Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
  • A61B5/053—Measuring electrical impedance or conductance of a portion of the body
  • A61B5/0536—Impedance imaging, e.g. by tomography
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
  • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
  • A61B5/7271—Specific aspects of physiological measurement analysis
  • A61B5/7285—Specific aspects of physiological measurement analysis for synchronising or triggering a physiological measurement or image acquisition with a physiological event or waveform, e.g. an ECG signal

Definitions

• the present invention relates to systems, methods, and devices for non- invasive measurement of analyte concentration in a subject.
• the present invention provides systems, methods, and devices for monitoring blood glucose levels through the use of electrical impedance tomography (EIT).
• EIT electrical impedance tomography
• Diabetes or diabetes mellitus, is a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia) (see, e.g., Tierney et al. (2002). Current medical Diagnosis & Treatment. International edition. New York: Lange Medical Books/McGraw-Hill, pp. 1203-1215, herein incorporated by reference in its entirety). Diabetes affects more that 250 million people worldwide and is the fourth leading cause of death in the United States.
• Diabetes refers to the group of diseases that lead to high blood glucose levels due to defects in either insulin secretion or insulin action (see, e.g., Rother, KI (2007) N Engl J Med 356 (15): 1499-1501; herein incorporated by reference in its entirety). Diabetes develops due to a diminished production of insulin (in type 1) or resistance to its effects (in type 2 and gestational) ( World Health Organisation Department of Noncommunicable Disease Surveillance (1999). Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications; herein incorporated by reference in its entirety).
• Both types of diabetes lead to hyperglycemia, which largely causes the acute signs of diabetes: excessive urine production, resulting compensatory thirst and increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism. All forms of diabetes have been treatable since insulin became medically available in 1921, but there is no cure.
• the injections by a syringe, insulin pump, or insulin pen deliver insulin, which is a basic treatment of type 1 diabetes.
• Type 2 is managed with a combination of dietary treatment, exercise, medications and insulin supplementation.
• frequent and accurate testing of blood glucose levels is essential to treatment. Control and outcomes of both types 1 and 2 diabetes may be improved by patients using home glucose meters to regularly measure their glucose levels (Gray et al.
• Glucose monitoring is both expensive (largely due to the cost of the consumable test strips) and requires significant commitment on the part of the patient. Regular blood testing is helpful to keep adequate control of glucose levels and to reduce the chance of long term side effects of the disease. The market for self testing products in 2006 was $6 billion worldwide and $3 billion in the United States.
• Current blood glucose testing methods involve drawing blood from a subject. Blood is commonly withdrawn from the finger of a subject. Blood in the finger is contained in veins, arteries and the capillaries. Lancing the finger using traditional blood glucose monitoring devices draws out blood from the capillaries. The blood sample is applied to a testing strip and analyzed by a blood glucose meter.
• Typical meters use changes in color/light or impedance to measure the blood glucose level.
• Blood draws for testing are painful to the subject and the repeated use of testing strips can be a significant cost. Testing the recommended six times per day can result in costs in excess of $1000 annually. Because of the need for blood to be drawn, testing usually must be done in private causing a significant social impact on diabetics. Improved devices and related methods are needed for measuring blood glucose levels. A correlation between impedance and blood glucose concentration has been demonstrated by impedance spectroscopy.
• the present invention provides systems, methods, kits, and devices for non-invasive measurement of analyte concentration (e.g., blood glucose concentration) in a subject through the use of electrical impedance tomography (EIT).
• EIT electrical impedance tomography
• the present invention provides a method of measuring analyte concentration in a region of interest in a subject comprising: a) measuring electrical impedance of a region of interest in a subject, and b) correlating the electrical impedance to an analyte concentration, wherein the electrical impedance is dependent on analyte concentration.
• measuring electrical impedance comprises: i) placing a plurality of electrodes around a body portion on the skin of the subject, ii) emitting an electrical current from an electrode, wherein the current is applied at a specific frequency, and iii) measuring the voltage resulting from the electrical current at a one or more electrodes.
• the present invention further provides: iv) repeating steps ii-iii, wherein a plurality of electrodes successively act as the emitting electrode. In some embodiments, the present invention further provides: v) repeating steps ii-iv, wherein voltages are applied at a range of frequencies.
• measuring electrical impedance comprises electrical impedance tomography.
• correlating electrical impedance to analyte concentration comprises correlating the change in electrical impedance with respect to emitted frequency to analyte concentration.
• the region of interest comprises the blood of a subject. In some embodiments the region of interest comprises interstitial fluid.
• the analyte comprises glucose. In some embodiments, the subject suffers from diabetes. In some embodiments, the electrical current comprises a current between 0.1 and 10 miliamperes.
• the present invention provides an electrical impedance tomography device.
• the devices are not limited to particular configurations.
• the devices comprise, for example, a series of electrodes, wherein the electrical impedance tomography device is configured to measure analyte concentration in a region of interest in a subject.
• the series of electrodes are configured in a ring or portion of a ring.
• the analyte comprises glucose.
• the region of interest comprises blood.
• the region of interest comprises interstitial fluid.
• the device is configured to fit around a body part of a subject.
• the body part of a subject comprises a finger.
• the series of electrodes are configured to emit and receive electrical current for the purposes of EIT.
• the device comprises a cylindrical body.
• the present invention further provides elements selected from the list of display element, processing element, power element, power switch, manual controls, memory element and electrical components.
• the device comprises a single unit. In some embodiments, the device comprises a plurality of units.
• the present invention provides methods for measuring analyte concentration in a region of interest in a subject comprising: a) measuring electrical impedance of a region of interest in a subject, wherein electrical impedance is measured at a range of frequencies, and b) correlating the change in electrical impedance with respect to frequency to analyte concentration.
• measuring electrical impedance comprises electrical impedance tomography.
• measuring electrical impedance of the region of interest comprises making a plurality of electrical impedance measurements from a plurality of electrodes.
• the plurality of electrical impedance measurements are combined to provide an electrical impedance map for the region of interest.
• the electrical impedance map is constructed for each frequency measured.
• the region of interest comprises the blood of said subject.
• the analyte comprises glucose.
• the subject suffers from diabetes.
• Figure 1 shows a schematic representing paths of current transmitted from one electrode and received by a plurality of other electrodes situated in a circle.
• Figure 2 shows a schematic of a portion of an exemplary device of the present invention.
• Figure 3 shows a schematic of a portion of an exemplary device of the present invention.
• Figure 4 shows a schematic of a portion of an exemplary device of the present invention.
• Figure 5 shows a flow chart delineating an exemplary method of use of the present invention to measure blood glucose in a subject.
