Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2001-02-20
2004-04-13
Hindenburg, Max F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S317000
Reexamination Certificate
active
06721582
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to instruments and methods for performing non-invasive measurements of analyte concentrations and for monitoring, analyzing and regulating tissue status, such as tissue glucose levels.
2. Description of the Background
Diabetes is a chronic life threatening disease for which there is presently no cure. It is the fourth leading cause of death by disease in the United States and at least 175 million people worldwide are estimated to be diabetic. Diabetes is a disease in which the body does not properly produce or respond to insulin. The high glucose concentrations that can result from this affliction can cause severe damage to vital organs, such as the heart, eyes and kidneys.
Type I diabetes (juvenile diabetes or insulin-dependent diabetes mellitus) is the most severe form of the disease, comprising approximately 10% of the diabetes cases in the United States. Type I diabetics must receive daily injections of insulin in order to sustain life. Type II diabetes, (adult onset diabetes or non-insulin dependent diabetes mellitus) comprises the other 90% of the diabetes cases. Type II diabetes is often manageable with dietary modifications and physical exercise, but may still require treatment with insulin or other medications. Because the management of glucose to near-normal levels can prevent the onset and the progression of complications of diabetes. Persons afflicted with either form of the disease are instructed to monitor their blood glucose concentration in order to assure that the appropriate level is achieved and maintained.
Traditional methods of monitoring the blood glucose concentration of an individual require that a blood sample be taken. This method can be painful, inconvenient, costly, and pose the risk of infection. Another glucose measuring method involves urine analysis, which, aside from being inconvenient, may not reflect the current status of the patient's blood glucose because glucose appears in the urine only after a significant period of elevated levels of blood glucose. An additional inconvenience of these traditional methods is that they require testing supplies such as collection receptacles, syringes, glucose measuring devices and test kits. Although disposable supplies have been developed, they are costly and can require special methods for disposal.
Many attempts have been made to develop a painless, non-invasive external device to monitor glucose concentrations. Various approaches have included electrochemical and spectroscopic technologies, such as near-infrared spectroscopy and Raman Spectroscopy. Despite extensive efforts, however, none of these methods has, so far, yielded a non-invasive device or method for the in vivo measurement of glucose that is sufficiently accurate, reliable, convenient and cost-effective for routine use.
The phenomenon of endogenous skin fluorescence, as well as endogenous fluorescence of other biological tissues, has been well documented in the literature. Methods for non-invasively measuring skin fluorescence have been developed and incorporated into commercially available instruments (e.g. Skin Skan or Fluorolog). In skin, important fluorophores include tryptophan-containing proteins, which fluoresces in the 350-450 nm region, and fluorophores associated with collagen cross links, skin oils, NADH, FAD, other flavoproteins, elastin, and quinones, which fluoresce in a broad region from 420 to 650 nm (J. Invest. Dermatol. 111:776-780, 1998, and references therein).
Fluorescence has been used to predict malignancies in tissue, e.g., cervical tissue, bladder tissue, and the buccal cavity. Fluorescence of dyes (fluorescence associated with dyes that selectively bind to biological compounds) has also been used to study in vivo cellular processes.
SUMMARY OF THE INVENTION
The invention overcomes problems and disadvantages associated with current strategies and designs and provides new instruments and methods for monitoring, analyzing and regulating in vivo glucose levels or other analyte levels in an individual.
In one general aspect, the invention features a non-invasive glucose monitoring instrument useful in vivo. The instrument comprises a radiation source, a radiation detector and a processing circuit or analyzing means. The radiation source is capable of directing excitation radiation to a portion of a tissue surface of a patient and emits radiation at at least one wavelength that excites a target in the tissue to emit radiation. The tissue surface may be an exterior or an interior tissue surface of a patient. For example, the surface may be a mucosal area, such as the gums or other mucosal area, the eyeballs, and surrounding areas, such as the eyelids. More preferably, the surface is the patient's skin. Alternately, the tissue surface may be an interior surface such as the serosal or mucosal surface of an organ.
The excited target provides information that can be correlated with the patient's glucose level. More specifically, the radiation emitted from the excited target and received at the tissue surface correlates with the glucose level of the tissue and thus provides a glucose level indication of the patient. A glucose level indication is a quantitative, qualitative or relative measurement that correlates with the blood glucose content or concentration of the patient.
The radiation detector is positioned to receive the radiation emitted from the tissue surface. Radiation received at the surface may be quenched or amplified by one or more matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, in the tissue. A processing circuit is operatively connected to the radiation detector that translates emitted radiation to a measurable signal to obtain the glucose level indication. Alternately, analyzing means is operatively connected to the radiation detector for analyzing radiation detected by the radiation detector and translating the detected radiation to an indication of the tissue glucose level.
The excited target is not glucose itself, but a molecular component of the patient such as, for example, a component of skin or other tissue, that is related, is sensitive to, or co-varies with glucose concentration, such as tryptophan, elastin, collagen or collagen cross links, NADH, or FAD. Suitable targets are structural components, and compounds and molecules that reflect alterations in the environment of matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, of the tissue and are sensitive to or correlate with tissue glucose concentration. The target may provide an emitted fluorescence signal that is related to the patient's blood glucose level, and/or absorb certain portions of the returned signal creating a unique signal correlatable with glucose concentration, or a combination of the two.
The radiation detector is responsive to the emission band of the target or species in the skin. Preferably, the excitation radiation is ultraviolet radiation or visible light, such as blue light. The radiation emitted at the tissue surface is preferably fluorescence radiation from the excitation of the non-glucose target.
The instrument may further include means for measuring scattering re-emitted or scattered radiation remitted from the irradiated skin and means for measuring absorbance, such as absorption from skin chromophores, like oxy- and/or deoxyhemoglobin, and melanin. The radiation emitted, reflected or transmitted from the excited target and signal therefrom correlates with the blood glucose of the patient.
Another embodiment of the invention is directed to a non-invasive analyte monitoring instrument comprising a radiation source for directing excitation radiation to a portion of a tissue surface, (i.e., about 0.5 to 4 square centimeters of skin), a radiation detector, and a processing circuit. Preferably, the analyte being “detected” maybe correlated with glucose. The radiation source is a visible light source or an ul
Brand Derek
Freeman Jenny
Hopmeier Michael J.
Kollias Nikiforos
Mansfield James
Argose, Inc.
Elrifi Ivor R.
Hindenburg Max F.
Kremer Matthew
Mintz Levin Cohn Ferris Glovsky & Popeo PC
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