WO2001088521A1 - Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression - Google Patents

Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression

Info

Publication number
WO2001088521A1
WO2001088521A1 PCT/US2001/040749 US0140749W WO0188521A1 WO 2001088521 A1 WO2001088521 A1 WO 2001088521A1 US 0140749 W US0140749 W US 0140749W WO 0188521 A1 WO0188521 A1 WO 0188521A1
Authority
WO
WIPO (PCT)
Prior art keywords
assemblage
electrodes
body part
hematocrit
electrode
Prior art date
Application number
PCT/US2001/040749
Other languages
English (en)
Inventor
Robert Gail Billings
Justin S. Clark
Jon Neese
Original Assignee
Microcor, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/571,459 external-priority patent/US6766191B1/en
Application filed by Microcor, Inc. filed Critical Microcor, Inc.
Priority to AU2001261847A priority Critical patent/AU2001261847A1/en
Publication of WO2001088521A1 publication Critical patent/WO2001088521A1/fr

Links

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
    • A61B5/0535—Impedance plethysmography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0295—Measuring blood flow using plethysmography, i.e. measuring the variations in the volume of a body part as modified by the circulation of blood therethrough, e.g. impedance plethysmography
    • 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
    • A61B5/14535—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 haematocrit
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6825—Hand
    • A61B5/6826—Finger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683—Means for maintaining contact with the body
    • A61B5/6838—Clamps or clips

