Spatially offset Raman spectroscopy (SORS) is a spectroscopic technique that allows for the non-invasive chemical characterization of diffusely scattering materials, ranging from opaque plastics to biological tissues. SORS has been explored for a range of applications, including disease diagnosis, the detection of explosives through unopened containers and the in-depth, non-destructive analysis of pharmaceutical products and objects of art. This Primer introduces the reader to the basic concepts underpinning SORS, details best practices for its implementation, highlights its use across multiple fields and provides insight into its limitations. The Primer concludes by discussing potential applications and envisaging future developments in the field.
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Pelletier, M. J. in Analytical Applications of Raman Spectroscopy 10–105 (Wiley, 1999).
Matousek, P. Spatially offset Raman spectroscopy for non-invasive analysis of turbid samples. Trends Analyt. Chem. 103, 209–214 (2018).
Long, D. A. The Raman Effect: A Unified Treatment of the Theory of Raman Scattering by Molecules (Wiley, 2002).
Jones, R. R., Hooper, D. C., Zhang, L., Wolverson, D. & Valev, V. K. Raman techniques: fundamentals and frontiers. Nanoscale Res. Lett. 14, 231 (2019).
Tuschel, D. Raman thermometry. Spectroscopy 31, 8–13 (2016).
Iwata, K., Ozawa, R. & Hamaguchi, H. Analysis of the solvent- and temperature-dependent Raman spectral changes of S1 trans-stilbene and the mechanism of the trans to cis isomerization: dynamic polarization model of vibrational dephasing and the C=C double-bond rotation. J. Phys. Chem. A 106, 3614–3620 (2002).
Singh, A., Gangopadhyay, D., Nandi, R., Sharma, P. & Singh, R. K. Raman signatures of strong and weak hydrogen bonds in binary mixtures of phenol with acetonitrile, benzene and orthodichlorobenzene. J. Raman Spectrosc. 47, 712–719 (2016).
Wang, H. et al. Effects of hydrogen bond and solvent polarity on the C=O stretching of bis(2-thienyl)ketone in solution. J. Chem. Phys. 136, 124509 (2012).
Hashimoto, K., Badarla, V. R., Kawai, A. & Ideguchi, T. Complementary vibrational spectroscopy. Nat. Commun. 10, 4411 (2019).
Matousek, P. & Morris, M. D. Emerging Raman Applications and Techniques in Biomedical and Pharmaceutical Fields (Springer, 2010).
Nicolson, F., Kircher, M. F., Stone, N. & Matousek, P. Spatially offset Raman spectroscopy for biomedical applications. Chem. Soc. Rev. 50, 556–568 (2021).
Matousek, P. Deep non-invasive Raman spectroscopy of living tissue and powders. Chem. Soc. Rev. 36, 1292 (2007).
Matousek, P. et al. Subsurface probing in diffusely scattering media using spatially offset Raman spectroscopy. Appl. Spectrosc. 59, 393–400 (2005). This paper is the first conceptual demonstration of SORS.
Martelli, F., Bianco, S. del, Ismaelli, A. & Zaccanti, G. Light Propagation Through Biologial Tissue and Other Diffusive Media: Theory, Solutions, and Software (Bellingham, 2009).
Pfefer, T. J., Schomacker, K. T., Ediger, M. N. & Nishioka, N. S. Multiple-fiber probe design for fluorescence spectroscopy in tissue. Appl. Opt. 41, 4712 (2002).
Shi, L. & Alfano, R. Deep Imaging in Tissue and Biomedical Materials: Using Linear and Non-linear Optical Methods (CSC, 2017).
Iping Petterson, I. E., Esmonde-White, F. W. L., de Wilde, W., Morris, M. D. & Ariese, F. Tissue phantoms to compare spatial and temporal offset modes of deep Raman spectroscopy. Analyst 140, 2504–2512 (2015).
Gardner, B., Matousek, P. & Stone, N. Temperature spatially offset Raman spectroscopy (T-SORS): subsurface chemically specific measurement of temperature in turbid media using anti-stokes spatially offset Raman spectroscopy. Anal. Chem. 88, 832–837 (2016).
Everall, N. et al. Measurement of spatial resolution and sensitivity in transmission and backscattering Raman spectroscopy of opaque samples: impact on pharmaceutical quality control and Raman tomography. Appl. Spectrosc. 64, 476–484 (2010).
