CA2319480C - Method and apparatus for non-invasive blood constituent monitoring - Google Patents
Method and apparatus for non-invasive blood constituent monitoring Download PDFInfo
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- CA2319480C CA2319480C CA002319480A CA2319480A CA2319480C CA 2319480 C CA2319480 C CA 2319480C CA 002319480 A CA002319480 A CA 002319480A CA 2319480 A CA2319480 A CA 2319480A CA 2319480 C CA2319480 C CA 2319480C
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- 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
- A61B5/6843—Monitoring or controlling sensor contact pressure
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- 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
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- 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
- A61B5/1455—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 using optical sensors, e.g. spectral photometrical oximeters
- A61B5/14551—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 using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
- A61B5/14552—Details of sensors specially adapted therefor
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- 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
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- 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
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- 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
Abstract
This invention is a system for determining a biologic constituent including hematocrit trans-cutaneously, non-invasive, and continuously.
A finger clip assembly (6) includes at least a pair of emitters, and a photo-diode in appropriate alignment to enable operation in either a transmissive mode or a reflectance mode. At least one predetermined wavelength of light is passed into or through body tissues (7) such as a finger, earlobe, or scalp, etc., and attenuation of light at that wavelength is detected. Likewise, the change in blood flow is determined by various techniques including optical, pressure, piezo and strain gage methods.
Mathematical manipulation of the detected values compensates for the effects of body tissue, fluid, and determines the hematocrit value. If an additional wavelength of light is used which attenuates light substantially differently by oxyhemoglobin, and reduced hemoglobin, then the blood oxygen saturation value, independent of hematocrit may be determined. Further, if an additional wavelength of light is used which greatly attenuates light due to bilirubin (440 nm) or glucose (1060 nm), then the bilirubin or glucose value may also be determined.
Also, determination of the hematocrit with a two step DC analysis technique is disclosed.
A finger clip assembly (6) includes at least a pair of emitters, and a photo-diode in appropriate alignment to enable operation in either a transmissive mode or a reflectance mode. At least one predetermined wavelength of light is passed into or through body tissues (7) such as a finger, earlobe, or scalp, etc., and attenuation of light at that wavelength is detected. Likewise, the change in blood flow is determined by various techniques including optical, pressure, piezo and strain gage methods.
Mathematical manipulation of the detected values compensates for the effects of body tissue, fluid, and determines the hematocrit value. If an additional wavelength of light is used which attenuates light substantially differently by oxyhemoglobin, and reduced hemoglobin, then the blood oxygen saturation value, independent of hematocrit may be determined. Further, if an additional wavelength of light is used which greatly attenuates light due to bilirubin (440 nm) or glucose (1060 nm), then the bilirubin or glucose value may also be determined.
Also, determination of the hematocrit with a two step DC analysis technique is disclosed.
Description
METHOD AND APPARATUS FOR NON-INVASIVE
BLOOD CONSTITUENT MONITORING
BACKGROUND
The present invention is related to U.S. Patent rdumbers 5,372,136 and 5,499,62? .
THE FIELD OF INVENTION
The present invention relates to improvements in the systems and methods for non-invasively measuring one or more biologic constituent concentration values.
More particularly, the present invention relates to non-invasive spectrophotometric systems and methods for quantitatively and continuously monitoring the hematocrit and other blood parameters.
Modern medical practice utilizes a number of procedures and indicators to assess a patient's condition. One of these indicators is the patient's hematocrit. I-iematocrit (often abbreviated as HCT) is the volume expressed as a percentage of the patient's blood which is occupied by red corpuscles, commonly referred to as red blood cells. The present invention is presented in the context of hematocrit. However, it is to be understood that the teachings of the present invention apply to any desired biologic constituent parameter.
Medical professionals routinely desire to know the hematocrit of a patient. In order to determine hematocrit using any of the techniques available to date, it is necessary to draw a sample of blood by puncturing a vein or invading a capillary. Then, using widely accepted techniques, the sample of blood is subjected to either high-speed centrifuge, cell counting, ultrasonic, conductometric or photometric methods of evaluating the sample of blood in a fixed container. Prior U.S. Patent Number 5,372,136 indicates a system and methodology for determining the hematocrit non-invasively, without puncturing or invading the body, spectrophotometrically and continuously in a subject. The present invention relates to improvements upon the above cited system.
Beyond the above referenced patent, others have suggested various means of noninvasive measurement of hematocrit. Specifically, Mendelson, U.S. Patent Number 5,277,181; Seeker, U.S. Patent 5,188,108; Gonatas, U.S. Patent Number 5,528,365; Ishikawa, U.S.
Patent Number 5,522,388; Shiga, U.S. Patent Number 4,927,264; Tsuchiya, U.S. Patent Numbers 5,441,054, 5,529,065, 5,517,987 and 5,477,051; and Chance, U.S. Patent Numbers 5,353,799, 5,402,778, and 5,673,701 have attempted to define means of directly measuring desired biologic constituents such as hematocrit. Even though the various patents indicate the need to utilize multiple wavelengths measured at different detection sites and/or the need to perform differential or ratiometric operations on the detected optical signal, all fail to isolate and resolve the individual and specific scattering and absorption coefficients of the desired constituent. At best they address only bulk attenuation coefficients and/or bulk diffusion constants of the scattering media while attempting to resolve such constraints as tissue nonhomogeneity. As an example, tissue may be considered to contain a bulk absorptive coefficient due to blood, collagen, water, fibers, bone, fingernail, etc. Hence, in order to determine the absorptive coefficient of the blood itself, the bulk value of the tissue per se must be prorated by the amounts of the above constituents. Secondly, the actual absorptive coefficient of the blood must then be decoupled or isolated from its proration factor as well.
BLOOD CONSTITUENT MONITORING
BACKGROUND
The present invention is related to U.S. Patent rdumbers 5,372,136 and 5,499,62? .
THE FIELD OF INVENTION
The present invention relates to improvements in the systems and methods for non-invasively measuring one or more biologic constituent concentration values.
More particularly, the present invention relates to non-invasive spectrophotometric systems and methods for quantitatively and continuously monitoring the hematocrit and other blood parameters.
Modern medical practice utilizes a number of procedures and indicators to assess a patient's condition. One of these indicators is the patient's hematocrit. I-iematocrit (often abbreviated as HCT) is the volume expressed as a percentage of the patient's blood which is occupied by red corpuscles, commonly referred to as red blood cells. The present invention is presented in the context of hematocrit. However, it is to be understood that the teachings of the present invention apply to any desired biologic constituent parameter.
Medical professionals routinely desire to know the hematocrit of a patient. In order to determine hematocrit using any of the techniques available to date, it is necessary to draw a sample of blood by puncturing a vein or invading a capillary. Then, using widely accepted techniques, the sample of blood is subjected to either high-speed centrifuge, cell counting, ultrasonic, conductometric or photometric methods of evaluating the sample of blood in a fixed container. Prior U.S. Patent Number 5,372,136 indicates a system and methodology for determining the hematocrit non-invasively, without puncturing or invading the body, spectrophotometrically and continuously in a subject. The present invention relates to improvements upon the above cited system.
Beyond the above referenced patent, others have suggested various means of noninvasive measurement of hematocrit. Specifically, Mendelson, U.S. Patent Number 5,277,181; Seeker, U.S. Patent 5,188,108; Gonatas, U.S. Patent Number 5,528,365; Ishikawa, U.S.
Patent Number 5,522,388; Shiga, U.S. Patent Number 4,927,264; Tsuchiya, U.S. Patent Numbers 5,441,054, 5,529,065, 5,517,987 and 5,477,051; and Chance, U.S. Patent Numbers 5,353,799, 5,402,778, and 5,673,701 have attempted to define means of directly measuring desired biologic constituents such as hematocrit. Even though the various patents indicate the need to utilize multiple wavelengths measured at different detection sites and/or the need to perform differential or ratiometric operations on the detected optical signal, all fail to isolate and resolve the individual and specific scattering and absorption coefficients of the desired constituent. At best they address only bulk attenuation coefficients and/or bulk diffusion constants of the scattering media while attempting to resolve such constraints as tissue nonhomogeneity. As an example, tissue may be considered to contain a bulk absorptive coefficient due to blood, collagen, water, fibers, bone, fingernail, etc. Hence, in order to determine the absorptive coefficient of the blood itself, the bulk value of the tissue per se must be prorated by the amounts of the above constituents. Secondly, the actual absorptive coefficient of the blood must then be decoupled or isolated from its proration factor as well.
OBJECTS OF THE INVENTION
Thus, it is an object of the present invention to provide an improvement in the systems and methods for the non-invasive (transcutaneous) and continuous determination of the blood Hematocrit in living tissue.
It is yet another object of the present invention to provide an improvement in the systems and methods for the non-invasive (transcutaneous) and continuous determination of the blood constituents, including glucose, bilirubin, cholesterol, tissue water, etc. in living tissue.
It is another object of the present invention to provide a system and method and apparatus for the display of both immediate and/or continuous visual information regarding the HCT of the subject.
It is yet another object of the present invention to provide a repeatable and reliable method and apparatus for the non-invasive determination of hematocrit transcutaneous(y and in real time even under varying physiological conditions.
Still another object of the present invention is to provide a method and apparatus for the instantaneous determination of the bulk absorption coefficient of the scattering media.
These and other objects and advantages of the invention will become more fully apparent from the description in the specification and claims, which follow.
SUMMARY OF THE INVENTION
In one aspect, the present invention accomplishes the transcutaneous, noninvasive, real-time and continuous measurement of the hematocrit and other blood constituents of the patient.
That is, the electronic circuitry necessary is included to receive signals from a detector and to generate appropriate signals at various input sites as described in U.S.
Patent Number 5,372,136.
Yet another aspect of the present invention is the ability to extract the blood absorption coefficient from the bulk tissue diffusion constant or the bulk absorption coefficient of the scattering media by requiring both physical and mathematical operations.
BRIEF DESCRIPTION OF THE DRAWINGS
Figures 1 and 1 A show a finger placed into a clam-shell type fixture constituting a receiving means for detector and emitter arrays operating in a transmission mode and the blood conduit which in the figures is the finger.
Figures 1B and 1 C are similar to Figure I A, but show the detector and emitter arrays operating in a reflectance mode.
Figure 1D is a schematic diagram for a mylar base with a detector, emitters and either a strain gage or a pressure transducer for inclusion in the clam-shell fixture.
Figure lE is a schematic diagram for a detector emitter array using a single, moveable emitter in a transmission mode.
Figure 2 shows actual patient data plot of ln(i) vs. d.
Figure 3 illustrates actual patient data of the (d ila I)li dependence on d.
Figure 4 shows the blood absorption coefficient's dependence on hematocrit.
Figure 5 indicates the nonlinear relationship between the V~ ll~I and pressure.
Figure 6 shows the electrical circuit diagram of the piezo film / strain gage transducer means.
Figure 7 is the plot ofd vs. measured Hematocrit.
Figure 8 shows the instantaneous time derivatives of (d ilc7t)li and a Plat versus time during one cardiac pulse.
Figure 9 plots (ailat)li versus a Plat for a given human pulse at d,, d~, d3, and d,.
Figure 10 plots (Bilc7ty(a Plat) versus time during a single cardiac pulse cycle.
Figure 11 is the circuit diagram of the pressure transducer means.
Figure 12 plots a versus Xb at a fixed Hematocrit.
Figure 13 gives the patient data of the new transcutaneous Hematocrit method and system plotted versus the measured Hematocrit standard.
DETAILED DESCRIPTION OF THE TNVENTION
In a preferred embodiment of the invention, measurements are conducted using a modified version of the apparatus described in U.S. Patent Numbers 5,456,253 and 5,372,136. Both of these patents form part of the present disclosure.
Thus, in a preferred embodiment, hematocrit is measured in living tissue located at some convenient location on the body, such as, an ear lobe, finger tip, nose or other accessible tissue sites. In a preferred embodiment the apparatus and signal manipulations described in U.S. Patent Number 5,372,136 are utilized to measure various optical parameters that will be described hereafter. The numbered components in Figures l, 1 A, 1 B, and 1 C are similar to the numbers in Figure 1 ofU.S. Patent Number 5,456,253.
In the present disclosure, Figure 1 shows the finger 7 of an individual placed into a clam-shell type fixture 6 wherein the optical and other physical measurements can be easily performed.
The clam-shell type holder allows for adaptability to various finger sizes.
However, other fixture methods such as Figures 1B through lE, can be used to obtain similar physical data as using the clam-shell fixture.
THEORETICAL BASIS OF THE SPECTROPHOTOMETRIC AND MATHEMATICAL
ANALYSIS FOR TRANSCUTANEOUS HEMATOCRIT MEASUREMENT
Non-invasive, transcutaneous hematocrit measurement using a spectroscopic method is described below:
I. Introduction Earlier spectrophotometric techniques have fallen short of being able to fully characterize the individual blood absorbance coe~cients. The following discussion demonstrates the method of decoupling, or isolating from the bulk tissue attenuation parameters (including the convoluted absorptive and scattering parameters) the individual blood absorptive constants. This unique method identifies, isolates and compartmentalizes each of the contributing biologic elements of the tissue media. This decoupling process can either isolate the blood absarbance of interest and/or eliminate the scattering contribution from the bulk media measurement.
From photon diffusion analysis:
sL'I'(P~ - aZ 'I'(P~= -SIPS. ( 1 ) aP? D
where, D = ~.-. (2) 3 (K + S) a = J3K(K+ S) (3) K KbXb+~~+K,VX", (~) Kb = I~ (Q,oSAT + ( 1 - SAT)au) + ( 1 - I~KP (5) V
S=SeXb+SsX, (6) Sb = .~li(1-Hl(1.4-Hl (7) v and where, a = Bulk attenuation coefficient of the tissue sample K = Bulk absorption coefficient of the tissue sample S = Bulk scattering coeffccient of the tissue sample D = Diffusion constant Kb = Macroscopic absorption coefficient for whale blood (WB) Sb = Macroscopic transport - corrected scattering coefficient for WB
KD = Macroscopic absorption coefficient for plasma K, = Macroscopic absorption coeffcient for skin, & other non water/blood components Kw = Macroscopic absorption coefficient for water i' = Volume of a red blood cell (RBC) H = Hematocrit, volume fraction of RBCs to total blood volume SAT = Oxygen saturation a~ = Absorption cross - section of oxygenated RBCs Qo, = Absorption cross - section of deoxygenated IZBCs Q, = Transport - corrected scattering cross-section of RBCs Xb = Fractional volume of blood per total tissue volume X, = Fractional volume of skin, & non water/blood components per total tissue volume X" = Fractional volume of water per totai tissue volume ~F(p) = The photon density at a distance p S(p) = The source function.
II. Analysis The light flux, or intensity, i, is given by i = Due. When evaluated at p = d, one ap solution to equation ( I ) is:
i = A eaa (8}
e~'~ - I
where A is a nontrivial function of the tissue scattering coefficient, S, the distance, d (if small), and the bulk attenuation coefficient, a. If a d >=~ 1, then (8) becomes:
i = Ae'a° (9) where A = a [d° ~ (1-a ~"d)] or (1/d2 + 1/ad) for 0<n<2, where n is the power that d is raised to.
Figure (2) shows the actual patient data plot of ln(i) vs. d, where a is determined directly from the slope of the line.
The attenuation coefficient, a, is a bulk term which encompasses the attenuation measurement sensitivity to variations in skin color, presence of bone, callous, blood and water content, etc. In addition, a expresses the optical "path lengthening"
effects of both the absorption and scattering characteristics of the tissue. Therefore, since a is a function of HCT and the intensity of the transmitted light can be measured, the HCT can be calculated by manipulation of the preceding relationships.
Beginning with equation (9), the troublesome and complex tissue function, A, can be eliminated by taking the logarithm of (9) and differentiating with respect to the distance, d Unfortunately the term Xb is not known but changes with time as a result of a patient's cardiac cycle. Therefore, by differentiating with respect to time, this parameter becomes the time rate of change of blood volume which can be obtained through several methods described below. These time and distance derivatives may be performed in either order.
[1) Taking the logarithm of (9) and differentiating with respect to the distance, d, yields:
a = ~[ ln(i)1 ( 10) ad Next the derivative of (10) with respect to time, t, gives:
a ~tn(c) a -a~r ~ (l l) a«
ar - ar [2) Alternatively, first differentiate (9) with respect to time, t, to get:
-~~ she+~~'s+~! ~,. (12) at aXb c'Y a.Y, cf aXw at When ~ 7~ and ~ ~" are negligible, and normalizing (12) by i yields:
ax, ~ axw ~
agar ' axb a« a _ 1 a ~ or, (13) A ax ar Cax b b ~ =~,c (d - do) , where do =J... _ - 2d (13a) i at a e~° - 1 Figure 3 plainly demonstrates the offset term when the various graph lines are extrapolated to d = 0. The amount of offset is shown along the y-axis.
