title: Nanoliter serum sample analysis by mid-infrared spectroscopy for minimally invasive blood-glucose monitoring.
abstract: The aim of this study was to demonstrate that mid-infrared spectroscopy is able to quantify glucose in a serum matrix with sample volumes well below 1 muL. For this, we applied mid-infrared attenuated total reflectance (ATR) or transmission-based spectroscopic methods to glucose quantification in microsamples of dry-film sera, either undiluted or diluted 10 times in distilled water. The sample series spanned physiological glucose concentrations between 50 and 600 mg/dL and volumes of 80, 8, and 1 nL. Calibration was carried out using multivariate partial least-squares (PLS) modeling with spectral data between 1180 and 940 cm(-1). Best performance was achieved in the ATR experiments. For raw ATR spectra, the optimum standard error of prediction (SEP) of 13.3 mg/dL was obtained for the 8 nL sample series with subsequent 10-fold dilution. With respect to the coefficient of variation of the glucose assay, CV(pred), we obtained a value of 3% for the 80 nL volume samples with spectral preprocessing using matrix protein absorption bands as an internal standard, 4% for the 8 nL samples, and 6% for the 1 nL samples with raw data. Spectral standardization resulted in significant improvement, especially for the 80 nL volume sample series. By contrast, the accuracy of the glucose assay for the 1 nL sample volume series could not be improved either by internal standardization or by considering the dry film areas for normalization, which we attribute to varying topographies of the dry films.
authors.affiliation: Bayer Technology Services, Biophysics Competence Center, D-51368 Leverkusen, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Diessel
authors.forename: Peter
authors.initials: P
authors.lastname: Kamphaus
authors.forename: Klaus
authors.initials: K
authors.lastname: Grothe
authors.forename: Roland
authors.initials: R
authors.lastname: Kurte
authors.forename: Uwe
authors.initials: U
authors.lastname: Damm
authors.forename: H Michael
authors.initials: HM
authors.lastname: Heise
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods*; D001786:Blood Glucose / Q000032:analysis*; D008832:Microchemistry / Q000379:methods*; D036103:Nanotechnology / Q000379:methods*; D012031:Refractometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
chemical_list: D001786:Blood Glucose