ARUP Institute for Clinical & Experimental Pathology
Mark Kushnir is Scientific Director, Mass Spectrometry R&D at ARUP Institute for Clinical and Experimental Pathology and Adjunct Assistant Professor at the Department of Pathology, University of Utah School of Medicine. Mark received PhD in Analytical Chemistry from Uppsala University (Uppsala, Sweden); his main areas of interest include development, application and clinical evaluation of novel mass spectrometry based clinical diagnostic methods for small molecule, protein and peptide biomarkers. He is author/coauthor of over 100 scientific peer reviewed publications.
Hsuan-Chieh (Joyce) Liao, PhD, NRCC, DABCC
University of Washington
Dr. Joyce Liao has more than ten years of clinical and management experience in laboratory medicine. She was a medical laboratory scientist in the newborn screening lab and obtained her Ph.D. degree in Clinical Medicine. She completed postdoctoral fellowship training in Clinical Chemistry at the University of Washington and Seattle Children’s Hospital. She is a board-certified Clinical Chemist and now served as an Associate Director at Harborview Medical Center, focusing on toxicology and mass spectrometry testing. She continues to focus on the translation of the analytical power of mass spectrometry to real clinical applications. Her interests include toxicology, mass spectrometry, and laboratory utilization.
Liang Li, PhD
Metabolomics Innovation Centre of Canada & University of Alberta
Dr. Li obtained his B.Sc. degree in Chemistry from Zhejiang (Hangzhou) University, China, in 1983, and his Ph.D. degree in Chemistry from the University of Michigan, Ann Arbor, USA, in 1989, under the direction of Professor David M. Lubman. After graduation, he joined the Department of Chemistry at the University of Alberta, Edmonton, Alberta in July 1989. He was an Assistant Professor from 1989 to 1994 and an Associate Professor from 1994 to 1999. He has been a Full Professor since July 1999. He has also been an Adjunct Professor of Biochemistry Department, Faculty of Medicine, since January 2008. He holds a Visiting Professorship at Zhejiang University supported by K. P. Chao’s Hi-Tech Foundation for Scholars and Scientists since 2006. He is a co-PI of The Metabolomics Innovation Centre (TMIC) mainly supported by Genome Canada. He was a co-PI of the Human Metabolome Database (HMDB) Project; his laboratory generated the HMDB MS/MS spectral library of the endogenous human metabolites that has been widely used by the metabolomics community for unknown metabolite identification based on spectral matches. Dr. Li was a visiting scientist at Hewlett Packard Research Lab (now Agilent), Palo Alto, CA (on sabbatical leave) from July 1998 to June 1999. He served as Director, Alberta Cancer Board Proteomics Resource Lab from February 2000 to December 2005. He served as Chair, Analytical Chemistry Division of Chemistry Department from July 2007 to June 2019. He serves as a Co-Director of TMIC since July 2019. He is a founder of Nova Medical Testing, Inc., a university spin-off company focusing on developing mass spectrometry based analytical solutions for medical and health diagnostic applications, including targeted diagnostic-panel analysis and global biomarker analysis.
Dr. Li is an elected fellow of the Royal Society of Canada (Academy of Science) (2019) (watch this video on Youtube). He is a Canada Research Chair in Analytical Chemistry (Tier 1, 2005-2012; renewed for 2012-2019). He has won several awards including McBryde Medal (2001) from the Canadian Society for Chemistry, Faculty of Science Outstanding Research Award (2002), McCalla Professorship (2002-2003), and Killam Annual Professorship (2004-2005) from the University of Alberta. He received the Young Explorers Prize from the Canadian Institute for Advanced Research (CIAR), which was given to Canada’s top twenty researchers aged forty or under in science and engineering (2002) as chosen by a panel of international judges. He was the recipient of the Rutherford Memorial Medal in Chemistry from the Royal Society of Canada (2003). He received The F.P. Lossing Award from the Canadian Society for Mass Spectrometry in 2006, The Maxxam Award from the Canadian Society for Chemistry in 2009 and Gerhard Herzberg Award from the Canadian Society for Analytical Sciences and Spectroscopy in 2010. He was one of the seven researchers selected as Brightest Minds 2016 by Canadian Institutes of Health Research. He is a fellow of the Chemical Institute of Canada since 2001.
