Cutting edge Omics research delivers biological knowledge that can revolutionize human health. Our collaborations with trusted, globally renowned partners and experts in OMICS research enable us to develop workflow and technology advancements that drive life science research. As a result, we provide you with continuously more productive and reliable solutions to discover, identify, and quantitate biomolecules in complex biological systems.

With the demand for data acquisition and interpretation into results outpacing the supply of human experts, developing solutions for managing this ever-increasing workload and complex data is a crucial task.  This requires a new set of tools that can handle large volumes of rich analytical data quickly and accurately and draw on the power of artificial intelligence (AI). Guest speakers from the OMICS community and Thermo Fisher Scientific share their visions of cutting-edge technologies and innovative techniques that are advancing science.

The state of healthcare today and tomorrow can be best described as complex and unpredictable. From chronic diseases to neurodegenerative diseases such as Alzheimer’s, infectious diseases, cancer, reproductive health issues to the opioid crisis and drug misuse – all require sensitive, specific, reliable and reproducible analytical platforms that provide comprehensive, robust and confident data.
 
The application of LC-MS in clinical laboratories has significantly increased in the past decade and found utility to address critical needs across several application areas, enabling researchers and physicians to make confident decisions about diagnosing disease and optimizing therapeutic regimens. Today’s presentations will focus on critical clinical research areas that address the role of LC-MS in disease, reproductive health and the drug epidemic.

Mass spectrometry-based proteomics is a powerful technique for the analyses of thousands of proteins, fueling biomarker research and drug discovery. With the rich complex data from each precious sample and large cohorts, new developments in the field of deep learning with the INFERYS platform deliver improved confidence in proteomics results. Its application to large amounts of high-quality training data can unlock this dimension and enable novel data analysis workflows on readily available CPU and end-user infrastructure.  Fusing deep learning approaches with established toolchains allows the extraction of more identifications from difficult proteomic samples measured label-free or using tandem mass tags.                                     

The World Alzheimer's Report estimates that ~50M people live with dementia, of which Alzheimer's disease (AD) represents approximately 60-80% of all cases. Early diagnosis is imperative for early treatment and prevention, which offer the greatest chances for changing the future trajectory of AD. An urgent medical need exists for accurate, simple, lower-cost, radiation-free, and widely accessible blood-based tests to improve the diagnostic evaluation of patients with memory impairment and at risk for AD. A blood-based test (PrecivityAD™) was introduced into the clinic in 2020 as a CLIA-certified laboratory developed test performed by C2N Diagnostics. The test relies on LC-MS/MS to measure in plasma amyloid beta (Aβ) protein isoforms Aβ42 and Aβ40 and detect the presence of Apolipoprotein E (ApoE)-specific peptides. The data strongly support the test's role as a clinically useful tool to identify brain amyloid pathology, as well as its role in aiding the AD diagnostic evaluation process among individuals presenting to their clinicians with cognitive impairment.

Lipids are important effector molecules, however current methodologies are not sufficient for global lipidomic profiling in biological systems. Learn how new innovations using Thermo Scientific™ Orbitrap™ Tribrid™ technology provides higher-confidence small-molecule analysis with intelligent decision-based triggering of MSn scan events to increase certainty in annotation, improve structure assignment of lipid isomers, and search - driven unknown characterization.

Technologies that enable intraoperative tissue analysis and diagnosis are critically needed to guide surgical procedures and improve patient outcomes. Here we demonstrate the MasSpec Pen technology as a handheld device, integrated with a mass spectrometer, for rapid and direct molecular analysis of biological samples. Coupled with statistical modeling, we show that this rapid (<15s), non-destructive technology enables tissue classification and cancer diagnosis with high accuracy. Today’s presentation will describe recent developments and results translating MasSpec Pen technology integrated with a Thermo Scientific™ Orbitrap™ mass spectrometer to the clinic and operating rooms for in vivo tissue analysis and diagnosis. Technical developments and diagnostic performance in cancer surgery will also be discussed, as well as new opportunities and applications in the clinical setting.

