generation of plasma
on the outer surface of the nail is assisted by a flow of gas
toward the nail, an inductively coupled plasma, a microwave induced
plasma and/or capacitively coupled radio frequency induced plasma.
Tissue under the nail can be effectively connected through the body
to a second electrode during the plasma generation on the surface
of the nail or it may by electrically disconnected from any
electrodes and remain at a floating potential whose value is
determined by a variety of factors including tissue properties,
body size, quality of plasma above the surface of the nail and
others.
[0017] Creating a strong electric field within nail bed and within
the nail may be accomplished via pulsation of the voltage applied
to the polarizing fluid covering the outer surface of the nail.
This is due to the fact that the nail bed tissue and possibly the
nail contain a certain amount of electrolyte having electrical
conductivity on the order of 1 S/m. It is known that any
electrically conducting medium including electrolytes found in
tissues can sustain electric field for only a limited amount of
time before sufficient separation of electrical charges in the
tissue electrolytes screens the electric field from within the
tissue bulk bringing the net field magnitude there to zero. One can
roughly estimate using the following expression for the electric
field in linear conducting materials as a function of time:
.differential. E .fwdarw. ( r .fwdarw. , t ) .differential. t +
.sigma. E .fwdarw. ( r .fwdarw. , t ) = 0 ##EQU00001##
where {right arrow over (E)}({right arrow over (r)}, t) is the
electrostatic field at locations in space indicated by vector
{right arrow over (r)} from the origin of the coordinate system at
a time t, while .sigma. is the tissue conductivity and .epsilon. is
its dielectric constant. This expression follows directly from the
fact that the sum of the displacement and conduction currents in
tissue is zero after the initial field excitation by a voltage
pulse applied to the surface of the nail. The above equation can be
easily solved to yield:
E .fwdarw. ( r .fwdarw. , t ) = E .fwdarw. 0 ( r .fwdarw. ) exp ( -
.sigma. t ) = E .fwdarw. 0 ( r .fwdarw. ) exp ( - t .tau. )
##EQU00002##
where {right arrow over (E)}.sub.0 ({right arrow over (r)}) is the
initial value of the electrostatic field at any position {right
arrow over (r)} and
.tau. = .sigma. ##EQU00003##
is the characteristic time during which the screening occurs and
the initial electrostatic field effectively decays to zero in
tissue. Assuming that the permittivity of tissue is about the same
as that of water, .epsilon..apprxeq.10.sup.-9 Farads per meter.
Taking the tissue conductivity to be about .sigma.=1 Siemens per
meter we find the characteristic time to be about .tau.=1
nanosecond. From these very simple estimates it can be concluded
that the electric field can penetrate conducting tissue for a
period of few nanoseconds. The actual electric field penetration
time can vary from 1 to 1000 ns depending on the actual
conductivity of the nail and nail bed that is likely to be below 1
Siemens per meter. Thus, to achieve longer effective time of the
electrostatic field presence in the nail and nail bed, it is
important to repeat voltage pulses whose duration can be varied
from about 1 ns to 1000 ns, several times per second. Frequency of
such pulses may also be varied from only a few Hertz to several
thousand Hertz.
[0018] In accordance with further aspects, the techniques disclosed
herein can be used in combination with the application of heating
(via conduction, infrared light, plasma, or other electrical) or
cooling. In accordance with a preferred embodiment, heating is also
applied to the tissue being treated. Thus plasma can be applied in
addition to the heating, such that the tissue is being exposed to
heat, reactive ion species generated by the plasma, light emission
from the plasma, and electric field generated within the plasma.
The heat can be generated in whole or in part by the plasma or in
combination with a second heating source. By way of further
example, most or all of the heat can be provided from a source in
addition to the plasma. Such a source of heat can included a
resistive heater, convective heater (forced air), infrared LED's,
heating lamps, and the like.
[0019] Additional features are disclosed herein to facilitate the
safe usage of exemplary devices by untrained personnel to treat
differently-shaped portions of the body. These include safety
protections, control schemes, ergonomic holding structures,
electrode structures, and spacing means, among other features.
Estimated treatment time is preferably at least a tenth of a second
and preferably no more than 1 hour, and in any desired time
increment therebetween in increments of one minute or a multiple of
minutes or in increments of one second or multiple seconds, as
desired.
[0020] Thus, in accordance with one embodiment, a system for
applying a plasma discharge is provided. The system includes an
electrode adapted to be placed proximate an anatomical region of
interest, a power supply in electrical communication with the
electrode, the power supply being adapted and configured to apply
power to the electrode to generate a plasma proximate the
electrode.
[0021] In some implementations, the electrode can be flexible
and/or resilient. The electrode can be shaped like a stylus having
an insulating tip (e.g., of silicone) to permit plasma to form
along the surface of the tip, and along the surface of the nail
being treated. The power supply can be adapted and configured to
apply a pulsed voltage waveform to the electrode to generate a
plasma proximate the electrode. The pulsed voltage waveform can
have pulses with durations that are shorter or longer than the time
required for the formation of microdischarges between the electrode
and the anatomical region of interest. If desired, the electrode
can be substantially inflexible.
[0022] The pulse duration of the waveform can be between at least
one of (i) about 0.000000010 seconds and about 0.00000010 seconds,
(ii) about 0.0000000010 seconds and about 0.000000010 seconds,
(iii) about 0.00000000010 seconds and about 0.0000000010 seconds,
(iv) about 0.000000001 seconds and about 0.001 seconds, and (v)
about 0.000001 seconds and about 0.001 seconds. The flexible
electrode can include a layer of conductive material. If desired,
the system can further include a flexible dielectric layer
substantially surrounding the flexible electrode, the flexible
dielectric layer being adapted and configured to be disposed
against the anatomical region of interest. The layer of conductive
material can be a continuous layer or an interrupted layer. The
interrupted layer can be etched and/or a mesh, or be in a
predetermined pattern. In some embodiments, at least a portion of
the layer of conductive material can be transparent, and if
desired, include indium tin oxide (ITO).
[0023] If desired, the layer of conductive material can be a
conductive fluid disposed within the dielectric layer. The
dielectric layer and conductive fluid can be formed into a shape
matching the tissue (e.g., nail plate). If desired, the dielectric
layer can include an adhesive layer for placement against the
region of interest to hold the flexible electrode against the
tissue (e.g., nail). The system can further include a removable
protective layer disposed on the adhesive layer.
[0024] In an alternative embodiment, the electrode can have a
single curved dielectric layer or a plurality of curved bumps such
that the curvature(s) is (are) opposite the curvature of the nail
plate (i.e. defining small area(s) or point(s) of contact between
the nail plate and dielectric-covered electrode. With this
configuration, the electric field (and resulting plasma in some
instances) will be more readily concentrated at and below the
point(s) of contact within the nail plate and any pores that are
present. Simultaneously, some plasma will usually form around the
periphery of the curved dielectric layer(s) in use and conduct to
the surface of the nail plate. This plasma is helpful for killing
any fungus, bacteria, or other infectious microorganisms that may
be present on the surface of the nail. In this fashion, the
infection may be killed within the nail plate and on top of the
nail plate simultaneously. By moving such an electrode over the
entire surface of the nail plate and surrounding nail matrix, it is
possible to treat the entire nail. Such methods include serpentine,
spiral, or random path scanning or step-and-repeat stationary
exposures in an array across the entire area such as by using an
electrode having an array of conductors that can be selectively
activated and deactivated to help establish desired treatment
goals. A conducting pad can be placed near the anatomical region of
interest (e.g., under the toe(s) of the patient) and the current
passing through the conducting pad can be measured constantly by a
controller of the system that adjusts the amount of applied voltage
to establish a desired electric field and/or magnitude of plasma
formation in the treatment area.
[0025] An additional benefit from using a curved electrode or array
of curved bumps on the electrode is that the distance between the
dielectric layer and the nail plate will necessarily vary. It is
possible to maintain a variable distance also with a flat
electrode, so long as the nail plate is sufficiently curved. This
variable distance generally makes it more difficult for plasma to
form microdischarges (or "sparks") that self-organize and create
strong local current flows. Such strong local current flows can
lead to excessive local heat generation and pain.
[0026] In some embodiments, the system can further include a gas
supply in operable communication with the electrode, wherein the
gas supply can be adapted and configured to supply gas to the
anatomical region of interest. If desired, the system can further
include a fastener for holding the flexible region against the
anatomical region of interest. The fastener can include at least
one of (i) a hook and loop fastener, (ii) adhesive and (iii) an
elastic strap, as desired.
[0027] The system can further include an exposure indicator. The
exposure indicator can be adapted to indicate the amount of
exposure of the anatomical region of interest to the plasma. In
some embodiments, the exposure indicator can include at least one
compound that reacts to the exposure from plasma. The exposure
indicator can provide a visual indication of exposure to plasma.
The exposure indicator can change color when exposed to plasma. The
exposure indicator can include an optical sensor in operable
communication with a processor adapted and configured to control
the power supply. The exposure indicator can include an electrical
sensor in operable communication with a processor adapted and
configured to control the power supply.
[0028] In some embodiments, the system can further include a
controller for controlling the power supply. The controller can be
adapted and configured to receive operational data indicative of
the operation of the system, to process the operational data, to
determine at least one action to take in response to the processed
data, and to implement the at least one action. The electrode can
include a continuity sensor to determine if the electrode is in
adequate physical contact with the anatomical region of interest.
The continuity sensor can be adapted and configured to measure the
impedance of tissue which the sensor is in contact with. The
operational data can relate to at least one of (i) a tissue
impedance measurement, (ii) gas temperature, (iii) tissue
temperature, (iv) light emission of the plasma, and (v) electrical
current flowing into the tissue. The conditions sustaining the
plasma can be modulated in response to the operational data. The
conditions that are modulated can include at least one of (i) a
change in the pulse shape of a waveform applied to the electrode,
(ii) the frequency of the applied waveform, (iii) the voltage of
the applied waveform and (iv) flowrate of a gas used to help
sustain the plasma.
