Terahertz spectroscopy for non-invasive detection and monitoring of analytes through the skin.

Non-invasive continuous glucose monitoring (CGM) has long been considered a holy grail of optical biosensing. Diabetes affects more than 1 in 10 adults worldwide and has no cure, while existing monitoring tools either require fingerpricking, with associated discomfort, infection risk and poor compliance, or rely on minimally invasive CGM devices that still cause pain, skin irritation and offer limited accuracy. This thesis investigates two complementary optical strategies for glucose detection in biological media: terahertz time-domain spectroscopy (THz-TDS) and Band-Pass Raman (BPR) spectroscopy. In the former, contrast arises from glucose-induced, watermediated changes in the broadband dielectric response of the sample; in the latter, from narrow vibrational features of glucose. I demonstrate THz-based detection of glucose in aqueous tissue phantoms at physiologically relevant concentrations using an attenuated total reflection (ATR) geometry for enhanced sensitivity and a measurement protocol explicitly designed to sample experimental variability. The results show that a pure THz-TDS configuration can achieve robust and unbiased glucose quantification in the physiological range, providing a feasibility demonstration for THz-based detection of small solutes in liquids and adding a fundamentally different light-matter interaction mechanism to the CGM landscape. In parallel, I develop and validate a compact and portable BPR spectroscopy system for in vitro glucose detection in optical tissue phantoms with varying lactate content. By implementing wavelength selection in hardware and rejecting redundant spectral information, the system achieves sub-physiological limits of detection under both no lactate and normal lactate conditions, confirming the clinical promise of this approach. Finally, I explore time-dependent THz-ATR responses in ex vivo porcine skin and develop a protocol for functionalization of skin samples, assessing its applicability for ex vivo investigation of THz-based non-invasive glucose detection. Overall, this work contributes to clarify the potential and limitations of THz spectroscopy and push the capabilities of Raman spectroscopy for non-invasive CGM and, more broadly, for optical biosensing in complex aqueous media.