• Figure 6 shows graph of impedance versus frequency for multiple blood glucose concentrations.
• *A* represents 100 mg/dL
• *B* represents 200 mg/dL
• *C* represents 4 th degree
• *D* represents 150 mg/dL.
• Figure 7 shows bar graphs of coefficients extracted from polynomials fit to impedance versus frequency curves for multiple blood glucose concentrations, wherein in each of the bar graphs the data is presented per variable in the following order: 100 mg/dL, 150 mg/dL, and 200 mg/dL.
• EIT is a medical imaging technique in which an image of the conductivity or permittivity of a part or parts of a body or body region is inferred from surface electrical measurements.
• electrical impedance tomography may be used to measure the concentration of an analyte in a subject.
• application of small alternating currents through conducting electrodes attached to the skin of a subject at a particular body region permits the measurement of electric potentials for the respective body region.
• the measured electric potentials can be used to obtain an image of the conductivity or permittivity of the respective body region, from which conductivity for the region of interest can extracted.
• the embodiments described herein overcome such invasive limitations, and provide non- invasive techniques for measuring analyte concentrations.
• the present invention provides systems, methods, kits, and devices for non-invasive measurement of analyte concentration (e.g., blood glucose concentration) in a subject through the use of electrical impedance tomography (EIT).
• EIT electrical impedance tomography
• the present invention provides systems, kits, methods and devices for measuring analyte concentration in a subject (e.g., a subject suffering from type 1 diabetes or type 2 diabetes) through application of electrical impedance tomography (EIT).
• a subject e.g., a subject suffering from type 1 diabetes or type 2 diabetes
• EIT electrical impedance tomography
• the present invention is not limited to measuring the concentration of a particular type of analyte. Indeed, the concentration of any type of analyte within a subject can be measured with the systems, kits, devices, and/or methods of the present invention.
• analytes include, but are not limited to, white blood cells, erythrocytes, red blood cells, hemoglobin, leukocytes, platelets, fibrinogen,thromboplastin prothrombin, myoglobin, antibodies (e.g., general antibodies, antitrypsin, tumor markers, antinuclear, antistreptolysin, antiviral (e.g., anti-human immunodeficiency virus), IgA, IgG, IgE, IgM, etc.), alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, ailirubin, blood gas (e.g., pH, p ⁇ 2 and pCO 2
• Analyte concentration may be measured within any type of tissue utilizing the systems, kits, methods, and/or devices of the present invention.
• tissue include, but are not limited to, connective tissue, muscle tissue, nervous tissue, or epithelial tissue.
• analyte concentration is measured in specialized connective tissues (e.g., blood, bone, or cartilage).
• analyte concentration is measured in blood.
• the systems, methods, and devices of the present invention are configured to measure glucose concentration in the blood (e.g., blood glucose level) of a subject (e.g., a subject suffering from type 1 diabetes or type 2 diabetes) through use of EIT.
• the systems, kits, methods, and devices are not limited to a measuring a particular concentration range of glucose concentration.
• the present invention is configured to measure blood glucose levels between 0 and 2000 milligrams of glucose per deciliter of blood (mg/dL).
• the present invention is configured to measure blood glucose levels between 1 and 1500 mg/dL.
• the present invention is configured to measure blood glucose levels between 2 and 1200 mg/dL.
• the present invention is configured to measure blood glucose levels between 5 and 1000 mg/dL. In some embodiments, the present invention is configured to measure blood glucose levels between 10 and 800 mg/dL. In some embodiments, the present invention is configured to measure blood glucose levels between 20 and 500 mg/dL. In some embodiments, the present invention is configured to measure blood glucose levels between 30 and 400 mg/dL. In some embodiments, the present invention is configured to measure biologically relevant blood glucose levels. In some embodiments, the systems, methods and devices of the present invention are configured to measure blood glucose concentration for purposes of monitoring a medical condition (e.g., monitor the blood glucose concentration of a person suffering from diabetes or a person requiring frequent blood glucose concentration measurement).
• a medical condition e.g., monitor the blood glucose concentration of a person suffering from diabetes or a person requiring frequent blood glucose concentration measurement.
• non-invasive analyte concentration measurement may be accomplished at a finger, thumb, wrist, arm, leg, toe, ankle, chest, torso, abdomen, head, etc.
• the site for noninvasive analyte concentration measurement is a digit (e.g., thumb, finger, toe, etc.).
• the site for non-invasive analyte concentration measurement is a finger.
• a suitable finger for use with the present invention is selected on a subject to subject basis (e.g., based on finger width and length).
• a device of the present invention partially or fully encloses around a body part which serves as the site for non-invasive analyte concentration measurement (e.g., digit).
• the device partially or fully encloses around a digit (e.g., finger, thumb, etc.) which provides a site for non-invasive analyte concentration measurement.
• the device e.g., a device having an electrode ring; described in more detail below
• the device may be positioned at any portion of the digit (e.g., the distal, intermediate, or proximal phalanx regions of the digit).
• the systems, methods, kits, and devices of the present invention may be used with any kind of subject, including, but not limited to, human beings, apes, dogs, cats, rats, mice, tigers, monkeys, cows, horses, etc (e.g., mammals).
• the subject is a human requiring monitoring of, for example, blood glucose levels.
• the subject is a human being suffering from diabetes (e.g., type 1 diabetes, type 2 diabetes).
• any body part(s) and/or body region may be used with the systems, methods and devices of the present invention (e.g., neck, ear, tongue, nose, arm, elbow, wrist, finger, waist, chest, hip, knee, leg, ankle, toe, foot, etc.).
• the systems, kits, methods, and devices of the present invention are not limited to particular uses. Indeed, the systems, kits, methods, and devices of the present invention are designed for use in any setting wherein a subject requires measurement of a particular analyte concentration. Such uses include any and all medical, veterinary, and research applications. In addition, the systems and devices of the present invention may be used in agricultural settings, manufacturing settings, mechanical settings, or any other application where measurement of a particular analyte concentration is required.
• the present invention is not limited to a particular manner of measuring analyte concentration in a subject with EIT.
• the present invention provides systems, kits, methods and devices configured to measure the concentration of an analyte in a subject with EIT in a non-invasive (e.g., no removal of body fluids, no breaking of skin) (e.g., painless, reduced pain) manner.
• the present invention is not limited to a particular non-invasive manner of measuring analyte concentration in a subject with EIT.
• the present invention provides a device configured to wrap around a body region (e.g., ankle, foot, toe, finger, wrist, arm, torso, etc.) and measure analyte concentration in a subject with EIT.
• the present invention is not limited to a particular type or kind of device configured to measure analyte concentration in a subject with EIT.
