8th October 2019 | Journal of Biophotonics

Determination of inclusion depth in ex vivo animal tissues using surface enhanced deep Raman spectroscopy

Sara Mosca, Priyanka Dey, Tanveer A. Tabish, Francesca Palombo, Nicholas Stone & Pavel Matousek


This work presents recent developments in spatially offset and transmission Raman spectroscopy for noninvasive detection and depth prediction of a single SERS inclusion located deep inside ex vivo biological tissues. The concept exploits the differential attenuation of Raman bands brought about by their different absorption due to tissue constituents enabling to predict the inclusion depth. Four different calibration models are tested and evaluated to predict the depth of surface enhanced Raman scattering labelled nanoparticles, within an up to 40 mm slab of porcine tissue. An external measurement carried out in transmission mode, with a noninvasively built model on the analysed sample, is shown to be insensitive to variations of the overall thickness of the tissue yielding an average root‐mean‐square error of prediction of 6.7%. The results pave the way for future noninvasive deep Raman spectroscopy in vivo enabling to localise cancer biomarkers for an early diagnosis of multiple diseases.

9th September 2019 | Advanced Functional Materials

Novel Au–SiO2–WO3 Core–Shell Composite Nanoparticles for Surface‐Enhanced Raman Spectroscopy with Potential Application in Cancer Cell Imaging

Pablo Martinez Pancorbo, Kunyapat Thummavichai, Louise Clark, Tanveer A. Tabish, Jessica Mansfield, Ben Gardner, Hong Chang, Nick Stone & Yanqiu Zhu


With the rapid development of nanotechnology during the last decades, the ability to detect and control individual objects at the nanoscale has enabled us to deal with complex biomedical challenges. In cancer imaging, novel nanoparticles (NPs) offer promising potential to identify single cancer cells and precisely label larger areas of cancer tissues. Herein, a new class of size tunable core–shell composite (Au–SiO2–WO3) nanoparticles is reported. These nanoparticles display an easily improvable ≈103 surface‐enhanced Raman scattering (SERS) enhancement factor with a double Au shell for dried samples over Si wafers and several orders of magnitude for liquid samples. WO3 core nanoparticles measuring 20–50 nm in diameter are sheathed by an intermediate 10–60 nm silica layer, produced by following the Stöber‐based process and Turkevich method, followed by a 5–20 nm thick Au outer shell. By attaching 4‐mercaptobenzoic acid (4‐MBA) molecules as Raman reporters to the Au, high‐resolution Raman maps that pinpoint the nanoparticles' location are obtained. The preliminary results confirm their advantageous SERS properties for single‐molecule detection, significant cell viability after 24 h and in vitro cell imaging using coherent anti‐stokes Raman scattering. The long‐term objective is to measure SERS nanoparticles in vivo using near‐infrared light.

19th July 2019 | Analytical Chemistry

Subsurface Chemically Specific Measurement of pH Levels in Biological Tissues Using Combined Surface-Enhanced and Deep Raman

Benjamin Gardner, Pavel Matousek & Nicholas Stone


There is much interest in using nanosensors to monitor biologically relevant species such as glucose, or cellular pH, as these often become dysregulated in diseases such as cancer. This information is often inaccessible at depth in biological tissue, due to the highly scattering nature of tissue. Here we show that gold nanoparticles labeled with pH-sensitive reporter molecules can monitor pH at depth in biological tissues. This was achieved using deep Raman spectroscopy (spatially offset Raman and transmission Raman) in combination with surface-enhanced Raman spectroscopy, allowing chemical information to be retrieved significantly deeper than conventional Raman spectroscopy permits. Combining these approaches with chemometrics enabled pH changes to be monitored with an error of ±∼0.1 pH units noninvasively through 22 mm of soft tissue. This development opens the opportunity for the next generation of light-based medical diagnostic methods, such as monitoring of cancers, known to significantly alter pH levels.

17th June 2019 | Analytical Chemistry

Spatially Offset and Transmission Raman Spectroscopy for Determination of Depth of Inclusion in Turbid Matrix

Sara Mosca, Priyanka Dey, Tanveer A. Tabish, Francesca Palombo, Nicholas Stone & Pavel Matousek


We propose an approach for the prediction of the depth of a single buried object within a turbid medium combining spatially offset Raman spectroscopy (SORS) and transmission Raman spectroscopy (TRS) and relying on differential attenuation of individual Raman bands brought about by the spectral variation of matrix absorption (and scattering). The relative degree of the Raman band changes is directly related to the path length of Raman photons traveling through the medium, thereby encoding the information on the depth of the object within the matrix. Through a calibration procedure with root mean square error of calibration (RMSEC) = 3.4%, it was possible to predict the depth of a paracetamol (acetaminophen) inclusion within a turbid matrix consisting of polyethylene (PE) by monitoring the relative intensity of two Raman bands of paracetamol exhibiting differential absorption by the matrix. The approach was shown to be largely insensitive to variations of the amount of the inclusion (paracetamol) and to the overall thickness of the turbid matrix (PE) with a root mean square error of prediction (RMSEP) maintained below 10% for the tested cases. This represents a major advantage over previously demonstrated comparable depth determination Raman approaches (with the exception of full Raman tomography requiring complex mathematical reconstruction algorithms). The obtained experimental data validate the proposed approach as an effective tool for the noninvasive determination of the depth of buried objects in turbid media with potential applications including determining noninvasively the depth of a lesion in cancer diagnosis in vivo.

3rd May 2019 | Analyst

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

Benjamin Gardner, Pavel Matousek & Nick Stone


Here we demonstrate light mediated heating of nanoparticles confined deep inside mammalian tissue, whilst directly monitoring their temperature non-invasively using a form of deep Raman spectroscopy, T-SESORS. One of the main barriers to the introduction of photo-thermal therapies (PTT) has been recognised as the inability to directly monitor the local temperature deep within the tissue at the point of therapy. Here Au nanoparticles with a Raman reporter molecule (temperature reporters) are used in combination with Au nanoshells (heat mediators) to provide simultaneously heating under NIR illumination and direct spectroscopic monitoring of local temperature deep within mammalian tissues. The surface enhanced Raman signal was read out at the tissue surface using a transmission geometry in this example and the temperature of the tissue was ascertained from the anti-Stokes to Stokes Raman reporter. This approach opens the prospect of non-invasive hyperthermia treatments with direct temperature feedback from deep inside within tissue, where nanoparticles can be used to both provide localised heating and accurately monitor the local temperature.