Multiplex imaging of live breast cancer tumour models through tissue using handheld surface enhanced spatially offset resonance Raman spectroscopy (SESORRS)

Nicolson, Fay; Jamieson, Lauren E.; Mabbott, Samuel; Plakas, Konstantinos; Shand, Neil C.; Detty, Michael R.; Graham, Duncan; Faulds, Karen

doi:10.1039/c8cc04267e

Cited by 32 publications

(40 citation statements)

References 19 publications

(5 reference statements)

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“…In this instance gold nanostars were suspended in an agarose gel phantom and shielded by a monkey skull with a thickness of 5 mm. The detection of ex vivo multicellular tumor spheroids has also been reported using the SESORS technique through depths of 15 mm of tissue using a handheld SORS spectrometer 49, 50.…”

Section: Introductionmentioning

confidence: 98%

Non-invasive In Vivo Imaging of Cancer Using Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS)

et al. 2019

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Rationale: The goal of imaging tumors at depth with high sensitivity and specificity represents a significant challenge in the field of biomedical optical imaging. 'Surface enhanced Raman scattering' (SERS) nanoparticles (NPs) have been employed as image contrast agents and can be used to specifically target cells in vivo. By tracking their unique “fingerprint” spectra, it becomes possible to determine their precise location. However, while the detection of SERS NPs is very sensitive and specific, conventional Raman spectroscopy imaging devices are limited in their inability to probe through tissue depths of more than a few millimetres, due to scattering and absorption of photons by biological tissues. Here, we combine the use of "Spatially Offset Raman spectroscopy" (SORS) with that of "surface-enhanced resonance Raman spectroscopy" (SERRS) in a technique known as "surface enhanced spatially offset resonance Raman spectroscopy" (SESO(R)RS) to image deep-seated glioblastoma multiforme (GBM) tumors in vivo in mice through the intact skull.Methods: A SORS imaging system was built in-house. Proof of concept SORS imaging was achieved using a PTFE-skull-tissue phantom. Imaging of GBMs in the RCAS-PDGF/N-tva transgenic mouse model was achieved through the use of gold nanostars functionalized with a resonant Raman reporter to create SERRS nanostars. These were then encapsulated in a thin silica shell and functionalized with a cyclic-RGDyK peptide to yield integrin-targeting SERRS nanostars. Non-invasive in vivo SORS image acquisition of the integrin-targeted nanostars was then performed in living mice under general anesthesia. Conventional non-SORS imaging was used as a direct comparison.Results: Using a low power density laser, GBMs were imaged via SESORRS in mice (n = 5) and confirmed using MRI and histopathology. The results demonstrate that via utilization of the SORS approach, it is possible to acquire clear and distinct Raman spectra from deep-seated GBMs in mice in vivo through the skull. SESORRS images generated using classical least squares outlined the tumors with high precision as confirmed via MRI and histology. Unlike SESORRS, conventional Raman imaging of the same areas did not provide a clear delineation of the tumor.Conclusion: To the best of our knowledge this is the first report of in vivo SESO(R)RS imaging. In a relevant brain tumor mouse model we demonstrate that this technique can overcome the limitations of conventional Raman imaging with regards to penetration depth. This work therefore represents a significant step forward in the potential clinical translation of SERRS nanoparticles for high precision cancer imaging.

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Section: Introductionmentioning

confidence: 98%

Non-invasive In Vivo Imaging of Cancer Using Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS)

et al. 2019

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“…SERS can provide a significant enhancement of the normally weak Raman signal of biological samples . Moreover, SERS nanoparticles (NPs) can be optimised and functionalised in order to target specific biomarkers of interest and provide in vivo diagnosis of multiple diseases . The combination of SERS and SORS techniques (ie, SESORS) opens new prospects for detecting a number of disease conditions in vivo due to the depth and concentration sensitivity with high chemical specificity.…”

Section: Introductionmentioning

confidence: 99%

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

Mosca

Dey

Tabish

et al. 2019

Journal of Biophotonics

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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.

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“…20,21 By combining SERRS with SORS to yield surface enhanced spatially offset resonance Raman spectroscopy (SESORRS), SERRS nanotags present in ex vivo breast cancer tumour models were detected through depths of 15 mm of tissue. 22,23 However, in this instance, we aim to demonstrate the powerful capabilities of handheld conventional Raman instrumentation for detecting SERS analytes at significant depth, without the need for SORS techniques.…”

Section: Introductionmentioning

confidence: 99%

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

Nicolson

Jamieson

Mabbott

et al. 2018

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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.

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Multiplex imaging of live breast cancer tumour models through tissue using handheld surface enhanced spatially offset resonance Raman spectroscopy (SESORRS)

Abstract: Through utilizing the depth penetration capabilities of SESORS, multiplexed imaging and classification of three singleplex nanotags and a triplex of nanotags within breast cancer tumour models is reported for the first time through depths of 10 mm using a handheld SORS instrument.

Cited by 32 publications

References 19 publications

Non-invasive In Vivo Imaging of Cancer Using Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS)

Non-invasive In Vivo Imaging of Cancer Using Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS)

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

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

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