Next differentiate {13) with respect to distance, d, to eliminate that offset term to get:
~a~~ar~
a ; axb a_« _ _a«
- ar axb at (14) Equations (3) - (7) are now used to extract the hemato;,rit from a. Squaring (3) and differentiating with respect to time results in:
~a a« _ ~ a!~ (~~ +s)+xas {ls) at at at Substituting the derivatives of (4) and (6) into ( 1 s) and rearranging:
o« 3 a l' aX aX,. 16 -_ ~~~h+ ~~.f+ ~~~. (2~+s)+~. as°sn+aassl~ ( ) at at at i« ~ at -ax , ax, , b axw axb s » aX~ s.~ ~,d rc ax At SOS nm' ath ~e » at ~'~ ' at K° » ~ :at K~ ' at ° at < < S so that ( 16) can be simplified to:
s~L = ~.. ~a (KeS + ~~ ( 17) ar 2« ar By using the 805 nm wavelength the red blood cell absorption cross-section constants are equal, aQO = oy, and Kp is negligible. The hematocrit can then be determined directly from Kb as (S) simplifies to:
H = V Kb ( 17a) a, Figure 4 shows the linearity of Kb(H).
IfKb,S » KSb, where S is approximately 1.0 / mm in human tissue, then solving (17) for Kb and substituting into ( 17a) gives:
2 V a_a (18) H- 3aa a at a xb s at To rewrite in terms of measurable intensity, i, (10) and (14) are substituted into (18) to obtain:
2V- a~ln(i)~ a ~(al;'at~~i]
a~ as H- axb s (19) ar IfKbS' is not » KS~, then substituting (5) and (7) into (17a) and rearranging terms yields:
_ _2a _aa a Xb a Q ~ a f _ H 3 at at S ~, +l~ V ~~. KX1.4-H~~ (18a) Alternatively from (13a) : H ~ a-l~ilatlil (18b) (d-do) ' X'b Equation (18a) indicates a small nonlinearity in H may occur based on the magnitude of K for a given individual.
It should be reiterated that the change in received intensity with time is a result of the change in normalized blood volume resulting from the cardiac cycle itself as blood pulses through the examined tissue. As the intensity of the received light is measured, its time rate of change can be calculated. The change with distance can be determined by placing multiple emitters (such as 1-4 in Figure 1 A) and/or multiple detectors such that multiple thicknesses of tissue and hence, lengths of tissue are penetrated.
To examine ~ further, the following can be defined for the illuminated tissue:
ar Yb = Volume of blood, V", = Volume of water, and Vs = Volume of skin, tissue and other non-water or blood components.
By definition, Xb = Va (2~) Vb+Vw+Y, differentiating (20) with respect to time gives:
(Yw + V~ ~a _ Va s~Yw = at cf (21) ar (Vb + YW + VJ)z Since ~w_ « ~ and Yb « VW + VJ, (21 ) simplifies to:
ar ar ~a (22) at V~r It is emphasized that a is a function of the bulk absorption and scattering coefficients, K and S, as well as hematocrit, H. Further, that K and S are functions of the fractional volumes of each constituent, Xb X,, and X",, which must be used to prorate the individual absorption and scattering coefficients, Kb Kf, K~. Sb and S=. Therefore, the transducer system must be responsive not only to a change in volume (O V) due to the influx of the blood, but must also be responsive to the normalized change in volume of blood, normalized to the total volume of the finger (Vf)or tissue being measured, D V~
Vr For Reflectance (R) measurements in homogenous tissue:
R = Ae'"', where A ~ ( 1/~ + 1/ar), where r is the radial distance, and ~F = a' (r/(a2 ~- ar)) R
However, for tissue, which is typically non-homogeneous with a dermal and subcutaneous layer, the reflectance will not be a trivial function but can be described as approximately:
R = L(C~ + Cz) exP (-C3 ' r)~/r"
Where C1 and Ci are inter-related photon flux densities between the dermal layer I2 and the subcutaneous layer, I2a (see Figures 1C and IE). Likewise, C3 is a strong function of z,, z2, al, and a2; i.e., the thickness of the dermis or dermal layer 12, subcutaneous layer 12a, and their respective a's.
Since C,' is a function of the inter-related photon flux densities C, and/or C2 and if Xb', does not equal Xb'2, then the slope C3' will not be nulled out by the Xb' monitors mentioned. Therefore, Xb2 must be greater than Xb,'. Then the pressure or piezo monitors will compensate correctly. The circular pressure balloon is ideal for not only sensing the change in a pressure, but also providing. a pressure against the denmis causing Xb,' to be small. However, recognizing that the penetration depth of the 800 nm light typically extends through dermal layer 12 into the deep tissue, subcutaneous layer 12a, a different wavelength selection is appropriate. Thusly, when the photons only penetrate into the dermal layer 12, C3' will only be a function of z, and a,. Those selected wavelengths, as mentioned in U.S.
Patent No. 5,372,136, would be the green (570-595 nm) wavelength and 1300 nm wavelength. The green wavelengths are used as the hematocrit bearing wavelength and the 1300 nm wavelength is used as the non-hematocrit bearing, or reference wavelength. That is, for reflectance measurements the green (Gr)-1300 wavelength pair would give the hematocrit information as:
~Gr / Gr ~ ,~, = f (HCT) X1300/1300 a,3~
III. Methods of ~ measurement ar axJar can be measured and compensated for through the use of a number of different methods - (a) a pressure transducer, (b) a strain transducer such as piezo electric film or strain gage, (e) a different wavelength of light, such as 1300 nm, which also holds o~Jd t information, but holds little hematocrit information, or (d) other transducers. The individual methods of obtaining aXb/at are addressed below.
A. Pressure Transducer Measurement of ~
at Consider a pressure transducer system 36 with a gas filled bladder 38 surrounding a finger tip 10 of a patient contained within a fixed volume clam shell fixture 6, see Figures 1, lA- 1D. The same derivations, equations, and results would apply to any other body appendage or tissue that could be contacted such that a change in the tissue volume would change the pressure of the contacted pressure transducer system. For a finger note:
y<<o,~ = V~.= + Vi ( ) where V~,o,~ = Clam-shell fixture volume Vryl = Bladder system volume V~ = Finger volume Also ~Yf= -AVrys. The system will have a bulk modulus of elasticity, p, such that:
(24) Substituting (23) into (24) results in:
0 y~ _ ym.~ _ 1 ~
V~ ~ (25) Since G1 V~ = d Va then from (25) we have:
DP
8 Xa __ V~,~ _ 1 m (ZSa) at Vj As stated above, (3 is a constant of the pressure transducer system. However, an empirical solution for V~~m _ 1 was found to have a nonlinear relation to the pressure of V~
the transducer system. For a given clam shell - pressure transducer embodiment a polynomial, F(p), can accurately describe y r~~~ _ Il., see Figure 5 V~
B. Strain Transducer (Strain Gage/Piezo Electric Film) Measurement of ~b at Again it is assumed that ~ Ya = ~ Vj, and that the finger changes volume only by a change in diameter. A strain gage or piezo electric film is secured tightly around the finger (again any applicable body appendage or tissue would apply) such that a change in diameter would produce a strain in the transducer. Specifically assuming a cylindrical finger:
~ _ ~.~V~ _ ~ = 2~czr ~, (26) al al at al Normalizing with respect to V~ yields:
2~tzr~
~'a =_ ~
a'Y V,«ar , trzrz r al (27) A change in the length of the transducer element is related to a change in finger WO 99/39631 PCT/US99t02586 radius by OL = 2nOr, therefore:
~ = 2.~I~t) = 2 Y(t) (28) at L, where y(t) _ ~ is the rate of change in the strain as a function of time. For a strain L
gage this value can be measured from an appropriate electrical circuit, see Figure 6, as it is proportional to the rate of change in the gage resistance.
For a piezo electric film the voltage produced is proportional to the strain, therefore:
7~ø _ ~ v t (29) at g"T ar where, g" is the piezoelectric coefficient for the stretch axis, z is the film thickness and v(t) is the open-circuit output voltage.
C. 1300 nm Light Measurement of ?~
at The selection of the 1300 nm wavelength is based on criteria established in U.S.
Patent Number 5,372,136. The approach here is not to solve for a.Y~/a, and substitute into (19) but to ratiometrically eliminate aX~dt. In the case of the 1300 nm reference wavelength, the assumptions following equation (12) are no longer valid; i.e., aXfat and aX"/at are not negligible, since water absorption at 1300 nm is so large. Hence, for the 1300 nm equations (13), (14) and (15) would result in:
as 3 ~(2K+S)Kb+KSb~+{~2K+S~K,+h'S,~+
at ,~ - 2a ar at ( ~(21~' + S)K~, at where, a, and the bulk and material specific K, and S are wavelength (.1) dependent.
Recalling that, Xb + X, + XW = 1, by definition, and that:
~_s3~_ ° ~
ar a/ ar (31 ) By substituting (31) into (30) and noting that K",3 = Kb,~, the following is obtained:
a« ax~
« {xs~ }aa n + ~(ZK + SxK, - x~.]+ h,s, } ar (32) n Since, ~, » ~_, (32) becomes:
ar ar a« ~ -_ 3 {~S } a xb ..
ar " 2«" b .a ar (33) Therefore, to eliminate ~ arid solve for the hematocrit, (17) is divided by (33) ar yielding:
(a«~a r )g -_ «" Kb s Sg -, (a«~a~)I~ «a Ke sb " (34) Since S8 and K,3 are weal behaved and known (let 1f,3 /Ss = G) in human tissue and the ratio ~ is a function of H, then rearranging (34) gives:
Sem Ca«~
«$ ar a G (35) a«
(ar) Where ~c can be measured using (11) or (14). See Figure 7 for,f~.
at D. Other aXb/at measurements such as doppler, ultrasonic, electrical conductivity, magnetic permeability and other techniques have similar derivations. The important consideration is that aX8/at is a normalized time varying quantity.
IV. Analytical implementation If hematocrit is constant over a given time interval, averaging can eliminate system noise whose frequency components have corresponding periods much shorter than the interval. In addition, by observing the data variance during the interval it may be determined that the data is invalid. In the present system, the data acquisition rate is approximately 1000 data samples per second. This means that within a typical human pulse about 1000 samples of data are available for appropriate numerical analysis, averaging and qualification.
Recognizing that both the intensity of light and the pressure in the transducer system are changing in time during the influx of blood is of great importance. Since the parametric relationship of aalat as a function of c7Plat (where P is pressure) during the cardiac cycle, should be linear, a multiplicity of data points facilitate qualification of the signal for accuracy and linearity. Whereas, prior techniques involving only the peak and valley values of the cardiac cycle require numerous pulses to qualify the data set. See Figures 8, 9 and 10.
Fig. 8 shows di/dt/i as well as dP/dt verses time during the cardiac pulse -it is a pulse showing ~ 200+ data samples during the pulse.
Fig. 9 shows (di/dt)/i vs dP/dt showing that within one cardiac pulse 200 plus data samples are li en arfv related, i.e. trace up out of the "0" origin up to a maximum value and then back down toward the origin again.
Fig. 10 shows da/dt/dP/dt versus time during one single cardiac pulse with 200 plus samples of data from time 15 - 45 giving a value of about 4.5 thousandths. The data can then be averaged, as if 200+ individuals pulse (max-min) values were actually taken as present day oxymeters do.
A. ymogen Since the above derivations are based on the assumption of tissue homogeneity (i.e.,c7Xb~t = aXb~a t , A,= AZ, c?A,/c7Xb = c7Az/aXb, a, = a,, etc.), high-speed, single-pulse, multiple parameter sampling allows for mathematical qualification of homogeneity, by requiring linearity of In(i) vs. d and (ailat)li vs. d Under these constraints and when qualified as homogeneous, (c7alc7t)l(aPlc7t) also may be assumed to be linear over the entire pulse contour.
Finally, both a and c7a/at must also be linear, further assuring homogeneity in Xb, and in c7X~t.
B. Circuitry See U.S. Patent Number 5,372,136 for the operational circuitry description, which allows for high speed sampling of the optical intensities. See Figures 6 and 10 for similar circuitry considerations for sampling of pressure, peizo, and strain-gage measurements.
The circuitry shown and discussed in US Patent Number 5,372,136 is programmable by conventional techniques to solve and implement the equations and calculations presented in this application. Figure 6 shows a piezo transducer circuit having a transducer 50 connected to a series of operational amplifiers, resistors and capacitors in accordance with the figure. The circuit terminates in an analog output 52 for connection to the "E" connection shown in the middle left side of Fig. 9D in U.S. Patent Number 5,372,136. Figure 11, on the other hand, shows a pressure transducer circuit having a pressure transducer made 62 connected to a series of operational amplifiers, a capacitor, resistors and variable resistors as shown in the figure. The circuit .
terminates in an analog output also connected to the aforementioned "E"
connection.
Referring more specifically to FIG. 6, a crystal oscillator is connected to ground and to the non-inverting input of a first operational amplifier, which may be an LM158.
The non-inverting input of the first operational amplifier is connected to ground by a .047 I1F
capacitor C3. The first operational amplifier's feedback path to its inverting input includes a 470 K
resistor R8. The first operational ampftf er is suitably biased at the junction of a 220 S2 resistor R7 and a 150 pF
capacitor C4 that are connected between VCC and ground.
A second operational amplifier, which may also be an LM 158, receives the output of the first operational amplifier at its inverting input via a 10 KS2 resistor R5.
The second operational amplifier's non-inverting input is connected to several locations:
~ to a voltage VB51, which may be 4.096 volts, through a 10 K~2 resistor R2;
~ to a middle node of a voltage divider, the voltages divider extending between the non-inverting input of the first operational amplifier via a 10 MS2 resistor R4 to the middle node, and via a 10 Kf2 resistor R1 to ground;
~ to the inverting input of the first operational amplifier via a 10 KS2 resistor R9; and ~ to ground via a 220 pF capacitor C5.
The second operational amplifier's feedback path to its inverting input includes a parallel arrangement of a 0.1 pF capacitor C2 and a 47 KS~ resistor R6. The second operational amplifier drives the A/D output 52 via a 10 KS~ resistor R3, the output connected to ground via a 1 pF
capacitor C 1.
Of course, the particular choice, arrangement and values of components shown in FIG. 6 may be varied while still remaining within the scope of the invention.
Referring now to FIG. 10, first through fourth operational amplifiers, which may be LM348s, are illustrated. The operational amplifiers are powered and biased by voltages VCC and VEE.
The first operational amplifier's non-inverting input is set to a value determined by the tap setting of a 1 KS~ adjustable resistor RZ that extends between VCC and VEE.
The DAC input drives the first operational amplifier's inverting input via a 1 KSZ resistor R1. The first operational amplifier's feedback path includes a SO KS2 adjustable resistor R4. The first operational amplifier drives the second operational amplifier's inverting input through an 11 KS2 resistor R3. The feedback path to the inverting input of the second operational amplifier includes a 100 SZ resistor R5.
A transducer 62, which may include a Motorola MPX20100P, has opposite terminals that drive the non-inverting inputs of the second and third operational amplifiers, respectively. The other two opposite terminals of the transducer are connected to VCC and ground, respectively.
The second operational amplifier drives the inverting input of the third operational amplifier via a 750 f~ resistor R6. The third operational amplifier's feedback path to its inverting input includes a parallel arrangement of a 93.1 KSa resistor R10 and a .001 pF
capacitor C1.
The third operational amplifier drives the non-inverting input of the fourth operational amplifier via a 1 IC~2 resistor R7. The inverting input of the fourth operational amplifier is connected to ground via a 1 KSZ resistor R8. The feedback path to the inverting input of the fourth operational amplifier includes a 50 ICI adjustable resistor R9. The fourth operational amplifier drives the output of the FIG. 11 circuit.
Of course, the particular choice, arrangement and values of components shown in FIG. 10 may be varied while still remaining within the scope of the invention.
C. Preferred Embodiment Physical embodiments as shown in Figure 1 include the optical array, pressure transducer/balloon system and clam-shell fixture. Requisites of the preferred embodiment include a holder for the finger (or other tissue) such as seen in Figures 1 and 1 A
and IB. This clam-shell fixture not only secures the tissue but also the optical array, and transducer system.
Figure 1D is a schematic diagram for a mylar base member 38 that is shaped generally like a cross. As oriented in Figure 1 D, vertically extending portion 52 crosses with a horizontally extending portion 54 to yield top leg 56, bottom leg 58, and side legs 60, 62.
In use, a finger 7 lies along the longitudinally extending portion 52 with the finger tip placed on the top leg 56 to properly cover the arrangement of LED's 32 and photodetector 34, which are arranged like those on Figures 1 A - 1 C. A piezoelectric pressure transducer or strain gage 66 spans the horizontally extending portion 54 from near the tip of side leg 60 to the tip of side leg 62. In this orientation, the transducer or gage may be wrapped around the finger 7 for use in measurements.
The optical array 30, seen in Figure 1D, shows the arrangement of multiple LED's 32 spaced at known separation distances from the detector 34. This array provides for the instantaneous distance, or "d", derivative, by the transmission mode shown in Figure lA or in reflectance modes shown in Figures IB and IC. However, as shown in Figure lE, a single LED
42 swept across the finger 7 or tissue surface 9 with a stepper motor 44 would provide a d derivative as would a cantilevered clam-shell with an angular measurement device. In any case, d must be known and/or fixed. Also the detectors and emitters may be placed anywhere about the finger.
