WO2000030530A1 - Non-invasive sensor capable of determining optical parameters in a sample having multiple layers - Google Patents
Non-invasive sensor capable of determining optical parameters in a sample having multiple layers Download PDFInfo
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- WO2000030530A1 WO2000030530A1 PCT/US1999/026687 US9926687W WO0030530A1 WO 2000030530 A1 WO2000030530 A1 WO 2000030530A1 US 9926687 W US9926687 W US 9926687W WO 0030530 A1 WO0030530 A1 WO 0030530A1
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Classifications
-
- 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
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
- A61B2562/0242—Special features of optical sensors or probes classified in A61B5/00 for varying or adjusting the optical path length in the tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/04—Arrangements of multiple sensors of the same type
- A61B2562/043—Arrangements of multiple sensors of the same type in a linear array
Definitions
- This invention relates to devices and methods for measuring optical parameters of a sample, e. g., a sample of tissue in a human body. More specifically, this invention relates to devices and methods for the non-invasive determination of one or more optical parameters in vivo in tissues comprising a plurality of layers.
- Non-invasive monitoring of metabolites by optical devices and methods is an important tool for clinical diagnostics.
- the ability to determine an analyte, or a disease state, in a human subject without performing an invasive procedure, such as removing a sample of blood or a biopsy specimen, has several advantages. These advantages include ease in performing the test, reduced pain and discomfort to the patient, and decreased exposure to potential biohazards. These advantages will result in increased frequency of testing when necessary, accurate monitoring and control, and improved patient care.
- Representative examples of non-invasive monitoring techniques include pulse oximetry for oxygen saturation (U. S. Patent Nos. 3,638,640; 4,223,680; 5,007,423; 5,277,181 ; 5,297,548).
- Another example is the use of laser Doppler flowmetry for diagnosis of circulation disorders (Toke et al, "Skin microvascular blood flow control in long duration diabetics with and without complication", Diabetes Research, Vol. 5 (1987), pages 189-192).
- Other examples of techniques include determination of tissue oxygenation (WO 92/20273), determination of hemoglobin (U. S. Patent No. 5,720,284) and of hematocrit (U. S. Patent Nos. 5,553,615; 5,372,136; 5,499,627; WO 93/13706). Measurements in the near-infrared region of the electromagnetic spectrum have been proposed, or used, in prior art technologies.
- the 600 nm to 1300 nm region of the electromagnetic spectrum represents a window between the visible hemoglobin and melanin absorption bands and the strong infrared water absorption bands.
- Light having a wavelength of 600 nm to 1300 nm can penetrate deep enough into the skin to allow use thereof in a spectral measurement or a therapeutic procedure.
- Oximetry measurement is very important for critical patient care, especially after the use of anesthesia. Oxygenation measurements of tissue are also important diagnostic tools for measuring oxygen content of the brain of the newborn during and after delivery, for monitoring tissue healing, and in sports medicine.
- Non-invasive determination of hemoglobin and hematocrit values in blood would offer a simple, non-biohazardous, painless procedure for use in blood donation centers, thereby increasing the number of donations by offering an alternative to the invasive procedure, which is inaccurate and could lead to the rejection of a number of qualified donors.
- Non-invasive determination of hemoglobin and hematocrit values would be useful for the diagnosis of anemia in infants and mothers, without the pain associated with blood sampling.
- Non- invasive determination of hemoglobin has been considered as a method for localizing tumors and diagnosis of hematoma and internal bleeding.
- Non- invasive determination of hematocrit values can yield important diagnostic information on patients with kidney failure before and during dialysis.
- Diabetes mellitus is a chronic disorder of carbohydrate, fat, and protein metabolism characterized by an absolute or relative insulin deficiency, hyperglycemia, and glycosuria. At least two major variants of the disease have been identified. "Type I” accounts for about 10% of diabetics and is characterized by a severe insulin deficiency resulting from a loss of insulin-secreting beta cells in the pancreas. The remainder of diabetic patients suffer from "Type II", which is characterized by an impaired insulin response in the peripheral tissues (S. L. Robbins, S.
- diabetes can result in a variety of adverse clinical manifestations, including retinopathy, atherosclerosis, microangiopathy, nephropathy, and neuropathy. In its advanced stages, diabetes can cause blindness, coma, and ultimately death.
- the principal treatment for Type I diabetes involves periodic injection of insulin. Appropriate insulin administration can prevent, and even reverse, some of the adverse clinical manifestations of Type I diabetes. Frequent adjustments of the level of glucose in blood can be achieved either by discrete injections of insulin or, in severe cases, by an implanted insulin pump or artificial pancreas.
- the amount and frequency of insulin administration is determined by frequent or, preferably, continuous testing of the level of glucose in blood (i. e., blood glucose level).
- Portable personal glucose meters are the most popular devices for monitoring blood glucose levels.
- a drop of blood is obtained by sticking a patient's finger with a sharp object, and the blood obtained is analyzed by means of chemical reactions on a strip. These reactions provide an optical or electrochemical signal.
- This type of device provides a convenient way to monitor blood glucose level.
- the pain associated with collecting samples of blood, the potential contamination at the puncturing site, the disposal of biohazardous testing materials, the cumbersome procedures, and the chance of making mistakes often prevent patients from using the meters as frequently as recommended by physicians.
- Implantable biosensors have also been proposed for glucose measurement. (G. S. Wilson, et al., "Progress toward the development of an implantable sensor for glucose”, Clin. Chem., Vol. 38 (1992), pages 1613-1617). These biosensors are electrochemical devices having enzymes immobilized at the surface of an electrochemical transducer. They are usually implanted into a patient's tissue by means of a surgical procedure.
- Non-invasive glucose-monitoring techniques measure in vivo glucose concentrations without collecting a blood sample.
- a “non-invasive” technique is one that can be used without removing a sample from, or without inserting any instrumentation into, the tissues.
- the concept upon which most such technologies are based involves irradiating a vascular region of the body with electromagnetic radiation and measuring the spectral information that results from at least one of four primary processes: reflection, absorption, scattering, and emission. The extent to which each of these processes occurs is dependent upon a variety of factors, including the wavelength and polarization state of the incident radiation and the concentration of analytes in the body part.
- Concentrations of an analyte are determined from the spectral information by comparing the measured spectra to a calibration curve or by reference to a physical model of the tissue under examination.
- NIR Near-infrared
- MIR mid-infrared
- FIR far-infrared
- NIR involves the wavelength range from about 600 nm to about 1300 nm
- MIR involves the wavelength range from about 1300 nm to about 3000 nm
- FIR involves the wavelength range from about 3000 nm to about 25000 nm.
- infrared or IR is taken to mean a range of wavelengths from about 600 nm to about 25000 nm.
- U. S. Patent Nos. 5,086,229; 5,324,979; and 5,237,178 describe non-invasive methods for measuring blood glucose level involving NIR radiation.
- a blood-containing body part e. g., a finger
- one or more detectors detect the light that is transmitted through the body part.
- a blood glucose level is derived from a comparison to reference spectra for glucose and background interferents.
- This NIR spectral region has been used for determination of blood oxygen saturation, hemoglobin, hematocrit, and tissue fat content. It is also used for exciting and detecting compounds in photodynamic therapy. At longer wavelengths, water absorption bands dominate tissue spectra. There are some narrower spectral windows in the 1500 nm to 1900 nm range and the 2100 nm to 2500 nm range, where both in vitro and in vivo tissue measurements were performed.
- scattered photons Light striking a tissue will undergo absorption and scattering. Most of the scattered photons are elastically scattered, i. e., they have the same frequency as the incident radiation (Rayleigh scattering). A small fraction of the scattered light (less than one in a thousand incident photons) is inelastically scattered (Raman scattering). Unless otherwise indicated herein, “scattering” refers to elastic scattering.
- tissue scattering information includes cell size and cell shape, depth of the tissue layer in which scattering occurs, and refractive index of intracellular fluids and extracellular fluid.
- Absorption information includes absorption by tissue components, such as hemoglobin, melanin, and bilirubin, and the overtone absorption of water, glucose, lipids, and other metabolites.
- Spatially resolved diffuse reflectance (SRDR) techniques are a subset of the elastic scattering methods previously described.
- SRDR spatially resolved diffuse reflectance
- FIG. 1A light is introduced into the surface of a tissue sample, such as a body part, at an introduction site.
- the diffusely reflected light is measured at two or more detection sites located on the surface of the sample (e. g., the skin) at different distances, r, from the introduction site.
- the dependence of the intensity of the diffusely reflected light, i. e., reflectance R, as a function of the detection distance (r) is used to derive scattering and absorption coefficients of the tissue sample. These coefficients, in turn, are related to the concentration of analyte(s).
- Frequency-domain reflectance measurements use optical systems similar to those used for spatially resolved light scattering (reflectance (R) as a function of distance (r)), except that the light source is modulated at a high frequency and a synchronized detector is used (U. S. Patent Nos. 5,187,672 and 5,122,974). The difference in phase angle and modulation between the incident beam of light and the reflected beam of light is used to calculate the scattering coefficient and the absorption coefficient of the tissue or scattering medium.
- U. S. Patent No. 5,492,769 describes frequency domain method and apparatus for the determination of a change in the concentration of an analyte
- U. S. Patent No. 5,492, 118 describes a method and apparatus for determination of the scattering coefficient of tissues.
- This invention involves a method and apparatus for non-invasively measuring at least one parameter of a sample of tissue, such as the absorption coefficient or the scattering coefficient of a layer of skin. Such parameters can be used to determine the concentration of an analyte of interest in the sample of tissue.
- the present invention measures light that is reflected, scattered, absorbed, or emitted by the sample of tissue from a first pair of average sampling depths, d av1 , d av2 and from at least one other pair of average sampling depths d av3 , d av4 , where d av3 and d av4 are greater than d av2 and d av1 .
- sampling depths are preferably less than 3 mm, more preferably less than 2 mm. Confining the sampling depth in the tissue is achieved by appropriate selection of the distance separating the site at which light is introduced into the sample and the site at which light is collected from the sample after being reflected, scattered, absorbed, or emitted by the sample.
- Confining the sampling depth in the tissue provides several advantages. First, confining the sampling depth allows determinations of the optical properties of a specific layer of the sample, e.g., epidermis, and decreases interference from other layers, e. g., stratum corneum, in these determinations. Secondly, the tissue region that is sampled can be more homogeneous than the tissue regions sampled by the devices described in prior art. Thirdly, the signal is obtained from a region of tissue having a substantially uniform temperature. Accordingly, the signal is not likely to be affected by the temperature gradient running from the surface of the tissue into the interior of the tissue.
- this invention involves a method and apparatus for non-invasively measuring at least one parameter of a sample by means of a light introduction site and a plurality of light collection sites, each light collection site comprising a plurality of light collecting elements.
- the site at which light is introduced into the sample and the sites at which the light reflected, scattered, absorbed, or emitted by the sample is collected for detection occupy a small area on the surface of the tissue.
- the minimum distance between the site at which light is introduced into the sample and the closest site at which the light is collected is approximately equal to or less than the transport mean free path of a photon in the sample.
- the transport mean free path is the average distance that a photon can be propagated in a sample without undergoing an absorption event or a scattering event.
- This minimum distance is on the order of 1 mm for light in the near infrared region of the electromagnetic spectrum in typical samples of tissues.
- the maximum distance between the site at which light is introduced into the sample and any site at which the light is collected should be less than ten times that of the transport mean free path of a photon in the sample. This maximum distance is on the order of 1 cm for light in the near infrared region of the electromagnetic spectrum in typical samples of tissues.
- the minimum distance between the site at which light is introduced into the sample and the closest site at which the light re-emitted from the sample is collected is less than 0.5 mm, and the maximum distance between the site at which light is introduced into the sample and the furthest site at which the light re-emitted from the sample is collected is less than 6 mm.
- this invention involves a method for determining at least one optical parameter of a sample having a plurality of layers, wherein the layers have different properties.
