Surface enhanced resonance Raman spectroscopy (SERRS) for probing through plastic and tissue barriers using a handheld spectrometer

Abstract

The ability to probe through barriers and tissue non-invasively is an urgent unmet need in both the security and biomedical imaging fields. Surface enhanced Raman spectroscopy (SERS) has been shown to yield superior enhancement in signal over conventional Raman techniques. Furthermore, by utilising a resonant Raman reporter to produce surface enhanced resonance Raman spectroscopy (SERRS), even greater enhancement in chemical signal can be generated. Here we show the benefit of using red-shifted chalcogenpyrylium based Raman reporters for probing through large thicknesses of plastic and tissue barriers using a conventional Raman instrument. In addition, the benefit of using a resonant Raman reporter for superior levels of through barrier detection is demonstrated, and we aim to show the advantage of using resonant nanotags in combination with conventional Raman spectroscopy to probe through plastic and tissue barriers. Raman signals were collected from SERRS active nanotags through plastic thicknesses of up to 20 mm, as well as the detection of the same SERRS nanotags through up to 10 mm of tissue sections using a handheld conventional Raman spectrometer. The ability to detect SERRS-active nanotags taken up into ex vivo tumour models known as multicellular tumour spheroids (MTS), through depths of 5 mm of tissue is also shown. The advantages of applying multivariate analysis for through barrier detection when discriminating analytes with similar spectral features as the barrier is also clearly demonstrated. To the best of our knowledge, this is the first report of the assessment of the maximum level of through barrier detection using a conventional handheld Raman instrument for SERS applications as well as demonstration of the power of resonant nanotags for probing through barriers using conventional Raman spectroscopy.

Defocused Spatially Offset Raman Spectroscopy in Media of Different Optical Properties for Biomedical Applications Using a Commercial Spatially Offset Raman Spectroscopy Device

“…In contrast to conventional confocal Raman spectroscopy that only effectively measures to a depth of a few hundred microns (depending on the sample optical properties), SORS has been able to acquire specific molecular signals from centimeter depths. 8 These signals can then be recovered by using different spectral demixing approaches, including such multivariate techniques 9,10 as band-target entropy minimization (BTEM), 11,12 ordinary least squares (OLS), 13 or by simple scaled subtraction. 9…”

“…Over the last decade, SORS has been successfully employed in a number of biological applications including transcutaneous animal 8,14 and in vivo human bone measurements, 15 as well as for calcification measurements in chicken 16 and human breast tissue. 17 Variants of the basic SORS configuration include combination with SERS nanoparticles buried in pork tissue 10 and inverse SORS for bone measurement in animal tissue. 18,19 Additionally, SORS on a microscale has become a popular alternative for users of conventional confocal Raman microscopes by defocusing the laser and/or Raman collection optics.…”

Towards establishing a minimal nanoparticle concentration for applications involving surface enhanced spatially offset resonance Raman spectroscopy (SESORRS) in vivo

“…Dye 823 also has a larger Raman cross section in comparison to BPE, making it a superior Raman scatterer as well as being in resonance with the excitation wavelength. 23 Figure 3(a) shows the 8 mm offset spectra of BPE nanotags (green) and dye 823 nanotags (purple) at a concentration of 11 pM. As shown, there is a clear difference in the signal to noise ratio between the two nanotags.…”

“…21,22 Such depth penetration was achieved through the use of chalcogenpyrylium Raman reporters with a tuneable absorption maxima in the near infrared (NIR). We have also demonstrated, using both conventional Raman 23 and SORS, 21 that by using a Raman reporter that is in resonance with the laser excitation wavelength, it is possible to detect SERS nanotags through larger thicknesses in comparison to when non-resonant Raman reporters are used. Previous reports have shown these reporter molecules to be particularly useful at longer wavelengths including 1280 nm 24 and 1550 nm 25 , outperforming commercially available Raman reporter molecules such as BPE.…”

Raman Imaging: An Impending Approach Towards Cancer Diagnosis

“…Surface‐enhanced resonance Raman scattering (SERRS) is another advanced form of Raman spectroscopy in which the Raman spectral intensity could enhance by additional several orders of magnitude when the laser wavelength matches the optical absorption of Raman signature molecules [109,110] . Kircher and co‐workers formulated a SERRS nanostar for imaging tumor margins, microscopic tumor invasion and metastasis (Figure 7B).…”