Abbott Laboratories Corporation

Charles F Hanna

Omar S Khalil

Shu-jen Yeh

Xiaomao Wu

Tzyy-Wen Jeng

Stanislaw Kantor

Thomas F Zurek

Johannes Sake Kanger

Frits Frans Maria De Mul

Arnold F Stalder

Eric B Shain

Michael G Lowery

Gary M Oosta

Joseph Larry Pezzaniti

John M Lindberg

Hugh W Graham

Kevin R Genger

Rene&prime; Alexander Bolt

David C Wender

Ren&eacute; A Bolt

Ete Z Szuts

Denise A Grigalauski

Frits F M De Mul

Denise G Huff

Carole L Coleman

Rene' Alexander Bolt

A method for collecting optical data at two morphologically similar, substantially non-overlapping, and preferably adjacent, areas on the surface of a tissue, while the temperature in each area is being maintained or modulated according to a temperature program. The optical data obtained are inserted into a mathematical relationship, e.g., an algorithm, that can be used to predict a disease state (such as the diabetes mellitus disease state) or the concentration of an analyte for indicating a physical condition (such as blood glucose level). This invention can be used to differentiate between disease status, such as, for example, diabetic and non-diabetic. The method involves the generation of a calibration (or training) set that utilizes the relationship between optical signals emanating from the skin under different thermal stimuli and disease status, e.g., diabetic status, established clinically. This calibration set can be used to predict the disease state of other subjects. Structural changes, as well as circulatory changes, due to a disease state are determined at two morphologically similar, but substantially non-overlapping areas on the surface of human tissue, e.g., the skin of a forearm, with each area being subjected to different temperature modulation programs. In addition to determination of a disease state, this invention can also be used to determine the concentration of an analyte in the tissues. This invention also provides an apparatus for the determination of a disease state, such as diabetes, or concentration of an analyte, such as blood glucose level, by the method of this invention.

Method for optical measurements of tissue to determine disease state or concentration of an analyte

Devices and methods for non-invasively measuring at least one parameter of a sample, such as the presence of a disease condition, progression of a disease state, presence of an analyte, or concentration of an analyte, in a biological sample, such as, for example, a body part. In these devices and methods, temperature is controlled and is varied between preset boundaries. The methods and devices measure light that is reflected, scattered, absorbed, or emitted by the sample from an average sampling depth, d, that is confined within a region in the sample wherein temperature is controlled. According to the method of this invention, the sampling depth d, in human tissue is modified by changing the temperature of the tissue. The sampling depth increases as the temperature is lowered below the body core temperature and decreases when the temperature is raised within or above the body core temperature. Changing the temperature at the measurement site changes the light penetration depth in tissue and hence d. Change in light penetration in tissue as a function of temperature can be used to estimate the presence of a disease condition, progression of a disease state, presence of an analyte, or concentration of an analyte in a biological sample. According to the method of this invention, an optical measurement is performed on a biological sample at a first temperature. Then, when the optical measurement is repeated at a second temperature, light will penetrate into the biological sample to a depth that is different from the depth to which light penetrates at the first temperature by from about 5% to about 20%.

Method for modulating light penetration depth in tissue and diagnostic applications using same

A method for the determination of hemoglobin and hematocrit by means of an apparatus that is capable of controlling the temperature of a defined subcutaneous volume of human skin. The method involves a calculation of hemoglobin concentration and hematocrit value that takes into consideration the values of optical parameters of the sample at various pre-set temperatures. The apparatus and method employ steady state optical measurements of samples, such as, for example, human tissue, by means of a reflectance tissue photometer and localized control of the temperature of the sample. According to the method of this invention, an optical signal from a defined subcutaneous volume of human skin is measured as the temperature of this volume is controlled. The method and apparatus of this invention allow determination of hemoglobin concentration and hematocrit value non-invasively in a population of subjects having different skin colors by means of steady state reflectance measurements. The method of this invention for determination of hemoglobin concentration and hematocrit value is useful for monitoring patients, testing at the point of care, and screening for anemia. In contrast to other attempts in the prior art that rely on signals of cardiac pulses, the method of this invention has the advantage for the determination of analytes in weak cardiac pulse situations, such as, for example, in elderly patients.

