U.S. patent application number 14/058973 was filed with the patent office on 2014-02-13 for apparatus and method for electromagnetic treatment of plant, animal, and human tissue, organs, cells, and molecules.
The applicant listed for this patent is Arthur A. PILLA. Invention is credited to Arthur A. PILLA.
Application Number | 20140046117 14/058973 |
Document ID | / |
Family ID | 34680788 |
Filed Date | 2014-02-13 |
United States Patent
Application |
20140046117 |
Kind Code |
A1 |
PILLA; Arthur A. |
February 13, 2014 |
APPARATUS AND METHOD FOR ELECTROMAGNETIC TREATMENT OF PLANT,
ANIMAL, AND HUMAN TISSUE, ORGANS, CELLS, AND MOLECULES
Abstract
An apparatus and method for electromagnetic treatment of plants,
animals, and humans comprising: configuring at least one waveform
according to a mathematical model having at least one waveform
parameter, said at least one waveform to be coupled to a target
pathway structure; choosing a value of said at least one waveform
parameter so that said at least waveform is configured to be
detectable in said target pathway structure above background
activity in said target pathway structure; generating an
electromagnetic signal from said configured at least one waveform;
and coupling said electromagnetic signal to said target pathway
structure using a coupling device.
Inventors: |
PILLA; Arthur A.; (Oakland,
NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PILLA; Arthur A. |
Oakland |
NJ |
US |
|
|
Family ID: |
34680788 |
Appl. No.: |
14/058973 |
Filed: |
October 21, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12772002 |
Apr 30, 2010 |
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14058973 |
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11003108 |
Dec 3, 2004 |
7744524 |
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12772002 |
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60527327 |
Dec 5, 2003 |
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Current U.S.
Class: |
600/14 |
Current CPC
Class: |
A61N 2/02 20130101; A01G
22/00 20180201; A61N 1/40 20130101; A61N 2/00 20130101; A61N 2/008
20130101 |
Class at
Publication: |
600/14 |
International
Class: |
A61N 2/00 20060101
A61N002/00; A61N 2/02 20060101 A61N002/02 |
Claims
1. A method of modulating calcium binding to calmodulin within a
target tissue using a lightweight electromagnetic treatment device,
the method comprising: placing a lightweight applicator of an
electromagnetic treatment device adjacent to a target tissue;
activating the electromagnetic treatment device so that the
applicator delivers a burst of waveforms having a burst duration
and a burst repetition rate which induces an a peak induced
magnetic field between about 1 .mu.T and about 20 .mu.T and an
electric field having an amplitude of less than 100 mV/cm at the
target tissue, such that at least one frequency component of the
induced electric field falls within the bandpass of the kinetics of
the Ca/CaM pathway in the target tissue with sufficient amplitude
so that the induced electric field is above background electrical
activity in the Ca/CaM pathway in the target tissue.
2. The method of claim 1, further comprising configuring the
induced electric field using a mathematical model which
incorporates a SNR or PSNR analysis so that at least one frequency
component of the induced electric field falls within the bandpass
of the kinetics Ca/CaM pathway.
3. The method of claim 1, wherein the induced electric field has an
amplitude of between about 1 .mu.V/cm to about 100 mV/cm in the
target tissue and a peak induced magnetic field less than about 20
.mu.T, and further wherein the induced electric field comprises a
burst of waveforms having a burst duration of greater than about
0.065 msec and a burst repetition rate.
4. The method of claim 1, wherein the induced electric field has an
amplitude of between about 1 .mu.V/cm to about 100 mV/cm in the
target tissue, and further wherein the induced electric field
comprises a burst of waveforms having a burst duration of greater
than about 0.5 msec.
5. The method of claim 1, wherein the step of activating comprises
applying a burst of waveforms repeating at a frequency of less than
100 MHz and having a duty cycle less than 1.
6. The method of claim 1, wherein the waveforms are selected from
the group of wave shapes consisting of: sinusoidal, square,
chaotic, random, symmetrical, asymmetrical, half- or full-wave
rectified.
7. The method of claim 1, wherein the waveforms have a frequency of
approximately 27.12 MHz.
8. The method of claim 1, further comprising modulating the calcium
binding to calmodulin in the target tissue to treat pain.
9. The method of claim 1, further comprising the step of using at
least one of standard medical therapies and non-standard medical
therapies adjunctively with said electromagnetic treatment.
10. The method of claim 1, further comprising the step of using at
least one of standard physical therapies and non-standard physical
therapies conjunctively with said electromagnetic treatment.
11. The method of claim 1, further comprising the step of using
said electromagnetic treatment to modulate the production and
utilization of growth factors, cytokines, and regulatory substances
by living cells.
12. The method of claim 1, further comprising modulating the
calcium binding to calmodulin in the target tissue to treat
edema.
13. The method of claim 1, further comprising modulating the
calcium binding to calmodulin in the target tissue to modulate
tissue growth and repair.
14. The method of claim 1, further comprising the step of using
said electromagnetic treatment to reduce chronic and acute pain of
musculoskeletal and neural origin.
15. The method of claim 1, further comprising the step of using
said electromagnetic treatment for treatment of diabetic and
pressure ulcers wherein said ulcers are chronic.
16. The method of claim 1, further comprising the step of using
said electromagnetic treatment for at least one of increasing blood
flow and microvascular blood perfusion.
17. The method of claim 1, further comprising the step of using
said electromagnetic treatment for at least one of
neovascularization and angiogenesis.
18. The method of claim 1, further comprising the step of using
said electromagnetic treatment to enhance immune response for
malignant and benign conditions.
19. The method of claim 1, further comprising the step of using
said electromagnetic treatment to enhance transudation.
