U.S. patent application number 09/827130 was filed with the patent office on 2001-11-01 for diagnostic complex for measurement of the condition of biological tissues and liquids.
Invention is credited to Aruntyunyan, Asmik, Khatchatrian, Ashot P., Khatchatrian, Robert G..
Application Number | 20010037055 09/827130 |
Document ID | / |
Family ID | 25374324 |
Filed Date | 2001-11-01 |
United States Patent
Application |
20010037055 |
Kind Code |
A1 |
Khatchatrian, Robert G. ; et
al. |
November 1, 2001 |
Diagnostic complex for measurement of the condition of biological
tissues and liquids
Abstract
Disclosed is an assembly kit for an apparatus for simultaneously
obtaining a biological sample and measuring the electrical
resistance of said sample at at least two different frequencies for
diagnosis of a condition of said sample. The assembly kit of the
invention includes a main case; an aspirating needle adapted to be
connected to the main case; a liquid collector adapted to be
connected to said aspirating needle; and an electroimpedancemeter.
The aspirating needle is used for obtaining a sample of biological
liquid. The liquid collector receives said sample of said
biological liquid and having a metal conductor in electrical
contact with said needle and a metal piston. The
electroimpedancemeter simultaneously measures electrical resistance
of the sample at at least two different frequencies. Also disclosed
is a method simultaneously obtaining a biological sample and
measuring electrical impedance of the sample for the purpose of
diagnosis of a condition of the sample. The method includes the
steps of: contacting a biological tissue with an electrically
conductive hook having a pointed end as a first electrode and a
second electrode; measuring electrical impedance of the biological
tissue contacted with the first and second electrodes at at least
two different frequencies; and excising a part of the biological
tissue with the pointed end of the hook to obtain a sample of the
biological tissue.
Inventors: |
Khatchatrian, Robert G.;
(Glendale, CA) ; Khatchatrian, Ashot P.;
(Glendale, CA) ; Aruntyunyan, Asmik; (Glendale,
CA) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
620 NEWPORT CENTER DRIVE
SIXTEENTH FLOOR
NEWPORT BEACH
CA
92660
US
|
Family ID: |
25374324 |
Appl. No.: |
09/827130 |
Filed: |
April 5, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09827130 |
Apr 5, 2001 |
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09339439 |
Jun 24, 1999 |
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09339439 |
Jun 24, 1999 |
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08879523 |
Jun 20, 1997 |
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5987353 |
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08879523 |
Jun 20, 1997 |
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08831689 |
Apr 10, 1997 |
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Current U.S.
Class: |
600/215 |
Current CPC
Class: |
A61B 5/0538 20130101;
A61B 5/053 20130101; A61B 10/0051 20130101; A61B 2017/00026
20130101; A61B 10/0045 20130101 |
Class at
Publication: |
600/215 |
International
Class: |
A61B 001/32 |
Claims
What is claimed is:
1. An assembly kit for an apparatus for simultaneously obtaining a
biological sample and measuring the electrical resistance of said
sample at at least two different frequencies for diagnosis of a
condition of said sample, comprising: a main case comprising a tube
and demountable handle; an aspirating needle adapted to be
connected to the main case at least partially inside said tube, for
obtaining a sample of biological liquid and for serving as an
active electrode in contact with said biological sample; a liquid
collector adapted to be connected to said aspirating needle to
receive said sample of said biological liquid, said liquid
collector comprising a metal conductor in electrical contact with
said needle and a metal piston, wherein at the determination of
said condition of said biological liquid said needle executes the
role of active electrode, and said metal piston executes the role
of passive electrode; and an electroimpedancemeter adapted to be
electrically connected to said active and passive electrodes, for
simultaneous measurement of said electrical resistance of the
sample at at least two different frequencies.
2. The assembly kit as defined in claim 1, further comprising a
hook adapted to be attached to said tube, said hook comprising a
pointed end for obtaining a sample of biological tissue, wherein at
the determination of said condition of said biological tissue said
needle executes the role of active electrode, and said hook
executes the role of passive electrode.
3. The assembly kit as defined in claim 1, wherein the main case
has an electrical plug adapted to be electrically connected to each
of said active and passive electrodes when assembled, wherein said
electroimpedancemeter is electrically connected to said active and
passive electrodes through the electrical plug.
4. The assembly kit as defined in claim 1, wherein the
electroimpedancemeter comprises a source of alternating current
voltage consisting of two generators, one for a first frequency
voltage and the other for a second frequency voltage, the second
frequency is higher than the first frequency.
5. The assembly kit as defined in claim 4, wherein the first
frequency is in the range from about 0.5 to about 10 kHz.
6. The assembly kit as defined in claim 5, wherein the first
frequency is in the range from about 1 to about 5 kHz.
7. The assembly kit as defined in claim 6, wherein the first
frequency is in the range from about 1 to about 3 kHz.
8. The assembly kit as defined in claim 4, wherein the second
frequency is in the range from about 10 to about 1000 kHz.
9. The assembly kit as defined in claim 8, wherein the second
frequency is in the range from about 20 to about 500 kHz.
10. The assembly kit as defined in claim 9, wherein the second
frequency is in the range from about 50 to about 300 kHz.
11. A method of simultaneously obtaining a biological sample and
measuring electrical impedance of the sample for the purpose of
diagnosis of a condition of the sample comprising: contacting a
biological tissue with an electrically conductive hook comprising a
pointed end as a first electrode and a second electrode; measuring
electrical impedance of the biological tissue contacted with the
first and second electrodes at at least two different frequencies;
and excising a part of the biological tissue with the pointed end
of the hook to obtain a sample of the biological tissue.
12. The method as defined in claim 11, wherein the second electrode
comprises an aspirating needle connected to a syringe, the method
further comprising: inserting the aspirating needle into the
biological tissue when contacting the biological tissue;
withdrawing a sample of biological liquid retained in the
biological tissue into the syringe through the aspirating needle;
and measuring electrical impedance of the sampled biological liquid
in the syringe at at least two different frequencies.
13. The method as defined in claim 11, wherein the electrical
impedance of the biological tissue or liquid is measured at a first
and a second frequency.
14. The method as defined in claim 13, wherein the first frequency
is in the range from about 0.5 to about 10 kHz.
15. The method as defined in claim 14, wherein the first frequency
is in the range from about 1 to about 5 kHz.
16. The method as defined in claim 15, wherein the first frequency
is in the range from about 1 to about 3 kHz.
17. The method as defined in claim 13, wherein the second frequency
is in the range from about 10 to about 1000 kHz.
18. The method as defined in claim 17, wherein the second frequency
is in the range from about 20 to about 500 kHz.
19. The method as defined in claim 18, wherein the second frequency
is in the range from about 50 to about 300 kHz.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of application Ser. No.
08/879,523, filed Jun. 20, 1997, which is a continuation-in-part of
application Ser. No. 08/831,689, filed Apr. 10, 1997, now
abandoned.
FIELD OF THE INVENTION
[0002] The present invention relates to electroimpedance
measurements of mammalian biological tissues and liquids with the
use of an apparatus and method for simultaneously sampling a
biological tissue or liquid and for measuring the complete
electrical resistance of the biological tissue or liquid for the
purpose of diagnosis of the condition of the tissue or liquid.
BACKGROUND OF THE INVENTION
[0003] Studies of the dielectrical properties of human tissue types
have been made since the late 19th century. All cells and
biological tissues conduct electric charge to some degree. The
conduction of charge within a cell is known to be affected by a
variety of intrinsic and extrinsic factors. The cell has maximal
electric conductivity at resistance measurement frequencies equal
to 10 kHz and above (B. N. Tarusov. Biological Physics. Higher
School Press, 1968). The raising of electric conductivity occurs at
the expense of a reduction in capacitance producing complex
resistance. At low frequencies of resistance measurement the direct
transfer of charge carriers is hindered by the determined
structures of a tissue or sub-cell membranes. These structures play
a key role in cell polarization phenomena. In contrast,
measurements at high frequencies show no influences of polarization
phenomena on conductivity.
[0004] Thus, it is known that an increase of frequency of a
measuring current decreases the complex resistance of a biological
tissue or liquid. This phenomenon, named as the dispersion of
resistance, is a property of a live cell or tissue. The dispersion
of resistance is explained by the presence of polarization
phenomena in the biological object--tissue or liquid. At the
deterioration of a functional condition of a biological object the
ability to achieve polarization decreases. The death of a
biological object excludes the dispersion of its resistance and,
hence, the ability of the cell to achieve polarization.
[0005] Thus, polarization as a phenomenon bears information about
the functional condition of a biological object. Therefore, it is
possible to evaluate a condition of a biological tissue or liquid
with the relation of resistance measured at low frequency to
resistance measured at high frequency, that is, with a factor of
dispersion.