Oelkrug, D., Ostertag, E. & Kessler, R. W. Quantitative Raman spectroscopy in turbid matter: reflection or transmission mode? Anal. Bioanal. Chem. 405, 3367–3379 (2013).
Zaccanti, G., Del Bianco, S. & Martelli, F. Measurements of optical properties of high-density media. Appl. Opt. 42, 4023 (2003).
Pogue, B. W. & Patterson, M. S. Frequency-domain optical absorption spectroscopy of finite tissue volumes using diffusion theory tissue volumes using diffusion theory. Phys. Med. Biol. 39, 1157–1180 (1994).
Spinelli, L. et al. Calibration of scattering and absorption properties of a liquid diffusive medium at NIR wavelengths. Time-resolved method. Opt. Express 15, 6589 (2007).
Bouchard, J.-P. et al. Reference optical phantoms for diffuse optical spectroscopy. Part 1 — error analysis of a time resolved transmittance characterization method. Opt. Express 18, 11495 (2010).
Patterson, M. S., Chance, B. & Wilson, B. C. Time resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties. Appl. Opt. 28, 2331–2336 (1989).
Mosca, S. et al. Estimating the reduced scattering coefficient of turbid media using spatially offset Raman spectroscopy. Anal. Chem. https://doi.org/10.1021/acs.analchem.0c04290 (2021).
Das, B. B., Liu, F. & Alfano, R. R. Time-resolved fluorescence and photon migration studies in biomedical and model random media. Rep. Prog. Phys 60, 227 (1997).
Brenan, C. J. H. & Hunter, I. W. Volumetric Raman microscopy through a turbid medium. J. Raman Spectrosc. 27, 561–570 (1996).
Mosca, S. et al. Optical characterisation of porcine tissues from various organs in the 650–1100 nm range using time-domain diffuse spectroscopy. Biomed. Opt. Express 11, 1697–1706 (2020).
Stevens, O., Iping Petterson, I. E., Day, J. C. C. & Stone, N. Developing fibre optic Raman probes for applications in clinical spectroscopy. Chem. Soc. Rev. 45, 1919–1934 (2016).
McGee, R., Blanco, A., Presly, O. & Stokes, R. J. Portable spatially offset Raman spectroscopy for rapid hazardous materials detection within sealed containers. Spectroscopy 33, 24–30 (2018).
Matousek, P., Towrie, M. & Parker, A. W. Fluorescence background suppression in Raman spectroscopy using combined Kerr gated and shifted excitation Raman difference techniques. J. Raman Spectrosc. 33, 238–242 (2002).
Cebeci-Maltaş, D., Wang, P., Alam, M. A., Pinal, R. & Ben-Amotz, D. Photobleaching profile of Raman peaks and fluorescence background. Eur. Pharm. Rev. 22, 18–21 (2017).
Ghirardello, M. et al. Time-resolved photoluminescence microscopy combined with X-ray analyses and Raman spectroscopy sheds light on the imperfect synthesis of historical cadmium pigments. Anal. Chem. 90, 10771–10779 (2018).
Afseth, N. K., Bloomfield, M., Wold, J. P. & Matousek, P. A novel approach for subsurface through-skin analysis of salmon using spatially offset Raman spectroscopy (SORS). Appl. Spectrosc. 68, 255–262 (2014).
Conti, C., Colombo, C., Realini, M. & Matousek, P. Subsurface analysis of painted sculptures and plasters using micrometre-scale spatially offset Raman spectroscopy (micro-SORS). J. Raman Spectrosc. 46, 476–482 (2015).
Conti, C. et al. Noninvasive analysis of thin turbid layers using microscale spatially offset Raman spectroscopy. Anal. Chem. 87, 5810–5815 (2015).
American National Standard Institute. American National Standard for Safe Use of Lasers (ANSI Z136.1-2014) (Laser Institute of America, 2014).
Born, M. & Wolf, E. Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light 7th edn (Cambridge Univ. Press, 2005).
Matousek, P. et al. Noninvasive Raman spectroscopy of human tissue in vivo. Appl. Spectrosc. 60, 758–763 (2006).
Ghita, A., Matousek, P. & Stone, N. High sensitivity non-invasive detection of calcifications deep inside biological tissue using transmission Raman spectroscopy. J. Biophotonics 11, e201600260 (2018).
