Method for correlating electrical properties of a tissue portion with one or more metabolic condition and / or physiological properties prior application information

Abstract

Described herein is a device that can detect the metabolic, catabolic and anabolic condition and changes that change the electrical permeability of biological tissues. The device measures electrical activity in the skin immediately under the device to a desired depth with a coplanar arrangement of at least three interdigitated portions or sensors.

Description

[0001] METHOD FOR CORRELATING ELECTRICAL PROPERTIES OF A TISSUE PORTION WITH ONE OR MORE METABOLIC CONDITION AND / OR PHYSIOLOGICAL PROPERTIES PRIOR APPLICATION INFORMATION

[0002] The instant application claims the benefit of US Provisional Patent Application Serial Number 63 / 633,394, filed April 12, 2024 and entitled “METHOD FOR CORRELATING ELECTRICAL PROPERTIES OF A TISSUE PORTION WITH ONE OR MORE METABOLIC CONDITION AND / OR PHYSIOLOGICAL PROPERTIES”, which is incorporated herein by reference for all purposes.

[0003] BACKGROUND OF THE INVENTION

[0004] Body tissues function like a combined resistor and capacitor, and their values constantly change over short durations (milliseconds) and longer durations (seconds, minutes, hours, days ...).

[0005] For example, metabolic functions involve the exchange of ions (negative electrons or positively charged hydrogen protons).

[0006] Free ions come from concentrations of electrolytes (potassium, sodium, calcium, and magnesium etc.). The concentration of free ions is inversely proportional to resistance.

[0007] Ion concentrations change the tissue’s resistance.

[0008] Interstitial fluid contains both electrolytes and fuels (glucose or ketones). Fuels are less conductive (more resistive) and electrolytes are more conductive (less resistive).

[0009] Muscle contractions involve the consumption of ATP from one or more of four sources: free ATP (for immediate use), phosphocreatine, glycolysis, and cellular respiration for progressively longer duration uses. Fueling muscle contractions falls into two basic types: aerobic and anaerobic. Both processes involve the consumption of electrolytes, calcium, and magnesium. Muscle contraction results in an immediate change in electrical properties as the electrolytes are temporarily depleted. Resistance changes quickly due to the use of calcium and magnesium being consumed during muscle contractions and concentrations return to normal levels over the next few minutes as they are replenished. Depletion is followed by a slow rise in resistance, as the electrolyte imbalance is restored.

[0010] Nerve impulses from the neurons of a neuromuscular junction also electrically stimulate a muscle to contract. This triggers the reduction of electrolytes to support the contraction, and this shows up as a precursory change in resistance.

[0011] Capacitance changes are a function of intercellular communication. For example, gap junctions, ephaptic coupling and intercellular bridges form intercellular links. In the case of gap junctions, they are called a connexon pair and connect between the cytoplasms of adjacent cells. The connexon pairs can transport water and can very rapidly turn on and off as required. These are also facilitating electrical conductance that can be rapidly turned on and off, resulting in a variety of potential signaling combinations. Gap junctions can also function to form a direct connection to the exterior of a cell, paralleling the functioning of the protein cousin, the pannexins.

[0012] Dipoles are a function of inter-cellular electrical isolation or communication. Dipoles change capacitance.

[0013] Specifically, capacitance drops as cells communicate their need for oxygen or fuel. In the presence of insulin, cell walls open conduit ports to allow the flow of fuel into the cell. Similarly, when the cells do not need fuel, the ports are closed, cells are more isolated, and capacitance rises.

[0014] Capacitance changes due to the opening of channels in the cell walls to allow for the inflow of fuel (glucose, as triggered by insulin or alternately the availability of p- hydroxybutyrate) which is in turn a function of ionic activity related to the hydrogen ion protons produced in the conversion of ATP from mono- and di-adenosine triphosphate. Some research indicates as much as 500 mv are involved in these reactions.

[0015] US 20200205701 A1 teaches measuring change in electric resistance and capacitance, using a two-electrode probe as a sensing membrane between the two electrodes degrades in the presence of hydrogen peroxide.

[0016] US 2021 / 0137431 teaches a similar process except that they wick the interstitial fluid that contains the hydrogen peroxide out of the body, expose it to their degradable sensing membrane and measure the resistance and capacitance changes.

[0017] US 9,247,905 teaches a method and a device for determining glucose level in tissue using measurements between 1 -200 kHz, 0.2 MHz-100MHz and above 1 GHz.

[0018] SUMMARY OF THE INVENTION

[0019] According to an aspect of the invention, there is provided a device comprising (i) an interdigitated portion having two opposing ends and configured for contacting skin or being proximal to skin of a subject and measuring skin capacitance, skin resistance and phase; (ii) a capacitance meter; (iii) a resistance meter; and (iv) a phase meter responsive to the relationship between resistance and capacitance (also referred to as the relativity); and (v) an indication system that provides a signal or signal value representative of a difference of the current skin capacitance, skin resistance and phase measurements from a comparative skin capacitance, skin resistance, and phase value determined at a known blood glucose value at a different time. Phase is a function of the distance travelled through the tissue and the electrical properties of the tissues. The measurements can be continuous, can be at fixed periods, can be at the initiation of a user, or can be triggered by an activity or condition. The capacitance meter and resistance meter can be provided as separate meters, or can be provided in a single sensor system. The signal or signal value can indicate a change in blood glucose from detection of a change in capacitance, resistance, and / or phase. The signal or signal value can also indicate a trend or direction of change (e.g., increasing or decreasing, or rate of increase or decrease), or a value of blood glucose when the device is calibrated to provide a value of blood glucose based on measurements of the capacitance, resistance and phase - e.g., by corelating measurements with known blood glucose levels in this user or in a representative population.

[0020] Some embodiments of the present invention provide a method for non-invasively detecting a subject's blood glucose, comprising providing a device comprising a number of interdigitated portions for measuring capacitance, resistance and phase of surface and the various layers of tissue below the surface of the skin of the subject, said interdigitated portion having at least two separate electrical contacts and at least two different spacings; a power source; and a signal or indicator or display responsive to one end of the interdigitated portion, said signal or indicator or display being activated when a skin capacitance, skin resistance and / or phase measurement of the subject changes compared to skin capacitance, skin resistance and / or phase values of the subject when a blood glucose value reading was previously taken; placing the device on a body of the subject such that two electrical contacts of the interdigitated portions are contacting or adjacent to the skin of the subject; said device measuring the capacitance, resistance and / or phase of the skin of the subject; and said device activating the signal or indicator or display when the skin capacitance, resistance and / or phase measurement is different from the reference capacitance, resistance and / or phase measurement of the subject taken previously, as discussed herein. Alternatively, as discussed herein, the device and the method of using the device may be continuously monitoring glucose or ketone uptake, thereby following trends, rather than necessarily focusing on specific blood glucose numbers.

[0021] As will be appreciated by those of skill in the art, from an electrical perspective, ketosis looks very similar to glucose uptake in that both electrical mechanisms are encouraging the uptake of fuel to the cell but because of the different chemical make-up involve different electrical properties at different times in their processes. For example, when going into ketosis, glucose measurements fall to a plateau then the liver makes glucose reserves available. Since we can continuously measure the electrical properties and know the precursor electrical conditions, we can interpret the current situation as we continue to measure electrical property changes even though the metabolism has switched over to using ketones.

[0022] According to another aspect of the invention, there is provided a method for training or enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0023] (i) a power source;

[0024] (ii) a coplanar arrangement of at least three interdigitated portions or sensors arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion;

[0025] (iii) a display system for data entry;

[0026] (iv) an analysis system; and

[0027] (v) a memory module; activating the device such that at least one current at at least one frequency passes from at least a respective one interdigitated portion to at least one respective other interdigitated portion; the analysis system analyzing the received current at the at least one respective other interdigitated portion and determining capacitance, resistance and phase at a frequency skin depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the frequency skin depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

[0028] For example, by having several interdigitated electrical portions on an unchanging coplanar surface (that is, in the same unchanging plane) their location, relative to all other electrical sensors, is always known for overall system modelling.

[0029] According to another aspect of the invention, there is provided a method for training or enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0030] (i) a power source;

[0031] (ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion;

[0032] (iii) a display system for data entry;

[0033] (iv) an analysis system; and

[0034] (v) a memory module; activating the device such that on an ongoing basis: a current at at least one frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least one frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the third interdigitated portion; the analysis system analyzing the received current at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a second frequency depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first frequency depth and at the second frequency depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic and / or physiological event.

[0035] According to another aspect of the invention, there is provided a method for training or enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0036] (i) a power source;

[0037] (ii) at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;

[0038] (iii) a display system for data entry;

[0039] (iv) an analysis system; and

[0040] (v) a memory module; activating the device such that on an ongoing basis: a current at at least a first frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least a second frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; a current at at least a third frequency is transmitted from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; the analysis system analyzing the received currents at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first frequency depth, at the second frequency depth, at the third frequency depth and at the fourth frequency depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

[0041] Each frequency may be between 0-100 kHz or between 5-95 kHz. Specifically, once the broad range for the best depth has been determined by space size, differentiation by frequency yields a more specific signal detail and can refine the depth measurements within the depth range established by the space.

[0042] As will be appreciated by those of skill in the art, the frequency difference is a function of the size and location of the thing that is being interrogated. For example, increments of 10 KHz yields a nice pattern of the changes going from deep fat tissue to surface evaporation. Alternatively, with a frequency difference of 0.001 KHz, the signal becomes indicative of the influence of very small particles. For example, the particle size interrogated by the difference between 5000 kHz and 5000.001 kHz is approximately 0.3 nanometers, reflecting how sensitive changes in wavelength are to small frequency shifts.