[0006] Devices for definition of a condition of biological tissues
and liquids are known which function by measurement of biological
tissue and liquid electrical resistance. The methods of electrical
impedanceometry, based on measurement of active and reactive
elements of the impedance, are widely applied in medicine for
diagnosis of pathology of the cardiovascular system, diseases of
lungs, etc. However, with the help of present methods of
impedanceometry it is possible to receive only general information
on changes in organs of the body. Such information in the majority
of cases does not reflect the underlying structural changes in
tissues. Separate elements of impedance have only been studied,
which although reveal the dependence of electrical resistance of
tissues on their structure, do not, however, provide sharp
diagnostic information. Additionally, in many technical areas, the
reliability of data received as a result of measurements of the
information is considerably reduced with a reduction in the time of
measurement. A reduction in the reliability of resistance
measurements is also known to occur with a reduction in the time of
measurement.
[0007] The majority of known devices for research of a functional
condition of biological tissues and liquids, enabling the
investigation of electrical parameters of biological tissues and
liquids, do not provide sufficient accuracy of measurement of a
module of the complete electrical resistance. This is because of
errors, caused by drift of the voltage of displacement of zero in
the operating amplifier, the influence of "parasitic capacities" in
the measuring circuit and non-equivalence of a factor of
transformation of signals of detectors under the effect of temporal
and climatic factors.
[0008] In a known device in European Patent Application 0050353 A1,
the condition of tissue is evaluated on a degree of distinction
between the modules of complete electrical resistance of the
tissue, measured serially at low and high frequencies. However,
with serial measurement of modules of complete electrical
resistance at different frequencies, loss or "failure" of
information occurs, leading to a doubtful final result, as the
condition of a biological object at the small site of measurement
does not remain constant in the interval between measurements at
high and low frequencies.
[0009] A device for researching the gastroenteric tract is known,
the purpose of which is increasing the accuracy in diagnosis of
peptic ulcer (Certificate of USSR Nr. 1514347). The device consists
of a flexible probe with movable half-cylindrical tubes inside the
probe case, on the ends of which are fixed metal electrodes, of
which the calomel electrode is attached to a hand of the patient
and joins to a pH-meter via a switch plug. The design of this
device limits the opportunity of the researcher, as it does not
permit one to conduct a sampling of histological and cytological
material with simultaneous measurement of electrical resistance of
the researched object. This device addresses a problem of
measurement of the pH of the gastric juice and cannot be used for
multifunctional research studies.
[0010] Thus, there is a need for an improved multifunctional
apparatus and method for obtaining mammalian biological tissue or
liquid samples and for diagnosis of the condition of a mammalian
biological tissue or liquid employing electrical resistance
measurements.
SUMMARY OF THE INVENTION
[0011] One aspect of the invention is an apparatus for
simultaneously obtaining a sample of mammalian biological tissue or
liquid and measuring the electrical resistance of the tissue or
liquid at at least two different frequencies for the purpose of
diagnosis of the condition of the tissue or liquid, comprising: a
main case, comprising a tube and demountable handle; a hook
attached to the tube, comprising a pointed end, for obtaining a
sample of the biological tissue and for serving as a passive
electrode in contact with the biological tissue; an aspirating
needle at least partially inside the tube, for obtaining a sample
of the biological liquid and for serving as an active electrode in
contact with the biological liquid or tissue; a liquid collector,
connected to the aspirating needle, comprising a metal conductor in
contact with the biological liquid and a piston, which at the
determination of the condition of the biological liquid the needle
executes the role of active electrode, and the metal conductor
executes the role of passive electrode; an electroimpedancemeter
electrically connected to the active and passive electrodes, for
simultaneous measurement of the electrical resistance at at least
two different frequencies; and an electrical plug, located in the
handle and connected by electrical leads with the main case or hook
and with the needle and in one embodiment to the syringe metal
conductor, the electrical plug allowing electrical connection with
an electroimpedancemeter. In one embodiment of the apparatus, the
liquid collector is a syringe. In one embodiment of the apparatus,
the electroimpedancemeter comprises: a source of alternating
current voltage consisting of two generators, one for a first
frequency voltage and the other for a second, higher frequency
voltage. In a preferred embodiment, the first frequency is in the
range from about 0.5 to about 10 kHz. In another preferred
embodiment, the first frequency is in the range from about 1 to
about 5 kHz. In another preferred embodiment, the first frequency
is in the range from about 1 to about 3 kHz. In another preferred
embodiment, the second frequency is in the range from about 10 to
about 1000 kHz. In another preferred embodiment, the second
frequency is in the range from about 20 to about 500 kHz. In
another preferred embodiment, the second frequency is in the range
from about 50 to about 300 kHz. In yet another preferred
embodiment, there is a factor of at least 10.times. in kHz between
the first and second frequencies. In another embodiment of the
electroimpedancemeter of the apparatus, wherein the
electroimpedancemeter comprises a source of alternating current
voltage consisting of two generators, one for a first frequency
voltage and one for a second frequency voltage, the
electroimpedancemeter further comprises a voltage sum-up unit, the
output voltage of which the first frequency voltage and second
frequency voltage are present, serving for elimination of temporal
intervals between moments of measurement of electrical resistance
at first and second frequencies. In another embodiment, the
aforementioned electroimpedancemeter further comprises a negative
feedback circuit, comprising a rectifier and a filter of the first
frequency for elimination of pulsations in the target voltage of
the rectifier. In another embodiment, the aforementioned
electroimpedancemeter further comprises a stabilized source of
current, enabling the standardization of a measuring current
proceeding through the biological tissue or liquid. In another
embodiment, the aforementioned electroimpedancemeter further
comprises an amplifier having an input and an output. In another
embodiment, the aforementioned electroimpedancemeter further
comprises a filter of the first frequency and a filter of the
second frequency. In another embodiment, the aforementioned
electroimpedancemeter further comprises a detector of the first
frequency which produces a first output voltage and a detector of
the second frequency which produces a second output voltage. In
another embodiment, the aforementioned electroimpedancemeter
further comprises a converter to divide the first output voltage by
the second output voltage and a digital display having an input for
displaying the output of the converter. In another embodiment, the
aforementioned electroimpedancemeter further comprises a source of
independent power. In a preferred embodiment, the
electroimpedancemeter wherein: the outputs of the generators of
first and second frequency voltage are connected to inputs of the
sum-up unit. In a preferred embodiment, the electroimpedancemeter
wherein: the output of the sum-up unit is directed through the
rectifier and the filter of first frequency of the negative
feedback circuit and is thereafter connected to the inputs of the
generators of the first and second frequency voltage. In a
preferred embodiment, the electroimpedancemeter wherein: the output
of the sum-up unit is directed through the stabilized source of
current and is connected with the active electrode. In a preferred
embodiment, the electroimpedancemeter wherein: the active electrode
is connected with the input of the amplifier. In a preferred
embodiment, the electroimpedancemeter wherein: the output of the
amplifier is connected with the inputs of the filters of first and
second frequency, the outputs of which are connected accordingly
with the inputs of the detectors of first and second frequency. In
a preferred embodiment, the electroimpedancemeter wherein: the
outputs of said detectors of first and second frequency are
connected to the respective inputs of the converter. In a preferred
embodiment, the electroimpedancemeter wherein: the outputs of the
converter are connected to the inputs of the digital display.
[0012] In another aspect of the invention, a method is provided for
simultaneously obtaining a sample of biological tissue and
measuring the electrical resistance of the tissue at at least two
different frequencies for the purpose of diagnosis of the condition
of the tissue comprising the steps of: moving a tube into a space
containing the biological tissue; contacting the biological tissue
with an active and passive electrode; measuring the electrical
resistance of the biological tissue at at least two different
frequencies with an electroimpedancemeter; obtaining a sample of
the biological tissue with the active and passive electrodes; and
moving the tube containing the sample away from the space. In a
preferred embodiment of the method, the tissue is bronchopulmonary
tissue and the condition is benign or malignant tissue growth.
Preferably, the malignant tissue growth is bronchus cancer. In
another preferred embodiment of the method, the tissue is gastric
mucosa and the condition is benign or malignant tissue growth or
chronic inflammation. Preferably, the malignant tissue growth is
gastroenteric cancer. In another preferred embodiment of the
method, the tissue is thyroid tissue and the condition is benign or
malignant tissue growth. Preferably, the malignant tissue growth is
thyroid cancer. In another preferred embodiment of the method, the
tissue is breast tissue and the condition is benign or malignant
growth. Preferably, the malignant growth is breast cancer. In
another preferred embodiment of the method, the tissue is larynx
tissue and the condition is benign or malignant tissue growth.
Preferably, the malignant tissue growth is larynx cancer. In yet
another preferred embodiment of the method, the tissue is soft
tissue and the condition is healthy or thermally injured. In
another prefered embodiment of the method, the at least two
different frequencies comprise a first frequency in the range from
about 0.5 to about 10 kHz, and a second frequency in the range from
about 10 to about 1000 kHz. Preferably, the first frequency is in
the range from about 1 to about 5 kHz, and the second frequency is
in the range from about 20 to about 500 kHz. More preferably, the
first frequency is in the range from about 1 to about 3 kHz, and
the second frequency is in the range from about 50 to about 300
kHz. In another preferred embodiment of the method, a lower of the
at least two different frequencies is a first frequency and a
higher of the at least two different frequencies is a second
frequency, and there is a factor of at least 10.times. in kHz
between the first and second frequencies.
