US 2003/0191377 A1 · Apparatus and method for non-invasive spectroscopic measurement of analytes in tissue using a matched reference analyte

Abstract

A method is provided for building improved calibration models or for improving modifications to these models or validation of the models used in the non-invasive spectroscopic measurement of an analyte or attribute of tissue. The method uses a matched reference sample and measurement of that sample to ensure that the correct relationship between the spectra and analyte is made during the model building, modification or calibration process. A matched reference sample is one in which the analyte of interest or attribute of interest in the reference sample is representative of the analyte or attribute at the site being non-invasively sampled or the agreement between the reference concentration and the non-invasively sampled concentration is clinically significant.

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Claims48

Dependent claims

A method for performing modifications to calibration models in the non-invasive spectroscopic measurement of an analyte or attribute of tissue, the method comprising the steps of:

providing a means for irradiating tissue with infrared energy;
providing an output element, the output element operatively connected to a means for measuring a spectrum;
irradiating tissue with the infrared energy so that there is absorption of at least a portion of the infrared energy in the tissue;
collecting at least a portion of the infrared energy exiting the tissue through the output element and measuring the resulting spectrum;
collecting at least one matched reference sample that is assayed to determine at least one reference value of the analyte or attribute of tissue;
and
using the at least one reference value with the spectral measurement to perform a modification to the calibration model.

4 more elements

Dependencies are inferred from the claim text.

Description11,125 words

Summary2,942 words

#The present invention generally relates to a quantitative spectroscopy system for measuring analyte concentrations or other attributes of tissue utilizing non-invasive techniques in combination with multivariate analysis. More specifically, the present invention relates to a method for building improved calibration models which uses a matched analyte reference measurement to ensure that the correct relationship between the spectra and reference measurement of the analyte is made during the calibration process and a system incorporating the developed calibration model.

#The need for an accurate and non-invasive method for determining attributes of or analyte concentrations in bodily tissues, bodily fluids or other biological samples is well documented. For example, accurate non-invasive measurement of blood glucose levels in diabetic patients would greatly improve diabetes treatment. U.S. Pat. No. 5,379,764 to Barnes et al. discloses the necessity for diabetics to frequently monitor blood glucose levels. The more frequent the blood glucose levels are measured, the less likely the occurrence of large swings in blood glucose levels. These large swings are associated with the very undesirable short-term symptoms and long-term complications of diabetes. Such long-term complications include heart disease, arteriosclerosis, blindness, stroke, hypertension, kidney failure, and premature death.

#Several systems have been proposed for the non-invasive measurement of blood glucose levels. However, despite these efforts, direct and invasive measurements (e.g., blood sampling by a lancet cut into the finger) are still necessary for most if not all presently FDA approved and commercially available glucose monitors. This is believed so compromising to the diabetic patient that frequent blood glucose measurement, which is necessary to ensure effective diabetes management, is rarely achieved.

Brief description of the drawings15 figures

#FIG. 1 is a general representation of a tissue compartment that shows glucose transport through the tissue;

#FIG. 2 is a flowchart describing a meancentering process during tailoring;

#FIG. 3 is a flowchart describing a composite tailoring model (robustification);

Detailed description7,932 words

#In order to understand why different analyte references are appropriate in different circumstances with the present invention, it is necessary to examine the process by which glucose moves through the body, and the kinetics involved. Glucose is essential to all living cells. Sources of glucose include food intake and glycogen breakdown, while sinks include liver, kidney, central nervous system, red blood cells and peripheral tissue. These compartments are linked by blood flow, as illustrated in FIG. 1, which schematically show a tissue section 10. As illustrated, glucose is carried to the various tissues via arterial blood 12, whereupon it passes with the blood into capillaries 14. From there, it diffuses from the capillary blood 14 into the interstitial fluid space 16, and from there into the intracellular space 18. Glucose may be used by the cells through metabolism 22, lost as waste in urine 24 or go to storage 26 such as in proteins. Glucose that has not been used by the cells will diffuse back into the venous blood 20 if the blood glucose concentration is less than the interstitial fluid glucose concentration.

#Because diffusion is generally a slow process, glucose transport into and out of the various compartments is not instantaneous. Consequently, the glucose concentration in finger capillary blood is not necessarily the same as the glucose concentration in other compartments such as venous blood or interstitial fluid. The relationship between the concentrations in these compartments depends on the kinetics of the diffusion process.

#When glucose levels are rising or falling rapidly, (for example, in response to a meal or an insulin dose) the glucose concentration in the arterial and capillary blood will respond almost instantaneously. The same is true for the brain. The brain has an absolute dependence on glucose and is incapable of storing more than a few minutes of glucose as glycogen. It is the major consumer of glucose in the body in the fasting state. The glucose levels in other compartments will not respond to the stimuli as rapidly, however. The interstitial fluid glucose concentration can lag behind the capillary glucose concentration, and the venous blood glucose concentration can lag it even further. The rate of glucose transfer between compartments depends on physiological factors that vary from person to person and can even vary for a single person. For example, if the air is cold, capillaries near the skin surface will constrict and blood will be shunted away from the skin. In this case, the capillary surface area across which glucose transfer takes place will be severely reduced, the rate of glucose transfer will decrease, and the difference between finger capillary blood glucose and the glucose in other fluid compartments in the body will be exacerbated as blood glucose levels continue to change. Consequently, there are many situations in which the finger capillary glucose concentration will not match the interstitial fluid concentration.

Apparatus and method for non-invasive spectroscopic measurement of analytes in tissue using a matched reference analyte

Life of this patent

Apparatus and method for non-invasive spectroscopic measurement of analytes in tissue using a matched reference analyte

Life of this patent

Life of this patent

Abstract

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Claims48

Description11,125 words

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Classification4 codes

Life of this patent

Description11,125 words