Location: De Anza 1 (Portola Hotel > Ground Floor)

Albert Tsai, MD, PhD Stanford Dr. Tsai received his undergraduate training at the University of California, Los Angeles (B.S., Biochemistry, summa cum laude), followed by combined medical and graduate training at the University of Southern California (M.D., Ph.D., Biochemistry). He completed anatomic and clinical pathology (AP/CP) residency and hematopathology fellowship at Stanford University, receiving board certification in AP/CP and hematopathology. As an instructor, he performed clinical diagnostic duties on the hematopathology service while doing postdoctoral training in the laboratory of Dr. Sean Bendall, with funding from the Damon Runyon Cancer Research Foundation. As a physician and hematopathologist, he seeks to mechanistically dissect myelodysplastic syndromes (MDS) using highly-multiplexed immunophenotyping — mass cytometry / cytometry by time-of-flight (CyTOF) and multiplexed ion beam imaging (MIBI). MDS is an especially complex and heterogeneous disease of abnormal blood cell development with increasing prevalence and few treatments. By combining practical experience clinically diagnosing MDS, next generation single cell proteomic approaches, fundamental discoveries in the biology of MDS, and knowledge of clinical laboratory testing, we hope to develop new clinical diagnostics for personalizing MDS therapies and therapeutic monitoring. His clinical diagnostic duties are on the hematopathology service, primarily in the diagnosis of MDS, leukemias, lymphomas, and other hematopoietic diseases from blood, bone marrow, and tissue samples.

How pathologists diagnose human tissue samples differs markedly from how many researchers study them. Research approaches often seek to reduce two-dimensional tissue imaging to single cell data, i.e. cytometry-on-a-slide. However, these methods are complicated by technical aspects of tissue processing, and they may miss the overarching histologic patterns which underlie pathologic diagnosis. Thus, early engagement with pathologists is useful not only for obtaining tissue samples, but also for understanding structure-function relationships and relevance to disease. Furthermore, pathologists regularly integrate multiple data modalities to classify diseases, e.g. histology with antibody-based protein detection and DNA sequencing. Their understanding of the utilities of each modality within the larger diagnostic context is helpful for identifying potential roles for new technologies.

Location: De Anza 1 (Portola Hotel > Ground Floor)

Kristina Schwamborn, MD, PhD Technical University of Munich

Matrix assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) combines the excellence in molecular characterization of mass spectrometry with microscopic imaging capabilities of stained tissue samples, enabling the precise location of different analyte classes (e.g., proteins, peptides, lipids, glycans) directly within intact tissue. In particular in the field of pathology, that can aid in tumor diagnosis, tumor subtyping, biomarker identification, prognostic prediction, and characterization of tumor margins during tumor resection procedures. Since MALDI MSI goes far beyond microscopy, it is ideal for these endeavors. It can generate molecular maps of tissue sections that can elucidate the underlying biochemistry or provide information on how therapeutics or toxins influence the function or misfunction of an organ. Thus, it has the potential to overcome limitations of other approaches in the identification and routine diagnostic measurement of new marker molecules/profiles.

Different applications in the field of pathology/ oncology will be presented that highlight possible applications of MALDI MSI in Pathology. Combining MALDI MSI, histology, and statistical analysis allows for reliable and fast subtyping in a number of different tumor types while also conserving material that could be used for additional testing.

Location: Steinbeck 1 (Conference Ctr > 2nd Floor)

Margret Thorsteinsdottir, PhD University of Iceland Professor in Pharmaceutical Analytical Chemistry at the Faculty of Pharmaceutical Sciences, University of Iceland and R&D Director of ArcticMass LTd, Reykjavik, Iceland. Dr. Thorsteinsdóttir received her PhD from Uppsala University, Sweden in 1998. From 2000 to 2009 she was the managing director of Bioanalytical Laboratories at deCODE Genetics, Reykjavik, Iceland. She has extensive experience in development of analytical methods for metabolite profiling and quantification of clinical biomarkers in various biofluids utilizing chemometrics with the goal of improved clinical management of patients towards personalized patient care. Her current research interest includes studies of lipid metabolism in cancer cells and profiling plasma derived biomarkers for early detection of BRCA-related breast cancer. She is responsible for implementation of clinical mass spectrometry for support of diagnostics and therapeutic drug monitoring in collaboration with ArcticMass and the Landspitali University Hospital, Reykjavik, Iceland with major focus on quantitative targeted proteomics for clinical diagnosis. She is a principal investigator of the Icelandic Research Rannis projects, profiling metabolites for breast cancer diagnosis and search for novel biomarkers for early breast cancer diagnosis by metabolomics. Dr. Thorsteinsdóttir is a principal investigator for the Marine Biotechnology ERA-net project CYNOBESITY and the Horizon 2020 project MossTech, with the main task to isolate, identify and structurally characterize bioactive compounds from cyanobacteria, Icelandic mosses and liverworts. She is one of the founders of Females in Mass Spectrometry (FeMS), she is a vice-leader of the working group clinical significance and applications of (epi)lipidomics in the pan-European network, EpiLipidNET and vice-chair of the Nordic Metabolomics Society.

