Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.

We present instrumentation for probing of volar side fingertip capillary beds with free space coupled near infrared light while collecting Raman, Rayleigh, and Mie scattered light as well as fluorescence. Fingertip skin capillary beds are highly vascularized relative to other tissues and present a desirable target for noninvasive probing of blood. But human hands and fingers in particular are also highly idiosyncratic body parts requiring specific apparatus to allow careful and methodical spectroscopic probing. The apparatus includes means for precise and reproducible placement of the tissues relative to the optical aperture. Appropriate means are provided for applying and maintaining pressure to keep surface tissues immobile during experiments while obtaining the desired blood content and flow. Soft matter, e.g., skin, extrudes into the aperture in response to any applied pressure, e.g., to keep the tissue in registration with the optical system, so the position, contact area, pressure, and force are continuously measured and recorded to produce feedback for an actuator applying force and to discern the compliance of the test subject. The compliance strongly affects the reliability of the measurement and human factors must be adequately managed in the case of in vivo probing. The apparatus produces reproducible observations and measurements that allow consistent probing of the tissues of a wide range of skin types.

Abstract.We report simultaneous observation of elastic scattering, fluorescence, and inelastic scattering from in vivo near-infrared probing of human skin. Careful control of the mechanical force needed to obtain reliable registration of in vivo tissue with an appropriate optical system allows reproducible observation of blood flow in capillary beds of human volar side fingertips. The time dependence of the elastically scattered light is highly correlated with that of the combined fluorescence and Raman scattered light. We interpret this in terms of turbidity ͑the impeding effect of red blood cells on optical propagation to and from the scattering centers͒ and the changes in the volume percentages of the tissues in the irradiated volume with normal homeostatic processes. By fitting to a model, these measurements may be used to determine volume fractions of plasma and RBCs.

Silver has high reflectivity in the visible and infrared but cannot be used fully because of its distressing lack of durability. A technique that uses the surface plasmon resonance phenomenon offers a sensitive method for studying the corrosion of silver and assessing improvements. It has been used in the investigation of the effects of flashing a thin layer, approximately 1 nm thick, of copper over silver in an attempt at cathodic protection. Tests include exposing silver and silver-copper films to air, 94% relative humidity, water, and hydrogen sulfide.