Current Analytical Biomedical Approaches to Global Health Threats

The World Health Organization (WHO) published a report on the “Ten Threats to Global Health in 2019”, which highlighted the main threats to human health across the globe. The comprehensive list comprised an array of well-known threats including non-communicable diseases such as cancer, type-2-diabetes, cardiovascular disease, and stroke, as well as emerging threats such as antimicrobial resistance.

It was, therefore, no surprise that Pittcon 2019 featured biomedical researchers from around the world who were working diligently to address these important health issues through the development of new techniques and technologies.

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The Pittcon 2019 Technical Program was held in Philadelphia from March 17^th-21^st, 2019 and showcased a range of biomedical methodologies which can provide improved diagnostics, better treatments, faster discovery and ultimately improved medical outcomes.

Spectroscopic Approaches to Global Health Threats

Spectroscopy is fast becoming one of the greatest advances in biomedicine. Raman spectroscopy is one of the many spectroscopic techniques that featured at Pittcon 2019. Raman is a low-energy, non-destructive and non-invasive technique that can be used to image even delicate tissues in situ. The only limitation of Raman is the signal to noise ratio, as low energy signals can be swamped and lost in the noise. This has been addressed through the development of combinatorial techniques such as Stimulated Raman Scattering (SRS), which has recently been used to image brain tissue in Alzheimer’s disease.

To demonstrate how Raman spectroscopy can be coupled with photoacoustic imaging, Professor Dan Fu of the University of Washington presented his research at Pittcon 2019 in a talk entitled “Label-Free Chemical Imaging of Brain Structure and Function at Subcellular Resolution”. In this presentation he explained that Stokes Raman Scattering (SRS) is able to detect synaptic acetylcholine, plaque structure, and even complex cell organization without any labelling in Alzheimer’s research.

Raman spectroscopy has slipped into biomedical science proving its utility in medical diagnostics for diseases as diverse as cancer, cardiovascular disease and bacterial infections. Raman is proving its value in both the diagnostic laboratory and the clinical environment.

Professor Jurgen Popp is a great advocate for Raman spectroscopy and is an expert in his field. He received the 2016 Pittsburgh Spectroscopy Award at Pittcon 2016 and gave a presentation entitled “Clinical Cell and Tissue Diagnostics by Multimodal Molecular Spectroscopy”. The work examined advances in spectroscopic methods, especially Raman spectroscopy and combinatorial spectroscopic or optical procedures to analyze cells and tissue in pathological samples. Popp also demonstrated the potential of Raman spectroscopy as a point-of-care method for a fast identification of pathogens.

Transmission Raman spectroscopy (TRS) is a further example of a developing biomedical Raman technique. The method works by illuminating the sample on one-side and collecting the transmitted light on the other side. This technique has become a non-invasive technique for the analysis of breast calcification detected from mammograms.

Nick Stone, Professor of Biomedical Imaging and Biosensing at the University of Exeter, presented his research paper at Pittcon 2019 entitled “Biomedical Spectroscopic Tools for Rapid Analysis of Disease Specific Changes Using Novel Raman and IR Techniques”. This showed how Raman and IR spectroscopy is being used for the rapid and accurate analysis of tissues in pathology, high-speed spectral histopathology.

Microfluidic lab-on-a-chip technology, combined with spectroscopy has the potential to become a new biomedical analytical phenomenon. Microfluidic systems are more cost effective than traditional methods, require minimal training, provide faster results and improved accuracy.

Dr Ester Segal of Technion is an expert in microfluidics and presented a talk entitled “On-Chip Rapid Diagnostic Susceptibility Testing of Bacteria and Fungi from Clinical Samples” at Pittcon 2019. This showcased the testing of microorganisms for antibiotic resistance using a functionalized photonic 2D silicon microarray as a platform.

MALDI Imaging

Immunohistochemistry and radiolabelling have revolutionized the visualization and detection of compounds in pathological tissue samples. But now, high-throughput, high-speed MALDI (matrix assisted laser desorbed ionization) mass spectrometry imaging has arrived. MALDI Imaging mass spectrometry (MALDI-IMS) can be used to analyse complex mixtures ranging from small molecules to complex peptides in a proteome. This method also has the advantage that it does not harm the sample.

A recognized authority in mass spectrometry imaging, Professor Pierre Chaurand of the University of Montreal, presented his research in a presentation entitled “Image MS of Tissue Biopsies to Assess Diagnosis, Prognosis and Response to Therapies” at Pittcon 2019.

Biomarker Discovery

Researchers are continually searching for new biomarkers for health threats, including cancer, neurological diseases, and cardiovascular diseases. If molecular signatures of disease can be identified early then rapid and targeted treatment can improve patient survival providing an economic advantage.

A potential method for discovering new biomarkers in lung disease is exhaled breath condensate (EBC). EBC is a body fluid matrix in which biomarkers may be identified and is considered by many to be equivalent to blood, sweat, tears, urine and saliva.

A presentation entitled “Human Exhaled Breath Aerosol Collection in the Clinical Setting - Techniques, Concerns, and Considerations” was provided by Professor Michael D Davis of the Children's Hospital of Richmond, Virginia Commonwealth University (VCU). The talk provided an overview of collection techniques and analysis for EBC.

An area where biomarkers are needed urgently is Alzheimer’s disease (AD). AD is a major public health issue; the condition is the 6^th leading cause of death in the US and around 5.7 million American citizens live with the disease at any one time. Currently, a definitive diagnosis of AD requires post-mortem slides of neural material. It is hoped that a series of new biomarkers will provide a definitive diagnosis for living patients and help scientists to understand the progression of the disease at a molecular level. Two approaches that are currently being utilized for the discovery of new biomarkers are proteomics and lipidomics studies on blood and post-mortem tissues.

The potential of these techniques was outlined by Dr Rena Robinson of Vanderbilt University, who presented her paper at Pittcon 2019, entitled “Comprehensive Proteomics and Lipidomics Strategies to Advance Alzheimer's Disease Research”. This will define a high-throughput quantitative proteomics method to provide hundreds of proteins distinct to specific disease genotypes.

Biomarkers and Metabolomics

Metabolites are the intermediates and products of metabolism. Cells constantly carry out discrete physiological processes and these can be affected by human disease. To determine the structure and regulation of metabolic pathways is essential especially in brain tissue for researching AD.

Monitoring brain chemistry metabolites is, however, a challenging area. In this case, biosensors have been used to understand brain energy metabolism and neurotransmission. The sensors provide timed temporal resolution and enzymatic assaying of any redox or non-redox molecule. This can be of great help in the real-time monitoring of brain chemistry during the course of traumatic brain injury (TBI). However, despite the miniature size of the of the biosensors, implantation is often considered dangerous and comes with major health risks.

At Pittcon 2019, Dr Stéphane Marinesco of INSERM gave a presentation entitled “Ultra-small Microelectrode Biosensors based on Platinized Carbon Fibers for Brain Injury Monitoring”. This research demonstrated how ultra-small microelectrodes are implanted in the brain to provide accurate estimates of oxygen, glucose and lactate and other essential compounds. The idea is that this technology could monitor changes occurring in traumatic brain injury and provide improved diagnosis.

References

1. Ten threats to global health in 2019, https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 Accessed 4th March 2019
2. M Ji, S Lewis, S Camelo-Piragua, SH Ramkissoon, M Snuderl, S Venneti, Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy, Science translational medicine 7 (309), 2010, 309ra163-309ra163
3. Nadine Vogler, Sandro Heuke, Thomas W. Bocklitz, Michael Schmitt, Jürgen Popp, Multimodal Imaging Spectroscopy of Tissue, Annual Review of Analytical Chemistry 2015 8:1, 359-387
4. Ghita, A, Matousek, P. and Stone, N. (2018), High sensitivity non‐invasive detection of calcifications deep inside biological tissue using Transmission Raman Spectroscopy. J. Biophotonics, 11: e201600260.
5. Leonard, Heidi & Colodner, Raul & Halachmi, Sarel & Segal, Ester. (2018). Recent Advances in the Race to Design a Rapid Diagnostic Test for Antimicrobial Resistance. ACS Sensors. 3. 10.1021/acssensors.8b00900
6. P Chaurand, Imaging mass spectrometry of thin tissue sections: a decade of collective efforts, 2012, Journal of proteomics 75 (16), 4883-4892
7. Albert B. Arul and Renã A. S. Robinson, Sample Multiplexing Strategies in Quantitative Proteomics, Analytical Chemistry, 2019, 91 (1), 178-189, DOI: 10.1021/acs.analchem.8b05626
8. Tholance Y, Barcelos GK, Dailler F, Renaud B, Marinesco S, Perret-Liaudet A. Biochemical neuromonitoring of poor-grade aneurysmal subarachnoid hemorrhage: comparative analysis of metabolic events detected by cerebral microdialysis and by retrograde jugular vein catheterization. Neurological Research, 2015, 37: 578-87. PMID 25668478 DOI: 10.1179/1743132815Y.0000000012

About Pittcon

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