Mass spectrometry-based proteomics methods are finding increasing use in structural biology research. Beyond simple interaction networks, information about stable protein-protein, protein-ligand or protein-DNA or RNA complexes help to elucidate the biological functions of proteins and nucleic acids in a wider cellular context. New workflow developments and data processing will be discussed as how protein-RNA or DNA interactions can be detected and localized at the single amino acids.

Mass spectrometry technology provides systems-level insights to comprehensive metabolism and can identify specific pathways that are altered in connection with phenotypes. Currently, insufficient metabolome annotation limits biological interpretation for untargeted metabolomics studies. By capturing more low-abundance analytes and leveraging streamlined data analysis and mass spectral prediction tools, learn how the combined power of HRAM Thermo Scientific™ Orbitrap™ mass analyzer technology with intelligent MSn acquisition addresses the identification bottleneck, reinventing the way metabolomics is done today.

The concentration of Circulating microparticles (CMPs) increases more than two-fold during pregnancy and offers a minimally invasive means to “biopsy” maternal-fetal tissues. CMPs obtained at the end of the first trimester, are a good source of protein biomarkers to detect physiologic changes systemically such that the risk of spontaneous preterm delivery (sPTB) at <35 weeks can be stratified.

Extended clinical validations of the sPTB biomarkers, have demonstrated that CMP-associated proteins, obtained at 12 weeks’ gestation, may predict the overall risk of early preeclampsia and indicate distinct subtypes of pathophysiology and clinical morbidity. The approach is being extended to a placental disease called placenta accreta, a life-threatening condition wherein the placenta grows too deeply into the uterine wall and does not deliver readily during birth. The early detection of a host of diseases and complications of pregnancy, using vesicular content derived from maternal and fetal compartments and, systemically, from a broad range of tissues and pathophysiological processes, could lead to better management and early interventions that improve birth outcomes and save lives.

Imaging mass spectrometry (IMS) can produce thousands of ion images, providing molecular context to classical histological analysis. New LC-MS proteomics methodologies that have single-cell level sensitivity can now be extended to quantitative proteome mapping using a “voxelation” approach. This has resulted in a depth of proteome coverage and robust quantitation superior to those of existing IMS platforms. The application of this innovative platform to proteome mapping clearly demonstrates the exciting potential of proteome imaging to advance biomedical research.

According to the National Forensics Laboratory Information System (NFLIS), the number of fentanyl-related reported cases increased from 945 cases in 2013 to 71,341 cases in 2017 while case load has risen minimally over this same time span.  Laboratories have established methods for known fentanyl analogs and other clinically relevant opioids, but the list of new illicit fentanyl analogs is rapidly expanding and can be challenging for laboratories to confirm without certified reference standards.  Here we present a method for fentanyl screening and semi-quantitation in urine for all 212 fentanyl analog compounds contained in the Centers for Disease Control (CDC) Fentanyl Analog Screening (FAS) Kit and Emergent Panels V1-V3 using HRAM mass spectrometry on the Thermo Scientific™ Orbitrap Exploris™ 120 mass spectrometer.

Targeted metabolic profiling enables confident measurements for known compounds of interest, yet to reproducibly measure concentration levels for these key metabolites, especially in large-scale applications, analytical rigor is required. While confidently identified, profiling select targets of the observed phenotype may not fully explain underlying biochemical mechanisms necessitating subsequent sample analyses. High-resolution accurate-mass Thermo Scientific™ Orbitrap™ technology enables unbiased compound detection for the accurate and quantitative analysis of target metabolites and the retro-mining of data to discover unknown biomarkers.

Since 2008, when the synthetic cannabinoid receptor agonists (SCRAs) JWH-018 and CP47,497 were first detected, a total of over 200 SCRAs have now been reported worldwide.  Whilst the drivers for change in these compounds are not fully understood, the fact is that these compounds are generally around for a couple of years before disappearing. Over this time, whilst trying to keep up with the latest compounds we have developed methods and strategies for the ongoing detection of SCRAs and their metabolites in drug seizures, herbal incense, hair, biological fluids and gummys all based on Thermo Scientific™ Orbitrap™HRAM technology.  The methods have been used in postmortem work, drug driving, workplace drug testing, forensic drug analysis and several bespoke population studies. Some examples of methodologies and associated results will be shown. The latest findings in the UK are also presented together with metabolism data.

