SERS Measurement of Bile Juice for Identification of Gallbladder Diseases using Diverse Nanostructured SERS Substrate

Abstract

This thesis is composed of two different sections. In the first chapter, a unique surface-enhanced Raman scattering (SERS) combine with external voltage application measurement scheme to discriminate gall bladder (GB) polyp and GB cancer by analysis of bile juice has been demonstrated. Raman spectra of aqueous phases extracted from raw bile juice samples were acquired using the Au nanodendrites constructed on a screen-printed electrode (AuND@SPE) at voltages from -300 to 300 mV. The observed SERS signal of bile juice were mainly from bilirubin and bilirubin derivatives. Discrimination of GB polyp and GB cancer became apparent when the spectra were acquired at a voltage of -100 mV. Investigation of bilirubin and urobilinogen shows that, SERS signal as well as electrochemical signal of urobilinogen suddenly increase at -100 mV due to potential-driven strong adsorption of urobilinogen on AuND at -100 mV which elevate SERS intensity. The content of urobilinogen in the bile juice of a GB cancer patient was presumed to be higher than that of a GB polyp patient, and its signal was highlighted by applying -100 mV. Next, the voltage-applied SERS measurement scheme has been further demonstrated for discrimination of GB polyp and stone. Two-trace two-dimensional (2T2D) correlation analysis employing a pair of spectra acquired under external perturbation was used to highlight the minutely dissimilar spectral variations. When the two spectra of a sample collected with application of +100 and +300 mV was adopted for the analysis, the features of subsequent 2T2D slice spectra became more characteristic for the identification GB stone and GB polyp samples, thus improving the discrimination. In the second chapter, a three-dimensional nickel foam (NF) caging Ag-Au bimetallic nanostructure (Ag-Au@NF) has been demonstrated as a highly rugged and sensitive SERS substrate. NF was used as a cage to secure the internal nanostructures owing to its strength and porous structure. A Ag-Au bimetallic nanostructure was constructed within the NF cage, combining the high SERS efficiency of Ag and the good surface stability of Au. The Ag-Au@NF were rugged, showing small Raman signal drops after sandpaper abrasion or sonication. Finally, NF caging AuND (AuND@NF) bridged with a paper strip (PS-AuND@NF) for pretreatment-free SERS measurement of raw bile juice for the identification of GB polyp and stone was demonstrated. For the preparation, the PS-AuND@NF was built by simply positioning AuND@NF on a paper strip, which functioned as a channel for sample introduction to AuND@NF and a subsequent sample drain. With the continuous elution of raw bile juice, non-specific adsorption of SERS-inactive constituents on the Au surface could be minimized. 2T2D correlation analysis was carried and the principal component (PC) scores obtained from the 2T2D slice spectra improved the discrimination accuracy to 88.9% from 81.5% obtained when using only the PC scores of the raw spectra.