Medicine and Health Sciences Commons^™

Raman Spectroscopic Analysis Of Human Serum Samples Of Convalescing Covid-19 Positive Patients, Hugh Byrne, Naomi Jackson, Jaythoon Hassan

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Rapid screening, detection and monitoring of viral infection is of critical importance, as exemplified by the rapid spread of SARS-CoV-2, leading to the worldwide pandemic of COVID-19. This is equally the case for the stages of patient convalescence as for the initial stages of infection, to understand the medium and long terms effects, as well as the efficacy of therapeutic interventions. Optical spectroscopic techniques potentially offer an alternative to currently employed techniques of screening for the presence, or the response to infection. In this study, the ability of Raman spectroscopy to distinguish between samples of the serum of convalescent COVID-19 …

Estimating The Analytical Performance Of Raman Spectroscopy For Quantification Of Active Ingredients In Human Stratum Corneum, Hichem Kichou, Emilie Munnier, Yuri Dancik, Kamilia Kemel, Hugh Byrne, Ali Tfayli, Dominique Bertrand, Martin Soucé, Igor Chourpa, Franck Bonnier

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Confocal Raman microscopy (CRM) has become a versatile technique that can be applied routinely to monitor skin penetration of active molecules. In the present study, CRM coupled to multivariate analysis (namely PLSR—partial least squares regression) is used for the quantitative measurement of an active ingredient (AI) applied to isolated (ex vivo) human stratum corneum (SC), using systematically varied doses of resorcinol, as model compound, and the performance is quantified according to key figures of merit defined by regulatory bodies (ICH, FDA, and EMA). A methodology is thus demonstrated to establish the limit of detection (LOD), precision, accuracy, sensitivity (SEN), and …

The Potential Of Raman Spectroscopy In The Diagnosis Of Dysplastic And Malignant Oral Lesions, Ola Ibrahim, M. Toner, Steven Flint, Hugh Byrne, Fiona Lyng

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Early diagnosis, treatment and/or surveillance of oral premalignant lesions are important in preventing progression to oral squamous cell carcinoma (OSCC). The current gold standard is through histopathological diagnosis, which is limited by inter and intra observer and sampling errors. The objective of this work was to use Raman spectroscopy to discriminate between benign, mild, moderate and severe dysplasia and OSCC in formalin fixed paraffin preserved (FFPP) tissues. The study included 72 different pathologies from which 17 were benign lesions, 20 mildly dysplastic, 20 moderately dysplastic, 10 severely dysplastic and 5 invasive OSCC. The glass substrate and paraffin wax background were …

Biomedical Applications Of Vibrational Spectroscopy: Oral Cancer Diagnostics, Hugh Byrne, Isha Behl, Genecy Calado, Ola Ibrahim, M. Toner, Sheila Galvin, Claire M. Healy, Steven Flint, Fiona Lyng

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Vibrational spectroscopy, based on either infrared absorption or Raman scattering, has attracted increasing attention for biomedical applications. Proof of concept explorations for diagnosis of oral potentially malignant disorders and cancer are reviewed, and recent advances critically appraised. Specific examples of applications of Raman microspectroscopy for analysis of histological, cytological and saliva samples are presented for illustrative purposes, and the future prospects, ultimately for routine, chairside in vivo screening are discussed.

Discrimination Of Immune Cell Activation Using Ramanmicro-Spectroscopy In Anin-Vitro & Ex-Vivo Model, Neha Chaudhary, Thi Nguyet Que Nguyen, Daniel Cullen, Aidan Meade, Claire Wynne

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Activation and proliferation of immune cells such as lymphocytes and monocytes are appropriate inflammatory responses to invading pathogens and are key to overcoming an infection. In contrast, uncontrolled and prolonged activation of these cellular signalling pathways can be deleterious to the body and result in the development of autoimmune conditions. The understanding of cellular activatory status therefore plays a significant role in disease diagnosis and progression. Conventional automated approaches such as enzyme linked immunosorbent assays (ELISA) and immune-labelling techniques are time-consuming and expensive, relying on a commercially available and specific antibody to identify cell activation. Developing a label-free method for …

Vibrational Spectroscopy Of Liquid Biopsies For Prostate Cancer Diagnosis, Dinesh Medipally, Daniel Cullen, Valérie Untereiner, G.D. Sockalingum, Adrian Maguire, T.N.Q. Nguyen, Jane Bryant, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Aidan Meade, Fiona Lyng

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Background: Screening for prostate cancer with prostate specific antigen and digital rectal examination allows early diagnosis of prostate malignancy but has been associated with poor sensitivity and specificity. There is also a considerable risk of over-diagnosis and overtreatment, which highlights the need for better tools for diagnosis of prostate cancer. This study investigates the potential of high throughput Raman and Fourier Transform Infrared (FTIR) spectroscopy of liquid biopsies for rapid and accurate diagnosis of prostate cancer.