[0029] In further embodiments, the system can further include a
ground pad for providing a ground to prevent injury to tissue in
the anatomical region of interest. The ground pad can be integrated
into the electrode. The ground pad can be embedded into the
electrode, or can be formed about a periphery of the electrode. The
ground pad can alternatively be separate from the electrode. The
flexible electrode can be adapted to be applied to the anatomical
region of interest without an intervening dielectric layer.
[0030] The disclosure further provides a system for applying a
plasma discharge. The system includes a flexible electrode adapted
to be placed proximate an anatomical region of interest, and a
power supply in electrical communication with the flexible
electrode, the power supply being adapted and configured to deliver
power to the electrode to generate a plasma between the electrode
and the anatomical region of interest. The plasma can be a corona
discharge plasma, a dielectric barrier discharge plasma, a
microdischarge plasma, an inductively coupled plasma, a microwave
induced plasma, or a capacitively coupled radio frequency induced
plasma.
[0031] In some embodiments, the flexible electrode can include a
layer of conductive material. The system can further include a
flexible dielectric layer substantially surrounding the flexible
electrode, the dielectric layer being adapted and configured to be
disposed against the anatomical region of interest. The layer of
conductive material can be a continuous layer or an interrupted
layer. The interrupted layer can be etched, and/or be a mesh. The
layer of conductive material may be, transparent, and may include
indium tin oxide (ITO), as desired.
[0032] The disclosure further provides a method of generating a
plasma discharge. The method includes providing an electrode
adapted to be placed proximate an anatomical region of interest,
and applying a pulsed voltage waveform to the electrode to generate
a plasma proximate the electrode, the pulsed voltage waveform
having pulses with durations that are shorter than the time
required for the formation of microdischarges between the electrode
and the anatomical region of interest. The waveform can have a
pulse duration between at least one of (i) about 0.000000010
seconds and about 0.00000010 seconds, (ii) about 0.0000000010
seconds and about 0.000000010 seconds, and (iii) about
0.00000000010 seconds and about 0.0000000010 seconds. The electrode
can be flexible.
[0033] The power deposited by the plasma on the anatomical region
of interest can be between about 1.0 milliwatts per square
centimeter and about 10.0 watts per square centimeter. The power
deposited by the plasma on the anatomical region of interest can be
between about 10.0 milliwatts per square centimeter and about 1.0
watts per square centimeter. The power deposited by the plasma on
the anatomical region of interest can be between about 100.0
milliwatts per square centimeter and about 0.5 watts per square
centimeter. The anatomical region of interest can be exposed to the
plasma for between about one tenth of a second and about one hour.
The anatomical region of interest can be exposed to the plasma for
between about five seconds and about fifteen minutes. The
anatomical region of interest can be exposed to the plasma for
between about thirty seconds and about ten minutes. The anatomical
region of interest can be exposed to the plasma for between about
three minutes and about seven minutes.
[0034] The disclosure provides a method of treating a disorder in a
treatment area. The method includes generating a plasma proximate
the treatment area, and causing reactive ion species in the plasma
to interact with tissue in the treatment area including the
disorder, such as an infectious disorder, such as onychomycosis
and/or some other nail disease such as psoriasis or other
infection. The disorder can be on or in an animal or human. The
plasma can be a corona discharge plasma, a dielectric barrier
discharge plasma, a microdischarge plasma, an inductively coupled
plasma, a microwave induced plasma, a plasma jet, or a capacitively
coupled radio frequency induced plasma.
[0035] In further aspects, the method can further include
controllably flowing a gas proximate the treatment area. The gas
composition and flowrate can be selected to accomplish at least one
of (i) exposing the treatment area to a desired wavelength spectrum
of light, (ii) heating the treatment area, (iii) directing
electrical current through the treatment area and (iv) delivering
chemical species to the treatment area. Reactive oxygen chemical
species are delivered to the treatment area in accordance with any
embodiment herein. The wavelength spectrum and the intensity of the
light can be selected to stimulate blood flow to the treatment
area. At least some of the light can be in (i) the near-infrared
range, (ii) the infrared range, (iii) the ultraviolet range and
(iv) the visible range. At least some of the light can be in the
UVA range, and the method can further include applying psoralen to
the treatment area. Reactive nitrogen species can be present in the
plasma. At least some of the light can be in the UVB range, and the
tissue (e.g., nail) disorder can be psoriasis or vitiligo. The
methods can further include applying a sensitizing material to the
treatment area prior to application of the plasma to the treatment
area. Similarly, the methods can include applying a blocking
material to tissue proximate the treatment area to protect the
tissue from plasma.
[0036] In accordance with further aspects, the power deposited by
the plasma on tissue in the treatment area including the disorder
can be between about 10.0 milliwatts per square centimeter and
about 1.0 watts per square centimeter. The power deposited by the
plasma on the tissue in the treatment area including the disorder
can be between about 100.0 milliwatts per square centimeter and
about 0.5 watts per square centimeter. The tissue in the treatment
area including the disorder can be exposed to the plasma for
between about thirty seconds and about ten minutes in any desired
time increment of one second. For example, the tissue in the
treatment area including the disorder can be exposed to the plasma
for between about three minutes and about seven minutes.
[0037] The disclosure further provides a method of treating an
infection (e.g., a fungal based infection) in a treatment area. The
method includes generating a plasma proximate the treatment area,
and causing reactive ion species in the plasma to interact with
infected tissue in the treatment area. The infection can be on or
in an animal or human. The infection can be a bacterial, fungal,
viral, or parasitic infection. The plasma can be a corona discharge
plasma, a dielectric barrier discharge plasma, a microdischarge
plasma, an inductively coupled plasma, a microwave induced plasma,
a plasma jet, or a capacitively coupled radio frequency induced
plasma. The method can further include controllably flowing a gas
proximate the treatment area. The gas composition and flowrate can
be selected to accomplish at least one of (i) exposing the
treatment area to a desired wavelength spectrum of light, (ii)
heating the treatment area, (iii) directing electrical current
through the treatment area, (iv) delivering chemical species to the
treatment area. Reactive oxygen chemical species can be delivered
to the treatment area. The wavelength spectrum and the intensity of
the light can be selected to stimulate blood flow to the treatment
area. At least some of the light can be in (i) the near-infrared
range, (ii) the infrared range, (iii) the ultraviolet range and
(iv) the visible range. The method can further include applying a
sensitizing material to the treatment area prior to application of
the plasma to the treatment area, and or applying a blocking
material to tissue proximate the treatment area to protect the
tissue from plasma.
[0038] In some further aspects, the power deposited by the plasma
on tissue in the treatment area including the disorder can be
between about 10.0 milliwatts per square centimeter and about 1.0
watts per square centimeter. The power deposited by the plasma on
the tissue in the treatment area including the disorder can be
between about 100.0 milliwatts per square centimeter and about 0.5
watts per square centimeter. The tissue in the treatment area
including the disorder can is exposed to the plasma for between
about thirty seconds and about ten minutes. The tissue in the
treatment area including the disorder can be exposed to the plasma
for between about three minutes and about seven minutes
[0039] In accordance with further aspects, the method can further
include providing an exposure indicator, the exposure indicator
being adapted to indicate the amount of exposure of the tissue to
be treated to the plasma, and detecting the exposure of the tissue
to the plasma. The exposure indicator can include at least one
compound that reacts to the exposure from plasma. The exposure
indicator can provide a visual indication of exposure to plasma.
The method can further include applying a sensitizing material to
the tissue to be treated prior to application of the plasma and/or
applying a blocking material to tissue proximate the treatment area
to protect the tissue proximate the treatment area from plasma.
[0040] The disclosure further provides a processor-readable
computer program stored on a tangible non-transient medium for
operating a plasma treatment device including a controller, a power
source operably coupled and controlled by the controller, and an
electrode in operable communication with the power source and
controller. The program includes instructions to cause the
controller to operate the power source to induce a plasma between
the electrode and a treatment area, or any other method step or
aspect of any system recited in this disclosure. For example, the
plasma treatment device can further include a controllable gas
delivery system for directing gas to the treatment area, and the
computer program can further include instructions for controlling
the flow of gas to the treatment area.
[0041] In accordance with further aspects of the disclosure, a
method of treating an infection, such as a fungal infection, is
provided that includes providing an electrode adapted to be placed
proximate an anatomical region of interest having a fungal
infection, and applying an electric field to the region of interest
to kill the fungal infection. The method can alternatively include
providing an electrode adapted to be placed proximate an anatomical
region of interest having a fungal infection, and applying a plasma
to the region of interest to kill the fungal infection.
[0042] In accordance with further aspects, the fungal infection can
include onychomycosis, psoriasis and the like. The method can
include applying a pulsed voltage waveform to the electrode to
generate a plasma proximate the electrode, the pulsed voltage
waveform having pulses with durations that are shorter than the
time required for the formation of microdischarges between the
electrode and the anatomical region of interest. For example, the
waveform ca have a pulse duration between at least one of (i) about
0.000000010 seconds and about 0.00000010 seconds, (ii) about
0.0000000010 seconds and about 0.000000010 seconds, and (iii) about
0.00000000010 seconds and about 0.0000000010 seconds. The electrode
can be flexible and/or resilient. The power deposited by the plasma
on the anatomical region of interest can be between about 1.0
milliwatts per square centimeter and about 10.0 watts per square
centimeter, between about 10.0 milliwatts per square centimeter and
about 1.0 watts per square centimeter, or between about 100.0
milliwatts per square centimeter and about 0.5 watts per square
centimeter, among others. The anatomical region of interest can be
exposed to the plasma for between about one tenth of a second and
about one hour, between about five seconds and about fifteen
minutes, between about thirty seconds and about ten minutes, and
between about three minutes and about seven minutes, among
others.