Definitions

  • TECHNICAL FIELD This invention relates generally to devices and methods for noninvasive in vivo measurement of blood hematocrit and, more specifically, to devices and methods for such measurement that use impedance and pressure plethysmography.
  • hematocrit of blood, which is defined as the percentage of whole blood volume occupied by erythrocytes (i.e., red blood cells), is an important measure of patient well being in cases of trauma, blood loss by disease, iron depletion in pregnancy, dietary iron deficiency, and a number of more specific medical conditions.
  • Hematocrit has traditionally been measured by centrifuging a column of blood, which has been extracted from the patient, in a glass tube, until the erythrocytes are compacted by centrifugal force to one end of the tube.
  • the hematocrit is determined by measuring the length of the tube containing dark red material and dividing by the total length of the liquid column in the tube. These length observations are usually made visually, but are also made, in some cases, by automated optical means of various designs.
  • centrifugal hematocrit determinations hematocrit is also derived and reported by various automated blood analyzers which count erythrocytes optically in unpacked blood. This erythrocyte count correlates with packed cell hematocrit and the derived hematocrit is reported.
  • Hematocrit has been successfully determined by measuring the impedance of blood that has been extracted from the patient and placed in an impedance measuring cell of controlled dimensions, where a fixed volume of the blood is contained, maintained at a known temperature, and agitated to maintain uniform cell distribution. Examples of such successful measurements are given by Okada and Schwan in "An Electrical Method to Determine Hematocrits," IRE Transactions in Medical Electronics, ME-7: 188-192 (1960) and by deNries et al.
  • U.S. Patent 5,526,808 (hereinafter "the '808 Patent”), issued to Kaminsky and assigned to Microcor, Inc., the assignee of the present invention, describes another impedance method for measuring hematocrit noninvasively and in vivo. This method draws upon the observation that hematocrit determines the frequency vs. impedance profile of blood.
  • the method of the '808 Patent uses the pulsatile change of impedance in a finger or other limb of the body that occurs when each heartbeat pushes new blood into the organ where the measurement is made to separate the non-blood tissue impedance from the blood impedance.
  • the mathematical model upon which this method is based relies upon the assumption that, as blood pulses into a finger or other body part where the hematocrit measurement is being made, the admittance (i.e., the reciprocal of impedance) change that occurs is due to the increased volume of blood providing a new current path in parallel with the old current path present before the pulse occurs.
  • the difference in admittance between baseline, when no new blood is in the limb, and during the pulse, when new arterial blood has entered the limb is due to the new blood.
  • the numerical value of this admittance difference is proportional to the volume of the new blood times the admittance of the new blood.
  • the admittance vs. frequency characteristics of blood have a characteristic shape that depends upon hematocrit. Comparing the shapes of either the magnitude or the phase versus the frequency of the admittance, derived for the pulsed blood, against known characteristic hematocrit-dependent shapes gives a measure of hematocrit.
  • the known characteristic shapes can be derived from a database obtained from patients having hematocrits independently measured by the centrifugal method previously described.
  • U.S. Patent 5,642,734 (hereinafter "the '734 Patent"), issued to Ruben et al. and assigned to Microcor, Inc., the assignee of the present invention, describes some additional methods to obtain in vivo hematocrit results.
  • the '734 Patent describes using pressurized cuffs, in various ways, to change the amount of blood in the organ (e.g., the finger) at which hematocrit is noninvasively measured.
  • the '734 Patent describes a unique electronic system for driving electrodes attached to the body part under measurement and for deriving phase, as well as amplitude information from impedance measurements of the body part.
  • the '734 Patent teaches the use of a neural network computer algorithm to relate measured impedance and other data to hematocrit based upon matching a database obtained from a number of prior measurements of patients with separately-determined hematocrits.
  • U.S. Patent 5,111,817 (hereinafter "the '817 Patent"), issued to Clark et al., observes that the accurate measurement of blood oxygen saturation levels in arteries (S a O 2 ) in a body part under measurement, such as a finger, is typically hindered by different blood oxygen saturation levels in capillaries (S c O 2 ) in the body part.
  • the '817 Patent teaches a method for correcting measurements of S a O 2 for the effects of S c O 2 .
  • a pressure cuff applies a pressure to the body part under measurement that is equal to the mean arterial blood pressure in the body part.
  • the present invention includes apparatus configured for use in the noninvasive measurement of the hematocrit of a patient.
  • Apparatus incorporating teachings of the present invention include two or more pairs of electrodes.
  • a pressurization component may also be associated with the apparatus of the present invention.
  • a first embodiment of electrodes incorporating teachings of the present invention includes four individual electrodes that are paired in inner and outer sets. The electrodes may be substantially L-shaped.
  • a first member of each electrode is configured to contact and to be at least partially wrapped around a body part at which hematocrit is to be noninvasively measured.
  • a second member of each electrode is configured to communicate with external electrical componentry that will either apply a voltage to the body part or measure impedance at the body part, as will be described hereinafter in greater detail.
  • one or more of the electrodes may be substantially linear, with a first end thereof configured to be at least partially wrapped around a body part and a second end thereof configured to be connected to external electronic componentry.
  • a second embodiment of electrodes useful in apparatus of the present invention has two elements, each including a pliable substrate and two electrodes, an electrode of an outer set and an electrode of an inner set.
  • the pliable substrate preferably conforms to the shape of the body part at which hematocrit is to be noninvasively measured and may be include a substantially planar member or be configured to at least partially receive the body part (e.g., an open- or close-ended tube configured to at least partially receive a finger).
  • the electrodes may be substantially L-shaped and include a first member and a second member. At least a portion of the first member of each electrode is secured to and carried by the pliable substrate.
  • the first member of each electrode is also at least partially wrapped around the body part.
  • one or more of the electrodes may be substantially linear, with a first end thereof configured to be at least partially wrapped around a body part and a second end thereof configured to be connected to external electronic componentry.
  • a third embodiment of electrodes includes a single, pliable substrate that at least partially carries four electrodes arranged relative to the substrate in inner and outer sets.
  • the pliable substrate preferably conforms to the shape of the body part at which hematocrit is to be noninvasively measured and may be include a substantially planar member or be configured to at least partially receive the body part (e.g., as an open- ended or close-ended tube configured to at least partially receive a finger).