Mosca, S. et al. Spatially offset and transmission Raman spectroscopy for determination of depth of inclusion in turbid matrix. Anal. Chem. 91, 8994–9000 (2019).
Esmonde-White, F. W. L., Esmonde-White, K. A. & Morris, M. D. Minor distortions with major consequences: correcting distortions in imaging spectrographs. Appl. Spectrosc. 65, 85–98 (2011).
Thomas, G. et al. Evaluating feasibility of an automated 3-dimensional scanner using Raman spectroscopy for intraoperative breast margin assessment. Sci. Rep. 7, 1–14 (2017).
Qin, J. et al. A line-scan hyperspectral Raman system for spatially offset Raman spectroscopy. J. Raman Spectrosc. 47, 437–443 (2016).
Olds, W. J. et al. Spatially offset Raman spectroscopy (SORS) for the analysis and detection of packaged pharmaceuticals and concealed drugs. Forensic Sci. Int. 212, 69–77 (2011).
Maher, J. R. & Berger, A. J. Determination of ideal offset for spatially offset Raman spectroscopy. Appl. Spectrosc. 64, 61–65 (2010).
Ghita, A., Matousek, P. & Stone, N. Sensitivity of transmission Raman spectroscopy signals to temperature of biological tissues. Sci. Rep. 8, 1–7 (2018).
Hossain, M. N., Igne, B., Anderson, C. A. & Drennen, J. K. Influence of moisture variation on the performance of Raman spectroscopy in quantitative pharmaceutical analyses. J. Pharm. Biomed. Anal. 164, 528–535 (2019).
Mestari, A., Gaufrès, R. & Huguet, P. Behaviour of the calibration of a Raman spectrometer with temperature changes. J. Raman Spectrosc. 28, 785–789 (1997).
ASTM E1840-96. Standard Guide for Raman Shift Standards for Spectrometer Calibration (ASTM International, 2014).
Allen, M. W. & Mattley, Y. Innovative Raman sampling. New technique addresses challenges associated with explosives and other sensitive samples. Optik Photonik 8, 44–47 (2013).
Bloomfield, M. et al. Non-invasive identification of incoming raw pharmaceutical materials using spatially offset Raman spectroscopy. J. Pharm. Biomed. Anal. 76, 65–69 (2013).
Matousek, P. Inverse spatially offset Raman spectroscopy for deep spectroscopy of turbid media. Appl. Spectrosc. 60, 1341–1347 (2006).
Keller, M. D. et al. Development of a spatially offset Raman spectroscopy probe for breast tumor surgical margin evaluation. J. Biomed. Opt. 16, 077006 (2011).
Ma, J. & Ben-Amotz, D. Rapid micro-Raman imaging using fiber-bundle image compression. Appl. Spectrosc. 51, 1845–1848 (1997).
Liao, Z., Sinjab, F., Gibson, G., Padgett, M. & Notingher, I. DMD-based software-configurable spatially-offset Raman spectroscopy for spectral depth-profiling of optically turbid samples. Opt. Express 24, 12701 (2016).
Schulmerich, M. V., Dooley, K. A., Morris, M. D., Vanasse, T. M. & Goldstein, S. A. Transcutaneous fiber optic Raman spectroscopy of bone using annular illumination and a circular array of collection fibers. J. Biomed. Opt. 11, 060502 (2006).
Eliasson, C., Claybourn, M. & Matousek, P. Deep subsurface Raman spectroscopy of turbid media by a defocused collection system. Appl Spectrosc 61, 1123–1127 (2007).
Conti, C., Realini, M., Colombo, C. & Matousek, P. Comparison of key modalities of micro-scale spatially offset Raman spectroscopy. Analyst 140, 8127–8133 (2015).
Matousek, P. & Parker, A. W. Bulk Raman analysis of pharmaceutical tablets. Appl. Spectrosc. 60, 1353–1357 (2006). This paper is the first demonstration of TRS volumetric sensing capability.
Stone, N., Faulds, K., Graham, D. & Matousek, P. Prospects of deep Raman spectroscopy for noninvasive detection of conjugated surface enhanced resonance Raman scattering nanoparticles buried within 25 mm of mammalian tissue. Anal. Chem. 82, 3969–3973 (2010). This paper is the first conceptual demonstration of SESORS.
Stone, N. et al. Surface enhanced spatially offset Raman spectroscopic (SESORS) imaging — the next dimension. Chem. Sci. 2, 776 (2011). This paper is the first demonstration of SESORS imaging.