Dr. Li has published more than 300 research papers mainly in the area of analytical mass spectrometry. He has given many invited talks including Hong Kong Polytechic University Distinguished Lecture in 2011, Distinguished Lectureship on Cerebrating the 50th Anniversary of Hong Kong Baptist University Faculty of Science in 2011, and Thermo Fisher Scientific Distinguished Scientist Lecture at the University of Montreal in 2013.
Dr. Li is currently an editor of Analytica Chimica Acta, an international journal on analytical chemistry with an Impact Factor of 6.558 in 2020 (2005-present). He is a member of the editorial advisory boards for Current Analytical Chemistry (2004-present), Journal of Advanced Research (Elsevier) (2014-), Biophysics Reports (Springer) (2015-), and Chemical Data Collections (Elsevier) (2015-). Dr. Li was a member of the editorial advisory boards for Journal of the American Society for Mass Spectrometry (2001-2006), Canadian Journal of Chemistry (2004-2006), Clinical Proteomics (2011-2016), and Analytical Chemistry Insights (2006-2018). He was a member of Analytical Chemistry’s A-Page Advisory Panel (2006-2008).
Adam McShane, PhD
Cleveland Clinic
1. Is There a Better Way to Plan and Perform Experiments? Introduction to Experimental Design
Mark Kushnir
Experimental design (DOE) is a technique that allows to be more efficient in planning, conducting and interpreting results of experiments. In Analytical Chemistry, DOE can be used during method development and optimization, troubleshooting performance and method evaluation. The DOE technique is also very helpful for identifying critical parameters, which have the most significant effect on performance of the methods, products, processes, or systems. The participants will learn why DOE is better than performing experiments by changing one variable at a time, learn about cause-and-effect relationships and interactions between factors. The participants will be introduced to several types of DOE, will learn some of the principles and guidelines for planning experiments.
2. Do Identical Instruments Produce Comparable Patient Results? A Stumbling Block of Harmonizing LC-MS/MS Assays in Clinical Laboratories
Joyce Liao
Clinical mass spectrometry laboratories usually validate individual assays on more than one instrument for continuous operation. Instrument comparison is a requirement of the College of American Pathologists and should be monitored at least twice a year to ensure comparability of results. Although the same style of liquid chromatography-tandem mass spectrometry system is preferred to minimize the variations between instruments, labs will inevitably encounter bias between two or more identical LC-MS/MS systems. Even in the absence of bias, the same instrument model with two different serial numbers may require different instrument settings to obtain similar sensitivity and specificity. In this roundtable session, we will review several comparison data sets from the same extractions injected and analyzed on two LC-MS/MS systems of the same make and model. We will discuss the potential factors, including mass spectrometer hardware (probe type and cleanness) and software settings (gradients, transitions, cone voltages, and collision energies) that could bias patient results and how to establish quality assurance policies to ensure adequate data review and accurate resulting. Examples of challenges we have faced and approaches we have found useful will be presented as a starting point for discussion.
3. Challenges and Possible Solutions on Direct Metabolome Profiling for Clinical Applications
Liang Li
Metabolomics is mainly used for disease biomarker discovery with an objective of translating newly discovered metabolite biomarkers into clinical applications. On the other hand, direct metabolome profiling of human biofluids may be used for monitoring health status of individuals on a population scale. However, there are a number of challenges in realizing this goal. This roundtable discussion will focus on exchanging views on several key areas of technical development that are needed to bring large-scale metabolome profiling to clinical settings. These include sample type, sample handling, analytical platforms, data processing, clinical metabolome informatics, cost and scale, etc.
