Anand Mehta, D.Phil., is the SmartState Endowed Chair in Proteomic Biomarkers and Professor, Department of Cell and Molecular Pharmacology at the Medical University of South Carolina. Dr. Mehta’s laboratory is focused on understanding and developing diagnostic methods and treatments for hepatocellular carcinoma (HCC). HCC is a primary cancer of the liver and kills close to 1 million people every year. The Mehta lab was one of the first to perform total serum glycan analysis for biomarker detection and one of the first to perform serum glycoproteomics. His laboratory remains on the forefront in the development of tools for the analysis of complex carbohydrates and the discovery and validation of biomarkers of HCC.

I will talk about how our first biomarker discovery was made and failed to be commercialized by us - but was commercialized by others.

I graduated in analytical chemistry from the faculty of chemistry at Shahid Beheshti University (Tehran,Iran).For my Master's thesis I was working on the Optimization of solid phase microextraction and electromembrane extraction techniques to measure certain pollutants and drugs. During my studies,I was also awarded medals and honorary diplomas from international and national competitions and expositions because of my inventions. In June 2017, I started my Glysign PhD project, conducting research at Genos Ltd., Zagreb, Croatia, and the Leiden University Medical Centre in Leiden, the Netherlands. My research is geared towards the quantification of serum protein glycosylation for patient stratification in early-onset and other diabetes types.

# Originally scheduled to be presented at MSACL 2020 US. Moved from August 10 make-up session due to timing conflict.

Introduction

Type 2 diabetes mellitus (T2D) represents a major public health challenge. The total plasma N-glycome (TPNG) reflects the levels and glycosylation of major plasma glycoproteins, among which are immunoglobulins, acute-phase proteins and apolipoproteins. Although associations of TPNG with T2D have been recently reported by us and others, data on the association between TPNG and T2D complications are scarce. Here, we applied our new ultrahigh-resolution MS method to assess associations of TPNG with T2D complications.

Methods

We determined the TPNG in a subsample of the Hoorn Diabetes Care System cohort (n = 1519 T2D cases and 192 nondiabetic controls from the New Hoorn study cohort) using our Fourier-transform ion cyclotron resonance MS method. Blood plasma samples were randomized over 21 96-well plates, together with technical replicates. Prior to MS analysis, N-glycans were released using PNGase F. For stabilization and linkage differentiation, sialic acids were derivatized. Released glycans were purified and spotted using an automated liquid handling platform. In total, 68 individual glycan compositions were quantified after total-area normalization and summarized into derived traits representing structural features. By applying logistic regression models, we tested for associations of TPNG with case-control status and micro- or macrovascular complications, such as nephropathy, retinopathy, or cardiovascular disease (cross-sectional). T2D complications were also assessed prospectively by Cox regression. Models were adjusted for age, sex, and T2D risk factors. The outputs were meta-analyzed together with our MALDI-TOF-MS data from the independent cohort DiaGene (1815 T2D cases and 836 controls) which we obtained and described previously.

Results

The recently developed method using MALDI-FTICR-MS improved resolution, mass accuracy, dynamic range and the signal-to-noise ratio, especially for larger glycans, in comparison to our previous MALDI-TOF workflow. The relative standard deviation over the 68 detected glycan species was on average 6.6%, based on the relative intensities from 93 technical replicates of pooled plasma, representing total method repeatability.

We found significant associations of all major glycosylation traits, i.e. sialylation, fucosylation, galactosylation, bisection, and glycan complexity with T2D in the meta-analyses of both cross-sectional and prospective data. For example, the bisection and galactosylation of immunoglobulin-related glycans were associated with macrovascular complications and nephropathy. We aim to confirm these results in the near future on protein-specific level, by isolating IgG prior to released-glycan analysis.

Conclusions

Our new method improved the detection of several glycan species, thus providing possible new insights into the association between TPNG and T2D. Our results will be taken forward to improve personalized approaches in T2D and related complications in the future.