[0043] In accordance with still further aspects, the anatomical
region of interest can be wetted with a beneficial agent during the
treatment or not wetted with a beneficial agent. As such, the
anatomical region of interest can be wetted with a beneficial agent
prior to applying plasma or an electric field to the region of
interest. The beneficial agent can be water, and/or one or more
materials selected from the group including organic materials,
gaseous materials, gelatinous materials, liquid materials amino
acids, saline, deionized water, and phosphate buffered saline. If
desired, a plasma and/or an electric field can be applied to the
region of interest before being wetted and after being wetted. The
plasma and/or electric field can be applied to the region of
interest more than once when the region of interest is wetted. The
infection being treated can be in and/or on an animal or a human or
other location where the infection is present. For example, a
fungal or other infection could be present on a plant, building
surface or other object to be disinfected.
[0044] In accordance with further aspects, the plasma can be a
corona discharge plasma, a dielectric barrier discharge plasma, a
microdischarge plasma, an inductively coupled plasma, a microwave
induced plasma, a plasma jet, or a capacitively coupled radio
frequency induced plasma. The method can further include
controllably flowing a gas proximate the region of interest. The
gas composition and flowrate can be selected to accomplish at least
one of (i) exposing the region of interest to a desired wavelength
spectrum of light, (ii) heating the region of interest, (iii)
directing electrical current through the region of interest, (iv)
delivering chemical species to the region of interest. In any
embodiment herein, reactive ion chemical species can be delivered
to a desired location, or region of interest, and/or such reactive
ion chemical species can be created in situ, such as by application
of an electric field, although the presence of an electric field on
its own independent of the presence of plasma formation is believed
by Applicant to have therapeutic benefit. The wavelength spectrum
and the intensity of the light can be selected to stimulate blood
flow to the region of interest. At least some of the light can be
in (i) the near-infrared range, (ii) the infrared range, (iii) the
ultraviolet range and/or (iv) the visible range. Some of the light
can be in the UVA range, and the method can further include
applying psoralen to the region of interest. In some
implementations, reactive oxygen species and/or reactive nitrogen
species can be delivered to the region of interest. In other
implementations, at least some of the light can be in the UVB
range, and the infection can include psoriasis or vitiligo. If
desired, the method can further include applying a sensitizing
material to the region of interest prior to application of plasma
to the region of interest. A blocking material can be applied to
tissue proximate the region of interest to protect the tissue from
plasma. Tissue in the region of interest including the disorder can
be exposed to the plasma for between about thirty seconds and about
ten minutes. Tissue in the region of interest including the
disorder can be exposed to the plasma for between about three
minutes and about seven minutes.
[0045] The disclosure still further provides a processor-readable
computer program stored on a tangible non-transient medium for
operating a plasma treatment device or device adapted to administer
an electric field to a region of interest, including a controller,
a power source operably coupled and controlled by the controller,
and an electrode in operable communication with the power source
and controller, wherein the program includes instructions to cause
the controller to operate the power source to induce a plasma
and/or apply an electric field between the electrode and the region
of interest. The plasma treatment device can further include a
controllable gas delivery system for directing gas to the region of
interest, and the computer program can further include instructions
for controlling the flow of gas to the region of interest.
[0046] The disclosure further provides a system for applying a
plasma discharge and/or electric field. The system includes a
controller, an electrode in operable communication with the
controller, the electrode being adapted to be placed proximate an
anatomical region of interest, the electrode having an array of
conductors adapted and configured to be selectively activated and
deactivated by the controller. The system further includes a power
supply in electrical communication with the electrode and
controller, the power supply being adapted and configured to apply
power to the electrode to generate a moving plasma over time in the
anatomical region of interest by activating a plurality of
conductors in the array of conductors.
[0047] In accordance with further aspects, the electrode can be
made from material that is resilient and/or flexible. The power
supply can be adapted and configured to apply a pulsed voltage
waveform to the electrode to generate a plasma proximate the
electrode. The pulsed voltage waveform can have pulses with
durations that are shorter than the time required for the formation
of microdischarges between the electrode and the anatomical region
of interest, if desired. If desired, the electrode can be
substantially inflexible. The waveform can have a pulse duration
between at least one of (i) about 0.000000010 seconds and about
0.00000010 seconds, (ii) about 0.0000000010 seconds and about
0.000000010 seconds, (iii) about 0.00000000010 seconds and about
0.0000000010 seconds, (iv) about 0.000000001 seconds and about
0.001 seconds, and (v) about 0.000001 seconds and about 0.001
seconds. The system can further include a conducting pad adapted to
be disposed at a location remote from the electrode in electrical
communication with the electrode through the anatomical region of
interest. The controller can be adapted and configured to adjust
the applied voltage in response to a signal received from the
conducting pad to maintain a controlled and substantially uniform
power deposition in the anatomical region of interest. The
electrode can have a distal tip made from a resilient material,
wherein the distal tip can have a rounded distal tip to facilitate
formation of a surface plasma thereon.
[0048] In further accordance with the disclosure, a kit is provided
including a beneficial agent as described herein in a dispenser and
a treatment tip for a plasma treatment device. The dispenser can be
adapted and configured to dispense beneficial agent onto a nail
plate. The beneficial agent can include a conductive gel for
application to a nail plate. The beneficial agent can include a
material selected from the group consisting of organic materials,
gaseous materials, gelatinous materials, liquid materials amino
acids, saline, deionized water, and phosphate buffered saline.
[0049] The disclosure further provides a method of treatment,
including providing an electrode adapted to be placed proximate an
anatomical region of interest to be treated, and applying an
electric field to the region of interest to treat the anatomical
region of interest. The treatment can be performed to treat an
infection. The infection can include a fungal or other infection.
Illustrative fungal infections in clued onychomycosis and
psoriasis. The method can further include applying a pulsed voltage
waveform to the electrode to generate a time varying electric field
over the anatomical region of interest, the pulsed voltage waveform
having pulses with durations that are shorter than the time
required for electrical charges in electrolytes in the tissue to
screen the electric field. The pulsed waveform can have a pulse
duration between at least one of (i) about 0.000000010 seconds and
about 0.00000010 seconds, (ii) about 0.0000000010 seconds and about
0.000000010 seconds, and (iii) about 0.00000000010 seconds and
about 0.0000000010 seconds. The electrode can be flexible and/or
resilient, or may not be flexible or resilient. The power deposited
by the electric field in the anatomical region of interest can be
between about 1.0 milliwatts per square centimeter and about 10.0
watts per square centimeter, between about 10.0 milliwatts per
square centimeter and about 1.0 watts per square centimeter, or
between about 100.0 milliwatts per square centimeter and about 0.5
watts per square centimeter, among others. The anatomical region of
interest can be exposed to the electric field for between about one
tenth of a second and about one hour. The anatomical region of
interest can be exposed to the electric field for between about
five seconds and about fifteen minutes, between about thirty
seconds and about ten minutes, or between about three minutes and
about seven minutes, among others. The anatomical region of
interest may or may not be wetted with a beneficial agent during
the treatment. The anatomical region of interest can be wetted with
a beneficial agent prior to applying the electric field. The
beneficial agent can be water, and/or organic materials, gaseous
materials, gelatinous materials, liquid materials amino acids,
saline, deionized water, and phosphate buffered saline. The
electric field can be applied before being wetted and/or after
being wetted. The electric field can be applied more than once when
the region of interest is wetted. The anatomical region of interest
can be on or in an animal, a human, or other living tissue or
inanimate object to be disinfected. The electric field can have a
strength between about 3,000 V/mm and 20,000 V/mm, among others. In
some implementations, the electric field may not result in
substantial formation of plasma in the anatomical region of
interest. In some instances, the electric field may result in no
detectable plasma formation in or on the anatomical region of
interest.
[0050] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and are intended to provide further explanation of the embodiments
disclosed herein. The accompanying drawings, which are incorporated
in and constitute part of this specification, are included to
illustrate and provide a further understanding of the methods and
systems of the disclosure. Together with the description, the
drawings serve to explain the principles of the disclosed
embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0051] FIG. 1 is a schematic showing an exemplary single, rigid
plasma electrode, high voltage supply and treatment of a nail.
[0052] FIG. 2 is a schematic showing an exemplary multi-electrode
device and how it may be used to treat multiple nails.
[0053] FIG. 3 is a schematic of an exemplary semi-flexible to
flexible plasma electrode.
[0054] FIG. 4 is a schematic of an exemplary plasma-jet device and
its application to a nail.
[0055] FIG. 5 is a schematic showing an exemplary treatment
electrode employing a surface plasma.
[0056] FIG. 6 is a schematic showing an exemplary treatment
electrode employing small holes to help initiate the plasma
formation at lower voltages and/or less complex waveforms.
[0057] FIG. 7 is a schematic showing an exemplary flexible
treatment electrode with an integrated spacer.
[0058] FIGS. 8a-8b illustrate side and top views of an assembly for
testing formation of plasma in small gaps.
[0059] FIGS. 9a-9c present photographic evidence of plasma
discharge formation.
[0060] FIG. 10 is a depiction of an exemplary plasma treatment
device for treating onychomycosis and other infections.
DETAILED DESCRIPTION
[0061] Reference will now be made in detail to the present
preferred embodiments of the disclosure, examples of which are
illustrated in the accompanying drawings. The methods and
corresponding steps of the disclosed embodiments will be described
in conjunction with the detailed description of the exemplary
systems.
[0062] By way of introduction, plasma, sometimes referred to as the
"fourth state of matter", typically includes partially and/or fully
ionized gas molecules and can be produced and directed in a variety
of ways and geometries. More specifically, a plasma can be thought
of as a gas having molecules that can be partially or fully ionized
and electrons that have kinetic energy sufficient to strip at least
one electron from at least one of the gas molecules through
collisions, such that the resulting plasma includes a mixture of
positively charged ions in a sea of free electrons that may or may
not also include neutral species mixed therewith. Plasmas can be
used for a variety of purposes, including sterilization, blood
coagulation, ozone generation, chemical processing, light sources,
ion sources (for propulsion) and heat sources, among others. As a
result of the relative simplicity of the construction of gas
discharges as opposed to other emitters, such as solid state
lasers, it is possible to create a variety of structures to provide
a distributed energy source at an economical cost. Perhaps the best
example of such arrays is the plasma television.