Sharma, B., Frontiera, R. R., Henry, A., Ringe, E. & Van Duyne, R. P. SERS: materials, applications, and the future surface enhanced Raman spectroscopy (SERS) is a powerful vibrational. Mater. Today 15, 16–25 (2012).
Jeanmaire, D. L. & Van Duyne, R. P. Surface Raman spectroelectrochemistry. Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode. J. Electroanal. Chem. 84, 1–20 (1977).
Hao, E. & Schatz, G. C. Electromagnetic fields around silver nanoparticles and dimers. J. Chem. Phys. 120, 357–366 (2004).
Qian, X. et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 26, 83 (2007).
Moore, T. J. et al. In vitro and in vivo SERS biosensing for disease diagnosis. Biosensors 8, 46 (2018).
Schlücker, S. Surface-enhanced Raman spectroscopy: concepts and chemical applications. Angew. Chemie Int. Ed. 53, 4756–4795 (2014).
Gardner, B., Stone, N. & Matousek, P. Noninvasive simultaneous monitoring of pH and depth using surface-enhanced deep Raman spectroscopy. J. Raman Spectrosc. 51, 1078–1082 (2020). This paper is the first conceptual demonstration of SESORS to measure pH.
Laing, S., Gracie, K. & Faulds, K. Multiplex in vitro detection using SERS. Chem. Soc. Rev. 45, 1901–1918 (2016).
Conti, C., Colombo, C., Realini, M., Zerbi, G. & Matousek, P. Subsurface Raman analysis of thin painted layers. Appl. Spectrosc. 68, 686–691 (2014). This paper is the first conceptual demonstration of micro-SORS, a high-resolution variant of spatially offset Raman spectroscopy.
Matousek, P., Conti, C., Realini, M. & Colombo, C. Micro-scale spatially offset Raman spectroscopy for non-invasive subsurface analysis of turbid materials. Analyst 141, 731–739 (2016).
Buckley, K. et al. Non-invasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags. Analyst 141, 1678–1685 (2016).
Di, Z. et al. Spatially offset Raman microspectroscopy of highly scattering tissue: theory and experiment. J. Mod. Opt. 62, 97–101 (2015).
Conti, C. et al. Analytical capability of defocused µ-SORS in the chemical interrogation of thin turbid painted layers. Appl Spectrosc. 70, 156–161 (2016).
Gardner, B., Stone, N. & Matousek, P. Noninvasive determination of depth in transmission Raman spectroscopy in turbid media based on sample differential transmittance. Anal. Chem. 89, 9730–9733 (2017).
Widjaja, E. et al. Band-target entropy minimization (BTEM) applied to hyperspectral Raman image data. Appl. Spectrosc. 57, 1353–1362 (2003).
Churchwell, J. H. et al. Adaptive band target entropy minimization: optimization for the decomposition of spatially offset Raman spectra of bone. J Raman Spectrosc. 51, 66–78 (2020).
Chen, K., Massie, C. & Berger, A. J. Soft-tissue spectral subtraction improves transcutaneous Raman estimates of murine bone strength in vivo. J. Biophotonics 13, 1–11 (2020).
Matousek, P. et al. Numerical simulations of subsurface probing in diffusely scattering media using spatially offset Raman spectroscopy. Appl. Spectrosc. 59, 1485–1492 (2005).
Keller, M. D., Wilson, R. H., Mycek, M.-A. & Mahadevan-Jansen, A. Monte Carlo model of spatially offset Raman spectroscopy for breast tumor margin analysis. Appl. Spectrosc. 64, 607–614 (2010).
Rencher, A. C. Methods of multivariate analysis. Choice Rev. Online 33, 33-1586–33-1586 (1995).
Griffen, J. A., Owen, A. W., Burley, J., Taresco, V. & Matousek, P. Rapid quantification of low level polymorph content in a solid dose form using transmission Raman spectroscopy. J. Pharm. Biomed. Anal. 128, 35–45 (2016).
Kwang, S. Y. & Frontiera, R. R. Spatially offset femtosecond stimulated Raman spectroscopy: observing exciton transport through a vibrational lens. J. Phys. Chem. Lett. 11, 4337–4344 (2020).
Samuel, A. Z., Yabumoto, S., Kawamura, K. & Iwata, K. Rapid microstructure characterization of polymer thin films with 2D-array multifocus Raman microspectroscopy. Analyst 140, 1847–1851 (2015).