I am an analytical chemist focused on infection metallomics and clinical mass spectrometry (MS). From 1991 I have had the main contract with the Institute of Microbiology in Prague, where I run an analytical lab with 25 employees now benefitting from mass spectrometry, nuclear magnetic resonance spectroscopy, and electron microscopy (https://ms.biomed.cas.cz/). As a professor of analytical chemistry, I am also active at Palacky University in Olomouc, CZ, providing me with access to elemental imaging mass spectrometry and infection models. I have a scientific profile with 3582 citations (access date May 21, 2020), 1517 citations since 2015. My current h-index is 30 (Google Scholar). In 2020 I contributed to 11 peer-reviewed papers, nine of them I corresponded.

*This talk was originally scheduled to be presented at MSACL 2020 US. It is expected to be about 35-45 minutes, not including Q&A.

Background: The detection and quantitation of siderophores in urine represents an innovative early indication of pathogenic microorganisms in a host [1]. In this presentation, we document why the general application of siderophores in invasive infectious diagnostics will soon represent the same clinical breakthrough as ribosomal protein typing ten years ago. In addition to handling co-infections or polymicrobial frenemies, with mass spectrometry, we can monitor the antimicrobial drug metabolism [2].

Methods: A database of 700 microbial siderophores was used for screening a patient’s status with invasive infections caused by Aspergillus fumigatus, Pseudomonas aeruginosa, and zygomycetes. Human urine samples were examined by liquid chromatography and Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer [3]. The biomarkers were quantified against matrix-matched standards, and our in-house tool called CycloBranch (https://ms.biomed.cas.cz/cyclobranch) was used for compound dereplication [4].

Results: For the diagnosis of aspergillosis, we used an array of ferri-triacetylfusarinine C (TAFC)/ferri-ferricrocine (FC)/gliotoxin (GTX) in a cohort of 28 patients (14 positive and 14 negative controls). LOD for TAFC in human urine was 0.1 ng/mL. The maximum experienced concentration was 1.7 ug/mL. In the working dataset of critically ill, mostly non-neutropenic humans, the TAFC/FC/GTX sensitivity in urine was 93% compared to standard GM in serum (36%). The kinetic profiles upon antimycotic treatment showed a quick drop in siderophore production in vivo. In the same cohort, ferri-pyoverdines and pyochelin were detected as urinal biomarkers in the patients with Pseudomonas aeruginosa. The LOD for Fe-PVD in urine was 10 ng/mL. In serum samples, the LOD and LOQs were 1 and 5 ng/mL, respectively. In the seminar I will also show the co-infecting frenemies studied in animal models of bacterial [5] or fungal infections [6].

Conclusion: Urinal samples are analytically attractive due to less chemical background compared to serum and clinically interesting due to non-invasive applications. Optimized sample preparation could soon move siderophore analysis from FTICR equipment to standard MALDI-Biotyper-type labs.

References:

1. Luptáková, D.; Pluhá?ek, T.; Pet?ík, M.; Novák, J.; Palyzová, A.; Sokolová, L.; Škríba, A.; Šedivá, B.; Lemr, K. and Havlí?ek, V. Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass spectrometry. Sci Rep 2017, 7, 16523.

2. Houst, J.; Spizek, J. and Havlicek, V. Antifungal Drugs. Metabolites 2020, 10, article No. 106.

3. Pluhacek, T.; Skriba, A.; Novak, J.; Luptakova, D. and Havlicek, V. Analysis of Microbial Siderophores by Mass Spectrometry. In: SK Bhattacharya (ed) Metabolomics: Methods and Protocols 2019: 131-153.

4. Novák, J.; Škríba, A. and Havlí?ek, V. CycloBranch 2: Molecular Formula Annotations Applied to imzML Data Sets in Bimodal Fusion and LC-MS Data Files. Anal Chem 2020, 92, 6844-6849.

5. Petrik, M.; Umlaufova, E.; Raclavsky, V.; Palyzova, A.; Havlicek, V.; Haas, H.; Novy, Z.; Dolezal, D.; Hajduch, M. and Decristoforo, C. Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography. Sci Rep 2018, 8, 15698.

6. Skriba, A.; Pluhacek, T.; Palyzova, A.; Novy, Z.; Lemr, K.; Hajduch, M.; Petrik, M. and Havlicek, V. Early and Non-invasive Diagnosis of Aspergillosis Revealed by Infection Kinetics Monitored in a Rat Model. Front Microbiol 2018, 9, 2356.