20. A method of modulating the kinetics of calcium binding to
calmodulin within a target tissue using a lightweight electromagnet
treatment device, the method comprising: activating the lightweight
electromagnetic treatment device to emit a burst of waveforms
having a burst duration of greater than 65 .mu.sec and a burst
period of between about 0.1 to about 10 seconds; inducing an
electrical field of amplitude of less than 100 mV/cm at the target
tissue to modulate the kinetics of calcium binding to calmodulin
within the target tissue, wherein a at least some of the frequency
components of the induced electrical field fall within the time
constant of Ca/CaM binding with an amplitude sufficient so that the
induced electric field is detectable above background electrical
activity in the Ca/CaM pathway in the target tissue.
21. The method of claim 20, wherein the induced electrical field is
configured using a mathematical model to be detectable in the
Ca/CaM target pathway above background electrical activity in the
Ca/CaM target pathway.
22. The method of claim 20, wherein the induced electrical field
comprises a plurality of frequency components fall within the time
constant of Ca/CaM binding with an amplitude sufficient so that the
induced electric field is detectable above background electrical
activity in the Ca/CaM pathway in the target tissue.
23. The method of claim 20, further comprising placing the device
adjacent to the tissue to be treated.
24. The method of claim 20, wherein the induced electric field has
an amplitude of between about 1 .mu.V/cm to about 100 mV/cm in the
target tissue, and further wherein the induced electric field
comprises a burst of waveforms having a burst duration greater than
about 0.5 msec.
25. The method of claim 20, wherein the step of activating
comprises applying a burst of waveforms repeating at a frequency of
less than 100 MHz and having a duty cycle less than 1.
26. The method of claim 20, wherein the waveforms are selected from
the group of wave shapes consisting of: sinusoidal, square,
chaotic, random, symmetrical, asymmetrical, half- or full-wave
rectified.
27. The method of claim 20, wherein the waveforms have a frequency
of approximately 27.12 MHz.
28. The method of claim 20, further comprising modulating the
kinetics of calcium binding to calmodulin in the target tissue to
treat pain.
29. The method of claim 20, further comprising modulating the
kinetics of calcium binding to calmodulin in the target tissue to
treat edema.
30. The method of claim 20, further comprising modulating the
kinetics of calcium binding to calmodulin in the target tissue to
modulate tissue growth and repair.
31. A method of treating pain and edema in a target tissue using a
low-power, lightweight electromagnetic treatment device, the method
comprising: placing an applicator of the low-power, lightweight
electromagnetic treatment device adjacent to the target tissue;
activating the low-power, lightweight electromagnetic treatment
device to emit a burst of waveforms having a burst duration of
greater than 65 .mu.sec and a burst period of between about 0.1 and
about 10 seconds; reducing pain and edema by inducing an electrical
field peak amplitude of less than 100 mV/cm at the target tissue
and a magnetic field of peak amplitude of less than about 20
.mu.T.
32. The method of claim 31, wherein the step of placing the
applicator comprises wearing the applicator adjacent to the tissue
to be treated.
33. The method of claim 31, wherein the step of placing the
applicator comprises conforming a lightweight wire applicator to
the target anatomy.
34. The method of claim 31, wherein the step of activating the
low-power, lightweight electromagnetic treatment device comprises
emitting a burst of waveforms having a frequency less than 100
MHz.
35. The method of claim 31, wherein the step of activating the
low-power, lightweight electromagnetic treatment device comprises
emitting a burst of waveforms having a burst duration greater than
about 0.5 msec.
36. The method of claim 31, further comprising continuing treatment
for multiple applications of a prescribed duration.
37. The method of claim 31, further comprising continuing treatment
for a treatment duration of between about 1 minute to about 30
minutes.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 12/772,002, filed Apr. 30, 2010, entitled "APPARATUS AND
METHOD FOR ELECTROMAGNETIC TREATMENT OF PLANT, ANIMAL, AND HUMAN
TISSUE, ORGANS, CELLS, AND MOLECULES," Publication No. US
2010/0222631 A1, which is a continuation of U.S. patent application
Ser. No. 11/003,108, filed Dec. 3, 2004 entitled "APPARATUS AND
METHOD FOR ELECTROMAGNETIC TREATMENT OF PLANT, ANIMAL, AND HUMAN
TISSUE, ORGANS, CELLS, AND MOLECULES," now U.S. Pat. No. 7,744,524
which claims the benefit under 35 U.S.C. .sctn.119 of U.S.
Provisional Patent Application No. 60/527,327, filed Dec. 5, 2003,
titled "APPARATUS AND METHOD FOR ELECTROMAGNETIC TREATMENT OF
PLANT, ANIMAL, AND HUMAN TISSUE, ORGANS, CELLS AND MOLECULES," each
of which is herein incorporated by reference in its entirety.
INCORPORATION BY REFERENCE
[0002] All publications and patent applications mentioned in this
specification are herein incorporated by reference in their
entirety to the same extent as if each individual publication or
patent application was specifically and individually indicated to
be incorporated by reference.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] This invention pertains generally to an apparatus and a
method for in vitro and in vivo therapeutic and prophylactic
treatment of plant, animal, and human tissue, organs, cells and
molecules. In particular, an embodiment according to the present
invention pertains to use of non-thermal time-varying magnetic
fields configured for optimal coupling to target pathway structures
such as molecules, cells, tissue, and organs, using power and
amplitude comparison analysis to evaluate a signal to thermal noise
ratio ("SNR") in the target pathway structure. Another embodiment
according to the present invention pertains to application of
bursts of arbitrary waveform electromagnetic signals to target
pathway structures such as molecules, cells, tissues, and organs
using ultra lightweight portable coupling devices such as inductors
and electrodes, and driver circuitry that can be incorporated into
a positioning device such as knee, elbow, lower back, shoulder,
foot, and other anatomical wraps, as well as apparel such as
garments, footware, and fashion accessories.