  • the electrodes may be L-shaped, as described previously herein with respect to the first and second electrode embodiments, or substantially linear, and are configured to communicate with external electronic componentry.
  • Apparatus incorporating teachings of the present invention also include a pressurization component configured to apply a predetermined amount of pressure to the body part at which hematocrit is to be noninvasively measured.
  • a first embodiment of the pressurization component includes a pliable bladder configured to be at least partially wrapped around the body part, over the inner and outer pairs of electrodes, so as to apply increased pressure to the body part as pressure within the bladder is increased (e.g., with air or another fluid).
  • a pliable substrate upon which portions of the electrodes are carried comprises a pliable bladder. Accordingly, at least a portion of at least one electrode of each of the inner and outer electrode pairs may be secured to or otherwise carried by the pliable bladder. Prior to introducing pressure into the pliable bladder, the bladder may be substantially planar or configured to at least partially receive the body part at which hematocrit is to be noninvasively measured (e.g., as an open- ended or close-ended tube configured to at least partially receive a finger).
  • pliable bladder embodiments of the pressurization component are configured to be connected to a source of pressure. As the pliable bladder is pressurized (e.g., by air pressure or pressure of another fluid), pressure is applied to at least a portion of the body part.
  • these pliable bladders may line a receptacle formed in a rigid member and configured to at least partially receive the body part.
  • inner and outer pairs of electrodes are placed in contact with and at least partially wrapped around a body part at which hematocrit will be measured.
  • the body part is at least partially inserted into a pressure chamber, which is in fluid communication with a source of positive pressure. Portions of one or both electrodes of the inner and outer pairs of electrodes in contact with the body part may also be inserted into the pressure chamber.
  • a pressure chamber which is in fluid communication with a source of positive pressure.
  • Portions of one or both electrodes of the inner and outer pairs of electrodes in contact with the body part may also be inserted into the pressure chamber.
  • an at least partial seal is formed around the body part. Accordingly, as a positive pressure forms within the pressure chamber, pressure will be applied to the body part.
  • a system for noninvasively measuring the hematocrit of blood perfusing a living body part in accordance with teachings of the present invention includes a non-invasive hematocrit measurement apparatus and external electronic componentry associated therewith.
  • the electronic componentry of the system includes circuitry that drives first and second alternating currents of different frequencies (e.g., 100 KHz and 10 MHz) between separate points on the body part. The alternating currents may be applied to the body part through input electrodes attached to the body part at the separate points.
  • additional circuitry monitors first and second signals (e.g., voltage waveforms) induced in the body part by the first and second currents (e.g., by monitoring output electrodes attached to the body part), and other circuitry generates first and second pulsatile signals and first and second baseline signals from the first and second induced signals. Determining circuitry then calculates the hematocrit of the blood from the first and second pulsatile signals and the first and second baseline signals. This calculation may be performed, for example, by determining the hematocrit (H) from the following equation:
  • ⁇ Nolt H and ⁇ Nolt L are the first and second pulsatile signals
  • N H and N L are the first and second baseline signals.
  • a system for measuring the hematocrit of blood perfusing a living body part includes electrodes positioned on the surface of the body part.
  • a measuring device measures the electrical impedance at one or more frequencies between the electrodes.
  • a chamber is positioned to surround the body part between the electrodes, and a measuring apparatus measures pulsatile blood volume by the pulsatile-related change in internal pressure within the chamber.
  • a calculating device e.g., a programmed microprocessor determines the blood hematocrit from the measurements of impedance and pulsatile blood volume. The device may determine the hematocrit H in accordance with the following equations:
  • ⁇ N is the change in pulsatile blood volume at any point in time
  • ⁇ Z is the change of impedance at the same point in time
  • L is a constant which will be described below
  • Z 0 is the baseline impedance at the beginning of each pulse.
  • the system for determining blood hematocrit includes circuitry that produces a current signal including a first, relatively low frequency portion and a second, relatively high frequency portion, and the hematocrit measuring apparatus, which stimulates a living body part containing blood with the current signal. Also, additional circuitry of the hematocrit measuring apparatus is used to sense voltages at the first and second frequencies induced in the body part by the stimulation thereof, and further circuitry detects signal envelopes of the sensed voltages, with each signal envelope having a pulsatile component and a baseline component.
  • Isolation circuitry isolates the pulsatile components and baseline components of the detected signal envelopes, and extraction circuitry extracts one or more sets of time-matched segments of the isolated pulsatile components and one or more sets of time-matched segments of the isolated baseline components. Further, other circuitry effectively correlates the blood hematocrit to the product of the ratio of the time-matched segments of the pulsatile components and the inverse ratio of the squares of the time-matched segments of the baseline components.
  • Another embodiment of the system includes an apparatus for determining the hematocrit of blood perfusing a living body part from relatively low frequency pulsatile and baseline signals induced in the body part, and from relatively high frequency pulsatile and baseline signals also induced in the body part, includes circuitry that effectively determines the ratio of the product of the relatively high frequency pulsatile signal and the square of the relatively low frequency baseline signal to the product of the relatively low frequency pulsatile signal and the square of the relatively high frequency baseline signal.
  • the apparatus also includes circuitry that correlates the blood hematocrit to the effectively determined ratio.
  • Other embodiments of the invention include methods of measuring the hematocrit of blood perfusing a living body part, and a method of determining blood hematocrit, that generally correspond to the systems and apparatus described above.
  • FIG. 1 is a top view of a substantially linear electrode useful in apparatus according to the present invention
  • FIG. 1A is a variation of the substantially linear electrode shown in FIG. 1;
  • FIG. 2 is a top view of a variation of the electrode shown in FIG. 1, wherein the electrode is configured with an L-shape;
  • FIG. 3 is a perspective view depicting four of the electrodes shown in FIG. 2 partially wrapped around a finger of a patient;
  • FIG. 4 is a top view of an embodiment of an element of an apparatus incorporating teachings of the present invention that includes two of the electrodes shown in FIG. 2 being carried by a substantially planar substrate;