[0043] Each pair of interdigitated portions is synchronized according to frequency. This can be best understood as “the output is looking for signals that have an identical frequency to the input signal”. In this manner, the interdigitated portions can function in pairs.

[0044] The metabolic condition and / or physiological event may be blood glucose level and the metabolic condition and / or physiological event may be marked by the individual taking a blood glucose level reading. That is, in this manner, a specific blood glucose level reading for the individual is correlated with specific electrical tissue properties, as discussed herein.

[0045] The device may be configured such that amplitude of the current or voltage can be changed, for example, increased by up to 50%.

[0046] According to another aspect of the invention, there is provided a method for determining blood glucose level of an individual, said method comprising: placing a device onto a tissue portion of the individual, said device comprising:

[0047] (i) a power source;

[0048] (ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;

[0049] (iii) a display system for data entry;

[0050] (iv) an analysis system; and

[0051] (v) a memory module; activating the device such that on an ongoing basis: a current at at least a first frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least a second frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; a current at at least a third frequency is transmitted from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; the analysis system analyzing the received currents at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom; and said analysis system determining blood glucose level status from said analysis.

[0052] The blood glucose level status may be that blood glucose is increasing or decreasing over time, that is, over the current time period that measurements are being taken or over a user-defined time period.

[0053] Alternatively, the blood glucose level status may be a blood glucose level for the individual determined from a plurality of corroborative blood glucose levels of the individual or determined from a plurality of corroborative blood glucose levels of a plurality of subjects.

[0054] The device may have at least four or four interdigitated portions.

[0055] Each transmission between a first interdigitated portion and a second interdigitated portion may be done at at least three frequencies, for example, at three, four, five, six, seven, eight, nine or ten frequencies or at at least four, at least five, at least six, at least seven, at least eight, at least nine or at least ten frequencies.

[0056] According to another aspect of the invention, there is provided a device configured to be placed onto a tissue portion of an individual, for detecting metabolic, catabolic and anabolic changes in the tissue portion over time, said device comprising:

[0057] (i) a power source;

[0058] (ii) at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;

[0059] (iii) a display system for data entry;

[0060] (iv) an analysis system; and

[0061] (v) a memory module; said device configured to transmit a current at at least a first frequency from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; transmit a current at at least a second frequency from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; transmit a current at at least a third frequency from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; transmit a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; analyze the received currents at the second interdigitated portion and determine capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and analyze the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom.

[0062] Each frequency may be between 0-100 kHz or between 5-95 kHz.

[0063] Each pair of interdigitated portions may be synchronized according to frequency, as discussed herein.

[0064] The device may be configured such that amplitude of the current or voltage can be changed, as discussed herein.

[0065] For example, with two contacts we measure activity at one depth (AB). With three (ABC) we measure 3 depths (AB, BC, AC), with 4 (A, B, C, D) we measure 6 depths (AB, AC, AD, BC, BD, CD), with 5 (A, B, C, D, E), we measure 10 depths (AB, AC, AD, AE, BC, BD, BE, CD, CE, DE) and so on with the unique combinations of contacts.

[0066] According to another aspect of the invention, there is provided a device comprising (i) an interdigitated portion having two opposing ends and configured for contacting skin or being proximal to skin of a subject and measuring skin capacitance, resistance and / or phase; (ii) a capacitance meter; (iii) a resistance meter; and (iv) a phase meter responsive to the relationship between resistance and capacitance (also referred to as the relativity); and (v) an indication system that provides a signal representative of the difference of the current skin capacitance, resistance and / or phase measurements from a comparative capacitance, resistance, and / or phase value determined during known, localized muscle contraction at a different time. The measurements can be continuous, can be at fixed periods, can be at the initiation of user, or can be triggered by an activity or condition (e.g., electrolyte concentration changes. The capacitance meter and resistance meter can be provided as separate meters, each with a sensor, or can be provided in a single sensor system. The signal can indicate a change in localized muscle contraction from detection of a change in capacitance, resistance, or phase. The signal can also indicate a trend or direction of change (e.g., increasing or decreasing, or rate of increase or decrease), or a value related to degree or intensity of muscle contraction when the device is calibrated to provide a value related to muscle contraction based on measurements of the capacitance, resistance and phase - e.g., by corelating measurements with known values related to degree or intensity of muscle contraction in this user or in a representative population.

[0067] Some embodiments of the present invention provide a method for non-invasively detecting a subject's muscle contraction, comprising providing a device comprising a number of interdigitated portions for measuring capacitance, resistance and / or phase of surface and the various layers below the surface of the skin of the subject, said interdigitated portion having at least two separate electrical contacts and at least two different spacings; a power source; and a signal responsive to one end of the interdigitated portion, said signal changes when a skin capacitance, resistance and / or phase measurement of the subject changes compared to values of the subject when a muscle contraction reading was previously taken; placing the device on a body of the subject such that two electrical contacts of the interdigitated portions are contacting the skin or are proximal to the skin of the subject; said device measuring the capacitance, resistance and / or phase of the skin of the subject; and said device activating the signal when the skin capacitance resistance and phase measurement is different from the reference capacitance, resistance and phase measurement of the subject.

[0068] BRIEF DESCRIPTION OF THE DRAWINGS

[0069] Figure 1 is a schematic diagram of a circuit diagram of a capacitance meter of the present invention.

[0070] Figure 2 is a schematic diagram showing four differently spaced interdigitated contact sensors, showing penetration depths associated with each respective pair based on the differential spacing.

[0071] DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0072] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned hereunder are incorporated herein by reference.

[0073] Described herein is a device that can detect the metabolic, catabolic and anabolic changes that change the electrical permeability of biological tissues.

[0074] As discussed herein, the device measures electrical activity in the skin immediately under the device to a desired depth, for example, in some embodiments, a depth of about 0.060 inches. Electrical activity is measured as resistance, capacitance, and phase. These all change with different metabolic conditions, as discussed below.

[0075] As discussed herein, the device measures electrical activity in the skin immediately under the device to various desired depths, for example, in some embodiments, at various desired depths up to a depth of about 0.060 inches, which then includes the lower fat layer, the blood vessels and capillaries, the lymph system and the interstitial fluids layers. Electrical activity is measured as resistance, capacitance, and phase. These all change with different metabolic conditions, for example, different blood glucose levels, as discussed below. The spacing, the width and the frequency can all be adjusted to interrogate a desired depth or depth range.

[0076] According to another aspect of the invention, there is provided a method for training or enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0077] (i) a power source;

[0078] (ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion;

[0079] (iii) a display system for data entry;

[0080] (iv) an analysis system; and

[0081] (v) a memory module; activating the device such that at least one current at at least one frequency passes from at least a respective one interdigitated portion to at least one respective other interdigitated portion; the analysis system analyzing the received current at the at least one respective other interdigitated portion and determining capacitance, resistance and phase at a frequency skin depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the frequency skin depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

[0082] According to another aspect of the invention, there is provided a method for training a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0083] (i) a power source;

[0084] (ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion;

[0085] (iii) a display system for data entry;

[0086] (iv) an analysis system; and

[0087] (v) a memory module; activating the device such that on an ongoing basis: a current at at least one frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least one frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the third interdigitated portion; the analysis system analyzing the received current at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a second frequency depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first frequency depth and at the second frequency depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

[0088] According to another aspect of the invention, there is provided a method for training or enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0089] (i) a power source;

[0090] (ii) at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;

[0091] (iii) a display system for data entry;

[0092] (iv) an analysis system; and

[0093] (v) a memory module; activating the device such that on an ongoing basis: a current at at least a first frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least a second frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; a current at at least a third frequency is transmitted from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; the analysis system analyzing the received currents at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first frequency depth, at the second frequency depth, at the third frequency depth and at the fourth frequency depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

[0094] Each frequency may be between 0-100 kHz or between 5-95 kHz.

[0095] Each pair of interdigitated portions is synchronized according to frequency. This can be best understood as “the output is looking for signals that have an identical frequency to the input signal”. In this manner, the interdigitated portions can function in pairs.

[0096] In all embodiments discussed herein, the metabolic condition and / or physiological event may be blood glucose level and the metabolic condition and / or physiological event may be marked by the individual taking a blood glucose level reading. That is, in this manner, a specific blood glucose level reading for the individual is correlated with specific electrical tissue properties, as discussed herein. The metabolic condition may be a blood glucose level taken by the user so that a specific blood glucose level is correlated with specific capacitance, resistance and / or phase measurements at the respective frequencies. Furthermore, once the user knows their blood glucose level, they can take appropriate steps depending on the specific blood glucose level. For example, at a blood glucose level or blood sugar level above 200 mg per dL, the user might add 2 units of insulin. For a blood sugar level of 150 to 200 mg per dL, the user might add 1 unit of insulin. For a blood sugar level or blood glucose level of 100 to 149 mg per dL, the user may take no action. For a blood sugar or blood glucose level of 70 to 100 mg per dL, the user might subtract 1 unit of insulin.

[0097] The device may be configured such that amplitude of the current or voltage can be changed, for example, increased by up to 50%.

[0098] According to another aspect of the invention, there is provided a method for determining blood glucose level of an individual, said method comprising: placing a device onto a tissue portion of the individual, said device comprising:

[0099] (i) a power source;

[0100] (ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;

[0101] (iii) a display system for data entry; (iv) an analysis system; and

[0102] (v) a memory module; activating the device such that on an ongoing basis: a current at at least a first frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least a second frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; a current at at least a third frequency is transmitted from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; the analysis system analyzing the received currents at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom; and said analysis system determining blood glucose level status from said analysis.

[0103] The blood glucose level status may be that blood glucose is increasing or decreasing over time, that is, over the current time period that measurements are being taken or over a user-defined time period.

[0104] Alternatively, the blood glucose level status may be a blood glucose level for the individual determined from a plurality of corroborative blood glucose levels of the individual or determined from a plurality of corroborative blood glucose levels of a plurality of subjects.