The pressure/balloon, strain gage, or peizo transducer system incorporated within the clam-shell fixture ( see Section III, A, B, C and Figure 1 A) provides the contact surface area needed to define the c3X,fc3t.
High-speed sampling provides for a closer approximation of the instantaneous time, t, derivative, a/dt, as opposed to peak-valley values, see Figure 8. Therefore, the above embodiments allow for the direct measurement of In (i) at d,, d~, d3 and d, cotemporaneously, thereby determining the actual a of the sampled tissue. Likewise (ailc3t)li can be directly measured at d,, d~" dj and d,,, cotemporaneously during the pulse which determines the instantaneous dalat.
The above mentioned optical array can be utilized transmissively and/or reflectively provided the separation distance between the detector and first emitter (d,) is greater than 3mm.
D. Choice of Non-Ionizing Waveleng~ht Since hematocrit is an example of the desired biological constituent concentration value of interest, selection criteria of the preferred wavelength must include an understanding of equation (5). That is, a wavelength whose coefficients Kr K~, Kp are small compared to Kb and which are also insensitive to oxygen saturation status must be selected. Such wavelengths include 805 nm, 590 nm, 569 nm and other isobestic wavelengths with negligible water absorption. While non-isobestic wavelengths, with small water absorption, could function, a second wavelength is needed to null out the oxygen saturation effects.
If the desired biologic constituent value of interest is the blood giucose, bilirubin, cholesterol or other parameters, then a second wavelength must be chosen. The first wavelength, 805 nm, is used to measure the hematocrit, H, after which a KpBOS (the absorbance of plasma at ~.
= 805 nm) can be determined. Then, knowing the H, a second wavelength, 570 nm, is chosen where ICps,o is less than ICp8o5. Similarly, if the first wavelength used to measure the H and the reference glucose, ICn (glucose) is 570 nm, the second wavelength, 1060 nm, is chosen where ICps,~ is much less than ICPI~. In the case of bilirubin, the first wavelength used to measure the H
and the reference bilirubin, ICp (bilirubin), is 570 nm, the second wavelength, 440 nm, is then chosen when ICPS~o is much less than ICI,"o. The selection of these above mentioned wavelengths therefore assures uniqueness for the measurement of the desired biologic constituent.
Additionally for glucose determination, recall that the 1300 nm wavelength is not hematocrit or hemoglobin dependent but will be glucose sensitive. This is primarily due to the dependence of the scattering coefficient on the difference between the index of refraction of pure water and glucose, i.e.: recall Sb8 = H (1-H) a,g (from equation 7) where:
Q,B = 8'rz2yo ('~1'e - 1 )Z ' b" / ~2 where rl'8 = index of refraction of the RBC~hemoglobin at 800 nm relative to plasma rlo (the plasma index of refraction), and, Sbl3 = H (1-H) a,13 (also from equation 7) where:
Qsl3 - 87C2 1'~0 (Tl'13 - 1 )2 ' b" / ~.Z
rl'13 = the index of refraction of glucose at 1300 nm relative to rlo.
Therefore, the 8 13 ratio has both hematocrit ~ glucose information. Whereas the a$~a'g/OP
(equation 18a) ratio has only hematocrit information. Therefore the differential combination of those ratios will be a strong function of glucose only.
E. Improved Accuracy Pulse Oximeter Device The accuracy of present day pulse oximeters suffers from 4 major problems:
tissue perfusion (low Xb and low c7X~t), d dependence (varying finger sizes), tissue nonhomogeneity ( the tissue penetration depth for 660 nm light is not the same as for 940 nm light), and H dependence (see equation (5)).
All of the above mentioned deficiencies in pulse oximetry can be eliminated by understanding equation (13). Equation (13) indicates an "offset term", _ ~ ~.
A c7Xb Hence, while merely dividing (Dili)x, by (Aili)x2 mitigates the effect of c7X~lc7t, the ds do not completely cancel, thereby yielding the above mentioned problems. To improve pulse oximeter accuracy, a derivative is needed as in ( 14), which eliminates the "offset term". Hence, the ratio of (aaldt)8osl(aaltl)~ results in no H, d, or Xb dependence and the use of the multiple LED array and high-speed sampling as mentioned in section IV qualifies the tissue as homogeneous.
V. A Simplified Two Step Approach (A) Determination of H and Xb The bulk attenuation coefficient, a, can be easily measured with the optical array, at 805 nm, utilizing equation (10) and as described in Section IV(C). Notice that at 805 nm, a is a strong function of H and X6 since K,8 K",8, Kp8 are small, see Figure 12.
Therefore, by knowing Xb itself, H can be determined. Xb itself can be determined using a WO 99/39631 PC'T/US99/02586 strain gage in the following two step approach. Step One, measure the strain gage resistance when the finger is made bloodless, by squeezing finger, such as with a stepper motor. Step Two, measure the strain gage resistance when the finger is blood filled, for example by suction.
Mathematically, at 805 nm and when Kr, Kp K", are small, equation (3) is approximated by:
a2 ~ 3KS (36) or a~ ~ 3IKbXbJfs~b + S~sJ (37) Substituting (5) and (7) into (37) yields:
0=3 H~° Xb H(1-H)(1.4-H) V Xs+SrXJJ-a- (38) v C
With Xb and a measured and known, and with the a's and S~. Xl approximately constant, H
can be solved with a quadratic formula or a polynomial fit.
The strain gage determination of Xb is as follows:
Let V° = the volume of a bloodless finger. Let V~ = the volume of blood filled finger, and again considering the finger as a cylinder:
Y° _ ~rZZ = ys + y,. (39) yf- nR~z = yb +, VJ + Vw and V" -CrJ, (41) V~
From equation (20) Xb = ~~ y V - 1 _ ~ (42) Substituting (41) into (42):
Xb 1 ~ Rl (43) Where the strain gage resistances are proportional to the radius, r and R, of the finger.
(B) j2eterm~nation of tissue water content X, Choosing the wavelength of 1300 nm, where K, and K" are significant, the tissue water content, XW, can be determined. Recall that 1 - Xb - Xw = X, and substituting into (3) yields:
az ~a = 3((Kb - K~~~Yb ~' {KW - ~s)XW '~ ~'~
(~~~b-KJI + (Sb-~r~~b + ~~K~r-~s~ -SfJXw~+ Kt ~" Si With a,~" Xb and H determined and because K~. Kj, ~'". S~, and S, are known coefficient values at 1300 nm, Xw is solved with either a quadratic formula or a polynomial fit.
RESULTS .
Figure 13 demonstrates preliminary results with 30 patients the application of the method and apparatus and the application of Equation 19 on numerous patients with a correlation of r =
0.96.
As implied throughout, those skilled in the art will also appreciate that the methods for determining blood hematocrit values within the scope of the present invention may be adapted for determining other non-hematocrit biologic constituent values such as glucose, bilirubin, cholesterol, tissue water, etc.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. While the foregoing described embodiments are~to be considered in all respects only as illustrative of the claimed invention, they are not intended to restrict the scope of the claims. The scope of the invention is, therefore, indicated by the following appended claims rather than by the foregoing description. All changes within the meaning and range of equivalency of the claims are to be embraced within their scope.
Thus, it is an object of the present invention to provide an improvement in the systems and methods for the non-invasive (transcutaneous) and continuous determination of the blood Hematocrit in living tissue.
It is yet another object of the present invention to provide an improvement in the systems and methods for the non-invasive (transcutaneous) and continuous determination of the blood constituents, including glucose, bilirubin, cholesterol, tissue water, etc. in living tissue.
It is another object of the present invention to provide a system and method and apparatus for the display of both immediate and/or continuous visual information regarding the HCT of the subject.
It is yet another object of the present invention to provide a repeatable and reliable method and apparatus for the non-invasive determination of hematocrit transcutaneous(y and in real time even under varying physiological conditions.
Still another object of the present invention is to provide a method and apparatus for the instantaneous determination of the bulk absorption coefficient of the scattering media.
These and other objects and advantages of the invention will become more fully apparent from the description in the specification and claims, which follow.
SUMMARY OF THE INVENTION
In one aspect, the present invention accomplishes the transcutaneous, noninvasive, real-time and continuous measurement of the hematocrit and other blood constituents of the patient.
That is, the electronic circuitry necessary is included to receive signals from a detector and to generate appropriate signals at various input sites as described in U.S.
Patent Number 5,372,136.
Yet another aspect of the present invention is the ability to extract the blood absorption coefficient from the bulk tissue diffusion constant or the bulk absorption coefficient of the scattering media by requiring both physical and mathematical operations.
BRIEF DESCRIPTION OF THE DRAWINGS
Figures 1 and 1 A show a finger placed into a clam-shell type fixture constituting a receiving means for detector and emitter arrays operating in a transmission mode and the blood conduit which in the figures is the finger.
Figures 1B and 1 C are similar to Figure I A, but show the detector and emitter arrays operating in a reflectance mode.
Figure 1D is a schematic diagram for a mylar base with a detector, emitters and either a strain gage or a pressure transducer for inclusion in the clam-shell fixture.
Figure lE is a schematic diagram for a detector emitter array using a single, moveable emitter in a transmission mode.
Figure 2 shows actual patient data plot of ln(i) vs. d.
Figure 3 illustrates actual patient data of the (d ila I)li dependence on d.
Figure 4 shows the blood absorption coefficient's dependence on hematocrit.
Figure 5 indicates the nonlinear relationship between the V~ ll~I and pressure.
Figure 6 shows the electrical circuit diagram of the piezo film / strain gage transducer means.
Figure 7 is the plot ofd vs. measured Hematocrit.
Figure 8 shows the instantaneous time derivatives of (d ilc7t)li and a Plat versus time during one cardiac pulse.
Figure 9 plots (ailat)li versus a Plat for a given human pulse at d,, d~, d3, and d,.
Figure 10 plots (Bilc7ty(a Plat) versus time during a single cardiac pulse cycle.
Figure 11 is the circuit diagram of the pressure transducer means.
Figure 12 plots a versus Xb at a fixed Hematocrit.
Figure 13 gives the patient data of the new transcutaneous Hematocrit method and system plotted versus the measured Hematocrit standard.
DETAILED DESCRIPTION OF THE TNVENTION
In a preferred embodiment of the invention, measurements are conducted using a modified version of the apparatus described in U.S. Patent Numbers 5,456,253 and 5,372,136. Both of these patents form part of the present disclosure.
Thus, in a preferred embodiment, hematocrit is measured in living tissue located at some convenient location on the body, such as, an ear lobe, finger tip, nose or other accessible tissue sites. In a preferred embodiment the apparatus and signal manipulations described in U.S. Patent Number 5,372,136 are utilized to measure various optical parameters that will be described hereafter. The numbered components in Figures l, 1 A, 1 B, and 1 C are similar to the numbers in Figure 1 ofU.S. Patent Number 5,456,253.
In the present disclosure, Figure 1 shows the finger 7 of an individual placed into a clam-shell type fixture 6 wherein the optical and other physical measurements can be easily performed.
The clam-shell type holder allows for adaptability to various finger sizes.
However, other fixture methods such as Figures 1B through lE, can be used to obtain similar physical data as using the clam-shell fixture.
THEORETICAL BASIS OF THE SPECTROPHOTOMETRIC AND MATHEMATICAL
ANALYSIS FOR TRANSCUTANEOUS HEMATOCRIT MEASUREMENT
Non-invasive, transcutaneous hematocrit measurement using a spectroscopic method is described below:
I. Introduction Earlier spectrophotometric techniques have fallen short of being able to fully characterize the individual blood absorbance coe~cients. The following discussion demonstrates the method of decoupling, or isolating from the bulk tissue attenuation parameters (including the convoluted absorptive and scattering parameters) the individual blood absorptive constants. This unique method identifies, isolates and compartmentalizes each of the contributing biologic elements of the tissue media. This decoupling process can either isolate the blood absarbance of interest and/or eliminate the scattering contribution from the bulk media measurement.
From photon diffusion analysis:
sL'I'(P~ - aZ 'I'(P~= -SIPS. ( 1 ) aP? D
where, D = ~.-. (2) 3 (K + S) a = J3K(K+ S) (3) K KbXb+~~+K,VX", (~) Kb = I~ (Q,oSAT + ( 1 - SAT)au) + ( 1 - I~KP (5) V
S=SeXb+SsX, (6) Sb = .~li(1-Hl(1.4-Hl (7) v and where, a = Bulk attenuation coefficient of the tissue sample K = Bulk absorption coefficient of the tissue sample S = Bulk scattering coeffccient of the tissue sample D = Diffusion constant Kb = Macroscopic absorption coefficient for whale blood (WB) Sb = Macroscopic transport - corrected scattering coefficient for WB
KD = Macroscopic absorption coefficient for plasma K, = Macroscopic absorption coeffcient for skin, & other non water/blood components Kw = Macroscopic absorption coefficient for water i' = Volume of a red blood cell (RBC) H = Hematocrit, volume fraction of RBCs to total blood volume SAT = Oxygen saturation a~ = Absorption cross - section of oxygenated RBCs Qo, = Absorption cross - section of deoxygenated IZBCs Q, = Transport - corrected scattering cross-section of RBCs Xb = Fractional volume of blood per total tissue volume X, = Fractional volume of skin, & non water/blood components per total tissue volume X" = Fractional volume of water per totai tissue volume ~F(p) = The photon density at a distance p S(p) = The source function.
II. Analysis The light flux, or intensity, i, is given by i = Due. When evaluated at p = d, one ap solution to equation ( I ) is:
i = A eaa (8}
e~'~ - I
where A is a nontrivial function of the tissue scattering coefficient, S, the distance, d (if small), and the bulk attenuation coefficient, a. If a d >=~ 1, then (8) becomes:
i = Ae'a° (9) where A = a [d° ~ (1-a ~"d)] or (1/d2 + 1/ad) for 0<n<2, where n is the power that d is raised to.
Figure (2) shows the actual patient data plot of ln(i) vs. d, where a is determined directly from the slope of the line.
The attenuation coefficient, a, is a bulk term which encompasses the attenuation measurement sensitivity to variations in skin color, presence of bone, callous, blood and water content, etc. In addition, a expresses the optical "path lengthening"
effects of both the absorption and scattering characteristics of the tissue. Therefore, since a is a function of HCT and the intensity of the transmitted light can be measured, the HCT can be calculated by manipulation of the preceding relationships.
Beginning with equation (9), the troublesome and complex tissue function, A, can be eliminated by taking the logarithm of (9) and differentiating with respect to the distance, d Unfortunately the term Xb is not known but changes with time as a result of a patient's cardiac cycle. Therefore, by differentiating with respect to time, this parameter becomes the time rate of change of blood volume which can be obtained through several methods described below. These time and distance derivatives may be performed in either order.
[1) Taking the logarithm of (9) and differentiating with respect to the distance, d, yields:
a = ~[ ln(i)1 ( 10) ad Next the derivative of (10) with respect to time, t, gives:
a ~tn(c) a -a~r ~ (l l) a«
ar - ar [2) Alternatively, first differentiate (9) with respect to time, t, to get:
-~~ she+~~'s+~! ~,. (12) at aXb c'Y a.Y, cf aXw at When ~ 7~ and ~ ~" are negligible, and normalizing (12) by i yields:
ax, ~ axw ~
agar ' axb a« a _ 1 a ~ or, (13) A ax ar Cax b b ~ =~,c (d - do) , where do =J... _ - 2d (13a) i at a e~° - 1 Figure 3 plainly demonstrates the offset term when the various graph lines are extrapolated to d = 0. The amount of offset is shown along the y-axis.
Next differentiate {13) with respect to distance, d, to eliminate that offset term to get:
~a~~ar~
a ; axb a_« _ _a«
- ar axb at (14) Equations (3) - (7) are now used to extract the hemato;,rit from a. Squaring (3) and differentiating with respect to time results in:
~a a« _ ~ a!~ (~~ +s)+xas {ls) at at at Substituting the derivatives of (4) and (6) into ( 1 s) and rearranging:
o« 3 a l' aX aX,. 16 -_ ~~~h+ ~~.f+ ~~~. (2~+s)+~. as°sn+aassl~ ( ) at at at i« ~ at -ax , ax, , b axw axb s » aX~ s.~ ~,d rc ax At SOS nm' ath ~e » at ~'~ ' at K° » ~ :at K~ ' at ° at < < S so that ( 16) can be simplified to:
s~L = ~.. ~a (KeS + ~~ ( 17) ar 2« ar By using the 805 nm wavelength the red blood cell absorption cross-section constants are equal, aQO = oy, and Kp is negligible. The hematocrit can then be determined directly from Kb as (S) simplifies to:
H = V Kb ( 17a) a, Figure 4 shows the linearity of Kb(H).