• the body of a device has a shape (e.g., ring, cylinder, arc, etc.) such that the device is able to fit around, or partially around, a particular body region (e.g., a finger, an ankle, a toe, a wrist, etc.).
• a particular body region e.g., a finger, an ankle, a toe, a wrist, etc.
• the body of the device is a hemi- spherical array.
• FIG. 2 demonstrate embodiments of a device of the present invention (e.g., a device configured to measure analyte concentration in a subject with EIT) having a ring shape.
• a device of the present invention e.g., a device configured to measure analyte concentration in a subject with EIT
• the present invention is not limited to these or any shapes or configurations.
• an exemplary device provides a body unit 100 which comprises a cylinder 110.
• the cylinder has an opening 150 at one or both ends.
• a mounting ring 140 Mounted on the mounting ring 140 are series of electrodes 120 and pressure transducers 130.
• the body unit 100 may by fully enclosed (SEE FIG. 2) or only partially enclosed (SEE FIG. 4).
• the devices are not limited to particular sizes. In some embodiments, the devices are sized to accommodate any desired body region or part (e.g., a finger of a subject).
• the device is not limited to a particular shape.
• the shape of the body unit is circular, cylindrical, conical, an arc, or ring-shaped.
• the device contacting the particular body region is a fixed hemi-circular or crescent shaped.
• the body of the device is shaped to fit a particular body region so as to permit the device to be wrapped around the respective body region (e.g., shaped to fit wrapping around a knee, an elbow, a neck, a finger, etc.).
• the device is not limited to a particular flexibility.
• the device is rigid and not flexible (e.g., the flexibility of a traditional ring).
• the device is flexible so as to permit the wrapping around of several different body regions (e.g., knee, neck, waist, toe, finger).
• a device of the present invention is made of any suitable material or materials for the production of medical devices.
• a device of the present invention comprises one or more metals, alloys, plastics, polymers, natural materials, synthetic materials, fabrics, etc.
• a device of the present invention comprises one or more metals including but not limited to aluminum, antimony, boron, cadmium, cesium, chromium, cobalt, copper, gold, iron, lead, lithium, manganese, mercury, molybdenum, nickel, platinum, palladium, rhodium, silver, tin, titanium, tungsten, vanadium, and zinc.
• metals including but not limited to aluminum, antimony, boron, cadmium, cesium, chromium, cobalt, copper, gold, iron, lead, lithium, manganese, mercury, molybdenum, nickel, platinum, palladium, rhodium, silver, tin, titanium, tungsten, vanadium, and zinc.
• a device of the present invention comprises one or more alloys including but not limited to alloys of aluminium (e.g., Al-Li, alumel, duralumin, magnox, zamak, etc.), alloys of iron (e.g., steel, stainless steel, surgical stainless steel, silicon steel, tool steel, cast iron, Spiegeleisen, etc.), alloys of cobalt (e.g., stellite, talonite, etc.), alloys of nickel (e.g., German silver, chromel, mu-metal, monel metal, nichrome, nicrosil, nisil, nitinol, etc.), alloys of copper (beryllium copper, billon, brass, bronze, phosphor bronze, constantan, cupronickel, bell metal, Devarda's alloy, gilding metal, nickel silver, nordic gold, prince's metal, tumbaga, etc.), alloys of silver (e.g., sterling silver, etc.), alloys of silver (
• a device of the present invention comprises one or more plastics including but not limited to Bakelite, neoprene, nylon, PVC, polystyrene, polyacrylonitrile, PVB, silicone, rubber, polyamide, synthetic rubber, vulcanized rubber, acrylic, polyethylene, polypropylene, polyethylene terephthalate, polytetrafluoroethylene, gore-tex, polycarbonate, etc.
• elements of a device of the present invention a device of the present invention may also comprise glass, textiles (e.g., from animal, plant, mineral, and/or synthetic sources), liquids, etc. The device is not limited to a particular size.
• a device of the present invention may be of any size suitable for enclosing or partially enclosing a body part (e.g., finger, hand, write, arm, toe foot, ankle, torso, leg, etc.) within the device.
• a body part e.g., finger, hand, write, arm, toe foot, ankle, torso, leg, etc.
• a cylinder, ring , circular body, or hemi- cirular body of a device of the present invention is of any suitable diameter (e.g., >0.1 inches (e.g., >0.2 inches, >0.3 inches, >0.4 inches, >0.5 inches, >0.6 inches, >0.7 inches, >0.8 inches, >0.9 inches, >1.0 inch, >1.1 inches (e.g., >1.2 inches, >1.3 inches, >1.4 inches, >1.5 inches, >1.6 inches, >1.7 inches, >1.8 inches, >1.9 inches, >2.0 inches, >2.1 inches (e.g., >2.2 inches, >2.3 inches, >2.4 inches, >2.5 inches, >2.6 inches, >2.7 inches, >2.8 inches, >2.9 inches, >3.0 inches), and/or ⁇ 100 inches (e.g., ⁇ 90 inches, ⁇ 75 inches, ⁇ 50 inches, ⁇ 25 inches, ⁇ 10 inches, ⁇ 5 inches, ⁇ 4 inches, ⁇ 3 inches, ⁇ 2 inches, ⁇ 1 inches).
• ⁇ 100 inches e.g., ⁇ 90
• a device is housed in a single unit. In some embodiments, a device is housed in multiple operably connected units. In some embodiments, the size of the device may be adjusted (e.g., through flexibility of the device) so as to accommodate various body regions (e.g., knee, neck, waist, ankle, finger). In some embodiments, the size of the device is static (e.g., non adjustabable). In some embodiments, devices are custom designed to accommodate a particular body region(s) and respective size of a subject (e.g., the finger of a subject requiring frequent blood glucose concentration measurement).
• an annular ring of electrodes is interchangeable within cylinders of the present invention allowing multiple diameter rings to be inserted into the cylinder and powered through the electrical contacts in the main device.
• interchangeablilty of electrode rings and cylinders allows different subjects (e.g., different age, size, species, etc.) and different body parts (e.g., fingers, thumb, arm, leg, chest, etc.) to be imaged with the same main unit.
• an electrode ring of the present invention comprises 4 to 64 electrodes (e.g., 4, 8, 16, 32, 64, etc.). In some embodiments, the number of electrodes per electrode ring is dependent on the size of the ring.
• the number of electrodes per electrode ring is dependent on the degree of precision and accuracy desired from measurements.
• electrodes reside in a fixed annular array.
• electrodes reside in a hemi-array around an arc (e.g., 90° arc...120° arc...150° arc...180° arc...210° arc...240° arc...270° arc, etc.).