- the method comprises the steps of:
- the method of this invention for measuring at least one optical parameter of a sample having layers having differing properties comprises the steps of:
- each of the light collection sites comprises at least two light collecting elements and each of the light collection sites is located at a different distance from the light introduction site; c) determining the intensity of the light re-emitted at a first light collecting element of a light collection site located at a first distance from the light introduction site and the intensity of the light re-emitted at at least a second light collecting element of the light collection site located at the first distance from the light introduction site; d) determining the absorption coefficient and the scattering coefficient of the sample at a given depth of the sample by means of a mathematical relationship between intensity of the light re-emitted at the first light collecting element of the light collection site located at the first distance from the light introduction site and intensity of the light re-emitted at at least a second light collecting element of the light collection site located at the first distance from the light introduction site; e)
- the total number of light collection sites may vary. At a minimum, the number of light collection sites should be equal to the number of layers. Also, the separation between a particular light collection site and the light introduction site is determined by the depth and thickness of the particular layer in the sample for which this light collection site is designated. A minimum of two light collecting elements should be included in each light collection site. In order to provide for the mathematical relationships in steps d) and f), in any light collection site of light collecting elements, the first light collecting element in the light collection site and at least a second light collecting element in the light collection site must be located at different distances from the light introduction site.
- One example of the mathematical relation between the light collected at a first light collecting element at a first collection site (R ⁇ and the light collected at at least a second light collecting element at the first collection site (R 2 ) is the logarithm of 1/R., as a function of corresponding logarithm of R/R 2 .
- the mathematical relationship can be used to determine the absorption and scattering coefficients of the layer of tissue close to the surface of the sample (stratum corneum and epidermis) from the measured reflectance values and a calibration procedure based on known reflectance values.
- One possible calibration procedure involves construction of a calibration diagram by plotting the measured values of a function of reflectance at one light collection site distance, e. g., f(1/R.,), versus the measured values of another function of reflectance, e. g., f(R.,/R 2 ), at that light collection site distance for a series of materials of known measured absorption and scattering coefficients. These materials can be selected from solid plastic disks containing different levels of scattering and absorbing pigments, opaque or translucent glass, liquid suspensions of scattering materials, or the like. From the calibration diagram obtained, one can determine the scattering and absorption coefficients of an unknown sample based on its measured values of R and R 2 .
- Knowledge of the scattering and absorption coefficients can be used to determine the concentration of an analyte of interest in the layer of tissue close to the surface of the sample.
- the procedure described above can be repeated for layers of tissue that are located below the layer of tissue close to the surface of the sample.
- the method of this invention can be applied to any tissue comprising, in effect, two or more layers.
- the method of this invention is also applicable for an arrangement wherein a single light collection site and a plurality of light introduction sites are employed.
- the method is also capable of determining at least one optical parameter of a sample having a plurality of layers, wherein each of the layers has different properties.
- the method comprises the steps of: a) introducing a plurality of beams of light into a sample at a plurality of light introduction sites on a surface of the sample, a first light introduction site being at a first distance from a light collection site on the surface of the sample, a second light introduction site being at a second distance from the light collection site on the surface of the sample, the first distance being less than the second distance; b) determining the intensities of light re-emitted from the sample at the light collection site, the light collection site collecting light re-emitted mainly from a first layer of the sample and collecting light re-emitted mainly from a second layer in the sample, the light re-emitted from the first layer being introduced at the first light introduction site, the light re-emitted from the second layer being introduced at the second light introduction site; c) determining at least one optical parameter of a the first layer of the sample; and d) determining at least one optical parameter of the second layer of the sample, the first layer having an average depth, as measured
- the method is also capable of determining at least one optical parameter of a sample having layers having different properties.
- the method comprises the steps of:
- each of the light introduction sites comprises at least two illuminating elements, each of the light introduction sites located at a different distance from a light collection site; b) collecting light re-emitted from the sample at the light collection site; c) determining the intensity of the re-emitted light resulting from illumination by a first illuminating element of a light introduction site located at a first distance from the light collection site and the intensity of the re-emitted light resulting from illumination by at least a second illuminating element of the light introduction site located at the first distance from the light collection site; d) determining the absorption coefficient and the scattering coefficient of the sample at a given depth of the sample by means of a mathematical relationship between intensity of the re-emitted light resulting from illumination by the first illuminating element of the light introduction site located at the first distance from the light collection site and intensity of the re-emitted light resulting from illumination by at least a second
- the first illuminating element and at least a second illuminating element must be located at different distances from the light collection site.
- the total number of light introduction sites may vary.
- the number of light introduction sites should be equal to the number of layers.
- the separation between a particular light introduction site and the light collection site is determined by the depth and thickness of the particular layer in the sample for which this light introduction site is designated.
- a minimum of two illuminating elements should be included in each light introduction site.
- the present invention is particularly advantageous for samples of biological tissue where the presence of multiple layers of tissue, such as skin layers, may affect the result of determination of an optical parameter in a specific layer.
- Non-invasive measurements may be made on a body part of a patient, e. g., a finger, earlobe, lip, toe, skin fold, or bridge of the nose.
- the invention offers several advantages over the prior art.
- the invention makes it is possible to determine the effect of layers having different optical properties in tissue-simulating phantoms and in human skin.
- the majority of light collected has penetrated the tissue to only a shallow depth. If the separation of the light introduction site from the light collection site ranges over large distances (e. g., 0.5 cm to 7 cm), reflected light collected at the light collection site has been propagated through the stratum corneum, epidermis, dermis, as well as deeper regions of tissue.
- the light path may also include the subcutis (which has higher fatty adipose tissue content) and underlying muscle structures.
- tissue that is heterogeneous along dimensions substantially parallel to the surface of the skin, there is lower probability of photons encountering body components, such as hair, scar tissue, or vein structure, that will cause anomalies in the reflectance measurements. It is also possible to perform measurements on a small localized area of the skin with an optical instrument designed to have the light introduction site close to the light collection site rather than with a light introduction site that is located at a great distance from the light collection site. Thus, it is possible to detect blood vessels and hair fibers and determine their effect on the optical signals.
- optical instruments wherein the light introduction site is separated from the light collection site by a great distance require the use of a large body mass, such as the muscle of the arm, thigh, or the abdomen. Accordingly, the body locations where such an optical instrument can be used are limited, and substantial disrobing and inconvenience for the user are required.
- another advantage of the design of the apparatus of the present invention is that optical instruments wherein the distance from the light introduction site to the light collection site is 5 mm or less can be used, particularly with small body parts, such as ear lobes and fingers.
- optical instruments wherein the distance from the light introduction site to the light collection site is 5 mm or less can also be used with larger body parts, such as the forearm, thigh, or abdomen.
- Another advantage of a small distance between light introduction site and the light collection site is the higher signal to noise ratio obtainable at small separations, due to increases in the amount of light ultimately reaching the detector.
- simpler, inexpensive, rugged components such as light emitting diodes, small flash lamps, and incandescent lamps, can be used as sources of light, and inexpensive commercially available photodiodes can be used as detectors.
- Optical instruments having a large separation between the light introduction site and the light collection site require laser diodes as source of light and photomultiplier tubes as detector, because weaker signals are generated.
- FIGS. 1A and 1 B are a schematic diagrams illustrating (1) an arrangement of light collecting elements with respect to the light introduction site and (2) the average sampling depth, d av , for a given separation of light collections site from the light introduction site.
- FIG. 2 is a block diagram of a device of this invention.
- FIG. 3A is a diagram illustrating a bifurcated optical fiber bundle.
- FIG. 3B is a series of diagrams showing portions of the bifurcated optical bundle of FIG. 3A.
- FIG. 4 is a diagram illustrating the nominal separation distances, r, between light collecting elements and the illuminating element.
- FIG. 5 is a diagram illustrating a body interface used for human volunteer experiments.
- FIG. 6A is a graph illustrating the spatially resolved diffuse reflectance signal at 590 nm of a bulk scattering medium (a suspension comprising a lipids emulsion) with and without layers simulating the stratum corneum.
- FIG. 6B is a graph illustrating the sensitivity of the slope of the spatially resolved diffuse reflectance signal at 590 nm at different separations of the light introduction site from the light collection site to changes in the optical properties of a layer that simulates the stratum corneum.
- FIG. 7A is a graph illustrating the spatially resolved diffuse reflectance signal at 900 nm of a bulk scattering medium (a suspension comprising a lipids emulsion) with and without layers simulating the stratum corneum.
- FIG. 7B is a graph illustrating the sensitivity of the slope of the 900 nm spatially resolved diffuse reflectance signal at different separations of the light introduction site from the light collection site to changes in the optical properties of a layer that simulates the stratum corneum.
- FIG. 8A is a graph illustrating the spatially resolved diffuse reflectance signal at 590 nm of a bulk scattering medium (a suspension comprising a lipids emulsion with a blue dye added) with and without layers simulating the stratum corneum.
- a bulk scattering medium a suspension comprising a lipids emulsion with a blue dye added
- FIG. 8B is a graph illustrating the sensitivity of the slope of the 590 nm spatially resolved diffuse reflectance signal at different separations of the light introduction site from the light collection site to changes in the optical properties of a layer simulating the stratum corneum.
- FIG. 9A is a graph illustrating the spatially resolved diffuse reflectance signal at 900 nm of a bulk scattering medium (a suspension comprising a lipids emulsion with a blue dye added) with and without a layer simulating the stratum corneum.
- FIG. 9B is a graph illustrating the sensitivity of the slope of the 900 nm spatially resolved diffuse reflectance signal at different separations of the light introduction site from the light collection site to changes in the optical properties of a layer simulating the stratum corneum.
- FIG. 10A is a graph illustrating the spatially resolved diffuse reflectance signal at 590 nm of a Caucasian volunteer with and without a layer simulating the stratum corneum, the layer having a dominantly absorbing property.
- FIG. 10B is a graph illustrating the spatially resolved diffuse reflectance signal at 900 nm of a Caucasian volunteer with and without a layer simulating the stratum corneum, the layer having a dominantly absorbing property.
- FIG. 11A is a graph illustrating the spatially resolved diffuse reflectance signal at 590 nm of a Caucasian volunteer with and without a layer simulating the stratum corneum, the layer having a dominantly scattering property.
- FIG. 11 B is a graph illustrating the spatially resolved diffuse reflectance signal at 900 nm of a Caucasian volunteer with and without a layer simulating the stratum corneum, the layer having a dominantly scattering property.
- FIG. 12A is a graph illustrating the spatially resolved diffuse reflectance signal at 590 nm of a Caucasian volunteer with and without a layer simulating the stratum corneum, the layer having both absorbing and scattering properties.
- FIG. 12B is a graph illustrating the spatially resolved diffuse reflectance signal at 900 nm of a Caucasian volunteer with and without a layer simulating the stratum corneum, the layer having both absorbing and scattering properties.
- FIG. 13A is a graph illustrating the sensitivity of the slope of the spatially resolved diffuse reflectance signal at 590 nm, at different separations of the light introduction site from the light collection site, to changes in the optical properties of a layer simulating the stratum corneum.
- FIG. 13B is a graph illustrating the sensitivity of the slope of the spatially resolved diffuse reflectance signal at 900 nm, at different separations of the light introduction site from the light collection site, to changes in the optical properties of a layer simulating the stratum corneum.
- FIG. 14A is a graph illustrating the spatially resolved diffuse reflectance signal at 590 nm of the left arms of Caucasian (light-skinned) and African- American (dark-skinned) volunteers.
- FIG. 14B is a graph illustrating the sensitivity of the slope of the spatially resolved diffuse reflectance signal at 590 nm, at different separations of the light introduction site from the light collection site, to changes in the melanosome content of the top skin layers of the left arms of Caucasian (light-skinned) and African-American (dark-skinned) volunteers.
- optical properties refers to the absorption, scattering, emission, and depolarization properties of the tissues.
- optical parameter refers to a parameter that describes and defines an optical property of a medium and its components. Examples of optical parameters include absorption coefficients, scattering coefficients, anisotropy factors, transport optical mean free path, extinction coefficients of analytes.
- scattering medium refers to a medium that both scatters light and absorbs light.