Shin, K. & Chung, H. Wide area coverage Raman spectroscopy for reliable quantitative analysis and its applications. Analyst 138, 3335–3346 (2013).
Paudel, A., Raijada, D. & Rantanen, J. Raman spectroscopy in pharmaceutical product design. Adv. Drug Deliv. Rev. 89, 3–20 (2015).
Kim, M., Chung, H. & Jung, Y. M. Accurate determination of polyethylene pellet density using transmission Raman spectroscopy. J. Raman Spectrosc. 42, 1967–1976 (2011).
Hooijschuur, J. H., Iping Petterson, I. E., Davies, G. R., Gooijer, C. & Ariese, F. Time resolved Raman spectroscopy for depth analysis of multi-layered mineral samples. J. Raman Spectrosc. 44, 1540–1547 (2013).
Verkaaik, M. F. C., Hooijschuur, J. H., Davies, G. R. & Ariese, F. Raman spectroscopic techniques for planetary exploration: detecting microorganisms through minerals. Astrobiology 15, 697–707 (2015).
Matthiae, M. & Kristensen, A. Hyperspectral spatially offset Raman spectroscopy in a microfluidic channel. Opt. Express 27, 3782 (2019).
Loeffen, P. W. et al. in Optics and Photonics for Counterterrorism and Crime Fighting. VII; Optical Materials in Defence Systems Technology VIII; and Quantum-Physics-based Information Security Vol. 8189 (International Society for Optics and Photonics, 2011).
Eliasson, C. & Matousek, P. Noninvasive authentication of pharmaceutical products through packaging using spatially offset Raman spectroscopy. Anal. Chem. 79, 1696–1701 (2007).
Eliasson, C. & Matousek, P. RAMAN SPECTROSCOPY: spatial offset broadens applications for Raman spectroscopy. LaserFocusWorld https://www.laserfocusworld.com/test-measurement/test-measurement/article/16552969/raman-spectroscopy-spatial-offset-broadens-applications-for-raman-spectroscopy (2007).
Johansson, J., Sparen, A., Svensson, O., Folestad, S. & Claybourn, M. Quantitative transmission Raman spectroscopy of pharmaceutical tablets and capsules. Appl. Spectrosc. 61, 1211–1218 (2007).
Matousek, P. & Parker, A. W. Non-invasive probing of pharmaceutical capsules using transmission Raman spectroscopy. J. Raman Spectrosc. 38, 563–567 (2007).
Griffen, J. A., Owen, A. W., Andrews, D. & Matousek, P. Recent advances in pharmaceutical analysis using transmission Raman spectroscopy. Spectroscopy 32, 37–43 (2017).
FDA, Food and Drug Administration. CFR — Code of Federal Regulations Title 21 (FDA, 2018).
Aina, A., Hargreaves, M. D., Matousek, P. & Burley, J. C. Transmission Raman spectroscopy as a tool for quantifying polymorphic content of pharmaceutical formulations. Analyst 135, 2328 (2010).
Song, S. W. et al. Hyperspectral Raman line mapping as an effective tool to monitor the coating thickness of pharmaceutical tablets. Anal. Chem. 91, 5810–5816 (2019).
Eliasson, C., Macleod, N. A. & Matousek, P. Noninvasive detection of concealed liquid explosives using Raman spectroscopy. Anal. Chem. 79, 8185–8189 (2007).
Stokes, R. J. et al. in Optics and Photonics for Counterterrorism, Crime Fighting and Defence XII vol. 9995 (International Society for Optics and Photonics, 2016).
Zachhuber, B., Gasser, C., Chrysostom, E. T. H. & Lendl, B. Stand-off spatial offset Raman spectroscopy for the detection of concealed content in distant objects. Anal Chem 83, 9424–9438 (2011).
Cletus, B. et al. Combined time- and space-resolved Raman spectrometer for the non-invasive depth profiling of chemical hazards. Anal. Bioanal. Chem. 403, 255–263 (2012).
R. J. Hopkins, S. H. P. & Shand, N. C. Short-wave infrared excited spatially offset Raman spectroscopy (SORS) for through-barrier detection. Analyst 137, 4408 (2012).
Lewis, I. R., Daniel, N. W. & Griffiths, P. R. Interpretation of Raman spectra of nitro-containing explosive materials. Part I: group frequency and structural class membership. Appl. Spectrosc. 51, 1854–1867 (1997).
