Yoen-Joo Kim

Determination of glucose in whole blood samples by mid-infrared spectroscopy

We have determined the glucose concentration of whole blood from mid-infrared spectra without sample preparation or use of chemical reagents. We selected 1119-1022 cm(-1) as the optimal wavelength range for our measurement by making a first-loading vector analysis based on partial least-squares regression. We examined the influence of hemoglobin on samples by using different calibration and prediction sets. The accuracy of glucose prediction depended on the hemoglobin level in the calibration model; the sample set should represent the entire range of hemoglobin concentration. We obtained an accuracy of 5.9% in glucose prediction, and this value is well within a clinically acceptable range.

Determination of glucose concentration in a scattering medium based on selected wavelengths by use of an overtone absorption band.

A method and device for measuring glucose concentration in a scattering medium have been developed. A spectral range of 800-1800 nm is considered for wavelength selection because of its deeper penetration into biological tissue and the presence of a glucose absorption band. An algorithm based on selected wavelengths is proposed to minimize interference from other components. The optimal distance between the light source and the detector for diffuse reflectance measurement minimizes the influence of medium scattering. The proposed algorithm and measuring device are tested with a solution containing milk with added glucose. Glucose concentrations between 0 and 2000 mg/dl are determined with a correlation coefficient of 0.977. We also investigate the influence of concentration variations of other substances such as water, hemoglobin, albumin, and cholesterol when they are mixed in a scattering medium.

Multicomponent assay for human serum using mid-infrared transmission spectroscopy based on component-optimized spectral region selected by a first loading vector analysis in partial least-squares regression

Mid-infrared transmission spectroscopy with partial least-squares regression was used to determine the concentrations of blood components such as total protein, albumin, globulin, total cholesterol, HDL (high density lipoprotein) cholesterol, triglycerides, glucose, BUN (blood urea nitrogen), and uric acid in human serum. The optimal spectral region for each component was selected by first loading vector analysis. Positive peaks with positive value were assigned by first loading vector analysis. Because blood components in serum show a correlation among several components, a useful spectral region for predicting a particular component was selected such that its spectral feature was not overlapped by those of other components. Several regions with positive peaks by first loading vector were used to establish calibration models. The proposed method proved to be effective for a multicomponent assay and can also be used even when a single component spectrum in aqueous solution for all components is not known. Total protein, albumin, globulin, total cholesterol, triglycerides, and glucose have a mean percentage error of cross-validation (MPECV) of less than 5%. But HDL cholesterol, BUN, and uric acid have MPECVs between 12 and 18%. In terms of both the percentage error of cross-validation and clinically allowable error, six serum components, excepting HDL-cholesterol, BUN, and uric acid, were determined successfully.

Optical measurement of glucose levels in scattering media

A method for non-invasive determination of blood glucose on the basis of selective spectral analysis of reflected from or transmitted through biological tissues containing blood is demonstrated. Our proposed algorithm is based on a discrete number of wavelengths. The wavelengths are selected such that the measurements of glucose levels can be most sensitive and such that the influences of other substances such as water, hemoglobin, skin, etc. may be minimized. A compact instrument is developed for measurement. Verifications of the algorithm are successfully accomplished using scattering solutions whose glucose concentrations varied up to 1000 mg/dl.

Method and device for noninvasive blood glucose measurement

The method and device for non-invasive measurement of blood glucose concentration based on the diffuse reflectance from the transcutaneous layers is proposed. Original normalizing ratio algorithm permitting to separate glucose absorption from absorption of other blood components is suggested. It was shown that the influence of water and some other components such as hemoglobin, albumin, globulins and cholesterol concentration variations to the estimation of the glucose concentration can be compensated using spectral analysis of the reflection on several specially selected wavelengths and proposed algorithm. Device with optical geometry minimizing the effects of changes in the scattering background of biological tissues was developed. NIR spectral range 800 - 1800 nm was used because of its good transparency for biological tissue and presence of glucose absorption band. We used two kinds of light sources, namely LED array and Xe flash lamp. Tissue phantoms (different glucose concentration (0 - 1000 mg/dl) solutions with polystyrene beads or with milk) were used as samples. Scattering and absorption contribution to the dependence of diffuse reflection on glucose concentration was experimentally verified.

Reagentless/non-invasive diagnosis of blood substances

Determination of blood substances such as total hemoglobin, glucose, protein, cholesterol was investigated based on optical spectroscopy. Measurement was made either non-invasively or from blood or serum without using a test strip or wet chemistry.

Optimizations of preprocessing and wavelength selection in predicting human total hemoglobin concentrations based on VIS/NIR spectroscopy

The importance and effects of data preprocessing and wavelength selection were investigated in predicting total hemoglobin concentrations form absorption spectra. Spectra of the 1 nm interval between 500-900nm were measured from the whole blood samples taken form 165 patients whose hemoglobin concentrations ranged between 7-17 g/dl. The concentrations were predicted using the partial least squares regression. A total of 18 different combinations of preprocessing were tested. The partial least squares regression analysis provided quite different results depending on preprocessing methods and a wide range of prediction accuracy was obtained. For example, the sum of squares of difference ranged from 6-18.6, R2 varied from 0.8333 to 0.9477 and the root mean squared errors were from 0.5504-0.966 g/dl. The best results was obtained from the data processed by linear regression baseline fitting, unit area correction, mean centering and variance scaling. Instead of using all wavelengths in the broad-band spectra, a discrete number of wavelengths were selected to predict the concentrations using our algorithm, which will be advantageous in developing compact and less expensive commercial devices. It proves that a careful selection of wavelengths can provide a comparable accuracy obtained from using the broad-band spectra. For our particular experimental data, the measurement form only three discrete wavelengths could provide excellent results.

Non-invasive monitoring of blood glucose

Non-invasive methods for blood component analysis are attractive by their evident advantages such as real time monitoring, immunity to infection, possibility to control the concentrations of blood components, and providing painless measurement as often as necessary. A simple algorithm that uses the logarithmic ratio of two signals was successfully applied in the case of noninvasive bilirubin measurement. In contrast with bilirubin, glucose absorption takes place in the near infrared range where absorption by other components such as water, proteins, hemoglobin is significant. Therefore, a proper algorithm should use signal wavelengths, which are relatively free from the overlapping with the absorption bands of other major components. At the same time, the influence of other blood components whose concentrations may induce optically interfering signals should be minimized. The authors present here a simple, but efficient algorithm, which can be described on the base of analysis of the light propagation in blood. The algorithm may use any number of discrete wavelengths. A pulsed polychromatic light source is used. The light source emits a light pulse with a time duration of 500 /spl mu/s in wide bandwidth which includes light in the near infrared spectrum (energy of the pulse in near infrared range is 900 mW). Light source and detector unit was carefully designed so that reflected light from the skin surface was not measured. Prisms, fiber bundles, dispersing elements, etc. were used for propagating, directing and collecting oflight. The distance between the beam and detector, which could be adjusted between 2 and 10 mm, was set to be sufficient to avoid surface reflection and to minimize the effects of tissue scattering. Four interference filters as spectral selective elements around wavelengths 1625 nm, 1364 nm, 1300 nm and 1200 nm were used. Two different light sources, flash lamp and LED array were tried for the experiment.