- absorption coefficient i. e., ⁇ a
- absorption coefficient i. e., ⁇ a
- ⁇ s refers to the probability of light scattering per unit path length.
- anisotropy factor i. e., g
- anisotropy factor i. e., g
- reduced scattering coefficient i. e., ⁇ s '
- transport photon mean free path (i.
- 1/( ⁇ a + ⁇ s ') refers to the mean path length for a photon traveling in a medium between two consecutive photon-medium interactions.
- Photon-medium interactions include (1) a scattering event followed by a scattering event and (2) a scattering event followed by an absorption event.
- Penetration depth is related to to the change of light intensity in a scattering medium as a function of distance traveled by the light along the same path as the incident light.
- the expression “Monte Carlo simulation” refers to a statistical method that can be used to trace photon propagation in a scattering medium by means of numerical simulation.
- the expression “diffuse reflectance” means a measure of the intensity of light that is re-emitted from the surface of a sample in all directions except the direct reflection direction when the surface is illuminated by incident light.
- spatialally resolved diffuse reflectance refers to a measurement of light that is re-emitted from a sample and collected at several light collection sites and at a defined distance from a light introduction site.
- this expression can refer to the light collected at a given light collection site on the sample boundary as a result of introducing light at discrete light introduction sites located on the same boundary at defined distances from the light collection site.
- frequency domain measurement refers to a measurement of light involving the phase angle and/or the amplitude change of modulated incident light, at a given separation distance of a light introduction site from a light collection site, as the light transverses a scattering medium.
- beam of light means a group of photons traveling together in nearly parallel trajectories toward a sample and striking the surface of the sample in a predefined area only.
- the predefined area on the surface of a sample struck by a given beam of light is that area that is covered by an illuminating element, such as an optical fiber.
- the expression "light introduction site” means a location on the surface of a sample, e. g., a body part, tissue, or the like, at which light is injected or inserted into the sample.
- the source of the light can be located at the light introduction site or can be located remote from the light introduction site. If the source of light is located remote from the light introduction site, the light must be transmitted to the light introduction site by light transmitting means, such as, for example, optical fibers.
- illumination element means a component located at the light introduction site that delivers light to the sample, e. g., a body part, tissue, or the like.
- the illuminating element is typically an optical fiber that transmits light from a source of light to the light introduction site. However, if the source of light can be located at the light introduction site, the source of light can be the illuminating element.
- the expression "light collection site” means a location on the surface of a sample, e. g., a body part, tissue, or the like, at which light is that is re- emitted from the sample is accumulated.
- the detector which determines the intensity of the re-emitted light, can be located at the light collection site or can be located remote from the light collection site.
- the light must be transmitted to the detector by light transmitting means, such as, for example, optical fibers.
- the expression "light collecting element” means a component covering an area at the light collection site that accumulates light that is re-emitted from the sample, e. g., a body part, tissue, or the like.
- the light collecting element is typically an optical fiber that transmits light from the light collection site to a detector.
- the detector can be located at the light collection site, the detector can be the light collecting element.
- sample means a biological or non-biological material that scatters and absorbs light. Samples include, but are not limited to, tissue, blood, urine, and other biological solids and fluids.
- Samples can be homogeneous or heterogeneous and can consist of a single layer or a plurality of layers.
- tissue includes tissue of any animal, including humans.
- tissue is intended to include the intact tissue of a living animal, including humans.
- distance means (1) the distance as measured from the center of one site to the center of the other site when referring to the distance between two sites; (2) the distance from the center of one element to the center of the other element when referring to the distance between two elements; (3) the distance between the center of a given site and the center of an element not in that site when referring to the distance between a given site and an element not in that site.
- re-emitted light means a group of photons emerging from a sample as a result of the scattering, reflection, absorption, and emission of the light that illuminates the sample.
- the term 'light means electromagnetic radiation.
- the light has a wavelength ranging from about 400 nm to about 10,000 nm, more preferably from about 400 nm to about 2500 nm, most preferably from about 500 to about 1500 nm.
- I represents the light fluence at a distance, z, into the sample
- l 0 represents the intensity of incident light
- ⁇ t represents a total attenuation coefficient
- ⁇ is the sum of the absorption coefficient, ⁇ a , and the reduced scattering coefficient, ⁇ s '.
- the mean free path of a photon describes the average distance traveled by a photon either (1) between a first scattering event followed by a second scattering event or (2) between a scattering event followed by an absorption event, and is defined as 1/ ⁇ t .
- Tissue scattering occurs because of a mismatch between the indices of refraction of either the extracellular fluid (ECF) or the intracellular fluid (ICF) and the cellular membranes of the tissue.
- ECF extracellular fluid
- ICF intracellular fluid
- cellular membranes encompasses both the cell membrane as well as the membranes of organelles, such as mitochondria or collagen fibrils. Besides undergoing scattering and absorption, photons can be reflected at the interface between tissue and an illuminating element; photons can also be re-emitted out of the tissue.
- a practical approach for describing the transfer of light energy through a scattering medium uses radiative transport theory.
- light propagation is considered equivalent to the flow of discrete photons, which may be locally absorbed by the medium or scattered by the medium.
- the radiative transport theory can be simplified to yield the Diffusion Theory approximation.
- Typical values of g for tissues are 0.9 ⁇ g ⁇ 1.0 (forward scattering).
- the attenuation of photons in tissues is described by an effective attenuation coefficient, ⁇ eff , as follows:
- ⁇ ⁇ ff can be calculated from scattering measurements (such as by spatially resolved diffuse reflectance techniques) and both ⁇ a and ⁇ s ' can be derived from measurements of ⁇ under different conditions.
- changes in the values of ⁇ a and ⁇ s ' can be related to tissue parameters, such as the concentration of an analyte.
- the size of the scattering material in the tissue is near the wavelength of light, and the reduced scattering coefficient, ⁇ s ', can be expressed using Mie theory as follows:
- p represents the volume density, i. e., number of particles per unit volume
- a represents the radius of the scattering particle (e. g., cells, mitochondria, or collagen fibrils)
- n e ⁇ represents the refractive index of the medium (ECF or ICF)
- m (n in /n )
- the ratio of the refractive index of the scattering particle n jn to the refractive index of the medium n e ⁇ and ⁇ represents the wavelength of the light.
- ⁇ s ' changes directly with either the size of the scattering particle, "a", or the refractive index ratio "m", as shown in Equation (4). Because the refractive index of the scattering particles, n j remains relatively constant, ⁇ s ' is influenced mostly by n e ⁇ and particle radius "a". For example, an increase in concentration of glucose, or concentration of other solute, reduces tissue scattering by decreasing the difference in refractive index between the ICF/ECF and the cellular membranes. Variations in n ex are not specific for a particular analyte, however, and are affected by any change in the total concentration of solutes in the ECF, including salts and proteins.
- n is also susceptible to changes in physiological variables, such as temperature of the tissue. Determination of ⁇ a , ⁇ s , and g of a tissue at different wavelengths can give information on physical and chemical properties of the tissue, such as concentration of analytes, cell sizes, and tissue heterogeneity. Methods of determining ⁇ eff , ⁇ s ', and ⁇ a are known in the art. One of these methods is the measurement of diffuse reflectance of the skin tissue.
- the measured reflectance is a function of the reduced scattering coefficient ⁇ s ', the absorption coefficient ⁇ a , the refractive index of the scattering medium n s , and the refractive index of the surrounding layer n 0 , which is usually air.
- Another method of measuring the absorption and scattering coefficients is referred to as spatially resolved diffuse reflectance, wherein the value of reflectance is a function of the distance of the light introduction site from the light collection site.
- the intensity of the light re-emitted from a sample is measured at several distances from the site at which light is introduced into the sample. Under certain conditions, intensity of the re-emitted light is related to the separation of the light introduction site from the light collection site by the relationship:
- R(r) represents the intensity of light re-emitted from a sample at a light collection site, which is separated from the light introduction site by a distance r
- K 0 is a constant.
- the logarithm of the product of the intensity of the re- emitted light as a function of distance, R(r), times the separation distance between the light introduction site and the light collection site, r may be plotted against the separation distance r.
- the plot is linear at large separations of the light introduction site from the light collection site. This linear region is known as the diffusion theory limit. Under these conditions the absolute value of the slope of the line is the effective attenuation coefficient ⁇ r e swirlfr
- Other methods for determination of optical properties of tissues are described in the art. These methods include collimated transmittance and frequency domain measurements.
- the present invention involves methods and instruments for the measurement of optical properties of tissues taken across a skin boundary, while accounting for the effects of skin layers on the properties measured.
- the measurement of optical properties of tissue across a skin boundary is adversely affected by the non-homogeneity of the different layers of the skin.
- Prior art methods and devices ignore the effect of multiple layers of skin tissue on the measured optical properties.
- U. S. Patent Nos. 5,057,695; 5,551 ,422; 5,676,143; 5,492,118; 5,419,321 ; 5,632,273; and 5,513,642 are silent as to the effect of different layers of skin on optical measurements, and they disclose no methods or instruments that address this issue.
- the apparatus 100 of this invention comprises a means for introducing light into tissue through a defined light introduction site 102.
- the light is introduced by means of an illuminating element 104.
- a plurality of light collection sites 106 comprising light collecting elements 108, which collect the light re-emitted from tissue for measurement of the intensity of the re-emitted light at one or more detectors (not shown).
- the source of light (not shown) for providing light at the light introduction site 102 can be a focused beam of light, a collimated beam of light, or a surface-mounted light emitting diode or a laser diode in contact with the skin. Other sources of light can also be used.
- the source of light can be remote from the light introduction site 102, in which case a fiber tip can be used to carry light from the remote source of light.
- Re-emitted light is collected at several sites located at different distances from the light introduction site 102 and directed towards one or more detectors that measure the intensity of the collected light. Re-emitted light can be collected by any of several means.
- Representative examples of these means of collecting re- emitted light include, but are not limited to, fibers that are in contact with the skin and a mask with holes at predetermined distances from the light introduction site.
- the light thus collected can be imaged into a charge coupled device (CCD) camera, a series of photodiodes in contact with the skin or a one-dimensional or a two-dimensional photodiode array, or any other suitable type of detector.
- CCD charge coupled device
- a plurality of light introduction sites and a single light collection site can be used.
- a single light collection site replaces the light introduction site, and the light collection sites at distances r, through r n are replaced by a plurality of light introduction sites. See FIGS. 1A and 1 B for examples of distances through r n .
- the apparatus of the present invention requires that the sites for introducing light and for collecting light be closely spaced.
- the maximum distance between the light introduction site and any light collection site is less than 10 mm, preferably less than 6 mm, more preferably less than 4 mm.
- the minimum distance between the sites for introducing light and for collecting light must be less than the mean free path of a photon in the medium.
- the mean free path of a photon is defined as 1/( ⁇ a + ⁇ s ').
- the mean free path of a photon ranges from about 0.6 mm to about 1.2 mm.
- the penetration depth in the tissue ranges from about 0.7 mm to about 2 mm.
- the smallest separation between the light introduction site and the site at which re-emitted light is collected should be less than 600 micrometers, preferably from about 200 micrometers to about 400 micrometers. These distances are in contrast with those disclosed in an article by Kumar et al. Kumar et al. recommend that the separation between the light introduction site and the light collection site be greater than 4 mm, in order to avoid the structural effects of the surface of the skin. See G. Kumar, J. M. Schmitt, "Optical probe geometry for near-infrared spectroscopy of biological tissue", Applied Optics, Vol. 36 (1997), pages 2286- 2293.
- Another feature of the preferred embodiment of this invention is that there are two or more light collecting elements at each light collection site in the case of a single light introduction site. Similarly, there are two or more light introducing elements at each light introduction site in the case of a single light collection site.
- a plurality of light collection sites comprising a plurality of light collecting elements
- the light collecting elements at each light collection site are very close to each other.
- the light collecting elements at each light collection site are arranged to cover distances that are either in very close proximity to the light introduction site, near the light introduction site, or greatly separated from the light introduction site.
- the light collecting elements which can be optical fibers, are preferably adjacent to each other, i. e., almost touching each other, or are separated by a very small distance, which is typically less than the linear dimension of the cross section of a light collecting element.