[0063] Plasma is most often generated in some region of gas when
the electric field in this region exceeds a certain breakdown
value. This breakdown value may depend on a number of factors
including gas pressure, the type of gas, and the size of the
region. In atmospheric pressure air, when the size of the plasma
generation region exceeds several times the mean free path, the
break down field is about 3,000 Volts per millimeter. In practice,
the size of the region where this field needs to be exceeded to
generate plasma is on the order of few micrometers. For smaller
regions, it may not be possible to generate plasma within them
unless the electric field is substantially larger. Thus, as long as
the pores within the nail and the nail bed are larger than few
micrometers (1-2 micrometers), it should be possible to generate
plasma within these pores using electric fields in the range of
about 3,000-20,000 Volts per millimeter in increments, for example,
of one volt/mm (e.g., 3001 V/mm, 3002V/mm . . . ). However, larger
(e.g., 20,000-50,000 V/mm) or smaller (e.g., 100V/mm-3,000V/mm)
electric fields can be used, as desired, as the present disclosure
can provide merely applying electric field irrespective of whether
plasma is created as a result of the applied electric field. Since
the electric field in the nail and the nail bed can be generated
remotely, without necessarily direct contact with conducting
electrode, plasma in the pores of the nail and the nail bed can
also be generated remotely from any current conducting
electrode.
[0064] In accordance with the present disclosure, onychomycosis
treatment methods and related systems and machine readable programs
have been developed using atmospheric pressure plasmas and/or
electric fields, alone or in combination with other therapies
described herein. Atmospheric plasmas are typically considered to
be those plasmas that can exist in a room environment at standard
conditions or conditions that vary slightly therefrom (e.g. at
standard temperature and pressure "STP"). The plasma can be a
corona, dielectric barrier discharge, microdischarge; inductively
coupled plasma, microwave induced plasma, or capacitively coupled
radio frequency induced plasma. The plasma can also be induced as
the result of a laser exposure. In one embodiment, plasma is
created within the nail for a duration of at least one tenth of a
second and no more than one hour, or any duration therebetween in
increments of minutes, seconds, or tenths of seconds, as desired.
Other embodiments are also presented.
[0065] The plasma produces reactive chemical species such as
hydroxyl radicals (OH), nitrous oxide (NO.sub.2), nitric oxide
(NO), ozone (O.sub.3), superoxide (O.sub.2.sup.-) that kill the
pathogens responsible for the onychomycosis. The plasma can also
emit light of a variety of wavelengths, can generate heat, ions,
and electrons. The combination of these species and energy
emissions can react with or cause reactions within the tissue that
can affect the local cellular makeup, inflammation or other
cellular processes and thereby alleviate the symptoms of various
conditions.
[0066] For purposes of illustration only, and not limitation, FIG.
1 shows a schematic of an exemplary treatment electrode and nail
treatment method in accordance with the disclosure. A nail
(fingernail or toenail), 1, has a conductive media, 2, placed upon
it. The treatment electrode, 3, which can include a conductor that
is encapsulated by a dielectric layer, is placed in contact with
the conductive media, 2. The treatment electrode is connected to a
high-voltage power supply and control system, 4, which is connected
to an electrical ground, 5. FIG. 2 shows a schematic of an
electrode structure that can treat multiple nails at one time. The
electrode support structure, 1, has multiple treatment heads, 2,
which are placed and sized appropriately to address individual
nails, 3. The electrode support structure, 1, is connected to a
high voltage power supply and control system, 4, which is connected
to ground, 5. FIG. 3 shows a schematic of a flexible or
semi-flexible treatment electrode. This flexible or semi-flexible
treatment electrode, 1, can be bent to conform to the shape of the
target nail structure (not shown). The treatment electrode, 1, is
connected to a high voltage power supply and control system, 2,
which is connected to an electrical ground, 3. FIG. 4 shows a
schematic of a plasma jet device. The treatment electrode, 1, is
connected to a gas supply, 2, which provides a stream of gaseous
media that is excited into a plasma state when the high voltage
power supply and control system, 3, is activated. The high voltage
power supply and control system, 3, is connected to an electrical
ground, 4. Note that in this case, no external conductive media is
needed to be applied to the nail, 5, because the gas supply (which
becomes a plasma, 6) provides this conductive function.
[0067] In accordance with the disclosed embodiments, the treatment
electrode may include multiple materials and have multiple shapes
and surface finishes. Some example materials include aluminum or
other conductor and alumina (Al.sub.2O.sub.3) dielectric, copper or
other conductor and silicon nitride dielectric, conductor and
quartz dielectric, conductor with rubber or plastic dielectrics
(such as a metal conductor with silicone or epoxy with or without
glass reinforcement), and conductor with a foam dielectric (such as
silicone, polyurethane, or polyethylene foam). The choice of the
dielectric material is based on the dielectric breakdown strength,
dielectric constant, and the intended duration of usage. Some
material combinations may be more suitable for long-term usage
(such as copper and quartz), whereas other material combinations
may be more suitable for short-term or single time usage. In the
case of a foam dielectric, the pores of the foam are designed such
that a microdischarge may form in each of a plurality of pores.
These microdischarges are sufficiently numerous such that no
individual microdischarge has sufficient energy to cause damage,
pain, erythema, or irritation. The dielectric layers have a minimum
thickness of about 10 microns and are attached to the conductor,
for example, by molding, laminating, bonding, brazing, welding,
mechanical joining. Alternatively, the dielectric layer may be
applied via a coating process, such as anodizing or thermal
spraying or by an oxidation process. The shape of the conductor may
be flat or curved, which will affect the distribution, location and
intensity of the plasma created. If the treatment electrode is
smaller than the affected tissue area, then the operator will have
to sweep the electrode over the desired treatment area to generate
the plasma where required. Alternately, the treatment electrode may
have the same size or substantially the same size as the desired
treatment area, in which case the operator can apply the electrode
in contact with the desired treatment area and maintain its
position for the duration of treatment. The connection of the
treatment electrodes to the electrical support structure may be
rigid or adjustable.
[0068] In order to prevent formation of powerful microdischarges
that bridge the gap between the electrode surface and tissue (e.g.,
nail) and remain in one specific location on the tissue (e.g.,
nail) for a period longer than about 1 second, one or more of the
following exemplary techniques can be used: [0069] Electrodes
having non-uniform air (gas) gap and some portions of the electrode
surface extending so as to be in or near contact with tissue (e.g.,
nail) can be used to create plasma on the electrode surface and
guide this surface plasma toward the tissue (e.g., nail) localizing
around the point of contact or near contact between the electrode
and the tissue (e.g., nail). [0070] Scanning the electrode rapidly
(manually or with a motor) across the tissue (e.g., nail) so as to
treat areas that may not be sufficiently exposed to the plasma when
the electrode is immobile. [0071] Use of high voltage waveforms
that are similar to pulses having rise time and fall time in the
range between 1 picosecond and 100 nanoseconds so as to form plasma
where strong microdischarges do not have sufficient time to be
created. [0072] Varying the electrode Z-position (that is, the gap
between the electrode and the tissue (e.g., nail)) via vibration,
oscillation or other motions (such as with a piezomotor or other
oscillatory motor) such that plasma is formed between different
portions of the electrode area and the tissue (e.g., nail),
depending on the magnitude of the gap. [0073] Use of microdischarge
electrodes having sub-millimeter sizes and applying them in
stationary or scanning exposures.
[0074] As shown in FIG. 6, small openings or holes can be defined
in the dielectric layer. These holes can change the nature of the
plasma discharge. The characteristic dimension of the
microdischarges is on the order of 100 to 200 microns (diameter).
As shown in FIG. 5, when the hole diameter is significantly smaller
than the microdischarge diameter, the amount of current that can be
passed through the hole to the electrode can be significantly
restricted permitting generation of non-thermal plasma possibly
even without AC voltage waveform typical of a dielectric barrier
discharge.
[0075] In the case of pulsed operation, devices and associated
methods are provided that provide pulsed voltages over time with
very short duration. In accordance with one embodiment, the pulse
duration can use any suitable voltage and be between about 0.010
seconds and about 0.10 seconds. In accordance with another
embodiment, the pulse duration is between about 0.0010 seconds and
about 0.010 seconds. In accordance with still another embodiment,
the pulse duration is between about 0.00010 seconds and about
0.0010 seconds. In accordance with yet another embodiment, the
pulse duration is between about 0.000010 seconds and about 0.00010
seconds. In accordance with another embodiment, the pulse duration
is between about 0.0000010 seconds and about 0.000010 seconds. In
accordance with still another embodiment, the pulse duration is
between about 0.00000010 seconds and about 0.0000010 seconds. In
accordance with a further embodiment, the pulse duration is between
about 0.000000010 seconds and about 0.00000010 seconds. In
accordance with still a further embodiment, the pulse duration is
between about 0.0000000010 seconds and about 0.000000010 seconds.
In accordance with yet a further embodiment, the pulse duration is
between about 0.00000000010 seconds and about 0.0000000010 seconds.
In accordance with another embodiment, a waveform is provided with
a combination of pulses selected from the durations set forth
above. Use of pulses of such short duration are believed to result
in decreased streamer (microdischarge) formation on the basis that
the pulse is too short for the plasma to organize itself in a
manner in which it can form a streamer (microdischarge). It is also
believed that use of such pulsing can result in a large amount of
reactive ion species for treating the tissue (e.g., nail).
Moreover, it is possible to not use a dielectric material between
the electrode and tissue when using pulses of such short duration,
since the power applied to the area being treated is controlled by
microprocessor; although a dielectric layer can be included for
safety reasons. As such, this technique of using pulses of such
short duration differs from dielectric barrier discharge plasmas,
which require a dielectric layer to operate. Moreover, using such
short pulses also results in a more uniform plasma.
[0076] In accordance with further aspects, the disclosure provides
systems and methods for generating surface plasmas and techniques
for applying surface plasmas to a patient's tissue (e.g.,
nail).