Daniel, N. W., Lewis, I. R. & Griffiths, P. R. Interpretation of Raman spectra of nitro-containing explosive materials. Part II: the implementation of neural, fuzzy, and statistical models for unsupervised pattern recognition. Appl. Spectrosc. 51, 1868–1879 (1997).
Schulmerich, M. V. et al. in Biomedical Vibrational Spectroscopy III: Advances in Research and Industry (International Society for Optics and Photonics, 2006).
Dooley, M., McLaren, J., Rose, F. R. A. J. & Notingher, I. Investigating the feasibility of spatially offset Raman spectroscopy for in-vivo monitoring of bone healing in rat calvarial defect models. J. Biophotonics 13, e202000190 (2020).
Stone, N. & Matousek, P. Advanced transmission Raman spectroscopy: a promising tool for breast disease diagnosis. Cancer Res. 68, 4424–4430 (2008).
Stone, N., Baker, R., Rogers, K., Parker, A. W. & Matousek, P. Subsurface probing of calcifications with spatially offset Raman spectroscopy (SORS): future possibilities for the diagnosis of breast cancer. Analyst 132, 899–905 (2007).
Gardner, B., Matousek, P. & Stone, N. Subsurface chemically specific measurement of pH levels in biological tissues using combined surface-enhanced and deep Raman. Anal. Chem. 91, 10984–10987 (2019).
Keller, M. D., Majumder, S. K. & Mahadevan-Jansen, A. Spatially offset Raman spectroscopy of layered soft tissues. Opt. Lett. 34, 926–928 (2009).
Schulmerich, M. V., Finney, W. F., Fredricks, R. A. & Morris, M. D. Subsurface Raman spectroscopy and mapping using a globally illuminated non confocal fiber optic array probe in the presence of Raman photon migration. Appl Spectrosc. 60, 109 (2006).
Schulmerich, M. V. et al. Noninvasive Raman tomographic imaging of canine bone tissue. J. Biomed. Opt. 13, 020506 (2008).
Srinivasan, S. et al. Image-guided Raman spectroscopic recovery ofcanine cortical bone contrast in situ. Opt. Express 16, 12190 (2008).
Demers, J.-L. H., Esmonde-White, F. W. L., Esmonde-White, K. A., Morris, M. D. & Pogue, B. W. Next-generation Raman tomography instrument for non-invasive in vivo bone imaging. Biomed. Opt. Express 6, 793 (2015).
Demers, J.-L., Davis, S., Pogue, B. W. & Morris, M. D. in Biomedical Optics and 3-D Imaging, OSA Technical Digest (Optical Society of America, 2012).
Jiang, S., Pogue, B. W., Laughney, A. M., Kogel, C. A. & Paulsen, K. D. Measurement of pressure-displacement kinetics of hemoglobin in normal breast tissue with near-infrared spectral imaging. Appl. Opt. 48, D130–D136 (2009).
Sil, S. & Umapathy, S. Raman spectroscopy explores molecular structural signatures of hidden materials in depth: universal multiple angle Raman spectroscopy. Sci. Rep. 4, 5308 (2015).
Gardner, B., Stone, N. & Matousek, P. Non-invasive chemically specific measurement of subsurface temperature in biological tissues using surface-enhanced spatially offset Raman spectroscopy. Faraday Discuss. 187, 329–339 (2016). This paper is the first conceptual demonstration of T-SESORS, a variant of SESORS and TRS.
Gardner, B., Matousek, P. & Stone, N. Direct monitoring of light mediated hyperthermia induced within mammalian tissues using surface enhanced spatially offset Raman spectroscopy (T-SESORS). Analyst 144, 3552–3555 (2019).
Vardaki, M. Z. et al. Raman spectroscopy of stored red blood cell concentrate within sealed transfusion blood bags. Analyst 143, 6006–6013 (2018).
Vardaki, M. Z. & Kourkoumelis, N. Tissue phantoms for biomedical applications in Raman spectroscopy: a review. Biomed. Eng. Comput. Biol. 11, 1–15 (2020).
Nicolson, F. et al. Non-invasive in vivo imaging of cancer using surface-enhanced spatially offset Raman spectroscopy (SESORS). Theranostics 9, 5899–5913 (2019).