- Light collecting elements can be also arranged in groupings of three or more. Light collecting elements at a given light collection site are very close to each other and well separated from light collecting elements at other light collection sites.
- the light collecting elements can be arranged in a structure, such as a non-reflective plastic housing or a non-reflective metal housing to decrease the probability of scattered light re-entering the surface of the skin.
- a set of optical fibers mounted in a transparent plastic holder can be used to divert the re-emitted light away from the skin.
- Light collecting elements can be arranged in holes drilled in the housing.
- a preferred structure for an optical instrument of this invention involves arranging optical fibers in a hexagonal close-packed fiber bundle. Some of the fibers are used for illumination and others are used for collection of light. Other fibers can be used to divert scattered light away from the surface of the skin into a light trap, such as a non- reflective hollow cone, to prevent its re-introduction into the surface of the tissue. The diffusely reflected light is measured, at each wavelength, as a function of the distance between the light introduction site and the light collection site. The signal is amplified and is corrected for fluctuation of the light source and variation of the fiber throughput. The corrected signal is used for calculating the absorption coefficient and the scattering coefficient of the sample.
- Absorption and scattering coefficients can be determined from the output of the apparatus of this invention, Monte Carlo modeling, and a calibration procedure. Calibration can be carried out by determining the spatially resolved diffuse reflectance values of a set of materials of known optical properties. These materials are known as tissue-simulating phantoms. They include lipid suspensions, such as Intralipid® (Pharmacia, Clayton, NC) and Liposyn® (Abbott Laboratories, North Chicago, IL). The lipid suspension is diluted to generate suspensions having known values of scattering coefficients. A colored compound, hemoglobin, or blood is added to the suspension to generate different values of absorption coefficients. Alternatively, plastic rods or sheets containing colored pigments can be used. Also, polished pieces of scattering glass, such as opal glass, can be used to generate reference values for absorption and scattering coefficients. Absorption coefficients and scattering coefficients of these phantoms are usually determined by independent standard optical methods.
- An experimental calibration diagram can be established by measuring spatially resolved diffuse reflectance values R(r.,), R(r 2 ), R(r 3 ), ..., R(r n ) of a series of phantoms having known values of ⁇ a and ⁇ s '. After the spatially resolved diffuse reflectance values are obtained, one can plot one function of the magnitude of the measured reflectance values on one axis (the Y axis) versus the corresponding slope of the measured reflectance values (dRldr) on the X- axis for each pair of the absorption and scattering coefficients of the tissue- simulating phantoms. A set of scattering coefficient curves is obtained by connecting adjacent points in the plot that have the same scattering coefficient.
- a set of absorption coefficient curves is obtained by connecting adjacent points in the plot that have the same absorption coefficient.
- a given scattering coefficient curve shows how the absorption coefficient changes when the scattering coefficient is constant.
- a given absorption coefficient curve shows how the scattering coefficient changes when the absorption coefficient is constant.
- An example of such a calibration diagram involves plotting a function of reflectance at one distance, R n or 1/R n , versus a ratio such as R n /R m , where R n and R m are the reflectance values at two different distances r n and r m from the light introduction site.
- a preferred method for generating the two dimensional grid comprises the step of plotting 1/R., versus R.,/R 2 .
- R 1 represents the intensity of the re-emitted light at a first collection position. This first collection position is located at a very short distance from the light introduction site.
- R 2 represents the intensity of the re-emitted light at a second collection position. This second position is also located at a very short distance from the light introduction site.
- the first position is adjacent to the second position.
- the distance of the first position from the light introduction site is not equal to the distance of the second position from the light introduction site.
- the first position and the second position are positions of a closely spaced pair of light collecting elements at a given light collection site. As shown schematically in FIG.
- light collecting elements positioned close to the light introduction site mainly collect photons scattered in the layer close to the surface of the skin and have average penetration depth between d av1 and d av2 .
- a plot of 1/R 3 versus R 3 /R 4 yields another set of optical parameters.
- R 3 represents the intensity of re-emitted light at a third position. This third position is located at a distance farther from the light introduction site than the first and second positions.
- R 4 represents the intensity of re-emitted light at a fourth position. This fourth position is also located at a distance farther from the light introduction site than the first and second positions. The third position is adjacent to the fourth position.
- the distance of the third position from the light introduction site is not equal to the distance of the fourth position from the light introduction site.
- the third position and the fourth position are positions of a closely spaced pair of light collecting elements at a given light collection site.
- light collecting elements at positions relatively far from the light introduction site i. e., the third and fourth positions, collect photons scattered mainly in the deeper layers of skin and have average penetration depth between d av3 and d av4 , respectively.
- re-emitted light collected by light collecting elements positioned relatively close to the light introduction site contain information mainly on the optical properties of the surface layer, which extends to a depth of a few hundred micrometers
- re-emitted light collected by light collecting elements positioned relatively far from the light introduction site contain information mainly on the optical properties of the deeper tissue layers, which extend to a depth of 1 to 2 millimeters.
- the optical properties of the two layers may still affect the re-emitted light from both the closer and further light collection sites and may require special mathematical treatment of the data in order to obtain values for optical parameters specific to a given layer. It should be noted that the formation of a grid is not the only means for determining optical parameters.
- Optical parameters can be determined from tables of values, such as, for example, tables of values stored in a computer.
- the placement of the light collection sites (in the case of a single light introduction site) or the placement of the light introduction sites (in the case of a single light collection site) depends upon the number of layers in the sample and the thickness of each layer. In the case of a sample of skin tissue, the number of layers of skin and the thickness of each layer have been accurately reported in the art of dermatology.
- One such configuration comprises a single light collection site and a plurality of light introduction sites distributed at the appropriate distances from the light collection site.
- At least two light collection sites are required in the case of a single light introduction site. It is possible to use a greater number of light collection sites than two. In an alternative embodiment, at least two light introduction sites are required in the case of a single light collection site. It is possible to use a greater number of light introduction sites than two. Increasing the number of light collection sites or light introduction sites, depending on the embodiment employed, increases the resolution of the measurement. Balance between performance and cost may determine the number of possible light introduction sites or light collection sites.
- Instruments constructed according to the present invention differ from instruments of the prior art with respect to configuration.
- the scattering coefficient of the tissue must be much greater than the absorption coefficient of the tissue, and the mean free path of a photon in the tissue must be much smaller than the distance between the light introduction site and the light collection sites.
- the wavelength range of the instruments of the present invention includes ranges where the absorption coefficient is approximately equal to the scattering coefficient, and some of the distances from the light introduction site to the light collection sites are of the same magnitude as the transport photon mean free path.
- a Monte Carlo simulation model is preferred to the Diffusion Theory model for calculating absorption and scattering coefficients of the tissue to process the output of the instrument of the present invention.
- Determination of the concentration of an analyte in a given layer of tissue of a sample can be carried out by measuring the optical parameter(s) of the given layer of tissue of the sample and comparing the optical parameter(s) measured to optical parameter(s) that correspond to known concentrations of the analyte, whereby the concentration of analyte in the layer of tissue can be ascertained.
- the known concentrations of the analyte can be obtained by previously conducted in vivo or in vitro tests. The results of the previously conducted tests can be programmed into a data processor and used to predict concentrations of analytes by means of algorithms derived empirically.
- the method and apparatus of this invention addresses the layered structure of the skin and provides solutions for the effect of outer layers of the skin on the determination of the optical properties of inner layers of the skin.
- FIG. 2 is a block diagram illustrating an embodiment of an apparatus 10 of this invention.
- the apparatus 10 comprises a source of light module 12, a bifurcated optical fiber bundle 14, a human interface module 16, and a detector module 18.
- the source of light module 12 includes a source of modulated light (not shown), such as a Gilway L1041 lamp modulated with a Stanford Research Optical Chopper.
- a prism, a dichroic beam splitter, or the like may be used to direct a portion of the beam emerging from the source of light module 12 to a reference detector (not shown), such as a Hamamatsu S-2386-44K 6C silicon detector, in order to normalize the measurements for fluctuations in intensity of the source of light.
- the rest of the light emerging from the source of light module 12 is focused onto the end of the source tip of a bifurcated fiber 14 by means of at least one focusing lens (not shown). Additional optical elements (not shown), such as attenuators, optical filters, and irises may be inserted between the source of light and the source tip.
- the source tip is preferably held in an adapter (not shown) having provisions for adjusting the location of the source tip with respect to the beam emerging from the source of light.
- FIGS. 3A and 3B illustrate in detail a bifurcated optical fiber bundle 14.
- the bifurcated optical fiber bundle 14 was constructed from Anhydrous G Low OH VIS-NIR optical fibers.
- the bifurcated optical fiber bundle 14 comprises a source tip 20, a detector tip 22, and a common tip 24.
- the three distinct "tips" or termination sites of the bifurcated optical fiber bundle 14 are shown in FIG. 3B.
- the source tip 20 is contained within the source of light module 12
- the detector tip 22 is contained within the detector module 18
- the common tip 24 is contained within the human interface module 16.
- a single optical fiber 26 transmits light from the source tip 20 to the common tip 24.
- the common tip 24 is installed in the human interface module 16, which is placed against a body part during use. As shown in FIG. 3B, the common tip 24 comprises the fiber 26 that transmits light from the source tip 20 to the common tip 24 and the six fibers 28, 30, 32, 34, 36, 38 that collect the light that is re- emitted from the tissue sample and transmit the collected light to the detector tip 22.
- each of the fibers 28, 30, 32, 34, 36, 38 is located within the common tip 24 at increasing distances from the fiber 26.
- the nominal separation distances, r, between the center of the fiber 26 and the centers of the fibers 28, 30, 32, 34, 36, 38 of the common tip 24 are shown in FIG. 4.
- An important aspect of the present invention is that all of the fibers 28, 30, 32, 34, 36, 38 are located at separation distances, r, that are less than 4 mm away, and, preferably, less than 2 mm away from the fiber 26. As will be more thoroughly described below, positioning the fibers in this manner results in enhanced precision and accuracy as compared with the methods used in the prior art.
- the other ends of the fibers 28, 30, 32, 34, 36, 38 are arranged in a circle within the detector tip 22, as shown in FIG. 3B, with sufficient spacing to allow a shutter to interrogate each fiber individually.
- the detector module 18 receives the detector tip 22 and holds it adjacent to a rotating shutter (not shown) that allows detection of the light emitted from one fiber at a time.
- the shutter has a detent or other means to lock it in the six fiber positions.
- a pair of achromatic lenses (25 mm diameter, 60 mm focal length) focuses the light from the fiber of interest on a detector.
- the detector was a Hamamatsu S-2386-44K 6C silicon detector.
- the detector module 18 also comprises appropriate electronic signal processing instrumentation, such as large dynamic range amplifiers and lock-in amplifiers. Alternatively, the outputs of the six fibers can be directed to six detectors for parallel signal processing.
- FIG. 5 illustrates the human interface module 16, which comprises an aluminum disk 40, a thermoelectric cooling element 42, a thermocouple 44, a heat sink 46, the common tip 24, and an interface adapter 48.
- the aluminum disk contains an aperture 50, which receives the common tip 24 of bifurcated optical fiber bundle 14 and holds the common tip 24 against a body part.
- the temperature of the aluminum disk 40 (and of the tissue adjacent to the disk 40) is controlled by a thermoelectric cooling element 42, such as model number SP1507-01 AC (Mariow Industries).
- the thermoelectric cooling element 42 is powered by a temperature controller/power supply, such as model number SE5000-02 (Mariow Industries).
- a heat sink 46 is provided on the back of the thermoelectric cooling element 42 to enhance heat transfer.
- the interface adapter 48 is shaped to conform to a body part and may, for example, be cylindrical, flat, spheroidal, or any other shape.
- Example 1 The apparatus described in Example 1 was tested by measuring the quantity of light re-emitted from the forearms of several individuals.
- the distances of the light collecting elements from the light introduction site are shown in Table 1.
- FIG. 4 shows the spatial arrangement of the light collecting elements and the light introduction site.