# Originally scheduled for MSACL2020 US in the Scientific Session : Fentanyl at the Forefront : Using Non-traditional Approaches to Identify Fentanyl Analogs

Introduction

Deaths due to opioid overdoses have been on the rise in the United States, with a particular spike in this trend caused by the emergence of synthetic opioids including fentanyl and analogues. There have been numerous reported cases of synthetic opioids as adulterants in heroin, methamphetamine, cocaine, and counterfeit pills. As a result, they are often times consumed unknowingly, causing mixed toxidromes and confounding diagnosis. Proper routine drug monitoring is essential in addressing the ever-expanding magnitude of the opioid epidemic.

Objectives

The primary objective of this study was to observe prevalence of fentanyl analogs and other false positives in positive fentanyl screens of emergency medicine populations in order to evaluate trends in the dynamic landscape of substance abuse.

Methods

Analysis of remnant clinical samples was approved by the UCSF Institutional Review Board. Urine samples from emergency department (ED) patients with drugs-of-abuse screens performed were monitored from October 2018 to March 2019 for presence of fentanyl (via immunoassay). Samples with a positive fentanyl screen were collected and further characterized by high resolution mass spectrometry (LC-HRMS). Urine samples were diluted 1:5. Chromatography was performed using a Kinetex C18 column with a 10-minute gradient from 2%-100% organic. Data was collected on a SCIEX TripleTOF®5600 using a positive-ion mode TOF-MS survey scan with IDA-triggered collection of high resolution product ion spectra (20 dependent scans). Data was screened for fentanyl, norfentanyl, 13 literature-reported synthetic opioids, and compounds reported/suspected to cause false positives with fentanyl immunoassays.

Results

158 emergency department patient samples screened positive via EMIT fentanyl immunoassay (7.44% of all ED samples screened for drugs of abuse). These samples were analyzed via LC-HRMS and analysis was targeted for 15 synthetic opioids and commonly prescribed or over-the-counter pharmaceuticals with chemical structures similar to that of fentanyl. 6.9% of samples were found to be positive for both fentanyl and acetyl fentanyl. Additionally, risperidone, its metabolite 9-hydroxyrisperidone (paliperidone), and loperamide with its metabolite desmethylloperamide were discovered as sources of false positive for fentanyl screens.

Conclusion

This data reveals the non-trivial prevalence of fentanyl in the ED patient population being screened for drugs of abuse. In many of the cases, fentanyl was not suspected or discovered as exposure agent prior to more comprehensive testing or patient discharge. The identification of acetyl fentanyl along with fentanyl via HRMS analysis can hint to a changing trend in provenance of illicitly manufactured fentanyl. Finally, HRMS is a valuable tool to identify compounds responsible for reoccurring false positives that can inform better patient care and offer a more accurate picture of the continually evolving opioid epidemic.

I grew up in rural Michigan and during these formative years greatly enjoyed flyfishing and woodworking. Putting the latter interest to practical use, I constructed several riverboats (for fishing) while in high school and college. Chemistry interested me, especially Analytical Chemistry, as it offered an avenue to continue “building”. Not boats, but chemical instrumentation. To escape the cold I joined the Chemistry graduate program at the University of Florida and worked with Willard Harrison. Professor Harrison didn’t just guide my research, he taught me how to write, present, and think like a scientist. He was a gentleman in every sense of the word. Upon graduation in 2002, I moved to Charlottesville, Virginia to join the laboratory of Professor Don Hunt. At Virginia I met John Syka. Don and John both shared a passion for science that was as infectious as it was inspiring. Together we worked to develop electron transfer dissociation (ETD). ETD worked just as we had hoped and the dissociation technique is now commonly used for proteomics and has been commercially introduced by no fewer than four major instrument vendors. In 2005 I moved to Wisconsin to start my own program. And though we have been productive and impactful with ~ 200 published manuscripts, I am most proud to have produced nearly 20 Ph.D. scientists, and our academic family continues to grow.

