A novel non-imaging optics based Raman spectroscopy device for transdermal blood analyte measurement.

Due to its high chemical specificity, Raman spectroscopy has been considered to be a promising technique for non-invasive disease diagnosis. However, during Raman excitation, less than one out of a million photons undergo spontaneous Raman scattering and such weakness in Raman scattered light often require highly efficient collection of Raman scattered light for the analysis of biological tissues. We present a novel non-imaging optics based portable Raman spectroscopy instrument designed for enhanced light collection.

Combined confocal Raman and quantitative phase microscopy system for biomedical diagnosis.

We have developed a novel multimodal microscopy system that incorporates confocal Raman, confocal reflectance, and quantitative phase microscopy (QPM) into a single imaging entity. Confocal Raman microscopy provides detailed chemical information from the sample, while confocal reflectance and quantitative phase microscopy show detailed morphology. Combining these intrinsic contrast imaging modalities makes it possible to obtain quantitative morphological and chemical information without exogenous staining.

Wavelength selection-based nonlinear calibration for transcutaneous blood glucose sensing using Raman spectroscopy.

While Raman spectroscopy provides a powerful tool for noninvasive and real time diagnostics of biological samples, its translation to the clinical setting has been impeded by the lack of robustness of spectroscopic calibration models and the size and cumbersome nature of conventional laboratory Raman systems. Linear multivariate calibration models employing full spectrum analysis are often misled by spurious correlations, such as system drift and covariations among constituents. In addition, such calibration schemes are prone to overfitting, especially in the presence of external interferences that may create nonlinearities in the spectra-concentration relationship.

Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque.

Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery.

Effect of photobleaching on calibration model development in biological Raman spectroscopy.

A major challenge in performing quantitative biological studies using Raman spectroscopy lies in overcoming the influence of the dominant sample fluorescence background. Moreover, the prediction accuracy of a calibration model can be severely compromised by the quenching of the endogenous fluorophores due to the introduction of spurious correlations between analyte concentrations and fluorescence levels. Apparently, functional models can be obtained from such correlated samples, which cannot be used successfully for prospective prediction.

Development of robust calibration models using support vector machines for spectroscopic monitoring of blood glucose.

Sample-to-sample variability has proven to be a major challenge in achieving calibration transfer in quantitative biological Raman spectroscopy. Multiple morphological and optical parameters, such as tissue absorption and scattering, physiological glucose dynamics and skin heterogeneity, vary significantly in a human population introducing nonanalyte specific features into the calibration model. In this paper, we show that fluctuations of such parameters in human subjects introduce curved (nonlinear) effects in the relationship between the concentrations of the analyte of interest and the mixture Raman spectra.

Accurate spectroscopic calibration for noninvasive glucose monitoring by modeling the physiological glucose dynamics.

The physiological lag between blood and interstitial fluid (ISF) glucose is a major challenge for noninvasive glucose concentration measurements. This is a particular problem for spectroscopic techniques, which predominantly probe ISF glucose, creating inconsistencies in calibration, where blood glucose measurements are used as a reference. To overcome this problem, we present a dynamic concentration correction (DCC) scheme, based on the mass transfer of glucose between blood and ISF, to ensure consistency with the spectral measurements.

A multimodal spectroscopy system for real-time disease diagnosis.

The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting.

Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes.

Although the prevailing view of mechanoelectric feedback (MEF) in the heart is in terms of longitudinal cell stretch, other mechanical forces are considerable during the cardiac cycle, including intramyocardial pressure and shear stress. Their contribution to MEF is largely unknown. In this study, mechanical stimuli in the form of localized fluid jet pulses were applied to neonatal rat ventricular cells cultured as confluent monolayers.

Functional reentry in cultured monolayers of neonatal rat cardiac cells.

Previous studies of reentrant arrhythmias in the heart have been performed in computer models and tissue experiments. We hypothesized that confluent monolayers of cardiac cells can provide a simple, controlled, and reproducible experimental model of reentry. Neonatal rat ventricular cells were cultured on 22-mm-diameter coverslips and stained with the voltage-sensitive dye RH-237.