Methods: Blood samples (plasma and lymphocytes) were obtained from healthy control subjects and prostate cancer patients. FTIR and Raman spectra were recorded from plasma …

Comparability Of Raman Spectroscopic Configurations: A Largescale Cross-Laboratory Study, Shuxia Guo, Hugh Byrne, Shiyamala Duraipandian, Fiona Lyng, Claudia Beleites, Ute Neugebauer

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The variable configuration of Raman spectroscopic platforms is one ofthe major obstacles in establishing Raman spectroscopy as a valuable physicochemicalmethod within real-world scenarios such as clinical diagnostics. For such real worldapplications like diagnostic classification, the models should ideally be usable to predictdata from different setups. Whether it is done by training a rugged model with data frommany setups or by a primary-replica strategy where models are developed on a‘primary’setup and the test data are generated on‘replicate’setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable.However, Raman spectra can be highly sensitive to the …

Training And Technique Choices Predict Self-Reported Running Injuries: An International Study, Joe Warne, Allison H. Gruber, Roy Cheung, Jason Bonacci

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The aim of this study was to describe the self-reported injury, training, and running technique choices of regular runners in four international regions. Design and Setting 756 participants began an expert derived self-report online survey in Ireland, USA, Hong Kong and Australia. Participants 325 participants completed the survey (age=38±10years; weight=68.0±13.1kg; height=1.70±0.10m). Main Outcome Measures Descriptive statistics are reported examining injury incidence and location; shoe and orthosis choices; and training and technique practices. A backwards logistic regression was implemented to examine associations between injury and training choices. Results 68.3% reported having an injury in the last year. 81.45% of these injuries …

Adaptive Background Correction Of Crystal Image Datasets: Towards Automated Process Control, Luke Kiernan, Ian Jones, Lauri Kurki, Patrick J. Cullen, Toufic El Arnaout

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Improving the data descriptor calculation of crystal’s physical properties requires sophisticated imaging techniques and algorithms. It has been possible to construct 2D population balance models benefiting from characteristic measurements of both crystal’s length and width, compared to the single representative sizes used in 1D models. Our aim is to ameliorate the procedure of determining shape (and not only size) factors, in an automated fashion and directly from the process, for implementation in future models. Here, approaches suitable for real-time applications were employed including engineered imaging sensors and adaptive algorithms. We described the latter in detail for varying 2D image datasets. …

Data Mining Raman Microspectroscopic Responses Of Cells To Drugs In Vitro Using Multivariate Curve Resolution-Alternating Least Squares, David Perez-Guaita, Guillermo Quintas, Zeineb Farhane, Roma Tauler, Hugh Byrne

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Raman microspectroscopy is gaining popularity for the analysis of time-dependent biological processes such as drug uptake and cellular response. It is a label-free technique which acquires signals from a large variety of components, including cell biomolecules and exogenous compounds such as drugs and nanoparticles, and is commonly employed for in vitro analysis of cells and cell populations with no labelling or staining required. By monitoring the changes to the Raman spectra of the cell as a result of a perturbing agent (e.g. inoculation of a drug or toxic agent), one can study the associated changes in cell biochemistry involved in …

Recent Advances In The Vibrational Spectroscopic Diagnosis Of Non-Small Cell Lung Cancer, Declan O'Dea, Fiona Lyng, Siobhan Nicholson, Finbar O'Connell, Aoife Maguire, Alison Malkin

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Lung cancer is the leading cause of cancer deaths worldwide accounting for 1.69 million deaths in 2015. Studies have indicated a 5 year survival rate of 8%–15% in western countries, although a survival rate as low as 1% has been demonstrated for late stage diagnosis. With the advent of targeted therapies, it is imperative to accurately differentiate non-small cell lung cancer (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques for the diagnosis of NSCLC are increasingly part of the diagnostic algorithm and clinical work-up of lung cancer patients, however due to the limitation …

Effect Of Neoadjuvant Chemoradiation On Preoperative Pulmonary Physiology, Postoperative Respiratory Complications And Quality Of Life In Patients With Oesophageal Cancer, J. A. Elliott, L. O'Byrne, G. Foley, C. F. Murphy, Suzanne Doyle, S. King, E. M. Guinan, N. Ravi, V. Reynolds

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Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.

Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity …

Raman Spectral Analysis For Rapid Screening Of Dengue Infection, Tahir Mahmood, Haq Nawaz, A. Ditta, M.I. Majeed, M.A. Hanif, N. Rashid, H.N. Bhatti, H.F. Nargis, M. Saleem, Franck Bonnier, Hugh Byrne

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Infection with the dengue virus is currently clinically detected according to different biomarkers in human blood plasma, commonly measured by enzyme linked immunosorbent assays, including non-structural proteins (Ns1), immunoglobulin M (IgM) and immunoglobulin G (IgG). However, there is little or no mutual correlation between the biomarkers, as demonstrated in this study by a comparison of their levels in samples from 17 patients. As an alternative, the label free, rapid screening technique, Raman spectroscopy has been used for the characterisation/diagnosis of healthy and dengue infected human blood plasma samples. In dengue positive samples, changes in specific Raman spectral bands associated with …

Clinical Applications Of Infrared And Raman Spectroscopy: State Of Play And Future Challenges, Matthew Baker, Hugh Byrne, John Chalmers, Peter Gardner, Royston Goodacre, Alex Henderson, Sergei Kazarian, Francis Martin, Julian Moger, Nick Stone, Josep Sule-Suso

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Vibrational spectroscopies, based on Infrared absorption and/or Raman scattering provide a detailed fingerprint of a material, based on the chemical content. Diagnostic and prognostic tools based on these technologies have the potential to revolutionise our clinical systems leading to improved patient outcome, more efficient public services and significant economic savings. However, despite these strong drivers, there are many fundamental scientific and technological challenges which have limited the implementation of this technology in the clinical arena, although recent years have seen significant progress in addressing these challenges. This review examines (i) the state of the art of clinical applications of infrared …

Toxicological Assessment Of Nanomaterials: The Role Of In Vitro Raman Microspectroscopic Analysis, Esen Efeoglu, Marcus Maher, Alan Casey, Hugh Byrne

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The acceleration of nanomaterials research has brought about increased demands for rapid analysis of their bioactivity, in a multi-parametric fashion, to minimise the gap between potential applications and knowledge of their toxicological properties. The potential of Raman microspectroscopy for the analysis of biological systems with the aid of multivariate analysis techniques has been demonstrated. In this study, an overview of recent efforts towards establishing a ‘label-free high content nanotoxicological assessment technique’ using Raman microspectroscopy is presented. The current state of the art for cellular toxicity assessment and the potential of Raman microspectroscopy are discussed, and the spectral markers of the …

Ultra-Filtration Of Human Serum For Improved Quantitative Analysis Of Low Molecular Weight Biomarkers Using Atr-Ir Spectroscopy, Franck Bonnier, Luis Felipe Cs. Carvalho, Matthew J. Baker, Hugh Byrne, Igor Chourpa

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Infrared spectroscopy is a reliable, rapid and cost effective characterisation technique, delivering a molecular finger print of the sample. It is expected that its sensitivity would enable detection of small chemical variations in biological samples associated with disease. ATR-IR is particularly suitable for liquid sample analysis and, although air drying is commonly performed before data collection, just a drop of human serum is enough for screening and early diagnosis. However, the dynamic range of constituent biochemical concentrations in the serum composition remains a limiting factor to the reliability of the technique. Using glucose as a model spike in human serum, …

Screening The Low Molecular Weight Fraction Of Human Serum Using Atr-Ir Spectroscopy, Franck Bonnier, Matthew J. Baker, Hugh Byrne

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Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. …

Recent Advances In Optical Diagnosis Of Oral Cancers: Review And Future Perspectives, Ola Ibrahim, Hugh Byrne, Fiona Lyng, Surya Singh, Jopi Mikkonen, Arto Koistinen, Arja Kullaa

