Keywords: non-invasive glucose measurement, photoacoustic spectroscopy, photothermal spectroscopy, interstitial fluid glucoseWe have reported two methods to analyze glucose in the interstitial fluid of skin based on mid-infrared excitation with a tunable quantum cascade laser and photoacoustic or photothermal detection. These methods were evaluated for optimum skin locations to obtain reproducible glucose information. The lower part of the arm, the hypothenar, the tips of the index finger and the thumb were tested. The thumb appears to be the optimal skin location, followed by the index finger. Basic requirements for an optimum site are good capillary blood perfusion, low Stratum corneum thickness and the absence of fat layers. To obtain a correlation on such a site, spectra were recorded on volunteers continuously after blood glucose manipulation. However, continuous measurements on an in vivo sample such as the skin have to cope with physiological alterations such as the formation of sweat. We have used both detection schemes to investigate the acid mantle reformation after washing during time scales similar to continuous measurements for calibration spectra. We found that reconstitution of the acid mantle of skin may be seen in less than one hour. Precleaning of the measurement site may thus be useful for intermittent, but not for long term continuous measurements.

An infrared spectroscopic technique is described that employs a mid-IR broadband (980-1245 cm) tunable quantum cascade laser (QCL) to produce a pump beam, and a detection method based on photothermal deflection, enhanced by total internal reflection. The IR spectra thus obtained are depth-dependent by modulating the pump beam with different frequencies between 10 Hz and 500 Hz. A model system consisting of glucose and a polymer film is used to demonstrate the depth selectivity of this technique. We also apply this photothermal depth profiling method to record in vivo IR spectra of the human epidermis at different depths. This information can be used for a non-invasive glucose monitoring on diabetes patients, which is also demonstrated. Beyond biomedical infrared spectroscopy, there are numerous applications for total internal reflection enhanced photothermal deflection spectroscopy (TIR-PTDS). The high penetration depth of mid-IR light compared to the traditional ATR-FTIR technique and the easy sample access make this technique appropriate for in situ measurements, such as in industrial quality control. The depth selectivity of TIR-PTDS may be a convincing argument for its use in the analysis of multilayered samples or for the analysis of artwork, where the layers of interest are covered by a layer of varnish.

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