Challenges in application of Raman spectroscopy to biology and materials

Raman spectroscopy has become an essential tool for chemists, physicists, biologists and materials scientists. In this article, we present the challenges in unravelling the molecule-specific Raman spectral signatures of different biomolecules like proteins, nucleic acids, lipids and carbohydrates based on the review of our work and the current trends in these areas. We also show how Raman spectroscopy can be used to probe the secondary and tertiary structural changes occurring during thermal denaturation of protein and lysozyme as well as more complex biological systems like bacteria. Complex biological systems like tissues, cells, blood serum etc. are also made up of such biomolecules. Using mice liver and blood serum, it is shown that different tissues yield their unique signature Raman spectra, owing to a difference in the relative composition of the biomolecules. Additionally, recent progress in Raman spectroscopy for diagnosing a multitude of diseases ranging from cancer to infection is also presented. The second part of this article focuses on applications of Raman spectroscopy to materials. As a first example, Raman spectroscopy of a melt cast explosives formulation was carried out to monitor the changes in the peaks which indicates the potential of this technique for remote process monitoring. The second example presents various modern methods of Raman spectroscopy such as spatially offset Raman spectroscopy (SORS), reflection, transmission and universal multiple angle Raman spectroscopy (UMARS) to study layered materials. Studies on chemicals/layered materials hidden in non-metallic containers using the above variants are presented. Using suitable examples, it is shown how a specific excitation or collection geometry can yield different information about the location of materials. Additionally, it is shown that UMARS imaging can also be used as an effective tool to obtain layer specific information of materials located at depths beyond a few centimeters.

[1]  C. Eliasson,et al.  Non-invasive quantitative assessment of the content of pharmaceutical capsules using transmission Raman spectroscopy. , 2008, Journal of pharmaceutical and biomedical analysis.

[2]  Paul Ruffin,et al.  Raman monitoring and evaluation of the aging effects of rocket propellant stabilizers , 2017, Optical Engineering + Applications.

[3]  A. Kaczor,et al.  Raman spectroscopy of proteins: a review , 2013 .

[4]  Kamila Kochan,et al.  Raman and infrared spectroscopy of carbohydrates: A review. , 2017, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[5]  R. Dasari,et al.  Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes , 2017, Oncotarget.

[6]  J. Duguid,et al.  Raman spectroscopy of DNA-metal complexes. I. Interactions and conformational effects of the divalent cations: Mg, Ca, Sr, Ba, Mn, Co, Ni, Cu, Pd, and Cd. , 1993, Biophysical journal.

[7]  I. Lednev,et al.  Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia , 2015, Journal of biophotonics.

[8]  J. Shreeve,et al.  Synthesis and promising properties of a new family of high-density energetic salts of 5-nitro-3-trinitromethyl-1H-1,2,4-triazole and 5,5'-bis(trinitromethyl)-3,3'-azo-1H-1,2,4-triazole. , 2011, Journal of the American Chemical Society.

[9]  S. Asher,et al.  Dependence of the peptide amide III vibration on the phi dihedral angle. , 2001, Journal of the American Chemical Society.

[10]  A. Sikder,et al.  Review on Melt Cast Explosives , 2011 .

[11]  S. Hamodrakas,et al.  Laser Raman studies of protein conformation in the silkmoth chorion. , 1982, Biochimica et biophysica acta.

[12]  Andre K. Geim,et al.  Raman spectrum of graphene and graphene layers. , 2006, Physical review letters.

[13]  G. Thomas,et al.  Raman studies of nucleic acids. II. Aqueous purine and pyrimidine mixtures. , 1967, Biochimica et biophysica acta.

[14]  D. L. Jeanmaire,et al.  Surface raman spectroelectrochemistry: Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode , 1977 .

[15]  Mark R. Kagan,et al.  Reduction of Fluorescence Interference in Raman Spectroscopy via Analyte Adsorption on Graphitic Carbon , 1994 .

[16]  Y. Gupta,et al.  Raman spectroscopy of high-pressure-high-temperature polymorph of hexahydro-1,3,5-trinitro-1,3,5-triazine (epsilon-RDX). , 2010, The journal of physical chemistry. A.

[17]  R. Dasari,et al.  Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS) , 1997 .

[18]  D. Weitz,et al.  Diffusing wave spectroscopy. , 1988, Physical review letters.