Ma, K. et al. In vivo, transcutaneous glucose sensing using surface-enhanced spatially offset Raman spectroscopy: multiple rats, improved hypoglycemic accuracy, low incident power, and continuous monitoring for greater than 17 days. Anal. Chem. 83, 9146–9152 (2011).
Sharma, B., Ma, K., Glucksberg, M. R. & Van Duyne, R. P. Seeing through bone with surface-enhanced spatially offset Raman spectroscopy. J. Am. Chem. Soc. 135, 17290–17293 (2013).
Moody, A. S., Baghernejad, P. C., Webb, K. R. & Sharma, B. Surface enhanced spatially offset Raman spectroscopy detection of neurochemicals through the skull. Anal. Chem. 89, 5688–5692 (2017).
Moody, A. S., Payne, T. D., Barth, B. A. & Sharma, B. Surface-enhanced spatially-offset Raman spectroscopy (SESORS) for detection of neurochemicals through the skull at physiologically relevant concentrations. Analyst 145, 1885–1893 (2020).
Qin, J., Chao, K. & Kim, M. S. Nondestructive evaluation of internal maturity of tomatoes using spatially offset Raman spectroscopy. Postharvest Biol. Technol. 71, 21–31 (2012).
Morey, R. et al. Non-invasive identification of potato varieties and prediction of the origin of tuber cultivation using spatially offset Raman spectroscopy. Anal. Bioanal. Chem. 412, 4585–4594 (2020).
Ellis, D. I. et al. Through-container, extremely low concentration detection of multiple chemical markers of counterfeit alcohol using a handheld SORS device. Sci. Rep. 7, 12082 (2017).
Conti, C. et al. Advances in Raman spectroscopy for the non-destructive subsurface analysis of artworks: micro-SORS. J. Cult. Herit. 43, 319–328 (2020).
Botteon, A. et al. Non-invasive characterisation of molecular diffusion of agent into turbid matrix using micro-SORS. Talanta 218, 121078 (2020).
Janssens, K., Dik, J., Cotte, M. & Susini, J. Photon-based techniques for nondestructive subsurface analysis of painted cultural heritage artifacts. Acc. Chem. Res. 43, 814–825 (2010).
Tournié, A. et al. Ancient Greek text concealed on the back of unrolled papyrus revealed through shortwave-infrared hyperspectral imaging. Sci. Adv. 5, 1–9 (2019).
Brunetti, B. et al. Non-invasive investigations of paintings by portable instrumentation: the MOLAB experience. Top. Curr. Chem. 374, 1–35 (2016).
Realini, M., Conti, C., Botteon, A., Colombo, C. & Matousek, P. Development of a full micro-scale spatially offset Raman spectroscopy prototype as a portable analytical tool. Analyst 142, 351–355 (2017).
Botteon, A. et al. Non-invasive and in situ investigation of layers sequence in panel paintings by portable micro-spatially offset Raman spectroscopy. J. Raman Spectrosc. 51, 2016–2021 (2020).
Casadio, F., Daher, C. & Bellot-Gurlet, L. Raman spectroscopy of cultural heritage materials: overview of applications and new frontiers in instrumentation, sampling modalities, and data processing. Top. Curr. Chem. 374, 62 (2016).
Stone, N., Kendall, C. & Barr, H. in Handbook of Vibrational Spectroscopy (ed. Diem, M.) 203–230 (Wiley, 2008).
Isabelle, M. et al. Multi-centre Raman spectral mapping of oesophageal cancer tissues: a study to assess system transferability. Faraday Discuss. 187, 87–103 (2016).
Harvey, C. E. et al. Looking inside catalyst extrudates with time-resolved surface-enhanced Raman spectroscopy (TR-SERS). Appl. Spectrosc. 66, 1179–1185 (2012).
Corden, C., Matousek, P., Conti, C. & Notingher, I. Sub-surface molecular analysis and imaging in turbid media using time-gated Raman spectral multiplexing. Appl. Spectrosc. 75, 156–167 (2020).
Kekkonen, J., Nissinen, J. & Nissinen, I. Depth analysis of semi-transparent media by a time-correlated CMOS SPAD line sensor-based depth-resolving Raman spectrometer. IEEE Sens. J. 19, 6711–6720 (2019).
Bersani, D., Conti, C., Matousek, P., Pozzi, F. & Vandenabeele, P. Methodological evolutions of Raman spectroscopy in art and archaeology. Anal. Methods 8, 8395–8409 (2016).