Method and device for the noninvasive determination of hemoglobin and hematocrit

Non-invasive sensor having controllable temperature feature

Method for improving non-invasive determination of the concentration of analytes in a biological sample

Apparatus and method for non-invasively measuring at least one optical parameter of a sample, particularly a sample of tissue that comprises a plurality of layers. The at least one parameter can be used to determine the presence or concentration of an analyte of interest in the sample of tissue. The apparatus and method of the present invention (1) measure light that is substantially reflected, scattered, absorbed, or emitted from a shallower layer of the sample of tissue, (2) measure light that is substantially reflected, scattered, absorbed, or emitted from a deeper layer of the sample of tissue, (3) determine at least one optical parameter for each of these layers, and (4) account for the effect of the shallower layer on the at least one optical parameter of the deeper layer. Specifying the sampling depth allows determinations of the optical properties of a specific layer of the sample of the tissue, e.g., dermis, and decreases interference from other layers, e.g., stratum corneum and epidermis, in these determinations.

Non-invasive sensor capable of determining optical parameters in a sample having multiple layers

A method and apparatus for the measurement of trans-cutaneous diffuse reflectance at a single sampling distance for determining the concentration of an analyte in a biological sample, such as, for example, human tissue. The determination of the concentration of the analyte has been found to depend on the sampling distance and reaches an optimal result at a defined sampling distance for a given analyte and a given sample. The method involves measuring the light re-emitted from the sample at a distance from a light introduction site and correlating the intensity of the re-emitted light to the concentration of an analyte. For a given sample, the distance between the light collection site and a light introduction site (i.e., the sampling distance) corresponds to the depth from the surface into the sample at which scattering and absorption events significantly affect the intensity of re-emitted light (i.e., the sampling depth). Prior knowledge about the sample determines the optimal sampling depth for performing a measurement for a specific analyte and the corresponding sampling distance needed to reach that optimal sampling depth. Optimization of the sampling distance, as well as the correlation relationship, can be established in a calibration procedure.

Optical sensor having a selectable sampling distance for determination of analytes

A method for the determination of concentrations of analytes, e.g., glucose, and other metabolites in human tissue, wherein the temperature of a defined cutaneous volume of tissue, e.g., human skin, is controlled. The method involves calculating the concentration of an analyte in the tissue by taking into consideration the values of optical parameters of a sample of tissue measured in the defined cutaneous volume of the tissue at various temperatures. The selection of the defined volume is a function of the sampling distance along the surface of the tissue, the wavelength of light used to illuminate the tissue, and the temperature in the defined volume of tissue, which is a function of the temperature at the surface of the tissue. In one embodiment of the method of this invention, an optical signal re-emitted from a defined cutaneous volume of the tissue is measured, as the temperature of this volume is maintained at a constant value. In another embodiment of the method of this invention, the temperature of the defined cutaneous volume of the tissue is varied within a defined physiological range to change the depth of penetration of light into the tissue, thereby achieving a depth profile for the optical signal. The method of this invention is useful for monitoring the concentrations of analytes in tissues, testing at the point of care, and screening for diseases, such as, for example, diabetes. The method of this invention utilizes changes in temperature and selection of wavelengths to define cutaneous volumes below the surface of the tissue, in which volumes the concentration of an analyte can be determined.

Method for the non-invasive determination of analytes in a selected volume of tissue

Apparatus and method for non-invasively measuring at least one optical parameter of a sample, particularly a sample of tissue that comprises a plurality of layers. The at least one parameter can be used to determine the presence or concentration of an analyte of interest in the sample of tissue. The apparatus and method of the present invention (1) measure light that is substantially reflected, scattered, absorbed, or emitted from a shallower layer of the sample of tissue, (2) measure light that is substantially reflected, scattered, absorbed, or emitted from a deeper layer of the sample of tissue, (3) determine at least one optical parameter for each of these layers, and (4) account for the effect of the shallower layer on the at least one optical parameter of the deeper layer. Specifying the sampling depth allows determinations of the optical properties of a specific layer of the sample of the tissue, e.g., dermis, and decreases interference from other layers, e. g., stratum corneum and epidermis, in these determinations.