- ⁇ s ' and ⁇ a for several Caucasian, Oriental, and Mediterranean subjects were determined at 34° C, by means of spatially resolved diffuse reflectance signals from all the fiber positions.
- the average values of ⁇ s ' and ⁇ a at several illumination wavelengths were used to estimate the transport mean free path of the photons in the skin of these individuals. The results are shown in Table 2.
- the estimated mean free path is greater than the distance between the light introduction site and closest light collecting elements, while the distance between the light introduction site and the furthest light collecting elements is greater than the mean free path of photons in the tissue.
- the penetration depths achieved were less than or equal to about 2.0 mm.
- the majority of the re- emitted light was sampled at depths in the skin less than or equal to about 2 mm. Longer wavelengths, up to 2500 nm, can be selected to achieve shallower or deeper penetration depth.
- Example 2 The method of this example was carried out with the apparatus described in Example 1.
- This type of suspension has been used in the art to simulate the scattering of human tissue in the near-infrared region of the electromagnetic spectrum.
- the vial containing the suspension was inverted and placed on top of the optical fiber bundle at the human interface module 16 described in Example 1 , the polyethylene film contacting the optical fiber bundle. Reflectance as a function of distance from the light introduction site was determined. Complete reflectance curves are shown in FIG. 6A for wavelength 590 nm and are designated as bulk scattering. The ratio of the re- emitted light collected by the two light collecting fibers closest to the light introduction site (R/R;,), and the ratio of the re-emitted light collected by the two light collecting fibers furthest from the light introduction site (R 5 /R 6 ) are plotted in FIG. 6B. In FIG. 6B, R is the intensity of the light re-emitted at distance from the illuminating fiber.
- R 2 is the intensity of the light re-emitted at distance r 2 from the illuminating fiber.
- R 5 is the intensity of the light re-emitted at distance r 5 from the illuminating fiber.
- R 6 is the intensity of the light re-emitted at distance r 6 from the illuminating fiber.
- the values of r,, r 2 , r 5 , and r 6 are set forth in Table 1.
- the re-emitted light collected by the fibers closest to the light introduction site, R and R 2 mainly represents the signal generated close to the interface of the scattering medium and the optical instrument (in this case, the polyethylene film).
- the re- emitted light collected by the fibers further from the light introduction site, R 5 and R 6 mainly represents the signal generated in the bulk of the scattering medium (in this case, the Intralipid® suspension).
- a sheet of polyvinyl alcohol (80 micrometer thick) containing scattering hollow polystyrene particles (referred to hereinafter as PVA sheet) was added between the optical fiber bundle and the inverted covered vial.
- PVA sheet polyvinyl alcohol
- the effect of this sheet is to mimic the stratum corneum and create a layered structure where the outermost layer has absorption and scattering properties different from the bulk of the scattering medium.
- the refractive index of PVA sheet was 1.53, the thickness of the PVA sheet was 80 micrometers, the scattering centers were hollow polystyrene particles (0.8 micrometer), and the reduced scattering coefficient ranged from 4.5 mm "1 at 590 nm to 2.6 mm '1 at 950 nm.
- the effect of the scattering layer as measured at wavelength 590 nm is shown in FIG. 6A and FIG. 6B.
- a layer of polyvinyl alcohol sheet (80 micrometer thick) containing hollow polystyrene particles was inserted between the optical fiber bundle and the first PVA sheet covering the inverted covered vial.
- the total thickness of the PVA sheets was 160 micrometers.
- Silicon oil was applied to the interfaces of the PVA sheets o assure index matching between the layers simulating the stratum corneum.
- the effect of the second layer of polyvinyl alcohol sheet is to mimic a stratum corneum having an increased thickness, because different body parts have different thicknesses of the stratum corneum.
- the effect of the scattering layer is shown in FIGS. 6A and 6B for wavelength 590 nm.
- tissue-simulating phantom which comprised a suspension containing a lipids emulsion comprising 0.65% Intralipid® emulsion and 0.012% nigrosine dye (Eastman Kodak, Rochester, N. Y., Cat. No. C3536).
- a liquid phantom was constructed in the same manner as described in the first part of Example 2. Instead of the almost non-absorbing pure Intralipid® suspension used in Example 2, this blue dye solution was used to simulate both scattering and absorbing properties of human tissues.
- the absorption coefficients of dye-containing suspension at several measurement wavelengths are listed below.
- a PVA sheet 80 ⁇ m thick, the same as that used in Example 2 was inserted between the optical fiber bundle and the liquid phantom. Variations in the stratum corneum were further simulated by using two layers of the PVA sheet (160 ⁇ m thick), with silicon oil being applied to the interfaces of the PVA sheets to assure index matching between the layers simulating the stratum corneum. In spatially resolved diffused reflectance at 590 nm, a general increase in reflectance amplitude is noted when one or two layers of a sheet simulating the stratum corneum is inserted (FIG. 8A).
- R 1 /R 2 the large changes in R 1 /R 2 are greatly influenced by the changes in the topmost layer.
- the minimal changes in R 5 /R 6 represent the unchanged characteristics of the bulk part of the phantom.
- measurement at the smaller distances from the light introduction site r, and r 2 is useful for sensing the optical properties of the top layer of the phantom. This measurement is particularly useful when the contribution of the top layer to the measurement at greater distances from the light introduction site, r 5 and r 6 , needs to be accounted for.
- the apparatus and method of this invention were tested on human volunteers. The following experiments were performed to test the effect of changing the absorption and scattering characteristics of the outer layer of skin on the spatially resolved diffuse reflectance signal, which was measured at different distances from the light introduction site.
- the spatially resolved diffuse reflectance signal of the inner left arm of a Caucasian volunteer was measured. Room temperature was 22° C and temperature of the common tip 24 and aluminum disk 40 in FIG. 5 was set to 34° C. The temperature at the measurement site was allowed to equilibrate at 34° C for two minutes before the measurement was begun.
- the nearly purely absorbing layer was a polyacrylic material (Pale Grey #397, ROSCO, Stamford, CT), 64 ⁇ m thick, and having the transmittance characteristics shown below.
- FIGS. 10A and 10B depict the effects of the topmost layer on the measurement of the spatially resolved diffuse reflectance signal.
- FIGS. 10A and 10B depict the effects of the topmost layer on the measurement of the spatially resolved diffuse reflectance signal.
- FIG. 10A At the strongly absorbing wavelength 590 nm, an almost parallel downward shift of the reflectance curve can be seen (FIG. 10A).
- FIG. 10B At the nearly non-absorbing wavelength 900 nm, the parallel shift is still seen, but to a very small extent.
- This example illustrates that the effect of absorption in the topmost layers is to shift the R(r) curve downward, i. e., there is no preferred detection position for tracking such effect.
- This scattering layer was a sheet of white vellum paper having a thickness of 81 ⁇ m (Cat. # 3R3525, Xerox, Rochester, NY).
- FIGS. 11 A and 11 B depict the effects of the topmost layer on the measurement of the spatially resolved diffuse reflectance signal, at wavelengths 590 nm (FIG. 11 A) and 900 nm (FIG. 11 B). Due to the non-specificity of scattering with respect to wavelength, the effect of the top layer on the spatially resolved diffuse reflectance signal observed for both wavelengths was similar. The apparent curvature changes for the R(r) curves, which are much greater at small distances from the light introduction site, r 1 and r 2 , than at greater distances from the light introduction site, r 5 and r 6 , are evident.
- the slope of the R(r) curves at the smaller distance between the light introduction site and the light collection site has changed significantly, while only minimal changes are seen for the slope of the R(r) curves at the greater distance between the light introduction site and the light collection site (R 5 /R 6 ).
- FIGS. 12A and 12B depict the effects of the topmost layer on the measurement of the spatially resolved diffuse reflectance signal, at wavelengths 590 nm (FIG. 12A) and 900 nm (FIG. 12B). Due to both the absorbing and scattering characteristics of the top layer, both significant downward shift and the curvature change of the R(r) curves can be observed. The shift is much larger at the more absorbing wavelength 590 nm than at the less absorbing wavelength 900 nm. However, the curvature changes are similar at both wavelengths.
- FIGS. 13A and 13B summarize the results of the experiment described above regarding the effects of inserting additional stratum corneum simulating layers between the optical fiber bundle and the human forearm.
- the curvature changes for the R(r) curve from the arm measurement due to higher scattering top layers mainly occur at the smaller distance between the light introduction site and the light collection site, and r 2 (0.4 to 0.8 mm).
- the diffuse reflectance ratio R/Rg (which represents the slope of the R(r) curve at a small distance between the light introduction site and the light collection site) is much more sensitive than the diffuse reflectance ratio R 5 /R 6 (which represents the slope of the R(r) curve at a greater distance between the light introduction site and the light collection site).
- Measurement at short distances is preferred to measurement at long distances for a purely scattering top layer (middle pair of bars in FIGS. 13A and 13B). Measurement at short distances is preferred to measurement at long distances for a layer that has both an absorbing and scattering top layer (right pair of bars in FIGS. 13A and 13B).
- FIGS. 14A and 14B Another example of tests on human volunteers is summarized in FIGS. 14A and 14B.
- the following experiment was performed to test the effect of changing the absorption and scattering characteristics of the outer layer of skin on the spatially resolved diffuse reflectance signal, which was measured at different distances from the light introduction site.
- the spatially resolved diffuse reflectance values of the inner left arms of two Caucasian (light-skinned) volunteers and two African-American (dark-skinned) volunteers were measured.
- Room temperature was 22° C and temperature of the common tip 24 and aluminum disk 40 in FIG. 5 was set to 34° C.
- the temperature at the measurement site was allowed to equilibrate at 34° C for two minutes before the measurement was begun.
- FIG. 14A shows the spatially resolved diffuse reflectance signal for the dorsal forearm of the four volunteers at a wavelength of 560 nm. Noticeable differences in the slopes and magnitudes of the spatially resolved diffuse reflectance signal were observed for the light-skinned and dark- skinned volunteers.
- the mean of the Ln (R/R;,) (which represents the slope of R(r) curve) was 1.4 for the dark-skinned subjects and 0.9 for the light-skinned subjects.
- Melanosomes which are the pigment-containing particles of the skin, are known to be concentrated in the top layers of the skin. These pigmented particles have different absorption and scattering coefficients from the cells and fibers of the stratum corneum and the epidermis. It is these differences that primarily contribute to the differences in skin colors.
- the measurement at smaller distances between the light introduction site and the light collection site ( ⁇ 1 mm) carries more information about the top skin layer, including the stratum corneum and the epidermis.
- the measurement at greater distances between the light introduction site and the light collection site is less sensitive to such differences, and dominated by information about the deeper skin layer.
- Use of a signal measured only at the greater distances between the light introduction site and the light collection site would have led to erroneous values for the optical parameters for the test subjects.
- the use of a much greater distance between the light introduction site and the light collection site would lead to a complication of mixing of optical parameters of the dermis with those of the deeper adipose and muscle layers.