[0013] In another aspect of the invention, a method is provided for
simultaneously obtaining a sample of biological liquid and
measuring the electrical resistance of the liquid at at least two
different frequencies for the purpose of diagnosis of the condition
of the liquid comprising the steps of: inserting a tube into the
biological liquid; contacting the biological liquid with an active
and passive electrode; withdrawing a sample of the biological
liquid with an aspirating needle into the syringe; moving the tube
out of the biological liquid; and measuring in the syringe the
electrical resistance at at least two different frequencies of the
biological liquid with an electroimpedancemeter. In a preferred
embodiment of the method, the liquid is human blood and the
condition is acute blood loss. In another preferred embodiment of
the method, the liquid is human blood and the condition is selected
from the group consisting of: alkaline reserve of blood, globular
volume of blood, total circulating plasma, total circulating
protein, volume of circulating erythrocytes, hematocrit number,
blood alcohol, drug and anaesthetic content. In another preferred
embodiment of the method, the liquid is human milk and the
condition is lactostasis or mastitis. In another preferred
embodiment of the method, the at least two different frequencies
comprise a first frequency in the range from about 0.5 to about 10
kHz, and a second frequency in the range from about 10 to about
1000 kHz. More preferably, the first frequency is in the range from
about 1 to about 5 kHz, and the second frequency is in the range
from about 20 to about 500 kHz. More preferably, the first
frequency is in the range from about 1 to about 3 kHz, and the
second frequency is in the range from about 50 to about 300 kHz. In
another preferred embodiment of the method, a lower of the at least
two different frequencies is a first frequency and a higher of the
at least two different frequencies is a second frequency, and there
is a factor of at least 10.times. in kHz between the first and
second frequencies.
[0014] In another aspect of the invention, an apparatus is provided
for simultaneously obtaining a sample of mammalian biological
tissue or liquid and measuring the electrical resistance of the
tissue or liquid at at least two different frequencies for the
purpose of diagnosis of the condition of the tissue or liquid,
comprising: a main case, comprising a tube and demountable handle,
the tube being insertable at one end into the demountable handle of
gun or other type, the tube comprising corrosion-proof medical
steel or other conventional material suitable for medical
diagnostic use, the tube having at least one hole at one end; a
protective casing which fits over the tube, is demountable and
comprises a ring and spring-ball for fixing the spring-ball
location of the casing at the hole, the location representing a
maximum forward position or maximum reverse position of the casing;
a hook comprising a pointed end, fixed at one end of the tube away
from the handle and extending from the end for obtaining a sample
of the biological tissue and for serving as a passive electrode in
contact with the biological tissue; an aspirating needle, located
inside the tube, the distal end of said needle extending from the
end of the tube away from the handle, for obtaining a sample of the
biological liquid and for serving as an active electrode in contact
with the biological liquid or tissue, the proximal end of the
needle being finished by a metal flange for jointing with a
metal-glass syringe inside the main case handle; a metal-glass
syringe, consisting of a glass flask, metal conic tip and metal
piston, which at the determination of a condition of the biological
liquid the metal tip executes a role of active electrode, and the
metal piston executes a role of passive electrode; a fixing unit,
located inside the tube and serving simultaneously to fix the hook
at one end of the tube away from the handle and to isolate the area
of the biological tissue or liquid; an electroimpedancemeter
electrically connected to the active and passive electrodes, for
simultaneous measurement of complete electrical resistance at at
least two different frequencies; and an electrical plug, located in
the handle and connected by electrical leads with the main case and
the needle and optionally to said syringe metal piston, the
electrical plug allowing electrical connection with an
electroimpedancemeter. In one embodiment of the apparatus, the
electroimpedancemeter further comprises: a source of alternating
current voltage consisting of two generators, one for a first
frequency voltage and one for a second, preferably higher,
frequency voltage. In another embodiment of the
electroimpedancemeter of the apparatus, wherein the
electroimpedancemeter comprises a source of alternating current
voltage consisting of two generators, one for a first frequency
voltage and the other for a second frequency voltage, the
electroimpedancemeter further comprises a voltage sum-up unit, the
output voltage of which the first frequency voltage and second
frequency voltage are present, serving for elimination of temporal
intervals between moments of measurement of electrical resistance
at first and second frequencies. In another embodiment, the
aforementioned electroimpedancemeter further comprises a negative
feedback circuit, comprising a rectifier and a filter of the first
frequency for elimination of pulsations in the target voltage of
the rectifier. In another embodiment, the aforementioned
electroimpedancemeter further comprises a stabilized source of
current, enabling the standardization of a measuring current
proceeding through the biological tissue or liquid. In another
embodiment, the aforementioned electroimpedancemeter further
comprises an amplifier having an input and an output. In another
embodiment, the aforementioned electroimpedancemeter further
comprises a filter of the first frequency and a filter of the
second frequency. In another embodiment, the aforementioned
electroimpedancemeter further comprises a detector of the first
frequency which produces a first output voltage and a detector of
the second frequency which produces a second output voltage. In
another embodiment, the aforementioned electroimpedancemeter
further comprises a converter to divide the first output voltage by
the second output voltage and a digital display having an input for
displaying the output of the converter. In another embodiment, the
aforementioned electroimpedancemeter further comprises a source of
independent power.
[0015] In another aspect of the invention, an apparatus is provided
for simultaneously obtaining a sample of biological tissue and
measuring the electrical resistance of the tissue at at least two
different frequencies for the purpose of diagnosis of the condition
of the tissue, comprising: a flexible electrode probe comprising a
cable and an electrode tip, wherein the tip comprises an active
electrode and passive electrode for simultaneously obtaining the
sample of biological tissue and measuring the electrical resistance
of the tissue; and an electroimpedancemeter electrically connected
to the active and passive electrodes, for simultaneous measurement
of complete electrical resistance at at least two different
frequencies. In one embodiment, the apparatus further comprises an
endoscope with a channel, wherein the flexible electrode probe fits
inside the channel. In another embodiment, the apparatus further
comprises a holder, used to hold the flexible electrode probe in
direct contact with the skin of a finger.
[0016] In another aspect of the invention, a method is provided for
simultaneously obtaining a sample of biological tissue and
measuring electrical resistance of the tissue at at least two
different frequencies for the purpose of diagnosis of a condition
of the tissue comprising the steps of: placing a flexible electrode
probe into a space containing the biological tissue; contacting the
biological tissue with an active and a passive electrode; measuring
the electrical resistance of the biological tissue at at least two
different frequencies with an electroimpedancemeter; obtaining the
sample of the biological tissue with the active and passive
electrodes; and moving the flexible eletrode probe containing the
sample away from the space. In one embodiment of the method, the
placing is facilitated with an endoscope with a channel, wherein
the flexible electrode probe fits inside the channel. In another
embodiment of the method, the placing is facilitated with a holder,
used to hold the flexible electrode probe in direct contact with
the skin of a finger. In another embodiment of the method, the
condition is selected from the group consisting of blood alcohol,
drug and anaesthetic content.
[0017] In another aspect of the invention, a method is provided for
comparative diagnosis of the condition of two biological liquids,
comprising the steps of: placing a first biological liquid in a
first liquid chamber; placing a second biological liquid in a
second liquid chamber; measuring the electrical impedance at at
least two different frequencies of the first and second liquids
sequentially or simultaneously; and comparing the electrical
resistance measurements of the first and second liquids. In one
embodiment of the method, each of the two biological liquids is
human breast milk, wherein the first biological liquid is from one
breast and the second biological liquid is from the second
breast.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a general view of a preferred embodiment of the
apparatus of the invention without the electroimpedancemeter;
[0019] FIG. 2 is an expanded external and internal view of the
embodiment of the apparatus of the invention illustrated in FIG.
1;
[0020] FIG. 3 is a view of the embodiment of the apparatus of the
invention illustrated in FIG. 1 with pull-out protective casing and
opened instrument with sampling probe for research; and
[0021] FIG. 4 is a block diagram of one embodiment of the
electroimpedancemeter of the invention.
[0022] FIG. 5 is an electrical schematic-block diagram of a
preferred embodiment of the electroimpedancemeter of the
invention.
[0023] FIG. 6 illustrates an embodiment of the flexible electrode
probe of the invention.
[0024] FIG. 7 illustrates an enlarged view of the coaxial cable
electrode tip of the flexible electrode probe of the invention
illustrated in FIG. 6.