A method and apparatus for measuring the concentration of an analyte of interest, e.g. glucose, in blood non-invasively, i.e., without penetrating the skin or obtaining a biological sample from the body of a patient. The method and apparatus uses a plurality of measurement channels with appropriate wavelengths of interest to control variations of signal and to separate the contribution of the analyte of interest from those of interfering compounds. The method and apparatus of this invention can also be adapted to allow a portion of a body part to be engorged with blood to bring about greater accuracy in optical measurements. In the method of this invention, at least two similar, but not identical, measurements are made concurrently. For example, at least two measurements can be made with similar, but not identical, wavelengths of electromagnetic radiation. The two wavelengths should not be overlapping to allow maximum non-identity. By making measurements concurrently, each measurement channel in the system experiences variations as they occur substantially simultaneously in all channels. By selecting one of the channels as a reference channel and by normalizing the optical measurements of the other channels to this reference channel, the variations common to all channels are eliminated. Removing these common variations from the optical measurements by normalization, such as by calculating ratios of the measurement of each of the measuring channels to that of the reference channel, will allow the actual changes of the signal for a specific analyte of interest to be measured.

Method and apparatus for non-invasively measuring the amount of glucose

An improved device is used for performing solid-phase chemiluminescent immunoassays. The device comprises a container having a fibrous matrix and a porous absorbent material. An improvement in the device is the use of light absorbing material as the absorbent material or as a light barrier between the fibrous matrix and the absorbent material. A second improvement comprises a fibrous matrix of binderless fiber matrix, such as glass fiber. The invention improves the direct measurement of the chemiluminescent signal from a solid surface by reducing background signal. The device is disposable and is suitable for manual use or for use with an apparatus having programmed instructions. The device is designed to be employed in a variety of solid-phase diagnostic assays such as sandwich or competitive binding assays. The device is also designed for use with microparticle capture or ion capture methods of separating the immunochemical reaction products.

Device containing a light absorbing element for automated

A disposable device suitable for performing automated solid-phase diagnostic assays which employs microparticles to complex an analyte and where the microparticle complex becomes retained and immobilized on a fibrous matrix such that the presence of analyte on the microparticles can be detached by optical means. A device is disclosed having a plurality of well pairs comprising a sample well for receiving a sample and reagents for forming a reaction mixture, a read well comprising (a) an entrance port and holder for receiving and holding a quantity of sample and assay reagents, (b) a fibrous matrix for retaining and immobilizing microparticle/analyte complexes for detection, said fibrous matrix positioned below said holder, and having an average spatial separation of fibers greater than the average diameter of said microparticles, (c) absorbent material positioned below said fibrous matrix for assisting the flow of sample and assay reagents through said fibrous matrix, (d) walls or ribs for creating a substantially light-tight real surrounding the wells, (e) a vent for venting air entrapped in the absorbent material and which is displaced by fluids absorbed therein, and (f) a passage between the sample well and the read well whereby sample and reaction mixtures can be transferred and washed from said sample well into said read well without being contacted by any apparatus.

Device for performing solid-phase diagnostic assay

A method for performing a microparticle diagnostic assay in a device having a shallow sample well for receiving a sample and reagents for forming a reaction mixture, a read well positioned adjacent to said sample well and separated from said sample well by a wall which is constructed and arranged such that when wash fluid is injected into said sample well, sample and reaction mixtures are washed from said shallow sample well, over the wall and into said read well. The steps of the method comprise forming microparticle analyte complexes in said shallow sample well; washing said microparticle analyte complexes from said shallow sample well over the wall and into said read well where a fibrous matrix retains and immobilizes said microparticle analyte complexes; adding to said read well an indicator substance capable of forming an assay signal when said microparticle analyte complexes are present; and detecting said assay signal produced by said indicator substance.

Growing community of inventors

Libertyville, IL, United States of America

Charles F Hanna