  • FIG. 5 is a perspective view depicting two of the elements depicted in FIG. 4 secured to an finger of a patient;
  • FIG. 6 is a top view of another embodiment of apparatus according to the invention, including four of the electrodes shown in FIG. 1 secured to a substantially planar, pliable substrate;
  • FIG 7 is a perspective view illustrating the apparatus of FIG. 6 secured to a finger of a patient and electrically connected to external electronic componentry by way of an exemplary connector;
  • FIG. 8 is a perspective view illustrating four of the electrodes shown in FIG. 2 secured to a finger of a patient with a bladder embodiment of a separate pressurization component secured around the electrodes to the finger;
  • FIG. 9 is a top view of an embodiment of an apparatus of the present invention that includes four of the electrodes shown in FIG. 1 carried on a surface of a substantially planar pliable bladder;
  • FIG. 10 is a perspective view of the assembly of the apparatus shown in FIG. 9 and an electrical connector therefor;
  • FIG. 11 is a perspective view illustrating, wrapped around a finger of a patient, an element of yet another embodiment of an apparatus that includes a substantially planar bladder member with two of the electrodes shown in FIG. 1 secured to the surface thereof, as well as the element of FIG. 4 wrapped around an adjacent portion of the finger;
  • FIG. 12 is a perspective view of yet another embodiment of apparatus including electrodes shown in FIG. 1 carried on an inner surface of a tubular bladder configured to at least partially receive a finger;
  • FIG. 13 is a perspective view of a rigid member including a receptacle at least partially lined by the apparatus shown in FIG. 9;
  • FIG. 14 is a perspective view of another embodiment of a pressurization component of the present invention, including a close-ended pressure chamber configured to receive a finger of a patient;
  • FIG. 15 is a perspective view of still another embodiment of a pressurization component incorporating teachings of the present invention, including a pressure chamber with two open ends, through which a portion of a finger of a patient extends, and depicting a finger and the portions of four of the electrodes shown in FIG. 2 in contact therewith inside the pressure chamber;
  • FIG. 16 is a perspective view illustrating the pressure chamber of FIG. 15 being disposed around a finger of a patient and around portions of two electrodes of the type shown in FIG. 1 that contact the finger, as well as the element of FIG. 4 being wrapped around an adjacent portion of the finger;
  • FIG. 17 is a block diagram of a hematocrit measurement system in accordance with this invention.
  • FIG. 18 is a block diagram of another hematocrit measurement system in accordance with this invention.
  • FIG. 19 is a diagram of a calibration system of the hematocrit measurement system of FIG. 18.
  • FIG. 1 illustrates a first embodiment of an electrode 10 that is useful in effecting the method of the present invention.
  • Electrode 10 is formed from a conductive material, such as a thin metal or metal-lined sheet, and includes a first end 12 and an opposite, second end 14.
  • First end 12 is configured to contact and, preferably, to be at least partially wrapped around a body part, such as a finger, at which hematocrit is to be measured in accordance with teachings of the present invention.
  • Second end 14 is configured to be connected to external electronic componentry (not shown) that effects the hematocrit measurement.
  • First end 12 may include a retention component 17 thereon, depicted as being quantity of pressure sensitive adhesive, so as to hold electrode 10 in contact with or around a body part.
  • the pressure sensitive adhesive of retention component 17 is preferably an electrically conductive adhesive that secures electrode 10 directly to the body part.
  • exemplary conductive adhesives include that sold under the trade name HYDROGEL ® from a number of suppliers, such as Avery Dennison, Specialty Tape Division, of Painesville, Ohio, and that sold as AQUATRIXTM II by Hydromer, Inc. of Somerville, New Jersey.
  • adhesive retention component 17 is illustrated as covering substantially all of electrode 10, an adhesive retention component 17 may alternatively cover a much smaller region of electrode 10 that will adequately secure electrode 10 into contact with the body part.
  • the adhesive of retention component 17 may be disposed between electrode 10 and the body part, or retention component may be configured and located to adhere to another portion of electrode 10 and to secure the same at least partially around the body part.
  • Electrode 10' includes a retention component 17', in this case a sleeve, located between a first end 12' and a second end 14' of electrode 10'.
  • retention component 27' is configured to receive and retain first end 12 of electrode 10' as first end 12' is looped around a body part at which hematocrit is to be measured. By pulling second end 12' taught through retention component 27', electrode 10' may be snugly secured to the body part.
  • Electrode 20 is substantially L-shaped and includes a first member 22 and a second member 24. Electrode 20 is formed from a conductive material, such as a thin metal sheet or a metal-lined sheet. First member 22 of electrode 20 is configured to contact and, preferably, to be at least partially wrapped around a body part, such as a finger, at which hematocrit is to be measured in accordance with the method of the present invention.
  • FIG. 2 illustrates electrode 20 as including an exemplary retention component 27, which, as illustrated, includes a receptacle 28 at the junction between first member 22 and second member 24.
  • Receptacle 28 is configured to receive an end portion 29 of first member 22 as first member 22 is looped around a body part at which hematocrit is to be measured.
  • end portion 29 is configured with a series of retaining regions 29a, adjacent regions having therebetween constricted regions 29b of lesser widths.
  • Retaining regions 29a are wider than the width of receptacle 28, while the widths of constricted regions 29b are about the same or less than the width of receptacle 28.
  • a retaining region 29a that has been pulled through receptacle 28 secures end portion 29 within receptacle 28 to interconnect receptacle 28 and end portion 29. In this manner, receptacle 28 and end portion 29 interlock to securing first member 22 in place around a body part.
  • Second member 24 of electrode 20 is configured to be connected to external electronic equipment that effects the method of the present invention.
  • electrodes 10 or 20 may be formed from a deformable material that substantially sets upon deformation so as to retain a portion of electrode 10, 20 in contact with and secure that portion of electrode 10, 20 to the body part at which hematocrit is to be measured.
  • FIG. 3 shows first members 22 of four electrodes 20 in contact with and being wrapped around a body part, in this case a finger 1, at which hematocrit is to be measured in accordance with teachings of the present invention.
  • electrodes 20 are arranged in outer and inner sets 21O and 211, respectively, with electrodes 20 of inner set 211 spaced apart from one another and electrodes 20 of outer set 21O positioned adjacent and outside of electrodes 20 of inner set 211.
  • the adjacent electrodes 20 of inner set 211 and outer set 21O are spaced more closely to one another than electrodes 20 of inner set 211.
  • FIG. 4 depicts an assembly 30 including two electrodes 20 that are partially carried upon a pliable substrate 32.
  • pliable substrate 32 supports first members 22 of electrodes 20.
