Abstract
Summary form only given. Broadband mid-infrared spectroscopy of biofluids carries great potential for biological and biomedical applications, as it provides fast, reliable and label-free access to the molecular composition of the sample [1]. When applied to human blood serum, a range of molecular contents can be quantified [2] and specific changes in the absorption spectra, driven by diseases (e.g. cancer) can be identified and used for diagnostic purposes [3]. One remaining challenge is the complexity of human serum: physiological phenotypes are driven by minor changes in concentration of thousands of different molecules. At the same time, although many low-abundance molecules are very informative for disease detection, these are often not detectable with conventional Fourier-Transform Infrared (FTIR) spectroscopy and quantum-cascade laser (QCL) based approaches due to a lack of sensitivity and specificity. Here we show how field-resolved spectroscopy (FRS) [4] of few-cycle-excited molecular vibrations can be utilised to address these shortcomings and demonstrate its applicability for the measurement of human blood serum in a clinical setting. In a preparatory experiment, we quantitatively investigate the ability of FRS to detect small changes in the sample response by spiking blood serum with a defmed concentration of dimethyl sulfone (DMS02). We demonstrate that FRS is able to detect changes in molecular concentration down to the sub-μg/m1 level in human blood serum, outperforming the sensitivity of FTIR- and QCL-based approaches. Hence, the smallest changes currently detectable by FRS are fi ve orders of magnitude below the concentration of the most highly abundant molecules in blood, implying a detectable concentration dynamic range of 10 5 .