title: Effect of photobleaching on calibration model development in biological Raman spectroscopy.
abstract: 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. This work investigates the deleterious effects of photobleaching on prediction accuracy of implicit calibration algorithms, particularly for transcutaneous glucose detection using Raman spectroscopy. Using numerical simulations and experiments on physical tissue models, we show that the prospective prediction error can be substantially larger when the calibration model is developed on a photobleaching correlated dataset compared to an uncorrelated one. Furthermore, we demonstrate that the application of shifted subtracted Raman spectroscopy (SSRS) reduces the prediction errors obtained with photobleaching correlated calibration datasets compared to those obtained with uncorrelated ones.
authors.affiliation: Massachusetts Institute of Technology, G. R. Harrison Spectroscopy Laboratory, Laser Biomedical Research Center, Cambridge, Massachusetts 02139, USA. ishan@mit.edu
authors.forename: Ishan
authors.initials: I
authors.lastname: Barman
authors.forename: Chae-Ryon
authors.initials: CR
authors.lastname: Kong
authors.forename: Gajendra P
authors.initials: GP
authors.lastname: Singh
authors.forename: Ramachandra R
authors.initials: RR
authors.lastname: Dasari
mesh_terms: D016477:Artifacts; D001786:Blood Glucose / Q000032:analysis*; D002138:Calibration; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000592:standards*; D013059:Spectrum Analysis, Raman / Q000379:methods* / Q000592:standards*; D014481:United States
chemical_list: D001786:Blood Glucose