• electrodes comprise any suitable material (e.g., metal (e.g., steel, copper, silver, gold, platinum), alloy, commonly used electrode material for biomedical applications, combinations thereof, etc.).
• a body of a device provides a cylinder or ring with a width of approximately 1 to 4 inches in diameter (e.g., 1 inch...1.25 inches...1.5 inches, 2 inches...3 inches...4 inches, and any diameters therein).
• a device provides a cylinder or ring with a length of approximately 0.5 to 5 inches (e.g. 0.5 inches, 1 inch , 2 inches...2.25 inches, 2.5 inches...3 inches...4inches, 5 inches, and any lengths therein).
• the device is not limited to a particular type of ring (electrode ring).
• the material composition of the ring is a metal (e.g., steel, aluminum, gold, copper, iron, platinum, zinc, alloy, silver, etc.), a plastic (e.g., polystyrene, polyvinyl chloride, nylon, polyamide, rubber, synthetic rubber, acrylic, polyethylene) derivatives thereof, string, elastic, and combinations thereof.
• the ring is not limited to particular shape.
• the shape of the ring is such that it is able to wrap around a desired body region (e.g., a finger) (e.g., so as to provide the device a ring shape).
• the ring is configured such that it has thereon a series of electrodes.
• Devices are not limited to a particular number of electrodes positioned thereon (e.g., 1 electrode, 2 electrodes, 3 electrodes, 4 electrodes, 5 electrodes, 6 electrodes, 7 electrodes, 8 electrodes, 9 electrodes, 10 electrodes, 20 electrodes, 25 electrodes, 40 electrodes, 50 electrodes, 75 electrodes, 100 electrodes, 1000 electrodes, 10,000 or more electrodes, etc.).
• the devices have thereon a sufficient number of electrodes such that the devices are able to measure the concentration of an analyte (e.g., blood glucose concentration) in a body region (e.g., finger) of a subject (e.g., a subject suffering from type 1 or type 2 diabetes).
• an analyte e.g., blood glucose concentration
• a user cleans the area on the body to be imaged prior to imaging (e.g., soap and water, alcohol swipe, etc.).
• the electrodes positioned along a device are not limited to a particular function.
• one or more of the electrodes are configured to emit or apply an alternating current or voltage to the body region (e.g., finger) for which it is in contact.
• one or more of the electrodes are configured to measure voltage in the body region (e.g., finger) for which it is in contact.
• one or more of the electrodes are configured to emit or apply an alternating current and to measure voltage in the body region (e.g., finger) for which it is in contact.
• the electrodes positioned along the devices are not limited to emit or apply a particular amount of alternating current to the body region (e.g., finger) for which it is in contact.
• the current applied or emitted by electrodes positioned along the device is not greater than 100 milliamperes (mA) (e.g., ⁇ 100 mA, ⁇ 90 mA, ⁇ 80 mA, ⁇ 70 mA, ⁇ 60 mA, ⁇ 50 mA, ⁇ 40 mA, ⁇ 30 mA, ⁇ 20 mA, ⁇ 10 mA, ⁇ 9 mA, ⁇ 8 mA, ⁇ 7 mA, ⁇ 6 mA, ⁇ 5 mA, ⁇ 4 mA, ⁇ 3 mA, ⁇ 2 mA, ⁇ 1 mA, etc.).
• mA milliamperes
• the current applied or emitted by electrodes positioned along the device is greater than 0.01 mA (e.g., >0.01 mA, >0.05 mA, >0.1 mA, >0.2 mA, >0.3 mA, >0.4 mA, >0.5 mA, >0.6 mA, >0.6 mA, >0.8 mA, >0.9 mA, >1 mA, >2 mA, >3 mA, >4 mA, >5 mA, >6 mA, >7 mA, >8 mA, >9 mA, >10 mA, etc.).
• 0.01 mA e.g., >0.01 mA, >0.05 mA, >0.1 mA, >0.2 mA, >0.3 mA, >0.4 mA, >0.5 mA, >0.6 mA, >0.6 mA, >0.8 mA, >0.9 mA, >1 mA, >2 mA, >3
• the current applied or emitted by electrodes positioned along the device is between 0.1 and 10 mA (e.g., >0.5 and ⁇ 2 mA, >0.6 and ⁇ 1.5 mA, >0.7 and ⁇ 1.3 mA, >0.8 and ⁇ 1.2 mA, >0.9 and ⁇ 1.1 mA, etc.).
• the voltage measured by one or more electrodes positioned along the device is proportional to the amperage of the current emitted by one or more electrodes positioned along the device (e.g., a greater amperage emitted results in a greater voltage measured). In some embodiments, the voltage measured by one or more electrodes positioned along the device is proportional to the resistance of the tissues or tissues that the current traveled through (e.g., greater resistance of tissues results in lower voltage measured). Table 1 contains a list of exemplary resistivities for various tissues.
• Table 1 The calculated mean values and 95% confidence intervals of resistivities for various tissues, as well as the number of resistivities involved m the calculations, the number of primary sources and the water content.
• the electrodes positioned along the device are configured to deliver alternating current to the body region (e.g., finger) at a defined amperage (e.g., 0.1 mA...0.9 mA... l mA... l.l mA...10 mA, etc.).
• the present invention is not limited to delivery of alternating current at a particular defined amperage.
• the amperage is such that it permits measurement of the concentration of an analyte (e.g., blood glucose concentration) in a body region (e.g., finger) of a subject (e.g., a subject suffering from type 1 or type 2 diabetes).
• the alternating current emitted into the body region at a defined amperage travels through one or more tissues (e.g., bone, skin, blood, etc.).
• tissues e.g., bone, skin, blood, etc.
• alternating current emitted from one or more electrodes travels through skin, bone, blood blood vessels, and/or other tissues.
• the alternating current emitted into the body region of a subject at a defined amperage is detected by one or more electrodes positioned along the device and the respective voltage measured.
• the alternating current emitted by one of more electrodes positioned along the device is used to calculate the resistance, permittivity, and/or conductivity of the tissue or tissues along the path between the respective electrodes (e.g., the path between the electrode that emitted the alternating current at a defined amperage, and the electrode that measured the resulting voltage) (SEE FIG. 1).
• the path electricity will travel between the electrodes is known or can be calculated.
• alternating current at defined amperage is emitted by a plurality of electrodes in succession, the current received at a plurality of electrodes and the voltages measured, and the resistance or permittivity of the tissue or tissues along the different paths through the body region determined.
• the resistance or permittivity along the different paths through the body region are compiled to calculate a resistance/permittivity map of the body region.
• the determined resistivity or permittivity is used to identify the concentration of an analyte (e.g., blood glucose concentration).
• concentration of an analyte e.g., blood glucose concentration.