[0005] Yet another embodiment according to the present invention
pertains to application of steady state periodic signals of
arbitrary waveform electromagnetic signals to target pathway
structures such as molecules, cells, tissues, and organs. Examples
of therapeutic and prophylactic applications of the present
invention are musculoskeletal pain relief, edema reduction,
increased local blood flow, microvascular blood perfusion, wound
repair, bone repair, osteoporosis treatment and prevention,
angiogenesis, neovascularization, enhanced immune response, tissue
repair, enhanced transudation, and enhanced effectiveness of
pharmacological agents. An embodiment according to the present
invention can also be used in conjunction with other therapeutic
and prophylactic procedures and modalities such as heat, cold,
ultrasound, vacuum assisted wound closure, wound dressing,
orthopedic fixation devices, and surgical interventions.
[0006] 2. Discussion of Related Art
[0007] It is now well established that application of weak
non-thermal electromagnetic fields ("EMF") can result in
physiologically meaningful in vivo and in vitro bioeffects.
Time-varying electromagnetic fields, comprising rectangular
waveforms such as pulsing electromagnetic fields ("PEMF"), and
sinusoidal waveforms such as pulsed radio frequency fields ("PRF")
ranging from several Hertz to an about 15 to an about 40 MHz range,
are clinically beneficial when used as an adjunctive therapy for a
variety of musculoskeletal injuries and conditions.
[0008] Beginning in the 1960's, development of modern therapeutic
and prophylactic devices was stimulated by clinical problems
associated with non-union and delayed union bone fractures. Early
work showed that an electrical pathway can be a means through which
bone adaptively responds to mechanical input. Early therapeutic
devices used implanted and semi-invasive electrodes delivering
direct current ("DC") to a fracture site. Non-invasive technologies
were subsequently developed using electrical and electromagnetic
fields. These modalities were originally created to provide a
non-invasive "no-touch" means of inducing an electrical/mechanical
waveform at a cell/tissue level. Clinical applications of these
technologies in orthopaedics have led to approved applications by
regulatory bodies worldwide for treatment of fractures such as
non-unions and fresh fractures, as well as spine fusion. Presently
several EMF devices constitute the standard armamentarium of
orthopaedic clinical practice for treatment of difficult to heal
fractures. The success rate for these devices has been very high.
The database for this indication is large enough to enable its
recommended use as a safe, non-surgical, non-invasive alternative
to a first bone graft. Additional clinical indications for these
technologies have been reported in double blind studies for
treatment of avascular necrosis, tendinitis, osteoarthritis, wound
repair, blood circulation and pain from arthritis as well as other
musculoskeletal injuries.
[0009] Cellular studies have addressed effects of weak low
frequency electromagnetic fields on both signal transduction
pathways and growth factor synthesis. It can be shown that EMF
stimulates secretion of growth factors after a short, trigger-like
duration. Ion/ligand binding processes at a cell membrane are
generally considered an initial EMF target pathway structure. The
clinical relevance to treatments for example of bone repair, is
upregulation such as modulation, of growth factor production as
part of normal molecular regulation of bone repair. Cellular level
studies have shown effects on calcium ion transport, cell
proliferation, Insulin Growth Factor ("IGF-II") release, and IGF-II
receptor expression in osteoblasts. Effects on Insulin Growth
Factor-I ("IGF-I") and IGF-II have also been demonstrated in rat
fracture callus. Stimulation of transforming growth factor beta
("TGF-.beta.") messenger RNA ("mRNA") with PEMF in a bone induction
model in a rat has been shown. Studies have also demonstrated
upregulation of TGF-.beta. mRNA by PEMF in human osteoblast-like
cell line designated MG-63, wherein there were increases in
TGF-.beta.1, collagen, and osteocalcin synthesis. PEMF stimulated
an increase in TGF-.beta.1 in both hypertrophic and atrophic cells
from human non-union tissue. Further studies demonstrated an
increase in both TGF-.beta.1 mRNA and protein in osteoblast
cultures resulting from a direct effect of EMF on a
calcium/calmodulin-dependent pathway. Cartilage cell studies have
shown similar increases in TGF-.beta.1 mRNA and protein synthesis
from EMF, demonstrating a therapeutic application to joint repair.
U.S. Pat. No. 4,315,503 (1982) to Ryaby and U.S. Pat. No. 5,723,001
(1998) to Pilla typify the research conducted in this field.
[0010] However, prior art in this field applies unnecessarily high
amplitude and power to a target pathway structure, requires
unnecessarily long treatment time, and is not portable.
[0011] Therefore, a need exists for an apparatus and a method that
more effectively modulates biochemical processes that regulate
tissue growth and repair, shortens treatment times, and
incorporates miniaturized circuitry and light weight applicators
thus allowing the apparatus to be portable and if desired
disposable. A further need exists for an apparatus and method that
more effectively modulates biochemical processes that regulate
tissue growth and repair, shortens treatment times, and
incorporates miniaturized circuitry and light weight applicators
that can be constructed to be implantable.
SUMMARY OF THE INVENTION
[0012] An apparatus and a method for delivering electromagnetic
signals to human, animal and plant target pathway structures such
as molecules, cells, tissue and organs for therapeutic and
prophylactic purposes. A preferred embodiment according to the
present invention utilizes a Power Signal to Noise Ratio ("Power
SNR") approach to configure bioeffective waveforms and incorporates
miniaturized circuitry and lightweight flexible coils. This
advantageously allows a device that utilizes a Power SNR approach,
miniaturized circuitry, and lightweight flexible coils, to be
completely portable and if desired to be constructed as disposable
and if further desired to be constructed as implantable.