[0105] The device may have at least 2, at least 3, at least 4 or exactly 3 or exactly 4 interdigitated portions.

[0106] Each transmission between a first interdigitated portion and a second interdigitated portion may be done at at least three frequencies, for example, at three, four, five, six, seven, eight, nine or ten frequencies or at at least four, at least five, at least six, at least seven, at least eight, at least nine or at least ten frequencies, wherein each frequency is different by at least 0.001 kHz, as discussed herein.

[0107] According to another aspect of the invention, there is provided a device configured to be placed onto a tissue portion of an individual, for detecting metabolic, catabolic and anabolic changes in the tissue portion over time, said device comprising:

[0108] (i) a power source;

[0109] (ii) at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;

[0110] (iii) a display system for data entry;

[0111] (iv) an analysis system; and

[0112] (v) a memory module; said device configured to transmit a current at at least a first frequency from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; transmit a current at at least a second frequency from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; transmit a current at at least a third frequency from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; transmit a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; analyze the received currents at the second interdigitated portion and determine capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and analyze the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom.

[0113] Each frequency may be between 0-100 kHz or between 5-95 kHz.

[0114] Each pair of interdigitated portions may be synchronized according to frequency, as discussed herein.

[0115] The device may be configured such that amplitude of the current or voltage can be changed, as discussed herein.

[0116] For example, with two contacts we measure activity at one depth (AB). With three (ABC) we measure 3 depths (AB, BC, AC), with 4 (A, B, C, D) we measure 6 depths (AB, AC, AD, BC, BD, CD), with 5 (A, B, C, D, E), we measure 10 depths (AB, AC, AD, AE, BC, BD, BE, CD, CE, DE) and so on with the unique combinations of contacts, as shown schematically in Figure 2. As will be appreciated by those of skill in the art, a coplanar arrangement means that spacing between A and B is different from spacing between A and C.

[0117] However, in some embodiments, wherein there are three interdigitated contacts, AB spacing may be different from BC spacing.

[0118] Furthermore, in some embodiments, wherein there are four interdigitated contacts, spacing between AB, BC and CD may all be different and spacing between AC and BD may be different as well.

[0119] Yet further, in some embodiments, wherein there are five interdigitated contacts, spacing between AB, BC, CD and CE may all be different, while spacing between AC, BD and CE may be all different and spacing between AD and BE may be different.

[0120] According to another aspect of the invention, there is provided a method for training or enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:

[0121] (i) a power source;

[0122] (ii) four interdigitated portions arranged such that at least a distance between interdigitated portion A and interdigitated portion B is different from a distance between the interdigitated portion A and interdigitated portion C, said four interdigitated portions configured for pairwise transmission and receipt of current at different frequencies, said pairs comprising AB, AC, AD, BC, BD and CD;

[0123] (iii) a display system for data entry;

[0124] (iv) an analysis system; and

[0125] (v) a memory module; activating the device such that on an ongoing basis: a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion B at a first AB frequency between 5 kHz to 95 kHz at a first AB depth, at a second AB frequency between 5 kHz to 95 kHz at a second AB depth and at at least a third AB frequency between 5 kHz to 95 kHz at a third AB depth; a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion C at a first AC frequency between 5 kHz to 95 kHz at a first AC depth, at a second AC frequency between 5 kHz to 95 kHz at a second AC depth and at at least a third AC frequency between 5 kHz to 95 kHz at a third AC depth; a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion D at a first AD frequency between 5 kHz to 95 kHz at a first AD depth, at a second AD frequency between 5 kHz to 95 kHz at a second AD depth and at at least a third AD frequency between 5 kHz to 95 kHz at a third AD depth; a current is transmitted from the interdigitated portion B through the tissue portion to the interdigitated portion C at a first BC frequency between 5 kHz to 95 kHz at a first BC depth, at a second BC frequency between 5 kHz to 95 kHz at a second BC depth and at at least a third BC frequency between 5 kHz to 95 kHz at a third BC depth; a current is transmitted from the interdigitated portion B through the tissue portion to the interdigitated portion D at a first BD frequency between 5 kHz to 95 kHz at a first BD depth, at a second BD frequency between 5 kHz to 95 kHz at a second BD depth and at at least a third BD frequency between 5 kHz to 95 kHz at a third BD depth; a current is transmitted from the interdigitated portion C through the tissue portion to the interdigitated portion D at a first CD frequency between 5 kHz to 95 kHz at a first CD depth, at a second CD frequency between 5 kHz to 95 kHz at a second CD depth and at at least a third CD frequency between 5 kHz to 95 kHz at a third CD depth; the analysis system analyzing the received currents at the interdigitated portion B, the interdigitated portion C and the interdigitated portion D and determining capacitance, resistance and phase at the first AB depth, the second AB depth, the third AB depth, the first AC depth, the second AC depth, the third AC depth, the first AD depth, the second AD depth, the third AD depth, the first BC depth, the second BC depth, the third BC depth, the first BD depth, the second BD depth, the third BD depth, the first CD depth, the second CD depth and the third CD depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first AB depth, the second AB depth, the third AB depth, the first AC depth, the second AC depth, the third AC depth, the first AD depth, the second AD depth, the third AD depth, the first BC depth, the second BC depth, the third BC depth, the first BD depth, the second BD depth, the third BD depth, the first CD depth, the second CD depth and the third CD depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

[0126] Each pair of interdigitated portions is synchronized according to frequency. This can be best understood as “the output is looking for signals that have an identical frequency to the input signal”. In this manner, the interdigitated portions can function in pairs.

[0127] The metabolic condition and / or physiological event may be blood glucose level and the metabolic condition and / or physiological event may be marked by the individual taking a blood glucose level reading. That is, in this manner, a specific blood glucose level reading for the individual is correlated with specific electrical tissue properties, as discussed herein. ucose level reading for the individual is correlated with specific electrical tissue properties, as discussed herein.

[0128] The device may be configured such that amplitude of the current or voltage can be changed, for example, increased by up to 50%.

[0129] According to another aspect of the invention, there is provided a method for determining blood glucose level of an individual, said method comprising: placing a device onto a tissue portion of the individual, said device comprising:

[0130] (i) a power source;

[0131] (ii) four interdigitated portions arranged such that at least a distance between interdigitated portion A and interdigitated portion B is different from a distance between the interdigitated portion A and interdigitated portion C, said four interdigitated portions configured for pairwise transmission and receipt of current at different frequencies, said pairs comprising AB, AC, AD, BC, BD and CD;

[0132] (iii) a display system for data entry;

[0133] (iv) an analysis system; and

[0134] (v) a memory module; activating the device such that on an ongoing basis: a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion B at a first AB frequency between 5 kHz to 95 kHz at a first AB depth, at a second AB frequency between 5 kHz to 95 kHz at a second AB depth and at at least a third AB frequency between 5 kHz to 95 kHz at a third AB depth; a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion C at a first AC frequency between 5 kHz to 95 kHz at a first AC depth, at a second AC frequency between 5 kHz to 95 kHz at a second AC depth and at at least a third AC frequency between 5 kHz to 95 kHz at a third AC depth; a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion D at a first AD frequency between 5 kHz to 95 kHz at a first AD depth, at a second AD frequency between 5 kHz to 95 kHz at a second AD depth and at at least a third AD frequency between 5 kHz to 95 kHz at a third AD depth; a current is transmitted from the interdigitated portion B through the tissue portion to the interdigitated portion C at a first BC frequency between 5 kHz to 95 kHz at a first BC depth, at a second BC frequency between 5 kHz to 95 kHz at a second BC depth and at at least a third BC frequency between 5 kHz to 95 kHz at a third BC depth; a current is transmitted from the interdigitated portion B through the tissue portion to the interdigitated portion D at a first BD frequency between 5 kHz to 95 kHz at a first BD depth, at a second BD frequency between 5 kHz to 95 kHz at a second BD depth and at at least a third BD frequency between 5 kHz to 95 kHz at a third BD depth; a current is transmitted from the interdigitated portion C through the tissue portion to the interdigitated portion D at a first CD frequency between 5 kHz to 95 kHz at a first CD depth, at a second CD frequency between 5 kHz to 95 kHz at a second CD depth and at at least a third CD frequency between 5 kHz to 95 kHz at a third CD depth; the analysis system analyzing the received currents at the interdigitated portion B, the interdigitated portion C and the interdigitated portion D and determining capacitance, resistance and phase at the first AB depth, the second AB depth, the third AB depth, the first AC depth, the second AC depth, the third AC depth, the first AD depth, the second AD depth, the third AD depth, the first BC depth, the second BC depth, the third BC depth, the first BD depth, the second BD depth, the third BD depth, the first CD depth, the second CD depth and the third CD depth therefrom; and said analysis system determining blood glucose level status from said analysis.

[0135] The blood glucose level status may be that blood glucose is increasing or decreasing over time, that is, over the current time period that measurements are being taken or over a user-defined time period.

[0136] Alternatively, the blood glucose level status may be a blood glucose level for the individual determined from a plurality of corroborative blood glucose levels of the individual or determined from a plurality of corroborative blood glucose levels of a plurality of subjects.

