Quantitative biological Raman spectroscopy for non-invasive blood analysis

Abstract

The long term goal of this project is the measurement of clinically-relevant analytes in the blood tissue matrix of human subjects using near-infrared Raman spectroscopy, with the shorter term research directed towards glucose measurements for diabetic patients. This optical technique enables non-contact, painless measurements with no sample preparation and simultaneous determination of multiple analytes. Such a technology could greatly impact the healthcare practices for the entire population. This thesis presents advances in quantitative biological Raman spectroscopy along three avenues: instrument optimization, analyte-specific information extraction, and correction for sampling volume variations. In the first category, we have built a high-throughput instrument that integrates Raman and diffuse reflectance capabilities. Additionally, new algorithms have been developed to enhance wavelength precision and stability. Using this instrument, we have presented evidence of glucose-specific measurements in human and dog subjects. We believe that this is the first time glucose-specific information is extracted transcutaneously in vivo using Raman spectroscopy.

(cont.) Toward our ultimate goal of prospective prediction, we have developed two novel techniques: constrained regularization (CR) for improved information extraction and intrinsic Raman spectroscopy (IRS) to correct for sampling volume variations. CR utilizes additional prior information in the form of the target analyte spectrum during multivariate calibration, and thus generates more analyte-specific models compared to the most widely used method, partial least squares. IRS employs the newly-discovered relationship between measured Raman scattering and diffuse reflectance in turbid media. This relationship was revealed via photon migration-based analytical models and Monte Carlo simulations, and subsequently confirmed by in vitro experiments. Our recent advances and promising results from the in vivo studies demonstrate that Raman spectroscopy is a viable technique for non-invasive blood analysis.