[0013] Specifically, broad spectral density bursts of
electromagnetic waveforms, configured to achieve maximum signal
power within a bandpass of a biological target, are selectively
applied to target pathway structures such as living organs,
tissues, cells and molecules. Waveforms are selected using a unique
amplitude/power comparison with that of thermal noise in a target
pathway structure. Signals comprise bursts of at least one of
sinusoidal, rectangular, chaotic and random wave shapes, have
frequency content in a range of about 0.01 Hz to about 100 MHz at
about 1 to about 100,000 bursts per second, and have a burst
repetition rate from about 0.01 to about 1000 bursts/second. Peak
signal amplitude at a target pathway structure such as tissue, lies
in a range of about 1 .mu.V/cm to about 100 mV/cm. Each signal
burst envelope may be a random function providing a means to
accommodate different electromagnetic characteristics of healing
tissue. A preferred embodiment according to the present comprises a
20 millisecond pulse burst comprising about 5 to about 20
microsecond symmetrical or asymmetrical pulses repeating at about 1
to about 100 kilohertz within the burst. The burst envelope is a
modified 1/f function and is applied at random repetition rates. A
resulting waveform can be delivered via inductive or capacitive
coupling.
[0014] It is an object of the present invention to configure a
power spectrum of a waveform by mathematical simulation by using
signal to noise ratio ("SNR") analysis to configure an optimized,
bioeffective waveform then coupling the configured waveform using a
generating device such as ultra lightweight wire coils that are
powered by a waveform configuration device such as miniaturized
electronic circuitry.
[0015] It is another object of the present invention to evaluate
Power SNR for any target pathway structure such as molecules,
cells, tissues and organs of plants, animals and humans using any
input waveform, even if the electrical equivalents are non-linear
as in a Hodgkin-Huxley membrane model.
[0016] It is another object of the present invention to provide a
method and apparatus for treating plants, animals and humans using
electromagnetic fields selected by optimizing a power spectrum of a
waveform to be applied to a chosen biochemical target pathway
structure such as a molecule, cell, tissue and organ of a plant,
animal, and human.
[0017] It is another object of the present invention to employ
significantly lower peak amplitudes and shorter pulse duration.
This can be accomplished by matching via Power SNR, a frequency
range in a signal to frequency response and sensitivity of a target
pathway structure such as a molecule, cell, tissue, and organ, of
plants, animals and humans.
[0018] The above and yet other objects and advantages of the
present invention will become apparent from the hereinafter set
forth Brief Description of the Drawings, Detailed Description of
the Invention, and Claims appended herewith.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Preferred embodiments of the present invention will be
described below in more detail, with reference to the accompanying
drawings:
[0020] FIG. 1 is a flow diagram of a method for electromagnetic
treatment of plant, animal, and human target pathway structures
such as tissue, organs, cells, and molecules according to an
embodiment of the present invention;
[0021] FIG. 2 is a view of control circuitry and electrical coils
applied to a knee joint according to a preferred embodiment of the
present invention;
[0022] FIG. 3 is a block diagram of miniaturized circuitry
according to a preferred embodiment of the present invention;
[0023] FIG. 4A is a line drawing of a wire coil such as an inductor
according to a preferred embodiment of the present invention;
[0024] FIG. 4B is a line drawing of a flexible magnetic wire
according to a preferred embodiment of the present invention;
[0025] FIG. 5 depicts a waveform delivered to a target pathway
structure such as a molecule, cell, tissue or organ according to a
preferred embodiment of the present invention;
[0026] FIG. 6 is a view of a positioning device such as a wrist
support according to a preferred embodiment of the present
invention;
[0027] FIG. 7 is a graph illustrating maximally increased myosin
phosphorylation for a PMRF signal configured according to an
embodiment of the present invention; and
[0028] FIG. 8 is a graph illustrating a power consumption
comparison between a 60 Hz signal and a PEMF signal configured
according to an embodiment of the present invention.
DETAILED DESCRIPTION
[0029] Induced time-varying currents from PEMF or PRF devices flow
in a target pathway structure such as a molecule, cell, tissue, and
organ, and it is these currents that are a stimulus to which cells
and tissues can react in a physiologically meaningful manner. The
electrical properties of a target pathway structure affect levels
and distributions of induced current. Molecules, cells, tissue, and
organs are all in an induced current pathway such as cells in a gap
junction contact. Ion or ligand interactions at binding sites on
macromolecules that may reside on a membrane surface are voltage
dependent processes, that is electrochemical, that can respond to
an induced electromagnetic field ("E"). Induced current arrives at
these sites via a surrounding ionic medium. The presence of cells
in a current pathway causes an induced current ("J") to decay more
rapidly with time ("J(t)"). This is due to an added electrical
impedance of cells from membrane capacitance and time constants of
binding and other voltage sensitive membrane processes such as
membrane transport.
[0030] Equivalent electrical circuit models representing various
membrane and charged interface configurations have been derived.
For example, in Calcium ("Ca.sup.2+") binding, the change in
concentration of bound Ca.sup.2+ at a binding site due to induced E
may be described in a frequency domain by an impedance expression
such as:
Z b ( .omega. ) = R ion + 1 i .omega. C ion ##EQU00001##
which has the form of a series resistance-capacitance electrical
equivalent circuit. Where .omega. is angular frequency defined as
2.pi.f, where f is frequency, i=-1.sup.1/2, Z.sub.b(.omega.) is the
binding impedance, and R.sub.ion and C.sub.ion are equivalent
binding resistance and capacitance of an ion binding pathway. The
value of the equivalent binding time constant,
.tau..sub.ion=R.sub.ionC.sub.ion, is related to a ion binding rate
constant, k.sub.b, via .tau..sub.ion=R.sub.ionC.sub.ion=1/k.sub.b.
Thus, the characteristic time constant of this pathway is
determined by ion binding kinetics.
[0031] Induced E from a PEMF or PRF signal can cause current to
flow into an ion binding pathway and affect the number of Ca.sup.2+
ions bound per unit time. An electrical equivalent of this is a
change in voltage across the equivalent binding capacitance
C.sub.ion, which is a direct measure of the change in electrical
charge stored by C.sub.ion. Electrical charge is directly
proportional to a surface concentration of Ca.sup.2+ ions in the
binding site, that is storage of charge is equivalent to storage of
ions or other charged species on cell surfaces and junctions.