[0137] According to another aspect of the invention, there is provided a device configured to be placed onto a tissue portion of an individual, for detecting metabolic, catabolic and anabolic changes in the tissue portion over time, said device comprising:

[0138] (i) a power source;

[0139] (ii) four interdigitated portions arranged such that at least a distance between interdigitated portion A and interdigitated portion B is different from a distance between the interdigitated portion A and interdigitated portion C, said four interdigitated portions configured for pairwise transmission and receipt of current at different frequencies, said pairs comprising AB, AC, AD, BC, BD and CD;

[0140] (iii) a display system for data entry;

[0141] (iv) an analysis system; and

[0142] (v) a memory module; activating the device such that on an ongoing basis: a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion B at a first AB frequency between 5 kHz to 95 kHz at a first AB depth, at a second AB frequency between 5 kHz to 95 kHz at a second AB depth and at at least a third AB frequency between 5 kHz to 95 kHz at a third AB depth; a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion C at a first AC frequency between 5 kHz to 95 kHz at a first AC depth, at a second AC frequency between 5 kHz to 95 kHz at a second AC depth and at at least a third AC frequency between 5 kHz to 95 kHz at a third AC depth; a current is transmitted from the interdigitated portion A through the tissue portion to the interdigitated portion D at a first AD frequency between 5 kHz to 95 kHz at a first AD depth, at a second AD frequency between 5 kHz to 95 kHz at a second AD depth and at at least a third AD frequency between 5 kHz to 95 kHz at a third AD depth; a current is transmitted from the interdigitated portion B through the tissue portion to the interdigitated portion C at a first BC frequency between 5 kHz to 95 kHz at a first BC depth, at a second BC frequency between 5 kHz to 95 kHz at a second BC depth and at at least a third BC frequency between 5 kHz to 95 kHz at a third BC depth; a current is transmitted from the interdigitated portion B through the tissue portion to the interdigitated portion D at a first BD frequency between 5 kHz to 95 kHz at a first BD depth, at a second BD frequency between 5 kHz to 95 kHz at a second BD depth and at at least a third BD frequency between 5 kHz to 95 kHz at a third BD depth; a current is transmitted from the interdigitated portion C through the tissue portion to the interdigitated portion D at a first CD frequency between 5 kHz to 95 kHz at a first CD depth, at a second CD frequency between 5 kHz to 95 kHz at a second CD depth and at at least a third CD frequency between 5 kHz to 95 kHz at a third CD depth; analyze the received currents at the interdigitated portion B, the interdigitated portion C and the interdigitated portion D and determining capacitance, resistance and phase at the first AB depth, the second AB depth, the third AB depth, the first AC depth, the second AC depth, the third AC depth, the first AD depth, the second AD depth, the third AD depth, the first BC depth, the second BC depth, the third BC depth, the first BD depth, the second BD depth, the third BD depth, the first CD depth, the second CD depth and the third CD depth therefrom.

[0143] As will be appreciated by one of skill in the art, each depth is indicative of some metabolic condition functioning at that depth. By monitoring multiple depths almost simultaneously, we can “see” what is happening under the device. For example, we can see if the electrical pressure is encouraging fuel flow into the cells or if byproducts are making their way to the surface. Since we have information both at depths and over time, we know how the electrical conditions are changing at each depth and can model the processes involved.

[0144] Each pair of interdigitated portions may be synchronized according to frequency, as discussed herein.

[0145] The device may be configured such that amplitude of the current or voltage can be changed, as discussed herein.

[0146] One example of a correlation procedure is:

[0147] Depth = Dab, Dbc, Dac, Dad (Direct current as determined between each space) Duration = t (chronological time duration e.g. milli seconds, seconds, minutes, hours, days)

[0148] Alternating Current Resistance = ACRab:f1thru ACRab:f10, ACRbc:f1 thru ACRbc:f10, ACRac:f1 thru ACRac:f10, ACRad:f1 thru ACRad:f10 (Alternating Current Resistance as determined between each space and at each frequency).

[0149] Direct Current Resistance in Direction One = DCRab, DCRbc, DCRac, DCRad

[0150] Direct Current Resistance in the Opposite to Direction = DCRba, DCRcb, DCRca, DCRda

[0151] Capacitance = Cab:f1 thru Cab:f10, Cbc:f1 thru Cbc:f10, Cac:f1 thru Cac:f10, Cad:f1 thru Cad:f10

[0152] Phase = PHab:f1 thru PHab:f10, PHbc:f1 thru PHbc:f10, PHac:f1 thru PHac:f10, PHad:f1 thru PHad:f10 (Phase as measured at each space and at each frequency) Current = Amp1 thru 10 (all of the above as measured at varying amperages)

[0153] Voltage = V1 thru 10 (all of the above measured at varying voltages)

[0154] Correlated Outcome = CO (e.g. blood glucose)

[0155] CO is a function of the measured capacitance, as corrected by the absolute value of the amplitude of measured frequency response, which determines the depth at which the electrical activity is occurring, as refined by varying the current and voltage levels, then taking into consideration the changes in these activities as it gets closer to the skin surface as determined by depth (as differentiated primarily by Dab, Dbc, Dac and secondarily by f1 thu f 10), taken over a time period that is reflective of the metabolic function of interest, corrected for directional differences to eliminate directional variables (like blood flow, and tissue orientation) multiplied by a logarithmic function of PH which is a function of the tissue density through which the waves traveled.

[0156] As discussed herein, the differentiators used in this method include:

[0157] Depth - differentiated by spaces, current and voltage changes and determines the layer of the skin we are interested in (fat, interstitial fluid, capillaries etc.)

[0158] Time - short term vs long term etc. BP, muscle contraction etc.

[0159] ACR - a corollary and validator of capacitance (helpful since R and C are so non linear and exponential.

[0160] DCR - directional information about cell structures

[0161] PH - tissue densities

[0162] While 10 frequencies are shown in this example, it is important to note that in some embodiments, three or at least three frequencies are used and in these embodiments the procedure can be adapted accordingly.

[0163] Similarly, while 4 contacts are shown in this example, as discussed above, at least 3 contacts may be used or more than 4 contacts may be used and the procedure adapted accordingly.

[0164] For example, one way to infer glucose or ketone (glutone) values (as measured by a continuous glucose monitor and / or finger pricks, for example) from capacitance, resistance and phase of the various spaces and frequencies using a combination of exponential (for capacitances and the inverse of AC resistances) and geometric (for phase and DC resistances) functions of a Taylor series to approximate the convergence. This can be programmed into the device by using a computer algebra system (CAS) over a time interval of interest, where the variables are suspected to be interrelated. E.g. over an interval of 30 minutes for glucose and 90 minutes for ketones (1 second for pulse, 24 hours for fat burning). A correlation coefficient measures this relationship and can be calculated using the complex coefficient (ksaai).

[0165] Specifically, as will be appreciated by one of skill in the art, any condition that is initiated by or involves a metabolic action involves bio-electric activity and since the device constantly tracks electrical activity, it becomes a matter of differentiating the ratios of capacitance, resistance, and phase, and depth to determine the root cause of the activity.

[0166] Furthermore, short duration changes in fluid volumes that are introduced by arterial pulses can be measured by increasing the read frequency above the Nyquist frequency related to the pulse. The difference in magnitude of the measured changes of these fast readings also is an indication of the systolic and diastolic blood pressures.

[0167] As known by those of skill in the art, virtually all metabolic functions involve the exchange of ions (negative electrons or positively charged hydrogen protons). As such, the device measures, continuously and in real time, the electrical activities associated with metabolic physiological changes.

[0168] FIG. 1 is a schematic illustration of an example apparatus according to the present invention. The apparatus comprises an impedance meter and a voltage divider, connected through a dual switch to multiplexers and connect corresponding signals to an interdigitated sensor as in FIG. 2. A microcontroller receives and transmits signals to the impedance meter, voltage divider, and multiplexers to control operation of the sensors. A storage memory is connected to the microcontroller to accommodate program instructions as well as data storage, including for example data on configuration information for the user.

[0169] Power can be provided, e.g., by a battery or by a power supply. The apparatus can communicate with a user or with other systems via a display, a touch screen or buttons, and / or wireless or wired communication facility.

[0170] In operation, measurements can be made repeatedly or upon initiation, e.g. by a user button press or wireless or wired signal. The microcontroller configures the dual switch, the analog switches and multiplexers to route analog signals to and from the sensor.

[0171] Resistance changes primarily due to density and electrolyte concentrations as both effect resistance. Sustained muscle contraction must be maintained by ATP depletion and replenishment, and these are reflected in capacitance.

[0172] Issues involving intercellular communication (like glucose) as indicated by capacitance changes. Specifically, since capacitance is primarily a function of intercellular isolation or communication, readings change as the cells communicate their need, or lack of need, for fuel (glucose or ketone) in the production of ATP.

[0173] When the cells don’t need fuel, they are relatively isolated and insulated from their surroundings and the interstitial fluid. Internally, the cells break down glucose in a series of electrically active steps including the electron transport chain. Under these conditions, electrical properties change as glucose concentrations rise and fall in part due to the production and dissipation of hydrogen peroxide.

[0174] Capacitance then is a function of fuel consumption or the short-term change in fuel availability.

[0175] It is apparent from observations discussed below that capacitance can be proportional to changes in interstitial glucose levels as indicated by the changes in resistance and capacitance resulting from the presence or absence of hydrogen peroxide, as discussed herein.

[0176] It may also be true that the total fuel (glucose or ketone) consumed is proportional to the integral of capacitance i.e. the area under the capacitance curve.

[0177] Furthermore, since the readings reflects fuel use rather than glucose availability, capacitance anticipates any changes in available glucose as would be measured by a glucose monitor. This is also true when the fuel being consumed is a ketone since the fuel uptake mechanism is electrically similar, i.e. fuel flowing into the cells and waste products being eliminated.

[0178] In accordance with an example embodiment, a device uses skin capacitance, resistance, and / or phase to enable a determination of blood glucose.

[0179] A measurement of the surface capacitance and subsurface capacitance (where capacitance means the resistance to flow of alternating current), resistance (where resistance means the resistance to flow of direct current) and / or phase (the relationship between capacitance and resistance) can be made with various suitable meters; however, the meters must be coordinated to enable detection of the desired capacitance, resistance and phase of a subject. The " phase" of a subject is the relationship between the two above, e.g., the relative magnitudes.