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Optical diagnosis techniques offer several advantages over traditional approaches, including objectivity, speed and cost, and these label-free, non-invasive methods have the potential to change the future work-flow of cancer management. The oral cavity is particularly accessible and thus such methods may serve as alternate/adjunct tools to traditional methods. Recently, in vivo human clinical studies have been initiated with a view to clinical translation of such technologies. A comprehensive review of optical methods in oral cancer diagnosis is presented. Following an introduction to the epidemiology and aetiological factors associated with oral cancers currently employed diagnostic methods and their limitations are presented. …

Methodologies And Considerations For Bladder Cancer Detection With Raman Based Urine Cytology, Laura T. Kerr, Thérése M. Lynn, Ivor M. Cullen, Padraig J. Daly, Nigam Shah, Shirley O'Dea, Alison Malkin, Bryan M. Hennelly

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Bladder cancer has the highest recurrence rate of any cancer. The American Urological Association recommends cystoscopic surveillance every 3–6 months for 3 years, and at least once a year thereafter, particularly for high-risk patients; however, cystoscopy is invasive, expensive, and is not without insignificant morbidity for the patient. Urine cytology is often used as an adjunct to cystoscopy; however, it has a low sensitivity in detecting low grade bladder cancers. Recent studies have investigated the application of Raman micro-spectroscopy for the detection of bladder cancer via urine cytology, and it has been demonstrated to significantly improve the diagnostic sensitivity of …

Insole Antenna For On-Body Telemetry, Domenico Gaetano, Patrick Mcevoy, Max Ammann, Matthias John, Colm Brannigan, Louise Keating, Frances Horgan

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A 433 MHz antenna is proposed for integration with the insole of footwear for a body area network. The folded dipole design with an asymmetric groundplane radiates from its edges and considers the close proximity of the human foot and ground surfaces. It functions for different ground conductivity conditions and an on-body communication link with an Inverted F Antenna in the upper body area was evaluated on a static and dynamic human subject. The antenna solution was compliant with Specific Absorption Rate requirements, remains matched and links with upper-body nodes regardless of the body posture and node location.

Raman Micro Spectroscopy For In Vitro Drug Screening: Subcellular Localisation And Interactions Of Doxorubicin, Zeineb Farhane, Franck Bonnier, Alan Casey, Hugh Byrne

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Vibrational spectroscopy, including Raman spectroscopy, has been widely used over the last few years to explore potential biomedical applications. Indeed, Raman spectroscopy has been demonstrated to be a powerful non-invasive tool in cancer diagnosis and monitoring. In confocal microscopic mode, the technique is also a molecularly specific analytical tool with optical resolution which has potential applications in subcellular analysis of biochemical processes, and therefore as an in vitro screening tool of the efficacy and mode of action of, for example, chemotherapeutic agents.

In order to demonstrate and explore the potential in this field, established, model chemotherapeutic agents can be valuable. …

Optical Diagnostics – Spectropathology For The Next Generation, Malgorzata Baranska, Hugh Byrne

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Spectropathology For The Next Generation: Quo Vadis?, Hugh Byrne, Malgorzata Baranska, Gerwin J. Pupples, Nick Stone, Bayden Wood, Kathleen M. Gough, Peter Lasch, Phil Heraud, Josep Sulé-Suso, Ganesh Sockalingum

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Although the potential of vibrational spectroscopy for biomedical applications has been well demonstrated, translation into clinical practice has been relatively slow. This Editorial assesses the challenges facing the field and the potential way forward. While many technological challenges have been addressed to date, considerable effort is still required to gain acceptance of the techniques among the medical community, standardise protocols, extend to a clinically relevant scale, and ultimately assess the health economics underlying clinical deployment. National and international research networks can contribute much to technology development and standardisation. Ultimately, large-scale funding is required to engage in clinical trials and instrument …

Vibrational Microspectroscopy For Cancer Screening, Fiona Lyng, Ines Ramos, Ola Ibrahim, Hugh Byrne

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Vibrational spectroscopy analyses vibrations within a molecule and can be used to characterise a molecular structure. Raman spectroscopy is one of the vibrational spectroscopic techniques, in which incident radiation is used to induce vibrations in the molecules of a sample, and the scattered radiation may be used to characterise the sample in a rapid and non-destructive manner. Infrared (IR) spectroscopy is a complementary vibrational spectroscopic technique based on the absorption of IR radiation by the sample. Molecules absorb specific frequencies of the incident light which are characteristic of their structure. IR and Raman spectroscopy are sensitive to subtle biochemical changes …

