There are three main issues in non-invasive (NI) glucose measurements: namely, specificity, compartmentalization of glucose values, and calibration. There has been progress in the use of near-infrared and mid-infrared spectroscopy. Recently new glucose measurement methods have been developed, exploiting the effect of glucose on erythrocyte scattering, new photoacoustic phenomenon, optical coherence tomography, thermo-optical studies on human skin, Raman spectroscopy studies, fluorescence measurements, and use of photonic crystals. In addition to optical methods, in vivo electrical impedance results have been reported. Some of these methods measure intrinsic properties of glucose; others deal with its effect on tissue or blood properties. Recent studies on skin from individuals with diabetes and its response to stimuli, skin thermo-optical response, peripheral blood flow, and red blood cell rheology in diabetes shed new light on physical and physiological changes resulting from the disease that can affect NI glucose measurements. There have been advances in understanding compartmentalization of glucose values by targeting certain regions of human tissue. Calibration of NI measurements and devices is still an open question. More studies are needed to understand the specific glucose signals and signals that are due to the effect of glucose on blood and tissue properties. These studies should be performed under normal physiological conditions and in the presence of other co-morbidities.

Frequent determination of glucose concentrations in diabetic patients is an important tool for diabetes management. This requires repetitive lancing and finger bleeding. Use of noninvasive (NI) detection techniques offers several advantages, such as the absence of pain and exposure to sharp objects and biohazard materials, the potential for increased frequency of testing, and hence, tighter control of the glucose concentrations, and the potential for a closed-loop system including a monitor and an insulin pump. These potential advantages have led to considerable interest in the commercialization of NI glucose monitoring devices. Review of the scientific, patent, and commercial literature indicates that the spectroscopic basis for NI determination of glucose is not yet well established, and attempts at commercialization may be several steps ahead of our understanding the origin and characteristics of an in vivo glucose-specific or glucose-related signal. Several technologies have potential for leading to viable measuring devices, but most of the data are based on in vitro experimentation. Because of the technical complexity of in vivo glucose measurements, this review aims at discussing the gap between the established need and current technology limitations.

Background: Most proposed noninvasive methods for glucose measurements do not consider the physiologic response of the body to changes in glucose concentration. Rather than consider the body as an inert matrix for the purpose of glucose measurement, we exploited the possibility that noninvasive measurements of glucose can be approached by investigating their effects on the skin's thermo-optical response. Methods: Glucose concentrations in humans were correlated with temperature-modulated localized reflectance signals at wavelengths between 590 and 935 nm, which do not correspond to any near-infrared glucose absorption wavelengths. Optical signal was collected while skin temperature was modulated between 22 and 38°C over 2 h to generate a periodic set of cutaneous vasoconstricting and vasodilating events, as well as a periodic change in skin light scattering. The method was tested in a series of modified meal tolerance tests involving carbohydrate-rich meals and no-meal or highprotein/no-carbohydrate meals. Results: The optical data correlated with glucose values. Changes in glucose concentrations resulting from a carbohydrate-rich meal were predicted with a model based on a carbohydrate-meal calibration run. For diabetic individuals, glucose concentrations were predicted with a standard error of prediction <1.5 mmol/L and a prediction correlation coefficient 0.73 in 80% of the cases. There were run-to-run differences in predicted glucose concentrations. Non-carbohydrate meals showed a high degree of scatter when predicted by a carbohydrate meal calibration model. Conclusions: Blood glucose concentrations alter thermally modulated optical signals, presumably through physiologic and physical effects. Temperature changes

The luminescences of isomeric nitroanilines and their N-methylated derivatives, as observed in glassy media at 77°K, are reported. The o- and m-derivatives fluoresce only. The p-derivatives may fluoresce only, phosphoresce only, or show both a fluorescence and a phosphorescence whose relative intensities are dependent on the polarity of the medium and the exciting wavelength. These p-derivatives which possess the largest ground-state dipole moments exhibit the largest phosphorescence yields; they also exhibit a dependence of φp/φf on excitation energies which lie within the wavelength compass of the lowest-energy absorption band, a ``red-edge'' effect, and different fluorescence and phosphorescence excitation spectra. Some suggestions as to the interpretation of these effects are made.

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