Electrical impedance measurements, as well as direct kinetic
analyses of binding rate constants, provide values for time
constants necessary for configuration of a PMF waveform to match a
bandpass of target pathway structures. This allows for a required
range of frequencies for any given induced E waveform for optimal
coupling to target impedance, such as bandpass.
[0032] Ion binding to regulatory molecules is a frequent EMF
target, for example Ca.sup.2+ binding to calmodulin ("CaM"). Use of
this pathway is based upon acceleration of wound repair, for
example bone repair, that involves modulation of growth factors
released in various stages of repair. Growth factors such as
platelet derived growth factor ("PDGF"), fibroblast growth factor
("FGF"), and epidermal growth factor ("EGF") are all involved at an
appropriate stage of healing. Angiogenesis is also integral to
wound repair and modulated by PMF. All of these factors are
Ca/CaM-dependent.
[0033] Utilizing a Ca/CaM pathway a waveform can be configured for
which induced power is sufficiently above background thermal noise
power. Under correct physiological conditions, this waveform can
have a physiologically significant bioeffect.
[0034] Application of a Power SNR model to Ca/CaM requires
knowledge of electrical equivalents of Ca.sup.2+ binding kinetics
at CaM. Within first order binding kinetics, changes in
concentration of bound Ca.sup.2+ at CaM binding sites over time may
be characterized in a frequency domain by an equivalent binding
time constant, .tau..sub.ion=R.sub.ionC.sub.ion, where R.sub.ion
and C.sub.ion are equivalent binding resistance and capacitance of
the ion binding pathway. .tau..sub.ion is related to a ion binding
rate constant, k.sub.b, via
.tau..sub.ion=R.sub.ionC.sub.ion=1/k.sub.b. Published values for
k.sub.b can then be employed in a cell array model to evaluate SNR
by comparing voltage induced by a PRF signal to thermal
fluctuations in voltage at a CaM binding site. Employing numerical
values for PMF response, such as V.sub.max=6.5.times.10.sup.-7
sec.sup.-1, [Ca.sup.2+]=2.5 .mu.M, K.sub.D=30 .mu.M,
[Ca.sup.2+CaM]=K.sub.D([Ca.sup.2+]+[CaM]), yields k.sub.b=665
sec.sup.-1 (.tau..sub.ion=1.5 msec). Such a value for .tau..sub.ion
can be employed in an electrical equivalent circuit for ion binding
while power SNR analysis can be performed for any waveform
structure.
[0035] According to an embodiment of the present invention a
mathematical model can be configured to assimilate that thermal
noise is present in all voltage dependent processes and represents
a minimum threshold requirement to establish adequate SNR. Power
spectral density, S.sub.n(.omega.), of thermal noise can be
expressed as:
S.sub.n(.omega.)=4kT Re[Z.sub.M(x,.omega.)]
where Z.sub.M(x, .omega.) is electrical impedance of a target
pathway structure, x is a dimension of a target pathway structure
and Re denotes a real part of impedance of a target pathway
structure. Z.sub.M(x, .omega.) can be expressed as:
Z M ( x , .omega. ) = [ R e + R i + R g y ] tanh ( yx )
##EQU00002##
[0036] This equation clearly shows that electrical impedance of the
target pathway structure, and contributions from extracellular
fluid resistance ("R.sub.e"), intracellular fluid resistance
("R.sub.i") and intermembrane resistance ("R.sub.g") which are
electrically connected to a target pathway structure, all
contribute to noise filtering.
[0037] A typical approach to evaluation of SNR uses a single value
of a root mean square (RMS) noise voltage. This is calculated by
taking a square root of an integration of S.sub.n(.omega.)=4 kT
Re[Z.sub.M(x,.omega.)] over all frequencies relevant to either
complete membrane response, or to bandwidth of a target pathway
structure. SNR can be expressed by a ratio:
SNR = V M ( .omega. ) RMS ##EQU00003##
where |V.sub.M(.omega.)| is maximum amplitude of voltage at each
frequency as delivered by a chosen waveform to the target pathway
structure.
[0038] Referring to FIG. 1, wherein FIG. 1 is a flow diagram of a
method for delivering electromagnetic signals to target pathway
structures such as molecules, cells, tissue and organs of plants,
animals, and humans for therapeutic and prophylactic purposes
according to an embodiment of the present invention. A mathematical
model having at least one waveform parameter is applied to
configure at least one waveform to be coupled to a target pathway
structure such as a molecule, cell, tissue, and organ (Step 101).
The configured waveform satisfies a SNR or Power SNR model so that
for a given and known target pathway structure it is possible to
choose at least one waveform parameter so that a waveform is
detectable in the target pathway structure above its background
activity (Step 102) such as baseline thermal fluctuations in
voltage and electrical impedance at a target pathway structure that
depend upon a state of a cell and tissue, that is whether the state
is at least one of resting, growing, replacing, and responding to
injury. A preferred embodiment of a generated electromagnetic
signal is comprised of a burst of arbitrary waveforms having at
least one waveform parameter that includes a plurality of frequency
components ranging from about 0.01 Hz to about 100 MHz wherein the
plurality of frequency components satisfies a Power SNR model (Step
102). A repetitive electromagnetic signal can be generated for
example inductively or capacitively, from said configured at least
one waveform (Step 103). The electromagnetic signal is coupled to a
target pathway structure such as a molecule, cell, tissue, and
organ by output of a coupling device such as an electrode or an
inductor, placed in close proximity to the target pathway structure
(Step 104). The coupling enhances a stimulus to which cells and
tissues react in a physiologically meaningful manner.