[0180] For example, as the magnitudes changes, we can tell if the concentrations are increasing or decreasing at any one depth and because we monitor multiple depths, we can determine whether the changes are due to migration or depletion. Furthermore, as discussed herein, there are two kinds of resistance measurements: AC resistance extracted from low frequency AC signals and DC. These two types of resistance are acquired differently, give different values, measure very different things, and are very different in their amplitude ranges. For example, DC resistances are very high whereas AC resistances are lower. Phase is only related to the AC resistance. DC resistance is flow directionally dependant (e.g. blood flow direction).

[0181] The subsurface capacitance of a subject is the capacitance of the internal layer of the subject's dermis and can be measured by capacitance as measured by lower frequencies and larger spaced contacts. The "sub surface resistance" of a subject is the resistance of the internal layer of the subject's dermis and can be measured by lower frequencies and larger spaced contacts. The "sub surface phase" of a subject is the relationship between the two above, e.g., the relative magnitudes of the two.

[0182] Furthermore, since the path and distance travelled between the interdigitated contacts are known, we know what the baseline phase is and that means that any variations from the anticipated phase shift is a function of different tissue density, as discussed herein.

[0183] FIG. 1 illustrates an embodiment of a circuit diagram of the capacitance meter of the present invention. FIG. 2 is a schematic illustration of an interdigitated sensor suitable for use with the present invention. The example comprises four separate conductive entities, designated in the figure as CONTACT A, CONTACT B, CONTACT C and CONTACT D. These four contacts can be utilized in various combinations, for example, in pairs, to effectively measure different locations and depths in the tissue, as illustrated in Figure 2. Other embodiments can have more or fewer contacts, and various patterns of interdigitation are contemplated other than the simple structure shown. As examples, parallel spirals, concentric part circles, two dimensional and three-dimensional arrays of contacts, fractal structures provide a large number of small, spatially related contacts, contacts with different width electrical conductors (that can correlate with different power injection characteristics), can be suitable.

[0184] The general skin capacitance of individuals can vary. Varying the spatial frequency of the interdigitated contact area changes the capacitance range and allows the device to be selectively matched to users with different baseline capacitances, resistances and phases. It is of note that even in a single person, and even though the device does not directly contact the skin, the capacitance and resistance variations for different spaces, different intimacies of contact, different surface wetness and the like are considerable so having a selection of space sizes ensures that a minimum number of contacts is always in a suitable range. In an example embodiment, the spatial frequency of the interdigitated area is approximately 1 , 2, and 3 per mm.

[0185] The contact area can also be interdigitated, electrically separated, or stainless (or other non- corroding, coated conductor) wires. The interdigitated contact area can be made of stainless steel or individual wires coated to prevent corrosion, or an exposed or graphene, or conductive ink or conductive ink tattoo coated printed circuit board or foil. In an example embodiment, the contact area can be a single use contact surface.

[0186] A power supply section of the meter can be of any suitable type and is illustrated in an alternating current (AC) signal, or equivalent. In an example embodiment, the supplied voltage is a variable alternating current ranging from DC or zero or a few hertz to the high MHz range. High frequencies can be useful to concentrate the current flow on the surface of the skin, especially when differentiated from the lower frequencies.

[0187] Higher frequencies, for example above the 100 MHz range, can cause tissue damage and are closely regulated whereas the low frequencies we can use are benign. By using the difference between two low frequencies we can interrogate for the same wavelength related particle size, as discussed herein. In an example embodiment of the present invention, the device includes both low frequency (0-5000 Hz) and high frequency (5000-95000 Hz) AC.

[0188] In this embodiment the current flow difference measured across the contact area using at least one lower frequency and at least one higher frequency AC is compared. This contrasts the contributions to capacitance that comes from the subcutaneous path to that of the surface capacitance, and can be used to determine depths in the tissue that correlate well in changes due to changes in blood glucose levels.

[0189] A device of the present invention, in an example embodiment, includes a processing system and it can also include a memory module and a transmitter to communicate with a smart phone for display of a blood glucose level or blood glucose level status or blood glucose status or blood glucose indication(s), as discussed herein.

[0190] The processing system can be a programmable processor included to execute program instructions to guide a data process module to directly store captured data into the memory module, to initiate data upload from the memory module of the measurement device, for example, to a computing means via data upload module, to compare current readings to initial reading, to manage energy usage and so forth. The memory module can include any appropriate type of memory now known or later developed including without limitation, read-only memory (ROM), random access memory (RAM), flash memory, and / or a set of registers included within the programmable processor.

[0191] In an example embodiment, the processing system can comprise a microprocessor such as the Maxim Health Sensor Platform MASXREFDESIOO#. Maxim MAXREFDESIOO# health sensor platform is an integrated sensor platform that helps customers evaluate Maxim's complex and innovative medical and high-end fitness solutions. The platform integrates one biopotential analog front-end solution (MAX30003), one pulse oximeter and heart-rate sensor (MAX30101 ), two human body temperature sensors (MAX30205), one 3- axis accelerometer, one 3D accelerometer and 3D gyroscope, and one absolute barometric pressure sensor. As will be apparent to one of skill in the art, in other embodiments, other suitable processing means can also be used.

[0192] In another embodiment, the device of the present invention can include wireless communication capabilities that would allow it to connect with a computing device, such as a laptop, a desktop, wireless devices such as cellular phones and pads, or to directly connect to the Internet. The information stored in the memory means can be downloaded into a computing device or a cloud system for storage or for further analysis or displaying results of measurement. Specifically, in some embodiments, the device is arranged to pass on relevant information or data or share relevant information or data with any interested party or device or for sharing the information with a care giver for example in the case of epileptic seizures or spasms. For example, relevant information, any irregularity or data can be passed to a storage device and / or a computing device such as for example but by no means limited to a server, cloud, tablet, PC, smartphone or other device for further data processing, post-processing data analysis and / or display or tabulation of results. For example, the data from many users can be shared and analyzed, for example, anonymously, at a single data storage site or storage entity.

[0193] In other embodiments, the device can comprise a microcontroller, memory, a display for visualization of data, a touch screen for user input, a battery and at least one sensor. n of data, a touch screen for user input, a battery and at least one sensor.

[0194] A device of the present invention may be used on any part of the body. The top of the fingertip is suited for measuring skin resistance, capacitance, and phase. The inside of the forearm is another suitable site. The ear lobe is another suitable site. The underside of the wrist is another suitable site, as is the stomach. The device can also be configured as a handheld device, for example, such as in combination with a handheld ultrasound imager to coordinate electrical properties with acoustic tissue densities. For example, the handheld device could be moved over various locations to cover large areas and the images could then be combined to show large area electrical properties as they are correlated with ultrasonic tissue densities.

[0195] For example, a three or four contact version could be fitted on a handheld device such as an ultrasound device or infrared thermometer, and the outputs coordinated to align the electrical properties image with the ultrasound image giving additional tissue properties associated with the varying tissue densities (for cancer detection, carotid artery blockage etc.) or wound (inflammation) or joint temperatures (arthritis detection).

[0196] In some embodiments, skin capacitance, resistance and / or phase measurement are compared to baseline values taken when the subject is measuring their blood glucose level using a different device such as those known in the art, for example, a glucose test strip or a glucose monitor, that is, the baseline skin capacitance resistance and phase values can represent the "normal" skin capacitance measurement or value of the subject.

[0197] Alternatively, in other embodiments, blood glucose level can be determined directly by referencing the skin capacitance, resistance and phase measurements values determined from testing on a variety of people. The capacitance, resistance and phase measurements can be correlated with reference to blood glucose level measurements, and the correlation stored as a table, or analyzed to produce a mathematical relationship, using calibration techniques known in the art. The calibration can be made using measurements from a single user (a user-specific calibration), or can be made using measurements from a plurality of users (a generic calibration). A generic calibration can be generic to all users, or can be limited to users within a single physiological category, e.g., weight, body mass index, body composition, age, ethnicity, etc. A calibration can also use such physiological information as part of the calibration, and can also use other information such as temperature, tissue hydration, etc. to increase the accuracy of blood glucose reports. Alternatively, in the case of general health monitoring no correlation or calibration is required and each individual can simply be aware of their own variations.

[0198] Furthermore, the device can detect metabolic changes that result from atmospheric pressure changes and altitude effects such a altitude sickness. This is useful for athletic training at altitude or mountain climbers and could be used as a non-invasive test for blood doping. The inventors have observed that tissue capacitance and tissue resistance are exponentially and inversely related. Sensor systems that allow selection of contact spacing and frequencies, like those described herein, can allow for successful sensing even when measurements would be off-the-scale for one spacing between contacts, or essentially unchanging for another spacing between contacts.

[0199] For example, blood pressure is normally measured in a resting state and most heart problems occur in a dynamically active state. With our continuously monitoring capability the device can detect and alert the user if unusually high measurements occur during exertion.

[0200] Normally when measuring capacitances and resistances, small spaces (e.g. 0.001 to 0.003 in) between the interdigitated strips of the contact sensor, the capacitance is high and resistance is low. For larger spaces the inverse is true: capacitance is low and resistance is high. Due to the exponential nature of these two response curves, it can be advantageous to use multiple spaces to determine where the best resistance and capacitance values can be achieved and compared. The spaces should also correspond to the electrical activity in the related subdermal layers of the skin. The depth of penetration into the tissue is a function of frequency, contact spacing and amplitude, (e.g., low frequencies 1 KHz to 10 KHz and large spaces 0.005 to 0.020 inch probing deeper (in the dermis and hypodermis) and high frequencies and small spaces (e.g., 25 to 100 KHz and 0.003 to 0.005 in.) reflecting the electrical activities at shallower depths (in the epidermis)). It is thought that the larger spaces reflect the electrical activity at a greater depth (the current device measures these depths to be between 0.02 in. for a space of 0.003 in and 0.06 for a space of 0.015 inches) due to the larger path length and influence of the arc of the current as it flows through the tissue. Depth can also be differentiated by frequencies between 5 KHz and 95 KHz at any one spacing. Once the broad range for the best depth has been determined by space size, differentiation by frequency yields a more specific signal detail and can refine the depth measurements within the depth range established by the space.