IfKb,S » KSb, where S is approximately 1.0 / mm in human tissue, then solving (17) for Kb and substituting into ( 17a) gives:
2 V a_a (18) H- 3aa a at a xb s at To rewrite in terms of measurable intensity, i, (10) and (14) are substituted into (18) to obtain:
2V- a~ln(i)~ a ~(al;'at~~i]
a~ as H- axb s (19) ar IfKbS' is not » KS~, then substituting (5) and (7) into (17a) and rearranging terms yields:
_ _2a _aa a Xb a Q ~ a f _ H 3 at at S ~, +l~ V ~~. KX1.4-H~~ (18a) Alternatively from (13a) : H ~ a-l~ilatlil (18b) (d-do) ' X'b Equation (18a) indicates a small nonlinearity in H may occur based on the magnitude of K for a given individual.
It should be reiterated that the change in received intensity with time is a result of the change in normalized blood volume resulting from the cardiac cycle itself as blood pulses through the examined tissue. As the intensity of the received light is measured, its time rate of change can be calculated. The change with distance can be determined by placing multiple emitters (such as 1-4 in Figure 1 A) and/or multiple detectors such that multiple thicknesses of tissue and hence, lengths of tissue are penetrated.
To examine ~ further, the following can be defined for the illuminated tissue:
ar Yb = Volume of blood, V", = Volume of water, and Vs = Volume of skin, tissue and other non-water or blood components.
By definition, Xb = Va (2~) Vb+Vw+Y, differentiating (20) with respect to time gives:
(Yw + V~ ~a _ Va s~Yw = at cf (21) ar (Vb + YW + VJ)z Since ~w_ « ~ and Yb « VW + VJ, (21 ) simplifies to:
ar ar ~a (22) at V~r It is emphasized that a is a function of the bulk absorption and scattering coefficients, K and S, as well as hematocrit, H. Further, that K and S are functions of the fractional volumes of each constituent, Xb X,, and X",, which must be used to prorate the individual absorption and scattering coefficients, Kb Kf, K~. Sb and S=. Therefore, the transducer system must be responsive not only to a change in volume (O V) due to the influx of the blood, but must also be responsive to the normalized change in volume of blood, normalized to the total volume of the finger (Vf)or tissue being measured, D V~
Vr For Reflectance (R) measurements in homogenous tissue:
R = Ae'"', where A ~ ( 1/~ + 1/ar), where r is the radial distance, and ~F = a' (r/(a2 ~- ar)) R
However, for tissue, which is typically non-homogeneous with a dermal and subcutaneous layer, the reflectance will not be a trivial function but can be described as approximately:
R = L(C~ + Cz) exP (-C3 ' r)~/r"
Where C1 and Ci are inter-related photon flux densities between the dermal layer I2 and the subcutaneous layer, I2a (see Figures 1C and IE). Likewise, C3 is a strong function of z,, z2, al, and a2; i.e., the thickness of the dermis or dermal layer 12, subcutaneous layer 12a, and their respective a's.
Since C,' is a function of the inter-related photon flux densities C, and/or C2 and if Xb', does not equal Xb'2, then the slope C3' will not be nulled out by the Xb' monitors mentioned. Therefore, Xb2 must be greater than Xb,'. Then the pressure or piezo monitors will compensate correctly. The circular pressure balloon is ideal for not only sensing the change in a pressure, but also providing. a pressure against the denmis causing Xb,' to be small. However, recognizing that the penetration depth of the 800 nm light typically extends through dermal layer 12 into the deep tissue, subcutaneous layer 12a, a different wavelength selection is appropriate. Thusly, when the photons only penetrate into the dermal layer 12, C3' will only be a function of z, and a,. Those selected wavelengths, as mentioned in U.S.
Patent No. 5,372,136, would be the green (570-595 nm) wavelength and 1300 nm wavelength. The green wavelengths are used as the hematocrit bearing wavelength and the 1300 nm wavelength is used as the non-hematocrit bearing, or reference wavelength. That is, for reflectance measurements the green (Gr)-1300 wavelength pair would give the hematocrit information as:
~Gr / Gr ~ ,~, = f (HCT) X1300/1300 a,3~
III. Methods of ~ measurement ar axJar can be measured and compensated for through the use of a number of different methods - (a) a pressure transducer, (b) a strain transducer such as piezo electric film or strain gage, (e) a different wavelength of light, such as 1300 nm, which also holds o~Jd t information, but holds little hematocrit information, or (d) other transducers. The individual methods of obtaining aXb/at are addressed below.
A. Pressure Transducer Measurement of ~
at Consider a pressure transducer system 36 with a gas filled bladder 38 surrounding a finger tip 10 of a patient contained within a fixed volume clam shell fixture 6, see Figures 1, lA- 1D. The same derivations, equations, and results would apply to any other body appendage or tissue that could be contacted such that a change in the tissue volume would change the pressure of the contacted pressure transducer system. For a finger note:
y<<o,~ = V~.= + Vi ( ) where V~,o,~ = Clam-shell fixture volume Vryl = Bladder system volume V~ = Finger volume Also ~Yf= -AVrys. The system will have a bulk modulus of elasticity, p, such that:
(24) Substituting (23) into (24) results in:
0 y~ _ ym.~ _ 1 ~
V~ ~ (25) Since G1 V~ = d Va then from (25) we have:
DP
8 Xa __ V~,~ _ 1 m (ZSa) at Vj As stated above, (3 is a constant of the pressure transducer system. However, an empirical solution for V~~m _ 1 was found to have a nonlinear relation to the pressure of V~
the transducer system. For a given clam shell - pressure transducer embodiment a polynomial, F(p), can accurately describe y r~~~ _ Il., see Figure 5 V~
B. Strain Transducer (Strain Gage/Piezo Electric Film) Measurement of ~b at Again it is assumed that ~ Ya = ~ Vj, and that the finger changes volume only by a change in diameter. A strain gage or piezo electric film is secured tightly around the finger (again any applicable body appendage or tissue would apply) such that a change in diameter would produce a strain in the transducer. Specifically assuming a cylindrical finger:
~ _ ~.~V~ _ ~ = 2~czr ~, (26) al al at al Normalizing with respect to V~ yields:
2~tzr~
~'a =_ ~
a'Y V,«ar , trzrz r al (27) A change in the length of the transducer element is related to a change in finger WO 99/39631 PCT/US99t02586 radius by OL = 2nOr, therefore:
~ = 2.~I~t) = 2 Y(t) (28) at L, where y(t) _ ~ is the rate of change in the strain as a function of time. For a strain L
gage this value can be measured from an appropriate electrical circuit, see Figure 6, as it is proportional to the rate of change in the gage resistance.
For a piezo electric film the voltage produced is proportional to the strain, therefore:
7~ø _ ~ v t (29) at g"T ar where, g" is the piezoelectric coefficient for the stretch axis, z is the film thickness and v(t) is the open-circuit output voltage.
C. 1300 nm Light Measurement of ?~
at The selection of the 1300 nm wavelength is based on criteria established in U.S.
Patent Number 5,372,136. The approach here is not to solve for a.Y~/a, and substitute into (19) but to ratiometrically eliminate aX~dt. In the case of the 1300 nm reference wavelength, the assumptions following equation (12) are no longer valid; i.e., aXfat and aX"/at are not negligible, since water absorption at 1300 nm is so large. Hence, for the 1300 nm equations (13), (14) and (15) would result in:
as 3 ~(2K+S)Kb+KSb~+{~2K+S~K,+h'S,~+
at ,~ - 2a ar at ( ~(21~' + S)K~, at where, a, and the bulk and material specific K, and S are wavelength (.1) dependent.
Recalling that, Xb + X, + XW = 1, by definition, and that:
~_s3~_ ° ~
ar a/ ar (31 ) By substituting (31) into (30) and noting that K",3 = Kb,~, the following is obtained:
a« ax~
« {xs~ }aa n + ~(ZK + SxK, - x~.]+ h,s, } ar (32) n Since, ~, » ~_, (32) becomes:
ar ar a« ~ -_ 3 {~S } a xb ..
ar " 2«" b .a ar (33) Therefore, to eliminate ~ arid solve for the hematocrit, (17) is divided by (33) ar yielding:
(a«~a r )g -_ «" Kb s Sg -, (a«~a~)I~ «a Ke sb " (34) Since S8 and K,3 are weal behaved and known (let 1f,3 /Ss = G) in human tissue and the ratio ~ is a function of H, then rearranging (34) gives:
Sem Ca«~
«$ ar a G (35) a«
(ar) Where ~c can be measured using (11) or (14). See Figure 7 for,f~.
at D. Other aXb/at measurements such as doppler, ultrasonic, electrical conductivity, magnetic permeability and other techniques have similar derivations. The important consideration is that aX8/at is a normalized time varying quantity.
IV. Analytical implementation If hematocrit is constant over a given time interval, averaging can eliminate system noise whose frequency components have corresponding periods much shorter than the interval. In addition, by observing the data variance during the interval it may be determined that the data is invalid. In the present system, the data acquisition rate is approximately 1000 data samples per second. This means that within a typical human pulse about 1000 samples of data are available for appropriate numerical analysis, averaging and qualification.
Recognizing that both the intensity of light and the pressure in the transducer system are changing in time during the influx of blood is of great importance. Since the parametric relationship of aalat as a function of c7Plat (where P is pressure) during the cardiac cycle, should be linear, a multiplicity of data points facilitate qualification of the signal for accuracy and linearity. Whereas, prior techniques involving only the peak and valley values of the cardiac cycle require numerous pulses to qualify the data set. See Figures 8, 9 and 10.
Fig. 8 shows di/dt/i as well as dP/dt verses time during the cardiac pulse -it is a pulse showing ~ 200+ data samples during the pulse.
Fig. 9 shows (di/dt)/i vs dP/dt showing that within one cardiac pulse 200 plus data samples are li en arfv related, i.e. trace up out of the "0" origin up to a maximum value and then back down toward the origin again.
Fig. 10 shows da/dt/dP/dt versus time during one single cardiac pulse with 200 plus samples of data from time 15 - 45 giving a value of about 4.5 thousandths. The data can then be averaged, as if 200+ individuals pulse (max-min) values were actually taken as present day oxymeters do.
A. ymogen Since the above derivations are based on the assumption of tissue homogeneity (i.e.,c7Xb~t = aXb~a t , A,= AZ, c?A,/c7Xb = c7Az/aXb, a, = a,, etc.), high-speed, single-pulse, multiple parameter sampling allows for mathematical qualification of homogeneity, by requiring linearity of In(i) vs. d and (ailat)li vs. d Under these constraints and when qualified as homogeneous, (c7alc7t)l(aPlc7t) also may be assumed to be linear over the entire pulse contour.
Finally, both a and c7a/at must also be linear, further assuring homogeneity in Xb, and in c7X~t.
B. Circuitry See U.S. Patent Number 5,372,136 for the operational circuitry description, which allows for high speed sampling of the optical intensities. See Figures 6 and 10 for similar circuitry considerations for sampling of pressure, peizo, and strain-gage measurements.
The circuitry shown and discussed in US Patent Number 5,372,136 is programmable by conventional techniques to solve and implement the equations and calculations presented in this application. Figure 6 shows a piezo transducer circuit having a transducer 50 connected to a series of operational amplifiers, resistors and capacitors in accordance with the figure. The circuit terminates in an analog output 52 for connection to the "E" connection shown in the middle left side of Fig. 9D in U.S. Patent Number 5,372,136. Figure 11, on the other hand, shows a pressure transducer circuit having a pressure transducer made 62 connected to a series of operational amplifiers, a capacitor, resistors and variable resistors as shown in the figure. The circuit .
terminates in an analog output also connected to the aforementioned "E"
connection.
Referring more specifically to FIG. 6, a crystal oscillator is connected to ground and to the non-inverting input of a first operational amplifier, which may be an LM158.
The non-inverting input of the first operational amplifier is connected to ground by a .047 I1F
capacitor C3. The first operational amplifier's feedback path to its inverting input includes a 470 K
resistor R8. The first operational ampftf er is suitably biased at the junction of a 220 S2 resistor R7 and a 150 pF
capacitor C4 that are connected between VCC and ground.
A second operational amplifier, which may also be an LM 158, receives the output of the first operational amplifier at its inverting input via a 10 KS2 resistor R5.
The second operational amplifier's non-inverting input is connected to several locations:
~ to a voltage VB51, which may be 4.096 volts, through a 10 K~2 resistor R2;
~ to a middle node of a voltage divider, the voltages divider extending between the non-inverting input of the first operational amplifier via a 10 MS2 resistor R4 to the middle node, and via a 10 Kf2 resistor R1 to ground;
~ to the inverting input of the first operational amplifier via a 10 KS2 resistor R9; and ~ to ground via a 220 pF capacitor C5.
The second operational amplifier's feedback path to its inverting input includes a parallel arrangement of a 0.1 pF capacitor C2 and a 47 KS~ resistor R6. The second operational amplifier drives the A/D output 52 via a 10 KS~ resistor R3, the output connected to ground via a 1 pF
capacitor C 1.
Of course, the particular choice, arrangement and values of components shown in FIG. 6 may be varied while still remaining within the scope of the invention.
Referring now to FIG. 10, first through fourth operational amplifiers, which may be LM348s, are illustrated. The operational amplifiers are powered and biased by voltages VCC and VEE.
The first operational amplifier's non-inverting input is set to a value determined by the tap setting of a 1 KS~ adjustable resistor RZ that extends between VCC and VEE.
The DAC input drives the first operational amplifier's inverting input via a 1 KSZ resistor R1. The first operational amplifier's feedback path includes a SO KS2 adjustable resistor R4. The first operational amplifier drives the second operational amplifier's inverting input through an 11 KS2 resistor R3. The feedback path to the inverting input of the second operational amplifier includes a 100 SZ resistor R5.
A transducer 62, which may include a Motorola MPX20100P, has opposite terminals that drive the non-inverting inputs of the second and third operational amplifiers, respectively. The other two opposite terminals of the transducer are connected to VCC and ground, respectively.
The second operational amplifier drives the inverting input of the third operational amplifier via a 750 f~ resistor R6. The third operational amplifier's feedback path to its inverting input includes a parallel arrangement of a 93.1 KSa resistor R10 and a .001 pF
capacitor C1.
The third operational amplifier drives the non-inverting input of the fourth operational amplifier via a 1 IC~2 resistor R7. The inverting input of the fourth operational amplifier is connected to ground via a 1 KSZ resistor R8. The feedback path to the inverting input of the fourth operational amplifier includes a 50 ICI adjustable resistor R9. The fourth operational amplifier drives the output of the FIG. 11 circuit.
Of course, the particular choice, arrangement and values of components shown in FIG. 10 may be varied while still remaining within the scope of the invention.
C. Preferred Embodiment Physical embodiments as shown in Figure 1 include the optical array, pressure transducer/balloon system and clam-shell fixture. Requisites of the preferred embodiment include a holder for the finger (or other tissue) such as seen in Figures 1 and 1 A
and IB. This clam-shell fixture not only secures the tissue but also the optical array, and transducer system.
Figure 1D is a schematic diagram for a mylar base member 38 that is shaped generally like a cross. As oriented in Figure 1 D, vertically extending portion 52 crosses with a horizontally extending portion 54 to yield top leg 56, bottom leg 58, and side legs 60, 62.
In use, a finger 7 lies along the longitudinally extending portion 52 with the finger tip placed on the top leg 56 to properly cover the arrangement of LED's 32 and photodetector 34, which are arranged like those on Figures 1 A - 1 C. A piezoelectric pressure transducer or strain gage 66 spans the horizontally extending portion 54 from near the tip of side leg 60 to the tip of side leg 62. In this orientation, the transducer or gage may be wrapped around the finger 7 for use in measurements.
The optical array 30, seen in Figure 1D, shows the arrangement of multiple LED's 32 spaced at known separation distances from the detector 34. This array provides for the instantaneous distance, or "d", derivative, by the transmission mode shown in Figure lA or in reflectance modes shown in Figures IB and IC. However, as shown in Figure lE, a single LED
42 swept across the finger 7 or tissue surface 9 with a stepper motor 44 would provide a d derivative as would a cantilevered clam-shell with an angular measurement device. In any case, d must be known and/or fixed. Also the detectors and emitters may be placed anywhere about the finger.
The pressure/balloon, strain gage, or peizo transducer system incorporated within the clam-shell fixture ( see Section III, A, B, C and Figure 1 A) provides the contact surface area needed to define the c3X,fc3t.
High-speed sampling provides for a closer approximation of the instantaneous time, t, derivative, a/dt, as opposed to peak-valley values, see Figure 8. Therefore, the above embodiments allow for the direct measurement of In (i) at d,, d~, d3 and d, cotemporaneously, thereby determining the actual a of the sampled tissue. Likewise (ailc3t)li can be directly measured at d,, d~" dj and d,,, cotemporaneously during the pulse which determines the instantaneous dalat.
The above mentioned optical array can be utilized transmissively and/or reflectively provided the separation distance between the detector and first emitter (d,) is greater than 3mm.
