Noninvasive glucose sensing by transcutaneous Raman spectroscopy.

We present the development of a transcutaneous Raman spectroscopy system and analysis algorithm for noninvasive glucose sensing. The instrument and algorithm were tested in a preclinical study in which a dog model was used. To achieve a robust glucose test system, the blood levels were clamped for periods of up to 45 min.

Predicting skin flap viability using a new intraoperative tissue oximetry sensor: a feasibility study in pigs.

Background:  Operations for soft-tissue reconstruction, orthopedic, vascular, and other types of surgery can be complicated by unexpected skin flap necrosis. At present, surgeons utilize subjective clinical judgment and physical findings to estimate the potential for tissue compromise. As the validity of these subjective methods is questionable, there is a need for objective, quantitative tools to determine the risk of flap necrosis during surgery.

Intrinsic Raman spectroscopy for quantitative biological spectroscopy part II: experimental applications.

We demonstrate the effectiveness of intrinsic Raman spectroscopy (IRS) at reducing errors caused by absorption and scattering. Physical tissue models, solutions of varying absorption and scattering coefficients with known concentrations of Raman scatterers, are studied. We show significant improvement in prediction error by implementing IRS to predict concentrations of Raman scatterers using both ordinary least squares regression (OLS) and partial least squares regression (PLS).

Intrinsic Raman spectroscopy for quantitative biological spectroscopy part I: theory and simulations.

We present a novel technique, intrinsic Raman spectroscopy (IRS), to correct turbidity-induced Raman spectral distortions, resulting in the intrinsic Raman spectrum that would be observed in the absence of scattering and absorption. We develop an expression relating the observed and intrinsic Raman spectra through diffuse reflectance using the photon migration depiction of light transport. Numerical simulations are employed to validate the theoretical results and study the dependence of this expression on sample size and elastic scattering anisotropy.

Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy.

Using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy, we have developed an algorithm that successfully classifies normal breast tissue, fibrocystic change, fibroadenoma, and infiltrating ductal carcinoma in terms of physically meaningful parameters. We acquire 202 spectra from 104 sites in freshly excised breast biopsies from 17 patients within 30 min of surgical excision. The broadband diffuse reflectance and fluorescence spectra are collected via a portable clinical spectrometer and specially designed optical fiber probe.

Determination of uncertainty in parameters extracted from single spectroscopic measurements.

The ability to quantify uncertainty in information extracted from spectroscopic measurements is important in numerous fields. The traditional approach of repetitive measurements may be impractical or impossible in some measurements scenarios, while chi-squared analysis does not provide insight into the sources of uncertainty. As such, a need exists for analytical expressions for estimating uncertainty and, by extension, minimum detectable concentrations or diagnostic parameters, that can be applied to a single noisy measurement.

Constrained regularization: hybrid method for multivariate calibration.

We present a hybrid multivariate calibration method, constrained regularization (CR), and demonstrate its utility via numerical simulations and experimental Raman spectra. In this new method, multivariate calibration is treated as an inverse problem in which an optimal balance between model complexity and noise rejection is achieved with the inclusion of prior information in the form of a spectral constraint. A key feature is that the constraint is incorporated in a flexible manner, allowing the minimization algorithm to arrive at the optimal solution.

Moving beyond traditional UV-visible absorption detection: cavity ring-down spectroscopy for HPLC.

We describe the use of liquid-phase continuous-wave cavity ring-down spectroscopy for the detection of an HPLC separation. This technique builds on earlier work by Snyder and Zare using pulsed laser sources and improves upon commercially available UV-visible detectors by a factor of up to 50. The system employs a compact doubled-diode single-mode continuous-wave laser operating at 488 nm and a previously described Brewster's-angle flow cell.