Abstract
Description
Claims
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JP3612324B1 (en) * | 2003-09-29 | 2005-01-19 | 株式会社日立製作所 | Blood glucose level display method and apparatus |
EP1522254A1 (en) * | 2003-10-08 | 2005-04-13 | Hitachi, Ltd. | Blood sugar level measuring method and apparatus |
JP3859158B2 (en) * | 2003-12-16 | 2006-12-20 | セイコーエプソン株式会社 | Microlens concave substrate, microlens substrate, transmissive screen, and rear projector |
US7254425B2 (en) * | 2004-01-23 | 2007-08-07 | Abbott Laboratories | Method for detecting artifacts in data |
JP3557424B1 (en) * | 2004-02-17 | 2004-08-25 | 株式会社日立製作所 | Blood glucose meter |
JP3557425B1 (en) * | 2004-02-17 | 2004-08-25 | 株式会社日立製作所 | Blood glucose meter |
JP3590053B1 (en) * | 2004-02-24 | 2004-11-17 | 株式会社日立製作所 | Blood glucose measurement device |
JP3590054B1 (en) * | 2004-02-26 | 2004-11-17 | 株式会社日立製作所 | Blood glucose measurement device |
US20060155178A1 (en) * | 2004-03-26 | 2006-07-13 | Vadim Backman | Multi-dimensional elastic light scattering |
JP3868963B2 (en) * | 2004-05-10 | 2007-01-17 | 株式会社日立製作所 | Blood glucose level measuring device |
US7251517B2 (en) * | 2004-06-30 | 2007-07-31 | Hitachi, Ltd. | Blood sugar level measuring apparatus |
US7215983B2 (en) * | 2004-06-30 | 2007-05-08 | Hitachi, Ltd. | Blood sugar level measuring apparatus |
US7282703B2 (en) * | 2004-08-11 | 2007-10-16 | Metrosol, Inc. | Method and apparatus for accurate calibration of a reflectometer by using a relative reflectance measurement |
US7399975B2 (en) * | 2004-08-11 | 2008-07-15 | Metrosol, Inc. | Method and apparatus for performing highly accurate thin film measurements |
US7804059B2 (en) * | 2004-08-11 | 2010-09-28 | Jordan Valley Semiconductors Ltd. | Method and apparatus for accurate calibration of VUV reflectometer |
US7663097B2 (en) * | 2004-08-11 | 2010-02-16 | Metrosol, Inc. | Method and apparatus for accurate calibration of a reflectometer by using a relative reflectance measurement |
US7511265B2 (en) * | 2004-08-11 | 2009-03-31 | Metrosol, Inc. | Method and apparatus for accurate calibration of a reflectometer by using a relative reflectance measurement |
JP3884036B2 (en) * | 2004-08-25 | 2007-02-21 | 株式会社日立製作所 | Blood glucose level measuring device |
JP2006094992A (en) * | 2004-09-29 | 2006-04-13 | Hitachi Ltd | Apparatus and method for measuring blood sugar |
JP2006115947A (en) * | 2004-10-19 | 2006-05-11 | Hitachi Ltd | Blood-sugar level measuring apparatus |
JP2006115948A (en) * | 2004-10-19 | 2006-05-11 | Hitachi Ltd | Blood-sugar level measuring apparatus |
US20080068592A1 (en) * | 2004-11-12 | 2008-03-20 | Shinji Uchida | Optical Element for Measuring Biological Information and Biological Information Measuring Device Using the Optical Element |
US20060129038A1 (en) * | 2004-12-14 | 2006-06-15 | Zelenchuk Alex R | Optical determination of in vivo properties |
US20070004976A1 (en) * | 2004-12-14 | 2007-01-04 | Zelenchuk Alex R | In vivo optical measurements of hematocrit |
US7706853B2 (en) * | 2005-02-10 | 2010-04-27 | Terumo Cardiovascular Systems Corporation | Near infrared spectroscopy device with reusable portion |
EP1871221B1 (en) * | 2005-04-18 | 2017-11-15 | GPX Medical AB | Human cavity gas measurement device and method |
KR101361697B1 (en) * | 2005-04-25 | 2014-02-10 | 유니버시티 오브 매사추세츠 | Systems and methods for correcting optical reflectance measurements |
US7570988B2 (en) * | 2005-05-02 | 2009-08-04 | Wisconsin Alumni Research Foundation | Method for extraction of optical properties from diffuse reflectance spectra |
US7627357B2 (en) * | 2005-06-30 | 2009-12-01 | General Electric Company | System and method for non-invasive glucose monitoring |
JP2007007267A (en) * | 2005-07-01 | 2007-01-18 | Kanazawa Univ | Bone density measuring equipment |
EP1907825A2 (en) * | 2005-07-25 | 2008-04-09 | Duke University | Methods, systems, and computer program products for optimization of probes for spectroscopic measurement in turbid media |
US7813778B2 (en) * | 2005-07-29 | 2010-10-12 | Spectros Corporation | Implantable tissue ischemia sensor |
US20070049813A1 (en) * | 2005-08-25 | 2007-03-01 | David Blouin | Optical sensor for sports equipment |
EP1760440A1 (en) * | 2005-08-31 | 2007-03-07 | The Procter and Gamble Company | Confocal raman spectroscopy for dermatological studies |
US7736382B2 (en) | 2005-09-09 | 2010-06-15 | Lockheed Martin Corporation | Apparatus for optical stimulation of nerves and other animal tissue |
JP4647447B2 (en) * | 2005-09-20 | 2011-03-09 | 富士フイルム株式会社 | Sample analyzer |
US20070093717A1 (en) * | 2005-10-20 | 2007-04-26 | Glucon Inc. | Wearable glucometer configurations |
US20070093698A1 (en) * | 2005-10-20 | 2007-04-26 | Glucon Inc. | Apparatus and methods for attaching a device to a body |
US8475506B1 (en) | 2007-08-13 | 2013-07-02 | Lockheed Martin Corporation | VCSEL array stimulator apparatus and method for light stimulation of bodily tissues |
US8945197B1 (en) | 2005-10-24 | 2015-02-03 | Lockheed Martin Corporation | Sight-restoring visual prosthetic and method using infrared nerve-stimulation light |
US8792978B2 (en) | 2010-05-28 | 2014-07-29 | Lockheed Martin Corporation | Laser-based nerve stimulators for, E.G., hearing restoration in cochlear prostheses and method |
US8956396B1 (en) | 2005-10-24 | 2015-02-17 | Lockheed Martin Corporation | Eye-tracking visual prosthetic and method |
US8744570B2 (en) * | 2009-01-23 | 2014-06-03 | Lockheed Martin Corporation | Optical stimulation of the brainstem and/or midbrain, including auditory areas |
US8012189B1 (en) | 2007-01-11 | 2011-09-06 | Lockheed Martin Corporation | Method and vestibular implant using optical stimulation of nerves |
US7988688B2 (en) * | 2006-09-21 | 2011-08-02 | Lockheed Martin Corporation | Miniature apparatus and method for optical stimulation of nerves and other animal tissue |
US8709078B1 (en) | 2011-08-03 | 2014-04-29 | Lockheed Martin Corporation | Ocular implant with substantially constant retinal spacing for transmission of nerve-stimulation light |
US8929973B1 (en) | 2005-10-24 | 2015-01-06 | Lockheed Martin Corporation | Apparatus and method for characterizing optical sources used with human and animal tissues |
US20070179368A1 (en) * | 2005-10-27 | 2007-08-02 | Northwestern University | Method of recognizing abnormal tissue using the detection of early increase in microvascular blood content |
US9314164B2 (en) | 2005-10-27 | 2016-04-19 | Northwestern University | Method of using the detection of early increase in microvascular blood content to distinguish between adenomatous and hyperplastic polyps |
US20090203977A1 (en) * | 2005-10-27 | 2009-08-13 | Vadim Backman | Method of screening for cancer using parameters obtained by the detection of early increase in microvascular blood content |
US20070129615A1 (en) * | 2005-10-27 | 2007-06-07 | Northwestern University | Apparatus for recognizing abnormal tissue using the detection of early increase in microvascular blood content |
JP4573752B2 (en) * | 2005-11-07 | 2010-11-04 | 花王株式会社 | Method and apparatus for determining pigmentation depth |
US20070176105A1 (en) * | 2006-01-13 | 2007-08-02 | Igor Trofimov | Photosensitive diagnostic device |
US7440659B2 (en) * | 2006-02-27 | 2008-10-21 | Wisconsin Alumni Research Foundation | Depth-resolved reflectance instrument and method for its use |
US7751039B2 (en) * | 2006-03-30 | 2010-07-06 | Duke University | Optical assay system for intraoperative assessment of tumor margins |
EP2520331A3 (en) | 2006-04-12 | 2013-02-20 | Proteus Digital Health, Inc. | Void-free implantable hermetically sealed structures |
CN101426419B (en) * | 2006-04-18 | 2012-12-26 | 皇家飞利浦电子股份有限公司 | Optical measurement device |
EP2047910B1 (en) | 2006-05-11 | 2012-01-11 | Raindance Technologies, Inc. | Microfluidic device and method |
US9074242B2 (en) | 2010-02-12 | 2015-07-07 | Raindance Technologies, Inc. | Digital analyte analysis |
CN101489471B (en) * | 2006-05-19 | 2014-08-27 | 北岸大学健康系统公司 | Apparatus for recognizing abnormal tissue using the detection of early increase in microvascular blood content |
KR100827138B1 (en) * | 2006-08-10 | 2008-05-02 | 삼성전자주식회사 | Apparatus for measuring living body information |
US8498699B2 (en) | 2008-10-03 | 2013-07-30 | Lockheed Martin Company | Method and nerve stimulator using simultaneous electrical and optical signals |
US8996131B1 (en) | 2006-09-28 | 2015-03-31 | Lockheed Martin Corporation | Apparatus and method for managing chronic pain with infrared light sources and heat |
US20080129986A1 (en) | 2006-11-30 | 2008-06-05 | Phillip Walsh | Method and apparatus for optically measuring periodic structures using orthogonal azimuthal sample orientations |
US7922738B2 (en) * | 2006-12-01 | 2011-04-12 | Insite Medical Technologies, Inc. | Devices and methods for accessing the epidural space |
US10085643B2 (en) | 2007-01-05 | 2018-10-02 | Jadran Bandic | Analytic methods of tissue evaluation |
WO2010093503A2 (en) * | 2007-01-05 | 2010-08-19 | Myskin, Inc. | Skin analysis methods |
SG177951A1 (en) * | 2007-01-05 | 2012-02-28 | Myskin Inc | System, device and method for dermal imaging |
US20090245603A1 (en) * | 2007-01-05 | 2009-10-01 | Djuro Koruga | System and method for analysis of light-matter interaction based on spectral convolution |
US7883536B1 (en) | 2007-01-19 | 2011-02-08 | Lockheed Martin Corporation | Hybrid optical-electrical probes |
WO2008097559A2 (en) | 2007-02-06 | 2008-08-14 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
WO2008103486A1 (en) * | 2007-02-23 | 2008-08-28 | Duke University | Scaling method for fast monte carlo simulation of diffuse reflectance spectra |
EP2143045A1 (en) * | 2007-03-14 | 2010-01-13 | Spectros Corporation | Metabolism-or biochemical-based anti-spoofing biometrics devices, systems, and methods |
WO2008130623A1 (en) | 2007-04-19 | 2008-10-30 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US9622694B2 (en) * | 2007-06-20 | 2017-04-18 | Vioptix, Inc. | Measuring cerebral oxygen saturation |
KR100905571B1 (en) * | 2007-07-19 | 2009-07-02 | 삼성전자주식회사 | Apparatus for measuring living body information |
WO2009037644A2 (en) * | 2007-09-20 | 2009-03-26 | Koninklijke Philips Electronics N.V. | Method and apparatus for estimating the content of an analyte in a multi-layer medium |
WO2009043050A2 (en) * | 2007-09-27 | 2009-04-02 | Duke University | Optical assay system with a multi-probe imaging array |
US8384033B2 (en) * | 2007-11-09 | 2013-02-26 | The Royal Institute For The Advancement Of Learning/Mcgill University | Quantification of an absorber through a scattering medium |
BRPI0905668A2 (en) * | 2008-01-07 | 2015-07-07 | Myskin Inc | System and method for analyzing light-matter interaction based on spectral convulation |
US20090177051A1 (en) * | 2008-01-09 | 2009-07-09 | Heal-Ex, Llc | Systems and methods for providing sub-dressing wound analysis and therapy |