[0025] FIG. 8 illustrates an enlarged end-on view of the coaxial
electrode tip of the flexible electrode probe of the invention
illustrated in FIG. 6.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0026] The major objects of the present invention are an apparatus
and method for simultaneously obtaining a sample of mammalian
biological tissue or liquid and for measuring the complete
electrical resistance of said biological tissue or liquid in-vivo
(tissue) or ex-vivo (liquid) for the purpose of diagnosis of the
condition of the tissue or liquid. The apparatus of the present
invention comprises a biological tissue or liquid sampling
apparatus and an electroimpedancemeter, or electrical impedance
measuring device, allowing for the simultaneous measurement of
complete electrical resistance at at least two different
frequencies, or dispersion of resistance. The dispersion of
resistance is a function of the state of the biological tissue or
liquid. Thus, the apparatus and method of the present invention
overcome the inherent precision and accuracy limitations of prior
art devices used for the investigation of electrical parameters of
biological tissues and liquids which at most relied upon serial
measurements of resistance at low and high frequencies. The
apparatus and method of the present invention also overcome the
limitations in device versatility of prior art devices, which
cannot simultaneously obtain a sample of biological tissue or
liquid and measure dispersion of resistance. The apparatus and
method of the present invention uniquely allow for obtaining a
sample of a biological tissue or liquid and measurement of its
electrical resistance at at least two different frequencies at the
same precise location, thus providing the opportunity to gather
more information from a single location and hence provide the
opportunity for a more accurate diagnosis of the condition of the
sample or organ or patient from which the sample derived. The
apparatus and method of the present invention achieve this by the
simultaneous usage of the sampling probes as electrodes for the
simultaneous resistance measurements made at at least two different
frequencies. An additional feature of the apparatus of the present
invention is the minimal effect on the biological tissue or liquid
of the measuring signal from the electroimpedancemeter. The
apparatus of the invention is portable and relatively inexpensive.
It permits the relatively rapid analysis of tissues in typically
1/2-10 minutes. The method of use and the equipment are easy and
reliable in application. The apparatus can be used by average
trained medical staff and additionally does not require special
service.
[0027] The apparatus and method of the present invention applies to
the general domain of clinical medicine and may be used to reveal
the early forms of malignancies, bronchus cancer, gastroenteric
cancer, thyroid cancer, breast cancer, larynx cancer,
comedocarcinoma and soft tissue thermal injury. The present
invention also allows one to determine the degree of acidity of
gastric juice and to diagnose chronic forms of gastritis during
endoscopy, to define the alkaline reserve of blood, blood volume
and it's components and to diagnose and forecast the course of
lactational mastitis.
[0028] The apparatus and method of the present invention may be
utilized for measuring blood components such as alcohol, drugs and
anaesthetics. Thus, the apparatus and method of the invention are
suitable for blood alcohol or drug testing and are also suitable
for determining the proper amount of anaesthetic to use, as well as
to monitor the level of anaesthetic and to keep the level of
anaesthetic constant.
[0029] The apparatus and method of the present invention may be
utilized for man or animals, and is thus suitable for use with all
mammals.
[0030] The apparatus of the present invention for simultaneously
obtaining a sample of biological tissue or liquid and measuring the
electrical resistance of the tissue or liquid at at least two
different frequencies for the purpose of diagnosis of the condition
of the tissue or liquid, comprises:
[0031] a. a main case, the main case comprising a tube and
demountable handle;
[0032] b. a hook attached to the tube, the hook comprising a
pointed end, for obtaining a sample of the biological tissue and
for serving as a passive electrode in contact with the biological
tissue;
[0033] c. an aspirating needle at least partially inside the tube,
for obtaining a sample of the biological liquid and for serving as
an active electrode in contact with the biological liquid or
tissue;
[0034] d. a liquid collector, connected to the aspirating needle,
comprising a metal conductor in contact with the biological liquid
and a piston, which at the determination of the condition of the
biological liquid the needle executes the role of active electrode,
and the metal conductor executes the role of passive electrode;
[0035] e. an electroimpedancemeter electrically connected to the
active and passive electrodes, for simultaneous measurement of the
electrical resistance at at least two different frequencies;
and
[0036] f. an electrical plug, located in the handle and connected
by electrical leads with the main case or hook and with the needle,
and optionally to the syringe metal conductor, the electrical plug
allowing electrical connection with an electroimpedancemeter.
[0037] A preferred embodiment of the apparatus of the present
invention for simultaneously obtaining a sample of biological
tissue or liquid and measuring the electrical resistance of the
tissue or liquid at at least two different frequencies for the
purpose of diagnosis of the condition of the tissue or liquid,
comprises:
[0038] a. A main case, comprising a tube and demountable handle,
the tube being insertable at one end into the demountable handle of
gun or other type, the tube comprising corrosion-proof medical
steel or other conventional material suitable for medical
diagnostic use, the tube having at least one hole at one end;
[0039] b. A protective casing which fits over the tube, is
demountable and comprises a ring and spring-ball for fixing the
spring-ball location of the casing at the hole, the location
representing a maximum forward position or maximum reverse position
of the casing;
[0040] c. A hook comprising a pointed end, fixed at one end of the
tube away from the handle and extending from the end for obtaining
a sample of the biological tissue and for serving as a passive
electrode in contact with the biological tissue;
[0041] d. A aspirating needle, located inside the tube, the distal
end of the needle extending from the end of the tube away from the
handle, for obtaining a sample of the biological liquid and for
serving as an active electrode in contact with the biological
liquid or tissue, the proximal end of the needle being finished by
a metal flange for jointing with a metal-glass syringe inside the
main case handle;
[0042] e. A metal-glass syringe, consisting of a glass flask, metal
conic tip and metal piston, which at the determination of a
condition of the biological liquid the metal tip executes a role of
active electrode, and the metal piston executes a role of passive
electrode;
[0043] f. A fixing unit, located inside the tube and serving
simultaneously to fix the hook at one end of the tube away from the
handle and to isolate the area of the biological tissue or
liquid;
[0044] g. A electroimpedancemeter electrically connected to the
active and passive electrodes, for simultaneous measurement of
complete electrical resistance at at least two different
frequencies; and
[0045] h. A electrical plug, located in the handle and connected by
electrical leads with the main case and the needle and optionally
to the syringe metal piston, the electrical plug allowing
electrical connection with an electroimpedancemeter.
[0046] Another embodiment of the apparatus of the present invention
for simultaneously obtaining a sample of biological tissue and
measuring the electrical resistance of the tissue at at least two
different frequencies for the purpose of diagnosis of the condition
of the tissue, comprises:
[0047] a. a flexible electrode probe comprising a cable and an
electrode tip, wherein the tip comprises an active electrode and
passive electrode for simultaneously obtaining the sample of
biological tissue and measuring the electrical resistance of the
tissue; and
[0048] b. an electroimpedancemeter electrically connected to the
active and passive electrodes, for simultaneous measurement of
complete electrical resistance at at least two different
frequencies.
[0049] The apparatus of the invention comprising a flexible
electrode probe may be utilized in combination with an endoscope
with a channel. The flexible electrode probe is inserted into the
endoscope channel so that simultaneous sampling and impedance
readings of biological tissues such as gastrointestinal tissues may
be taken in locations which are inaccessible to other prior art
devices. Alternatively, the aforementioned apparatus of the
invention with a flexible electrode probe may be combined with a
thimble-like support part at the distal end of the flexible
electrode probe which contains the electrode tip comprising active
and passive electrodes. The thimble-like part can be placed over a
finger to hold the active and passive electrodes in place in direct
contact with the skin of a finger or fingertip. In this way, secure
monitoring of electrical impedance can take place as well as
sampling of the tissue of the finger or fingertip. The
aforementioned apparatus is particularly useful for monitoring of
the electrical impedance of blood for the purpose of determining
blood alcohol content or drug content in the blood. It is also
useful for determining the amount of anaesthetic utilized during an
anaesthesia procedure. It can be utilized to determine the proper
amount of anaesthetic to utilize prior to the anaesthesia procedure
as well as to keep the amount of anaesthetic utilized over a period
of time constant with the additional use of a feedback apparatus
which sends a signal from the electroimpedancemeter to the device
controlling the delivery of the anaesthetic.
[0050] The electroimpedancemeter is used to measure impedance at a
"low" frequency which is preferably in the range from about 0.5 to
about 10 kHz, more preferably in the range from about 1 to about 5
kHz, and still more preferably in the range from about 1 to about 3
kHz. The electroimpedancemeter also is used to measure impedance at
a "high" frequency which is preferably in the range from about 10
to about 1000 kHz, more preferably in the range from about 20 to
about 500 kHz, and still more preferably in the range from about 50
to about 300 kHz. It is preferred that there be a factor of at
least 10.times. between the low and high frequencies, although this
is not a requirement for all measurements. In the preferred
embodiment presented in the present detailed description of the
invention, the ratio between the two frequencies is 100.times.. In
other embodiments of the present invention, more than two
frequencies can be measured simultaneously. In such embodiments,
the selection of the first two frequencies should be as described
above and additional frequencies preferably spaced at logarithmic
(or 10.times. in kHz) intervals.
[0051] The electroimpedancemeter of the apparatus of the present
invention comprises:
[0052] a. A source of alternating current voltage consisting of two
generators, one for a first frequency voltage and the other for a
second frequency voltage;
[0053] b. A voltage sum-up unit, the output voltage of which the
components of said low frequency voltage and high frequency voltage
are present, serving for elimination of temporal intervals between
moments of resistance measurements at low and high frequency;
[0054] c. A negative feedback circuit, comprising a rectifier and a
filter of low frequency for elimination of pulsations in the target
voltage of the rectifier;
[0055] d. A stabilized source of current, enabling the
standardization of a measuring current proceeding through said
biological tissue or liquid;
[0056] e. An amplifier;
[0057] f. A filter of low frequency and a filter of high
frequency;
[0058] g. A low frequency detector and a high frequency
detector;
[0059] h. A converter to divide said low frequency detector voltage
output by said high frequency detector voltage output, such as an
analog-digital converter;
[0060] i. A digital display for displaying the output of said
converter;
[0061] j. A source of independent power.