4. Thyroid Function Testing Interference and How Mass Spectrometry Can Help: Interactive Case Studies
Adam McShane
Thyroid disease affects approximately 20 million Americans, and can lead to a multitude of symptoms. These are often grouped into 2 categories: hyperthyroidism (e.g., anxiety, weight loss, and sleep loss) and hypothyroidism (e.g. fatigue, weight gain, and forgetfulness). Clinicians rely heavily on biochemical assessment of the thyroid for accurate diagnosis to ensure prompt treatment. Routine thyroid function tests utilize immunoassays for their availability, speed, and automation. However, this testing suffers from a variety of interferences which can delay diagnosis or worse lead to miss diagnosis. Liquid chromatography-mass spectrometry (LC-MS) is a much more specific platform than immunoassays that can be utilized in the investigation of potential inferences. This session will utilize real-life, interactive cases to exemplify common thyroid function testing interferences, investigatory considerations, and how LC-MS can be utilized.
845
935
Molecular Phenomics in Systems, Synthetic, and Chemical Biology
Location: Steinbeck
John A. McLean, Ph.D.
Department of Chemistry, Vanderbilt University
John A. McLean is Stevenson Professor of Chemistry, Chair of the Department of Chemistry, Associate Provost for Graduate Education, and Director of the Center for Innovative Technologies at Vanderbilt University. He is an elected Fellow of the National Academy of Inventors and the American Association for the Advancement of Science. He earned his PhD at George Washington University in 2001 and subsequently performed postdoctoral research at Forschungszentrum Jülich in Germany and then at Texas A&M University before beginning at Vanderbilt University in 2006. McLean and colleagues have focused on the conceptualization, design, and construction of ion mobility-mass spectrometers and 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, personalized medicine, and ‘human-on-chip’ synthetic biology platforms. McLean has received a number of awards, including his laboratory serving as an Agilent Thought Leader Laboratory, a Waters Center of Innovation, the Chancellor’s Award for Research, the Thomas Jefferson Award, Excellence in Teaching Award from the student members of the American Chemical Society, a Defense Threat Reduction Agency Research Award, an American Society for Mass Spectrometry Research Award, and the Bunsen–Kirchhoff Prize from the GDCh (German Chemical Society), among others. He has served in many service roles to the profession including serving terms on the boards of professional societies, scientific companies, and major journals. He has published over 200 manuscripts and received over 30 patents in these and allied areas.
935
945
Intermission
Location: Steinbeck Foyer
945
1020
Plenary Keynote on Ion Mobility
Location: Steinbeck
Lingjun Li, PhD
University of Wisconsin - Madison
Lingjun Li is a Vilas Distinguished Achievement Professor and the Charles Melbourne Johnson Distinguished Chair Professor of Pharmaceutical Sciences and Chemistry at the University of Wisconsin-Madison (UW-Madison). Dr. Li received her B.E. degree in Environmental Analytical Chemistry from Beijing University of Technology, China and her Ph.D. degree in Analytical Chemistry/Biomolecular Chemistry from the University of Illinois at Urbana-Champaign (UIUC). She did three-way postdoctoral research at the Pacific Northwest National Laboratory, Brandeis University, and UIUC before joining the faculty at UW-Madison in 2002. Her research interests are in analytical neurochemistry, neuroproteomics and biological mass spectrometry. Dr. Li published more than 300 papers and has given more than 200 invited talks. She was the recipient of the ASMS Research Award, NSF CAREER Award, Sloan Fellowship, PittCon Achievement Award, and ASMS Biemann Medal, and was named one of the Top 50 most influential women in the analytical sciences and featured in the 2019 Top 100 Power List by the Analytical Scientist. She is currently an Associate Editor for the Journal of The American Society for Mass Spectrometry (JASMS) and serves on the Board of Directors for the US HUPO.
