Chemistry: analytical and immunological testing – Heterocyclic carbon compound – Hetero-o
Reexamination Certificate
2000-07-28
2003-10-21
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Heterocyclic carbon compound
Hetero-o
C436S164000, C436S171000
Reexamination Certificate
active
06635491
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the determination of the concentration of an analyte in a tissue non-invasively. More particularly, the invention relates to the determination of the concentration of an analyte in a tissue non-invasively by compensating for changes in the water content of the tissue resulting from a change in a disease condition or a change in a physiological condition.
2. Discussion of the Art
Optical monitoring of metabolites non-invasively is an important tool in clinical diagnostics. The ability to determine the concentration of an analyte or a disease state in a human subject without performing an invasive procedure has several advantages as compared with such determinations by invasive procedures. These advantages include, for example, ease of performing the test, reduction of pain, and decreased exposure to potential biohazards. The use of non-invasive procedures typically results in increased frequency of testing, increased accuracy in monitoring and control, and improved patient care. As used herein, a “non-invasive” technique (alternatively referred to herein as a “NI technique”) is one that can be used without removing a sample from, or without inserting any instrument into, the tissues of the body. Non-invasive techniques typically involve irradiating a vascular region of the body with electromagnetic radiation and measuring the spectral information that results from absorption, scattering, and emission of light by the tissue.
Measurements in the 550-1300 nm region of the electromagnetic spectrum are commonly used in the art of non-invasive determinations. This spectral region is located between the visible bands characteristic of hemoglobin absorption and the infrared bands characteristic of water absorption. Electromagnetic radiation penetrates to a sufficient depth in the tissue to allow use thereof in a spectral measurement or a therapeutic procedure.
Determination of hemoglobin and hematocrit values non-invasively would offer a simple, biohazard-free, painless procedure suitable for use in blood donation centers. Non-invasive determinations of hemoglobin and hematocrit values are useful for the diagnosis of anemia in infants and mothers, because these determinations avoid the pain associated with pediatric blood sampling. Non-invasive determination of hematocrit values can yield important diagnostic information for patients undergoing dialysis. A low hematocrit value will indicate incomplete dialysis, while a rapid increase in the hematocrit value during dialysis indicates that the patient may faint due to a reduction in blood pressure.
An important application for non-invasive diagnostics is in the field of diagnosis and monitoring of diabetes. Diabetes mellitus is a chronic metabolic disorder characterized by an absolute or relative insulin deficiency, hyperglycemia, and glycosuria. If uncontrolled, diabetes can result in a variety of adverse clinical manifestations, such as, for example, retinopathy, atherosclerosis, microangiopathy, nephropathy, and neuropathy. In its advanced stages, diabetes can cause blindness, coma, and ultimately death. Accurate control of blood glucose level in the “normal range”, 60-120 mg/dL, is necessary for diabetics to avoid or reduce complications resulting from hypoglycemia and hyperglycemia. As used herein, “blood glucose level” means the concentration of glucose in venous or capillary blood (depending on the sample used), expressed in mg/dL or as mM (molar) concentration.
The near-infrared region of the electromagnetic spectrum contains portions of the hemoglobin and water absorption bands. These bands are several orders of magnitude more intense than are glucose overtone absorption bands. Thus, measurement of blood glucose level will be greatly affected by changes in hemoglobin absorption and water absorption.
U.S. Pat. Nos. 5,086,229; 5,324,979; and 5,237,178 describe non-invasive techniques for measuring blood glucose level. In these methods, a blood-containing body part is illuminated and light that is transmitted through or reflected from the body part is detected. The blood glucose level is calculated from the signals measured. These patents are silent with respect to the effect of change in the water content of the body on the signal measured.
U.S. Pat. Nos. 5,187,672; 5,122,974; 5,492, 5,492,118; 5,713,352; and 5,770,454 describe frequency-domain methods and apparatus for determination of the scattering coefficient of tissues and calculation of the concentration of analytes, but are silent with respect to the effect of changes in the water content of the body on the scattering signal measured.
U.S. Pat. No. 5,337,745 describes a pulsatile-based method for determining the concentrations of compounds in the blood stream.
Spatially resolved diffuse reflectance techniques, described in U.S. Pat. Nos. 5,551,422; 5,676,143; 5,492,118; 5,057,695, European Patent Application EP 0810429, are silent with respect to the effect of change in the water content of the body on determination of blood glucose level from scattering data. Thus, two identical values of blood glucose level at different water contents of the body will result in different values for the scattering coefficient of the tissue.
Water is the major component of the human body. It is estimated that tissues contain from about 70% to about 80% water. Change in the water content of the tissue results in a large variability in the optical properties of the tissue. According to Wilson et al., the change in the scattering coefficient resulting from an increase of 5 mM (90 mg/dL) in blood glucose level is equivalent to the change in the scattering coefficient resulting from a 1% increase in the water content of the tissue. This change in scattering coefficient is also equivalent to the effect of a 0.5° C. decrease in temperature (J. Qu, B. Wilson, Journal of Biomedical Optics, 2(3), July 1997, pp. 319-325).
Although a variety of spectroscopic techniques are disclosed in the art, there is still no commercially available device that provides blood glucose level measurements non-invasively with an accuracy that is comparable to that of invasive methods. Thus, there is a continuing need for improved apparatus and methods for non-invasive determinations that are unaffected by variations in physiological conditions of tissues, such as water content, temperature, and perfusion. There is also a need for reagent-free, painless methods and devices for measuring blood glucose levels in diabetic patients.
SUMMARY OF THE INVENTION
This invention provides a method for determining the concentration of an analyte in tissue. The method involves compensating for a change in the value of an optical property of the tissue, such as, for example, the scattering coefficient, resulting from a change in the hydration status of the tissue. The method comprises the steps of:
(a) measuring at least one optical property of a tissue sample at at least one wavelength at an initial time;
(b) calculating the absorption coefficient and the scattering coefficient of the tissue sample at the initial time;
(c) repeating the measurement of the at least one optical property of the tissue sample at at least a later time at the at least one wavelength;
(d) calculating the absorption coefficient and the scattering coefficient of the tissue sample at at least the later time;
(e) calculating the change in the value of the absorption coefficient at the at least one wavelength to indicate the change in the water content of the tissue sample and the change in the value of the scattering coefficient to indicate both the change in the water content of the tissue sample and the change in concentration of an analyte in the tissue sample;
(f) correcting the value of the scattering coefficient to account for the effect of the change in the water content of the tissue sample; and
(g) calculating the concentration of the analyte by means of the corrected value of the scattering coefficient.
Wavelengths at which the absorption coefficient is determined correspon
Bolt Rene′ Alexander
de Mul Frits Frans Maria
Kanger Johannes Sake
Khalil Omar S.
Abbott Labortories
Gakh Yelena
Warden Jill
Weinstein David L.
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