[0077] For purposes of illustration, and not limitation, a further
embodiment of a treatment device is provided in FIG. 5. The
treatment device includes a handle (not shown) and a treatment
electrode including a conductor 1 surrounded at least in part by an
insulating material 2 defining an outer surface that may be placed
in direct contact with a patient's tissue (e.g., nail) 3. The
treatment device is used in this embodiment by applying a voltage
to the conductor 1 such that a surface plasma is generated along
the surface of the insulating material and between the surface of
the insulating material 2 and patient's nail in areas where they
are not in direct physical contact, and a gap is defined between
the nail and the insulating material. The behavior of surface
plasma is affected by a variety of variables, including the type
and overall shape of insulating material 2 used, as well as the
characteristics of surface of the insulating material 2.
[0078] If desired, the insulating material can be rigid or
flexible. If flexible, insulating material 2 can be, for example, a
silicone compound, synthetic rubber, polyurethane, or polyethylene.
These can be applied to the conductor via lamination or the
conductor can be plated or otherwise sprayed onto the base
insulating material. If rigid, insulating material can be a
moldable material, such as PTFE, PVDF, PC, PP and the like, and can
be molded such as by injection molding. As will be appreciated, the
texturing of the surface will have a surface finish that can be a
result of the molding process or other processing. Thus, in one
embodiment, such as where insulating material is injection molded,
a mold having a surface finish in accordance with SPI/SPE A1, A2,
A3, B1, B2, B3, C1, C2, C3, D1, D2 or D3 can be used. Moreover, if
desired, the mold can have a first, rougher, surface finish in one
region, and a second, smoother surface finish in another
region.
[0079] Regardless as to how it is formed, the resulting surface of
material 2 facing and/or contacting the tissue (e.g., nail) of the
patient/user can be provided with a surface having a region with a
mean surface roughness Ra between about 0.01-2000 microinches,
0.1-1000 microinches, 1-100 microinches, 5-50 microinches, 20-40
microinches, 100-200 microinches, 75-125 microinches, 1-4
microinches, 4-8 microinches, 8-12 microinches, 12-20 microinches,
20-30 microinches, 30-40 microinches, 40-50 microinches, 50-60
microinches, 70-80 microinches, 80-90 microinches, 90-100
microinches, or the like.
[0080] The surface of insulating material 2 that faces and/or
contacts a user's/patient's tissue (e.g., nail) can be provided
with one or more bumps, ridges or undulations 78 that are distinct
and on a generally larger scale than the surface finish, having an
average height of about 0.01 mm-5 mm, 0.1-0.5 mm, 0.5-1.0 mm,
1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5 mm, 2.5-3.0 mm, 3.0-3.5 mm, 3.5-4.0
mm, 4.0-4.5 mm, or 4.5-5.0 mm, among others. Distances between
adjacent bumps, ridges or undulations for the foregoing examples
can be between 0.01 mm-5 mm, 0.1-0.5 mm, 0.5-1.0 mm, 1.0-1.5 mm,
1.5-2.0 mm, 2.0-2.5 mm, 2.5-3.0 mm, 3.0-3.5 mm, 3.5-4.0 mm, 4.0-4.5
mm, or 4.5-5.0 mm, among others.
[0081] The material of the dielectric can also be provided with
pores. These pores can serve as microcavities for a plasma
microdischarge. These pores may be connected to one another or be
separate and distinct. Such pores could be regular, as in a
capillary array, or irregular in distribution. The shape of the
pores may be spherical, cylindrical, or other. The pores have a
characteristic dimension of 0.000 to 0.100 mm, 0.100 to 0.5 mm, 0.5
to 1.0 mm, 1.0-1.5 mm, 1.5-2.0 mm, 2.0-2.5 mm, 2.5-3.0 mm, 3.0-3.5
mm, 3.5-4.0 mm, 4.0-4.5 mm, or 4.5-5.0 mm, among others.
[0082] If desired, insulating material can be a semiconductor
material. Concentration of charge carriers (consisting of valence
and conduction electrons) in semiconductors can be modulated in a
variety of ways including changes in temperature, incident light
and electric field inside the material. The semiconducting material
properties at different locations can also be controlled through
incorporation of impurities that create either excess of conduction
or excess of valence electrons. Modulating charge carrier density
within the semiconducting material permits to exercise control over
current being delivered into the plasma. Charge carrier density
within the semiconductor may also change its electron emission
capabilities and the manner in which insulating material acts as an
electron emitter. Furthermore, charge carrier density within the
semiconducting material may result in changes of surface breakdown
enabling control over surface plasma discharge on semiconductor
surface.
[0083] It will be further appreciated that insulating material 2
can have a variety of different dielectric breakdown strengths,
such as rubber (450-700 V/mil), Teflon (1500 V/mil), glass
(2000-3000 V/mil), alumina (300-500 V/mil), polyimide (12000-18000
V/mil), PVDF (1700 V/mil), PVC, polyurethane, UHMW polyethylene,
etc. By comparison, air has a dielectric breakdown strength of
approximately 20 V/mil. The choice of the dielectric thickness is
determined by the magnitude of the applied voltage, the gap between
the dielectric and the tissue (or the profile of the dielectric, in
the case of a surface discharge), the thickness of the nail plate,
and the local surface profile of the tissue (which includes tissue
surface roughness and topographical variations due to swelling,
scarring, or gross curvature of the body). In such cases, a typical
thickness of approximately 0.010 to 4 mm for the dielectric layer
is suitable to account for the variations in the applied voltage,
electrode-tissue separation, tissue surface profile, etc.
Generally, the smaller the gap, the smaller the dielectric
thickness that is required.
[0084] The minimum gap between the dielectric and the tissue (e.g.,
nail) can be determined according to the Paschen curve, which shows
the relationship between the breakdown voltage of a gas as a
function of its pressure times the characteristic distance. In some
embodiments, the characteristic distance is the air gap between the
dielectric and the tissue. For atmospheric pressures, the Paschen
curve provides that minimum voltages of approximately 400 to 6000
volts are useful to generate a breakdown for gaps of approximately
0.01 to 1 mm, respectively. In order to form a plasma over a large
area as opposed to a single microdischarge, significantly higher
voltages are useful for generating plasma while overcoming the
variations induced by the tissue surface roughness, tissue
impedance variations, and local topographical variation of the
tissue. Such voltages range, for example, from about 500 to about
1000 volts, about 1000-about 10000 volts, and about 10000-about
50000 volts.
[0085] In further accordance with the disclosure, additional
features are provided to facilitate the use of plasma treatment
devices by lightly trained or untrained operators. In order to
maintain the same intensity of the dose of the plasma to the tissue
(e.g., nail), it is useful to apply the plasma treatment electrode
in close proximity to the tissue (for cases where the curved
electrode is not used) in a reliable and repeatable fashion.
Alternatively, a spacer made from a non-conductive material can be
used to set the distance between the plasma treatment electrode and
the tissue, as shown in FIG. 7, for example. The spacer/spacing
means can be provided around the periphery of the treatment
electrode, in which case it can also surround or encapsulate the
local gas. By surrounding the local gas, the structure can
facilitate concentration of the heat and reactive species in the
desired treatment area. Such a border can also incorporate an
ozone-absorbing material, such as carbon black, to absorb the ozone
that is commonly generated by the dielectric barrier discharge. In
some embodiments, a line, group of lines, a polygon or polygons, a
post or a plurality of posts, such as in the form of an array, or
other geometries at or around the central portion of the treatment
area can be included in the electrode insulating material to
prevent the tissue from rising up inside the region defined by the
spacer, which would adversely affect the maintenance of a constant
gap between the treatment electrode and the body. Alternately, the
spacer itself can be mounted on a spring or other resilient member
that provides a defined preload contact force between the plasma
treatment electrode and the tissue. When combined with an overload
protection interlock (such as a contact or proximity switch or
sensor) to prevent operation if the spring is fully compressed,
this mechanism can be used to prevent the tissue from coming too
close to the plasma treatment electrode.
[0086] In another embodiment, when microdischarges are employed to
generate the plasma in close proximity to the tissue to be treated
(e.g., nail), the size of the microcavities is preferably small
enough such that the spacing between the tissue and the plasma
treatment electrodes can be controlled without additional spacing
means, springs, or other mechanisms, as desired.
[0087] In accordance with some embodiments, the electrical output
is delivered by a power supply and affects the nature of the plasma
that is emitted. Thermal and non-thermal plasmas may be used. If
desired, the power supply can be connected to a control system that
provides control means (e.g., a controller) that controls turning
the device on an off, and may be used to control the dose (or
intensity) of the plasma, which can in turn be controlled by
adjusting the gas flow rate, applied voltage and hence applied
current, and the like. In order to maintain user safety, a variety
of controls are preferably employed. At the point of application to
the tissue, a temperature sensor (thermocouple or infrared sensor,
for example) is employed to ensure that the gas temperature does
not exceed the threshold for causing pain and erythema. Also, the
electrode can contain a fuse or fast circuit breaker to ensure that
the current does not increase dramatically as a result of electrode
damage, which can cause significant pain to the patient. This fuse
or circuit breaker can also be mounted within the power supply.
[0088] If desired, the controller can control a second set of
conductors proximate the plasma emitters to provide a magnetic
field proximate the plasma to help influence the direction of flow
of the plasma as well as its density, particularly the density of
free electrons within a given volume containing the tissue to be
treated. Electromagnets and/or permanent magnets can be used, for
example, to apply a dipole magnetic field across the tissue, thus
providing magnetic field lines that are substantially oblique to
the nail, thus influencing the motion of reactive species across
the tissue being treated.
[0089] The electrodes that are used to generate the plasma are
optionally configured to deliver the electrical energy
simultaneously or sequentially. In this manner, the entire plasma
emitter may be excited at one time or sequentially in lines, or
sub-regions may be excited sequentially (or at the same time or
substantially the same time, if desired). The control system
further provides the means (by way of software or hard-wired) to
excite the electrodes in the desired sequence. For sequential
excitation, the electrodes or sets of electrodes are individually
addressable by the control system. For sequential excitation, the
control system provides the means to vary the intensity and
duration of the exposure to the plasma. This variation is applied
spatially, allowing the user to deliver different plasma exposure
doses to different regions of the target nail or nails.