1025
1100
Differential Ion Mobility Spectrometry: Understanding the Chemistry in the Mass Spectrometer and How That Affects What Is Detected
Location: Steinbeck
Gary Glish, PhD
University of North Carolina
Professor Gary L. Glish earned his Ph.D. from Purdue University under the guidance of Graham Cooks. He spent 12 years as a staff scientist and group leader at Oak Ridge National Laboratory during which time he designed and built the first QTOF instrument and his group was the first to interface ESI to a quadrupole ion trap mass spectrometer. He left Oak Ridge to take his current position as a faculty member in the Department of Chemistry at the University of North Carolina. His group there focused a lot on the fundamentals and development of applications for quadrupole ion traps. More recently the lab has been involved in the development of differential ion mobility spectrometry and development of ionization techniques for real-time analysis of aerosols. He was an associate editor for the Journal of the American Society for Mass Spectrometry for 17 years and has served as VP for Arrangements, VP for Programs, and President of the American Society for Mass Spectrometry.
Differential Ion Mobility Spectrometry (DIMS) is a powerful tool that can help improve targeted detection of analytes using mass spectrometry (MS). DIMS has a number of advantages over more conventional drift type ion mobility techniques, but currently lacks the ability to determine collisional cross-sections. Some of the advantages of DIMS are: it is readily compatible with any type of mass analyzer; it is more orthogonal to MS because the separation is not based just on cross-section; and gas phase chemistry can be used to dramatically affect separation of analytes that are isomeric/isobaric and even have the same cross-section. A very under-appreciated aspect of DIMS is its ability to provide insight into the ionization chemistry and how that chemistry can significantly distort the resulting mass spectrum. This presentation will provide an overview of DIMS, examples of improvement of targeted analysis using DIMS with and without gas phase chemistry, and examples of how DIMS can provide understanding of chemistry occurring in the mass spectrometry experiment that can lead to inaccurate conclusions.
Discussion : Tackling Tough Issues in Toxicology LC-MS/MS Method Development
Location: Steinbeck 1
Hsuan-Chieh (Joyce) Liao, PhD, NRCC, DABCC
University of Washington
Dr. Joyce Liao has more than ten years of clinical and management experience in laboratory medicine. She was a medical laboratory scientist in the newborn screening lab and obtained her Ph.D. degree in Clinical Medicine. She completed postdoctoral fellowship training in Clinical Chemistry at the University of Washington and Seattle Children’s Hospital. She is a board-certified Clinical Chemist and now served as an Associate Director at Harborview Medical Center, focusing on toxicology and mass spectrometry testing. She continues to focus on the translation of the analytical power of mass spectrometry to real clinical applications. Her interests include toxicology, mass spectrometry, and laboratory utilization.
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
Heather Stieglitz, PhD, DABCC
The Ohio State University Wexner Medical Center
Dr. Stieglitz is currently an Assistant Professor at The Ohio State University Wexner Medical center and Co-Director of Clinical Chemistry and Toxicology. She received her PhD from Emory University and completed a postdoctoral fellowship in Clinical Chemistry at the University of North Carolina before joining Ohio State. She is board certified in Clinical Chemistry by the American Board of Clinical Chemistry. Her interests are in mass spectrometry-based clinical toxicology testing in adults and newborns.
Confirmatory urine drug testing by liquid chromatography tandem mass spectrometry (LC-MS/MS) remains a corner stone of clinical mass spectrometry testing. This testing offers significant financial and patient care advantages and thus represents an excellent opportunity for new labs looking to establish or expand their LC-MS/MS testing. A clinical laboratory aiming to setup such testing will be faced with what can seem like an overwhelming number of options and decisions, especially if the laboratory is new or has limited experience with LC-MS/MS testing. This interest group discussion aims to help labs navigate these complex decisions by highlighting some approaches used by three clinical chemists who oversee toxicology testing at three medical centers. Topics that will be discussed include 1. choosing what drug classes and analytes (parent drug, metabolites, etc) to include, 2. whether to detect conjugated or unconjugated drugs, and 3. determining appropriate measuring and reportable intervals. This interactive session will begin with an introduction of the topic using case examples of how each speaker approached the issue followed by an open discussion with the audience on the advantages and limitations of different approaches.
