Abstract: A method and apparatus for calibrating noninvasive or implantable glucose analyzers uses either alternative invasive glucose determinations or noninvasive glucose determinations for calibrating noninvasive or implantable glucose analyzers. Use of an alternative invasive or noninvasive glucose determination in the calibration allows minimization of errors due to sampling methodology, and spatial and temporal variations that are built into the calibration model. An additional embodiment uses statistical correlations between noninvasive and alternative invasive glucose determinations and traditional invasive glucose determinations to adjust noninvasive or alternative invasive glucose concentrations to traditional invasive glucose concentrations. The invention provides a means for calibrating on the basis of glucose determinations that reflect the matrix observed and the variable measured by the analyzer more closely.

Abstract: Sampling is controlled to enhance analyte concentration estimation derived from noninvasive sampling. Means of assuring that the same tissue sample volume is repeatably sampled are presented, thus minimizing sampling errors due to mechanical tissue distortion, specular reflectance, and probe placement. In a first embodiment of the invention, sampling is controlled using automated delivery of a coupling fluid to a region between a tip of a sample probe and a tissue measurement site in a manner requiring minimal user interaction. In a second embodiment of the invention, sampling is controlled by controlling temperature variations, preferably with a coupling fluid, at a region about the tip of a sample probe and a sample site. In a third embodiment, sampling is procedurally controlled via timing and location of coupling fluid delivery to a sample site.

Abstract: A near-infrared spectrometer-based analyzer attaches continuously or semi-continuously to a human subject and is used to collect spectral measurements of a tissue sample. The spectral readings are used to estimate a biological parameter in the sampled tissue noninvasively, such as glucose concentration. The preferred apparatus is a near-infrared analyzer that includes a base module and a sample module connected together with a communication bundle. The base module contains the bulk of the analyzer, such as a spectrograph and a central processing unit with an algorithm used for converting the optical signal into a glucose concentration. The sample module is typically in a smaller module that interfaces to a tissue sample. The sample module is preferably handheld and provides minimal sampling distortion due to heat or pressure.

Abstract: A method and apparatus using photo-stimulation to treat or pretreat a sample site prior to analyte concentration determination is presented. More particularly, photo-stimulation at or near at least one sample site is used to enhance perfusion of the sample site leading to reduced errors associated with sampling. Increased perfusion of the sample site leads to increased volume percentages of the target analyte and/or allows the blood or tissue constituent concentrations to more accurately and/or precisely track corresponding sample constituents in more well perfused body compartments or sites such as arteries, veins, or fingertips. In one embodiment, analysis of the photo-stimulated site is used in conjunction with glucose analyzers to determine the analyte concentration with greater ease, accuracy, or precision and may allow determination of the analyte concentration of another non-sampled body part or compartment.

Abstract: Spectrometer instruments are characterized by classifying their spectra into previously defined clusters. The spectra are mapped to the clusters and a classification is made based on similarity of extracted spectral features to one of the previously defined clusters. Calibration models for each cluster are provided to compensate for instrumental variation. Calibration models are provided either by transferring a master calibration to slave calibrations or by calculating a separate calibration for each cluster. A simplified method of calibration transfer maps clusters to each other, so that a calibration transferred between clusters models only the difference between the two clusters, substantially reducing the complexity of the model.

Abstract: An optical sampling interface system minimizes and compensates error resulting from sampling variations and measurement site state fluctuations. Components include: An optical probe placement guide having an aperture wherein the optical probe is received, facilitates repeatable placement accuracy on surface of a tissue measurement site with minimal, repeatable disturbance to surface tissue. The aperture creates a tissue meniscus that minimizes interference due to surface irregularities and controls variation in tissue volume sampled; an occlusive element placed over the tissue meniscus isolates the meniscus from environmental fluctuations, stabilizing hydration at the site and thus, surface tension; an optical coupling medium eliminates air gaps between skin surface and optical probe; a bias correction element applies a bias correction to spectral measurements, and associated analyte measurements. When the guide is replaced, a new bias correction is determined for measurements done with the new placement.

Abstract: A near IR spectrometer-based analyzer attaches continuously or semi-continuously to a human subject and collects spectral measurements for determining a biological parameter in the sampled tissue, such as glucose concentration. The analyzer includes an optical system optimized to target the cutaneous layer of the sampled tissue so that interference from the adipose layer is minimized. The optical system includes at least one optical probe. Spacing between optical paths and detection fibers of each probe and between probes is optimized to minimize sampling of the adipose subcutaneous layer and to maximize collection of light backscattered from the cutaneous layer. Penetration depth is optimized by limiting range of distances between paths and detection fibers. Minimizing sampling of the adipose layer greatly reduces interference contributed by the fat band in the sample spectrum, increasing signal-to-noise ratio.

Abstract: The invention involves the monitoring of a biological parameter through a compact analyzer. The preferred apparatus is a spectrometer based system that is attached continuously or semi-continuously to a human subject and collects spectral measurements that are used to determine a biological parameter in the sampled tissue. The preferred target analyze is glucose. The preferred analyzer is a near-IR based glucose analyzer for determining the glucose concentration in the body.

Abstract: Spectrometer instruments are characterized by classifying their spectra into previously defined clusters. The spectra are mapped to the clusters and a classification is made based on similarity of extracted spectral features to one of the previously defined clusters. Calibration models for each cluster are provided to compensate for instrumental variation. Calibration models are provided either by transferring a master calibration to slave calibrations or by calculating a separate calibration for each cluster. In one embodiment, a simplified method of calibration transfer maps clusters to each other, so that a calibration transferred between clusters models only the difference between the two clusters, substantially reducing the complexity of the model.

Abstract: The invention provides a design process that is used in the determination of the pattern of detector and illumination optical fibers at the sampling area of a subject. Information about the system, specifically a monochromator (e.g. to determine the optimal number of fibers at an output slit) and the bundle termination at a detector optics stack (e.g. to determine the optimal number of fibers at the bundle termination), is of critical importance to this design. It is those numbers that determine the ratio and number of illumination to detection fibers, significantly limiting and constraining the solution space. Additional information about the estimated signal and noise in the skin is necessary to maximize the signal-to-noise ratio in the wavelength range of interest. Constraining the fibers to a hexagonal perimeter and prescribing a hex-packed pattern, such that alternating columns contain illumination and detection fibers, yields optimal results.