Conti, C., Botteon, A., Colombo, C., Realini, M. & Matousek, P. Investigation of heterogeneous painted systems by micro-spatially offset Raman spectroscopy. Anal. Chem. 89, 11476–11483 (2017).
Botteon, A. et al. Exploring street art paintings by microspatially offset Raman spectroscopy. J. Raman Spectrosc. 49, 1652–1659 (2018).
Barnett, P. D. & Angel, S. M. Miniature spatial heterodyne Raman spectrometer with a cell phone camera detector. Appl. Spectrosc. 71, 988–995 (2017).
Kiefer, J. Transmission Raman spectroscopy for pharmaceutical analysis. American Pharmaceutical Review https://www.americanpharmaceuticalreview.com/Featured-Articles/358425-Transmission-Raman-Spectroscopy-for-Pharmaceutical-Analysis/ (2019).
Loeffen, P. W. et al. in Optics and Photonics for Counterterrorism, Crime Fighting, and Defence XII (eds Burgess, D. et al.) 12 (SPIE, 2016).
Waldron, A., Allen, A., Colón, A., Carter, J. C. & Angel, S. M. A monolithic spatial heterodyne Raman spectrometer: initial tests. Appl. Spectrosc. 75, 57–69 (2021).
Griffen, J. A., Owen, A. W. & Matousek, P. Development of transmission Raman spectroscopy towards the in line, high throughput and non-destructive quantitative analysis of pharmaceutical solid oral dose. Analyst 140, 107–112 (2015).
Loeffen, P. W. et al. in Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE). Sensing XII Vol. 8018, 80181E (International Society for Optics and Photonics, 2011).
Thomas, K. J., Sheeba, M., Nampoori, V. P. N., Vallabhan, C. P. G. & Radhakrishnan, P. Raman spectra of polymethyl methacrylate optical fibres excited by a 532 nm diode pumped solid state laser. J. Opt. A Pure Appl. Opt. 10, 1–6 (2008).
This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) grant EP/R020965/1.
The authors declare that they are bound by confidentiality agreements that prevent them from disclosing their competing interests in this work.
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ChemSpider database: http://www.chemspider.com/Spectra.aspx?st=R
Gaussian software package: https://gaussian.com/
KnowItAll Raman Spectral Database Collection: https://sciencesolutions.wiley.com/solutions/technique/raman/knowitall-raman-collection/
- Rayleigh scattering
The elastic scattering of electromagnetic radiation by particles smaller than the wavelength of the radiation.
The degree to which a molecular dipole changes in response to an external electric field.
- Raman scattering
The inelastic scattering of photons, where the frequency of the scattered photon is different from that of the incident photon.
- Photon shot noise
Fluctuations of the detected number of photons, caused by the inherent particle-like properties of photons.
- Lambert’s cosine law
A law describing the cosine dependence of light emission intensity with respect to the angle of incidence from the surface normal.
- Solid angle
A measure of the amount of the field of view that an object occupies from a particular point.
- Acceptance angle
The maximum incidence angle of an optical ray that is transmitted to the spectrograph, measured from the optical axis of the spectrograph.
- Cosmic rays
High-energy protons and atomic nuclei that move through space at nearly the speed of light.
- Surface plasmon resonance
A resonant oscillation of nanoparticle conduction electrons induced by incident light; its spectral properties are dependent on nanoparticle size, shape and metal type.
- Monte Carlo simulations
Numerical algorithms that rely on the random sampling of events.
- Imaging phantoms
Specially prepared samples that mimic the properties of real biological tissue for the purposes of optical imaging.
Identical chemicals of different crystalline forms.
Wave-like modulation of charge-coupled device (CCD) sensitivity across the sensor caused by light interference and associated with back-illuminated CCDs.
- Read-out noise
Noise induced by charge digitization circuitry, imprinted on the signal when it is read.
- Thermal noise
Noise induced by thermal fluctuations of charge carriers within a detection element.
- Instrument response function
In the context of spatially offset Raman spectroscopy, a combined spectrograph–detector spectral intensity profile in response to illumination by a spectrally uniform light source.
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Cite this article
Mosca, S., Conti, C., Stone, N. et al. Spatially offset Raman spectroscopy. Nat Rev Methods Primers 1, 21 (2021). https://doi.org/10.1038/s43586-021-00019-0
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