  • Exemplary materials from which pliable substrate 32 may be fabricated include, without limitation, fabrics, polymers, and other flexible materials.
  • pliable substrate 32 also includes a retention component 27, in this case a quantity of adhesive material, between first members 22.
  • Adhesive material 27 is preferably a pressure sensitive adhesive that will maintain contact between first members 22 and the body part at which hematocrit is to be measured, as well as to maintain the positions of first members 22 relative to the body part.
  • assemblies 30 are positioned upon a body part, in this case a finger 1, with first members 22 of electrodes 20 contacting the body part. As depicted, assemblies 30 are spaced a greater distance apart from one another than are electrodes 20 of each assembly 30.
  • FIG. 6 Another embodiment of an electrode assembly 40 that is useful in carrying out the method of the present invention is shown in FIG. 6.
  • Assembly 40 includes a pliable substrate 42, similar to that depicted in FIG. 4 and described with reference thereto, and four electrodes 10 carried thereby.
  • electrodes 10 are oriented upon pliable substrate 42 in substantially mutually parallel relation.
  • Assemblies with electrodes 10 that are not oriented parallel to one another are, however, also within the scope of the present invention.
  • Electrodes 10 are arranged in an inner set 111 and an outer set 11O.
  • Electrodes 10 of inner set 1 II are positioned adjacent one another and electrodes 10 of outer set 110 are positioned outside of electrodes 10 of inner set 111, with electrodes 10 of inner set 1 II being spaced apart a greater distance than each electrode 10 of inner set 111 and the adjacent electrode 10 of outer set 110.
  • Second ends 14 of electrodes 10 are preferably configured to couple with an electrical connector of a known type, such as connector 44 depicted in FIG. 7.
  • FIG. 7 illustrates the manner in which assembly 40 is used in determining the hematocrit of a patient.
  • Assembly 40 is positioned relative to a body part of a patient, such as finger 1, with first ends 12 of electrodes 10 (see FIG. 6) in contact with the body part. As shown, first ends 12 of electrodes 10 are at least partially wrapped around finger 1. Second ends 14 of electrodes 10 extend beyond an outer periphery of pliable substrate 42 and are coupled with corresponding terminals of an electrical connector 44, which communicates with external electronic components (not shown) that are used to effect the method of the present invention.
  • An apparatus may also include a pressurization device, such as an inflatable bladder 50 illustrated in FIG. 8.
  • Inflatable bladder 50 may be of any type known in the art, such as an infant blood pressure cuff, which may be secured around a body part, such as a finger, at which hematocrit is to be measured by known means, such as complementary hook and loop type fasteners.
  • bladder 50 is separate from electrodes 20, which are wrapped around a finger 1 in substantially the same manner as that depicted in and described with reference to FIG. 3.
  • Bladder 50 is at least partially wrapped around a body part at which hematocrit is to be measured, such as finger 1, so as to apply pressure thereto in order to facilitate the hematocrit measurement.
  • Bladder 50 may be positioned relative to the body part so as to apply pressure between the innermost pair 611' of electrodes.
  • bladder 50 or another pressurization component abuts or at least partially overlaps each electrode of innermost pair 611' so as to apply pressure to an entire portion of the body part located between innermost pair 611'.
  • Bladder 50 communicates with an external pressure source 54 as known in the art, such as by use of a conduit 52, such as a tube.
  • a conduit 52 such as a tube.
  • air or another fluid may be supplied to bladder 50 from external pressure source 54 by way of conduit 52.
  • FIG. 8 depicts bladder 50 as being wrapped around finger 1 and all four electrodes 20 thereon, bladder 50 may be positioned elsewhere on finger 1 or another body part, such as between electrodes 20 of inner set 211 or over two adjacent electrodes 20.
  • FIG. 9 illustrates another embodiment of an assembly 60 that may be used to measure hematocrit in accordance with teachings of the present invention.
  • Apparatus 60 includes a pliable substrate 40, which comprises a bladder 50' that may be pressurized.
  • Bladder 50' includes a port 51 to facilitate connection to an external pressure source, such as external pressure source 54 depicted in FIG. 8.
  • an external pressure source such as external pressure source 54 depicted in FIG. 8.
  • Apparatus 60 also includes four electrodes 10 carried upon a surface of bladder 50'. As depicted, apparatus 60 includes four electrodes 10 that are arranged in mutually parallel relation to one another.
  • Electrodes 10 are arranged in two sets, including an inner set 1 II and an outer set 110. Electrodes, 10 of inner set 1 II are spaced apart from one another, while electrodes 10 of outer set 11O are positioned outside of electrodes 10 of inner set 111, adjacent thereto, and spaced apart therefrom a lesser distance than electrodes 10 of inner set 111 are spaced apart from one another.
  • second end 14 of each electrode 10 includes a terminal end 15 that extends beyond an outer periphery of bladder 50' so as to facilitate electrical connection of electrodes 10 and assembly 60 to external electronic componentry (not shown) that effects the method of the present invention.
  • terminal ends 15 may at least partially wraparound a peripheral edge of bladder 50'.
  • FIG. 10 illustrates connection of assembly 60 to an electrical connector 70 of a type known in the art.
  • Electrical connector 70 includes terminals 72 that correspond to terminal ends 15 of electrodes 10 to connect electrodes 10 with the appropriate external electronic componentry (not shown).
  • FIG. 11 illustrates an assembly 60', which is a variation of apparatus 60, that includes two electrodes 10, as well as an electrical connector 70' configured to connect assembly 60' to external electronic componentry (not shown) that facilitates the determination of a patient's hematocrit in accordance with teachings of the present invention.
  • two additional electrodes such as electrodes 20 of assembly 30 must also be brought into contact with a body part, such as finger 1, at which hematocrit is to be measured.
  • the outermost electrode 20 of assembly 30 and the outermost electrode 10 of assembly 60' comprise an outer set 61O', while the innermost electrode 20 of assembly 30 and the adjacent electrode 10 of assembly 60' comprise an inner electrode set 611' to facilitate the measurement of hematocrit in accordance with teachings of the present invention.
  • the pliable substrate of assembly 60' is an inflatable bladder 50' that includes a port 51 ' through which bladder 50' may be pressurized and depressurized.
  • FIG. 12 illustrates yet another embodiment of an assembly 60" for measuring hematocrit in accordance with the method of the present invention.
  • Assembly 60" includes an inflatable bladder 50" having a tubular shape.
  • Bladder 50" includes a receptacle 56 configured to at least partially receive a body part, such as a finger, at which hematocrit is to be measured.
  • First ends 12 of electrodes 10 are at least partially carried upon an inner surface 57 of bladder 50" and exposed to receptacle 56.
  • first ends 12 of electrodes 10 contact the body part.
  • Second ends 14 of electrodes 10 are exposed at and may extend beyond an outer surface 58 of bladder 50" so as to facilitate connection of assembly 60" to external electronic componentry that effects the method of the present invention.
  • Bladder 50" also includes a port 51 " that facilitates pressurization and depressurization of bladder 50".