1645
1800
Discussion : Use of Reference Materials for Calibration and Validation in Clinical Mass Spectrometry Applications
Location: Steinbeck 2
Johanna Camara, PhD
NIST
Johanna began her employment at NIST as an NRC Postdoctoral Associate. Her activities have encompassed a wide variety of areas, including: MALDI-ToF mass spectrometry of bacteria, molecular cloning of stable-isotope labeled proteins for mass spectral internal standards, and the quantification of small organic molecules in pharmaceuticals, foods, and biological SRMs with liquid chromatography-mass spectrometry. She has participated in the Summer Undergraduate Research Fellowship program at NIST as an application reviewer and research mentor. Johanna is also the Clinical SRM Program Coordinator, the Quality Manager for the Organic Chemical Metrology Group, and the Deputy Quality Manager for the Chemical Sciences Division.
Reference materials (RMs), including certified reference materials (CRMs), are provided by the National Institute of Standards and Technology (NIST) and other RM producers to support global clinical measurement standardization. These materials are available in various forms, including neat powders, solutions, and clinical matrices. The intended RM uses include calibration and validation, depending on the material. Calibration with RMs may provide traceability to higher-order references when incorporated into specific measurement schemes. The choice of which RM to use and how to incorporate it into a measurement system depends on laboratory goals. This roundtable is designed to discuss RM production, availability, and options for incorporating RMs into clinical laboratory measurement applications. Many RMs are ideally suited for mass spectrometry-based measurement procedures. Many matrix matched RMs (blood serum, plasma, urine) are value assigned based on mass spectrometry-based Reference Measurement Procedures (RMPs). These RMPs typically separate and quantify individual metabolites, epimers, or other chemical variations of clinically relevant measurands that are not necessarily separated and detected by other laboratory techniques, such as immunoassays or microbiological assays. RM users may also need to propagate the measurement uncertainty of RM or other calibrator values to measurement results. NIST provides a publicly available online application ABACUS (Apps for Bayesian Analysis of Chemical quantities Using Shiny) intended as a tool for users to use all data from their experiments to calculate results with rigorous estimates of measurement uncertainty.
1645
1800
Discussion : Clinical LC-MS/MS User Training is Lacking : Moving Towards Training and Certification
Location: Colton
Judy Stone, MT (ASCP), PhD, DABCC
UCSF
Judy Stone, MT (ASCP), PhD, DABCC has worked with LC-MS in diagnostic laboratories since 1999. Her clinical practice involved small molecule method development, instrument to instrument and instrument to LIS interfacing, LC-MS automation, monitoring quality of LC-MS methods in production and staff training for clinical LC-MSMS. She served as faculty chair for the 2009 AACC online certificate program “Using Mass Spectrometry in the Clinical Laboratory”, as a scientific committee member for the MSACL Practical Training track, and is editor-in-chief for the AACC Clinical Laboratory News quarterly feature series on Clinical LC-MS. She enjoys documenting and presenting esoteric as well as absurdly common LC-MS problems in creative ways in order to help trainees learn troubleshooting (and avoid repeating her mistakes).
Currently, there exist no formal training programs or licensure prerequisites for medical laboratory quantitative LC-MS/MS method development scientists or technologists. Although rudimentary LC-MS/MS theory may be part of Medical Laboratory Scientist (MLS) or Medical Laboratory Technologist (MLT) programs, quantitative LC-MS/MS method development is highly complex and typically not included. Lab Directors who are authorized to approve LDT methods are not necessarily trained in the details of technical quantitative LC-MS/MS validation.
We see a need for training and certification. This round table aims to get input and discuss a way forward and discussion topics will include:
(1) Training options
Traveling Trainer
Laboratory Participant Training Sites
(2) Certification
how can we move forward?
What certification body is best?
This session is geared towards lab directors, lab scientists, and lab technologists.
The goal is to get input from the community about what is needed and how the needs can be addressed.