Abstract
Surface-enhanced, spatially offset Raman spectroscopy (SESORS) combines the remarkable enhancements in sensitivity afforded by surface-enhanced Raman spectroscopy (SERS) with the non-invasive, subsurface sampling capabilities of spatially offset Raman spectroscopy. Taken together, these techniques show great promise for in vivo Raman measurements. Herein, we present a step forward for this technique, demonstrating SESORS through tissue analogues of six known and varied thicknesses, with a large number of distinct spatial offsets, in a backscattering optical geometry. This is accomplished by spin-coating SERS-active nanoparticles (NPs) on glass slides and monitoring the relative spectral contribution from the NPs and tissue sections, respectively, as a function of both the tissue thickness and the spatial offset of the collection probe. The results show that SESORS outperforms SERS alone for this purpose, the NP signal can be attained at tissue thicknesses of >6.75 mm, and greater tissue thicknesses require greater spatial offsets to maximize the NP signal, all with an optical geometry optimized for utility. This demonstration represents a step forward toward the implementation of SESORS for non-invasive, in vivo analysis.
Highlights
Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique that relies on an enhanced electromagnetic field near the surface of a metal nanostructure to amplify a traditionally weak Raman signal to impressive levels,[1] facilitating detection at the single-molecule limit.[2,3] Theoretical electromagnetic enhancement factors on the order of 1010,11 have been reported,[4] vastly improving detection limits for a number of SERS-based assays
Offset spectrum c shows stretches from the subsurface PDMS (487, 616, 709, and 1409 cm−1), as well as a subtle trace of the surface (PS) layer, with a weak peak at 1001 cm−1. This serves as confirmation that the system, as assembled, is allowing collection of spatially offset Raman spectroscopy (SORS) spectra and gathering of spectral information from a subsurface layer when an offset is applied in the x-direction
This work shows an unprecedented advancement forward for SESORS in that it demonstrates the use of the methodology in a backscattering geometry with spin-coated NP tags, a layer-bylayer analysis of tissue thickness to determine the system’s limits, and the importance of modulating the spatial offset as a function of tissue thickness to maximize the NP tag signal
Summary
Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique that relies on an enhanced electromagnetic field near the surface of a metal nanostructure to amplify a traditionally weak Raman signal to impressive levels,[1] facilitating detection at the single-molecule limit.[2,3] Theoretical electromagnetic enhancement factors on the order of 1010,11 have been reported,[4] vastly improving detection limits for a number of SERS-based assays. The field of surface-enhanced, spatially offset Raman spectroscopy (SESORS) has emerged in an attempt to couple the sensitivity afforded by SERS with the subsurface probing of SORS to allow detection at even greater depths, with an eye toward performing measurements in vivo.
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