  • Apparatus 80 configured to position electrodes 10 in contact with a body part at which hematocrit is to be measured and to apply pressure to the body part in accordance with teachings of the present invention is illustrated in FIG. 13.
  • Apparatus 80 includes a rigid member 82, which may be formed from, for example, a polymer, that includes a receptacle 84 configured to at least partially receive a body part at which hematocrit is to be measured.
  • receptacle 84 Disposed within receptacle 84 is an assembly 60, such as that illustrated in and described with reference to FIG. 9.
  • Assembly 60 is disposed within receptacle 84 such that upon at least partial insertion of a body part, such as a finger, within receptacle 84, first ends 12 of all four electrodes 10 of assembly 60 contact the body part.
  • bladder 50' of assembly 60 also contacts the body pressure in a manner that will allow for the application of pressure of the body part upon pressurization of bladder 50' through port 51 ".
  • Terminal ends 15 of electrodes 10 communicate with electrical connectors 18 of a known type that are held within rigid member 82 and that facilitate connection of electrodes 10 to external electronic componentry (not shown) to effect a determination of hematocrit in accordance with the present invention.
  • FIG. 14 illustrates a pressurization chamber 90 that may be used to effect a hematocrit determination in accordance with the present invention.
  • pressurization chamber 90 includes a generally cylindrical, hollow, rigid member 91, a flexible, pliable member 95 therein, and a receptacle 94 within pliable member 95.
  • Receptacle 94 is configured to at least partially receive a body part, such as finger 1, at which hematocrit is to be determined.
  • the body part may be inserted into receptacle 94 through a first end 92 of pressurization chamber 90.
  • Pressurization chamber 90 also includes pressurization port 96 through which a pressurization bladder 97, formed by pliable member 95 and rigid member 91, may be either positively or negatively pressurized. As air or gas is introduced into pressurization bladder 97, pliable member 95 expands into receptacle 94, decreasing the volume thereof.
  • pressurization port 96 is configured to be coupled with a pressurization conduit 98, such as a tube, that communicates with an external pressure source 54. While FIG. 14 illustrates a finger 1 with first ends 22 of each of four electrodes 20 wrapped at least partially therearound disposed within receptacle 94, a portion of finger 1 or another body part with fewer than four electrodes 20 contacting same may be disposed within receptacle 94.
  • Pressurization chamber 90' includes a generally cylindrical, hollow, rigid member 91', and a flexible, pliable member 95' within rigid member 91 '. Pliable member 95' forms a receptacle 94' within pressurization chamber 90'. A pressurization bladder 97' is formed between rigid member 91 ' and 95'. Pressurization chamber 90' also includes two opposed, open ends 92' and 93'. Ends 92' and 93 ' are both continuous with a receptacle 94' of pressurization chamber 90'.
  • Pressurization chamber 90' communicates with an external pressure source 54 by way of a conduit 98 connected to a pressurization port 96' of pressurization chamber 90'.
  • Pressurization bladder 97' may be pressurized by introducing air, gas, or another pressurization medium therein through pressurization port 96'.
  • pliable member 95' is forced toward receptacle 94', decreasing the volume of receptacle 94'.
  • pliable member 95' is forced onto a finger 1 or other body part disposed within receptacle 94' and applies pressure thereto. As illustrated in FIG.
  • pressurization chamber 90' is configured to partially receive finger 1, with a base 3 of finger 1 extending through end 92' and a tip 2 of finger 1 extending through end 93 '.
  • FIG. 15 also shows that first ends 22 of all of four electrodes 20 that are wrapped around finger 1 are located within chamber 94'.
  • FIG. 15 depicts all four electrodes 20 contacting finger 1 as being disposed at least partially within chamber 94', as shown in FIG. 16, finger 1 or another body part at which hematocrit is to be measured may be positioned within a receptacle 94" of a pressurization chamber 90" such that fewer than four electrodes 10 are located within chamber 94".
  • electrodes 10 extend through rigid member 91 " and pliable member 95" of pressurization chamber 90".
  • FIG. 17 An embodiment of the present invention is shown in FIG. 17.
  • the pulsatile impedance and pulsatile pressure are measured in a chamber surrounding a patient's finger.
  • a finger has been chosen as an exemplary body part to illustrate this embodiment, it is important to note that other body parts may be used.
  • FIG. 17 illustrates some specific components, any assemblage of electrodes, pressurization apparatus, and other devices that incorporate teachings of the present invention may be used in the system to effect the hematocrit determination method of the invention.
  • An array of electrodes 10 is placed on a finger 1 with the outer electrodes 10O separated as widely as possible and the inner electrodes 101 each separated by approximately 5.0 mm from the closest of outer electrodes 10O and separated from each other by a distance as far as possible but necessarily limited by the length of finger 1.
  • the outer electrodes 10O are driven by an alternating current generator 5 which may be set to deliver a constant current at a frequency in the approximate range of 10 kHz to 200 kHz.
  • the optimum frequency for this system likely lies in the previously-mentioned range to achieve the goals of maximum current with no discernible neuromuscular stimulation and low phase difference between the current and voltage applied to the electrodes. While test results on an early prototype of this invention indicate that 100 kHz is appropriate for achieving satisfactory results, it is possible that another frequency may result in a more practical implementation.
  • the inner electrodes 101 are connected to the input of a high impedance voltage amplifier 6 which senses the voltage between these electrodes. Both the current generator 5 and the amplifier 6 are connected to a computing system 7, which combines these electrical signals with other signals from the pressure sensing apparatus (described below) to compute and display hematocrit.
  • the computing system 7 also has the purpose of controlling the automated operation of the measurement apparatus. The details of the computing system 7 are not depicted in FIG. 17 or in the description of this invention because any of a number of configurations, including, but not limited to, an appropriately programmed PC-type computer with an analog-to-digital converter and an output port control interface, or a dedicated monitor, will suffice for performance of this function.
  • a sealed pressure chamber 8 surrounds the finger with air tight, pressure- withstanding seals at its distal and proximal. These seals are located over, or in very close proximity to, the inner electrodes 101.
  • the first purpose of this chamber 8 is to contain the air in the closed volume of the chamber around the finger so that small pulse pressure rises occur in the chamber 8 when blood from the arterial system of the patient's circulation is pulsed into the finger.
  • the second purpose of this chamber 8 is to contain an externally applied bias pressure which causes blood vessels in the part of the finger that is enclosed by the chamber 8 to partially collapse. This partial collapse of the vessels results in greater blood flow into the finger on each cardiac pulse.
  • the larger blood flow pulses created as a result of the bias pressure, cause greater pressure pulses to occur within the chamber and greater voltage pulses to occur between the inner impedance sensing electrodes 101.