[19]  S. Bykov,et al.  Peptide secondary structure folding reaction coordinate: correlation between uv raman amide III frequency, Psi Ramachandran angle, and hydrogen bonding. , 2006, The journal of physical chemistry. B.

[20]  R. Tuma.  Raman spectroscopy of proteins: from peptides to large assemblies , 2005 .

[21]  Freek Ariese,et al.  Raman and mid-infrared spectroscopic imaging: applications and advancements , 2015 .

[22]  M. Diem,et al.  Parasites under the Spotlight: Applications of Vibrational Spectroscopy to Malaria Research. , 2018, Chemical reviews.

[23]  Kamila Kochan,et al.  Raman spectroscopy of lipids: a review , 2015 .

[24]  A. Rangarajan,et al.  Different Phases of Breast Cancer Cells: Raman Study of Immortalized, Transformed, and Invasive Cells , 2016, Biosensors.

[25]  F. Bonnier,et al.  Raman spectral analysis for rapid screening of dengue infection. , 2018, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[26]  R. McCreery,et al.  Raman Spectroscopy of Carbon Materials: Structural Basis of Observed Spectra , 1990 .

[27]  Kevin Petrecca,et al.  Raman spectroscopy detects distant invasive brain cancer cells centimeters beyond MRI capability in humans. , 2016, Biomedical optics express.

[28]  B. Vanderhyden,et al.  Raman micro‐spectroscopy applied to treatment resistant and sensitive human ovarian cancer cells , 2017, Journal of biophotonics.

[29]  C. García-Ruiz,et al.  Surface-enhanced Raman spectroscopy for the analysis of smokeless gunpowders and macroscopic gunshot residues , 2016, Analytical and Bioanalytical Chemistry.

[30]  Yukihiro Ozaki,et al.  Raman, Infrared, and Near-Infrared Chemical Imaging: Sasic/Chemical Imaging , 2010 .

[31]  T. Shimanouchi,et al.  Interpretation of the doublet at 850 and 830 cm-1 in the Raman spectra of tyrosyl residues in proteins and certain model compounds. , 1975, Biochemistry.

[32]  P. Carey,et al.  Raman crystallography and other biochemical applications of Raman microscopy. , 2006, Annual review of physical chemistry.

[33]  Jing Kong,et al.  Can graphene be used as a substrate for Raman enhancement? , 2010, Nano letters.

[34]  P. J. Hendra,et al.  Fiber optic probe for remote Raman spectrometry , 1983 .

[35]  M. Fleischmann,et al.  Raman spectra of pyridine adsorbed at a silver electrode , 1974 .

[36]  W. Xie,et al.  Medical applications of surface-enhanced Raman scattering. , 2013, Physical chemistry chemical physics : PCCP.

[37]  Volker Deckert,et al.  Tip-enhanced Raman spectroscopy of single RNA strands: towards a novel direct-sequencing method. , 2008, Angewandte Chemie.

[38]  S. Cai,et al.  Identification of beta-turn and random coil amide III infrared bands for secondary structure estimation of proteins. , 1999, Biophysical chemistry.

[39]  Development of a label-free Raman imaging technique for differentiation of malaria parasite infected from non-infected tissue. , 2018, The Analyst.

[40]  I. Harada,et al.  Characterization of individual tryptophan side chains in proteins using Raman spectroscopy and hydrogen-deuterium exchange kinetics. , 1988, Biochemistry.

[41]  Brandy Broadbent,et al.  Intraoperative Raman Spectroscopy. , 2017, Neurosurgery clinics of North America.

[42]  Salvador Ventura,et al.  Protein misfolding diseases , 2015, Future science OA.

[43]  David M. Tanenbaum,et al.  Remote spectroscopic analysis of ppm‐level air pollutants by Raman spectroscopy , 1973 .

[44]  Lim Chwee Ming,et al.  Real time near-infrared Raman spectroscopy for the diagnosis of nasopharyngeal cancer , 2017, Oncotarget.

[45]  S. Umapathy,et al.  Is Chemically Synthesized Graphene ‘Really’ a Unique Substrate for SERS and Fluorescence Quenching? , 2013, Scientific Reports.

[46]  Jean-Luc Bruneel,et al.  Raman spectroscopy as a tool for the analysis of carbon-based materials (highly oriented pyrolitic graphite, multilayer graphene and multiwall carbon nanotubes) and of some of their elastomeric composites , 2014 .