D. Choice of Non-Ionizing Waveleng~ht Since hematocrit is an example of the desired biological constituent concentration value of interest, selection criteria of the preferred wavelength must include an understanding of equation (5). That is, a wavelength whose coefficients Kr K~, Kp are small compared to Kb and which are also insensitive to oxygen saturation status must be selected. Such wavelengths include 805 nm, 590 nm, 569 nm and other isobestic wavelengths with negligible water absorption. While non-isobestic wavelengths, with small water absorption, could function, a second wavelength is needed to null out the oxygen saturation effects.
If the desired biologic constituent value of interest is the blood giucose, bilirubin, cholesterol or other parameters, then a second wavelength must be chosen. The first wavelength, 805 nm, is used to measure the hematocrit, H, after which a KpBOS (the absorbance of plasma at ~.
= 805 nm) can be determined. Then, knowing the H, a second wavelength, 570 nm, is chosen where ICps,o is less than ICp8o5. Similarly, if the first wavelength used to measure the H and the reference glucose, ICn (glucose) is 570 nm, the second wavelength, 1060 nm, is chosen where ICps,~ is much less than ICPI~. In the case of bilirubin, the first wavelength used to measure the H
and the reference bilirubin, ICp (bilirubin), is 570 nm, the second wavelength, 440 nm, is then chosen when ICPS~o is much less than ICI,"o. The selection of these above mentioned wavelengths therefore assures uniqueness for the measurement of the desired biologic constituent.
Additionally for glucose determination, recall that the 1300 nm wavelength is not hematocrit or hemoglobin dependent but will be glucose sensitive. This is primarily due to the dependence of the scattering coefficient on the difference between the index of refraction of pure water and glucose, i.e.: recall Sb8 = H (1-H) a,g (from equation 7) where:
Q,B = 8'rz2yo ('~1'e - 1 )Z ' b" / ~2 where rl'8 = index of refraction of the RBC~hemoglobin at 800 nm relative to plasma rlo (the plasma index of refraction), and, Sbl3 = H (1-H) a,13 (also from equation 7) where:
Qsl3 - 87C2 1'~0 (Tl'13 - 1 )2 ' b" / ~.Z
rl'13 = the index of refraction of glucose at 1300 nm relative to rlo.
Therefore, the 8 13 ratio has both hematocrit ~ glucose information. Whereas the a$~a'g/OP
(equation 18a) ratio has only hematocrit information. Therefore the differential combination of those ratios will be a strong function of glucose only.
E. Improved Accuracy Pulse Oximeter Device The accuracy of present day pulse oximeters suffers from 4 major problems:
tissue perfusion (low Xb and low c7X~t), d dependence (varying finger sizes), tissue nonhomogeneity ( the tissue penetration depth for 660 nm light is not the same as for 940 nm light), and H dependence (see equation (5)).
All of the above mentioned deficiencies in pulse oximetry can be eliminated by understanding equation (13). Equation (13) indicates an "offset term", _ ~ ~.
A c7Xb Hence, while merely dividing (Dili)x, by (Aili)x2 mitigates the effect of c7X~lc7t, the ds do not completely cancel, thereby yielding the above mentioned problems. To improve pulse oximeter accuracy, a derivative is needed as in ( 14), which eliminates the "offset term". Hence, the ratio of (aaldt)8osl(aaltl)~ results in no H, d, or Xb dependence and the use of the multiple LED array and high-speed sampling as mentioned in section IV qualifies the tissue as homogeneous.
V. A Simplified Two Step Approach (A) Determination of H and Xb The bulk attenuation coefficient, a, can be easily measured with the optical array, at 805 nm, utilizing equation (10) and as described in Section IV(C). Notice that at 805 nm, a is a strong function of H and X6 since K,8 K",8, Kp8 are small, see Figure 12.
Therefore, by knowing Xb itself, H can be determined. Xb itself can be determined using a WO 99/39631 PC'T/US99/02586 strain gage in the following two step approach. Step One, measure the strain gage resistance when the finger is made bloodless, by squeezing finger, such as with a stepper motor. Step Two, measure the strain gage resistance when the finger is blood filled, for example by suction.
Mathematically, at 805 nm and when Kr, Kp K", are small, equation (3) is approximated by:
a2 ~ 3KS (36) or a~ ~ 3IKbXbJfs~b + S~sJ (37) Substituting (5) and (7) into (37) yields:
0=3 H~° Xb H(1-H)(1.4-H) V Xs+SrXJJ-a- (38) v C
With Xb and a measured and known, and with the a's and S~. Xl approximately constant, H
can be solved with a quadratic formula or a polynomial fit.
The strain gage determination of Xb is as follows:
Let V° = the volume of a bloodless finger. Let V~ = the volume of blood filled finger, and again considering the finger as a cylinder:
Y° _ ~rZZ = ys + y,. (39) yf- nR~z = yb +, VJ + Vw and V" -CrJ, (41) V~
From equation (20) Xb = ~~ y V - 1 _ ~ (42) Substituting (41) into (42):
Xb 1 ~ Rl (43) Where the strain gage resistances are proportional to the radius, r and R, of the finger.
(B) j2eterm~nation of tissue water content X, Choosing the wavelength of 1300 nm, where K, and K" are significant, the tissue water content, XW, can be determined. Recall that 1 - Xb - Xw = X, and substituting into (3) yields:
az ~a = 3((Kb - K~~~Yb ~' {KW - ~s)XW '~ ~'~
(~~~b-KJI + (Sb-~r~~b + ~~K~r-~s~ -SfJXw~+ Kt ~" Si With a,~" Xb and H determined and because K~. Kj, ~'". S~, and S, are known coefficient values at 1300 nm, Xw is solved with either a quadratic formula or a polynomial fit.
RESULTS .
Figure 13 demonstrates preliminary results with 30 patients the application of the method and apparatus and the application of Equation 19 on numerous patients with a correlation of r =
0.96.
As implied throughout, those skilled in the art will also appreciate that the methods for determining blood hematocrit values within the scope of the present invention may be adapted for determining other non-hematocrit biologic constituent values such as glucose, bilirubin, cholesterol, tissue water, etc.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. While the foregoing described embodiments are~to be considered in all respects only as illustrative of the claimed invention, they are not intended to restrict the scope of the claims. The scope of the invention is, therefore, indicated by the following appended claims rather than by the foregoing description. All changes within the meaning and range of equivalency of the claims are to be embraced within their scope.
Claims (20)
1. A method for determining a desired biological constituent concentration of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient so as to be subjectable to transcutaneous examination in the body part, the body part defining a blood conduit and the method comprising the steps of:
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising a first quantity of radiation at a chosen radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value, and (c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising a second quantity of radiation at the chosen radiation wavelength; and (d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring the time rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized change of the pulsatile blood; and (e) operating exclusively on the second quantity of the radiation and the transduced energy to determine the desired biologic constituent concentration.
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising a first quantity of radiation at a chosen radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value, and (c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising a second quantity of radiation at the chosen radiation wavelength; and (d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring the time rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized change of the pulsatile blood; and (e) operating exclusively on the second quantity of the radiation and the transduced energy to determine the desired biologic constituent concentration.
2. A method as defined in claim 1, wherein the step of detecting the second quantity of radiation at the radiation wavelength comprises the steps of:
(a) determining the intensity of the radiation wavelength;
and (b) determining a radiation wavelength pulsatile value representing the intensities of a pulsatile component of the radiation wavelength at discreet time intervals during the pulse.
(a) determining the intensity of the radiation wavelength;
and (b) determining a radiation wavelength pulsatile value representing the intensities of a pulsatile component of the radiation wavelength at discreet time intervals during the pulse.
3. A method as defined in claim 1, wherein the step of detecting the transduced energy comprises the steps of:
(a) determining the electronic signal generated from the transduced energy; and (b) determining a transduced energy pulsatile value representing the intensities of a pulsatile component of the transduced energy at discreet time intervals during the pulse.
(a) determining the electronic signal generated from the transduced energy; and (b) determining a transduced energy pulsatile value representing the intensities of a pulsatile component of the transduced energy at discreet time intervals during the pulse.
4. A method as defined in claim 1, wherein the step of operating exclusively on the second quantities of the radiation at the radiation wavelength to determine the desired biologic constituent concentration of the patient comprises the steps of:
(a) mathematically operating on the second quantity of the radiation such that the time derivative of the pulsatile intensities is normalized by the average intensity over the pulse interval followed by a distance derivative of that quantity to produce a value proportional to ~.alpha./~t; and (b) mathematically operating on the second quantity of the radiation such that the logarithm of the intensity is distance differentiated to produce a value .alpha., where .alpha. is the bulk attenuation coefficient of a tissue sample and ~.alpha./~t is the time rate of change of the bulk attenuation coefficient.
(a) mathematically operating on the second quantity of the radiation such that the time derivative of the pulsatile intensities is normalized by the average intensity over the pulse interval followed by a distance derivative of that quantity to produce a value proportional to ~.alpha./~t; and (b) mathematically operating on the second quantity of the radiation such that the logarithm of the intensity is distance differentiated to produce a value .alpha., where .alpha. is the bulk attenuation coefficient of a tissue sample and ~.alpha./~t is the time rate of change of the bulk attenuation coefficient.
5. A method as defined in claim 1, wherein the step of operating exclusively on the transduced energy comprises the step of performing the time derivative of the normalized pulsatile transduced energy to obtain a value ~X b~t, where X b is the fractional volume of blood per total tissue volume and t is time.
6. A method as defined in claim 1, wherein the step of operating exclusively on the second quantity of the radiation and the transduced energy comprises the step of mathematically solving the relationship K b = .beta. .cndot. (.alpha. .cndot.
~.alpha./~t)/(~X b~t) with a polynomial function or empirically determined value, where K b is the macroscopic absorption coefficient for whole blood, .beta. is a constant of the blood conduit receiver, .alpha. is the bulk attenuation coefficient of the tissue sample, t is time, X b is the fractional volume of blood per total tissue volume, ~a/~t is the time rate of change of the bulk attenuation coefficient, and ~X b~t is the change in blood volume over time.
~.alpha./~t)/(~X b~t) with a polynomial function or empirically determined value, where K b is the macroscopic absorption coefficient for whole blood, .beta. is a constant of the blood conduit receiver, .alpha. is the bulk attenuation coefficient of the tissue sample, t is time, X b is the fractional volume of blood per total tissue volume, ~a/~t is the time rate of change of the bulk attenuation coefficient, and ~X b~t is the change in blood volume over time.
7. A method as defined in claim 1, wherein the desired biologic constituent comprises hematocrit or hemoglobin.
8. A method as defined in claim 1, wherein the first attenuation value is substantially the same amount for oxyhemoglobin and for reduced hemoglobin in the flowing blood and the second attenuation value is at least ten times smaller than said first attenuation value for any competing constituent in the flowing blood.
9. A method as defined in claim 1, wherein the radiation wavelength is in the range from about 790 nanometers to 850 nanometers.
10. A method as defined in claim 1, wherein the radiation wavelength is in the range from about 550 nanometers to 600 nanometers.
11. A method as defined in claim 1, wherein the energy transducer means is a pressure transducer element, a strain gage element, a piezo electric film element, or a doppler detection element.
12. A method for determining a desired biological constituent concentration of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient so as to be subjectable to transcutaneous examination in the body part, the body part defining a blood conduit and the method comprising the steps of:
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising:
(i) a first quantity of radiation at a first radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value, and (ii) a first quantity of radiation at a second radiation wavelength, distinct from said first wavelength, which, when directed into the flowing blood within the blood conduit, (A) has a third attenuation value which for varying concentrations in the flowing blood of the desired blood constituent is a non-fixed multiple of said first attenuation value; and (B) has a fourth attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which fourth attenuation value is at least ten times greater than said second attenuation value;
(c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising:
(i) a second quantity of radiation at the first radiation wavelength; and, (ii) a second quantity of radiation at the second radiation wavelength;
(d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring the time rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized blood change of the pulsatile blood; and (e) operating exclusively on the second quantities of the radiations and the transduced energy to determine the desired biologic constituent concentration.
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising:
(i) a first quantity of radiation at a first radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value, and (ii) a first quantity of radiation at a second radiation wavelength, distinct from said first wavelength, which, when directed into the flowing blood within the blood conduit, (A) has a third attenuation value which for varying concentrations in the flowing blood of the desired blood constituent is a non-fixed multiple of said first attenuation value; and (B) has a fourth attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which fourth attenuation value is at least ten times greater than said second attenuation value;
(c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising:
(i) a second quantity of radiation at the first radiation wavelength; and, (ii) a second quantity of radiation at the second radiation wavelength;
(d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring the time rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized blood change of the pulsatile blood; and (e) operating exclusively on the second quantities of the radiations and the transduced energy to determine the desired biologic constituent concentration.
13. A method as defined in claim 12, wherein the step of operating exclusively on the transduced energy comprises the step of performing the time derivative of the normal pulsatile transduced energy of the second radiation wavelength to obtain a value ~X b/~t, where X b is the fractional volume of blood per total tissue volume, and ~X b/~t is the time rate of change of the fractional blood volume.
14. A method as defined in claim 12, wherein the step of operating exclusively on the second quantities of the radiations and the transduced energy comprises the step of solving the relationship .function.(H)=G(.alpha.'~.alpha./.alpha.t) for the first wavelength divided by (.alpha.'~.alpha./~t) for the second wavelength with a polynomial function or empirically determined value, where H is hematocrit, G is a constant related to bulk tissue absorption and scattering, .alpha. is the bulk attenuation coefficient of a tissue sample, and t is time.
15. A method for determining a desired biological constituent concentration of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient so as to be subjectable to transcutaneous examination in the body part, the body part defining a blood conduit and the method comprising the steps of:
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising a first quantity of radiation at a chosen radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value;
(c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising a second quantity of radiation at the chosen radiation wavelength; and (d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring time rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized blood volume; and (e) operating exclusively on the second quantity of the radiation and the transduced energy to determine the desired biologic constituent concentration.
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising a first quantity of radiation at a chosen radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value;
(c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising a second quantity of radiation at the chosen radiation wavelength; and (d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring time rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized blood volume; and (e) operating exclusively on the second quantity of the radiation and the transduced energy to determine the desired biologic constituent concentration.
16. A method as defined in claim 15, wherein the step of operating exclusively on the transduced energy comprises the step of measuring the transduced energy when the blood conduit is blood-filled, then later made blood-less in order to obtain a value X b, which is the volume of blood per total tissue volume.
17. A method as defined in claim 16, wherein the step of determining X b is accomplished by solving (V0/V f)-1 where V0 is the volume of a bloodless finger and V f is the volume of a blood filled finger.
18. A method as defined in claim 16, wherein the step of determining, X b is accomplished by solving (V0/V f)-1 with a polynomial function and the energy transducer is a pressure transducer and where V0 is the volume of a bloodless finger and V f is the volume of a blood filled finger.
19. A method for determining a desired biologic constituent concentration of the blood of a patient, the blood flowing in a pulsatile fashion in a body part of the patient so as to be subjectable to transcutaneous examination in the body part, the body part defining a blood conduit and the method of comprising the steps of:
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising a first quantity of a radiation at a chosen radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value;
(c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising a second quantity of radiation at the chosen radiation wavelength;
(d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring the tame rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized change of the pulsatile blood; and (e) operating exclusively on the second quantity of the (e) operating exclusively on the second quantity of the radiation and the transduced energy to determine the desired biologic constituent concentration by quantifying the tissue's homogeneity from the linearity of the distance differentiation.
(a) placing the blood conduit within a blood conduit receiver with the blood flowing in the blood conduit;
(b) directing radiation into the flowing blood within the blood conduit using a radiation generator situated within said blood conduit receiver, said radiation defining a directed radiation comprising a first quantity of a radiation at a chosen radiation wavelength which, when directed into the flowing blood within the blood conduit, (A) has a first attenuation value which varies with the desired biologic constituent concentration in the flowing blood and (B) has a second attenuation value which varies with the concentration of components other than the desired biologic constituent in the flowing blood, which second attenuation value is at least ten times smaller than said first attenuation value;
(c) detecting the portion of said directed radiation which passes through both the blood conduit and the flowing blood therein using a radiation detector situated within said blood conduit receiver, said detected portion of said directed radiation comprising a second quantity of radiation at the chosen radiation wavelength;
(d) detecting energy from the flowing blood within the blood conduit using an energy transducer situated within said blood conduit receiver, said energy transducer for measuring the tame rate of change of blood volume, said energy defining a transduced energy comprising a quantity of energy which when detected from the flowing blood within the blood conduit, has a value which varies with the normalized change of the pulsatile blood; and (e) operating exclusively on the second quantity of the (e) operating exclusively on the second quantity of the radiation and the transduced energy to determine the desired biologic constituent concentration by quantifying the tissue's homogeneity from the linearity of the distance differentiation.