US20090219537A1 (en) * | 2008-02-28 | 2009-09-03 | Phillip Walsh | Method and apparatus for using multiple relative reflectance measurements to determine properties of a sample using vacuum ultra violet wavelengths |
WO2009126885A1 (en) * | 2008-04-11 | 2009-10-15 | Somanetics Corporation | System and method for differentiating between tissue-specific and systemic causes of changes in oxygen saturation in tissue and organs |
FR2930343B1 (en) * | 2008-04-18 | 2014-09-19 | Commissariat Energie Atomique | OPTICAL DEVICE FOR ANALYZING A DIFFUSING MEDIUM SUPPORTED BY A SUPPORT |
AU2009239460B2 (en) * | 2008-04-21 | 2015-04-23 | Drexel University | Methods for measuring changes in optical properties of wound tissue and correlating near infrared absorption (fNIR) and diffuse reflectance spectroscopy scattering (DRS) with tissue neovascularization and collagen concentration to determine whether wound is healing |
US20110105865A1 (en) * | 2008-04-24 | 2011-05-05 | Duke University | Diffuse reflectance spectroscopy device for quantifying tissue absorption and scattering |
US20100016732A1 (en) * | 2008-07-17 | 2010-01-21 | Lockheed Martin Corporation | Apparatus and method for neural-signal capture to drive neuroprostheses or control bodily function |
EP2315629B1 (en) | 2008-07-18 | 2021-12-15 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US20100076319A1 (en) * | 2008-09-25 | 2010-03-25 | Nellcor Puritan Bennett Llc | Pathlength-Corrected Medical Spectroscopy |
WO2010040142A1 (en) | 2008-10-03 | 2010-04-08 | Lockheed Martin Corporation | Nerve stimulator and method using simultaneous electrical and optical signals |
EP2348967A4 (en) * | 2008-11-06 | 2014-07-02 | Univ Drexel | Non-contact frequency domain near infrared absorption (fnir) device for assessing tissue damage |
US20100188649A1 (en) * | 2009-01-23 | 2010-07-29 | Scott Prahl | Distance measurement device and method of use thereof |
US8938279B1 (en) | 2009-01-26 | 2015-01-20 | VioOptix, Inc. | Multidepth tissue oximeter |
WO2010101525A1 (en) * | 2009-03-05 | 2010-09-10 | Agency For Science, Technology And Research | A method and system for enhancing a microscopy image |
US20100256483A1 (en) * | 2009-04-03 | 2010-10-07 | Insite Medical Technologies, Inc. | Devices and methods for tissue navigation |
TWI439254B (en) * | 2009-04-09 | 2014-06-01 | 私立中原大學 | Heart rate variability measurement headphones |
US8153987B2 (en) * | 2009-05-22 | 2012-04-10 | Jordan Valley Semiconductors Ltd. | Automated calibration methodology for VUV metrology system |
US20120095305A1 (en) * | 2009-06-15 | 2012-04-19 | O2 Medtech, Inc. | Spectrophotometric Monitoring Of Multiple Layer Tissue Structures |
US20110178375A1 (en) * | 2010-01-19 | 2011-07-21 | Avery Dennison Corporation | Remote physiological monitoring |
US9399797B2 (en) | 2010-02-12 | 2016-07-26 | Raindance Technologies, Inc. | Digital analyte analysis |
JPWO2011121694A1 (en) * | 2010-03-31 | 2013-07-04 | 株式会社日立ハイテクノロジーズ | Inspection apparatus and inspection method |
CN102858233B (en) | 2010-04-21 | 2015-11-25 | 皇家飞利浦电子股份有限公司 | The determination of fat water ratio |
US20120130215A1 (en) * | 2010-05-05 | 2012-05-24 | Ilya Fine | Optical measurement of parameters related to motion of light-scattering particles within a fluid by manipulating analog electrical signals |
US7884933B1 (en) * | 2010-05-05 | 2011-02-08 | Revolutionary Business Concepts, Inc. | Apparatus and method for determining analyte concentrations |
US9464983B2 (en) | 2010-07-12 | 2016-10-11 | Seiko Epson Corporation | Concentration determination apparatus, probe, concentration determination method, and program |
JP5626879B2 (en) * | 2010-10-20 | 2014-11-19 | セイコーエプソン株式会社 | Concentration determination apparatus, concentration determination method, and program |
JP5626880B2 (en) * | 2010-10-20 | 2014-11-19 | セイコーエプソン株式会社 | Concentration determination apparatus, concentration determination method, and program |
US8867041B2 (en) | 2011-01-18 | 2014-10-21 | Jordan Valley Semiconductor Ltd | Optical vacuum ultra-violet wavelength nanoimprint metrology |
WO2012112804A1 (en) | 2011-02-18 | 2012-08-23 | Raindance Technoligies, Inc. | Compositions and methods for molecular labeling |
US8565379B2 (en) | 2011-03-14 | 2013-10-22 | Jordan Valley Semiconductors Ltd. | Combining X-ray and VUV analysis of thin film layers |
WO2012126915A1 (en) * | 2011-03-22 | 2012-09-27 | Novartis Ag | Sensor |
CA2830551C (en) * | 2011-03-25 | 2019-09-24 | Hutchinson Technology Incorporated | Systems and methods for measuring oxygenation |
US9556470B2 (en) | 2011-06-02 | 2017-01-31 | Raindance Technologies, Inc. | Enzyme quantification |
US8658430B2 (en) | 2011-07-20 | 2014-02-25 | Raindance Technologies, Inc. | Manipulating droplet size |
JP2013103094A (en) | 2011-11-16 | 2013-05-30 | Sony Corp | Measurement device, measurement method, program, and recording medium |
GB2496690A (en) * | 2011-11-21 | 2013-05-22 | Univ Strathclyde | Measurement apparatus and method with variable path lengths and variable reflective surfaces |
US20130210058A1 (en) * | 2012-02-15 | 2013-08-15 | Lakeland Ventures Development, Llc | System for noninvasive determination of water in tissue |
US20130237852A1 (en) * | 2012-03-12 | 2013-09-12 | Ivwatch, Llc | Geometry of a Transcutaneous Sensor |
US9040917B2 (en) * | 2012-03-30 | 2015-05-26 | Korea Advanced Institute Of Science And Technology | Efficient data extraction method for high-temporal-and-spatial-resolution near infrared spectroscopy system |
US9585604B2 (en) | 2012-07-16 | 2017-03-07 | Zyomed Corp. | Multiplexed pathlength resolved noninvasive analyzer apparatus with dynamic optical paths and method of use thereof |
US9766126B2 (en) | 2013-07-12 | 2017-09-19 | Zyomed Corp. | Dynamic radially controlled light input to a noninvasive analyzer apparatus and method of use thereof |
US20160242682A1 (en) * | 2012-07-16 | 2016-08-25 | Sandeep Gulati | Noninvasive analyzer apparatus and method of use thereof for separating distributed probing photons emerging from a sample |
US9351671B2 (en) | 2012-07-16 | 2016-05-31 | Timothy Ruchti | Multiplexed pathlength resolved noninvasive analyzer apparatus and method of use thereof |
US9351672B2 (en) | 2012-07-16 | 2016-05-31 | Timothy Ruchti | Multiplexed pathlength resolved noninvasive analyzer apparatus with stacked filters and method of use thereof |
US20150018644A1 (en) * | 2012-07-16 | 2015-01-15 | Sandeep Gulati | Multiplexed pathlength resolved noninvasive analyzer apparatus with non-uniform detector array and method of use thereof |
US20160249836A1 (en) * | 2012-07-16 | 2016-09-01 | Sandeep Gulati | Sample optical pathlength control using a noninvasive analyzer apparatus and method of use thereof |
FR2993446B1 (en) * | 2012-07-20 | 2014-07-11 | Cosm O | METHOD FOR MEASURING AND EVALUATING OPTICAL CHARACTERISTICS OF A DIFFUSING MATERIAL AND ITS DEVICE FOR IMPLEMENTING IT |
TWI518306B (en) * | 2012-10-04 | 2016-01-21 | 原相科技股份有限公司 | Image retrieving device and optical motion estimation device |
BR112015009608A2 (en) | 2012-10-30 | 2017-07-04 | Truinject Medical Corp | cosmetic or therapeutic training system, test tools, injection apparatus and methods for training injection, for using test tool and for injector classification |
US9792836B2 (en) | 2012-10-30 | 2017-10-17 | Truinject Corp. | Injection training apparatus using 3D position sensor |
US10939869B2 (en) * | 2013-06-18 | 2021-03-09 | Lawrence Livermore National Security, Llc | Imaging system and method for enhanced visualization of near surface vascular structures |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
JP6372734B2 (en) * | 2013-10-24 | 2018-08-15 | Tdk株式会社 | Biosensor inspection apparatus and inspection method |
US9944977B2 (en) | 2013-12-12 | 2018-04-17 | Raindance Technologies, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
EP3175783B1 (en) | 2014-01-07 | 2022-01-19 | Opsolution GmbH | Device and method for determining a concentration in a sample |
CA2972754A1 (en) | 2014-01-17 | 2015-07-23 | Clark B. Foster | Injection site training system |
US10213550B2 (en) | 2014-01-23 | 2019-02-26 | Covidien Lp | Systems and methods for monitoring clinical procedures using regional blood oxygen saturation |
US9867561B2 (en) | 2014-01-27 | 2018-01-16 | Covidien Lp | Systems and methods for determining whether regional oximetry sensors are properly positioned |
US9861317B2 (en) | 2014-02-20 | 2018-01-09 | Covidien Lp | Methods and systems for determining regional blood oxygen saturation |
US10290231B2 (en) | 2014-03-13 | 2019-05-14 | Truinject Corp. | Automated detection of performance characteristics in an injection training system |
US10575766B2 (en) | 2014-03-31 | 2020-03-03 | Sony Corporation | Measurement device, measurement method, program, and recording medium |
WO2015151587A1 (en) * | 2014-03-31 | 2015-10-08 | ソニー株式会社 | Measurement device, measurement method, program, and recording medium |
US10405784B2 (en) * | 2014-05-14 | 2019-09-10 | Stryker Corporation | Tissue monitoring apparatus and method |
CN105510238B (en) * | 2014-09-28 | 2019-04-05 | 天津先阳科技发展有限公司 | Processing, modeling, prediction technique and the processing unit of multiposition diffusion spectroscopic data |
US9459201B2 (en) | 2014-09-29 | 2016-10-04 | Zyomed Corp. | Systems and methods for noninvasive blood glucose and other analyte detection and measurement using collision computing |
JP6664176B2 (en) * | 2014-09-30 | 2020-03-13 | キヤノン株式会社 | Photoacoustic apparatus, information processing method, and program |
KR101876606B1 (en) * | 2014-10-30 | 2018-07-11 | 한국과학기술원 | Optical spectroscopy system using broadband transceiver based on matched filter for robust data acquisition and control method thereof |
JP6551723B2 (en) * | 2014-11-13 | 2019-07-31 | 株式会社リコー | Optical sensor, optical inspection apparatus, and optical property detection method |
KR20170102233A (en) | 2014-12-01 | 2017-09-08 | 트루인젝트 코프 | Injection training tool emitting omnidirectional light |
WO2016106350A1 (en) | 2014-12-23 | 2016-06-30 | Bribbla Dynamics Llc | Confocal inspection system having non-overlapping annular illumination and collection regions |
US10718931B2 (en) * | 2014-12-23 | 2020-07-21 | Apple Inc. | Confocal inspection system having averaged illumination and averaged collection paths |
CN107209116B (en) | 2014-12-23 | 2020-08-07 | 苹果公司 | Optical inspection system and method including accounting for variations in optical path length within a sample |
CN104545812A (en) * | 2014-12-30 | 2015-04-29 | 中国科学院长春光学精密机械与物理研究所 | Detection depth adjustable non-invasive detection device for human body biochemical criteria |
US10328202B2 (en) | 2015-02-04 | 2019-06-25 | Covidien Lp | Methods and systems for determining fluid administration |
JP2016150081A (en) * | 2015-02-17 | 2016-08-22 | ソニー株式会社 | Optical unit, measurement system and measurement method |
US9395296B1 (en) * | 2015-02-20 | 2016-07-19 | The United States Of America, As Represented By The Secretary Of The Army | Two-dimensional optical spot location using a one-dimensional detector array |