[0062] A preferred embodiment of part of the apparatus of the
present invention for simultaneously obtaining a sample of
biological tissue or liquid and measuring the electrical resistance
of the tissue or liquid at at least two different frequencies for
the purpose of diagnosis of the condition of the tissue or liquid,
without the electroimpedancemeter, is illustrated in FIGS. 1-3.
FIG. 1 is a general view of a preferred embodiment of the apparatus
of the present invention without the electroimpedancemeter. FIG. 1
illustrates a multifunctional tool, comprising: a main case tube 1,
executed from corrosion-proof medical steel and a main case
demountable handle 3 of gun-type, consisting of two halves, tube 1
being insertable at one end into demountable handle 3. Tube 1 has a
hole in the form of slot 2 at the end which is insertable into
handle 3. There is an enlarged hole at each end of slot 2. A
protective casing 4 fits over tube 1. Casing 4 is demountable and
supplied with a ring 5 and spring-ball 6 for fixing the spring-ball
location of casing 4 at the hole at either end of slot 2 in tube 1,
this location representing a maximum forward position A or maximum
reverse position B of the casing 4. Hook 7 has a pointed end, is
electrically conductive and is utilized for sampling biological
tissue and also as the passive electrode in contact with the
biological tissue for the resistance measurements. Hook 7 is fixed
at one end of tube 1 away from handle 3 and extends from the end of
tube 1. Aspirating needle 8 is located inside tube 1. The distal
end of needle 8 extends from the end of tube 1 away from handle 3
and is utilized for sampling biological liquid and serves
additionally as an active electrode in contact with the biological
tissue or liquid. Needle 8 is electrically isolated by isolating
tubing 9, illustrated in FIG. 3. The proximal end of needle 8 is
rigidly fixed in handle 3 and finished with a metal flange 10
(FIGS. 1 and 2) for jointing with a metal-glass syringe 11 (FIG.
2), consisting of a glass flask 12a, metal conic tip 12b and metal
piston 13 (FIG. 2). Fixing unit 14 (FIG. 3), located in case 1,
fixes the position of needle 8 and performs simultaneously the role
of isolator. Electrical plug 15 (FIG. 2) is located in the bottom
part of handle 3. Lead 16 is soldered to needle 8 and connected to
plug 15. Lead 17 is soldered to case 1 and connected to the high
frequency leg of plug 15. The additional contact-jack 18 is
connected to the mass of plug 15.
[0063] Resistance measurements of sampled biological liquids are
made with lead 19 with clamp 20 connected to metal piston 13 and
probe 21 (FIG. 2) inserted into contact-jack 18. Here the metal
conic tip 12b serves as active electrode, and metal piston 13--as
passive electrode. Flange 10 is closed with a special cap when
syringe 11 is not attached to the flange (not shown).
[0064] Note that in other embodiments of the part of the apparatus
of the present invention without the electroimpedancemeter,
conventional flexible materials suitable for medical diagnostic use
can be employed for any or all parts of the aforementioned
apparatus so that the apparatus itself may be flexible and thus may
be used under medical diagnostic situations requiring a flexible
apparatus. It is to be understood that all electrical connections
will be maintained with the aforementioned flexible apparatus. For
example, a metal needle connected with flexible tubing to the
syringe can be electrically connected with the syringe and the
apparatus with electrical wire. Similarly, electrical connections
with the hook can be made with electrical wire.
[0065] It is not necessary to use a protective casing or fixing
unit as described above. Other conventional means can also be
employed to allow the apparatus of the present invention without
the electroimpedancemeter to perform its functions properly. For
example, other means of operating the hook for obtaining a sample
of biological tissue may be employed with the present invention. As
an example, the hook may be operated with an electromechanical
device such as a solenoid suitably connected to a piston, or
piston, pivot and lever. The electrical connection between the hook
itself, which serves as the passive electrode, and the remainder of
the apparatus can be made with electrical wire. In this instance,
the tube of the apparatus may serve as the protective casing and
the protective casing with the ring and spring ball is not
necessary.
[0066] Additionally, it is not necessary to use a glass syringe
with a metal tip and metal piston. A plastic syringe can also be
employed with conventional tip and piston. In this latter case, a
metal conductor in contact with the biological liquid inside the
syringe can be employed. In this case, the metal needle serves as
the active electrode and metal conductor as passive electrode.
Resistance measurements of sampled biological liquids are then made
with lead 19 with clamp 20 connected to the metal conductor and
probe 21 (FIG. 2) inserted into contact-jack 18. Any other suitable
liquid collector can also be employed, as long as all functional
and electrical requirements are met.
[0067] On FIG. 4 is shown one embodiment of the
electroimpedancemeter of the invention, including the source of low
and high frequency alternating current voltage consisting of two
generators 22 and 23, a voltage sum-up unit 24, a rectifier of the
negative feedback 25, a filter of low frequency of negative
feedback 26, a stabilizer of measuring current 27 enabling the
standardization of a measuring current proceeding through a
biological tissue or liquid, amplifier 28, a filter of high
frequency 29a, a filter of low frequency 29b, a detector of high
frequency 30, a detector of low frequency 31, converter of the
voltages' relation 32, a digital display device 33 and source of
independent power (not shown). The outputs of generators of low and
high frequency, 22 and 23 respectively, are connected to inputs of
the sum-up unit 24. The output of the sum-up unit 24 is directed
through rectifier 25 and the filter of low frequency of negative
feedback 26 and is thereafter connected to the inputs of the
generators of high and low frequency, 22 and 23 respectively. The
output of the sum-up unit 24 is directed through a stabilized
source of current 27 and is connected with the active electrode 8.
The active electrode 8 is connected with the input of the amplifier
28. A passive electrode 7 is connected to ground as well as the
biological object being measured. The output of the amplifier 28 is
connected with the inputs of the filters of low and high frequency,
29a and 29b respectively, the outputs of which are connected
accordingly with the inputs of the detectors of low and high
frequency, 30 and 31 respectively. The outputs of the detectors of
low and high frequency 30 and 31 are connected to the respective
inputs of the converter of the relation of voltage 32. This
converter is a division unit whose output indicates the ratio of
the low frequency detector output divided by the high frequency
detector output. The converter is typically a conventional
analog-to-digital converter. The outputs of the converter of the
relation of voltage 32 are connected to the inputs of the digital
display 33.
[0068] The two generators of low and high frequency 22 and 23 are
provided for the elimination of a temporal interval between moments
of measurements at low and high frequency. This is additionally
achieved with the sum-up unit 24 which produces a target voltage
which contains the components of low-frequency and high-frequency
voltage of alternating current. The two generators of low and high
frequency can produce various combinations of two frequencies, one
of which is preferably a low frequency such as 2 kHz and the other
of which is preferably a high frequency such as 200 kHz. The
selection of the appropriate frequencies is as previously described
and is known in the art. Preferably, there is at least a factor of
10.times. between the two frequencies, although this is not a
requirement for all measurements. Other ratios between the two
frequencies are also effective, as in the above, wherein a factor
of 100.times. exists between 2 kHz and 200 kHz. The negative
feedback circuit consisting of rectifier 25 and filter of low
frequency 26 between the output of unit 24 and the inputs of
generators 22 and 23 is included for stabilization of the amplitude
of the target voltage of the sum-up unit 24. The filter of low
frequency 26 is included for elimination of pulsations, present in
the target voltage of rectifier 25. The stabilizer of the measuring
current 27 insures that the measuring current proceeding through
the biological tissue does not exceed the requirements of
international standards. The amplification factor for amplifier 28
is generally about 5, but can be more or less depending upon the
specific need.
[0069] FIG. 5 is an electrical schematic-block diagram of a
preferred embodiment of the electroimpedancemeter of the invention.
Note that on this figure, the conventional electrical circuit
symbol for an electrical resistor component is not employed. An
electrical resistor component is represented by a small rectangular
box with an electrical lead at either end. A variable resistor
component is represented with the same symbol with the exception
that a third electrical lead is connected to the center of the
rectangular box. Components 7, 8 and 22-33 are as described in FIG.
4, with 28a representing an ejector source follower part of the
amplifier 28, the output of which is connected to the input of the
scale amplifier 28b. Component 32a represents a commutator part of
an analog-to-digital converter 32b. Additional components are as
follows: component 34 is an independent power source, representing
a 12 V battery, which is connected through a main power switch 35
to stabilizer circuitry 36 and thereafter to the commutator 32a.
Components 37, 38 and 39 are switches which are part of the control
circuitry of the analog-to-digital converter 32b, and are connected
to converter 32b via commutator 32a. Component 37 is a switch for
obtaining a readout on the digital display 33 of the high frequency
resistance of the biological sample and component 38 is a switch
for obtaining a readout on the digital display 33 of the low
frequency resistance of the biological sample. Component 39 is a
switch for obtaining a readout on the digital display of the
polarizability, PC, or dispersion of resistance, of the biological
sample.
[0070] Components of the above electroimpedancemeter can be
conventional commercially available components and are known to
those of ordinary skill in the construction of electrical devices.