• the present invention is not limited to a particular technique for utilizing determined resistivity or permittivity for purposes of identifying the concentration of an analyte.
• the present invention provides pressure transducers. In some embodiments, the present invention provides pressure transducers between electrodes. In some embodiments, pressure measurement is used to ensure proper contact between the electrodes and the body of interest. In some embodiments, the pressure measurements are used to measure pulse. In some embodiments, pressure transducers and/or other elements help stabilize the body region of interest (e.g., finger). In some embodiments, a thermistor is placed between two or more of the electrodes to measure the surface temperature of the body of interest. In some embodiments, a device of the present invention provides one or more accessory elements. The present invention is not limited to particular types or kinds of accessory elements.
• accessory elements of the present invention may comprise display (e.g., LCD, etc.), power switch, manual controls, power source (e.g., battery, AC adapter, etc.), electrical components (e.g., electrical circuits, logic components, etc.), microprocessor, memory, processor, etc.
• accessory elements are contained within a single housing separate from the body of the device (e.g., separate from the measurement cylinder). The devices are not limited to a particular location of attachment for the one or more accessory elements.
• one or more accessory elements are attached to the body portion of the device (e.g., cylinder portion, ring portion, etc.) (SEE FIGS. 2-4).
• accessory elements are contained within the body of the device.
• accessory components are contained within multiple housing elements.
• the devices utilize processors.
• the devices are not limited to particular types of processors.
• the devices are not limited to particular uses for the processors.
• the devices utilize processors that monitor and/or control and/or provide feedback concerning measured analyte concentrations (e.g., blood glucose concentration).
• a processor directs some or all of the measurement functions of a device.
• a processor is involved in all of some of pressure transducer operation, electrode operation, protocol selection, data storage, data analysis, memory access, data display, etc.
• a processor is configured to characterize a measured analyte concentration value as within or outside of an established normal analyte concentration value.
• the processor characterizes a measured analyte concentration value (e.g., obtained from a device of the present invention) through comparing the measured analyte concentration value with a database of information (e.g., standardized information (e.g., standardized analyte concentration levels)) for purposes of, for example, identifying analyte concentration levels that are within or outside of standardized (e.g., normal) levels.
• a database of information e.g., standardized information (e.g., standardized analyte concentration levels)
• the device compares measured analyte concentration values taken at different times (e.g., day-to-day comparison, time-of-day comparison, changes over time, etc.).
• an individual e.g., the user of a ring device (e.g., patient, doctor, health care professional)
• a particular course of action e.g., a course of medical treatment, a course of daily activity, a dietary plan
• a particular course of action e.g., a course of medical treatment, a course of daily activity, a dietary plan
• a processor is provided within a computer module or central processing unit (CPU).
• the computer module may also comprise software that is used by the processor to carry out one or more of its functions.
• the present invention provides software for regulating the frequency of how often a particular analyte concentration is measured, which particular analyte concentration is measured, different measurement protocols, analysis protocols, etc.
• the software is configured to provide information (e.g., monitoring information) in real time.
• the processor is configured for the creation of a database of information (e.g., measured analyte concentrations over a period of time for a subject, standardized analyte concentration levels).
• computer memory and “computer memory device” refer to any storage media readable by a computer processor.
• Examples of computer memory include, but are not limited to, random access memory (RAM), read-only memory (ROM), computer chips, optical discs (e.g., compact discs (CDs), digital video discs (DVDs), etc.), magnetic disks (e.g., hard disk drives (HDDs), floppy disks, ZIP.RTM. disks, etc.), magnetic tape, and solid state storage devices (e.g., memory cards, "flash” media, etc.).
• computer readable medium refers to any device or system for storing and providing information (e.g., data and instructions) to a computer processor.
• Examples of computer readable media include, but are not limited to, optical discs, magnetic disks, magnetic tape, solid-state media, and servers for streaming media over networks.
• processor and “central processing unit” or “CPU” are used interchangeably and refer to a device that is able to read a program from a computer memory device (e.g., ROM or other computer memory) and perform a set of steps according to the program.
• a computer memory device e.g., ROM or other computer memory
• the devices are configured to present and/or display information.
• the devices are not limited to a particular manner of presenting and/or displaying information.
• the devices have therein a display region configured to display information.
• the devices are not limited to displaying particular information.
• the information is the actual measured analyte concentration value (e.g., blood glucose concentration).
• the information pertains to the characterized measured analyte concentration value (e.g., within a normal range, outside a normal range, degree of change over a course of time, etc.).
• the devices are not limited to a particular manner of displaying information within the display region.
• the information is displayed audibly (e.g., the measured concentration value is announced) (e.g., various sounds (e.g., alarms) specific for types of information).
• the information is displayed visually (e.g., with a display screen or printer component).
• a device provides a LCD screen for displaying device information (e.g., battery power, current setting, impedance images, current measurements, recently measured analyte concentrations, measurement history, current activity, stored analyte concentrations, etc.).
• the device communicates with a processor.
• the device is not limited to a particular type of communication with the processor.
• the communication involves transferring and receiving information (e.g., the processor receiving information from the device) (e.g., the device receiving information from the processor).
• the device and processor are not limited to a particular type of information.
• the information is a measured impedance concentration values.
• the information is a measured analyte concentration value (e.g., a blood glucose concentration).
• the device and the processor are interconnected.
• the device and the processor are separated and the communication is wireless.
• the present invention provides a memory element configured to store data (e.g., images, impedance values, analyte concentrations, averages concentrations, etc.).
• the devices are not limited to a particular type or kind or storage capacity for the memory element.
• the present invention provides a processor which operates in conjunction and in communication with the memory element (e.g., a processor configured to analyze data, operate the device, perform calculations, etc.).
• the devices of the present invention are not limited to a particular type or kind of energy consumption.
• a device of the present invention provides an energy module (e.g., battery module, AC power module, DC power module, etc.).
• the device provides an element for AC power from an outlet (e.g., 120V/220V outlet).
• a device of the present invention is used in AC mode when it is used for continuous analyte (e.g., blood glucose) monitoring (e.g., in a hospital setting, at a bedside, etc.).
• a device provides a battery module.
• a battery module provides sufficient power to a device of the present invention.
• a battery module provides sufficient energy to power all of the functionalities of a device of the present invention.
• a battery module provides sufficient energy to power at least the elements required for the basic functionalities of a device of the present invention.
• the devices are configured to create digital signals.
• the devices are not limited to a particular manner of creating a digital signal.
• the present invention provides a programmable logic chip to create a digital signal of a certain frequency spectrum.
• a digital signal is distributed to pairs of electrodes around the electrode ring.