[0201] It is also of note that adjustment of frequency, amplitude of the test signal and selection of appropriate spacing of a sensor can be used for calibration of the device.

[0202] For example, we have learned that if two different, but very close frequencies are used they can identify features that have a cellular size like the wavelength difference between the two frequencies. This gives us the ability to use very benign low frequencies to look for things that would normally only show up when using much higher frequencies. For example, the particle size interrogated by the difference between 5000 kHz and 5000.001 kHz is approximately 0.3 nanometers, but the base frequency is benign and does not interfere with cellular function. Knowing the sensor sizes and locations we can model the interference patterns and move the 0.3 nanometer interrogation zone around to get a detailed image of that particle distribution. We can also vary the frequency differences to look for different particle sizes.

[0203] In some embodiments, the device can connect to and collect data from other wireless sensors located on user's body using its wireless communication module, for example, a continuous glucose monitor or pulse oximeter. These wireless sensors can collect the other type of data which may not be directly measured by the device, such as blood oxygen, body temperature, etc. A variety of data obtained by the device by direct measurement and collected from wireless sensors can be post-processed by the device itself or sent to a remote computer or a cloud system.

[0204] According to an aspect of the invention, there is provided an apparatus comprising: an interdigitated portion having two opposing ends and configured for contacting skin of a subject and measuring skin capacitance, resistance and phase; an analysis system that produces a signal responsive to the skin capacitance, resistance and phase measurements, where the signal is indicative of blood glucose level of the subject.

[0205] In some embodiments, the comparative capacitance, resistance and phase values form a baseline capacitance, resistance and phase measurement. In these embodiments, the signal may indicate that the capacitance, resistance and phase measurements are different from the baseline capacitance, resistance and phase measurements. For example, this difference may be linked to a particular threshold or may correspond to a certain percentage difference when trends are being measured.

[0206] In some embodiments of the invention, the analysis system compares the skin capacitance, resistance and phase measurements to calibration skin capacitance, resistance and phase measurements and corresponding blood glucose level measurements to provide an estimate of blood glucose level. Depending on the blood glucose level, the user may take appropriate steps to deal with the estimated blood glucose level, for example, eating, drinking or taking insulin. It is noted that specific steps taken for example by diabetics at certain blood glucose levels are well known in the art. For example, in general, fat build up in the cells is controlled by insulin and as a result of prolonged available of high glucose levels, higher insulin levels are need to encourage the cells to take on the surplus glucose to store as fat and resistance increases. The user can monitor the changes in capacitance as the insulin levels change from day to day and from meal to meal.

[0207] In some embodiments, the calibration measurements comprise a plurality of measurements of the present subject while in others, the calibration measurements comprise a plurality of measurements of a plurality of subjects corresponding to blood glucose level measurements from a number of individuals that may be grouped by one or more common characteristic, for example, age, weight, height, general condition, severity of diabetes, frequency of insulin injections or the like.

[0208] In some embodiments, the analysis system is further responsive to one or more of: the subject's age, weight, body mass index, ethnicity, and health status.

[0209] According to another aspect of the invention, there is provided a method of determining an indication of blood glucose level in a subject, comprising: providing a device as described above; using the interdigitated sensor at a plurality of interdigit separations to measure resistance, capacitance, and phase of a portion of the skin or tissue portion of the subject; comparing the measured resistance, capacitance, and phase with calibration resistance, capacitance, and phase values to determine an indication of blood glucose level.

[0210] In some embodiments of the invention, the indication comprises an indication that the blood glucose level has changed relative to the blood glucose level when the calibration values were measured.

[0211] In some embodiments, the indication comprises an indication of the current blood glucose level of the subject.

[0212] Differentiation abilities of the device

[0213] Continuous monitoring allows for signal differentiation by the following:

[0214] Depth

[0215] The device inputs and measures from the same locations (the input and output signals are frequency synchronized) and can therefore infer the depth of the various tissue properties.

[0216] Depth is a function of contact spacing and the device has interdigitated contact spacing giving a multiplicity of reading from the different contacts. In general, the penetration depth is about one half of the distance between electrodes and each pair can be interrogated bi-directionally. For example, close spaced contacts are more influenced by shallow tissue properties and wider space readings are influenced by deeper tissue properties.

[0217] Depth is also a function of frequency. In some embodiments, the device may interrogate at for example 10 different frequencies. High frequencies tend to remain near the surface while lower frequencies travel deeper into the tissues.

[0218] Duration

[0219] Long duration changes (hours or days) are representative of things that change slowly like weight loss.

[0220] Medium duration changes (minutes) are representative of things like glycolysis and ketosis.

[0221] Short duration changes (seconds) are representative of things like sustained muscle contractions.

[0222] Very short duration changes (milli seconds) are representative of things like pulse and blood pressure, nerve activation, tremors etc.

[0223] Rapid increases in resistance that are accompanied by rapid reductions of capacitance may be primarily due to muscle contractions and changes in electrolytes concentrations. Slow increases in resistance may be due to general energy consumption, ATP use and the call for energy production.

[0224] Slow increases in capacitance may be due to ATP production.

[0225] For example, the rate of change i.e. the first derivative of the variable, is used as well as the absolute value of the average readings over different periods of time. For example, micro changes may be due to pulse or muscle twitch whereas very longer durations may be due to fat build up or break down.

[0226] Furthermore, short duration changes in fluid volumes that are introduced by arterial pulses can be measured by increasing the read frequency above the Nyquist frequency related to the pulse. The difference in magnitude of the measured changes of these fast readings also is an indication of the systolic and diastolic blood pressures.

[0227] Resistance

[0228] A resistance derived from an alternating current (AC) implies a resistance measured bidirectionally and can be measured at multiple frequencies and at multiple spaces (depths).

[0229] DC resistance measures the steady state conductance, bidirectionally, at multiple spaces. AC implied resistance is measured bidirectionally at multiple frequencies and at multiple spaces.

[0230] Capacitance

[0231] Capacitance is measured at multiple frequencies and at multiple spaces.

[0232] Synchronized alternating current signals are measured at multiple frequencies and between all space combinations.

[0233] Phase

[0234] Distance travelled influences the phase shift. The timing of the phase shift is a function of the distance travelled and we know the distance between each of the input and output locations. The magnitude of the phase shift is also a function of the tissue’s properties, for example, tissue density.

[0235] The phase shift is measured at multiple frequencies and between all contact spaces.

[0236] The magnitude of the phase shift is a function of the tissue through which the signal travels.

[0237] For example, muscle tissue, particularly skeletal muscle, demonstrates a high electrical conductivity, (approximately 0.5 S / m and can be anisotropic, meaning conductivity varies depending on the direction), fat tissue has a lower conductivity (typically around 0.02 to 0.1 S / m), and blood is a good conductor (approximately 0.7 S / m).

[0238] Current

[0239] The strength of the input signal can be varied by varying the voltage and thus the current flow into the tissue giving further depth penetration information. Higher currents penetrate deeper into the tissues and can be differentiated from smaller current signals for each of the variables.

[0240] Device Function:

[0241] The device transmits and retrieves an electrical signal via interdigitated contacts on the underside of the device. Specifically, transmits from a respective one interdigitated contact and receives at a respective other interdigitated contact, both interdigitated contacts being frequency synchronized for this transmission, as discussed herein. The electrical signals are very low frequencies as well as low voltage and low current and therefore have minimal physiological impact and influences are well under all the FDA and 60601 guidelines and limitations. The synchronized return signal indicates the electrical field through which the signal travelled. The electrical field is influenced by blood, interstitial fluid, capillaries, muscle, bones and the like. Physiology:

[0242] Body tissues function like a combined resistor and capacitor, and their values constantly change over short (milliseconds), and longer durations (minutes to hours to days).

[0243] Two main drivers of electrical properties:

[0244] Cellular respiration:

[0245] Cellular respiration involves the production of ATP from glucose or the ketone - hydroxybutyrate. In preparation for glucose or ketone uptake, cells respond to the presence of the hormone insulin and communicate their need for glucose. Glycolysis is a complex metabolic process that converts glucose into pyruvate and the energy molecule adenosine triphosphate (ATP), and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions which are catalyzed by enzymes. Glucose is first oxidized, catalyzed, by glucose oxidase (as an external electron acceptor) to produce gluconate and hydrogen peroxide resulting in two hydrogen protons. During the time the cells are accepting glucose the cell walls are opened, due to the presence of insulin, with a related drop in capacitance since neighboring cells are sharing the same conductive interstitial fluid. The resulting electro-motive force created by a potential difference between the outside of the cells and the cell’s interior encourages the flow of glucose into the cells.

[0246] When the cells don’t need fuel, they are relatively isolated and insulated from their surroundings and the interstitial fluid. Internally the cells break down glucose in a series of electrically active steps including the electron transport chain. Under these conditions electrical properties change as glucose concentrations rise and fall because of the production and dissipation of hydrogen peroxide.

[0247] Note that glucose is nonconductive and when in ketosis, although p-hydroxybutyrate is an acid, it does not add conductance because it is electrically coupled in the fermentation process.