The sequencing of the human genome marked the beginning of a collective scientific expedition to understand complex organisms. Genes, of course, merely contain the instructions for which proteins will populate the cell. Untangling the multi-faceted networks that regulate complex organisms and their diseases will require innovative technologies to globally monitor many classes of biomolecules, including nucleic acids, proteins, and metabolites. High-throughput technologies for gene and transcript measurement are well-developed and broadly accessible, and, as such, have had a fantastic and transformative impact on modern biology and medicine. For numerous reasons, methods for global analysis of proteins and metabolites – crucial biological effector molecules – are less evolved and markedly less accessible. The overarching mission of my program is to (1) facilitate expedient, comprehensive analysis of proteins and metabolites by innovating new mass spectrometric technologies and (2) apply these techniques to advance biomedical research.

In this presentation I will describe numerous projects related to the development and application of high-throughput quantitative multi-omics. Examples include new proteomic methods and technologies to permit the deepest analysis of the human proteome to date and the discovery of thousands of alternatively spliced proteins and protein isoforms resulting from single nucleotide polymorphisms. In another example we use high throughput multi-omics to map the proteomes, lipidomes, and metabolomes of nearly 1,000 single gene knockout cell lines for large-scale functional mapping of genes. Finally, we use these same quantitative multi-omic technologies to study the molecular changes that occur during Covid-19 infection in a human cohort.

Assistant Professor at the Maastricht MultiModal Molecular Imaging (M4I) institute, I have more than 8 years of experience in the MSI imaging fields and had the opportunity to gain insights on different aspects, including instrumental development, sample preparation and quantification. Since I have earned my PhD at the School of Pharmaceutical Sciences (University of Geneva), I am now devoted to demonstrate how MSI can be employed to improve the accuracy of cancer diagnostics. I am strongly motivated by the translational aspect between the development of innovative instrumentation and direct application to clinical research – with a special focus on intraoperative mass spectrometry – and by the close collaboration with the Surgeons and Pathologists of the Maastricht University Medical Center + (MUMC+), and with the RWTH Aachen in Germany.

Peggi Angel is currently Assistant Professor at Medical University of South Carolina, where she works on technology advancements in MALDI imaging mass spectrometry (IMS) and biomarker imaging analyses for health disparities. Dr. Angel attended graduate school at the University of Georgia’s Complex Carbohydrate Research Center, graduating with a PhD in 2007. Her graduate research was on development of technologies for mapping N-linked glycan sites in mammalian development. After a postdoctoral fellowship at Emory University focused on membrane proteomics of fetal alcohol syndrome, she won a competitive Postdoctoral Fellowship with the Systems-based Consortium for Organ Design and Engineering. With the Fellowship, she worked at Vanderbilt University in the laboratory of Richard Caprioli on methods using MALDI IMS for developmental biology. Dr. Angel has developed IMS methods for increasing sensitivity of protein detection from tissues, analysis and identification of signaling lipids in negative mode, targeted metabolomics on tissue and cell culture, extracellular matrix protein detection in FFPE tissue, and N-glycomic strategies for proteins, cells, and tissue. Dr. Angel is a co-founder of Glycopath LLC, a company that focuses on glycosylation analysis as a prognostic or diagnostic tool. She serves on the board of N-Zyme Scientifics, a company that produces enzymes for mass spectrometry. Dr. Angel is committed to serving the imaging mass spectrometry community and serves on the Imaging Mass Spectrometry Society Executive Committee and the MSACL Scientific Committee.

Despite the disappointing postponement of OurCon 2020 due to the terrible COVID-19 pandemic, leaders from all over the globe have decided to unite and take up the challenge! Because we know and understand how much staying connected is important particularly in difficult times like the ones we are experiencing, we have decided to organize a unique virtual event where mass spectrometry imaging (or imaging mass spectrometry) will raise its voice for 24 hours from all over the world.

We are all happy to welcome you to the 24 hours of International Mass Spectrometry Imaging (24h-IMSI).

The event will start in Auckland on November, 19th at 8am NZST and end in Rio de Janeiro on November, 19th at 5pm UCT+3 (yes – that will make it 24 hours),

We hope that this unusual virtual event will give you the opportunity to exchange fruitfully and informally with participants from our amazing worldwide community!