• a digital to analog converter (DAC) creates a current or voltage at the frequency specified by the logic chip.
• the signal is sent through a demultiplexer to the appropriate pair of drive electrodes.
• voltages are measured at the receiving pairs of electrodes and sent to a multiplexer to be sent to main CPU for image reconstruction (e.g., as described herein).
• a device of the present invention comprises additional electrical (e.g., circuits, wiring, etc.), computational (e.g., chips, processors, printer, etc.) and functional (e.g., cuff, stabilization elements, mounting elements, etc.) elements not listed above. Additional elements and accessories are contemplated and should be considered within the scope of the present invention.
• the systems, kits, methods, and devices of the present invention are not limited to particular uses. Indeed, the systems, kits, methods, and devices of the present invention are designed for use in any setting wherein a subject requires measurement of a particular analyte concentration. As such, the present invention provides systems, methods, kits, and devices for non-invasive measurement of analyte concentration (e.g., blood glucose concentration) in a subject through the use of electrical impedance tomography (EIT).
• EIT electrical impedance tomography
• the present invention provides systems, methods, kits, and devices for non-invasive measurement of analyte concentration (e.g., blood glucose concentration) in a subject through the use of electrical impedance tomography (EIT).
• a device of the present invention provides periodic, non- continuous analyte (e.g., blood glucose) monitoring.
• a device of the present invention provides rapidly repeated analyte concentration measurements.
• devices of the present invention provide continuous analyte concentration measurement.
• the present invention provides repeated analyte (e.g., blood glucose) monitoring.
• a subject e.g., a human diagnosed with type 1 diabetes or type 2 diabetes
• a body part e.g., digit (e.g., finger or thumb)
• a user places a body part (e.g., digit) through a cylindrical channel in the device.
• a user places a body part into, across, over, adjacent to and/or through a measurement portion of a device.
• a user's body part e.g., digit
• pressure is applied by the device to a pre-determined pressure level.
• the devices have pressure transducers configured to apply pressure to a pre-determined pressure level.
• the devices are configured to notify a user that is properly fitted (e.g., a user holds a body part (e.g., digit) within the device and awaits confirmation that the pressure transducers are at a proper pre-determined pressure level (e.g., through a display region)).
• inability to achieve a proper pressure level results in, for example, in operation of the device and/or notification (e.g., notification through a display region).
• the device upon proper fitting of the device (e.g., appropriate pressure measurement through the pressure transducers), the device will commence taking measurements.
• the measurements include measuring the pulse of the subject.
• data acquisition e.g., impedance measurement
• the proper level of pressure applied by the device ensures stable and even electrode contact with the body part of the subject.
• the present invention provides devices for measurement of voltages at one or more electrodes (or electrode pairs) positioned along a device for purposes of measuring analyte concentration.
• the devices are not limited to a particular manner of measuring voltages at one or more electrodes (or electrode pairs) positioned along a device.
• an electric current is produced by one or more electrodes (or electrode pairs) emitting alternating current at defined amperage.
• the electric current travels a path through a subject and is received by one or more other electrodes.
• the electric current travels a path through the subject which is well understood or can be calculated by one of skill in the art (SEE FIG. 1).
• the voltage received by the one or more other electrodes is recorded.
• data regarding amperage and frequency emitted from the emitter electrode (or electrode pair) and voltage received by the receiver electrodes is stored in a memory element or used by the processor for calculations.
• the process of emitting alternating current at a defined amperage by one electrode (or electrode pair), and receiving/recording the resultant voltage at one or more other electrodes (or electrode pairs) is repeated.
• the process of emitting alternating current at a defined amperage by one electrode (or electrode pair), and receiving/recording the resultant voltage at one or more other electrodes (or electrode pairs) is repeated at the same frequency using a different electrode (or electrode pair) as the emitter.
• the process is repeated at the same frequency for each electrode (or electrode pair) of the device to function as the emitter electrode with the other electrodes receiving/recording the resultant voltages.
• a device provides separate emitter and receiver electrodes.
• electrodes function as both emitter and receiver electrodes.
• the process of emitting current from each electrode (or electrode pair) and receiving the current at the other electrodes is repeated at one or more other frequencies (e.g., a range of frequencies).
• data regarding amperage and frequency emitted from the emitter electrode (or electrode pair) and voltage received by the receiver electrodes is stored in a memory element or used by the processor for calculations.
• the measured voltages provide data for constructing an impedance, resistance or permittivity map of the tissues within the region of the body being examined (e.g., finger).
• an impedance, conductance and/or permittivity map is calculated based on the impedance data collected at a single frequency.
• the current emitted, voltages recorded, and paths traveled by the current are combined to create a map (e.g., impedance map, permittivity map, resistance map, etc.) of the body region undergoing EIT.
• a map created by the data acquired results in a 2D or 3D image of the region.
• a finite element model is used as a basis (e.g., reference) for creating a permittivity map (e.g., image).
• a finite element model is used as a reference for calculating an impedance, conductance or permittivity map.
• a reference dataset is created a priori using a homogeneous impedance phantom with known impedance values.
• a 2D or 3D mesh is created from a priori information about common bone structure in the body part to be imaged.
• a theoretical 2D or 3D mesh is created to represent the region of the body of a subject.
• the 2D or 3D mesh comprises a series of nodes.
• the nodes are converted to impedance values based on voltage data and literature values (e.g., resistivity, permittivity, impedance, etc.).
• conversion of the nodes on a two-dimensional or three-dimensional mesh to impedance values creates an image of the region of interest.
• software is used to create a two-dimensional mesh, three-dimensional mesh, convert the nodes of the mesh to impedance values, and/or create an image of the region of interest (e.g., EIDORS (Electrical Impedance and Diffuse Optical Reconstruction Software)).
• EIDORS Electrode Impedance and Diffuse Optical Reconstruction Software
• the present invention uses finite element method (FEM) in creation of an impedance image, two-dimensional mesh, three-dimensional mesh, cross-section, and/or map.
• FEM finite element method
• the present invention provides a two-dimensional cross-sectional image of the region of interest.
• the present invention provides a three-dimensional image of the region of interest.
• the present invention creates an image of the region of interest using the emitted current and received voltage data at a single frequency.
• the present invention creates separate images for each frequency for which data is acquired.
• the current applied to one electrode (or electrode pair) is measured as voltage simultaneously (or near simultaneously) at each remaining electrode (or electrode pair).
• current is applied through one adjacent pair of drive electrodes and measured at the remaining adjacent pairs.
• the drive pair of electrodes are switched until each pair of adjacent electrodes in the ring had are utilized as the current applying electrodes.
