One or more basis sets are applied to a spectroscopic signal during analysis to produce an accurate spectral representation from which analyte concentration may be accurately determined. A basis set includes all interfering components found in a sample, such as serum. With regard to an analyte, such as glucose, it is necessary to define those components of a sample that have a larger interference than that of glucose. A basis set may be generated, for example, that produces a transform for the red blood cells that interfere or scatter the light; and also for skin effects. Once the spectra of all these components is known, it is then necessary to determine how each of these components interact, e.g. taking serum data, extracting each of the components, and then comparing the spectra for the individual components with that of the components in solution. The invention characterizes each component in a sample, as well as all other possible interferants and, after producing an accurate representation of each component at each frequency of interest, identifies and subtracts each interferant from the spectra produced at the frequency of interest. The basis sets may take the form of transforms that may be stored in a look-up table for use during analysis.

A device for the in vivo measurement of the concentration of an analyte in an aqueous solution comprises a transmitter for illuminating a body part with light at a plurality of predetermined wavelengths. A detector receives light from such body part and generates input signals representative of the intensity of received light at each of the predetermined wavelengths, and a computer coupled to the detector generates an output signal representative of the analyte concentration in the body part by analysis of the input signals received from the detector. The detector is adapted to generate input signals representative of the intensity of light received at three discrete wavelengths, and a formula is provided for calculating the output signal on the basis thereof.

A method for determining the concentration of an analyte in tissues. The method involves compensating for a change in the value of an optical property of the tissues, such as, for example, the scattering coefficient, resulting from a change in the hydration status of the tissues. 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 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.

Methods and apparatus for noninvasive determination of blood analytes, such as glucose, through NIR spectroscopy utilize optical properties of tissue as reflected in key spectroscopic features to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured absorbance spectrum of skin and reflect a modification in the effective pathlength of light, leading to a biased noninvasive glucose measurement. Changes in the optical properties of tissue are detected by identifying key features responsive to physiological variations. Conditions not conducive to noninvasive measurement of glucose are detected. Noninvasive glucose measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, glucose is measured indirectly based on natural physiological response of tissue to glucose concentration. A spectroscopic device capable of such measurements is provided.

The absence of a defined optical pathlength for in vivo measurements creates problems for the noninvasive measurement of analyte concentration. These problems can be reduced by combining measurements made at several wavelengths and using the fact that normal renal function causes the concentration of water in whole blood to be tightly controlled. Hence, the concentration of water in arterial blood can serve as a useful internal standard for such measurements. The measurements are then procured so as to remove the dependency of concentration on path length traversed by the illuminating radiation and on the scattering properties of the volume through which the illuminating radiation propagates. Using this method, one can create improved calibration for measurements of absorbing constituents in arterial blood and thereby provide absolute concentration measurements of constituents such as hemoglobin and glucose in arterial blood.