[0039] FIG. 2 illustrates a preferred embodiment of an apparatus
according to the present invention. A miniature control circuit 201
is coupled to an end of at least one connector 202 such as wire.
The opposite end of the at least one connector is coupled to a
generating device such as a pair of electrical coils 203. The
miniature control circuit 201 is constructed in a manner that
applies a mathematical model that is used to configure waveforms.
The configured waveforms have to satisfy a SNR or Power SNR model
so that for a given and known target pathway structure, it is
possible to choose waveform parameters that satisfy SNR or Power
SNR so that a waveform is detectable in the target pathway
structure above its background activity. A preferred embodiment
according to the present invention applies a mathematical model to
induce a time-varying magnetic field and a time-varying electric
field in a target pathway structure such as a molecule, cell,
tissue, and organ, comprising about 10 to about 100 msec bursts of
about 1 to about 100 microsecond rectangular pulses repeating at
about 0.1 to about 10 pulses per second. Peak amplitude of the
induced electric field is between about 1 uV/cm and about 100
mV/cm, varied according to a modified 1/f function where
f=frequency. A waveform configured using a preferred embodiment
according to the present invention may be applied to a target
pathway structure such as a molecule, cell, tissue, and organ for a
preferred total exposure time of under 1 minute to 240 minutes
daily. However other exposure times can be used. Waveforms
configured by the miniature control circuit 201 are directed to a
generating device 203 such as electrical coils via connector 202.
The generating device 203 delivers a pulsing magnetic field
configured according to a mathematical model, that can be used to
provide treatment to a target pathway structure such as knee joint
204. The miniature control circuit applies a pulsing magnetic field
for a prescribed time and can automatically repeat applying the
pulsing magnetic field for as many applications as are needed in a
given time period, for example 10 times a day. A preferred
embodiment according to the present invention can be positioned to
treat the knee joint 204 by a positioning device. The positioning
device can be portable such as an anatomical support, and is
further described below with reference to FIG. 6. Coupling a
pulsing magnetic field to a target pathway structure such as a
molecule, cell, tissue, and organ, therapeutically and
prophylactically reduces inflammation thereby reducing pain and
promotes healing. When electrical coils are used as the generating
device 203, the electrical coils can be powered with a time varying
magnetic field that induces a time varying electric field in a
target pathway structure according to Faraday's law. An
electromagnetic signal generated by the generating device 203 can
also be applied using electrochemical coupling, wherein electrodes
are in direct contact with skin or another outer electrically
conductive boundary of a target pathway structure. Yet in another
embodiment according to the present invention, the electromagnetic
signal generated by the generating device 203 can also be applied
using electrostatic coupling wherein an air gap exists between a
generating device 203 such as an electrode and a target pathway
structure such as a molecule, cell, tissue, and organ. An advantage
of the preferred embodiment according to the present invention is
that its ultra lightweight coils and miniaturized circuitry allow
for use with common physical therapy treatment modalities and at
any body location for which pain relief and healing is desired. An
advantageous result of application of the preferred embodiment
according to the present invention is that a living organism's
wellbeing can be maintained and enhanced.
[0040] FIG. 3 depicts a block diagram of a preferred embodiment
according to the present invention of a miniature control circuit
300. The miniature control circuit 300 produces waveforms that
drive a generating device such as wire coils described above in
FIG. 2. The miniature control circuit can be activated by any
activation means such as an on/off switch. The miniature control
circuit 300 has a power source such as a lithium battery 301. A
preferred embodiment of the power source has an output voltage of
3.3 V but other voltages can be used. In another embodiment
according to the present invention the power source can be an
external power source such as an electric current outlet such as an
AC/DC outlet, coupled to the present invention for example by a
plug and wire. A switching power supply 302 controls voltage to a
micro-controller 303. A preferred embodiment of the
micro-controller 303 uses an 8 bit 4 MHz micro-controller 303 but
other bit MHz combination micro-controllers may be used. The
switching power supply 302 also delivers current to storage
capacitors 304. A preferred embodiment of the present invention
uses storage capacitors having a 220 uF output but other outputs
can be used. The storage capacitors 304 allow high frequency pulses
to be delivered to a coupling device such as inductors (Not Shown).
The micro-controller 303 also controls a pulse shaper 305 and a
pulse phase timing control 306. The pulse shaper 305 and pulse
phase timing control 306 determine pulse shape, burst width, burst
envelope shape, and burst repetition rate. An integral waveform
generator, such as a sine wave or arbitrary number generator can
also be incorporated to provide specific waveforms. A voltage level
conversion sub-circuit 308 controls an induced field delivered to a
target pathway structure. A switching Hexfet 308 allows pulses of
randomized amplitude to be delivered to output 309 that routes a
waveform to at least one coupling device such as an inductor. The
micro-controller 303 can also control total exposure time of a
single treatment of a target pathway structure such as a molecule,
cell, tissue, and organ. The miniature control circuit 300 can be
constructed to apply a pulsing magnetic field for a prescribed time
and to automatically repeat applying the pulsing magnetic field for
as many applications as are needed in a given time period, for
example 10 times a day. A preferred embodiment according to the
present invention uses treatments times of about 10 minutes to
about 30 minutes.
[0041] Referring to FIGS. 4A and 4B a preferred embodiment
according to the present invention of a coupling device 400 such as
an inductor is shown. The coupling device 400 can be an electric
coil 401 wound with multistrand flexible magnetic wire 402. The
multistrand flexible magnetic wire 402 enables the electric coil
401 to conform to specific anatomical configurations such as a limb
or joint of a human or animal. A preferred embodiment of the
electric coil 401 comprises about 10 to about 50 turns of about
0.01 mm to about 0.1 mm diameter multistrand magnet wire wound on
an initially circular form having an outer diameter between about
2.5 cm and about 50 cm but other numbers of turns and wire
diameters can be used. A preferred embodiment of the electric coil
401 can be encased with a non-toxic PVC mould 403 but other
non-toxic moulds can also be used.