[47]  Rekha Gautam,et al.  Review of multidimensional data processing approaches for Raman and infrared spectroscopy , 2015, EPJ Techniques and Instrumentation.

[48]  Soo Yeol Lee,et al.  Dual-modal cancer detection based on optical pH sensing and Raman spectroscopy , 2017, Journal of biomedical optics.

[49]  Mike Bailey,et al.  New capability for hazardous materials ID within sealed containers using a portable spatially offset Raman spectroscopy (SORS) device , 2016, Security + Defence.

[50]  Jonas Johansson,et al.  Quantitative Transmission Raman Spectroscopy of Pharmaceutical Tablets and Capsules , 2007, Applied spectroscopy.

[51]  Duncan Graham,et al.  Surface-enhanced Raman scattering , 1998 .

[52]  A. Dunker,et al.  Determination of the secondary structure of proteins from the amide I band of the laser Raman spectrum. , 1981, Journal of molecular biology.

[53]  Maria Lepore,et al.  Micro-Raman Spectroscopy for Monitoring Changes in Periodontal Ligaments and Gingival Crevicular Fluid , 2014, Sensors.

[54]  M. Procházka,et al.  Drop coating deposition Raman spectroscopy of liposomes: role of cholesterol. , 2013, Chemistry and physics of lipids.

[55]  Luc Moens,et al.  A decade of Raman spectroscopy in art and archaeology. , 2007, Chemical reviews.

[56]  William F. Finney,et al.  Subsurface Probing in Diffusely Scattering Media Using Spatially Offset Raman Spectroscopy , 2005, Applied spectroscopy.

[57]  K. Somasundaram,et al.  Raman and infra-red microspectroscopy: towards quantitative evaluation for clinical research by ratiometric analysis. , 2016, Chemical Society reviews.

[58]  I. Holen,et al.  Raman spectroscopic analysis differentiates between breast cancer cell lines , 2015 .

[59]  R. Das,et al.  Raman spectroscopy: Recent advancements, techniques and applications , 2011 .

[60]  P. Dore,et al.  Raman analysis of insulin denaturation induced by high‐pressure and thermal treatments , 2012 .

[61]  G. Bergmann,et al.  Die Intensität des Ramanspektrums polykristalliner Substanzen , 1967 .

[62]  P. Matousek,et al.  Micro-scale spatially offset Raman spectroscopy for non-invasive subsurface analysis of turbid materials. , 2016, The Analyst.

[63]  Hideo Takeuchi,et al.  Raman structural markers of tryptophan and histidine side chains in proteins. , 2003, Biopolymers.

[64]  Siva Umapathy,et al.  Raman spectroscopy explores molecular structural signatures of hidden materials in depth: Universal Multiple Angle Raman Spectroscopy , 2014, Scientific Reports.

[65]  S. Umapathy,et al.  Applications of Raman and Infrared Microscopy to Materials and Biology , 2018 .

[66]  Asifullah Khan,et al.  Random Forest-Based Evaluation of Raman Spectroscopy for Dengue Fever Analysis , 2017, Applied spectroscopy.

[67]  P. Guest,et al.  Affinity depletion of plasma and serum for mass spectrometry-based proteome analysis. , 2013, Methods in molecular biology.

[68]  B. Hernández,et al.  All characteristic Raman markers of tyrosine and tyrosinate originate from phenol ring fundamental vibrations , 2016 .

[69]  Volker Deckert,et al.  Advances in TERS (tip-enhanced Raman scattering) for biochemical applications. , 2012, Biochemical Society transactions.

[70]  George J. Thomas,et al.  Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes , 2005 .

[71]  Jimmie C. Oxley,et al.  The Chemistry of Explosives , 1998 .

[72]  Belén Hernández,et al.  Characteristic Raman lines of phenylalanine analyzed by a multiconformational approach , 2013 .

[73]  J. Agrawal,et al.  High Energy Materials , 2010 .

[74]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[75]  J. Rantanen,et al.  Quantification of microwave‐induced amorphization of celecoxib in PVP tablets using transmission Raman spectroscopy , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[76]  Benoît Igne,et al.  Analytical Method Development Using Transmission Raman Spectroscopy for Pharmaceutical Assays and Compliance with Regulatory Guidelines—Part I: Transmission Raman Spectroscopy and Method Development , 2018, Journal of Pharmaceutical Innovation.

