The application of a novel open, windowless cell for the photoacoustic infrared spectroscopy of human skin is described. This windowless cavity is tuned for optimum performance in the ultrasound range between 50 and 60 kHz. In combination with an external cavity tunable quantum cascade laser emitting in the range from ∼1000 cm−1 to 1245 cm−1, this approach leads to high signal-to-noise-ratio (SNR) for mid-infrared spectra of human skin. This opens the possibility to measure in situ the absorption spectrum of human epidermis in the mid-infrared region at high SNR in a few (∼5) seconds. Rapid measurement of skin spectra greatly reduces artifacts arising from movements. As compared to closed resonance cells, the windowless cell exhibits the advantage that the influence of air pressure variations, temperature changes, and air humidity buildup that are caused by the contact of the cell to the skin surface can be minimized. We demonstrate here that this approach can be used for continuous and non-invasive monitoring of the glucose level in human epidermis, and thus may form the basis for a non-invasive monitoring of the glucose level for diabetes patients.

An infrared spectroscopic technique is described that employs a mid-IR broadband (980–1245 cm⁻¹) 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.

Background: A prototype of a noninvasive glucometer combining skin excitation by a mid-infrared quantum cascade laser with photothermal detection was evaluated in glucose correlation tests including 100 volunteers (41 people with diabetes and 59 healthy people). Methods: Invasive reference measurements using a clinical glucometer and noninvasive measurements at a finger of the volunteer were simultaneously recorded in five-minute intervals starting from fasting glucose values for healthy subjects (low glucose values for diabetes patients) over a two-hour period. A glucose range from >50 to <350 mg/dL was covered. Machine learning algorithms were used to predict glucose values from the photothermal spectra. Data were analyzed for the average percent disagreement of the noninvasive measurements with the clinical reference measurement and visualized in consensus error grids. Results: 98.8% (full data set) and 99.1% (improved algorithm) of glucose results were within Zones A and B of the grid, indicating the highest accuracy level. Less than 1% of the data were in Zone C, and none in Zone D or E. The mean and median percent differences between the invasive as a reference and the noninvasive method were 12.1% and 6.5%, respectively, for the full data set, and 11.3% and 6.4% with the improved algorithm. Conclusions: Our results demonstrate that noninvasive blood glucose analysis combining mid-infrared spectroscopy and photothermal detection is feasible and comparable in accuracy with minimally invasive glucometers and finger pricking devices which use test strips. As a next step, a handheld version of the present device for diabetes patients is being developed.