  • the electrodes 10 may be integral with the chamber 8, or may be separate from the chamber 8 and applied to the finger independently of its insertion into the chamber.
  • a pressure transducer 9 is pneumatically connected to the pressure chamber 8 and electrically connected to the computing system 7 for sensing the bias pressure and the pulse pressure from which blood volume on each pulse is computed, and for transmitting signals representative of pressure to the computing system 7.
  • Also connected pneumatically to the pressure chamber 8 is a bias pressure source 54 with a solenoid valve 55 controlled by the computing system 7.
  • This valve 55 allows enough flow from the bias pressure source 54 to achieve the desired bias pressure, then shuts off to lock the bias pressure in.
  • the pressure source 54 may be of any configuration having the ability to supply air at a pressure as high as approximately 200 mmHg above the ambient atmospheric pressure.
  • the level of pressure supplied may optionally be controlled by the computing system 7.
  • a calibration device 57 which can inject a precisely known volume of air into the chamber 8 to calibrate the pressure change that represents a given volume.
  • This calibration device 57 may be as simple as a small calibrated medical syringe, as shown in FIG. 17, which can be manually operated, or it can be a more complex device, controlled by the computing system 7, capable of producing precise volume pulses of close to the same magnitude as the cardiac pulses for dynamic calibration.
  • ⁇ V is the change in blood volume at any point in time
  • ⁇ Z is the change of impedance at the same point in time
  • p is the resistivity of the blood
  • L is the distance between the impedance sensing inner electrodes 101
  • Z 0 is the baseline impedance at the beginning of each pulse.
  • H percent hematocrit
  • ⁇ V blood volume change
  • the accuracy of both the impedance and direct volume measurements can be improved by producing larger arterial pulses in the finger.
  • the imposition of a bias pressure m the chamber 8, having a magnitude above a substantial fraction of the systolic blood pressure at the finger, and preferably having a magnitude equal to the mean arterial blood pressure in the finger, has been shown experimentally to increase the pulse volume by as much as a factor often.
  • the increase in pulse volume achieved by this means increases the accuracy of the hematocrit measurement by improving the signal-to-noise ratios on both the impedance and pressure channels going to the computing system 7. More importantly, the arterial component of the pulse volume becomes greater with respect to pulsatile volume changes in other vessels in the finger (such as the capillaries), which makes the derived hematocrit more nearly a true value.
  • p L is the resistivity of blood at the lower of the two frequencies
  • p H is the resistivity of the blood at the higher of the two frequencies
  • Z L is the baseline impedance for the low frequency
  • Z H is the baseline impedance for the high frequency
  • ⁇ Z H is the change in impedance at a point in time for the high frequency
  • ⁇ Z L is the change in impedance at a corresponding point in time for the low frequency.
  • equation (5) offers the distinct advantage of canceling the geometric factors ⁇ V and L.
  • the hematocrit H can be adequately represented as a function of (p L /p ⁇ )*
  • the measurement of (P I /P H ) -fr° m equation (5) can be represented in terms of measurable voltages and currents by:
  • ⁇ Volt, Volt, and I represent measurable pulse voltages, baseline voltages, and currents, respectively.
  • equation (6) can be simplified to:
  • p p is the resistivity of plasma
  • f is a form factor (determined by Geddes and Sadler to be 1.75 for human red blood cells when their orientation is random).
  • the effect of frequency on blood resistivity is explained by noting that the red blood cell membrane behaves as an insulator at low frequencies, causing p L to be predictably higher with increasing hematocrit H.
  • the red blood cell membrane reactance is virtually eliminated, which causes the intracellular fluid to participate fully in the blood impedance measurement. This reduces the p H sensitivity to hematocrit H.
  • x is the red blood cell to plasma conductivity ratio
  • Waveform generators 100 for both lOOKHz and lOMHz frequencies are laboratory instruments, although of course these signals would typically be generated by internal oscillators in a hematocrit measurement instrument to be used in the field.
  • An exemplary host computer 102 is a fully equipped IBM-compatible system running general-purpose laboratory data processing software, custom configured for the computations required for these studies. In the field, the host computer 102 would typically comprise a dedicated processor with dedicated software or firmware.
  • the computer 102 is equipped with a multi-channel analog-to-digital converter 104 for monitoring the physiological signals of a patient.
  • a finger 106 or, alternatively, a calibration resistor string (for experimental purposes) is driven by a constant amplitude current source 108 at both the low and high frequencies.
  • the mixed voltage is picked up by the inner electrode pair (see FIG. 17), amplified by a sensing amplifier 110, then separated by a complementary pair 112 of low-pass and high-pass filters into two signals.
  • the separated signals at both frequencies are then rectified with rectifiers 114 to provide DC signals at the baseline levels with the pulses superimposed on these DC levels.
  • the pulses are then separated from the baseline voltages by subtracting a low-pass filtered signal from the pulse-containing signal using pulse separators 116.
  • factor C is an instrumentation calibration factor.
  • the primes on the voltage parameters represent voltage measurements as opposed to true voltages existing at the measurement site.
  • C which includes the fixed current ratio I H /I L , and circuit gain ratios, then becomes:
  • a H and A L are the net amplification factors for the V H and V L channels, respectively; and DA H and DA L are the net pulse amplification factors for the respective frequencies.
  • the system can be calibrated by a single adjustment of the calibration factor C.
  • One method to obtain a value for C uses a string of three resistors, connected either manually or by switching after the calibration is automated, in place of the finger. This puts the resistor string (shown as 120 in FIG. 19) in the circuit.
  • the string of three resistors preferably approximates the resistance of a body part, such as a finger, at which hematocrit is to be measured.
  • the resistors may each have a resistance of about 500 ⁇ or of about 560 ⁇ .
  • the constant amplitude current source 108 pushes the fixed currents at both frequencies through the resistors 120 (of FIG. 19) and the sensing amplifier 110 receives the differential signal from the two ends of the center resistor.
  • a fourth resistor 122 of FIG. 19, which is larger and variable, can be placed in parallel with the center resistor and varied by some means
  • One embodiment for the parallel resistor 122 is a semiconductor photoresistor 121 enclosed in an opaque cylinder, which also contains a light emitting diode 123. The current drive to the diode 123 will be varied in the shape of an arterial impedance pulse from a signal generated in the computer 102.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Surgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pathology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Optics & Photonics (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Cardiology (AREA)
  • Physiology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)