We look forward to connecting with you soon!

Tiffany Porta Siegel (Maastricht) and Peggi Angel (Charleston), Chairs

John A. McLean is Stevenson Professor of Chemistry, Chair of the Department of Chemistry, Past Chair of the Faculty Senate, Director of the Center for Innovative Technologies, Deputy Director of the Institute for Integrative Biosystems Research and Education at Vanderbilt University. He received his Ph.D. from George Washington University, was a postdoctoral fellow at Forschungszentrum Jülich in Germany with Prof. Dr. Sabine Becker, and a postdoctoral at Texas A&M University with Prof. David H. Russell before joining the Vanderbilt Faculty as an assistant professor in 2006. McLean and colleagues focus on the conceptualization, design, and construction of structural mass spectrometers, specifically targeting complex samples in systems, synthetic, and chemical biology. His group applies these strategies to forefront translational research areas in drug discovery, precision medicine, and ‘human-on-chip’ synthetic biology platforms. He served on the board of directors for the American Society for Mass Spectrometry and serves in an editorial role on the boards of several leading scientific journals. He has been honored to work closely with the NAS and NSF in several roles, including recently co-authoring an NSF report on big data science in chemistry. He has received many professional and teaching awards including his laboratory being designated as a Waters Center of Innovation and an Agilent Thought Leader Laboratory for their work in ion mobility-mass spectrometry and translational biosciences. He has published over 150 manuscripts and 30 patents in the areas of innovative bioanalytical chemistry and quantitative sciences.

One of the predominant challenges in systems-wide analyses and molecular phenomics is the broad-scale characterization of the molecular inventory in cells, tissues, and biological fluids. Advances in computational systems biology rely heavily on the experimental capacity to make omics measurements, i.e. integrated metabolomics, proteomics, lipidomics, glycomics, etc., accompanied with fast minimal sample preparation, fast measurements, high concentration dynamic range, low limits of detection, and high selectivity. This confluence of figures-of-merit place demanding challenges on analytical platforms for such analyses. Ion mobility-mass spectrometry (IM-MS) provides rapid (ms) gas-phase electrophoretic separations on the basis of molecular structure and is well suited for integration with rapid (us) mass spectrometry detection techniques. This report will describe recent advances in IM-MS integrated omics measurement strategies in the analyses of complex biological samples of interest in systems, synthetic, and chemical biology in clinical chemistry applications. New advances in bioinformatics and biostatistics will also be described to approach biological queries from an unbiased and untargeted perspective and to quickly mine the massive datasets gathered to provide targeted and actionable information.

Jen leads the Global Discovery & Bioanalytical Sciences group at Novartis, where she directs the scientific and operational strategy for the bioanalysis of small and large molecule therapeutics. Jen is also responsible for identifying new bioanalytical technologies and solutions to support the Novartis portfolio. Jen received her BSc in Chemistry from the University of Alberta in Edmonton, AB Canada, then completed her graduate studies receiving a MS and a PhD in Chemistry from the University of Michigan. Jen then completed her postdoctoral fellowship in the analytical chemistry department at Pfizer in Ann Arbor, MI. Jen has worked for numerous pharmaceutical companies over the past 2 decades in the bioanalytical field, spanning the pipeline from discovery through the clinic. She also developed expertise in large molecule mass spectrometry analysis while working at the Proteomics Core facility at Oregon Health and Science University in Portland, OR.

Grace is an LC-MS/MS Applications Development Specialist at St Paul’s Hospital in Vancouver BC. She is passionate about developing the most user friendly and streamlined LC-MS/MS assays as possible for routine use in the Special Chemistry Mass Spec Lab. She loves troubleshooting, especially when the cause of problem has been discovered and the issue solved!

Candice is an Assistant Chemist at the Pacific Environmental Science Centre, working under the supervision of Dr. Dayue Shang. She is also currently a 4th year Honours Chemistry undergraduate student at the University of British Columbia.