[0042] Referring to FIG. 5 an embodiment according to the present
invention of a waveform 500 is illustrated. A pulse 501 is repeated
within a burst 502 that has a finite duration 503. The duration 503
is such that a duty cycle which can be defined as a ratio of burst
duration to signal period is between about 1 to about 10.sup.-5. A
preferred embodiment according to the present invention utilizes
pseudo rectangular 10 microsecond pulses for pulse 501 applied in a
burst 502 for about 10 to about 50 msec having a modified 1/f
amplitude envelope 504 and with a finite duration 503 corresponding
to a burst period of between about 0.1 and about 10 seconds.
[0043] FIG. 6 illustrates a preferred embodiment according to the
present invention of a positioning device such as a wrist support.
A positioning device 600 such as a wrist support 601 is worn on a
human wrist 602. The positioning device can be constructed to be
portable, can be constructed to be disposable, and can be
constructed to be implantable. The positioning device can be used
in combination with the present invention in a plurality of ways,
for example incorporating the present invention into the
positioning device for example by stitching, affixing the present
invention onto the positioning device for example by Velcro.RTM.,
and holding the present invention in place by constructing the
positioning device to be elastic.
[0044] In another embodiment according to the present invention,
the present invention can be constructed as a stand-alone device of
any size with or without a positioning device, to be used anywhere
for example at home, at a clinic, at a treatment center, and
outdoors. The wrist support 601 can be made with any anatomical and
support material, such as neoprene. Coils 603 are integrated into
the wrist support 601 such that a signal configured according to
the present invention, for example the waveform depicted in FIG. 5,
is applied from a dorsal portion that is the top of the wrist to a
plantar portion that is the bottom of the wrist. Micro-circuitry
604 is attached to the exterior of the wrist support 601 using a
fastening device such as Velcro.RTM. (Not Shown). The
micro-circuitry is coupled to one end of at least one connecting
device such as a flexible wire 605. The other end of the at least
one connecting device is coupled to the coils 603. Other
embodiments according to the present invention of the positioning
device include knee, elbow, lower back, shoulder, other anatomical
wraps, and apparel such as garments, fashion accessories, and
footware.
Example 1
[0045] The Power SNR approach for PMF signal configuration has been
tested experimentally on calcium dependent myosin phosphorylation
in a standard enzyme assay. The cell-free reaction mixture was
chosen for phosphorylation rate to be linear in time for several
minutes, and for sub-saturation Ca.sup.2+ concentration. This opens
the biological window for Ca.sup.2+/CaM to be EMF-sensitive. This
system is not responsive to PMF at levels utilized in this study if
Ca.sup.2+ is at saturation levels with respect to CaM, and reaction
is not slowed to a minute time range. Experiments were performed
using myosin light chain ("MLC") and myosin light chain kinase
("MLCK") isolated from turkey gizzard. A reaction mixture consisted
of a basic solution containing 40 mM Hepes buffer, pH 7.0; 0.5 mM
magnesium acetate; 1 mg/ml bovine serum albumin, 0.1% (w/v) Tween
80; and 1 mM EGTA12. Free Ca.sup.2+ was varied in the 1-7 .mu.M
range. Once Ca.sup.2+ buffering was established, freshly prepared
70 nM CaM, 160 nM MLC and 2 nM MLCK were added to the basic
solution to form a final reaction mixture. The low MLC/MLCK ratio
allowed linear time behavior in the minute time range. This
provided reproducible enzyme activities and minimized pipetting
time errors.
[0046] The reaction mixture was freshly prepared daily for each
series of experiments and was aliquoted in 100 .mu.L portions into
1.5 ml Eppendorf tubes. All Eppendorf tubes containing reaction
mixture were kept at 0.degree. C. then transferred to a specially
designed water bath maintained at 37.+-.0.1.degree. C. by constant
perfusion of water prewarmed by passage through a Fisher Scientific
model 900 heat exchanger. Temperature was monitored with a
thermistor probe such as a Cole-Parmer model 8110-20, immersed in
one Eppendorf tube during all experiments. Reaction was initiated
with 2.5 .mu.M 32P ATP, and was stopped with Laemmli Sample Buffer
solution containing 30 .mu.M EDTA. A minimum of five blank samples
were counted in each experiment. Blanks comprised a total assay
mixture minus one of the active components Ca.sup.2+, CaM, MLC or
MLCK. Experiments for which blank counts were higher than 300 cpm
were rejected. Phosphorylation was allowed to proceed for 5 min and
was evaluated by counting 32P incorporated in MLC using a TM
Analytic model 5303 Mark V liquid scintillation counter.
[0047] The signal comprised repetitive bursts of a high frequency
waveform. Amplitude was maintained constant at 0.2G and repetition
rate was 1 burst/sec for all exposures. Burst duration varied from
65 .mu.sec to 1000 .mu.sec based upon projections of Power SNR
analysis which showed that optimal Power SNR would be achieved as
burst duration approached 500 .mu.sec. The results are shown in
FIG. 7 wherein burst width 701 in .mu.ec is plotted on the x-axis
and Myosin Phosphorylation 702 as treated/sham is plotted on the
y-axis. It can be seen that the PMF effect on Ca.sup.2+ binding to
CaM approaches its maximum at approximately 500 .mu.sec, just as
illustrated by the Power SNR model.
[0048] These results confirm that a PMF signal, configured
according to an embodiment of the present invention, would
maximally increase myosin phosphorylation for burst durations
sufficient to achieve optimal Power SNR for a given magnetic field
amplitude.
Example 2
[0049] According to an embodiment of the present invention use of a
Power SNR model was further verified in an in vivo wound repair
model. A rat wound model has been well characterized both
biomechanically and biochemically, and was used in this study.
Healthy, young adult male Sprague Dawley rats weighing more than
300 grams were utilized.
[0050] The animals were anesthetized with an intraperitoneal dose
of Ketamine 75 mg/kg and Medetomidine 0.5 mg/kg. After adequate
anesthesia had been achieved, the dorsum was shaved, prepped with a
dilute betadine/alcohol solution, and draped using sterile
technique. Using a #10 scalpel, an 8-cm linear incision was
performed through the skin down to the fascia on the dorsum of each
rat. The wound edges were bluntly dissected to break any remaining
dermal fibers, leaving an open wound approximately 4 cm in
diameter. Hemostasis was obtained with applied pressure to avoid
any damage to the skin edges. The skin edges were then closed with
a 4-0 Ethilon running suture. Post-operatively, the animals
received Buprenorphine 0.1-0.5 mg/kg, intraperitoneal. They were
placed in individual cages and received food and water ad
libitum.
[0051] PMF exposure comprised two pulsed radio frequency waveforms.
The first was a standard clinical PRF signal comprising a 65 pec
burst of 27.12 MHz sinusoidal waves at 1 Gauss amplitude and
repeating at 600 bursts/sec. The second was a PRF signal
reconfigured according to an embodiment of the present invention.
For this signal burst duration was increased to 2000 .mu.sec and
the amplitude and repetition rate were reduced to 0.2G and 5
bursts/sec respectively. PRF was applied for 30 minutes twice
daily.
[0052] Tensile strength was performed immediately after wound
excision. Two 1 cm width strips of skin were transected
perpendicular to the scar from each sample and used to measure the
tensile strength in kg/mm.sup.2. The strips were excised from the
same area in each rat to assure consistency of measurement. The
strips were then mounted on a tensiometer. The strips were loaded
at 10 mm/min and the maximum force generated before the wound
pulled apart was recorded. The final tensile strength for
comparison was determined by taking the average of the maximum load
in kilograms per mm.sup.2 of the two strips from the same
wound.
[0053] The results showed average tensile strength for the 65 psec
1 Gauss PRF signal was 19.3.+-.4.3 kg/mm.sup.2 for the exposed
group versus 13.0.+-.3.5 kg/mm.sup.2 for the control group
(p<0.01), which is a 48% increase. In contrast, the average
tensile strength for the 2000 .mu.sec 0.2 Gauss PRF signal,
configured according to an embodiment of the present invention
using a Power SNR model was 21.2.+-.5.6 kg/mm.sup.2 for the treated
group versus 13.7.+-.4.1 kg/mm.sup.2 (p<0.01) for the control
group, which is a 54% increase. The results for the two signals
were not significantly different from each other.
[0054] These results demonstrate that an embodiment of the present
invention allowed a new PRF signal to be configured that could be
produced with significantly lower power. The PRF signal configured
according to an embodiment of the present invention, accelerated
wound repair in the rat model in a low power manner versus that for
a clinical PRF signal which accelerated wound repair but required
more than two orders of magnitude more power to produce.
Example 3
[0055] In this example Jurkat cells react to PMF stimulation of a
T-cell receptor with cell cycle arrest and thus behave like normal
T-lymphocytes stimulated by antigens at the T-cell receptor such as
anti-CD3. For example in bone healing, results have shown both 60
Hz and PEMF fields decrease DNA synthesis of Jurkat cells, as is
expected since PMF interacts with the T-cell receptor in the
absence of a costimulatory signal. This is consistent with an
anti-inflammatory response, as has been observed in clinical
applications of PMF stimuli. The PEMF signal is more effective. A
dosimetry analysis performed according to an embodiment of the
present invention demonstrates why both signals are effective and
why PEMF signals have a greater effect than 60 Hz signals on Jurkat
cells in the most EMF-sensitive growth stage.
[0056] Comparison of dosimetry from the two signals employed
involves evaluation of the ratio of the Power spectrum of the
thermal noise voltage that is Power SNR, to that of the induced
voltage at the EMF-sensitive target pathway structure. The target
pathway structure used is ion binding at receptor sites on Jurkat
cells suspended in 2 mm of culture medium. The average peak
electric field at the binding site from a PEMF signal comprising 5
msec burst of 200 .mu.sec pulses repeating at 15/sec, was 1 mV/cm,
while for a 60 Hz signal it was 50 .mu.V/cm.
[0057] FIG. 8 is a graph of results wherein Induced Field Frequency
801 in Hz is plotted on the x-axis and Power SNR 802 is plotted on
the y-axis. FIG. 8 illustrates that both signals have sufficient
Power spectrum that is Power SNR.apprxeq.1, to be detected within a
frequency range of binding kinetics. However, maximum Power SNR for
the PEMF signal is significantly higher than that for the 60 Hz
signal. This is because a PEMF signal has many frequency components
falling within the bandpass of the binding pathway. The single
frequency component of a 60 Hz signal lies at the mid-point of the
bandpass of the target pathway. The Power SNR calculation that was
used in this example is dependant upon .tau..sub.ion which is
obtained from the rate constant for ion binding. Had this
calculation been performed a priori it would have concluded that
both signals satisfied basic detectability requirements and could
modulate an EMF-sensitive ion binding pathway at the start of a
regulatory cascade for DNA synthesis in these cells. The previous
examples illustrated that utilizing the rate constant for Ca/CaM
binding could lead to successful projections for bioeffective EMF
signals in a variety of systems.
[0058] Having described embodiments for an apparatus and a method
for delivering electromagnetic treatment to human, animal and plant
molecules, cells, tissue and organs, it is noted that modifications
and variations can be made by persons skilled in the art in light
of the above teachings. It is therefore to be understood that
changes may be made in the particular embodiments of the invention
disclosed which are within the scope and spirit of the invention as
defined by the appended claims.
* * * * *