Abstract

L'invention concerne des assemblages destinés à mesurer de façon non invasive l'hématocrite du sang (c'est-à-dire le pourcentage du volume du sang complet occupé par les globules rouges) par le biais d'une partie du corps, notamment un doigt, d'un individu. Chacun des assemblages comprend deux paires d'électrodes (20). Les électrodes (20) de l'assemblage peuvent être supportées par un substrat (32) (fig. 4). Un assemblage de l'invention peut éventuellement comprendre un composant de rétention (27) (fig. 2) destiné à fixer les électrodes à la partie du corps. Un composant de pressurisation (50) (fig. 8) peut faire partie de l'assemblage en vue d'appliquer une pression externe à la partie du corps.
PCT/US2001/040749 2000-05-16 2001-05-16 Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression WO2001088521A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001261847A AU2001261847A1 (en) 2000-05-16 2001-05-16 System and method for in-vivo hematocrit measurement using impedance and pressure plethysmography

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/571,459 US6766191B1 (en) 1990-10-04 2000-05-16 System and method for in-vivo hematocrit measurement using impedance and pressure plethysmography
US09/571,459 2000-05-16

Publications (1)

Publication Number Publication Date
WO2001088521A1 true WO2001088521A1 (fr) 2001-11-22

Family

ID=24283790

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/040749 WO2001088521A1 (fr) 2000-05-16 2001-05-16 Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression

Country Status (3)

Country Link
AU (1) AU2001261847A1 (fr)
TW (1) TW577726B (fr)
WO (1) WO2001088521A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1955650A3 (fr) * 2007-02-08 2010-06-23 BIOTRONIK CRM Patent AG Appareil médical implantable
US10598583B1 (en) 2016-05-31 2020-03-24 Verily Life Sciences Llc Compact blood hematocrit sensing device

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0417796A2 (fr) * 1989-09-13 1991-03-20 Kabushiki Kaisha Toyota Chuo Kenkyusho Appareil de mesure d'hématocrite
WO1996032883A1 (fr) * 1995-04-20 1996-10-24 Microcor, Inc. Procede et appareil de determination non invasive de l'hematocrite
US5642734A (en) * 1990-10-04 1997-07-01 Microcor, Inc. Method and apparatus for noninvasively determining hematocrit
WO1999009883A1 (fr) * 1997-08-28 1999-03-04 Microcor, Inc. Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0417796A2 (fr) * 1989-09-13 1991-03-20 Kabushiki Kaisha Toyota Chuo Kenkyusho Appareil de mesure d'hématocrite
US5642734A (en) * 1990-10-04 1997-07-01 Microcor, Inc. Method and apparatus for noninvasively determining hematocrit
US6128518A (en) * 1990-10-04 2000-10-03 Microcor, Inc. System and method for in-vivo hematocrit measurement using impedance and pressure plethysmography
WO1996032883A1 (fr) * 1995-04-20 1996-10-24 Microcor, Inc. Procede et appareil de determination non invasive de l'hematocrite
WO1999009883A1 (fr) * 1997-08-28 1999-03-04 Microcor, Inc. Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1955650A3 (fr) * 2007-02-08 2010-06-23 BIOTRONIK CRM Patent AG Appareil médical implantable
US8271085B2 (en) 2007-02-08 2012-09-18 Biotronik Crm Patent Ag Implantable medical device for blood conductivity, blood impedance, and/or hematocrit measurement
US10598583B1 (en) 2016-05-31 2020-03-24 Verily Life Sciences Llc Compact blood hematocrit sensing device

Also Published As

Publication number Publication date
AU2001261847A1 (en) 2001-11-26
TW577726B (en) 2004-03-01

Similar Documents

Publication Publication Date Title
US6128518A (en) System and method for in-vivo hematocrit measurement using impedance and pressure plethysmography
CA2218281C (fr) Procede et appareil de determination non invasive de l'hematocrite
CN101160091B (zh) 用于测量血流和血容量的系统、方法和设备
US5642734A (en) Method and apparatus for noninvasively determining hematocrit
CN100571613C (zh) 测量血流和血容量的系统、方法和装置
JP3935937B2 (ja) 人、動物の体液に関する生物学的パラメータを体内に挿入することなく測定する装置
US4548211A (en) Computer assisted admittance plethysmograph
US4836214A (en) Esophageal electrode array for electrical bioimpedance measurement
AU2003217230B2 (en) Tissue monitoring system for intravascular infusion
KR101223079B1 (ko) 살아있는 조직의 이산화탄소 분압의 생체-내 또는 생체-외 측정용 전기화학 센서
US6761695B2 (en) Method and apparatus for non-invasive measurement of changes in intracranial pressure
US7011631B2 (en) Noninvasive method of measuring blood density and hematocrit
ATE219644T1 (de) Vorrichtung zur blutstrommessungsmittelsanalyse der biologischen impedanz
KR20070052781A (ko) 센서
WO2003092495A1 (fr) Sonde permettant de mesurer l'impedance intracavitaire
EP0730429A1 (fr) Tonometre a membrane flexible et procede d'utilisation
US6766191B1 (en) System and method for in-vivo hematocrit measurement using impedance and pressure plethysmography
US20080039703A1 (en) Sensor
US7354417B1 (en) Methods and apparatus for measuring the volume of fluid in the peritoneal cavity
EP1538979B1 (fr) Moniteur d'insuffisance cardiaque congestive
WO2001088521A1 (fr) Systeme et procede de mesure de l'hematocrite in vivo dans lesquelles on utilise la plethysmographie par impedance et pression
Patil et al. Design of bioimpedance spectrometer
US8185182B1 (en) Noninvasive glucose measurement
Wen et al. An impedance method for blood pressure measurement in awake rats without preheating.
US11298055B2 (en) In vivo, noninvasive, bioelectromagnetic glucose sensor system and method

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 69(1) EPC. EPO FORM 1205A DATED 23.04.03

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP