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    Tae-woong Koo

    Raman spectroscopy has advantages over infrared absorption spectroscopy. Combined with a novel multivariate technique, hybrid linear analysis (HLA), low prediction error is expected. A near-infrared (NIR) light source excited Raman... more
    Raman spectroscopy has advantages over infrared absorption spectroscopy. Combined with a novel multivariate technique, hybrid linear analysis (HLA), low prediction error is expected. A near-infrared (NIR) light source excited Raman signals, and a charge coupled device (CCD) camera was used to collect the signal. Samples were collected from 69 individuals for 7 weeks. The standard multivariate calibration technique, partial least squares (PLS) and HLA were both used to analyze the collected spectra. A Clarke error grid was used to evaluate the usefulness of the glucose measurement in serum. The root mean squared error of prediction (RMSEP) for glucose in serum obtained with PLS is 21 mg/dL, and the RMSEP obtained with HLA is 17 mg/dL. In whole blood, the PLS RMSEP for glucose was 79 mg/dL, and HLA predictions had an RMSEP of 63 mg/dL. The measurement technique was robust over the 7-week period. HLA was shown to generate a lower prediction error than PLS. The predictions by both PLS and HLA were clinically acceptable. The result with whole blood requires further improvement.
    To obtain a coding system for multiplex detection, we have developed a method to synthesize a new type of nanomaterial called composite organic-inorganic nanoparticles (COINs). The method allows the incorporation of a broad range of... more
    To obtain a coding system for multiplex detection, we have developed a method to synthesize a new type of nanomaterial called composite organic-inorganic nanoparticles (COINs). The method allows the incorporation of a broad range of organic compounds into COINs to produce surface enhanced Raman scattering (SERS)-like spectra that are richer in variety than fluorescence-based signatures. Preliminary data suggest that COINs can be used as Raman tags for multiplex and ultrasensitive detection of biomolecules.
    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... more
    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. This work builds on established concepts from estimation theory, such as the Cramer-Rao lower bound on estimator covariance, to present an analytical formula for estimating uncertainty expressed as a simple function of measurement noise, signal strength, and spectral overlap. This formalism can be used to evaluate and improve instrument performance, particularly important for rapid-acquisition biomedical spectroscopy systems. We demonstrate the experimental utility of this expression in assessing concentration uncertainties from spectral measurements of aqueous solutions and diagnostic parameter uncertainties extracted from spectral measurements of human artery tissue. The measured uncertainty, calculated from many independent measurements, is found to be in good agreement with the analytical formula applied to a single spectrum. These results are intended to encourage the widespread use of uncertainty analysis in the biomedical optics community.
    Achieving high signal amplification in surface-enhanced Raman scattering (SERS) is important for reaching single molecule level sensitivity and has been the focus of intense research efforts. We introduce a novel chemical enhancer,... more
    Achieving high signal amplification in surface-enhanced Raman scattering (SERS) is important for reaching single molecule level sensitivity and has been the focus of intense research efforts. We introduce a novel chemical enhancer, lithium chloride, that provides an additional order of magnitude increase in SERS relative to previously reported enhancement results. We have duplicated single molecule detection of the DNA base adenine that has previously been reported, thereby providing independent validation of this important result. Building upon this work, we show that the chemical enhancer LiCl produces strong SERS signal under a wide range of experimental conditions, including multiple laser excitation wavelengths and target molecule concentrations, for nucleotides, nucleosides, bases, and dye molecules. This is significant because while selection of anions used in chemical enhancement is well known to affect the degree of amplification attained, cation selection has previously been reported to have no major effect on the magnitude of SERS enhancement. Our findings indicate that cation selection is quite important in ultra-sensitive SERS detection, opening the door to further discussion and theory development involving the role of cations in SERS.
    Concentrations of multiple analytes were simultaneously measured in whole blood with clinical accuracy, without sample processing, using near-infrared Raman spectroscopy. Spectra were acquired with an instrument employing nonimaging... more
    Concentrations of multiple analytes were simultaneously measured in whole blood with clinical accuracy, without sample processing, using near-infrared Raman spectroscopy. Spectra were acquired with an instrument employing nonimaging optics, designed using Monte Carlo simulations of the influence of light-scattering-absorbing blood cells on the excitation and emission of Raman light in turbid medium. Raman spectra were collected from whole blood drawn from 31 individuals. Quantitative predictions of glucose, urea, total protein, albumin, triglycerides, hematocrit, and hemoglobin were made by means of partial least-squares (PLS) analysis with clinically relevant precision (r(2) values >0.93). The similarity of the features of the PLS calibration spectra to those of the respective analyte spectra illustrates that the predictions are based on molecular information carried by the Raman light. This demonstrates the feasibility of using Raman spectroscopy for quantitative measurements of biomolecular contents in highly light-scattering and absorbing media.