[0090] The gas delivery from a gas supply, if provided, can be
controlled by a valve or set of valves. In one embodiment, the
operator opens the valve to provide continuous gas flow. In an
alternate embodiment, the valve or series of valves is electrically
controlled via the control system.
[0091] In an alternate embodiment, there is no gas container
structure. The electrodes are then used to excite the surrounding
ambient air to generate the plasma. When the emitter is applied to
the nail, a spacing means/spacer is used to ensure that sufficient
air is available to generate the plasma that is to be directed at
the nail. The spacing means can be a number of cavities,
microcavities, microchannels, or other depressions having negative
skewness. Alternatively, the spacing means can have positive
skewness, such as posts, pillars, raised lines, or other structures
that extend above the main surface of the device. The spacing means
also provides isolation of the electrodes from the nail.
[0092] In order to treat the desired nail section with the plasma
the following exemplary method can be used:
[0093] 1. Apply a polarizable material to the target area of the
nail surface. The polarizable material may be water, gel, or some
other conductor.
[0094] 2. Apply the plasma emitter/electrode to the polarizable
material on the target area of the nail such that the emission
surface(s) are aimed towards the desired treatment area. Depending
on the duration of treatment, the plasma emitter may be held in
place via hand pressure, gravity, or a securing means, such as an
adhesive, hook and loop fastener (e.g., from Velcro, Inc.), latch,
springs, or elastic straps.
[0095] 3. Once the plasma emitter is in place, the user activates
the device using a control means. Once activated, the emitter
delivers plasma to the target nail and/or creates plasma within the
target nail (as required).
[0096] 4. Upon completion of the treatment, the user deactivates
the device using a control means. The control means alternatively
provides an automatic shutoff once the desired dose has been
delivered.
[0097] 5. The user then removes the plasma emitter from the target
treatment area.
[0098] In an alternate embodiment, a flexible electrode is applied
directly to the nail. In this case, a conductive gel is optionally
applied prior to application of the flexible electrode. Such
conductive gel may be integrated into an adhesive patch thereby
enabling simultaneous application of the electrode and the gel.
[0099] In an alternate method to treat the target nail with plasma,
sensitizing and/or blocking materials can be used to provide
differential dosing for different sections of the nail. Such
sensitizing materials can include water-based creams, ointments,
lotions, sprays, gels, or other fluids. They can also include
hydrophilic materials, such as glycerin, which can be used to
attract water and water-based materials. These fluids are
preferably applied topically.
[0100] The sensitizing materials can act in a variety of ways.
These ways include promoting the generation of higher
concentrations of specific reactive species, promoting emission of
particular light wavelengths, modulating the electric field
strength and direction, or other. For example, fluids such as
hydrogen peroxide, saline, antioxidants such as N-acetyl cysteine
(NAC) and others can react with the plasma to generate a variety of
reactive species. Other suitable fluids are described, for example,
in International Patent Application No. PCT/US2011/046382, filed
Aug. 3, 2011 which is incorporated by reference herein in its
entirety for any purpose whatsoever. These fluids may also become
highly acidic, continue to penetrate the nails post-treatment, and
thereby enhance the pathogen killing efficacy. Moreover, the
sensitizing material can include organic materials, as well as
being in a gaseous, gelatinous or liquid state. The sensitizing
material may likewise include an amino acid such as Cysteine. In
certain embodiments, the sensitizing material is dissolved in a
liquid. Suitable liquids include saline, deionized water, phosphate
buffered saline, or a combination thereof. The amount of organic
material in the sensitizing material may vary. In certain
embodiments, the organic material in the is at a concentration of
at least about 2.5 mM. In other embodiments, the organic material
in the sensitizing material is at a concentration of at least about
5 mM. In still other embodiments, the organic material in the
sensitizing material, or composition, is at a concentration of at
least about to mM.
[0101] The blocking materials can include anhydrous (such as
oil-based) creams, ointments, gels, or other fluids. They can also
include hydrophobic materials which are used to repel water and
water-based materials. An exemplary illustrative method can have
the following steps:
[0102] 1. Apply the plasma sensitizing and/or blocking materials to
the desired treatment region (or protection region) of the nail. In
the case of sensitizing materials, it may be necessary to wait for
a certain period of time (an incubation period) for the sensitizing
materials to be absorbed by the target regions of the nail.
[0103] 2. Apply the plasma emitter to the target area of the nail
such that the emission surface is aimed towards the desired
treatment area. Depending on the duration of treatment, the plasma
emitter may be held in place via hand pressure, gravity, or a
securing means, such as an adhesive, Velcro, latches, springs, or
elastic straps.
[0104] 3. Once the plasma emitter is in place, the user activates
the device using a control means. Once activated, the emitter
delivers plasma to the target nail.
[0105] 4. Upon completion of the treatment, the user deactivates
the device using a control means. The control means alternatively
provides an automatic shutoff once the desired dose has been
delivered.
[0106] 5. The user then removes the plasma emitter from the target
treatment area.
[0107] In still another embodiment, heat, ultraviolet light, and/or
infrared radiation can be applied in concert with the plasma in
order to further accelerate the killing of pathogens. In another
embodiment, topical and/or systemic drugs can be used in
synergistic combination with the plasma treatment in order to
further increase the effectiveness and speed of killing the
pathogens. If thermal plasma or heat enhancements such as infrared
radiation are employed, it may be desirable to cool the tissue
surrounding the nail for greater patient comfort. The tissue may be
cooled by flowing or spraying water or cryogen at it.
[0108] In accordance with a further aspect, a plasma sensitizer can
also be used. In one aspect, the sensitizer can act as a conductive
fluid to direct the plasma in a desired direction, such as toward
the nail. In another aspect, the sensitizer can additionally or
alternatively provide chemicals that react with the plasma, thereby
enabling other reactions with the nail to occur. This can result in
faster reactions at the nail. Suitable materials to be used as
sensitizers can include, for example, water, saline, deionized
water, or any fluid containing organic compounds, as well as
materials including antioxidants.
[0109] In another embodiment, a layer containing an exposure
indicator is applied to the plasma treatment electrode. By using
the exposure indicator, the user will obtain direct feedback about
the amount and level of exposure applied to the body. The exposure
indicator can contain one or more compounds that react to the
exposure from plasma such that the exposure can be detected and/or
metered upon removal from the tissue. The indicator may change
color or otherwise provide a visual indication of exposure. This
change may occur immediately or after exposure to a developer or
other chemical. An example of an exposure indicator is a
photosensitive material that responds to the light emitted by the
plasma. Another example of an exposure indicator is a material that
changes color upon exposure to different pH levels or other
chemical species, such as litmus paper. A combination of different
materials may be employed to indicate different exposure levels.
Such materials can be provided in sheet form, and can be replaced
with each subsequent use of the treatment device if the device is
otherwise intended to or capable of being reusable.
[0110] In some alternative embodiments, the exposure level is
monitored automatically using optical sensors, electronic sensors,
or a combination thereof. The optical sensors, for example, can
detect visible, ultraviolet, or infrared emissions from the plasma.
The electrical sensors can detect current flow or electrical field
variation and the like as generated by the plasma emission. The
information from these sensors can then be delivered to the power
supply and control system to enable closed loop control of the
exposure dose and intensity. Such closed loop control may be
desirable to account for patient-specific anatomical or disease
variations that affect the plasma intensity, for example. The gas
delivery from the gas supply can be controlled by a valve or set of
valves. In one embodiment, the operator opens the valve to provide
continuous gas flow. In an alternate embodiment, the valve or
series of valves is electrically controlled via the control
system.
[0111] In another alternate embodiment, the power supply and
control system are connected to the electrode by a high-voltage
cable. This cable preferably has sufficient length to enable
targeting any single portion of the body or multiple areas of the
body. The electrode dimensions and weight are set so to enable
comfortable hand gripping while a plastic or other insulating
material shields the operator from any high-voltage exposure.
Alternately, the electrode may be curved (i.e. to match or nearly
match the curvature of the desired treatment) and/or flexible (as
shown in FIG. 7). A treatment electrode can have a variety of
shapes, including squares, circles, rectangles, and the like that
enable it to conform to the desired treatment area while
maintaining the desired gap or surface discharge configuration as
appropriate. The shape may be standardized for all patients or
custom-made based on casting, molding, optical scanning or other
measurement methods to create an electrode that more precisely
conforms to the anatomy of the specific patient to be treated.
Alternately, the electrode, power supply and control system can be
integrated into a single handheld unit. This unit optionally
contains batteries and/or a cable port to connect to a wall
outlet.
[0112] In still another embodiment, heat, ultraviolet light,
visible light, and/or infrared radiation can be applied in concert
with or in alternating fashion with the plasma in order to further
accelerate the killing of pathogens, alleviation of inflammation,
and/or activation of other cellular processes and chemistry. In
another embodiment, topical and/or systemic drugs can be used in
synergistic combination with the plasma treatment in order to
further increase the effectiveness and speed of killing and/or
other reactions. In another embodiment, the electrode itself is
heated and thereby provide conductive heating of the tissue, which
can combine with the non-thermal plasma to enhance the
effectiveness and speed of killing and/or other reactions.
[0113] If thermal plasma or heat enhancements such as infrared
radiation are employed, it may be desirable to cool the tissue
surrounding the treatment area for greater patient comfort. The
tissue may be cooled by flowing or spraying water or cryogen at it.
Alternatively, when the electrode is in contact with the tissue
being treated, it can be cooled and thereby provide conductive
cooling to the local tissue region being treated. In another
embodiment, after-care creams, gels, or other materials may be
applied to the treated tissue to help alleviate or repair pain,
irritation, erythema, or other unwanted effects, such as cellular
or DNA damage. For example, anti-oxidants may be used to help
reduce post-treatment levels of reactive oxygen species and promote
DNA repair.