20. A method as defined in claim 19, wherein the step of operating exclusively on the second quantity of the radiation at the radiation wavelength to determine the desired biologic constituent concentration of the patient comprises the steps of:
(a) mathematically operating on the second quantity of the radiation wavelength such that the logarithm of the intensity is distance differentiated to produce a value .alpha., where .alpha. is the bulk attenuation coefficient of a tissue sample;
(b) mathematically operating on the second quantity of the radiation wavelength such that the time derivative of the pulsatile intensities is normalized by the average intensity over the pulse interval followed by a distance derivative of that quantity to produce a value proportional to ~.alpha./~t; which is the change in the bulk attenuation coefficient over time;
(c) mathematically determining the linearity and deviation of the logarithm of the intensity and the (~i/~t)/i values versus distance where i is light intensity and t is time; and (d) mathematically decoupling, isolating, and determining the individual constituent absorptive and scattering coefficients from the values of .alpha., the bulk attenuation coefficient, ~.alpha./~t and ~X b/~t, the change in blood volume over time.
(a) mathematically operating on the second quantity of the radiation wavelength such that the logarithm of the intensity is distance differentiated to produce a value .alpha., where .alpha. is the bulk attenuation coefficient of a tissue sample;
(b) mathematically operating on the second quantity of the radiation wavelength such that the time derivative of the pulsatile intensities is normalized by the average intensity over the pulse interval followed by a distance derivative of that quantity to produce a value proportional to ~.alpha./~t; which is the change in the bulk attenuation coefficient over time;
(c) mathematically determining the linearity and deviation of the logarithm of the intensity and the (~i/~t)/i values versus distance where i is light intensity and t is time; and (d) mathematically decoupling, isolating, and determining the individual constituent absorptive and scattering coefficients from the values of .alpha., the bulk attenuation coefficient, ~.alpha./~t and ~X b/~t, the change in blood volume over time.
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PCT/US1999/002586 WO1999039631A1 (en) | 1998-02-05 | 1999-02-05 | Method and apparatus for non-invasive blood constituent monitoring |
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Families Citing this family (282)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6725072B2 (en) * | 1990-10-06 | 2004-04-20 | Hema Metrics, Inc. | Sensor for transcutaneous measurement of vascular access blood flow |
US7758503B2 (en) * | 1997-01-27 | 2010-07-20 | Lynn Lawrence A | Microprocessor system for the analysis of physiologic and financial datasets |
US6018673A (en) | 1996-10-10 | 2000-01-25 | Nellcor Puritan Bennett Incorporated | Motion compatible sensor for non-invasive optical blood analysis |
US9042952B2 (en) | 1997-01-27 | 2015-05-26 | Lawrence A. Lynn | System and method for automatic detection of a plurality of SPO2 time series pattern types |
US9468378B2 (en) | 1997-01-27 | 2016-10-18 | Lawrence A. Lynn | Airway instability detection system and method |
US8932227B2 (en) | 2000-07-28 | 2015-01-13 | Lawrence A. Lynn | System and method for CO2 and oximetry integration |
US7890158B2 (en) * | 2001-06-05 | 2011-02-15 | Lumidigm, Inc. | Apparatus and method of biometric determination using specialized optical spectroscopy systems |
US6628809B1 (en) | 1999-10-08 | 2003-09-30 | Lumidigm, Inc. | Apparatus and method for identification of individuals by near-infrared spectrum |
US9521971B2 (en) | 1997-07-14 | 2016-12-20 | Lawrence A. Lynn | System and method for automatic detection of a plurality of SPO2 time series pattern types |
US20070191697A1 (en) | 2006-02-10 | 2007-08-16 | Lynn Lawrence A | System and method for SPO2 instability detection and quantification |
ATE416668T1 (en) * | 1998-02-05 | 2008-12-15 | Hema Metrics Inc | METHOD AND DEVICE FOR NON-INVASIVE OBSERVATION OF BLOOD COMPONENTS |
US6804543B2 (en) | 1998-02-05 | 2004-10-12 | Hema Metrics, Inc. | Sensor for transcutaneous measurement of vascular access blood flow |
US6241663B1 (en) | 1998-05-18 | 2001-06-05 | Abbott Laboratories | Method for improving non-invasive determination of the concentration of analytes in a biological sample |
US6526298B1 (en) | 1998-05-18 | 2003-02-25 | Abbott Laboratories | Method for the non-invasive determination of analytes in a selected volume of tissue |
US7043287B1 (en) | 1998-05-18 | 2006-05-09 | Abbott Laboratories | Method for modulating light penetration depth in tissue and diagnostic applications using same |
US6662031B1 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratoies | Method and device for the noninvasive determination of hemoglobin and hematocrit |
US6662030B2 (en) | 1998-05-18 | 2003-12-09 | Abbott Laboratories | Non-invasive sensor having controllable temperature feature |
US6615061B1 (en) | 1998-11-23 | 2003-09-02 | Abbott Laboratories | Optical sensor having a selectable sampling distance for determination of analytes |
US6353226B1 (en) | 1998-11-23 | 2002-03-05 | Abbott Laboratories | Non-invasive sensor capable of determining optical parameters in a sample having multiple layers |
US6675031B1 (en) * | 1999-04-14 | 2004-01-06 | Mallinckrodt Inc. | Method and circuit for indicating quality and accuracy of physiological measurements |
US6816605B2 (en) | 1999-10-08 | 2004-11-09 | Lumidigm, Inc. | Methods and systems for biometric identification of individuals using linear optical spectroscopy |
US20040044287A1 (en) * | 2000-03-31 | 2004-03-04 | Wei-Chiang Lin | Identification of human tissue using optical spectroscopy |
US8224412B2 (en) | 2000-04-17 | 2012-07-17 | Nellcor Puritan Bennett Llc | Pulse oximeter sensor with piece-wise function |
EP2684514B1 (en) | 2000-04-17 | 2018-10-24 | Covidien LP | Pulse oximeter sensor with piece-wise function |
AU2000254395A1 (en) * | 2000-06-02 | 2001-12-17 | Hema Metrics, Inc | System and method for measuring blood urea nitrogen, blood osmolarity, plasma free haemoglobin and tissue water content |
US6635491B1 (en) | 2000-07-28 | 2003-10-21 | Abbott Labortories | Method for non-invasively determining the concentration of an analyte by compensating for the effect of tissue hydration |
US20060195041A1 (en) | 2002-05-17 | 2006-08-31 | Lynn Lawrence A | Centralized hospital monitoring system for automatically detecting upper airway instability and for preventing and aborting adverse drug reactions |
US9053222B2 (en) | 2002-05-17 | 2015-06-09 | Lawrence A. Lynn | Patient safety processor |
US6591122B2 (en) | 2001-03-16 | 2003-07-08 | Nellcor Puritan Bennett Incorporated | Device and method for monitoring body fluid and electrolyte disorders |
US7239902B2 (en) * | 2001-03-16 | 2007-07-03 | Nellor Puritan Bennett Incorporated | Device and method for monitoring body fluid and electrolyte disorders |
US7657292B2 (en) * | 2001-03-16 | 2010-02-02 | Nellcor Puritan Bennett Llc | Method for evaluating extracellular water concentration in tissue |
US8135448B2 (en) * | 2001-03-16 | 2012-03-13 | Nellcor Puritan Bennett Llc | Systems and methods to assess one or more body fluid metrics |
US7167734B2 (en) | 2001-04-13 | 2007-01-23 | Abbott Laboratories | Method for optical measurements of tissue to determine disease state or concentration of an analyte |
KR100612827B1 (en) * | 2001-04-19 | 2006-08-14 | 삼성전자주식회사 | Method and apparatus for noninvasively measuring hemoglobin concentration and oxygen saturation |
US20070093721A1 (en) * | 2001-05-17 | 2007-04-26 | Lynn Lawrence A | Microprocessor system for the analysis of physiologic and financial datasets |
US6754516B2 (en) | 2001-07-19 | 2004-06-22 | Nellcor Puritan Bennett Incorporated | Nuisance alarm reductions in a physiological monitor |
US6748254B2 (en) * | 2001-10-12 | 2004-06-08 | Nellcor Puritan Bennett Incorporated | Stacked adhesive optical sensor |
US7009180B2 (en) | 2001-12-14 | 2006-03-07 | Optiscan Biomedical Corp. | Pathlength-independent methods for optically determining material composition |
US6862534B2 (en) | 2001-12-14 | 2005-03-01 | Optiscan Biomedical Corporation | Method of determining an analyte concentration in a sample from an absorption spectrum |
KR100455289B1 (en) * | 2002-03-16 | 2004-11-08 | 삼성전자주식회사 | Method of diagnosing using a ray and apparatus thereof |
DE10213692B4 (en) * | 2002-03-27 | 2013-05-23 | Weinmann Diagnostics Gmbh & Co. Kg | Method for controlling a device and device for measuring ingredients in the blood |
US20080200775A1 (en) * | 2007-02-20 | 2008-08-21 | Lynn Lawrence A | Maneuver-based plethysmographic pulse variation detection system and method |
US6711425B1 (en) | 2002-05-28 | 2004-03-23 | Ob Scientific, Inc. | Pulse oximeter with calibration stabilization |
US6865407B2 (en) * | 2002-07-11 | 2005-03-08 | Optical Sensors, Inc. | Calibration technique for non-invasive medical devices |
US7190986B1 (en) | 2002-10-18 | 2007-03-13 | Nellcor Puritan Bennett Inc. | Non-adhesive oximeter sensor for sensitive skin |
US7006856B2 (en) * | 2003-01-10 | 2006-02-28 | Nellcor Puritan Bennett Incorporated | Signal quality metrics design for qualifying data for a physiological monitor |
US7016715B2 (en) | 2003-01-13 | 2006-03-21 | Nellcorpuritan Bennett Incorporated | Selection of preset filter parameters based on signal quality |
FI115109B (en) * | 2003-01-22 | 2005-02-28 | Nokia Corp | An authentication arrangement and a mobile station comprising an authentication arrangement |
US7347365B2 (en) * | 2003-04-04 | 2008-03-25 | Lumidigm, Inc. | Combined total-internal-reflectance and tissue imaging systems and methods |
US7460696B2 (en) * | 2004-06-01 | 2008-12-02 | Lumidigm, Inc. | Multispectral imaging biometrics |
US7539330B2 (en) * | 2004-06-01 | 2009-05-26 | Lumidigm, Inc. | Multispectral liveness determination |
US7668350B2 (en) * | 2003-04-04 | 2010-02-23 | Lumidigm, Inc. | Comparative texture analysis of tissue for biometric spoof detection |
US7751594B2 (en) | 2003-04-04 | 2010-07-06 | Lumidigm, Inc. | White-light spectral biometric sensors |
AU2004227886A1 (en) * | 2003-04-04 | 2004-10-21 | Lumidigm, Inc. | Multispectral biometric sensor |
US7627151B2 (en) * | 2003-04-04 | 2009-12-01 | Lumidigm, Inc. | Systems and methods for improved biometric feature definition |
US7633621B2 (en) * | 2003-04-11 | 2009-12-15 | Thornton Robert L | Method for measurement of analyte concentrations and semiconductor laser-pumped, small-cavity fiber lasers for such measurements and other applications |
US7283242B2 (en) * | 2003-04-11 | 2007-10-16 | Thornton Robert L | Optical spectroscopy apparatus and method for measurement of analyte concentrations or other such species in a specimen employing a semiconductor laser-pumped, small-cavity fiber laser |
US7271912B2 (en) | 2003-04-15 | 2007-09-18 | Optiscan Biomedical Corporation | Method of determining analyte concentration in a sample using infrared transmission data |
DE10319281B4 (en) * | 2003-04-29 | 2006-06-29 | United Business Gmbh & Co. Consulting Kg | Apparatus and method for detecting the life of a body part in a biometric test method |
US20050007582A1 (en) * | 2003-07-07 | 2005-01-13 | Lumidigm, Inc. | Methods and apparatus for collection of optical reference measurements for monolithic sensors |
CN101912257B (en) * | 2003-10-09 | 2013-04-24 | 日本电信电话株式会社 | Living body information detection circuit and living body information measurement apparatus |
US7247143B2 (en) * | 2003-10-29 | 2007-07-24 | Hema Metrics, Inc. | Bladder-based cuff for measuring physiological parameters and method of measuring physiological parameters using same |
JP4568578B2 (en) * | 2004-02-19 | 2010-10-27 | ニュースキン インターナショナル インコーポレイテッド | Biophotonic feedback control apparatus and method |
US7120479B2 (en) * | 2004-02-25 | 2006-10-10 | Nellcor Puritan Bennett Inc. | Switch-mode oximeter LED drive with a single inductor |
US7162288B2 (en) * | 2004-02-25 | 2007-01-09 | Nellcor Purtain Bennett Incorporated | Techniques for detecting heart pulses and reducing power consumption in sensors |
US7190985B2 (en) | 2004-02-25 | 2007-03-13 | Nellcor Puritan Bennett Inc. | Oximeter ambient light cancellation |
US7194293B2 (en) * | 2004-03-08 | 2007-03-20 | Nellcor Puritan Bennett Incorporated | Selection of ensemble averaging weights for a pulse oximeter based on signal quality metrics |
US7534212B2 (en) * | 2004-03-08 | 2009-05-19 | Nellcor Puritan Bennett Llc | Pulse oximeter with alternate heart-rate determination |
US7277741B2 (en) * | 2004-03-09 | 2007-10-02 | Nellcor Puritan Bennett Incorporated | Pulse oximetry motion artifact rejection using near infrared absorption by water |
US7508965B2 (en) * | 2004-06-01 | 2009-03-24 | Lumidigm, Inc. | System and method for robust fingerprint acquisition |
US8229185B2 (en) * | 2004-06-01 | 2012-07-24 | Lumidigm, Inc. | Hygienic biometric sensors |
US8787630B2 (en) * | 2004-08-11 | 2014-07-22 | Lumidigm, Inc. | Multispectral barcode imaging |
US20060122520A1 (en) * | 2004-12-07 | 2006-06-08 | Dr. Matthew Banet | Vital sign-monitoring system with multiple optical modules |
US7392075B2 (en) | 2005-03-03 | 2008-06-24 | Nellcor Puritan Bennett Incorporated | Method for enhancing pulse oximetry calculations in the presence of correlated artifacts |
CN100355390C (en) * | 2005-03-15 | 2007-12-19 | 深圳迈瑞生物医疗电子股份有限公司 | Method of blood oxygen probe sealing wire of silica gel finger sleeve and its mold |
EP1867277A4 (en) * | 2005-04-08 | 2014-07-09 | Terumo Corp | Sphygmomanometry instrument |
US7801338B2 (en) | 2005-04-27 | 2010-09-21 | Lumidigm, Inc. | Multispectral biometric sensors |
US7657294B2 (en) | 2005-08-08 | 2010-02-02 | Nellcor Puritan Bennett Llc | Compliant diaphragm medical sensor and technique for using the same |
US7657295B2 (en) | 2005-08-08 | 2010-02-02 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7590439B2 (en) | 2005-08-08 | 2009-09-15 | Nellcor Puritan Bennett Llc | Bi-stable medical sensor and technique for using the same |
EP1931239B1 (en) * | 2005-08-09 | 2012-08-08 | Flore, Ingo | Medical measuring device |
US20070060808A1 (en) * | 2005-09-12 | 2007-03-15 | Carine Hoarau | Medical sensor for reducing motion artifacts and technique for using the same |
US8092379B2 (en) * | 2005-09-29 | 2012-01-10 | Nellcor Puritan Bennett Llc | Method and system for determining when to reposition a physiological sensor |
US7725147B2 (en) * | 2005-09-29 | 2010-05-25 | Nellcor Puritan Bennett Llc | System and method for removing artifacts from waveforms |
US7904130B2 (en) * | 2005-09-29 | 2011-03-08 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7725146B2 (en) | 2005-09-29 | 2010-05-25 | Nellcor Puritan Bennett Llc | System and method for pre-processing waveforms |
US7899510B2 (en) * | 2005-09-29 | 2011-03-01 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7869850B2 (en) | 2005-09-29 | 2011-01-11 | Nellcor Puritan Bennett Llc | Medical sensor for reducing motion artifacts and technique for using the same |