Currently laboratory research demands more application versatility and certainty for metabolite identification, targeted compound screening, and identification of unknown compounds. One challenge is the increasing number of prohibited substances, which require large custom compound databases and spectral libraries for screening and testing. Learn more about how small-molecule specific mass spectrometers with intelligent decision-based triggering of MSn translate high-quality Thermo Scientific™ Orbitrap™ mass spectra into confidently assigned small-molecule structures.

Hydrogen deuterium exchange (HDX) mass spectrometry (MS) is a powerful tool for studying structural dynamics of protein-based therapeutics.  The pharmaceutical industry has become very good at finding molecules that selectively bind to proteins and inhibit or activate them.  Once discovered, understanding the mechanism of action and details of target engagement are essential to moving forward. As targets become more and more challenging, finding ways to reliably obtain this information in a timely fashion have become critical. An integrated approach where the dynamics information is used synergistically with other biochemical tools has proven most beneficial. Here, 2-3 case studies are shown illustrating how HDX-MS can be used in both small- and large-molecule drug discovery.

Adeno-associated viral (AAV) vectors have emerged as the leading gene delivery platform for gene therapy.  Capsid proteins play an important role in cell binding, internalization, and trafficking, however conventional AAV capsid protein characterization methods such as ELISA and SDS-PAGE are time consuming and do not provide direct viral capsid identification information.

In order to successfully characterize AAV viral proteins one can take advantage of a Thermo Scientific™ Orbitrap™ mass analyzer which provides ultra-high resolution and sensitivity, enabling excellent quality of MS and MS2 data for full AAV capsid protein characterization through intact, top- down and peptide mapping approaches. You are invited to join us to learn how AAV capsid proteins and associated PTMs can be characterized rapidly, even at very low concentration levels, using an LC-Orbitrap MS platform.

Impurities in products may give rise to toxicities, but often represent only minor components. Thus the ability to detect these low abundant analytes in the presence of higher amounts of product is a challenge. Once detected, the correct structure assignment to the impurity or degradation by-products is the next hurdle. Here, learn how Ultraviolet Photodissociation (UVPD) can be utilized in the analysis of impurities as a unique fragmentation mode for overall improved analysis of unknowns. UVPD combined with the high sensitivity and wide dynamic range of the Thermo Scientific™ Orbitrap™ Tribrid™ mass spectrometer provides unique structurally diagnostic information. This otherwise unobtainable information improves the certainty of identification.

Large RNA, including messenger RNA (mRNA), has recently become a new prospective class of drug products. The potential of mRNA technology for rapid vaccine development has recently been highlighted by the successful development of mRNA vaccines. Current analytical methods to characterize RNA therapeutics are limited and the development of analytical methods for the analysis of large RNA (>1000 nucleotides), including mRNA drug products, is challenging.

Large RNAs are not suitable for direct intact MS analysis. Therefore, digestion of the RNA with appropriate RNase enzymes prior to LC-MS/MS methods for oligonucleotide identifications is required. In this session we demonstrate the development of specific RNase mapping workflows optimized for the analysis of large RNA, including mRNA therapeutics. High-throughput approaches have been developed in conjunction with automated software analysis that match fragment MS/MS sequence data to the native full sequence, resulting in high sequence coverage of the mRNA therapeutic.

As diseases are complex, the biopharmaceuticals developed for their treatment are becoming more complex as well.  Advanced analytical strategies and solutions are needed to support scientists on their journey to ensure the quality and efficiency of their biopharmaceutical molecules in development, including mAb therapies and exciting new modalities such as gene therapy products. Join us to learn, through presented examples and case studies, how this can be done with innovative LC-MS solutions leveraging a high-resolution accurate-mass mass spectrometer system.