Abstract: Example embodiments of the present invention provide methods and apparatuses that enable the detection of bubbles so that hemodynamic performance can be assured following an automated blood analyte measurement. An example apparatus according to the present invention comprises a blood access system, adapted to remove blood from a body and infuse at least a portion of the blood back into the body. The infusion of at least a portion of the blood back in to the body can be done in a manner to assure that no bubbles of clinical significance are injected into the patient. Additionally an example embodiment can assess for the presence of bubbles in the fluid column that can affect hemodynamic monitoring performance. If a condition exists where hemodynamic monitoring performance cannot be assured, an example embodiment can provide appropriate warning or corrective actions.

Abstract: The present invention provides an optical transmission device, comprising a chamber having a light input into the chamber, and having a first port allowing light to pass out of the chamber, and comprising internal surfaces where at least a portion of the surfaces is diffusely reflecting, and where at least a portion of the one or more surfaces is specularly reflecting, and where the light input and the first port and the one or more surfaces are configured such that substantially all light entering the chamber via the light source within a first predetermined aperture must encounter the diffusely reflecting portion before exiting the chamber via the first port within a second predetermined aperture. The invention can provide substantially homogenous light transmission, both as a source of light for optical systems and as a collector of light from a sample.

Abstract: The present invention relates generally to a non-invasive method and apparatus for measuring a fluid analyte, particularly relating to glucose or alcohol contained in blood or tissue, utilizing spectroscopic methods. More particularly, the method and apparatus incorporate means for detecting and quantifying changes in the concentration of specific analytes in tissue fluid. Also, the method and apparatus can be used to predict future levels of analyte concentration either in the tissue fluid or in blood in an adjacent vascular system.

Abstract: An improved method and apparatus for diffuse reflectance spectroscopy. A specular control device is provided that can discriminate between diffusely reflected light that is reflected from selected depths or layers within the tissue. The specular control device permits a spectroscopic analyzer to receive the diffusely reflected light that is reflected from, for example, a first layer or depth within the tissue, while preventing the remaining diffusely reflected light from reaching the spectroscopic analyzer. Furthermore, the specular control device may prevent the specularly reflected light (e.g. surface reflected light) from reaching the spectroscopic analyzer.

Abstract: The present invention provides methods for generating interferometric information. Interferometric information from refractively scanned interferometers can contain errors due to wavelength-dependent refractive indices. The wavelength-dependent refractive indices of elements of the interferometer can produce errors when the OPD at a reference wavelength is different than the OPD at a sample wavelength. The invention can provide correction of interferometric information using relationships between the OPD at the wavelengths of interest, which correction can also be dependent on physical relationships among elements of the interferometer.

Abstract: Systems and methods for establishing and/or maintaining the accuracy of a multivariate calibration model designed for quantitative optical spectroscopic measurement of attributes or analytes in bodily tissues, bodily fluids or other biological samples, which are particularly useful when the spectral absorbance of the attribute or analyte is small relative to the background. The present invention provides an optically similar reference sample to reduce the effect of instrument or environment variation on the measurement capability of the model. The optically similar reference can be a gel composition having scattering particles suspended therein. The reference gel can be directly applied to a spectroscopic instrument sampler, or can be in a container specifically designed for optimal coupling to a spectroscopic instrument.

Abstract: An interferometer spectrometer that has reduced alignment sensitivity is described herein. Parallelism of an output ray pair formed by a single input ray is not affected by variations in relative alignment of the components. In comparison to other compensated interferometer designs, lateral separation errors in the output ray pair due to optical component misalignment are reduced. The reduced alignment sensitivity may be accomplished by utilizing simple planar components that are common to both light paths. The reduced alignment sensitivity and simplicity in design provides a more compact and more robust interferometer, with reduced manufacturing costs associated therewith. An elliptical field of view light source that utilizes an array of collimator lenses is also described. The light source provides a more compact design than a single circular collimator lens of the same area, and is suitable for single channel or multi-channel use.

Abstract: A method and apparatus for measuring a biological attribute, such as the concentration of an analyte, particularly a blood analyte in tissue such as glucose. The method utilizes spectrographic techniques in conjunction with an improved instrument-tailored or subject-tailored calibration model. In a calibration phase, calibration model data is modified to reduce or eliminate instrument-specific attributes, resulting in a calibration data set modeling intra-instrument or intra-subject variation. In a prediction phase, the prediction process is tailored for each target instrument separately using a minimal number of spectral measurements from each instrument or subject.

Abstract: Methods of reducing the effects of measurement device artifacts on a measurement of a sample are presented. A number of reference measurements performed with the measurement device are observed to identify reference independent components of the reference measurements. The variations of the reference independent components are used as surrogates for possible artifacts of the measurement device. A number of measurements of subjects similar to the sample are observed, and similarity components of the subject measurements that vary in a manner similar to the reference independent components may be identified. The sample measurement is then adjusted to remove at least part of the similarity components that correspond to the variations in the reference independent components. The adjustment of the sample measurement is thereby improved by reducing the effects of artifacts of the measurement device.

