Noninvasive simultaneous monitoring of pH and depth using surface‐enhanced deep Raman spectroscopy

Abstract

Here we demonstrate the simultaneous recovery of multiplexed physical information of surface‐enhanced Raman scattering (SERS) nanoparticles (pH and depth) using deep Raman spectroscopy. As has been shown previously and in accordance with theory, inelastically scattered photons arising from spectral peaks that are suitably separated can exhibit different optical properties in the media through which they travel. These differences can impact the relative intensities of the Raman peaks as a function of the transmission path length; thereby, the depth of signal generation is inherently encoded in the spectra; assuming the target is clustered at a single depth or location, its depth can be readily determined. Moreover, Raman spectroscopy is very sensitive to chemistry of a sample, and changes in pH are observed not only as changes in peak intensity through relevant protonation and deprotonation but also as shifts in spectral features. Here, we show it is possible to precisely predict the depth (root‐mean‐square error [RMSE] 5 %) of SERS nanoparticles in scattering media (0.5% intralipid) while also being able to noninvasively monitor simultaneously the pH levels (RMSE ~0.2 pH units) of the media surrounding the nanoparticles. This is important as it demonstrates that nanoparticles can be used to report on multiple physical properties including their depth. This opens avenues for a range of new applications including the noninvasive diagnosis and localisation of cancer lesions in clinical environment in vivo.

Comparison of 4-Mercaptobenzoic Acid Surface-Enhanced Raman Spectroscopy-Based Methods for pH Determination in Cells

“…9,10,12–14,18,20,21 The frequency of the ν 8a ring breathing mode (around 1580 cm –1 ) is also known to shift with changing pH. 18,19,22 Other peaks are affiliated with the protonated or deprotonated state of the molecule, but have much lower intensity relative to the spectral features described. Indeed other molecules have pH-sensitive properties, but the MBA molecule is prominently used in the SERS literature, and thus the focus of the current study.…”

Self-absorption corrected non-invasive transmission Raman spectroscopy (of biological tissue)

“…[12][13][14] Over time the sophistication of signal retrieval has increased from identifying a single compound, 5,15 to multiplexed signal recovery, 13 physical property signal recovery 16 and depth localisation. [17][18][19][20][21] A number of publications have demonstrated how differential optical properties in a scattering medium, i.e. tissue, between different Raman components can also be exploited for depth localisation.…”

“…These examples have been demonstrated in well-controlled samples, wherein the sample has typically a uniform thickness in transmission geometry. [19][20][21] However, in the real world there is often little control of the sample thickness, when performing deep Raman on biological samples. This variation can arise undesirably in two key ways, firstly with thickness variation within a sample during Raman mapping, secondly due to differences in thickness between different samples.…”

Spatially offset Raman spectroscopy for biomedical applications

“…87 More recently, a similar approach showed that it was possible to also precisely predict the depth at which SERS NPs were buried in a turbid phantom (0.5% intralipid) and simultaneously monitor changes in pH of the media surrounding the NPs. 88 need to establish more rapid, effective methods capable of quantifying neurotransmitter concentrations in vivo. With this in mind, SESORS has since been utilized for the measurement of melatonin, serotonin and epinephrine at concentrations as low as 100 mM in a brain tissue mimic through a cat skull.…”