[0248] Muscle contraction:

[0249] Muscle contractions involve the consumption of ATP from four sources: free ATP (for immediate use), phosphocreatine, glycolysis, and cellular respiration for progressively longer duration uses. Fueling muscle contractions fall into two basic types: aerobic and anaerobic. Both processes involve the consumption of electrolytes, calcium, and magnesium. Electrolytes are very conductive. Muscle contraction results in an immediate change in electrical properties as the electrolytes are temporarily depleted. Depletion is followed by a slow rise, as the electrolyte imbalance is restored. In the case of obesity and / or insulin resistance, the cells are forced to take more glucose than they would normally need to function and to store the excess glucose as fat. This requires a higher concentration of insulin which precipitates a greater electrical potential to encourage the glucose into the cells.

[0250] Ions and Dipoles:

[0251] In the above and other bodily functions electrical properties change primarily due to two mechanisms:

[0252] 1 . Free ions change resistance. a. Free ions which come from concentrations of electrolytes (potassium, sodium, calcium, and magnesium etc.). The concentration of free ions is inversely proportional to resistance. b. Interstitial fluid contains both electrolytes and fuels (glucose or ketones). Fuels are less conductive electrolytes are more conductive (less resistive). c. Positively charged hydrogen protons are released from hydrogen peroxide during cellular respiration.

[0253] 2. Dipoles change capacitance. a. Dipoles are a function of cellular electrical isolation or intercellular communication. b. Capacitance drops as cells communicate their need for oxygen or fuel. In the presence of insulin, cell walls open conduit ports to allow the flow of fuel into the cell. Similarly, when the cells do not need fuel, the ports are closed, cells are more isolated, and capacitance rises.

[0254] Capacitance of biological tissues is primarily influenced by:

[0255] Cell Membranes: Cell membranes act as dielectric barriers, contributing to the capacitive properties of tissues. The presence of cell membranes and their arrangement play a major role in determining the capacitance.

[0256] Tissue Structure: The internal structure and arrangement of cells within a tissue affect its capacitive behavior. Tissues with different cellular structures exhibit characteristic impedance spectra due to varying capacitance.

[0257] Tissue Geometry: The geometry of the tissue, such as its cross-sectional area and length, can influence the overall capacitance, as capacitance increases with increasing cross- sectional area or length. Intercellular Communication: The electromagnetic field generated by tunneling nanotubules (TNTs) or microtubules, composed of identical tubulin heterodimers with periodic organization and containing electric dipoles and gap junctions.

[0258] Short duration changes in fluid volumes that are introduced by arterial pulses can be measured by increasing the read frequency above the Nyquist frequency related to the pulse. The difference in magnitude of the measured changes of these fast readings also is an indication of the systolic and diastolic blood pressures.

[0259] Capacitance also changes due to the opening of channels in the cell walls to allow for the inflow of fuel (glucose, as triggered by insulin or alternately the availability of p- hydroxybutyrate) which is in turn a function of ionic activity related to the hydrogen ion protons produced in the conversion of ATP from mono and di adenosine triphosphate. Some research indicates as much as 500 mv are involved in these reactions.

[0260] Since capacitance is thought to be primarily a function of intercellular isolation or communication, the device readings change as the cells communicate their need, or lack of need, for fuel (glucose or ketone) in the production of ATP. Capacitance then is a function of fuel consumption or the gradual change of fuel. It may also be true that the total fuel (glucose or ketone) available or consumed, is proportional to the integral of capacitance i.e. the area under the capacitance curve. The device reflects fuel use rather than glucose availability.

[0261] Conductivity (the inverse of resistance) of biological tissues is influenced by:

[0262] Ionic Content: Conductivity in tissues is primarily due to the movement of mobile ions within the aqueous biological medium. Tissues with higher ionic content, such as muscle and blood, exhibit higher conductivity compared to fat tissue.

[0263] Water Content: Tissues with higher water and electrolyte content, such as fat-free body (FFB) mass, have higher conductivity compared to fat tissue, which has lower water content.

[0264] Temperature: The mobility of ions in tissues is temperature-dependent, affecting the overall conductivity. Electrical properties change with localized or generalized inflammation such as blunt force trauma and cytokine activity.

[0265] Tissue Type: Different tissue types, such as muscle, liver, blood, and fat, have varying conductivity values due to their varying compositions and structures.

[0266] Resistance is primarily a function of electrolyte conductivity (more specifically calcium and magnesium absorption due to muscle contractions), resistance immediately increases when muscles use ATP. Conversely resistance drops as electrolyte levels build up in the interstitial fluid.

[0267] Four examples of metabolic states:

[0268] Fuel from the blood in the form of either glucose or p-hydroxybutyrate is transported by the arteries to the capillaries and deposited into the interstitial fluid to be available for use by the individual cells.

[0269] Capacitance:

[0270] 1 . Fuel availability is high, and the cells need fuel. a. Capacitance will be low due to high intercellular communication.

[0271] 2. Fuel availability is high, and the cells do not need fuel. a. Capacitance will be high due to lack of intercellular communication.

[0272] 3. Fuel availability is low, and the cells need fuel. a. Capacitance will be low due to high intercellular communication.

[0273] 4. Fuel availability is low, and the cells do not need fuel. a. Capacitance will be high due to the lack of intercellular communication.

[0274] Muscle contraction resistance:

[0275] Electrolytes are availability at normal homeostatic levels and the muscles need fuel. Resistance will drop quickly due to the use of calcium and magnesium being consumed during muscle contractions and then return to normal levels over the next few minutes as they are replenished.

[0276] Intercellular conductance is also facilitated by microtubules and actin filaments which bioelectrically connect the cells.

[0277] Interactions:

[0278] During muscle contractions there is an immediate rise in resistance (due to the loss of electrolytes) and an immediate drop in capacitance due to the increased resistance and these are immediately followed by a recovery of the next few minutes, as an asymptotic return to their previous states.

[0279] Summary:

[0280] Very rapid changes in resistance capacitance and phase are related to fluid volume changes due to pulse.

[0281] Rapid increases in resistance are accompanied by rapid reductions of capacitance and are primarily due to muscle contractions and changes in electrolytes concentrations. Slow increases in resistance are due to general energy consumption, ATP use and the call for energy production.

[0282] Slow increases in capacitance are due to ATP production.

[0283] It is apparent from our observations that capacitance is directly proportional to changes in interstitial glucose levels as indicated by the changes in capacitance resulting from the presence or absence of hydrogen peroxide, (this was confirmed by in vitro testing of the reactions of 3% hydrogen peroxide on glucose dissolved in simulated interstitial fluid) except when resistance is increasing, the capacitance is seen to be inversely proportional to glucose.

[0284] Relationship Between pH and Electrical Resistance:

[0285] Potential of hydrogen or 'pH' is the measure of hydrogen ion concentration. The body’s normal range is from 7.35 to 7.45. pH. The scale ranges from 0 acidic, 7 neutral, and 14 alkaline. Note that above 7.8 or below 6.8 are life threatening.

[0286] Electrical conductivity (the opposite of resistance) is directly proportional to the concentration of both positively and negatively charged ions measured in Micro Siemens per cm (pS / cm).

[0287] Hydrogen ions impact the pH and directly influence conductivity. However, hydrogen ions make up only a small part of the total ion concentration, so conductance is the comparison of hydrogen ions to other concentrations of non-pH determining ions.

[0288] Every cellular process - including metabolism, membrane potential, cell growth, proliferation, polymerization of the cytoskeleton (with its microtubules), and movement of substances across the membrane, are affected by changes in intracellular pH by pushing fuel into the cells and extractive waste byproducts.

[0289] Since we are measuring at a depth where the nerves reside, we-are also measuring the base voltage of the action potential of the nerves (-70mV).

[0290] Bidirectional Measurement Influences:

[0291] In some embodiments, we measure a directional difference in all measurements, (i.e. from a to b as well as from b to a) and therefore can differentiate different tissue properties such as elastin (because of its hydrophilic hydrophobic ends) from more randomly polarized materials such as hydration.

[0292] Veins tend to be closer to the surface than arteries, so it is possible to depth differentiate by space and frequency and further analyze the signals by virtue of electrical directionality (a-b as differentiated from b-a etc.). Measures the presence of hydrogen peroxide directly as a function of the hydrogen protons that are released in the production of gluconate.

[0293] Note veins are closer to the surface of the underside of the wrist.

[0294] Stratum Corneum (Dead skin top layer)

[0295] Approx: 0.0016 in. depth

[0296] Living Epidermis

[0297] Approx: Thickness = 0.01 in. at a depth = 0.01 in.

[0298] 100 - 1000 Q m resistance

[0299] 104permittivity

[0300] Dermis

[0301] Approx: Thickness = 0.02 in. at a depth = 0.03 in.

[0302] 10 O m resistance

[0303] 104permittivity

[0304] Hypodermis

[0305] Approx: Thickness = 0.035 in. at a depth = 0.05

[0306] 10 O m resistance

[0307] 104permittivity

[0308] SC + LE + D + HD - Collectively - 72.9 permittivity 0.491 Elec. Cond. (S / m) Subcutaneous - 0.04 in.

[0309] 127.0 permittivity 0.0684 Q m resistance Muscle

[0310] 660 permittivity 0.708 Q m resistance Blood

[0311] 768 permittivity 1 .23 Q m resistance

[0312] For example, while the upper layers of the skin are at a uniform depth, some fine tuning of depth may be needed per individual to locate the lower layers, identified above. Typically, fat is the bottom layer.

[0313] Interstitial Fluid

[0314] Interstitial fluid is extracellular (and outside of the blood vessels) fluid and is 75% water, plus solutes, including electrolytes, sugars, salts, acids, hormones, neurotransmitters, and cell waste. Electrolytes supplies ions that can diffuse through the interstitial fluid or undergo directional flow. Interstitial fluid surrounds the tissue cells and supplies the cells with oxygen and nutrients, while it also removes products of metabolism and carbon dioxide. A person has a total of about 10-12 liters of interstitial fluid and this decreases with age.