Abstract: A linear positioning apparatus includes an intermediate portion having an axis, and first and second end portions mounted with flexure legs thereto. The flexure legs accommodate motion of the intermediate portion relative to the end portions along the axis, but inhibit motion of the intermediate portion relative to the end portions in directions not parallel to the axis. The apparatus can accommodate forces having off-axis components, and produce motion that comprises substantially no off-axis component. The apparatus is useful in, for example, optical systems where precise linear motion is required.

Abstract: Apparatus and methods for spectroscopic analysis of human tissue to classify an individual as diabetic or non-diabetic, or to determine the probability, progression or level of diabetes in an individual. Tissue optical information of an individual, including at least a measurement of at least one wavelength or group of wavelengths indicative of glycosylated collagen content in tissue, is analyzed using multivariate techniques. The multivariate techniques include an algorithm developed from optical information from individuals having a known disease state. At least one factor in the algorithm is dependent on or a function of the measurement of the at least one wavelength or group of wavelengths indicative of glycosylated collagen content in tissue from the optical information of individuals forming the database.

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.

Abstract: The present invention relates generally to a non-invasive method and apparatus for measuring a fluid analyte, particularly relating to glucose or alcohol contained in blood or tissue, utilizing spectroscopic methods. More particularly, the method and apparatus incorporate means for detecting and quantifying changes in the concentration of specific analytes in tissue fluid. Also, the method and apparatus can be used to predict future levels of analyte concentration either in the tissue fluid or in blood in an adjacent vascular system.

Abstract: The present invention provides an improved interferometer design. Embodiments of the present invention provide a beam splitter, mounted with first and second reflective elements. An OPD element mounts relative to the other elements such that an optical path in the interferometer passes through the OPD element. The OPD element can be, for example, a plate comprising a refractive material mounted such that the thickness of the refractive material encountered by the optical path through the OPD element is variable. Various arrangements of components are described, and methods of constructing and methods of aligning such interferometers are also described.

Abstract: The present invention provides means for correcting interferometer alignment errors through the use of corrective elements. The corrective elements allow reduced accuracy in the assembly process. Residual alignment errors caused by imprecise mounting of permanently mounted components can be corrected using relatively low precision positioning of corrector components. The technique can be particularly applicable to the mass production of interferometers, for which achieving and maintaining the required assembly tolerances might otherwise be prohibitively expensive. Interferometers according to the present invention can be used, for example, in optical spectroscopy and in interferometers.

Abstract: Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

Abstract: An apparatus and method for non-invasive measurement of glucose in human tissue by quantitative infrared spectroscopy to clinically relevant levels of precision and accuracy. The system includes six subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The six subsystems include an illumination subsystem, a tissue sampling subsystem, a calibration maintenance subsystem, an FTIR spectrometer subsystem, a data acquisition subsystem, and a computing subsystem.

Abstract: An illumination subsystem for use in optical analysis which provides spatially and angularly homogenized radiation to the sample being analyzed. The system eliminates the illumination system as an interferent in the overall optical analysis. Thus, modest translations or rotations of the illumination source or changing the illumination source does not require recalibration of the instrument or prior modeling of illumination variability due to such changes. Illumination stability is achieved by incorporating a light pipe which both angularly and spatially homogenizes the light. Further, a series of filters and/or lenses are incorporated to provide bandpass filtering which eliminates unwanted wavelengths or bands of wavelengths from contacting the tissue and allows for a higher signal-to-noise ratio when the sample is tissue, while preventing thermal damage.

Abstract: An optical sampling subsystem and method that reduces the effect of errors in an optical sampling subsystem when heterogeneously distributed samples are measured in the path of a spectrometer. The optical sampling subsystem is used to collect the non-uniformly distributed radiation exiting the heterogeneous sample and produce a uniform irradiance at its output. The output is then directed into the wavenumber (inverse of wavelength in centimeters) dispersive or modulating device of the spectrometer. The resulting spectra exhibit less spectral complexity arising from components of the sampling subsystem design and the heterogeneous sample, in particular, the effect of wavenumber shift is minimized. Improved quantitative predictions, qualitative analysis and calibration transfer are direct consequences of the reduced spectral complexity.

Abstract: A vertical cavity surface-emitting laser (VCSEL) package utilized as a laser reference for use in interferometry. The primary disadvantage of VCSELs, in terms of interferometry, has been found to be the relatively poor wavenumber stability of the beam. The present invention is a method and apparatus that makes viable a VCSEL package suitable for use as a reference in interferometry. The VCSEL package incorporates current control, temperature control and an algorithm for correcting wavenumber drift. The algorithm is derived from spectroscopic analysis of a reference sample having a known spectrum and comparing the generated spectrum to the known spectrum.