• the frequency of the current applied ranges from 1 MHz to 500 MHz (e.g. 1 MHz...2 MHz...5 MHz...10 MHz...20 MHz...50 MHz...100 MHz...200MHz...500 MHz, etc.).
• the frequency of the current applied is within the beta dispersion range of cells.
• the process of emitting current from each electrode (or electrode pair) and receiving the current at the other electrodes is repeated at one or more other frequencies (e.g., a range of frequencies).
• data is collected at a plurality of frequencies.
• a data set is collected for each individual frequency.
• an impedance, conductance or permittivity map is created for each collected frequency.
• a FEM is used as the reference (or basis) for calculating the map at the first frequency.
• maps for subsequent frequencies are created using prior maps as references (e.g., the map of the second frequency uses map of the first frequency as a basis).
• map quality increases as more data sets are collected and more impedance, conductance or permittivity maps can be used as references.
• the process of collecting datasets at a plurality of frequencies and creating EIT images (e.g., permittivity maps) for each dataset is repeated until the all desired frequencies have been collected and analyzed.
• current applied by the present invention is steady-state or alternating, DC or AC.
• the impedance, conductance, or resistivity of some tissues and analytes change as a function of the alternating frequency applied.
• a current is supplied to a drive pair of electrodes and the voltage recorded at another pair or pairs.
• the devices of the present invention are used to create an electrical impedance map for a body region (e.g., finger) for purposes of measuring the concentration of an analyte (e.g., blood glucose levels).
• a theoretical two-dimensional mesh is created to represent the body region of the subject.
• the two-dimensional mesh comprises a series of nodes.
• the nodes are converted to impedance values based on voltage data and literature resistivity values.
• conversion of the nodes on a two-dimensional mesh to impedance values creates an image of the region of interest.
• the recordings are reconstructed using filtered back projection.
• the image reconstruction is reconstructed using the Finite Element Method (FEM).
• FEM Finite Element Method
• the image is reconstructed using reconstruction algorithms that maximize low impedance values in the range of blood and minimizes high impedance values like bone.
• the reconstruction algorithm maximizes values near the periphery of the 2D circle or 3D cylinder and minimizes values near the center.
• the images are reconstructed using iterative reconstruction techniques.
• the images are reconstructed using non-linear techniques.
• the device creates a 2D or 3D EIT image.
• a 2D or 3D EIT image is used to measure the impedance of veins, arteries and capillaries (e.g., automatically measured).
• the image of the first frequency is used as a reference for the reconstruction algorithms of succeeding images.
• tissues which are not of interest are excluded (or segmented out) from one or more of the permittivity maps (e.g., EIT images). Exclusion (or segmenting out) of regions not of interest facilitates construction of impedance, conductance or permittivity maps for regions of interest within a measurement zone without regions of non-interest.
• tissues which are not of interest e.g., skin and bone
• the well- known impedance of body tissues are used to automatically segment out regions of non-interest from the image.
• the outer skin layer is automatically removed from any images to reduce uncertainty or errors caused by skin conditions (e.g., dirt, sweat, oil, hair, etc.).
• a CPU segments out region and tissues that are not of interest in the analysis (e.g., bone and skin).
• tissue that are not of interest in the analysis
• automated analysis can be performed. Based on published literature, many different impedance values for various tissues are known at different frequencies. For example, bone has a permittivity that is 2-3 orders of magnitude higher than blood or skin. Skin has a permittivity that is twice as high as blood.
• regions of interest are selected where desired.
• regions of interest are selected around veins, arteries, capillaries, etc.
• exclusion and inclusion of regions of tissue occurs automatically based on an algorithm.
• a 2D or 3D EIT image is a digital set of values that correlates permittivity to known spatial locations.
• a 2D or 3D image of a body part is obtained.
• segmenting occurs automatically.
• CPU determines regions of interest (e.g., blood vessels, arteries and capillaries).
• regions of interest may be 2D or 3D.
• an algorithm that digitally removes or ignores specific sets of values is utilized to select out tissues that are not of interest (e.g., skin and bone) from regions of interest.
• known thickness, location, and permittivity values can be exploited to digitally remove or accept regions within selected spatial or permittivity values.
• known thickness, location, and permittivity values of skin can be exploited so an algorithm can further digitally remove or ignore values that are within a certain spatial margin around the object being imaged and/or above a known threshold.
• the original 2D or 3D image is reduced in size leaving only certain digital values that are of interest (e.g., blood vessels, etc.).
• the present invention provides conductance or permittivity measurements within a given tissue (e.g., blood) which is affected by changes in the concentration of a given analyte (e.g., glucose) in that tissue. In some embodiments, detection of these changes permits measurement of the concentration of the analyte (e.g., glucose) causing such changes.
• Calculated permittivity can be converted into impedance values for tissues and regions within a measurement zone, and analyte concentration (e.g., glucose concentration) for a given tissue or region (e.g., blood) can be determined based on the impedance value for that region.
• analyte concentration e.g., glucose concentration
• an automatic region of interest is created by searching (e.g., automated search, manual search, computational search, etc.) for shapes of interest (e.g., circular shapes, shapes resembling blood vessels, etc.) within the 2D/3D image that have impedance values within the known range of a tissue of interest (e.g., blood).
• shapes of interest comprise arteries or veins containing a strong signal for blood analyte (e.g., glucose) concentrations.
• a large percentage of the selected values represent the digitally derived permittivity values of the blood in the object being imaged.
• the excluded or segmented-out values are not considered in further calculations and analysis.
• the selected values of the region of interest are averaged.
• the selected values for each individual data set e.g., frequency
• are averaged to provide an average value for each data set e.g., average permittivity, average impedance, etc.
• an average impedance is calculated for the region of interest at each frequency (e.g., average impedance over the region of interest at: 100 MHz, 150 MHz, 200 MHz, etc.).
• averaging the selected values provides a Figure of Merit (FOM).
• FOM Figure of Merit
• a data collection, data selection, and data averaging procedure is repeated for impedance values at different frequencies (e.g., frequencies in the 1 MHz to 300 Mhz range).
• impedance values for the blood vessels (e.g., veins, arteries, capillaries, etc.) of a subject are used to infer blood analyte concentration (e.g., glucose level).
• impedance values for the interstitial fluid of the finger are used to infer blood analyte concentration.
• changes in blood glucose levels of a subject affect the electrical impedance of blood vessels in a predictable manner.
• changes in the analyte concentration results in changes in blood vessel electrical impedance.
• the change in impedance as a function of frequency correlates to the analyte concentration in the region or interest.
• the impedance values over a frequency spectrum are used to create a curve of impedance versus frequency.
• the shapes of these curves are used to determine blood analyte concentration.