[77]  Anita Mahadevan-Jansen,et al.  Clinical characterization of in vivo inflammatory bowel disease with Raman spectroscopy. , 2017, Biomedical optics express.

[78]  Jakub Bielecki,et al.  Molecular characterization of DNA double strand breaks with tip-enhanced Raman scattering. , 2014, Angewandte Chemie.

[79]  R. Goodacre,et al.  Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques , 2017, Scientific Reports.

[80]  Hugh J. Byrne,et al.  Improved protocols for pre-processing Raman spectra of formalin fixed paraffin preserved tissue sections , 2017 .

[81]  M. S. Dresselhausa,et al.  Raman spectroscopy of carbon nanotubes , 2004 .

[82]  V. Kopecký,et al.  Instability of cerebrospinal fluid after delayed storage and repeated freezing: a holistic study by drop coating deposition Raman spectroscopy , 2014, Clinical chemistry and laboratory medicine.

[83]  À. Sierra,et al.  The Lipid Phenotype of Breast Cancer Cells Characterized by Raman Microspectroscopy: Towards a Stratification of Malignancy , 2012, PloS one.

[84]  H. Östmark,et al.  Fourier Transform Raman Spectroscopy of the Four Crystallographic Phases of α, β, γ and ε 2,4,6,8,10,12‐Hexanitro‐2,4,6,8,10,12‐hexaazatetracyclo[5.5.0.05,9.03,11]dodecane (HNIW, CL‐20) , 2004 .

[85]  Menglin Cheng,et al.  Label-Free Raman Spectroscopy Detects Stromal Adaptations in Premetastatic Lungs Primed by Breast Cancer. , 2017, Cancer research.

[86]  Hao Ding,et al.  In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy. , 2017, Biomedical optics express.

[87]  Y. Ozaki,et al.  Conformational changes in seventeen cystine disulfide bridges of bovine serum albumin proved by Raman spectroscopy , 1997, FEBS letters.

[88]  J. Popp,et al.  Quantitative assessment of the degree of lipid unsaturation in intact Mortierella by Raman microspectroscopy , 2015, Analytical and Bioanalytical Chemistry.

[89]  S. Sikdar,et al.  Ascorbate protects neurons against oxidative stress: a Raman microspectroscopic study. , 2015, ACS chemical neuroscience.

[90]  Eric C Le Ru,et al.  Single-molecule surface-enhanced Raman spectroscopy. , 2012, Annual review of physical chemistry.

[91]  M. Dresselhaus,et al.  Perspectives on carbon nanotubes and graphene Raman spectroscopy. , 2010, Nano letters.

[92]  D. Basko,et al.  Raman spectroscopy as a versatile tool for studying the properties of graphene. , 2013, Nature nanotechnology.

[93]  Saranjam Khan,et al.  Lactate based optical screening of dengue virus infection in human sera using Raman spectroscopy. , 2017, Biomedical optics express.

[94]  C. Krishna,et al.  Raman spectroscopic studies of oral cancers: correlation of spectral and biochemical markers , 2014 .

[95]  J. Benevides,et al.  Characterization of DNA structures by Raman spectroscopy: high-salt and low-salt forms of double helical poly(dG-dC) in H2O and D2O solutions and application to B, Z and A-DNA. , 1983, Nucleic acids research.

[96]  M. Procházka,et al.  Drop-Coating Deposition Raman (DCDR) Spectroscopy as a Tool for Membrane Interaction Studies: Liposome–Porphyrin Complex , 2015, Applied spectroscopy.

[97]  J L Lippert,et al.  Determination of the secondary structure of proteins by laser Raman spectroscopy. , 1976, Journal of the American Chemical Society.

[98]  P. Barber.  Absorption and scattering of light by small particles , 1984 .

[99]  M. Albrecht,et al.  Anomalously intense Raman spectra of pyridine at a silver electrode , 1977 .

[100]  D. A. Stuart,et al.  In vivo glucose measurement by surface-enhanced Raman spectroscopy. , 2006, Analytical chemistry.

[101]  R. Bonomo,et al.  Following the reactions of mechanism-based inhibitors with beta-lactamase by Raman crystallography. , 2003, Biochemistry.