Multivariate Statistical Methodologies Applied In Biomedical Raman Spectroscopy: Assessing The Validity Of Partial Least Squares Regression Using Simulated Model Datasets, Mark E. Keating, Haq Nawaz, Franck Bonnier, Hugh Byrne

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Raman spectroscopy is fast becoming a valuable analytical tool in a number of biomedical scenarios, most notably disease diagnostics. Importantly, the technique has also shown increasing promise in the assessment of drug interactions on a cellular and subcellular level, particularly when coupled with multivariate statistical analysis. However, an important consideration, both with Raman spectroscopy and the associated statistical methodologies, is the accuracy of these techniques and more specifically the sensitivities which can be achieved and ultimately the limits of detection of the various methods. The purpose of this study is thus the construction of a model simulated data set with …

Raman Microspectroscopy For The Early Detection Of Pre-Malignant Changes In Cervical Tissue, Nosheen Rashid, Haq Nawaz, Kelvin W. Poon, Franck Bonnier, Salih Bakhiet, Cara Martin, John O'Leary, Hugh Byrne, Fiona Lyng

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Cervical cancer is the third most common cancer affecting women worldwide. The mortality associated with cervical cancer can, however, be significantly reduced if the disease is detected at the pre-malignant stage. The aim of this study was to evaluate the potential of Raman microspectroscopy for elucidation of the biochemical changes associated with the pre-malignant stages of cervical cancer. Formalin fixed paraffin preserved tissue sections from cervical biopsies classified as negative for intraepithelial lesion and malignancy (NILM), low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL) were analysed by Raman spectral mapping. Raman mapping, with K-Means Cluster …

Antibody-Drug Gold Nanoantennas With Raman Spectroscopic Fingerprints For In Vivo Tumour Theranostics., Joao Conde, Chenchen Bao, Daxiang Cui, Pedro V. Baptista, Furong Tian

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Inspired by the ability of SERS nanoantennas to provide an integrated platform to enhance disease targeting in vivo, we developed a highly sensitive probe for in vivo tumoral recognition with the capacity to target specific cancer biomarkers such as epidermal growth factor receptors (EGFR) on human cancer cells and xenograft tumour models. Here, we used ~90 nm gold nanoparticles capped by a Raman reporter, encapsulated and entrapped by larger polymers and a FDA antibody-drug conjugate –Cetuximab (Erbitux®) – that specifically targets EGFR and turns off a main signalling cascade for cancer cells to proliferate and survive. These drug/SERS gold nanoantennas …

Improved Protocols For Vibrational Spectroscopic Analysis Of Body Fluids, Franck Bonnier, François Petitjean, Matthew Baker, Hugh Byrne

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The applications of vibrational spectroscopy to the examination of human blood serum are explored. Although FTIR spectra can be recorded in aqueous solutions at (gelatin) concentrations as low as 100mg/L, the high-wavenumber region remains obscured by water absorption. Using Raman spectroscopy, high quality spectra of gelatine solutions as low as 10mg/L can be achieved, also covering the high-wavenumber regions. In human serum, spectral profiles are weak and partially obscured by water features. Dried deposits are shown to be physically and chemically inhomogeneous resulting in reduced measurement reproducibility. Concentration of the serum using commercially available centrifugal filter devices results in an …

Comparison Of Semi-Automated And Manual Measurements Of Carotid Intima-Media Thickening, Oscar Mac Ananey, G Mellotte, V Maher

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Carotid intima-media thickening (CIMT) is a marker of both arteriosclerotic and atherosclerotic risks. Technological advances have semiautomated CIMT image acquisition and quantification. Studies comparing manual and automated methods have yielded conflicting results possibly due to plaque inclusion in measurements. Low atherosclerotic risk subjects (n = 126) were recruited to minimise the effect of focal atherosclerotic lesions on CIMT variability. CIMT was assessed by high-resolution B-mode ultrasound (Philips HDX7E, Phillips, UK) images of the common carotid artery using both manual and semiautomated methods (QLAB, Phillips, UK). Intraclass correlation coefficient (ICC) and the mean differences of paired measurements (Bland-Altman method) were used …

Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne

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Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …