Toward a Glucose Biosensor Based on Surface-Enhanced Raman Scattering

Abstract

This work presents the first step toward a glucose biosensor using surface-enhanced Raman spectroscopy (SERS). Historically, glucose has been extremely difficult to detect by SERS because it has a small normal Raman cross section and adsorbs weakly or not at all to bare silver surfaces. In this paper, we report the first systematic study of the direct detection of glucose using SERS. Glucose is partitioned into an alkanethiol monolayer adsorbed on a silver film over nanosphere (AgFON) surface and thereby, it is preconcentrated within the 0-4 nm thick zone of electromagnetic field enhancement. The experiments presented herein utilize leave-one-out partial least-squares (LOO-PLS) analysis to demonstrate quantitative glucose detection both over a large (0-250 mM) and clinically relevant (0-25 mM) concentration range. The root-mean-squared error of prediction (RMSEP) of 1.8 mM (33.1 mg/dL) in the clinical study is near that desired for medical applications (1 mM, 18 mg/dL). Future studies will advance toward true in vivo, real time, minimally invasive sensing.

Towardsin vivointradermal surface enhanced Raman scattering (SERS) measurements: silver coated microneedle based SERS probe

“…Raman intensities at these positions increase with the glucose concentration, in contrast to the unchanged Raman intensity peaks at 714, 889, 1073 and 1128 cm -1 attributed to 1-decanethiol adsorbed on the Ag-coated surface (concentration at 0 mM). Raman peaks at 914, and 840 cm -1 are only noted for glucose in crystalline state, which is also similar to other substrates [5] reported in the literature. In contrast, without this SERS probe, glucose Raman peaks cannot be detected at all as shown by the spectrum at the bottom of Figure 3(a).…”

“…These spectra were obtained by averaging data from five different microneedles and phantom locations with a standard deviation of less than 10%. Note that the Ag-coated microneedle was incubated with 1-decanethiol (1 mM) in ethanol for 16 hours prior to SERS measurements because decanethiol-modified Ag was reported in other type of SERS substrates [5] for effective SERS glucose detection. Prominent Raman peaks are observed at about 1076 and 1124 cm -1 , which can be attributed to the C-C, and C-O-H deformation of glucose [22], respectively.…”

“…We utilized the partial least square (PLS) regression and a leave-one-out (LOO) technique [5,14] to process all data points to assess the efficacy of the Agcoated microneedle-based SERS probe in glucose concentration estimation. A public domain Matlab code [15] was modified to implement PLS-LOO analysis.…”

“…This procedure was repeated by leaving out a different data point until the glucose concentrations corresponding to all data points have been estimated once. The root-mean-squared error of estimation (RMSE) [5],…”

“…Although Raman measurements can be achieved from a depth of about 200 mm under the skin [3], the measurements of dermal components deeper than 700 mm is difficult. Moreover, the detection sensitivity is limited by the small Raman scattering cross section (10 -29 -10 -32 cm 2 ) of endogenous biomolecules [5]. In contrast, surface-enhanced Raman scattering (SERS) technique can amplify Raman signals up to 10 14 folds using metallic surfaces [e.g., silver (Ag) and gold] [6].…”