CN105987881B (en) * | 2015-03-05 | 2019-07-23 | 天津先阳科技发展有限公司 | Spectroscopic data disturbance restraining method, modeling method, prediction technique and processing unit |
EA031413B1 (en) * | 2015-04-16 | 2018-12-28 | Белорусский Государственный Университет (Бгу) | Method for determination of toxic bilirubin transformation speed into non-toxic, and water-soluble photoisomer lumirubin |
WO2016191307A1 (en) * | 2015-05-22 | 2016-12-01 | Cercacor Laboratories, Inc. | Non-invasive optical physiological differential pathlength sensor |
WO2017070391A2 (en) | 2015-10-20 | 2017-04-27 | Truinject Medical Corp. | Injection system |
US10799129B2 (en) * | 2016-01-07 | 2020-10-13 | Panasonic Intellectual Property Management Co., Ltd. | Biological information measuring device including light source, light detector, and control circuit |
US10393652B2 (en) * | 2016-01-26 | 2019-08-27 | Tubitak | Portable optical apparatus for diffuse reflectance spectroscopy |
CN109348727B (en) * | 2016-01-26 | 2022-11-29 | 耐克创新有限合伙公司 | Near infrared spectroscopy techniques for sensing glycogen in muscle tissue |
WO2017151441A2 (en) | 2016-02-29 | 2017-09-08 | Truinject Medical Corp. | Cosmetic and therapeutic injection safety systems, methods, and devices |
EP3423972A1 (en) | 2016-03-02 | 2019-01-09 | Truinject Corp. | Sensory enhanced environments for injection aid and social training |
WO2017151716A1 (en) | 2016-03-02 | 2017-09-08 | Truinject Medical Corp. | System for determining a three-dimensional position of a testing tool |
US9554738B1 (en) | 2016-03-30 | 2017-01-31 | Zyomed Corp. | Spectroscopic tomography systems and methods for noninvasive detection and measurement of analytes using collision computing |
EP3446084A1 (en) | 2016-04-21 | 2019-02-27 | Apple Inc. | Optical system for reference switching |
US11642051B2 (en) * | 2016-06-28 | 2023-05-09 | Benjamin Mbouombouo | Common sample zone noninvasive glucose concentration determination analyzer apparatus and method of use thereof |
US10650703B2 (en) | 2017-01-10 | 2020-05-12 | Truinject Corp. | Suture technique training system |
WO2018136901A1 (en) | 2017-01-23 | 2018-07-26 | Truinject Corp. | Syringe dose and position measuring apparatus |
JP2018187143A (en) * | 2017-05-09 | 2018-11-29 | ソニー株式会社 | Optical constant measuring device and optical constant measuring method |
DK3324173T3 (en) * | 2017-07-03 | 2019-05-13 | Fyla Laser S L | A light inspection system of the surface and the interior of a sample |
CN107421905A (en) * | 2017-09-15 | 2017-12-01 | 中国科学院合肥物质科学研究院 | A kind of sample measuring table and non-invasive measurement device and method for keratoderma composition measurement |
CN112512421A (en) | 2018-04-27 | 2021-03-16 | 海德罗斯塔西斯公司 | Tissue hydration monitor |
WO2020018451A1 (en) | 2018-07-16 | 2020-01-23 | Bruin Biometrics, Llc | Perfusion and oxygenation measurement |
JP7117733B2 (en) * | 2018-08-23 | 2022-08-15 | 株式会社リコー | optical sensor |
WO2020210000A1 (en) * | 2019-04-10 | 2020-10-15 | Exxonmobil Research And Engineering Company | Gathering and segregation of heterogeneous crude sources |
KR20220124468A (en) * | 2021-03-03 | 2022-09-14 | 삼성전자주식회사 | Apparatus and method for estimating target component |
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0627619A1 (en) * | 1993-06-02 | 1994-12-07 | Hamamatsu Photonics K.K. | Method for measuring scattering medium and apparatus for the same |
US5490506A (en) * | 1994-03-28 | 1996-02-13 | Colin Corporation | Peripheral blood flow evaluating apparatus |
US5524617A (en) * | 1995-03-14 | 1996-06-11 | Nellcor, Incorporated | Isolated layer pulse oximetry |
US5632273A (en) * | 1994-02-04 | 1997-05-27 | Hamamatsu Photonics K.K. | Method and means for measurement of biochemical components |
WO1997027800A1 (en) * | 1996-02-05 | 1997-08-07 | Diasense, Inc. | Methods and apparatus for non-invasive glucose sensing: non-invasive probe |
US5676143A (en) * | 1992-11-09 | 1997-10-14 | Boehringer Mannheim Gmbh | Apparatus for analytical determination of glucose in a biological matrix |
EP0843986A2 (en) * | 1996-11-26 | 1998-05-27 | Matsushita Electric Works, Ltd. | Device for non-invasive determination of glucose concentration in blood |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3638640A (en) | 1967-11-01 | 1972-02-01 | Robert F Shaw | Oximeter and method for in vivo determination of oxygen saturation in blood using three or more different wavelengths |
US4281645A (en) | 1977-06-28 | 1981-08-04 | Duke University, Inc. | Method and apparatus for monitoring metabolism in body organs |
US4655225A (en) | 1985-04-18 | 1987-04-07 | Kurabo Industries Ltd. | Spectrophotometric method and apparatus for the non-invasive |
US5122974A (en) | 1989-02-06 | 1992-06-16 | Nim, Inc. | Phase modulated spectrophotometry |
JPH06103257B2 (en) | 1988-12-19 | 1994-12-14 | 大塚電子株式会社 | Method and apparatus for measuring absorption coefficient of substance using light scattering |
US5187672A (en) | 1989-02-06 | 1993-02-16 | Nim Incorporated | Phase modulation spectroscopic system |
US5237178A (en) | 1990-06-27 | 1993-08-17 | Rosenthal Robert D | Non-invasive near-infrared quantitative measurement instrument |
US5086229A (en) | 1989-01-19 | 1992-02-04 | Futrex, Inc. | Non-invasive measurement of blood glucose |
US5902235A (en) | 1989-03-29 | 1999-05-11 | Somanetics Corporation | Optical cerebral oximeter |
US5007423A (en) | 1989-10-04 | 1991-04-16 | Nippon Colin Company Ltd. | Oximeter sensor temperature control |
US5419321A (en) | 1990-05-17 | 1995-05-30 | Johnson & Johnson Professional Products Limited | Non-invasive medical sensor |
US5324979A (en) | 1990-09-26 | 1994-06-28 | Futrex, Inc. | Method and means for generating synthetic spectra allowing quantitative measurement in near infrared measuring instruments |
US6181958B1 (en) | 1998-02-05 | 2001-01-30 | In-Line Diagnostics Corporation | Method and apparatus for non-invasive blood constituent monitoring |
US5372136A (en) | 1990-10-06 | 1994-12-13 | Noninvasive Medical Technology Corporation | System and method for noninvasive hematocrit monitoring |
DE69229554T2 (en) | 1991-05-16 | 2000-02-10 | Non Invasive Technology Inc | HEMOGLOBIN MEASUREMENT FOR DETERMINING THE METABOLISM SIZE OF A PERSON |
US5277181A (en) | 1991-12-12 | 1994-01-11 | Vivascan Corporation | Noninvasive measurement of hematocrit and hemoglobin content by differential optical analysis |
WO1993013706A2 (en) | 1992-01-17 | 1993-07-22 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Optical method for monitoring arterial blood hematocrit |
US5297548A (en) | 1992-02-07 | 1994-03-29 | Ohmeda Inc. | Arterial blood monitoring probe |
US5492769A (en) | 1992-09-17 | 1996-02-20 | Board Of Governors Of Wayne State University | Method for the production of scratch resistance articles and the scratch resistance articles so produced |
CA2174719C (en) * | 1993-08-24 | 2005-07-26 | Mark R. Robinson | A robust accurate non-invasive analyte monitor |
US5492118A (en) | 1993-12-16 | 1996-02-20 | Board Of Trustees Of The University Of Illinois | Determining material concentrations in tissues |
US5553615A (en) | 1994-01-31 | 1996-09-10 | Minnesota Mining And Manufacturing Company | Method and apparatus for noninvasive prediction of hematocrit |
DE4417639A1 (en) | 1994-05-19 | 1995-11-23 | Boehringer Mannheim Gmbh | Analysis of concns. of substances in a biological sample |
US5513642A (en) | 1994-10-12 | 1996-05-07 | Rensselaer Polytechnic Institute | Reflectance sensor system |
DE19612425C2 (en) | 1995-03-31 | 2000-08-31 | Nihon Kohden Corp | Apparatus for measuring hemoglobin concentration |
US5725480A (en) | 1996-03-06 | 1998-03-10 | Abbott Laboratories | Non-invasive calibration and categorization of individuals for subsequent non-invasive detection of biological compounds |
JP3617576B2 (en) * | 1996-05-31 | 2005-02-09 | 倉敷紡績株式会社 | Optical measuring device for light scatterers |
US6070093A (en) | 1997-12-02 | 2000-05-30 | Abbott Laboratories | Multiplex sensor and method of use |
-
1998
- 1998-11-23 US US09/198,094 patent/US6353226B1/en not_active Expired - Lifetime
-
1999
- 1999-11-10 EP EP99960286A patent/EP1133253A1/en not_active Withdrawn
- 1999-11-10 WO PCT/US1999/026687 patent/WO2000030530A1/en not_active Application Discontinuation
- 1999-11-10 JP JP2000583421A patent/JP2003510556A/en not_active Withdrawn
- 1999-11-10 CA CA002352201A patent/CA2352201A1/en not_active Abandoned
-
2001
- 2001-12-21 US US10/036,826 patent/US6630673B2/en not_active Expired - Lifetime
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5676143A (en) * | 1992-11-09 | 1997-10-14 | Boehringer Mannheim Gmbh | Apparatus for analytical determination of glucose in a biological matrix |
EP0627619A1 (en) * | 1993-06-02 | 1994-12-07 | Hamamatsu Photonics K.K. | Method for measuring scattering medium and apparatus for the same |
US5632273A (en) * | 1994-02-04 | 1997-05-27 | Hamamatsu Photonics K.K. | Method and means for measurement of biochemical components |
US5490506A (en) * | 1994-03-28 | 1996-02-13 | Colin Corporation | Peripheral blood flow evaluating apparatus |
US5524617A (en) * | 1995-03-14 | 1996-06-11 | Nellcor, Incorporated | Isolated layer pulse oximetry |
WO1997027800A1 (en) * | 1996-02-05 | 1997-08-07 | Diasense, Inc. | Methods and apparatus for non-invasive glucose sensing: non-invasive probe |
EP0843986A2 (en) * | 1996-11-26 | 1998-05-27 | Matsushita Electric Works, Ltd. | Device for non-invasive determination of glucose concentration in blood |
Non-Patent Citations (2)
Title |
---|
TSUCHIYA Y ET AL: "Quantitation of absorbing substances in turbid media such as human tissues based on the microscopic Beer-Lambert law", OPTICS COMMUNICATIONS,NL,NORTH-HOLLAND PUBLISHING CO. AMSTERDAM, vol. 144, no. 4-6, 15 December 1997 (1997-12-15), pages 269 - 280, XP004098881, ISSN: 0030-4018 * |
WILSON B C ET AL: "OPTICAL REFLECTANCE AND TRANSMITTANCE OF TISSUES: PRINCIPLES AND APPLICATIONS", IEEE JOURNAL OF QUANTUM ELECTRONICS,US,IEEE INC. NEW YORK, vol. 26, no. 12, 1 December 1990 (1990-12-01), pages 2186 - 2199, XP000453579, ISSN: 0018-9197 * |
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JP2005506517A (en) * | 2001-01-26 | 2005-03-03 | センシス メディカル インク | Noninvasive measurement of glucose by optical properties of tissue |
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KR100893432B1 (en) | 2001-01-26 | 2009-04-17 | 센시스 메디칼 인코포레이티드 | A method for noninvasive measurement of a target analyte property in a tissue sample and an apparatus therefor |
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Also Published As
Publication number | Publication date |
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US6353226B1 (en) | 2002-03-05 |
CA2352201A1 (en) | 2000-06-02 |
JP2003510556A (en) | 2003-03-18 |
US6630673B2 (en) | 2003-10-07 |
US20020084417A1 (en) | 2002-07-04 |
EP1133253A1 (en) | 2001-09-19 |
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