Utilizing pulse dynamics for non-invasive Raman spectroscopy of blood analytes

Non-invasive measurement methods offer great benefits in the field of medical diagnostics with molecular-specific techniques such as Raman spectroscopy which is increasingly being used for quantitative measurements of tissue biochemistry in vivo. However, some important challenges still remain for label-free optical spectroscopy to be incorporated into the clinical laboratory for routine testing. In particular, non-analyte-specific variations in tissue properties introduce significant variability of the spectra, thereby preventing reliable calibration. For measurements of blood analytes such as glucose, we propose to decrease the interference from individual tissue characteristics by exploiting the known dynamics of the blood-tissue matrix. We reason that by leveraging the natural blood pulse rhythm, the signals from the blood analytes can be enhanced while those from the static components can be effectively suppressed. Here, time-resolved measurements with subsequent pulse frequency estimation and phase-sensitive detection are proposed to recover the Raman spectra correlated with the dynamic changes at blood-pulse frequency. Pilot in vivo study results are presented to establish the benefits as well as outline the challenges of the proposed method in terms of instrumentation and signal processing.