For example, digital display 33 is a conventional 4-digit
liquid-crystal type digital indicator.
[0071] Typical technical parameters of the electroimpedancemeter
are as follows: peak current consumed by the display panel: 8 mA;
maximum power: 10 mW; source of independent power: one storage
battery, 12 V; measuring current value: max. 10 mKA; and constant
operating time: 4 hours.
[0072] An electroimpedancemeter according to the present invention
can be constructed which can simultaneously measure more than two
frequencies simultaneously. This can be accomplished with
conventional parallel circuit design and construction methods,
i.e., 3 frequency generators, 3 filters, 3 detectors, etc. would be
employed for an electroimpedancemeter which measures 3 frequencies
simultaneously. The method employing the apparatus of the present
invention for simultaneously obtaining a sample of biological
tissue and measuring the electrical resistance of the tissue at at
least two different frequencies for the purpose of diagnosis of the
condition of the tissue generally comprises the steps of:
[0073] a. Moving the tube into a space containing the biological
tissue;
[0074] b. Contacting the biological tissue with the active and
passive electrodes;
[0075] c. Measuring the electrical resistance of the biological
tissue at at least two different frequencies with the
electroimpedancemeter;
[0076] d. Obtaining a sample of biological tissue with the active
and passive electrodes; and
[0077] e. Moving the tube containing the sample away from the
space.
[0078] The method employing the apparatus of the present invention
for simultaneously obtaining a sample of biological liquid and
measuring the electrical resistance of the liquid at at least two
different frequencies for the purpose of diagnosis of the condition
of the liquid generally comprises the steps of:
[0079] a. Inserting the tube into the biological liquid;
[0080] b. Contacting the biological liquid with the active and
passive electrode;
[0081] c. Withdrawing a sample of the biological liquid with the
aspirating needle into the syringe;
[0082] d. Moving the tube out of the biological liquid; and
[0083] e. Measuring in the syringe cell the electrical resistance
at at least two different frequencies of the biological liquid with
the electroimpedancemeter.
[0084] The preferred apparatus of the invention illustrated in
FIGS. 1-4 is utilized according to the method of the invention in
the following manner: holding handle 3, the researcher with
forefinger inside ring 5 moves casing 4 along the line of arrow A-B
(FIG. 1). The moving of casing 4 is limited by the length of slot 2
in main case tube 1, so as the distal part of casing 4 is moved
forward to position A, it completely overlaps elements 7 and 8.
Thus casing 4 takes a position at which the tool for sampling the
material (tissue, liquid) is completely closed--with the purpose of
minimal traumatizing of internal tissues (the distal edge of casing
are smoothed). The researcher then introduces the distal end of the
apparatus into the body at the location to be studied. Hook 7
serves for optionally clasping one piece of biological tissue, and
the needle 8, to be inserted inside the tissue fixes the location
of the apparatus for sampling and is also utilized for the optional
sampling of biological liquids.
[0085] At the moment of sampling, initiated by a gentle forward
push on handle 3, casing 4 comes back to the position "B," and
after this manipulation again approaches elements 7 and 8 in
position "A", promoting thus the tear-off of a piece of biological
tissue by hook 7.
[0086] In the moment of touching of the biological tissue or liquid
by needle 8 and hook 7 the electrimpedancemeter transfers a
measuring signal from the output of a stabilizer 27 through the
passive and active electrodes--hook 7 and needle 8 respectively.
Simultaneously, a measuring signal or current of high and low
frequency penetrates into the cell structures of the biological
tissue. As the variable measuring current flows through the tissue
a power failure between electrodes 7 and 8 occurs, proportional to
a module of complete electrical resistance of the tissue. The power
loss arrives simultaneously at the amplifier 28 and thereafter at
the inputs of filters of low and high frequency 29a and 29b, the
outputs of which constitute a variable voltage which arrives at the
inputs of detectors 30 and 31. A constant voltage, proportional to
resistance ZHf, is formed at the output of the detector of high
frequency 30. Similarly, a constant voltage, proportional to
resistance ZLf, is formed at the output of the detector of low
frequency 31. The outputs of detectors 30 and 31 are input into the
analog-digital converter 32, the output of which is a ratio of the
low frequency detector output voltage divided by the high frequency
detector output voltage and which constitutes the digital
information about the factor of tissue polarization.
[0087] After the completion of sampling the apparatus together with
protective casing 4 is removed from the body, following which
casing 4 is removed from main case tube 1. The selected piece of
tissue will then be passed for histological research.
[0088] The aspirating needle 8 for sampling a biological liquid is
used in the following manner: the protecting cap is removed from
flange 10, and the syringe 11 by tip 12b is tightly inserted into
flange 10. Piston 13 is initially in the input position (is
maximally proximate to tip 12b). The liquid from a body is then
aspirated in the syringe in a volume of about 0.5 to about 2
milliliters in the conventional manner by withdrawing piston
13.
[0089] Resistance measurements on the aforementioned biological
liquids are made as previously described in the following manner:
clamp 20 is connected to the acting end of metal piston 13 and
probe 21 is inserted into jack 18. In the "closed" electrical
circuit the syringe 11 with metal piston 13 and tip 12b serves as a
cell, in which the metal tip 12b serves as active electrode and
piston 13--as passive electrode. In other words--syringe 11 with
tip 12b provides reliable electrical contact with the flange 10,
and lead 19, connected by clamp 20 with piston 13 and inserted in
jack 18 by leg 21 allows the measurement of specific resistance in
the volume of the syringe cell 11 (in the volume of 2 milliliters).
All of the measurements of specific resistance of a biological
liquid in the syringe cell 11 are carried out similarly to
measurements of specific resistance on biological tissue.
[0090] The embodiment of the apparatus of the invention shown in
FIGS. 1-3 cannot be used to diagnose particular locations of
gastrointestinal tissue which are a substantial distance inside the
body. In consideration of this unmet need, it has been discovered
that a flexible electrode probe can be utilized in combination with
an endoscope with a channel and an electroimpedancemeter of the
invention to simultaneously obtain a tissue sample and take
impedance readings of the tissue sample in locations deep inside
the body. This apparatus is particularly well suited to sample and
measure gastrointestinal tissue deep inside the body. FIGS. 6, 7,
and 8 illustrate an embodiment of a flexible electrode probe which
has been developed for this purpose. The flexible electrode probe
illustrated in FIGS. 6-8 can be used in combination with the
apparatus of the invention illustrated in FIG. 5 to carry out the
method of the invention for simultaneously obtaining a sample of
biological tissue and measuring the electrical resistance of the
tissue at at least two different frequencies for the purpose of
diagnosis of the condition of the tissue. In this case, a sample of
tissue approximately corresponding to a needle biopsy is taken by
the flexible electrode probe illustrated in FIGS. 6-8.
[0091] FIG. 6 illustrates the flexible electrode probe 10. The
flexible electrode probe 10 comprises a flexible coaxial electrical
cable consisting of two separate electrical wires or cables. A
coaxial cable connector 30 is used to connect the coaxial electrode
cable comprising an external coaxial cable 40 and an internal
coaxial cable 45 to the input of the electrical apparatus of the
invention illustrated in FIG. 5. External coaxial cable 40 is
connected to the coaxial cable connector 30 and is in continuous
electrical connection with the internal coaxial cable 45 as well as
the coaxial connector 30. The coaxial cable connector 30 is
adjacent to rubber protectors 41 and 42, which are placed over
external coaxial cable 40 and are utilized to protect the external
coaxial cable 40 from damage due to bending, twisting and flexing
motions during normal usage. The external coaxial cable 40 is
continuously outside the body and is not inserted inside a channel
of an endoscope. The external coaxial cable 40 is generally from
10-150 cm in length. Preferably, it is between about 25 and 100 cm
in length. Most preferably, the external coaxial cable 40 is about
50 cm in length. An endoscope channel stop 50 is placed on the
outside of the distal end of the external coaxial cable 40. The
purpose of the endoscope channel stop 50 is to prevent the external
coaxial cable 40 from entering the endoscope channel (not shown).
The endoscope channel stop 50 controls the amount of the internal
coaxial cable 45 that is placed inside the endoscope channel. The
endoscope channel stop 50 may be moveable in alternative
embodiments of the flexible electrode probe 10. A rubber cable
protector 43 is placed on the outside of the external coaxial cable
40 adjacent to the endoscope channel stop 50 and is utilized to
protect the external coaxial cable 40 from damage due to bending,
twisting and flexing motions at this location during normal usage.
Adjacent to the endoscope channel stop 50 is a spring protector 60,
which is utilized to protect the internal coaxial cable 45 from
bending, twisting and flexing motions which may damage the cable.
The internal coaxial cable 45 is generally between about 50 and 250
cm in length. Preferably, it is between about 100-200 cm in length.
Most preferably, the internal coaxial cable 45 is about 150 cm in
length. The internal coaxial cable 45 is connected at its distal
end to a coaxial cable electrode tip 20.