[102]  S. Paul,et al.  Protein‐misfolding diseases and chaperone‐based therapeutic approaches , 2006, The FEBS journal.

[103]  N. Maiti,et al.  Raman spectroscopic characterization of secondary structure in natively unfolded proteins: alpha-synuclein. , 2004, Journal of the American Chemical Society.

[104]  J. Bandekar,et al.  Amide modes and protein conformation. , 1992, Biochimica et biophysica acta.

[105]  S. Umapathy,et al.  Density functional theoretical modeling, electrostatic surface potential and surface enhanced Raman spectroscopic studies on biosynthesized silver nanoparticles: observation of 400 PM sensitivity to explosives. , 2014, The journal of physical chemistry. A.

[106]  A. Volkmer,et al.  Subcellular Raman Microspectroscopy Imaging of Nucleic Acids and Tryptophan for Distinction of Normal Human Skin Cells and Tumorigenic Keratinocytes. , 2015, Analytical chemistry.

[107]  K. Somasundaram,et al.  Application of vibrational microspectroscopy to biology and medicine , 2012 .

[108]  Freek Ariese,et al.  Raman and Infra‐Red Microspectroscopy: Towards Quantitative Evaluation for Clinical Research by Ratiometric Analysis , 2016 .

[109]  F. Martin,et al.  Vibrational biospectroscopy coupled with multivariate analysis extracts potentially diagnostic features in blood plasma/serum of ovarian cancer patients , 2014, Journal of biophotonics.

[110]  P. Vandenabeele,et al.  Reference database of Raman spectra of biological molecules , 2007 .

[111]  H. Abramczyk,et al.  Angiogenesis - a crucial step in breast cancer growth, progression and dissemination by Raman imaging. , 2018, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[112]  U. Nongthomba,et al.  Raman spectroscopic studies on screening of myopathies. , 2015, Analytical chemistry.

[113]  R. Williams.  Protein secondary structure analysis using Raman amide I and amide III spectra. , 1986, Methods in enzymology.

[114]  S. Umapathy,et al.  Linking carbon metabolism to carotenoid production in mycobacteria using Raman spectroscopy. , 2015, FEMS microbiology letters.

[115]  Kevin Petrecca,et al.  A new method using Raman spectroscopy for in vivo targeted brain cancer tissue biopsy , 2018, Scientific Reports.

[116]  Sucbei Moon,et al.  Lamellar keratoplasty using position-guided surgical needle and M-mode optical coherence tomography , 2017, Journal of biomedical optics.

[117]  B. Wood,et al.  Raman spectroscopic analysis of Lactobacillus rhamnosus GG in response to dehydration reveals DNA conformation changes , 2017, Journal of biophotonics.

[118]  W. Caughey,et al.  Protein secondary structures in water from second-derivative amide I infrared spectra. , 1990, Biochemistry.

[119]  Holly J. Butler,et al.  Using Raman spectroscopy to characterize biological materials , 2016, Nature Protocols.

[120]  Oliver Stevens,et al.  Developing fibre optic Raman probes for applications in clinical spectroscopy. , 2016, Chemical Society reviews.

[121]  G. Loppnow,et al.  Raman spectroscopy as a discovery tool in carbohydrate chemistry. , 2000, Analytical chemistry.

[122]  Igor K Lednev,et al.  Ultraviolet Resonance Raman Spectroscopic Markers for Protein Structure and Dynamics. , 2017, Trends in analytical chemistry : TRAC.

[123]  Peter J. Artymiuk,et al.  The Structures of the Monoclinic and Orthorhombic Forms of Hen Egg-White Lysozyme at 6 Angstroms Resolution , 1981 .

[124]  C. Tropea,et al.  Light Scattering from Small Particles , 2003 .

[125]  Noor Mohammed,et al.  Raman spectroscopy of endoscopic colonic biopsies from patients with ulcerative colitis to identify mucosal inflammation and healing , 2016, Biomedical optics express.

[126]  Andrew Jirasek,et al.  Raman Spectroscopic Signatures Reveal Distinct Biochemical and Temporal Changes in Irradiated Human Breast Adenocarcinoma Xenografts , 2018, Radiation Research.

[127]  Wolfgang Kiefer,et al.  Recent Advances in linear and nonlinear Raman spectroscopy I , 2007 .

