Non-invasive chemically specific measurement of subsurface temperature in biological tissues using surface-enhanced spatially offset Raman spectroscopy

Abstract

Here we demonstrate for the first time the viability of characterising non-invasively the subsurface temperature of SERS nanoparticles embedded within biological tissues using spatially offset Raman spectroscopy (SORS). The proposed analytical method (T-SESORS) is applicable in general to diffusely scattering (turbid) media and features high sensitivity and high chemical selectivity. The method relies on monitoring the Stokes and anti-Stokes bands of SERS nanoparticles in depth using SORS. The approach has been conceptually demonstrated using a SORS variant, transmission Raman spectroscopy (TRS), by measuring subsurface temperatures within a slab of porcine tissue (5 mm thick). Root-mean-square errors (RMSEs) of 0.20 °C were achieved when measuring temperatures over ranges between 25 and 44 °C. This unique capability complements the array of existing, predominantly surface-based, temperature monitoring techniques. It expands on a previously demonstrated SORS temperature monitoring capability by adding extra sensitivity stemming from SERS to low concentration analytes. The technique paves the way for a wide range of applications including subsurface, chemical-specific, non-invasive temperature analysis within turbid translucent media including: the human body, subsurface monitoring of chemical (e.g. catalytic) processes in manufacture quality and process control and research. Additionally, the method opens prospects for control of thermal treatment of cancer in vivo with direct non-invasive feedback on the temperature of mediating plasmonic nanoparticles.

Raman spectroscopy: techniques and applications in the life sciences

“…So far applications for brain measurements through the skull have been proposed (see Figure 31) [411], as well as blood glucose monitoring [412] and Stokes/anti-Stokes temperature sensing of tissue [413,414].…”

Spatially offset Raman spectroscopy for non-invasive analysis of turbid samples

“…Very recently, Gardner et al demonstrated that apart from monitoring chemical properties of samples SORS and SESORS could be used to monitor their physical properties too, such as temperature [53,54]. The basic approach relies on monitoring the ratio of corresponding Stokes and anti-Stokes Raman bands.…”

Direct monitoring of light mediated hyperthermia induced within mammalian tissues using surface enhanced spatially offset Raman spectroscopy (T-SESORS)

“…The field of nanomaterials for photonics applications is rapidly expanding, with increasingly sophisticated materials being developed to monitor a plethora of physical and chemical properties, including but not limited to temperature, 1,2 pH, 3,4 redox, 3 glucose, 5 DNA 6 and proteins such as neurotransmitters, 7 with many of these being complex in vivo targets. One such active area is the development of advanced nanomaterials as therapeutics for the next generation of photothermal therapies for cancer treatment.…”

“…Potential nanomaterial mediated hyperthermia treatments require the temperature not only to be elevated, but also accurately monitored and maintained within relatively narrow therapeutic thermal windows (41-48°C) for effective and selective treatments. 9 However, until very recently non-invasive temperature sensing of tissue at depth was not possible 1,2,8,18 representing one of the main barriers to the introduction of photo thermal therapies (PTT). 9 Classically, Raman spectroscopy is seen as a technique limited to the sample surface in diffusely scattering samples such as biological tissues, with the sampling depth often limited to a few hundreds of micrometres.…”

“…This has led to a rapid expansion of the field with a variety of applications, including non-invasive chemically specific measurements of subsurface temperatures (T-SORS). 18 It is increasingly common to couple SORS/TRS with surface enhanced Raman spectroscopy (SERS), 1,26 in a so called SESORS modality, as this provides a great enhancement of the Raman signal, which is typically weak and further exacerbated when recovering a signal from depth. Recently, we demonstrated the coupling of T-SORS and SERS (T-SESORS) to deliver subsurface temperature probing capability.…”