[0114] In accordance with a further aspect, a plasma sensitizer can
also be used. In one aspect, the sensitizer can act as a conductive
fluid to direct the plasma in a desired direction, such as toward
the tissue (e.g., nail). In another aspect, the sensitizer can
additionally or alternatively provide chemicals that react with the
plasma, thereby enabling other reactions with the tissue to occur.
This can result in faster reactions at the tissue. Suitable
materials to be used as sensitizers can include, for example,
water, saline, deionized water, or any fluid containing organic
compounds, as well as materials including antioxidants. The plasma
sensitizing fluid can also be delivered to the tissue as part of
the device construction. The device can contain a spray, sponge or
vapor (aerosolized fluid) jet that has the sensitizing fluid and
controllably releases said fluid as desired by the user or
automatically upon contact by the electrode to the tissue. Finally,
a moistened fabric may be placed between the electrode and the
tissue. In this case, the discharge will occur within the cloth and
excessive streamer formation will also be avoided.
[0115] In order to deliver higher power levels to the body, it is
desirable to provide a grounding (dispersive) pad proximately
located to the plasma emitter. Such pads are commonly used in
conjunction with electrosurgical devices. As the current
transmission increases, there is a higher risk of burning the
tissue. The risk of creating tissue burns depends on the amount of
current divided by the area over which it is distributed, which is
also known as the current density. Nominally, the current density
at the ground pad is defined by the area of the pad. However, there
are some additional considerations:
[0116] 1. The entire ground pad is preferably securely attached to
the body of the patient. A partial attachment or removal of the
ground pad can cause the current density to increase.
[0117] 2. The ground pad preferably has sufficiently low resistance
to avoid generation of heat within the pad. Such a resistance can
range, for example, from about 0.1 to about 5000 ohms.
[0118] 3. The ground pad preferably radiates any heat generated
within the pad and/or can provide active cooling to minimize the
risk of burning.
[0119] In order to ensure that the ground pad is attached securely
to the patient, prior to treatment, remote monitoring of the pad
attachment can be employed as follows. First, two or more pads or
pad sections can be attached to the body in close proximity to one
another. These pads can have matching connectors and a cable or
cables that run back to the power supply and control system. Prior
to and during treatment, the power supply and control system can
send a small amount of current via one of the conductive pathways
to one of the ground pads. It then measures the return current that
is conducted by the second ground pad to determine the overall
impedance of the system. If the measured impedance deviates from
the nominal value, then the power supply and control system
prevents the treatment from starting and/or interrupts the
treatment. An indicator means (visual, audible, etc.) is provided
on the power supply and control system to inform the operator that
the grounding pad(s) are not fully attached to the body.
[0120] Optionally, the grounding pad(s) may be integrated with the
plasma emitter. Such a construction may provide advantages in ease
of application to the body, convenience, and/or lower cost. The
grounding pad can be provided within the plasma emitter, for
example, by providing a grounding conductor that is mounted around
the periphery or other non-treatment areas of the plasma emitter.
This grounding conductor is optionally mounted to the tissue via a
conductive tissue adhesive or gel. This conductor can be connected
to the power supply through a separate connector. As in the
previous discussion, it is possible to monitor the connection (and
thereby the overall current density) of the patch by sending a
small current to the grounding pad(s) and measuring the return
current to determine the overall impedance.
[0121] The plasma emitter can be connected to the power supply by a
variety of techniques. For example, short wires having an external
connector may be laminated, glued, soldered, or crimped onto the
conductive layer of the flexible plasma emitter. Alternatively, a
variety of connectors may be mounted (via soldering, lamination, or
gluing) on the conductor of the plasma emitter. These can include,
for example, snap connectors, surface mount connectors, pin holes,
crimp or clamps connectors, among others. Finally, the conductor of
the flexible plasma emitter can be formed into one half of a
connector, such as a conductive tab or pin. The plasma emitter can
be attached to the treatment area through a variety of
fasteners/attachment techniques, including hook and loop fastener,
straps, and tissue adhesives. The tissue adhesives may be
single-use or multi-use, such as in the case of hydrogels.
EXAMPLES
[0122] The following summarizes in vitro work performed by
Applicant evidencing that the disclosed systems and techniques are
useful for killing the fungus responsible for onychomycosis in
clinically-infected nail samples, including work done with a
microsecond and a nanosecond power supply.
[0123] Applicant recently demonstrated the ability of cold
atmospheric pressure plasma to kill T. rubrum, the fungus most
frequently associated with onychomycosis, in vitro in a simulated
nail model.
[0124] 0.7.times.0.7 cm sections of 317.5 micron thick shim stock
were cut and double washed in ethanol for 10 minutes. Next, 1 ml of
stock T. rubrum was homogenized with 4 ml of sterile SDM (Sabouraud
Dextrose media). The sterile shim stock was placed in 5 ml solution
of T. rubrum and inoculated for 2 hours. After removing the shim
stock from solution, it was plasma treated for varying time and
frequency settings: 1.5 or 3 kHz, 30 seconds or 3 minutes. The
treated shim stock was then placed on an SDA (agar) plate to grow
overnight. Experience has suggested that direct treatment of
microbes on agar can lead to modification of the agar itself
(making it acidic), potentially confounding the results. Hence, the
shim stock was inoculated and treated separately prior to placement
on fresh agar. Resulting sterilization of the shim stock was
determined by visual observation of "growth" or "no growth" as
shown in Table 1. We note that in these experiments, the shim stock
was still moist/wet with solution prior to treatment with plasma.
When the shim stock was allowed to dry after inoculation, the
resulting inhibition of fungal growth was less significant (2-3 day
delay, results not shown). Applicant believes that the plasma
treatment in the presence of fluids such as water creates a local
acidic environment that can enhance killing efficacy.
TABLE-US-00001 TABLE I Growth No Growth 2 Days Post Treatment
Control 1.5 kHz, 30 seconds 1.5 kHz, 3 minutes 3 kHz, 30 seconds 3
kHz, 3 minutes 9 Days Post Treatment Control 1.5 kHz, 30 seconds
1.5 kHz, 3 minutes 3 kHz, 30 seconds 3 kHz, 3 minutes Table 1:
Results of in vitro testing of plasma treatment of T. rubrum.
[0125] In onychomycosis, however, T. rubrum and other organisms can
often infect the nail bed or infect sections within the nail plate.
Like earthworms tunneling through dirt, these fungi can consume the
keratin within the nail plate, leaving microscopic pockets within
the nail plate. Accordingly, Applicant conducted tests to
demonstrate whether atmospheric pressure plasma could be generated
within microscopic air gaps of a similar size to those found within
nail plates.
[0126] FIGS. 8a-b respectively illustrate side and top views of an
experimental assembly to test generation of plasma within small
gaps ranging in size from 12 to 50 microns. The gaps were created
using shim stock and glass slides, which were then embedded in gel
(to avoid generation of plasma along the periphery). The mesh was
connected to ground and used as a transparent electrode to enable
visualization of plasma formation within the gap. As shown in FIG.
8, two glass slides were epoxied together, separated by two pieces
of shim stock having thicknesses of 50, 25 and 12.5 microns. In
each case, a high voltage electrode was brought into contact with
one side of the glass slides and a mesh was placed on the other
side and connected to ground. The entire construction was then
embedded in a gel. The mesh was used to enable visualization of the
plasma through the glass slide.
[0127] FIG. 9 presents photographic evidence of plasma discharge
formation within the small gaps at varying thicknesses from about
12.5 to about 50 microns. Applicant notes that the discharge is
likely non-uniform due to small differences in the gaps, surface
effects or other variations that could cause local concentrations
of electric field. These non-uniformities can be easily overcome
through appropriate design of the electrodes and power supplies. As
shown in FIG. 2, plasma was successfully generated within each of
the gaps, evidencing that plasmas can by analogy be generated in
nail structures that are infected with T. rubrum and/or other
organisms.
[0128] Finally, clinically-infected nail plates were harvested from
human volunteers. Control samples were taken, sliced into 50 micron
thick slices with a cryotome and cultured, confirming infection
throughout the nail plate with T. rubrum. The remaining samples
were treated with a pulsed dielectric barrier discharge at a
frequency of approximately 200-300 Hz and a voltage of 20 kV for a
duration of 5 minutes. The nail plates were treated three times for
this duration. The first time, the nail plate was treated face up
and then face down. The third time, the nail plate was embedded in
a gel in order to enable generation of plasma within gaps in the
nail plate. In all cases, the nail clippings were treated in their
"dry" state.
[0129] Upon completion of the treatment, the samples were frozen
and then sliced into 50 micron thick slices with a cryotome. The
slices were then placed on agar and incubated as before. Table 2
below shows the number of days that elapsed until growth was seen
on each slice. As shown, nearly all slices in the control sample
grew by day 2, whereas the treated samples took an average of 7
days to grow. It is known that vegetative T. rubrum populations
will double on average every 4.5 hours. Accordingly, this delay in
growth represents approximately 4-5 log reduction in the fungal
population.
TABLE-US-00002 TABLE 2 Days of Delayed Growth* 5 minute treatments
Control #1 #2 #3 #4 Slice 0-50 3 11 X 3 X (microns) 50-100 3 X 11 3
X 100-150 3 10 7 3 X 150-200 2 5 X 3 4 200-250 2 X 5 4 4 250-300 2
X 5 4 X 300-350 2 5 4 5 X 350-400 2 10 3 5 5 400-450 2 X 3 5 5
450-500 2 X 3 5 5 500-550 2 X X 4 4 550-600 2 X X 3 4 600-650 2 7 X
2 4 650-700 2 X X 3 4 700-750 2 X 11 2 4 750-800 2 X X 2 800-850 2
X 5 2 850-900 2 X 4 2 900-950 2 6 3 2 950-1000 2 6 3 2 Average 2.2
7.5 5.2 3.6 3.5 Adj. Average 2.2 11.4 8.3 3.6 6.2 Table 2: Days to
observable growth for-control (untreated) and plasma-treated nail
clippings (clinically infected with T. rubrum. The experiment was
monitored for 13 days. The `X` denotes that no growth was observed
after 13 days. The average growth is computed for all samples. The
adjusted average growth is calculated based on the assumption that
all remaining samples grew on Day 14.