[0092] The coaxial cable electrode tip 20 is shown in greater
detail in a side view in FIG. 7. The coaxial cable electrode tip 20
consists of a first impedance electrode 21 and a second impedance
electrode 25. Either of these impedance electrodes can represent
either the passive electrode 7 or the active electrode 8 in the
impedance circuitry illustrated in FIG. 5. Both impedance
electrodes 21 and 25 are constructed generally of solid metal. The
first impedance electrode 21 is in continuous electrical connection
with a flexible coaxial electrode cable 22 which in turn is
protected by a plastic insulation sheath 23. The approximate
external diameter of the plastic sheath 23 is about 1.2 mm. The
approximate external diameter of the first impedance electrode 21
is about 1 mm. Impedance electrode 21 is generally about 4 mm in
total length from the distal end of the plastic insulation sheath
23 to the distal sharp tip of the impedance electrode 21. The
second impedance electrode 25 is generally about 2 mm in length.
The second impedance electrode 25 is placed inside a circular duct
or channel (not shown) which is surrounded by the flexible coaxial
electrode cable 22. There is no electrical contact between the
first impedance electrode 21 and second impedance electrode 25
except through the biological sample between electrodes 21 and 25.
This lack of electrical contact between electrodes 21 and 25 is
maintained by an appropriate insulator placed between the two
electrodes (not shown).
[0093] FIG. 8 illustrates an end-on view of the coaxial cable
electrode tip 20. Shown in FIG. 8 are the first and second
impedance electrodes 21 and 25 respectively. Also shown is plastic
sheath 23 which surrounds both impedance electrodes 21 and 25. Not
shown in this Figure is the electrode insulation maintained between
electrodes 21 and 25 to prevent electrical connection between the
two electrodes.
[0094] The first and second impedance electrodes 21 and 25
respectively, can also be utilized to take a biopsy of the tissue
such as gastrointestinal tissue. Electrodes 21 and 25 are shaped
for this purpose as well as to make the proper electrical contact
with tissues so that a simultaneous impedance measurement can be
taken.
[0095] The preferred method of the invention employing the flexible
electrode probe 10 for obtaining a sample of gastrointestinal
tissue and measuring the electrical resistance or impedance of the
tissue comprises the steps of:
[0096] a. inserting the flexible electrode probe internal coaxial
cable 45 inside an appropriate channel of an endoscope;
[0097] b. simultaneously contacting the tissue with the first and
second impedance electrodes 21 and 25 respectively;
[0098] c. simultaneously measuring the electrical resistance of the
tissue at at least two different frequencies with the
electroimpedance meter of the invention illustrated in FIG. 5 and
sampling the tissue with the sharp ends of the impedance electrodes
21 and 25; and
[0099] d. moving the internal coaxial cable 45 containing the
sample of tissue out of the channel of the endoscope.
[0100] In an alternative embodiment of the apparatus and method of
the invention employing the flexible electrode probe 10 with
coaxial cable electrode tip 20 and associated parts, the first and
second impedance electrodes 21 and 25 may be retracted inside
plastic sheath 23 following the sampling of biological tissue and
completion of the impedance readings. This embodiment of the
apparatus and method of the invention employing the flexible
electrode probe 10 is made possible by insuring that the external
diameter of the first impedance electrode 21 is smaller than the
internal diameter of the plastic sheath 23, so that movement of the
flexible coaxial electrode cable 22 is allowed inside of plastic
sheath 23. In this way, a sample of biological tissue taken by the
first and second impedance electrodes 21 and 25 respectively can be
protected inside plastic sheath 23 following sampling. The sample
therefore would not be lost following sampling and could be safely
recovered for further histological analysis.
[0101] The entire construction of the flexible electrode probe 10
can be made with conventional plastic and metal materials which are
known in the art. Also, the geometries of the various parts of
flexible electrode probe 10 can be made appropriate to the
particular endoscope and endoscope channel employed along with the
flexible electrode probe 10, if an endoscope is used.
[0102] A general method of the invention employing a flexible
electrode probe for simultaneously obtaining a sample of biological
tissue and measuring electrical resistance of the tissue at at
least two different frequencies for the purpose of diagnosis of a
condition of the tissue comprises the steps of:
[0103] a. placing a flexible electrode probe into a space
containing the biological tissue;
[0104] b. contacting the biological tissue with an active and a
passive electrode;
[0105] c. measuring the electrical resistance of the biological
tissue at at least two different frequencies with an
electroimpedancemeter;
[0106] d. obtaining the sample of the biological tissue with the
active and passive electrodes; and
[0107] e. moving the flexible eletrode probe containing the sample
away from the space.
[0108] Yet another method of the invention employs an impedance
measuring cell with two separate chambers for holding biological
liquids, wherein one chamber is filled with a control sample of
biological liquid and the other chamber is filled with a test
sample of biological liquid. Impedance measurements are taken
sequentially or simultaneously of the liquids in the two chambers
and compared. It has been discovered that in this way, smaller,
more accurate and precise impedance difference measurements can be
obtained. For example, a sample of breast milk from the left breast
suspected to have a medical problem may be directly compared to a
sample of breast milk from the right breast known to be healthy.
This method of comparative diagnosis of biological liquids may also
be performed with two or more separate cells, each with one liquid
chamber, the number of cells corresponding to the number of
biological liquids to be compared.
[0109] The following examples are provided by way of illustration
only and are not intended as a limitation of the present invention,
many variations of which are possible without departing from the
spirit and scope thereof.
EXAMPLE 1
[0110] Diagnosis of bronchopulmonary tissue.
[0111] The embodiment of the apparatus of the invention shown in
FIGS. 1-4 is used with the method of the invention to diagnose
bronchopulmonary tissue. The casing 4, as shown in FIG. 3, is
mounted on main case tube 1. While holding the handle 3, the
researcher moves ring 5 and puts the casing 4 on the distal end of
tube 1, thus blocking the sampling and electrode elements 7 and 8,
and fixing the casing 4 in the slot 2 of tube 1 in the position
"A." The apparatus consisting of the main case tube, casing and
sampling and electrode elements is entered through a special tube
of a bronchoscope under the control of sight. The apparatus is then
included in the electrical circuit of the electroimpedancemeter
shown in FIG. 4 through the switch plug 15.
[0112] After the tool has reached a necessary depth and the
required location within the bronchial tract, the researcher puts
off the casing 4 by ring 5 to position "B". By the hook 7, he tears
off the piece of tissue, then again puts the protective casing 4 on
the tool in position "A". At the moment of reliable contact of hook
7 and needle 8 with the bronchopulmonary tissue the electrical
circuit of the electroimpedancemeter is completed, and through the
electrodes 7 and 8 the measuring signal in a sum of voltage of
alternating current of high and low frequency contacts the issue.
Power decreasing between the electrodes 7 and 8 is proportional to
the module of complete electrical resistance. The functional
condition of the bronchopulmonary tissue is evaluated according to
the relation of resistance measured at low frequency to resistance
measured at high frequency, that is to a factor of polarization. A
range of measurements from 20 up to 2000 Ohm includes main relative
error 1 + / - [ 2 , 5 + 0 , 25 ( Nlimiting Nmeasured - 1 ) ] .
[0113] Where Nlimiting--top border of measurements range
[0114] Nmeasured--measured significance of resistance.
[0115] The summarized voltage of the alternating current,
consisting of voltage of high frequency and voltage of low
frequency, permits to avoid the loss of information in the interval
between the measurements and is expressed by the formula:
Us=[UHf+ULf].times.Ks.,
[0116] where Us is the target total voltage of the sum-up unit and
Ks is the factor of amplification of the sum-up unit.
[0117] A direct voltage, proportional to the ZHf (f=200 kHz)
resistivity, is formed on the outlet of the detector of high
frequency 30, and the same process of formation of a direct
voltage, proportional to the ZLf (f=2 kHz) resistivity, occurs at
the outlet of the detector of low frequency 31. These voltages are
input to the respective high and low frequency input channels of
the converter 32. Digital information is formed in the output of
the converter of the relation of voltage 32. The digital
information is proportional to the relation of modules of complete
resistance at low and high frequencies, that is, the digital
information is proportional to the factor of polarization (FP) of
bronchopulmonary tissue under the known formula: 2 FPtissue = ZLf
ZHf
[0118] Once the resistance measurements have been taken, the
researcher under the control of eye removes the apparatus from the
researched area, the protective casing is accurately removed, and
the piece of bronchopulmonary tissue is transferred for
histological research. The combined set of data from resistance
measurements and histology test results can be compared with
published data relating bronchopulmonary tissue status with serial
resistance measurements and histology data. Alternatively, a new
set of information can be generated which correlates simultaneous
resistance measurements and histology test data with tissue status.
The results of the above diagnostic procedure employing the
apparatus and method of the present invention demonstrate that
precise, accurate and simple diagnosis of bronchopulmonary tissue
or other biological tissues and liquids can be achieved.
EXAMPLE 2
[0119] Diagnosis of gastric mucosal tissue.
[0120] The embodiment of the apparatus of the invention shown in
FIGS. 1-4 is used with the method of the invention according to
Example 1 to diagnose a particular location on the gastric mucosa.
