Molecular Spectroscopy to Study Disease Mechanisms and Treatment

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Thursday, June 2
Organizer: Dr. Andrew Whitley, Horiba Scientific

This symposium is organized by the Society for Applied Spectroscopy in collaboration with Pittcon.

The advent of the COVID-19 pandemic has brought investment and the use of molecular spectroscopy to study disease mechanisms and treatment in to sharper focus. This symposium, organized by the Society for Applied Spectroscopy, will provide a critical look at the most advanced applications of spectroscopic methods to address biomedical research and drug development. In this contribution we report on various innovative technological methods for bringing spectroscopy closer to the end-user including clinical use and vaccine release quality control. We will focus on molecular-sensitive spectroscopic methods. Applications will include intraoperative in-vivo examination, high throughput sorting and examination of cells, clinical environment in-vivo studies, spectroscopic chemical imaging of cancer pathology and treatment, theranostic nanomedicine and vaccine release quality control. The symposium will focus on translational research and medicine providing more meaningful, applicable results that directly benefit human health. With COVID the expectation is that there will be a faster translation of spectroscopy into practice, to allow faster bench-to-patient, point of care solutions.

Presentation 1
SESORS for Preclinical Imaging of Glioblastoma
Fay Nicolson, Cancer Institute and Harvard Medical School
The ability to image tumors at depth with high selectivity and specificity remains a significant challenge in the field of biomedical optical imaging. “Surface-enhanced Raman scattering” (SERS) nanoparticles can be employed as image contrast agents and in addition, when functionalized with biomolecules such as antibodies, can specifically target cells in vivo. However, while the detection of SERS contrast agents is extremely sensitive and specific, traditional Raman imaging approaches are limited in their ability to probe through tissue depths of more than a few millimeters. Here, we combine the use of “spatially offset Raman spectroscopy” (SORS) with that of SERS in a technique known as “surface enhanced spatially offset Raman spectroscopy” (SESORS) to image deep-seated tumors through the intact skull using mouse models of glioblastoma. We will discuss the optimization of SORS instrumentation and sampling methods, as well as the subsequent application of SESORS to pre-clinical cancer imaging and delineation of tumor margins. We demonstrate that our approach enables improvements in the non-invasive detection of glioblastoma due to improvements in SNR, spectral resolution, and depth acquisition.

Presentation 2
Integrated Raman-microfluidic Systems for Rapid Diagnosis and Cell Sorting
Huabing Yin, University of Glasgow
Single cell Raman spectra provide an intrinsic chemical ‘fingerprint’ of individual cells, which can characterise cell types and metabolic activates. By integrating microfluidics with Raman spectroscopy, we have developed serval platforms to study microbial communities at the single cell level. Our approaches enable quantitative and real time analysis of individual cells, without the need for external labelling processes. With this capability, we have recently realised rapid diagnosis of pathogens from sample to results within minutes. I will also introduce flow-based Raman activated cell sorting (RACS) platforms we have developed, which use Raman spectra as a readout for cell identification. Our platforms enable automated, high throughput isolation of individual cells of desirable traits in a community for down streaming culture or genetic analysis. They can be applied to a wide range of samples (from 1 μm bacteria to mammalian cells) and provide a versatile tool for function-based flow cytometry and sorting applications in the fields of microbiology, synthetic biology, life science and diagnostics.

Presentation 3
Direct and Indirect Raman Diagnostics of Covid-19
Juergen Popp Leibniz, Institute of Photonic Technology
The recent Corona Virus Disease 2019 (COVID-19) pandemic has illustrated how great the need for fast and reliable diagnostic approaches are. Continuous research aiming for the development of fast, specific, sensitive and simple diagnostic assays, together with antiviral drugs and vaccines are the key components for prevention future virus outbreaks and for limiting the subsequent damages. The current gold standard, allowing for the needed high specificity and sensitivity to diagnose viral infections, are Polymerase Chain Reaction (PCR) based methods. However, despite the advantage of PCR there are some drawbacks, most importantly PCR assays are rather expensive and require specialized laboratory settings with trained personnel and infrastructure. These drawbacks make a global surveillance strategy, which is applicable with minimal resources almost impossible. The sensitivity of the simple and fast lateral flow tests are lower than that of PCR. Thus, there is a great need for new fast and reliable Covid-19 diagnostic methods. In this context molecular spectroscopy and particularly Raman spectroscopy appears a promising option due to probing the molecular structure. Within this contribution we will introduce two promising SARS-CoV2-diagnostic tools with specially tailored sampling approaches which are focused on I) fast bead-based approach for direct pathogen detection and II) characterization of the host response applying Raman spectroscopic techniques. Acknowledgment: Financial support of the EU, the ”Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft”, the ”Thüringer Aufbaubank”, the Federal Ministry of Education and Research, Germany (BMBF), the German Science Foundation, the Fonds der Chemischen Industrie and the Carl-Zeiss Foundation are greatly acknowledged.

Presentation 4
Ensuring Quality of Vaccines and AAVs with A-TEEM Spectroscopy
Linda H Kidder, HORIBA Scientific
A-TEEM technique, a 2-in-1 method that incorporates multi-dimensional fluorescence with UV/Vis absorbance, is well aligned with the analytical needs of next generation therapeutics like vaccines and Adeno-Associated Virus (AAV) vectors. Commercial deployment of these next generation products depends on analytical tools to ensure product quality, but developments of these much needed tools often lags, particularly tools that provide rapid analyses. Standard optical spectroscopic methods such as Raman and NIR provide robust results for standard therapeutics, but can struggle with the complex and low concentration formulations that are common for many of these next generation products. A-TEEM has high sensitivity that enables low concentrations to be well characterized, and high specificity provides the ability to differentiate multiple components. We will present the ability of the A-TEEM method to accurately differentiate between four closely related combination vaccine formulations, and to accurately predict empty/full ratio of AAV standards, as well as differentiate between AAV serotypes.

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