Abstract

Surface Enhanced Raman Spectroscopy (SERS) enhances spontaneous Raman spectroscopy by the virtue of plasmon resonance of nanoparticles. Clinical application of SERS is challenging as nanoparticles remain in the body for long periods of time and a full toxicity analysis has yet to be extensively studied. In this study, Nanosphere lithography (NSL) was used to create optical fibers with nanoparticle enhanced tips for remote sensing using SERS. A custom designed RS collection setup was created for optimal collection of spectra from the optical fibers. It was found that an optical fiber with 0.5 numerical aperture (NA) allowed for better detection of Raman peaks while mitigating the fluorescence background of the optical fiber without any optical filters. Such a sensing platform can potentially be used to temporarily introduce nanoparticles into a sensing environment as it allows retracting the nanoparticles along with the tip. Nanoporous SERS platform has been fabricated using nanoporous silica glass with 7 nm and 17 nm pore diameters. An inexpensive fabrication approach of sputter deposition of Au layers was employed on prefabricated nanoporous silica glasses. 7 nm pore glasses provided larger enhancement than the glasses with 17 nm pores. A gold layer thickness of 25 nm was observed to produce largest enhancements. Nanoporous SERS substrates allow a larger effective SERS area compared to NSL based fabrication substrates and such nanoporous structures can be potentially fabricated on optical fiber tips for remote sensing. Finite Element Modeling (FEM) method was implemented for simulating single nanoparticles, an infinite periodic array of nanoparticles and nanoporous films using COMSOL Multiphysics software package. The extinction spectra obtained theoretically were found to match the experimental results for single nanoparticles. The maximum enhancement for the periodic array was two orders of magnitude larger than single particles while the integrated (average) enhancement was only two and a half times larger. Nanoporous films were also modelled using the FEM technique. Preliminary clinical data were collected from excised breast tissues for evaluating RS as a tool for cancer diagnostics. Spectral peaks from healthy tissues were found to be prominent than cancerous tissues and further experiments are needed to create a multivariate classification model for diagnostics.

Highlights

  • Biosensors that are efficient, low-cost, non-destructive, and label-free are desirable for identification of bio-markers that are used for clinical diagnosis[1]–[3]

  • Absorption measurements were performed on flat substrates to obtain extinction spectrum of the nanoparticles created

  • Increasing the NA of the fibers was found to improve the quality of spectra collected

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Summary

Introduction

Biosensors that are efficient, low-cost, non-destructive, and label-free are desirable for identification of bio-markers that are used for clinical diagnosis[1]–[3]. The ability to map the spatial distribution of bio-markers allows for identification of the regions of diseased areas in tissue, which aids in the early detection of disease and their development [4]. There have been many studies reporting the use of spectroscopic techniques towards diagnosing diseased conditions [6]–[9]. The degree of multiplexing (e.g. detecting multiple analytes through a single spectral acquisition) and versatility of spectral techniques in molecular sensing domain has been well established in the literature [4], [6], [8], [10]. In an extensive review performed by Dr Gambhir, he states: “In the future, more emphasis needs to be placed on developing new molecular imaging strategies whereby imaging agents are not required, yet a large diversity of targets can be interrogated.” [4]

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