US7483731B2 (en) | 2005-09-30 | 2009-01-27 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7486979B2 (en) * | 2005-09-30 | 2009-02-03 | Nellcor Puritan Bennett Llc | Optically aligned pulse oximetry sensor and technique for using the same |
US8062221B2 (en) * | 2005-09-30 | 2011-11-22 | Nellcor Puritan Bennett Llc | Sensor for tissue gas detection and technique for using the same |
US7881762B2 (en) * | 2005-09-30 | 2011-02-01 | Nellcor Puritan Bennett Llc | Clip-style medical sensor and technique for using the same |
US8233954B2 (en) * | 2005-09-30 | 2012-07-31 | Nellcor Puritan Bennett Llc | Mucosal sensor for the assessment of tissue and blood constituents and technique for using the same |
US20070106126A1 (en) | 2005-09-30 | 2007-05-10 | Mannheimer Paul D | Patient monitoring alarm escalation system and method |
US7555327B2 (en) * | 2005-09-30 | 2009-06-30 | Nellcor Puritan Bennett Llc | Folding medical sensor and technique for using the same |
US20070100220A1 (en) * | 2005-10-28 | 2007-05-03 | Baker Clark R Jr | Adjusting parameters used in pulse oximetry analysis |
US7668579B2 (en) * | 2006-02-10 | 2010-02-23 | Lynn Lawrence A | System and method for the detection of physiologic response to stimulation |
US20070208259A1 (en) * | 2006-03-06 | 2007-09-06 | Mannheimer Paul D | Patient monitoring alarm escalation system and method |
US8702606B2 (en) * | 2006-03-21 | 2014-04-22 | Covidien Lp | Patient monitoring help video system and method |
US8073518B2 (en) | 2006-05-02 | 2011-12-06 | Nellcor Puritan Bennett Llc | Clip-style medical sensor and technique for using the same |
US7790464B2 (en) * | 2006-05-04 | 2010-09-07 | Blaze Medical Devices, LLC | Blood hemolysis analyzer |
US20070282181A1 (en) * | 2006-06-01 | 2007-12-06 | Carol Findlay | Visual medical sensor indicator |
US8255025B2 (en) * | 2006-06-09 | 2012-08-28 | Nellcor Puritan Bennett Llc | Bronchial or tracheal tissular water content sensor and system |
US8380271B2 (en) | 2006-06-15 | 2013-02-19 | Covidien Lp | System and method for generating customizable audible beep tones and alarms |
US8175346B2 (en) * | 2006-07-19 | 2012-05-08 | Lumidigm, Inc. | Whole-hand multispectral biometric imaging |
US7995808B2 (en) * | 2006-07-19 | 2011-08-09 | Lumidigm, Inc. | Contactless multispectral biometric capture |
US8355545B2 (en) * | 2007-04-10 | 2013-01-15 | Lumidigm, Inc. | Biometric detection using spatial, temporal, and/or spectral techniques |
KR101349892B1 (en) * | 2006-07-19 | 2014-01-13 | 루미다임 인크. | Multibiometric multispectral imager |
US7804984B2 (en) | 2006-07-31 | 2010-09-28 | Lumidigm, Inc. | Spatial-spectral fingerprint spoof detection |
US7801339B2 (en) | 2006-07-31 | 2010-09-21 | Lumidigm, Inc. | Biometrics with spatiospectral spoof detection |
DE102006036920B3 (en) * | 2006-08-04 | 2007-11-29 | Nirlus Engineering Ag | Measuring glucose concentration in pulsating blood involves determining concentration in first measurement cycle, repeating, measuring transmission, scattering for near infrared wavelengths, computing indicator value, comparing with table |
US8145288B2 (en) | 2006-08-22 | 2012-03-27 | Nellcor Puritan Bennett Llc | Medical sensor for reducing signal artifacts and technique for using the same |
US20080064940A1 (en) * | 2006-09-12 | 2008-03-13 | Raridan William B | Sensor cable design for use with spectrophotometric sensors and method of using the same |
US8064975B2 (en) * | 2006-09-20 | 2011-11-22 | Nellcor Puritan Bennett Llc | System and method for probability based determination of estimated oxygen saturation |
US8219170B2 (en) * | 2006-09-20 | 2012-07-10 | Nellcor Puritan Bennett Llc | System and method for practicing spectrophotometry using light emitting nanostructure devices |
US8396527B2 (en) | 2006-09-22 | 2013-03-12 | Covidien Lp | Medical sensor for reducing signal artifacts and technique for using the same |
US8190224B2 (en) * | 2006-09-22 | 2012-05-29 | Nellcor Puritan Bennett Llc | Medical sensor for reducing signal artifacts and technique for using the same |
US8175671B2 (en) * | 2006-09-22 | 2012-05-08 | Nellcor Puritan Bennett Llc | Medical sensor for reducing signal artifacts and technique for using the same |
US20080076977A1 (en) * | 2006-09-26 | 2008-03-27 | Nellcor Puritan Bennett Inc. | Patient monitoring device snapshot feature system and method |
US7869849B2 (en) * | 2006-09-26 | 2011-01-11 | Nellcor Puritan Bennett Llc | Opaque, electrically nonconductive region on a medical sensor |
US7574245B2 (en) * | 2006-09-27 | 2009-08-11 | Nellcor Puritan Bennett Llc | Flexible medical sensor enclosure |
US8180419B2 (en) * | 2006-09-27 | 2012-05-15 | Nellcor Puritan Bennett Llc | Tissue hydration estimation by spectral absorption bandwidth measurement |
US8696593B2 (en) | 2006-09-27 | 2014-04-15 | Covidien Lp | Method and system for monitoring intracranial pressure |
US7922665B2 (en) | 2006-09-28 | 2011-04-12 | Nellcor Puritan Bennett Llc | System and method for pulse rate calculation using a scheme for alternate weighting |
US7796403B2 (en) * | 2006-09-28 | 2010-09-14 | Nellcor Puritan Bennett Llc | Means for mechanical registration and mechanical-electrical coupling of a faraday shield to a photodetector and an electrical circuit |
US7890153B2 (en) * | 2006-09-28 | 2011-02-15 | Nellcor Puritan Bennett Llc | System and method for mitigating interference in pulse oximetry |
US8728059B2 (en) * | 2006-09-29 | 2014-05-20 | Covidien Lp | System and method for assuring validity of monitoring parameter in combination with a therapeutic device |
US7848891B2 (en) | 2006-09-29 | 2010-12-07 | Nellcor Puritan Bennett Llc | Modulation ratio determination with accommodation of uncertainty |
US7684842B2 (en) | 2006-09-29 | 2010-03-23 | Nellcor Puritan Bennett Llc | System and method for preventing sensor misuse |
US20080097175A1 (en) * | 2006-09-29 | 2008-04-24 | Boyce Robin S | System and method for display control of patient monitor |
US7476131B2 (en) | 2006-09-29 | 2009-01-13 | Nellcor Puritan Bennett Llc | Device for reducing crosstalk |
US7925511B2 (en) * | 2006-09-29 | 2011-04-12 | Nellcor Puritan Bennett Llc | System and method for secure voice identification in a medical device |
US7706896B2 (en) * | 2006-09-29 | 2010-04-27 | Nellcor Puritan Bennett Llc | User interface and identification in a medical device system and method |
US8068891B2 (en) | 2006-09-29 | 2011-11-29 | Nellcor Puritan Bennett Llc | Symmetric LED array for pulse oximetry |
US20080082338A1 (en) * | 2006-09-29 | 2008-04-03 | O'neil Michael P | Systems and methods for secure voice identification and medical device interface |
US20080081956A1 (en) * | 2006-09-29 | 2008-04-03 | Jayesh Shah | System and method for integrating voice with a medical device |
US7680522B2 (en) * | 2006-09-29 | 2010-03-16 | Nellcor Puritan Bennett Llc | Method and apparatus for detecting misapplied sensors |
US8116852B2 (en) * | 2006-09-29 | 2012-02-14 | Nellcor Puritan Bennett Llc | System and method for detection of skin wounds and compartment syndromes |
US8175667B2 (en) | 2006-09-29 | 2012-05-08 | Nellcor Puritan Bennett Llc | Symmetric LED array for pulse oximetry |
US8068890B2 (en) * | 2006-09-29 | 2011-11-29 | Nellcor Puritan Bennett Llc | Pulse oximetry sensor switchover |
US8160668B2 (en) * | 2006-09-29 | 2012-04-17 | Nellcor Puritan Bennett Llc | Pathological condition detector using kernel methods and oximeters |
US7698002B2 (en) * | 2006-09-29 | 2010-04-13 | Nellcor Puritan Bennett Llc | Systems and methods for user interface and identification in a medical device |
EP2096989B1 (en) * | 2006-11-23 | 2012-11-21 | Flore, Ingo | Medical measuring device |
KR100871074B1 (en) | 2007-02-01 | 2008-11-28 | 삼성전자주식회사 | Noninvasive apparatus and method for measuring blood glucose |
US20080200819A1 (en) * | 2007-02-20 | 2008-08-21 | Lynn Lawrence A | Orthostasis detection system and method |
US7894869B2 (en) | 2007-03-09 | 2011-02-22 | Nellcor Puritan Bennett Llc | Multiple configuration medical sensor and technique for using the same |
US20080221416A1 (en) * | 2007-03-09 | 2008-09-11 | Nellcor Puritan Bennett Llc | System and method for detection of macular degeneration using spectrophotometry |
US8175665B2 (en) * | 2007-03-09 | 2012-05-08 | Nellcor Puritan Bennett Llc | Method and apparatus for spectroscopic tissue analyte measurement |
US20080220512A1 (en) * | 2007-03-09 | 2008-09-11 | Nellcor Puritan Bennett Llc | Tunable laser-based spectroscopy system for non-invasively measuring body water content |
US8357090B2 (en) * | 2007-03-09 | 2013-01-22 | Covidien Lp | Method and apparatus for estimating water reserves |
US7713196B2 (en) * | 2007-03-09 | 2010-05-11 | Nellcor Puritan Bennett Llc | Method for evaluating skin hydration and fluid compartmentalization |
US8280469B2 (en) * | 2007-03-09 | 2012-10-02 | Nellcor Puritan Bennett Llc | Method for detection of aberrant tissue spectra |
US8346327B2 (en) * | 2007-03-09 | 2013-01-01 | Covidien Lp | Method for identification of sensor site by local skin spectrum data |
US8265724B2 (en) * | 2007-03-09 | 2012-09-11 | Nellcor Puritan Bennett Llc | Cancellation of light shunting |
US8690864B2 (en) * | 2007-03-09 | 2014-04-08 | Covidien Lp | System and method for controlling tissue treatment |
US20080221426A1 (en) * | 2007-03-09 | 2008-09-11 | Nellcor Puritan Bennett Llc | Methods and apparatus for detecting misapplied optical sensors |
US20080221411A1 (en) * | 2007-03-09 | 2008-09-11 | Nellcor Puritan Bennett Llc | System and method for tissue hydration estimation |
JP2010522379A (en) * | 2007-03-21 | 2010-07-01 | ルミダイム インコーポレイテッド | Biometric authentication based on locally invariant features |
JP5568461B2 (en) * | 2007-03-27 | 2014-08-06 | ネイボン,アリエル | Apparatus and method for monitoring blood parameters |
US8412296B2 (en) * | 2007-07-20 | 2013-04-02 | General Electric Company | Non-invasive determination of the concentration of a blood substance |
ATE533399T1 (en) * | 2007-09-07 | 2011-12-15 | Flore Ingo | MEDICAL MEASURING DEVICE FOR BIOELECTRIC IMPEDANCE MEASUREMENT |
CN101848672A (en) * | 2007-09-13 | 2010-09-29 | 密苏里大学董事会 | Optical device components |
JP4569615B2 (en) * | 2007-09-25 | 2010-10-27 | ブラザー工業株式会社 | Printing device |
CN101903757B (en) * | 2007-10-04 | 2012-08-29 | 密苏里大学董事会 | Optical device components |
US8517941B1 (en) * | 2007-10-23 | 2013-08-27 | Pacesetter, Inc. | Implantable cardiac device and method for monitoring blood-glucose concentration |
US8175668B1 (en) | 2007-10-23 | 2012-05-08 | Pacesetter, Inc. | Implantable multi-wavelength venous oxygen saturation and hematocrit sensor and method |
US7961305B2 (en) | 2007-10-23 | 2011-06-14 | The Curators Of The University Of Missouri | Optical device components |
US8204567B2 (en) * | 2007-12-13 | 2012-06-19 | Nellcor Puritan Bennett Llc | Signal demodulation |
US8346328B2 (en) | 2007-12-21 | 2013-01-01 | Covidien Lp | Medical sensor and technique for using the same |
US8352004B2 (en) | 2007-12-21 | 2013-01-08 | Covidien Lp | Medical sensor and technique for using the same |
US8366613B2 (en) * | 2007-12-26 | 2013-02-05 | Covidien Lp | LED drive circuit for pulse oximetry and method for using same |
US8577434B2 (en) | 2007-12-27 | 2013-11-05 | Covidien Lp | Coaxial LED light sources |
US20090168050A1 (en) * | 2007-12-27 | 2009-07-02 | Nellcor Puritan Bennett Llc | Optical Sensor System And Method |
US20090171167A1 (en) * | 2007-12-27 | 2009-07-02 | Nellcor Puritan Bennett Llc | System And Method For Monitor Alarm Management |
US8442608B2 (en) * | 2007-12-28 | 2013-05-14 | Covidien Lp | System and method for estimating physiological parameters by deconvolving artifacts |
US8452364B2 (en) | 2007-12-28 | 2013-05-28 | Covidien LLP | System and method for attaching a sensor to a patient's skin |
US8092993B2 (en) | 2007-12-31 | 2012-01-10 | Nellcor Puritan Bennett Llc | Hydrogel thin film for use as a biosensor |
US20090171174A1 (en) * | 2007-12-31 | 2009-07-02 | Nellcor Puritan Bennett Llc | System and method for maintaining battery life |
US20090171166A1 (en) * | 2007-12-31 | 2009-07-02 | Nellcor Puritan Bennett Llc | Oximeter with location awareness |
US20090171173A1 (en) * | 2007-12-31 | 2009-07-02 | Nellcor Puritan Bennett Llc | System and method for reducing motion artifacts in a sensor |
US20090216096A1 (en) * | 2007-12-31 | 2009-08-27 | Nellcor Puritan Bennett Llc | Method and apparatus to determine skin sterol levels |
US8897850B2 (en) * | 2007-12-31 | 2014-11-25 | Covidien Lp | Sensor with integrated living hinge and spring |
US8199007B2 (en) * | 2007-12-31 | 2012-06-12 | Nellcor Puritan Bennett Llc | Flex circuit snap track for a biometric sensor |
US20090171226A1 (en) * | 2007-12-31 | 2009-07-02 | Nellcor Puritan Bennett Llc | System and method for evaluating variation in the timing of physiological events |
US8070508B2 (en) * | 2007-12-31 | 2011-12-06 | Nellcor Puritan Bennett Llc | Method and apparatus for aligning and securing a cable strain relief |
WO2009100423A1 (en) * | 2008-02-08 | 2009-08-13 | Cas Medical Systems, Inc. | Improved method for spectrophotometric blood oxygenation monitoring |
US8750953B2 (en) * | 2008-02-19 | 2014-06-10 | Covidien Lp | Methods and systems for alerting practitioners to physiological conditions |
US8275553B2 (en) * | 2008-02-19 | 2012-09-25 | Nellcor Puritan Bennett Llc | System and method for evaluating physiological parameter data |
KR100978907B1 (en) * | 2008-03-06 | 2010-08-31 | (주)참케어 | Oximeter |
JP5427362B2 (en) * | 2008-03-25 | 2014-02-26 | テルモ株式会社 | Method and apparatus for measuring hematocrit value or blood component concentration |
US10542919B2 (en) * | 2008-03-25 | 2020-01-28 | St. Louis Medical Devices, Inc. | Method and system for non-invasive blood glucose detection utilizing spectral data of one or more components other than glucose |
US20090247851A1 (en) * | 2008-03-26 | 2009-10-01 | Nellcor Puritan Bennett Llc | Graphical User Interface For Monitor Alarm Management |
US20090247854A1 (en) * | 2008-03-27 | 2009-10-01 | Nellcor Puritan Bennett Llc | Retractable Sensor Cable For A Pulse Oximeter |
US8140272B2 (en) * | 2008-03-27 | 2012-03-20 | Nellcor Puritan Bennett Llc | System and method for unmixing spectroscopic observations with nonnegative matrix factorization |
US8437822B2 (en) * | 2008-03-28 | 2013-05-07 | Covidien Lp | System and method for estimating blood analyte concentration |
US20090247850A1 (en) * | 2008-03-28 | 2009-10-01 | Nellcor Puritan Bennett Llc | Manually Powered Oximeter |
US8112375B2 (en) * | 2008-03-31 | 2012-02-07 | Nellcor Puritan Bennett Llc | Wavelength selection and outlier detection in reduced rank linear models |
US8292809B2 (en) | 2008-03-31 | 2012-10-23 | Nellcor Puritan Bennett Llc | Detecting chemical components from spectroscopic observations |
US8364224B2 (en) * | 2008-03-31 | 2013-01-29 | Covidien Lp | System and method for facilitating sensor and monitor communication |
FR2930343B1 (en) * | 2008-04-18 | 2014-09-19 | Commissariat Energie Atomique | OPTICAL DEVICE FOR ANALYZING A DIFFUSING MEDIUM SUPPORTED BY A SUPPORT |