Josh is a Laboratory Scientist in the Newborn Screening and Biochemical Genetics Laboratories at BC Children's Hospital in Vancouver, Canada. He has a BSc in Chemistry from Simon Fraser University and a MSc in Chemistry from the University of Toronto. After working in the clinical and pharmaceutical industry for 4 years Josh returned to academia and completed a PhD in Experimental Medicine from the University of British Columbia with a focus on cardiovascular disease. Josh is passionate about developing and implementing innovative analytical strategies in the clinical laboratory with a focus on mass spectrometry!

You are invited to join the British Columbia Mass Spectrometry User's Group meeting.
The virtual session will include:

Speaker: Jennifer Cunliffe, PhD
Title: Application of High Resolution Mass Spectrometry for Proteomics

Speaker: Grace van der Gugten
Title: When Mass Spec gives the wrong answer: Investigating where and why an assay went wrong.
Summary: Routinely unacceptable EQA results for our LC-MS/MS assay for 1,25-dihydroxyvitamin D prompted an investigation into our assay. This presentation will share the investigation steps taken, the possible causes and the resulting solution.

Speaker: Candice Chua
Title: Enhanced weathered crude oil analysis by GC/FID, GC/MS diagnostic ratios, and multivariate statistics
Summary: In a simulated case study, artificially weathered crude oil “spill” samples were matched to unweathered suspect “source” oils through a three-tiered approach as follows: Tier 1 gas chromatography-flame ionization detection (GC/FID), Tier 2 gas chromatography-mass spectrometry (GC/MS) diagnostic ratios, and Tier 3 multivariate statistics of GC/MS data. This study served as proof of concept for a promising and new method of crude oil forensics that applies principal component analysis (PCA) and partial least squares discriminant analysis (PLSDA) in tandem with traditional forensic oil fingerprinting tools to confer additional confidence in challenging oil spill cases.

Speaker: Joshua Dubland, PhD
Title: Making a sour analysis sweet again: Case studies
Summary: Case 1 - Post-validation, an LC-MS/MS assay shows dramatically reduced signal intensity for one analyte following a laboratory reorganization. Case 2 – Differentiating between two co-eluting isomers by GC-MS when changing the column isn’t an option.

Prof. Hewison is currently Professor of Molecular Endocrinology within the Institute of Metabolism and Systems Research (IMSR) at the University of Birmingham, UK, having worked from 2005 – 2014 at the University of California Los Angeles. Prof. Hewison’s main research interest is vitamin D and its importance to human health. He has published over 230 research papers on classical (skeletal) and non-classical (extra-skeletal) actions of vitamin D. Prof. Hewison’s group is at the forefront of research linking vitamin D and the immune system, with implications for a wide range of clinical disorders including infectious, inflammatory and autoimmune disease. Current studies are focused on the analysis of vitamin D-insensitivity in T lymphocytes from the inflamed joints of patients with rheumatoid arthritis. This may provide an explanation for the limited success of vitamin D supplementation in some clinical trials. Other projects have explored the role of cell metabolism pathways in mediating the immunomodulatory effects of vitamin D, and the opportunities this may provide for improved therapeutic use of vitamin D. The Hewison group has also pioneered a range of studies to explore alternative markers of vitamin D ‘status’. This includes development of novel high throughput liquid chromatography-tandem mass spectrometry technology to measure multiple metabolites of vitamin D – the vitamin D metabolome – and analysis of the role of the serum vitamin D binding protein as a determinant of vitamin D bioavailability within the immune system. Prof. Hewison is a recipient of a Royal Society Wolfson Fellowship. His research is supported by grants from the Medical Research Council and Biotechnology and Biological Sciences Research Council (UK), and the National Institutes of Health (USA).

Prof. Hewison’s group is at the forefront of research linking vitamin D and the immune system, with implications for a wide range of clinical disorders including infectious, inflammatory and autoimmune disease. Current studies are focused on the analysis of vitamin D-insensitivity in T lymphocytes from the inflamed joints of patients with rheumatoid arthritis. This may provide an explanation for the limited success of vitamin D supplementation in some clinical trials. Other projects have explored the role of cell metabolism pathways in mediating the immunomodulatory effects of vitamin D, and the opportunities this may provide for improved therapeutic use of vitamin D. The Hewison group has also pioneered a range of studies to explore alternative markers of vitamin D ‘status’. This includes development of novel high throughput liquid chromatography-tandem mass spectrometry technology to measure multiple metabolites of vitamin D – the vitamin D metabolome – and analysis of the role of the serum vitamin D binding protein as a determinant of vitamin D bioavailability within the immune system.