[0130] For reference, this fungus is estimated to double in
population every 4.5 hours. So, if nothing grew after about 7-8
days, this corresponds to at least 6 log reduction.
[0131] Exemplary Plasma Treatment System Overview
[0132] Applicant has developed a technology to deliver atmospheric
DBD plasma to toenails with a convenient disposable electrode. The
Plasma Pin.TM. device is applied to the tissue (e.g., nail) and
connected to a high voltage power supply and control system, as
shown in FIG. 10. This power supply generates the electric field
characteristics within the patch that are necessary to initiate the
formation of non-thermal DBD plasma proximate to the nail and
within the nail. The control system has settings to enable the user
to vary the intensity of the plasma as desired. Upon activation,
plasma forms as a result of the electric field generated between
the pin and the nail plate or nail bed below the contact point. It
forms along the surface of the dielectric (silicone in this
embodiment) and travels down towards the nail plate. Based on
laboratory studies, Applicant believes that the plasma also forms
within air pockets that may be within the nail plate or nail
bed.
[0133] In the resulting non-thermal plasma, the plasma serves as a
conductor, but at relatively low current is much lower (<1
milliamp) and, as described above, this non-thermal plasma can be
operated in a regime where no damage to tissue (e.g., nail) is
observed even over treatment times as long as 20 minutes. Moreover,
this current is distributed over a large area (e.g., about 27 sq.
mm). By virtue of this moderate local current density, it is
expected that the intensity and severity of any side effects will
be moderate to the extent that they occur.
[0134] As to treatment steps for applying the plasma to a subject,
it is contemplated that the following steps can be used: [0135] 1.
Clean the target treatment site (e.g., nail) for treatment with
isopropyl alcohol and allow to dry. [0136] 2. Connect the plasma
emitter device to its power supply. [0137] 3. Connect a Grounding
Pad (if provided) to the Ground wire of the Power Supply. [0138] 4.
Apply the Grounding Pad to skin next to the tissue (e.g., toenail)
to be treated. [0139] 5. Apply "Dry" Treatment: [0140] Verify
connections from plasma emitter device and ground pad to control
system. [0141] Set controls for frequency and amplitude to desired
levels for "Dry" Treatment according to Table 3 below [0142] Verify
trigger is set to `External` [0143] Turn system on. [0144] Set
timer to desired duration for Treatment `Dry` according to Table 3
[0145] Position plasma emitter device in contact with the infected
nail plate--light hand pressure is sufficient. [0146] Flip trigger
switch to `Internal` and activate timer. [0147] Starting in one of
the proximal corners of the nail plate, scan the plasma emitter
device in a serpentine path over the entire nail plate. Repeat
scanning until treatment duration is complete. [0148] Once
treatment has been completed, flip trigger switch to `External`
[0149] 6. Apply a "Wet" treatment by moistening the site (e.g.,
toenail site) with water. [0150] 7. Repeat step 5 for Treatment
`Wet` using the parameters listed in Table 3. Subjects will be
asked to undergo treatment until it is no longer tolerable (due to
pain, for example) or up to a maximum treatment time of 10 minutes.
Moisten the target toenail as needed (5-10 times during the
treatment). [0151] 8. Disconnect and remove and store Ground Pad
(one for each patient) after the wet treatment. [0152] 9. The
patient can then be sent home with e.g., anti-fungal cream and
instructions for usage in order to help prevent potential new
infections from surrounding tinea pedis if present.
TABLE-US-00003 [0152] TABLE 3 Dry Nail Wet Nail Frequency Amplitude
Duration Duration Group Setting Setting (min.) (min.) 1 10 10 2.5
2.5 (5 subjects) (1 kHz) (20 kV) 2 10 10 5 5 (5 subjects) (1 kHz)
(20 kV) 3 10 10 10 10 (5 subjects) (1 kHz) (20 kV)
[0153] It will be appreciated that the dry and wet treatments can
be applied exclusively from the other, or in any desired
succession. It will be further appreciated that an electric field
alone and/or in combination with plasma can be applied to treat the
onychomycosis. Applicant performed in vitro testing on nail
clippings using wet and dry techniques to gage their relative
efficacy. Two nail control clippings were set aside and then three
3 samples each were treated for 5 minutes per sample using the a
power supply at two different pulse repetition frequencies (approx.
400, 800 Hz) and using the same applied voltage (20 kV). All of
these treatments were done dry (i.e., without adding additional
water). Then the experiment was repeated (3 samples each, 2
frequencies) with wet nail samples. As is evident from the below
table, after eight days, there was no fungal growth observed on any
of the wet samples post treatment. The dry samples showed some
growth on the lower frequency treatment, but not on the higher
frequency. These results are summarized in Table 4 below:
TABLE-US-00004 TABLE 4 Total = 8 Days Dry Wet Control 1 2 2 Control
2 3 2 20 kV, 400 Hz 3 -- 20 kV, 400 Hz 3 -- 20 kV, 400 Hz 4 -- 20
kV, 800 Hz -- -- 20 kV, 800 Hz -- -- 20 kV, 800 Hz -- --
[0154] Entries in the above table denoting "---" indicate no
detected growth after eight days. In order to address various
issues and advance the art, the entirety of this application
(including the Cover Page, Title, Headings, Field, Background,
Summary, Brief Description of the Drawings, Detailed Description,
Claims, Abstract, Figures, Appendices and/or otherwise) shows by
way of illustration various embodiments in which the claimed
inventions may be practiced. The advantages and features of the
application are of a representative sample of embodiments only, and
are not exhaustive and/or exclusive. They are presented only to
assist in understanding and teach the claimed principles. It should
be understood that they are not representative of all disclosed
embodiments. As such, certain aspects of the disclosure have not
been discussed herein. That alternate embodiments may not have been
presented for a specific portion of the invention or that further
undescribed alternate embodiments may be available for a portion is
not to be considered a disclaimer of those alternate embodiments.
It will be appreciated that many of those undescribed embodiments
incorporate the same principles of the invention and others are
equivalent. Thus, it is to be understood that other embodiments may
be utilized and functional, logical, organizational, structural
and/or topological modifications may be made without departing from
the scope and/or spirit of the disclosure. As such, all examples
and/or embodiments are deemed to be non-limiting throughout this
disclosure. Also, no inference should be drawn regarding those
embodiments discussed herein relative to those not discussed herein
other than it is as such for purposes of reducing space and
repetition. For instance, it is to be understood that the logical
and/or topological structure of any combination of any program
components (a component collection), other components and/or any
present feature sets as described in the figures and/or throughout
are not limited to a fixed operating order and/or arrangement, but
rather, any disclosed order is exemplary and all equivalents,
regardless of order, are contemplated by the disclosure.
Furthermore, it is to be understood that such features are not
limited to serial execution, but rather, any number of threads,
processes, services, servers, and/or the like that may execute
asynchronously, concurrently, in parallel, simultaneously,
synchronously, and/or the like are contemplated by the disclosure.
As such, some of these features may be mutually contradictory, in
that they cannot be simultaneously present in a single embodiment.
Similarly, some features are applicable to one aspect of the
invention, and inapplicable to others. In addition, the disclosure
includes other inventions not presently claimed. Applicant reserves
all rights in those presently unclaimed inventions including the
right to claim such inventions, file additional applications,
continuations, continuations in part, divisions, and/or the like
thereof. As such, it should be understood that advantages,
embodiments, examples, functional, features, logical,
organizational, structural, topological, and/or other aspects of
the disclosure are not to be considered limitations on the
disclosure as defined by the claims or limitations on equivalents
to the claims. It is to be understood that, depending on the
particular needs and/or characteristics of a MOE.TM. individual
and/or enterprise user, database configuration and/or relational
model, data type, data transmission and/or network framework,
syntax structure, and/or the like, various embodiments of the
MOE.TM. may be implemented that enable a great deal of flexibility
and customization.
[0155] All statements herein reciting principles, aspects, and
embodiments of the disclosure, as well as specific examples
thereof, are intended to encompass both structural and functional
equivalents thereof. Additionally, it is intended that such
equivalents include both currently known equivalents as well as
equivalents developed in the future, i.e., any elements developed
that perform the same function, regardless of structure.
[0156] Descriptions herein of circuitry and method steps and
computer programs represent conceptual embodiments of illustrative
circuitry and software embodying the principles of the disclosed
embodiments. Thus the functions of the various elements shown and
described herein may be provided through the use of dedicated
hardware as well as hardware capable of executing software in
association with appropriate software as set forth herein.
[0157] In the disclosure hereof any element expressed as a means
for performing a specified function is intended to encompass any
way of performing that function including, for example, a) a
combination of circuit elements and associated hardware which
perform that function or b) software in any form, including,
therefore, firmware, microcode or the like as set forth herein,
combined with appropriate circuitry for executing that software to
perform the function. Applicant thus regard any means which can
provide those functionalities as equivalent to those shown
herein.
[0158] Similarly, it will be appreciated that the system and
process flows described herein represent various processes which
may be substantially represented in computer-readable media and so
executed by a computer or processor, whether or not such computer
or processor is explicitly shown. Moreover, the various processes
can be understood as representing not only processing and/or other
functions but, alternatively, as blocks of program code that carry
out such processing or functions.
[0159] The methods, systems, computer programs and mobile devices
of the present disclosure, as described above and shown in the
drawings, among other things, provide for improved magnetic
resonance methods, systems and machine readable programs for
carrying out the same. It will be apparent to those skilled in the
art that various modifications and variations can be made in the
devices, methods, software programs and mobile devices of the
present disclosure without departing from the spirit or scope of
the disclosure. Thus, it is intended that the present disclosure
include modifications and variations that are within the scope of
the subject disclosure and equivalents.
* * * * *