Patient S., a 48 year old, is inspected outpatiently. Conventional
gastroscopy is carried out. Flat ulcerous damage is visually
detected in the antral portion of the stomach on the small curve
side. Borders of the ulcer are indistinct, the ulcer base is
fibrinous and infiltration of the gastric wall during instrumental
palpation is not detected. The pylorus is clipped, has some
deformation and it's mucous is hyperemic. The endoscopic diagnosis
is an ulcer of the antral portion of the stomach. The apparatus of
the invention as in Example 1 is entered through a separate tube of
the endoscope and contacted with the tissue. Resistance
measurements are taken in two opposite borders of the ulcer and
expressed in terms of the polarizability, PC, of the tissue. The
results follow:
[0121] Location 1: Hf=245 cm, Lf=440 cm
[0122] PC=440/245=1.8
[0123] Location 2: Hf=210 cm, Lf=390 cm
[0124] PC=390/210=1.86
[0125] PC values of 1.8 or less have previously been correlated to
malignant degeneration of a tissue. PC values of 1.81 and higher
have previously been correlated to chronic inflammation. Thus, in
location 1, a diagnosis of malignant degeneration of the mucous
(granulating gastric cancer) is made. In location 2, a diagnosis of
chronic inflammation is made. Tissue biopsies taken from the same
locations and analysed according to standard histopathological
techniques confirm the diagnoses.
[0126] The apparatus and method of the invention allow one to
objectively characterize the condition of the abdominal mucosa. The
invention elevates the precision of morphologic diagnostics and
alleviates the need to take 3-4 tissue biopses. A single tissue
biopsy is sufficient for an accurate diagnosis, thus reducing the
cost of the procedure and trauma for the patient. In the case of a
tumor, the invention allows the determination of the borders of the
malignant growth, which is needed to properly select the operative
intervention. The method of the invention is simple and does not
require additional resources and services. Testing time is only 2-3
minutes. Studies carried out with the apparatus and method of the
invention have shown a coincidence with the results of histology
tests in 95.6% of 450 subjects.
EXAMPLE 3
[0127] Intraoperative diagnosis of thyroid cancer.
[0128] Preoperational clinical and special radioisotope methods of
diagnosis do not provide an analysis of morphostructural
characteristics of formed thyroid tissue nodes. At the moment the
determination of the pathology of the thyroid is derived during an
operation. In addition, surgery produces an analysis of pathology
visually and by palpation, both of which are deprived of objective
measurement. Also, the instant morphological diagnosis produced
during surgery is expensive and long term as to the time (30-40
minutes). Moreover, biopsies selected during surgery by visual
observation do not reduce the errors in the results. Lastly, the
process is complicated and it's implementation demands professional
skills.
[0129] The essence of the new method of the invention for
intraoperative diagnosis of thyroid cancer is in the impedance
measurement of thyroid tissues and measurement of all nodes during
the operation. It enables the following analysis: (1) A
determination of the benign or malignant nature of the tissue
growth process; (2) An identification of the biopsy location for
histologic examination, which raises the efficiency of the early
diagnosis of thyroid cancer from 80% to 93.3%; and (3) In the case
of the determination of the presence of a tumour, the present
invention allows one to determine the borders of the tumour and to
choose the tactics of the operative cure.
[0130] The apparatus and method of the invention utilised in
Example 1 was employed, without the bronchoscope. The apparatus of
the invention was brought into contact with the thyroid during
thyroid surgery. The time of testing is about 15 to about 30
seconds. The method is simple and does not require laboratory
services. Tests were conducted in Russia with 190 patients with
benign and malignant tumours of the thyroid. Test results are
compared to a set of data correlating electrical resistanc e
measurements with thyroid tissue status. Diagnosis with the
apparatus and method of the present invention was coincident with
diagnosis from histopathology studies in 93.3% of cases.
EXAMPLE 4
[0131] Detection of acute blood loss.
[0132] One of the most popular methods for detecting acute blood
loss in clinical practice is the radioisotope method. This method
has several disadvantages, however. The method requires 1-1.5 hours
and thus has limited application to emergency situations. The
method requires special laboratory services and equipment. Lastly,
the method exposes personnel and patients to some degree of danger
due to the utilisation of a radioisotope. The method of the
invention employing the apparatus of the invention, on the other
hand, is very simple, fast, inexpensive, and can be carried out in
any condition (e.g., in the clinic, on the highway, in remote
locations and in military conditions) by one person. The apparatus
and method of the invention allow one to determine not only the
rate of blood loss, but also the alkaline reserve of blood,
globular volume of blood, the scope of circulating plasma, total
circulating protein, the volume of circulating erythrocytes and
hematocrit number.
[0133] The apparatus and method of the invention for measuring
acute blood loss is illustrated in the present example as follows:
The apparatus and method of the invention utilised in Example 1 was
employed, without the bronchoscope and without tissue sampling. The
essence of the method is in the measurement of the electrical
resistance of 1.0 ml of a patient's blood. The time required for
testing is about 1-2 minutes. The aspirating needle 8 for sampling
blood is used in the following manner: the protecting cap is
removed from flange 10, and the syringe 11 by tip 12b is tightly
inserted into flange 10. Piston 13 is initially in the input
position (is maximally proximate to tip 12b). Blood is then
aspirated in the syringe in a volume of about 1.0 milliliters in
the conventional manner by withdrawing piston 13.
[0134] Resistance measurements on the blood sample are made in the
following manner: clamp 20 is connected to the acting end of metal
piston 13 and probe 21 is inserted into jack 18. In the "closed"
electrical circuit the syringe 11 with metal piston 13 and tip 12b
serves as a cell, in which the metal tip 12b serves as active
electrode and piston 13--as passive electrode. In other
words--syringe 11 with tip 12b provides reliable electrical contact
with the flange 10, and lead 19, connected by clamp 20 with piston
13 and inserted in jack 18 by leg 21 allows the measurement of
specific resistance in the volume of the syringe cell 11 (in the
volume of 1.0 milliliters). All of the measurements of specific
resistance of a blood sample in the syringe cell 11 are carried out
similarly to measurements of specific resistance on biological
tissue. Test results are compared to a set of data correlating
electrical resistance measurements to acute blood loss and specific
parameters such as globular volume of blood, scope of circulating
plasma, total circulating protein, volume of circulating
erythrocytes and hematocrit number.
EXAMPLE 5
[0135] Diagnosis and forecasting of lactation mastitis.
[0136] The apparatus and method of the invention utilised in
Example 4 was employed for the early instant diagnosis of
lactational mastitis. The essence of the method is in the
measurement of the electrical resistance of 0.5 ml of a female's
milk. The time required for testing is about 15-30 seconds. Test
results are compared to a set of data correlating electrical
resistance measurements of milk to mastitis disease state. The
results of the testing enable one to make the following
observations and conclusions:
[0137] (1) The initial degree of development of the inflammatory
process in the mammary gland can be monitored. The illness is
detected in the very early stages of development--14 days before
clinical signs of illness;
[0138] (2) One can differentiate lactostasis and mastitis;
[0139] (3) One can differentiate different forms of mastitis
(seasonal, infiltrative, maternal), which simplifies the choice of
tactics for cure;
[0140] (4) The course of the post-operative term during maternal
mastitis can be forecasted; and
[0141] (5) One can detect the degree of infectivity of the
milk.
EXAMPLE 6
[0142] Differential diagnosis of fibroadenoma and breast
cancer.
[0143] The apparatus and method of the invention enable the
differential diagnosis of fibroadenoma and breast cancer. The
apparatus and method of the invention utilised in Example 1 was
employed, without the bronchoscope. A diagnosis is produced via the
insertion of aciform electrodes in the mammary gland and
measurements of its impedance at different frequencies. Test data
are once again compared to a data set correlating electrical
resistance measurements to tissue status. The method allows one to
conduct a differential diagnosis between benign and malignant
mastoncus with a reliability of 90% and to differentiate different
morphologic forms of malign new growths (adenocarcinal carcinoma).
The time required for a diagnosis is 1-2 minutes. Again, no
additional laboratory equipment or specially trained personnel are
required. Diagnosis with the apparatus and method of the present
invention was coincident with diagnosis from histopathology studies
in 89.7% of cases.
EXAMPLE 7
[0144] Diagnosis of larynx cancer.
[0145] The apparatus and method enable the diagnosis of larynx
cancer. The apparatus and method of the invention utilized in
Example 1 is employed, without the bronchoscope. The diagnosis is
produced via the insertion of electrodes into the tissue of the
larynx and measuring the electrical resistance at two different
frequencies. Test data are compared with data on healthy larynx
tissue. The method enables the differentiation of the various
desease forms of the tissue in border states. The time required for
diagnosis is 2-4 minutes.
EXAMPLE 8
[0146] Diagnosis of thermal injury of soft tissues.
[0147] The apparatus and method of the invention utilized in
Example 1 was employed, without the bronchoscope. The diagnosis is
produced via the insertion of the electrodes into the soft tissue
to the depth depending on the amount of thermal injury and
measuring of the electrical resistance of the tissue at two
different frequencies. Test data are compared with data correlating
electrical resistance measurements of soft tissue with soft tissue
status, healthy or otherwise. The diagnosis with said apparatus and
method of the present invention was coincident with histology
diagnosis in 79.8% of cases.
* * * * *