[128]  Alex Henderson,et al.  Spectral discrimination of live prostate and bladder cancer cell lines using Raman optical tweezers. , 2008, Journal of biomedical optics.

[129]  J. Popp,et al.  Fast differentiation of SIRS and sepsis from blood plasma of ICU patients using Raman spectroscopy , 2014, Journal of biophotonics.

[130]  Zhongfan Liu,et al.  Graphene as a substrate to suppress fluorescence in resonance Raman spectroscopy. , 2009, Journal of the American Chemical Society.

[131]  M. Keshavarz,et al.  Raman spectroscopy combined with principle component analysis to investigate the aging of high energy materials , 2017 .

[132]  K A Okotrub,et al.  Raman spectroscopy for DNA quantification in cell nucleus , 2015, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[133]  H. Abramczyk,et al.  The biochemical, nanomechanical and chemometric signatures of brain cancer. , 2018, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[134]  J. Leszczynski,et al.  An analysis of stable forms of CL-20: A DFT study of conformational transitions, infrared and Raman spectra , 2007 .

[135]  Richard L. McCreery,et al.  Raman Spectroscopy for Chemical Analysis , 2000 .

[136]  D. Mcgloin,et al.  Raman spectroscopy for accurately characterizing biomolecular changes in androgen‐independent prostate cancer cells , 2017, Journal of biophotonics.

[137]  M. Delhaye,et al.  Raman confocal microprobing, imaging and fibre‐optic remote sensing: A further step in molecular analysis , 1994 .

[138]  Oliver A. C. Stevens,et al.  Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus. , 2014, Gastrointestinal endoscopy.

[139]  Holly J. Butler,et al.  Gold nanoparticles as a substrate in bio-analytical near-infrared surface-enhanced Raman spectroscopy† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4an01899k Click here for additional data file. , 2015, The Analyst.

[140]  M. Delhaye,et al.  Raman microprobe and microscope with laser excitation , 1975 .

[141]  Manojit Pramanik,et al.  Experimentally validated raman Monte Carlo simulation for a cuboid object to obtain raman spectroscopic signatures for hidden material , 2015 .

[142]  Ishan Barman,et al.  Raman spectroscopy provides a powerful, rapid diagnostic tool for the detection of tuberculous meningitis in ex vivo cerebrospinal fluid samples , 2013, Journal of biophotonics.

[143]  Paul R. Carey,et al.  Biochemical Applications of Raman and Resonance Raman Spectroscopies , 1982 .

[144]  P. Chaturvedi,et al.  In vivo Raman spectroscopy–assisted early identification of potential second primary/recurrences in oral cancers: An exploratory study , 2017, Head & neck.

[145]  Jianmin Wang,et al.  Lipid quantification by Raman microspectroscopy as a potential biomarker in prostate cancer. , 2017, Cancer letters.

[146]  C. García-Ruiz,et al.  Noninvasive detection of concealed explosives: depth profiling through opaque plastics by time-resolved Raman spectroscopy. , 2011, Analytical chemistry.

[147]  A. Matzger,et al.  Cocrystal Engineering of a Prototype Energetic Material: Supramolecular Chemistry of 2,4,6-Trinitrotoluene , 2010 .

[148]  A. Matzger,et al.  Cocrystal Engineering of a High Nitrogen Energetic Material , 2018 .

[149]  G. Thomas.  New structural insights from Raman spectroscopy of proteins and their assemblies. , 2002, Biopolymers.

[150]  Camilo L M Morais,et al.  Raman Spectroscopy to Diagnose Alzheimer's Disease and Dementia with Lewy Bodies in Blood. , 2018, ACS chemical neuroscience.

[151]  Sanchita Sil,et al.  Detection and classification of Bacteria using Raman Spectroscopy Combined with Multivariate Analysis , 2017 .

[152]  Muhammad Bilal,et al.  Optical diagnosis of malaria infection in human plasma using Raman spectroscopy , 2015, Journal of biomedical optics.

[153]  H. Byrne,et al.  Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems. , 2012, The Analyst.

[154]  A. Talari,et al.  Raman Spectroscopy of Biological Tissues , 2007 .

[155]  P. Matousek,et al.  Bulk Raman Analysis of Pharmaceutical Tablets , 2006, Applied spectroscopy.