[0315] 59-73 0.41-0.8 Q m resistance

[0316] We measure IT at approximately 2000 ohms to 20,000 ohms.

[0317] 50 - 60 pico farads depending on the pressure and which varies from 0 to 1000

[0318] Pascals or 0.15 psi

[0319] We measure IT at 0.02 nf (20 pico farads)

[0320] Harvesting of Interstitial fluid is typically done at a depth of 0.01 in. just into the dermis where interstitial fluid is predominant.

[0321] Stats for initial modelling:

[0322] Layer #1

[0323] Thickness = 0.02 inch = 0.508 millimeter

[0324] Resistance - 10 M ohm

[0325] Permittivity = 104F / m or 104x 0.000508 = 0.052832 F

[0326] Layer #2

[0327] Thickness = 0.02 inch = 0.508 millimeter

[0328] Resistance 10 O m

[0329] Permittivity 104F / m or 104x 0.000508 = 0.052832 F

[0330] Layer #3

[0331] Thickness = 0.055 inch = 1.397 millimeter

[0332] Resistance = 0.41-0.8 Q m

[0333] Permittivity = 50 - 60 pico / m or (50 x 0.001397) = 0.06985 F to (60 x 0.001397) =

[0334] 0.06985 F

[0335] Layer #4

[0336] Thickness = 0.2 inch = 5.08 millimeter

[0337] Resistance = 0.0684 Q m

[0338] Permittivity = 127.0 F / m or 127 x 0.00508 = 0.64516 F

[0339] Array Version:

[0340] In some embodiments, the interdigitated contacts may be arranged in an array.

[0341] For example, given a grid of closed spaced, fine, coated, wires (for example 32 gauge of 100 x 100 wires) the grid could be interrogated in the following way:

[0342] Row 1 to Row 2, Row 1 to Row 3, Row 1 to Row 4, ... etc. up to Row 1 to Row 100 Then in reverse order Row 100 to Row 1 , Row 100 to Row 99 ... etc. up to Row 100 to 1

[0343] Columns, at right angles to the rows, could be interrogated in a similar fashion along with other permutations of wire pair combinations such that all combinations and their associated depths had been interrogated. The resulting information could be recompiled using a finite element (or similar) model giving a full 3D image of the electrical properties under the device. This could then be combined with a corresponding ultrasound or Xray or MRI or CT scan image to relate the electrical properties to specific tissues or cancers.

[0344] Similarly sets of four wires could be moved around and interrogated to give higher localized special resolution.

[0345] For example, the array could be configured in a bed sheet that constantly monitors the patient’s electrical activities, especially at the contact zones. This could detect local bleeding, tissue death, and would be particularly helpful for the prevention of bed sores, where localized high pressures reduce the localized blood flow.

[0346] Furthermore, as the device detects the uptake of glucose, and since cancers have additional insulin receptors and high glucose uptake, as indicated by a PET scan, our device can be used similarly to detect the cancer.

[0347] Interference pattern generator. If, in the above-described array of wires, every other wire was excited continuously by 10 different frequencies starting from 5kHz and increasing by 10kHz up to 95kHz, there would exist a standing wave of interference patterns that would yield the electromagnetic properties of the tissues in the interference zones. This interference pattern would be reflective of any tissue properties in the interference zones, and could be interrogated by the other wires in the array, if the measurement data is analyzed using the equation: using the equation:

[0348] The interference pattern of 10 sine waves with frequencies starting from 5 kHz and differing by 10 kHz can be described by the equation:

[0349] Where:

[0350] • !Af) is the resulting wave function. is the starting frequency.

[0351] • J = 1()kHz is the difference between consecutive frequencies.

[0352] • n ranges from 1 to 10, representing the

[0353] 10 sine waves.

[0354] Furthermore, in the above referenced array, the electrical standing wave locations, can be measured and their locations controlled by varying the timing of the input waves such that the positions of the standing waves can be position over areas of interest such as cancers and then the power of the standing wave could be increased to interfere with the normal cell replication mechanisms.

[0355] It is believed that one of ordinary skill in the art can, based on the description presented herein, utilize the present invention to the full extent. All publications cited are incorporated by reference.

[0356] The present invention has been described in connection with various example embodiments. It will be understood that the above description is merely illustrative of the applications of the principles of the present invention, the scope of which is to be determined by the claims viewed in light of the specification. Other variants and modifications of the invention will be apparent to those skilled in the art.

Claims

CLAIMS1. A method for enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:(i) a power source;(ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion;(iii) a display system for data entry;(iv) an analysis system; and(v) a memory module; activating the device such that at least one current at at least one frequency passes from at least a respective one interdigitated portion to at least one respective other interdigitated portion; the analysis system analyzing the received current at the at least one respective other interdigitated portion and determining capacitance, resistance and phase at a frequency skin depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the frequency skin depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

2. A method for enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:(i) a power source;(ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the secondinterdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion;(iii) a display system for data entry;(iv) an analysis system; and(v) a memory module; activating the device such that on an ongoing basis: a current at at least one frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least one frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the third interdigitated portion; the analysis system analyzing the received current at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a second frequency depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first frequency depth and at the second frequency depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

3. A method for enabling a device to correlate electrical properties of a tissue portion with one or more metabolic condition and / or physiological property of an individual, said method comprising: placing a device onto the tissue portion of the individual, said device comprising:(i) a power source;(ii) at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission andreceipt of current at different frequencies;(iii) a display system for data entry;(iv) an analysis system; and(v) a memory module; activating the device such that on an ongoing basis: a current at at least a first frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least a second frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; a current at at least a third frequency is transmitted from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; the analysis system analyzing the received currents at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom; and said individual marking a metabolic condition and / or physiological event via the display system such that the capacitance, resistance and phase at the first frequency depth, at the second frequency depth, at the third frequency depth and at the fourth frequency depth at the time of the metabolic condition and / or physiological event is correlated with the metabolic condition and / or physiological event.

4. The method according to any one of claims 1-3 wherein each frequency is between 0-100 kHz.

5. The method according to any one of claims 1-3 wherein each frequencyis between 5-95 kHz.

6. The method according to claim 3 wherein each pair of interdigitated portions is synchronized according to frequency.

7. The method according to any one of claims 1-3 wherein the metabolic condition and / or physiological event is blood glucose level.

8. The method according to any one of claims 1-3 wherein the metabolic condition and / or physiological event is marked by the individual taking a blood glucose level reading.

9. The method according to any one of claims 1-3 wherein the device is configured such that amplitude of the current can be changed.

10. A method for determining blood glucose level of an individual, said method comprising: placing a device onto a tissue portion of the individual, said device comprising:(i) a power source;(ii) a coplanar arrangement of at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;(iii) a display system for data entry;(iv) an analysis system; and(v) a memory module; activating the device such that on an ongoing basis: a current at at least a first frequency is transmitted from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; a current at at least a second frequency is transmitted from the first interdigitated portion through the tissue portion at a second depth to the second interdigitatedportion; a current at at least a third frequency is transmitted from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion; a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; the analysis system analyzing the received currents at the second interdigitated portion and determining capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and the analysis system analyzing the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom; and said analysis system determining blood glucose level status from said analysis.

11. The method according to claim 10 wherein the blood glucose level status is whether blood glucose is increasing or decreasing over time.

12. The method according to claim 10 wherein the blood glucose level status is a blood glucose level for the individual determined from a plurality of corroborative blood glucose levels of the individual.

13. The method according to claim 10 wherein the blood glucose level status is a blood glucose level for the individual determined from a plurality of corroborative blood glucose levels of a plurality of subjects.

14. The method according to claim 10 wherein each frequency is between 0-100 kHz.

15. The method according to claim 10 wherein each frequency is between 5-95 kHz.

16. The method according to claim 10 wherein each pair of interdigitatedportions is synchronized according to frequency.

17. The method according to claim 10 wherein the device is configured such that amplitude of the current can be changed.

18. The method according to claim 10 wherein the device has 4 interdigitated portions.

19. The method according to claim 10 wherein each transmission between a first interdigitated portion and a second interdigitated portion is done at three frequencies.

20. A device configured to be placed onto a tissue portion of an individual, for detecting metabolic, catabolic and anabolic changes in the tissue portion over time, said device comprising:(i) a power source;(ii) at least three interdigitated portions arranged such that at least a distance between the first interdigitated portion and the second interdigitated portion is different from a distance between the first interdigitated portion and the third interdigitated portion, said at least three interdigitated portions configured for pairwise transmission and receipt of current at different frequencies;(iii) a display system for data entry;(iv) an analysis system; and(v) a memory module; said device configured to transmit a current at at least a first frequency from the first interdigitated portion through the tissue portion at a first depth to the second interdigitated portion; transmit current at at least a second frequency from the first interdigitated portion through the tissue portion at a second depth to the second interdigitated portion; transmit a current at at least a third frequency from the first interdigitated portion through the tissue portion at a third depth to the third interdigitated portion;transmit a current at at least a fourth frequency is transmitted from the first interdigitated portion through the tissue portion at a fourth depth to the third interdigitated portion; analyze the received currents at the second interdigitated portion and determine capacitance, resistance and phase at a first frequency depth and at a second frequency depth therefrom; and analyze the received current at the third interdigitated portion and determining capacitance, resistance and phase at a third frequency depth and a fourth frequency depth therefrom.21 . The device according to claim 20 wherein each frequency is between 0- 100 kHz.

22. The device according to claim 20 wherein each frequency is between 5- 95 kHz.

23. The device according to claim 20 wherein each pair of interdigitated portions is synchronized according to frequency.

24. The device according to claim 20 wherein the device is configured such that amplitude of the current can be changed.

25. The device according to claim 20 having 4 interdigitated portions.

26. The device according to claim 20 wherein each transmission between a first interdigitated portion and a second interdigitated portion is done at three frequencies.