EP2283443A1 (en) * | 2008-05-07 | 2011-02-16 | Lynn, Lawrence A. | Medical failure pattern search engine |
WO2009136311A2 (en) * | 2008-05-08 | 2009-11-12 | Koninklijke Philips Electronics N.V. | Contact pressure control for probe for material analysis |
EP3556290A1 (en) | 2008-05-22 | 2019-10-23 | St. Louis Medical Devices, Inc. | Method and system for non-invasive optical blood glucose detection utilizing spectral data analysis |
USD626561S1 (en) | 2008-06-30 | 2010-11-02 | Nellcor Puritan Bennett Llc | Circular satseconds indicator and triangular saturation pattern detection indicator for a patient monitor display panel |
US7887345B2 (en) | 2008-06-30 | 2011-02-15 | Nellcor Puritan Bennett Llc | Single use connector for pulse oximetry sensors |
US8077297B2 (en) | 2008-06-30 | 2011-12-13 | Nellcor Puritan Bennett Ireland | Methods and systems for discriminating bands in scalograms |
US8295567B2 (en) | 2008-06-30 | 2012-10-23 | Nellcor Puritan Bennett Ireland | Systems and methods for ridge selection in scalograms of signals |
US7880884B2 (en) * | 2008-06-30 | 2011-02-01 | Nellcor Puritan Bennett Llc | System and method for coating and shielding electronic sensor components |
US8827917B2 (en) * | 2008-06-30 | 2014-09-09 | Nelleor Puritan Bennett Ireland | Systems and methods for artifact detection in signals |
US20090327515A1 (en) * | 2008-06-30 | 2009-12-31 | Thomas Price | Medical Monitor With Network Connectivity |
US9895068B2 (en) * | 2008-06-30 | 2018-02-20 | Covidien Lp | Pulse oximeter with wait-time indication |
USD626562S1 (en) | 2008-06-30 | 2010-11-02 | Nellcor Puritan Bennett Llc | Triangular saturation pattern detection indicator for a patient monitor display panel |
US8071935B2 (en) * | 2008-06-30 | 2011-12-06 | Nellcor Puritan Bennett Llc | Optical detector with an overmolded faraday shield |
US8862194B2 (en) | 2008-06-30 | 2014-10-14 | Covidien Lp | Method for improved oxygen saturation estimation in the presence of noise |
EP2326239B1 (en) | 2008-07-03 | 2017-06-21 | Masimo Laboratories, Inc. | Protrusion for improving spectroscopic measurement of blood constituents |
US8203704B2 (en) | 2008-08-04 | 2012-06-19 | Cercacor Laboratories, Inc. | Multi-stream sensor for noninvasive measurement of blood constituents |
US8364220B2 (en) | 2008-09-25 | 2013-01-29 | Covidien Lp | Medical sensor and technique for using the same |
US20100076319A1 (en) * | 2008-09-25 | 2010-03-25 | Nellcor Puritan Bennett Llc | Pathlength-Corrected Medical Spectroscopy |
US8433382B2 (en) * | 2008-09-30 | 2013-04-30 | Covidien Lp | Transmission mode photon density wave system and method |
US8423112B2 (en) | 2008-09-30 | 2013-04-16 | Covidien Lp | Medical sensor and technique for using the same |
US8417309B2 (en) * | 2008-09-30 | 2013-04-09 | Covidien Lp | Medical sensor |
US8968193B2 (en) * | 2008-09-30 | 2015-03-03 | Covidien Lp | System and method for enabling a research mode on physiological monitors |
US8914088B2 (en) * | 2008-09-30 | 2014-12-16 | Covidien Lp | Medical sensor and technique for using the same |
US8386000B2 (en) * | 2008-09-30 | 2013-02-26 | Covidien Lp | System and method for photon density wave pulse oximetry and pulse hemometry |
US20100081912A1 (en) * | 2008-09-30 | 2010-04-01 | Nellcor Puritan Bennett Llc | Ultrasound-Optical Doppler Hemometer and Technique for Using the Same |
US8489165B2 (en) * | 2008-10-29 | 2013-07-16 | Cnoga Medical Ltd. | Finger deployed device for measuring blood and physiological characteristics |
US20100113899A1 (en) * | 2008-11-06 | 2010-05-06 | Mark Ries Robinson | Alignment System for Optically Sampling a Hand |
ES2338624B1 (en) | 2008-11-07 | 2011-09-13 | Sabirmedical,S.L. | SYSTEM AND APPARATUS FOR NON-INVASIVE MEASUREMENT OF GLUCOSE LEVELS IN BLOOD. |
US20090171172A1 (en) * | 2008-12-19 | 2009-07-02 | Nellcor Puritan Bennett Llc | Method and system for pulse gating |
US20100246902A1 (en) * | 2009-02-26 | 2010-09-30 | Lumidigm, Inc. | Method and apparatus to combine biometric sensing and other functionality |
DE102009011381A1 (en) | 2009-03-05 | 2010-09-09 | Flore, Ingo, Dr. | Diagnostic measuring device |
US8452366B2 (en) * | 2009-03-16 | 2013-05-28 | Covidien Lp | Medical monitoring device with flexible circuitry |
US20100240972A1 (en) * | 2009-03-20 | 2010-09-23 | Nellcor Puritan Bennett Llc | Slider Spot Check Pulse Oximeter |
US8221319B2 (en) | 2009-03-25 | 2012-07-17 | Nellcor Puritan Bennett Llc | Medical device for assessing intravascular blood volume and technique for using the same |
US20100249550A1 (en) * | 2009-03-25 | 2010-09-30 | Neilcor Puritan Bennett LLC | Method And Apparatus For Optical Filtering Of A Broadband Emitter In A Medical Sensor |
RU2595488C2 (en) * | 2009-04-01 | 2016-08-27 | Дзе Кьюрейторз Оф Дзе Юниверсити Оф Миссури | Optical spectroscopic device for non-invasive determination of glucose in blood and corresponding method of application |
US8509869B2 (en) * | 2009-05-15 | 2013-08-13 | Covidien Lp | Method and apparatus for detecting and analyzing variations in a physiologic parameter |
US8634891B2 (en) * | 2009-05-20 | 2014-01-21 | Covidien Lp | Method and system for self regulation of sensor component contact pressure |
US20100331631A1 (en) * | 2009-06-30 | 2010-12-30 | Nellcor Puritan Bennett Llc | Oxygen saturation ear sensor design that optimizes both attachment method and signal quality |
US8505821B2 (en) * | 2009-06-30 | 2013-08-13 | Covidien Lp | System and method for providing sensor quality assurance |
US9010634B2 (en) * | 2009-06-30 | 2015-04-21 | Covidien Lp | System and method for linking patient data to a patient and providing sensor quality assurance |
US8311601B2 (en) * | 2009-06-30 | 2012-11-13 | Nellcor Puritan Bennett Llc | Reflectance and/or transmissive pulse oximeter |
US8391941B2 (en) * | 2009-07-17 | 2013-03-05 | Covidien Lp | System and method for memory switching for multiple configuration medical sensor |
US10475529B2 (en) | 2011-07-19 | 2019-11-12 | Optiscan Biomedical Corporation | Method and apparatus for analyte measurements using calibration sets |
US8494786B2 (en) | 2009-07-30 | 2013-07-23 | Covidien Lp | Exponential sampling of red and infrared signals |
US20110029865A1 (en) * | 2009-07-31 | 2011-02-03 | Nellcor Puritan Bennett Llc | Control Interface For A Medical Monitor |
US8417310B2 (en) * | 2009-08-10 | 2013-04-09 | Covidien Lp | Digital switching in multi-site sensor |
CA2770325A1 (en) * | 2009-08-17 | 2011-02-24 | The Regents Of The University Of California | Distributed external and internal wireless sensor systems for characterization of surface and subsurface biomedical structure and condition |
US8494606B2 (en) * | 2009-08-19 | 2013-07-23 | Covidien Lp | Photoplethysmography with controlled application of sensor pressure |
US8428675B2 (en) * | 2009-08-19 | 2013-04-23 | Covidien Lp | Nanofiber adhesives used in medical devices |
BR122013021647A2 (en) * | 2009-08-26 | 2016-04-05 | Lumidigm Inc | object locating, object discrimination and background methods, and |
US8688183B2 (en) * | 2009-09-03 | 2014-04-01 | Ceracor Laboratories, Inc. | Emitter driver for noninvasive patient monitor |
US9579039B2 (en) * | 2011-01-10 | 2017-02-28 | Masimo Corporation | Non-invasive intravascular volume index monitor |
US8704666B2 (en) * | 2009-09-21 | 2014-04-22 | Covidien Lp | Medical device interface customization systems and methods |
US8788001B2 (en) * | 2009-09-21 | 2014-07-22 | Covidien Lp | Time-division multiplexing in a multi-wavelength photon density wave system |
US8494604B2 (en) * | 2009-09-21 | 2013-07-23 | Covidien Lp | Wavelength-division multiplexing in a multi-wavelength photon density wave system |
US8798704B2 (en) * | 2009-09-24 | 2014-08-05 | Covidien Lp | Photoacoustic spectroscopy method and system to discern sepsis from shock |
US8515511B2 (en) | 2009-09-29 | 2013-08-20 | Covidien Lp | Sensor with an optical coupling material to improve plethysmographic measurements and method of using the same |
US9554739B2 (en) | 2009-09-29 | 2017-01-31 | Covidien Lp | Smart cable for coupling a medical sensor to an electronic patient monitor |
US8376955B2 (en) * | 2009-09-29 | 2013-02-19 | Covidien Lp | Spectroscopic method and system for assessing tissue temperature |
US8401608B2 (en) | 2009-09-30 | 2013-03-19 | Covidien Lp | Method of analyzing photon density waves in a medical monitor |
US20110077470A1 (en) * | 2009-09-30 | 2011-03-31 | Nellcor Puritan Bennett Llc | Patient Monitor Symmetry Control |
US20110074342A1 (en) * | 2009-09-30 | 2011-03-31 | Nellcor Puritan Bennett Llc | Wireless electricity for electronic devices |
WO2011048556A2 (en) * | 2009-10-20 | 2011-04-28 | Reuven Gladshtein | Photoplethysmography at multiple depths |
US8570149B2 (en) | 2010-03-16 | 2013-10-29 | Lumidigm, Inc. | Biometric imaging using an optical adaptive interface |
US8391943B2 (en) | 2010-03-31 | 2013-03-05 | Covidien Lp | Multi-wavelength photon density wave system using an optical switch |
US8930145B2 (en) | 2010-07-28 | 2015-01-06 | Covidien Lp | Light focusing continuous wave photoacoustic spectroscopy and its applications to patient monitoring |
US8649838B2 (en) | 2010-09-22 | 2014-02-11 | Covidien Lp | Wavelength switching for pulse oximetry |
US20120253149A1 (en) * | 2011-03-30 | 2012-10-04 | Steuer Robert | Method and apparatus for non-invasive photometric blood constituent diagnosis |
US9848787B2 (en) | 2012-02-07 | 2017-12-26 | Laser Associated Sciences, Inc. | Perfusion assessment using transmission laser speckle imaging |
US9833146B2 (en) | 2012-04-17 | 2017-12-05 | Covidien Lp | Surgical system and method of use of the same |
US10342488B2 (en) | 2014-02-24 | 2019-07-09 | The Trustees Of The University Of Pennsylvania | Probes and pressure modulation algorithms for reducing extratissue contamination in hemodynamic measurement |
US10231670B2 (en) * | 2014-06-19 | 2019-03-19 | Masimo Corporation | Proximity sensor in pulse oximeter |
CN104483237B (en) * | 2015-01-06 | 2017-02-22 | 陈玉梅 | Multi-sample blood pressure product measuring method and device based on transmissivity changing |
WO2016191307A1 (en) * | 2015-05-22 | 2016-12-01 | Cercacor Laboratories, Inc. | Non-invasive optical physiological differential pathlength sensor |
EP3310256A4 (en) | 2015-06-22 | 2018-11-14 | Fresenius Medical Care Holdings, Inc. | Transcutaneous measurement of hemoglobin changes to calculate estimated blood volume change during peritoneal dialysis |
EP3111842A1 (en) * | 2015-06-30 | 2017-01-04 | Nokia Technologies Oy | An apparatus comprising a light detector, a light source and optics |
US10813597B2 (en) | 2017-04-14 | 2020-10-27 | The Regents Of The University Of California | Non-invasive hemodynamic assessment via interrogation of biological tissue using a coherent light source |
US20190029541A1 (en) * | 2017-07-31 | 2019-01-31 | Edwards Lifesciences Corporation | Finger cuff with an expandable coil to be used in measuring a patient's blood pressure by a blood pressure measurement system |
KR102437776B1 (en) | 2017-09-26 | 2022-08-26 | 삼성전자주식회사 | Apparatus for estimating biological component and operating method thereof |
US11690520B2 (en) | 2018-06-20 | 2023-07-04 | Samsung Electronics Co., Ltd. | Apparatus and method for measuring bio-information |
JP2023504766A (en) * | 2019-10-16 | 2023-02-07 | ヴィース・センター・フォー・バイオ・アンド・ニューロ・エンジニアリング | Optical communication in embedded systems |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4802486A (en) * | 1985-04-01 | 1989-02-07 | Nellcor Incorporated | Method and apparatus for detecting optical pulses |
US4927264A (en) | 1987-12-02 | 1990-05-22 | Omron Tateisi Electronics Co. | Non-invasive measuring method and apparatus of blood constituents |
US5111817A (en) * | 1988-12-29 | 1992-05-12 | Medical Physics, Inc. | Noninvasive system and method for enhanced arterial oxygen saturation determination and arterial blood pressure monitoring |
FI82366C (en) * | 1989-02-06 | 1991-03-11 | Instrumentarium Oy | MAETNING AV BLODETS SAMMANSAETTNING. |
DK0613653T3 (en) | 1990-02-15 | 1996-12-02 | Hewlett Packard Gmbh | Method for calculating oxygen saturation |
US5152296A (en) * | 1990-03-01 | 1992-10-06 | Hewlett-Packard Company | Dual-finger vital signs monitor |
US5372136A (en) | 1990-10-06 | 1994-12-13 | Noninvasive Medical Technology Corporation | System and method for noninvasive hematocrit monitoring |
JPH04276234A (en) * | 1991-03-01 | 1992-10-01 | Colleen Denshi Kk | Oscillometric type automatic hemadynamometer |
US5277181A (en) | 1991-12-12 | 1994-01-11 | Vivascan Corporation | Noninvasive measurement of hematocrit and hemoglobin content by differential optical analysis |
JP3107914B2 (en) | 1992-07-20 | 2000-11-13 | 浜松ホトニクス株式会社 | Apparatus and method for measuring absorption information inside scattering absorber |
JP3577335B2 (en) | 1993-06-02 | 2004-10-13 | 浜松ホトニクス株式会社 | Scattering absorber measurement method and device |
JP3345481B2 (en) | 1993-09-22 | 2002-11-18 | 興和株式会社 | Pulse wave spectrometer |
US5553615A (en) * | 1994-01-31 | 1996-09-10 | Minnesota Mining And Manufacturing Company | Method and apparatus for noninvasive prediction of hematocrit |
US5528365A (en) | 1994-03-01 | 1996-06-18 | The Trustees Of The University Of Pennsylvania | Methods and apparatus for imaging with diffuse light |
US5638816A (en) * | 1995-06-07 | 1997-06-17 | Masimo Corporation | Active pulse blood constituent monitoring |
ATE416668T1 (en) * | 1998-02-05 | 2008-12-15 | Hema Metrics Inc | METHOD AND DEVICE FOR NON-INVASIVE OBSERVATION OF BLOOD COMPONENTS |
-
1999
- 1999-02-05 AT AT99906774T patent/ATE416668T1/en not_active IP Right Cessation
- 1999-02-05 US US09/244,756 patent/US6181958B1/en not_active Expired - Lifetime
- 1999-02-05 DE DE69940053T patent/DE69940053D1/en not_active Expired - Lifetime
- 1999-02-05 WO PCT/US1999/002586 patent/WO1999039631A1/en active IP Right Grant
- 1999-02-05 CA CA002319480A patent/CA2319480C/en not_active Expired - Fee Related
- 1999-02-05 JP JP2000530139A patent/JP2002501803A/en active Pending
- 1999-02-05 EP EP99906774A patent/EP1052930B1/en not_active Expired - Lifetime
- 1999-02-05 AU AU26606/99A patent/AU2660699A/en not_active Abandoned
- 1999-02-05 KR KR10-2000-7008581A patent/KR100472736B1/en not_active IP Right Cessation
-
2001
- 2001-01-30 US US09/771,596 patent/US6671528B2/en not_active Expired - Fee Related
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2003
- 2003-12-12 US US10/733,236 patent/US6873865B2/en not_active Expired - Fee Related
Also Published As
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US20040127779A1 (en) | 2004-07-01 |
KR100472736B1 (en) | 2005-03-08 |
US6671528B2 (en) | 2003-12-30 |
AU2660699A (en) | 1999-08-23 |
ATE416668T1 (en) | 2008-12-15 |
JP2002501803A (en) | 2002-01-22 |
US20010039376A1 (en) | 2001-11-08 |
KR20010040703A (en) | 2001-05-15 |
WO1999039631A1 (en) | 1999-08-12 |
US6181958B1 (en) | 2001-01-30 |
US6873865B2 (en) | 2005-03-29 |
CA2319480A1 (en) | 1999-08-12 |
EP1052930A1 (en) | 2000-11-22 |
DE69940053D1 (en) | 2009-01-22 |
EP1052930A4 (en) | 2003-03-12 |
EP1052930B1 (en) | 2008-12-10 |
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