• the phase shift values over a frequency spectrum are used to create a curve of phase shift versus frequency.
• the shapes of phase and impedance curves are used to determine blood analyte concentration.
• a plot of impedance versus frequency is obtained (SEE FIG. 6). In some embodiments, a plot of phase versus frequency is obtained.
• a plot of phase shift versus frequency is obtained.
• 2D graphs of average impedance values in regions of interest versus frequency are constructed.
• 2D graphs of phase shift versus frequency are constructed for regions of interest.
• multi-order (e.g., third order, fourth order, fifth order, sixth order, seventh order, etc.) polynomials are fit to curves impedance and/or phase versus frequency.
• characteristics of impedance versus frequency graphs correlate to analyte concentration (e.g., blood glucose levels).
• characteristics of phase versus frequency graphs correlate to analyte concentration (e.g., blood glucose levels).
• coefficients of multi-ordered curve fitted polynomials describe the shape of the curve.
• curve fitting procedures, programs, and/or algorithms are well known to those in the art.
• coefficients of multi-ordered curve fitted polynomials, maximum and minimum values, and axis intercepts of impedance and phase are extracted from curve fit polynomials.
• the coefficients are a mathematical description of the impedance vs. frequency curve.
• the curve shape is dependent on analyte levels.
• coefficients of multi-ordered curve fitted polynomials, maximum and minimum values, and axis intercepts of impedance and phase are used to determine analyte (e.g., blood glucose) levels.
• analyte e.g., blood glucose
• coefficients extracted from polynomials fit to impedance data correlate to analyte concentration (SEE FIG. 7). In some embodiments, coefficients extracted from polynomials fit to impedance versus frequency plots correlate to analyte concentration. In some embodiments, coefficients extracted from polynomials fit to impedance versus frequency plots are compared to coefficients for known analyte concentrations (e.g., standard values for a population, measured values for an individual, etc.). In some embodiments, coefficients extracted from polynomials fit to impedance data provide a precise and accurate measure of analyte concentration.
• analyte e.g., blood glucose
• analyte concentration is displayed on a display (e.g., LCD screen) to the user in suitable units (e.g., mg/dL).
• suitable units e.g., mg/dL
• analyte concentration is stored in memory.
• stored analyte concentrations can be accessed by a user or analysis algorithms (e.g., to monitor analyte levels over time, to compare measurements taken at different times of day, to perform further analysis, etc.)
• a device is configured to monitor analyte concentrations over a course of time (e.g., continuous, every 20 seconds, every minute, every five minutes, every 20 minutes, every hour, every 6 hours, every 12 hours, every day, every week, every month, etc.).
• Example 1 Exemplary Method of Use
• a device of the present invention is used to measure the blood glucose level of a subject suffering from diabetes.
• This example is intended to provide an exemplary embodiment of the present invention and should not be viewed as limiting in any facet.
• Other uses, methods, devices, and systems of the present invention, not described in the following example, are contemplated.
• a device which is appropriately sized, in both length and diameter, to fit around the finger of the subject.
• the properly sized device fits snuggly but comfortably, and places the electrode ring over a central portion of the finger of the subject.
• the subject turns the device on using a switch on the control unit.
• the subject, or user may select automated data collection, a preset data collection protocol, or design a personalized protocol using the control interface and display. Once a protocol has been selected, the subject places a finger into the opening of the device and through the cylindrical channel within the device. The subject's finger extends into the device placing the electrode ring around the subject's finger.
• the pressure transducers measure the level of contact between the ring of electrodes and the finger, making sure the electrodes are within a certain strength of contact to ensure a more accurate measurement.
• a signal from the device alerts the user that the finger is properly positioned and that data collection will commence.
• Current at a preselected frequency is applied through one adjacent pair of drive electrodes and measured at the remaining adjacent pairs, according the selected data collection protocol. This process is repeated with successive pairs of electrodes until data has been collected from each pair.
• Data is collected from each electrode pair at frequencies varying from 1 to 200 MHz. Maximum and minimum frequencies used are based on the blood cell characteristics in the beta dispersion range.
• a 2D impedance image is calculated from the data set collected at the first frequency, using a finite element model as a reference basis.
• the image of the first frequency is used as a reference for the reconstruction algorithms of succeeding frequency images.
• An image is constructed for each measured frequency using previously calculated images as reference.
• 2D and 3D images are constructed by applying impedance measurements to an a priori constructed mesh. Regions of skin and bone are automatically computationally segmented out of the images based on knowledge of their location and expected high impedance values. Blood vessels are automatically computationally selected as regions of interest based on expected range of impedance values and known shapes. Average impedance values are calculated over the regions of interest providing a mean impedance value for each frequency measured. Curves of impedance values versus frequency and phase shift versus frequency are computationally constructed.
• Curves of impedance and phase are curve fit, and coefficients of multi-ordered polynomials are extracted.
• the values of the extracted coefficients are compared to known values for given blood glucose levels.
• the device displays the measured value.
• the device stores the measured blood glucose level in its memory.
• a variety of analyses tools within the device CPU access the most recent stored blood glucose value and compare the value to previous measured values and standard values.
• the user accesses comparisons to previous values, average values, comparisons to standard values, daily blood glucose trends, long-term blood glucose trend, short term changes, long term change, and other statistical analysis on the device.
• the user makes decisions about his/her health regimen (e.g., insulin, diet, exercise, etc.) based on the measure blood glucose level and subsequent analysis.
• his/her health regimen e.g., insulin, diet, exercise, etc.
• Impedance measurements were made on the wrist of a subject, under significantly difference blood glucose conditions, using impedance spectroscopy (see, e.g., Caduff et al. Biosensors and Bioelectronics 19 (2003) 209-217., herein incorporated by reference in its entirety.).
• the measured impedance values were graphed versus the frequency at which the measurements were obtained for blood glucose concentrations of 100 mg/dL and 200 mg/dL (SEE FIG. 6).
• Impedance values for 150 mg/dL were estimated based on the average of the measured values.
• Fourth, fifth, and sixth order polynomials were fit to the curves of the data, and the corresponding coefficients were extracted.
• Each coefficient, as well as the Y- intercept, varies in a predictable manner with respect to blood glucose concentration (SEE FIG. 7).
• the pattern of polynomial values is used to determine the blood glucose values from the measured impedance values. For example, for a 6 th order polynomial fit, the second order coefficient decreases as blood glucose levels increase (SEE FIG. 7C). For a 6 th order polynomial fit the first order coefficient increases as blood glucose levels increase.
• the values of coefficients fit to measured impedance values are compared to coefficient values for known blood glucose concentrations in order to determine blood glucose levels based on impedance measured by EIT.

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