SERS in the second biological window: towards in-vivo applications

Student thesis: Doctoral Thesis

Abstract

Surface-enhanced Raman spectroscopy (SERS) refers to the inelastic scattering of light from molecules adsorbed on or positioned close to an enhancing surface, typically consisting of the noble metals gold or silver. First observed in the 1970s, SERS gained attention as an analytical technique due to its excellent sensitivity and specificity, which is combined with rapid, non-destructive analysis. In recent decades, the analytical application of SERS has been realised for chemical and biological sensing in environmental science, industry and home security among other fields. More recently, SERS has attracted further interest due to potential clinical spectroscopy applications. It has been demonstrated that the high sensitivity of SERS enables the detection of gold nanoparticles obscured by a tissue barrier while still allowing resolution of distinct spectral features. SERS has therefore been proposed as a technique for non-invasive diagnostics, such as detection, imaging and monitoring of tumours, bacterial infections, and other artifacts beneath the skin. The development of surface-enhanced spatially offset Raman scattering (SESORS) has provided further impetus and interest for the use of SERS in tissue by extending the maximum tissue penetration depth up to 7 cm. Meanwhile, the large body of work investigating the proposed therapeutic applications of gold nanoparticles has created opportunities for them to be utilised as a combined diagnostic and therapeutic platform. As mammalian tissue is opaque to visible light, in-vivo applications require optimisation of the SERS process for near-infrared (NIR) light to maximise tissue penetration by the Raman excitation laser and minimise absorption of both the incident and the SERS photons. This has stimulated much research into SERS using NIR-I (approx. 650-1000 nm) wavelengths. However, there has been comparatively very little research into SERS in the second biological window (approx. 1000-1400 nm) due to the severe difficulties that are encountered when attempting to achieve strong SERS in this region. This is unfortunate, because NIR-II SERS is theorised to have several major advantages for clinical spectroscopy applications including safer lasers, higher transmission through most tissue types and reduced Raman and auto-fluorescent interference. In this thesis the prospects of NIR-II SERS for non-invasive clinical spectroscopy will be investigated. In the introductory chapter the important elements of Raman and SERS theory are described. In chapter three, red-shifted gold nanoparticles are investigated in an attempt to rationalise their prospects for NIR applications on the basis of their optical properties. In chapter four, this analysis is extended to nanoparticle aggregates and finding candidates for bright NIR-II SERS nanotags, which in chapter five will be deployed for multiplex detection through 1 cm of porcine tissue. Finally in chapter six the use of SESORS using a 1064 nm laser is demonstrated for the first time, highlighting the future potential of NIR-II clinical spectroscopy.
Date of Award3 Aug 2023
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorKaren Faulds (Supervisor) & Duncan Graham (Supervisor)

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