Dr. Hoofnagle's laboratory focuses on the precise quantification of recognized protein biomarkers in human plasma using LC-MRM/MS. In addition, they have worked to develop novel assays for the quantification of small molecules in clinical and research settings. His laboratory also studies the role that the systemic inflammation plays in the pathophysiology of obesity, diabetes, and cardiovascular disease.

Dr. Xin Yan received her Ph.D. in Chemistry from Purdue University in 2015 under the supervision of Professor R. Graham Cooks. After graduation, she did her postdoctoral research with Professor Richard N. Zare at Stanford University.
Dr. Xin Yan joined the chemistry department, Texas A&M University as an assistant professor in the summer of 2018. Her research centers around the development and application of droplet chemistry in lipid/metabolite analysis, reaction acceleration, and new synthetic methods.

Lipids play a vital role in maintaining cellular functions. Altered lipid metabolism is currently considered a hallmark of many diseases, which highlights the importance of the characterization of lipid composition in understanding, diagnosing, and treating pathologies. Discrimination of isomeric species is challenging in lipidomics. In this talk, I will introduce the microdroplet electrochemical methods capable of resolving different types of isomers commonly encountered in lipid samples using electrospray ionization mass spectrometry. The methods take advantage of the voltage-controlled and dramatically accelerated electrochemical derivatization of lipid isomers in microdroplets to achieve structural elucidation. Applications of the electrochemical mass spectrometry methods in real sample analysis will also be included.

R. Graham Cooks is the Henry Bohn Hass Distinguished Professor in the Department of Chemistry at Purdue University. He has served as major professor to 140 PhD students. Dr. Cooks’ was a pioneer in the conception and implementation of tandem mass spectrometry (MS/MS) and of desorption ionization, especially molecular secondary ionization mass spectrometry (SIMS). In 2015 his lab performed exploratory analysis of small molecules in cerebrospinal fluid from which the MRM-profiling method emerged. His work also includes the development of miniature portable mass spectrometers using ambient ionization and application of this combination to problems of trace chemical analysis at point-of-care. His interests in the fundamentals of ion chemistry focus on chiral analysis based on the kinetics of cluster ion fragmentation. His group also studies collisions of ions at surfaces for new methods of molecular surface tailoring and analysis, and nanomaterials preparation by soft-landing of ions and charged droplets. Dr. Cooks also launched new method of preparative mass spectrometry based on accelerated reactions in microdroplets. Dr. Cooks has been recognized with the Mass Spectrometry and the Analytical Chemistry awards of the American Chemical Society, the Robert Boyle Medal and the Centennial Prize of the Royal Society of Chemistry, and the Camille & Henry Dreyfus Prize in the Chemical Sciences. He is an elected fellow of the American Academy of Arts and Sciences, the Academy of Inventors and the U.S. National Academy of Sciences.

Nicolás is a third year PhD student under the supervision of Prof. Graham Cooks at Purdue University. He earned two bachelor’s degrees, one in Chemistry (cum laude, 2017) and one in Industrial Engineering (summa cum laude, 2018), from the Universidad de los Andes (Bogotá, Colombia). Since joining the Cooks’ group his research has focused on several applications of ambient ionization mass spectrometry for the rapid and simple analysis of complex mixtures, particularly oriented towards forensics and high throughput bioanalysis. Recently he was awarded the 2020-2021 Charles H. Viol Memorial fellowship for his work during his first years as doctoral student.

We describe an automated high throughput screening system which is used to acquire mass spectra at a rate of 6,000 samples/hour using desorption electrospray ionization (DESI). The system has been used to screen organic reactions and select optimum conditions for scaled-up drug synthesis, to analyze biological fluids without sample workup, to examine tissue library arrays and to perform label-free quantitative measurements of enzyme kinetics. Extensions of the instrumentation to collection of small amounts of synthesis products for in situ bioassays are also described.