Finnur Eiriksson, PhD ArticMass

Objectives

The objective of the workshop is to provide an introduction into design of experiments (DoE) for clinical application with special focus on optimization of MS-based clinical assays. The workshop is focused on practical implementation of DoE and will demonstrate how method development of sample preparation and UPLC-MS/MS method for quantification of clinical biomarkers can become much more efficient by utilizing DoE.

Summary

Design of experiments (DoE) is an efficient tool for development and optimization of UPLC-MS/MS platform for quantification of biomarkers in complex biological matrices. The UPLC-MS/MS platform is composed of several processes which involve many experimental factors that need to be simultaneously optimized to obtain a true maximum sensitivity with adequate resolution at minimum retention time. DoE offers a practical approach for performing experiments in accordance with a predefined plan, modelling by empirical functions, and graphical visualization. Basic concept of DoE will be presented with emphasis on practical implementation of DoE which includes the three main stages, screening, optimization, and robustness testing. To demonstrate the benefit of DoE, two case studies will be presented. The first case is DoE optimization of sample preparation in bottom-up targeted protein workflow. The second case is DoE optimization of UPLC-MS/MS assay for clinical diagnostic and therapeutic drug monitoring of patients with adenine phosphoribosyltransferase (APRT) deficiency. A polynomial model which corresponds to the objective of the case study is specified and an experimental design that supports the selected model is generated. Significant factors were studied via central composite design and related to responses utilizing partial least square regression. Both cases showed that DoE is an excellent tool for optimization of sample preparation for biological samples and UPLC- MS/MS quantification method for clinical biomarkers. A significant reduction of sample preparation time was achieved with increased yields for selected peptides and a reliable UPLC-MS/MS assay for simultaneous quantification of urinary 2,8-dihydroxyadenine (DHA) and adenine was optimized efficiently with DoE.

Syllabus

• Design of Experiments (DoE) – Get it right from the beginning
• Basic concept and assessment of DoE
• Optimization of sample preparation and UPLC-MS/MS clinical assay by DoE

Location: Steinbeck 2 (Conference Ctr > 2nd Floor)

Jerzy Adamski, PhD Metaron Diagnostics i.G., Technical University of Munich

CANCELLED : Due to the presenter being unable to attend (March 2, 2024).

Objective

This workshop will address study design challenges for metabolomics that must be performed prior to metabolomics measurement and data processing.

Summary

The workflow of a metabolomics experiment follows several interdependent phases. The scientific question determines the study model and the type of metabolite detection. Pilot studies are often performed to validate the research question and the analytical approach chosen. Sample identity, preanalytics, sample matrix, confounders, timing, randomization, budgeting and resources, contingency plan, legal issues, governance, and replication are important considerations in the study design phase. Metabolomics requires special quality control and quality assurance procedures because of the many variables involved in sample preparation and analysis. Analytical procedures include quality assurance, matrix-matched reference samples, and analytical quality control. Data validation is performed to verify technical parameters, evaluate sample quality, and identify outliers. In the initial phase of a project, it is critical to define the dataset to be released, which must include metabolomics data, SOPs, assays used, randomization type, normalization structure, and data imputation protocols.

Specific Topics

• understanding cohort structure
• essential clinical phenotyping
• procedures for sample selection
• sample quality assessment
• analytical assay selection
• randomization for measurements
• requirements for preparation for metadata and data depositories
• GOFAIR initiative for sustainable research

Location: Steinbeck 3 (Conference Ctr > 2nd Floor)

Christopher Chouinard, PhD Clemson University I received my PhD from University of Florida in 2016, where I developed ion mobility-mass spectrometry (IM-MS) methods for steroids and vitamin D metabolites. I then worked as a post-doctoral research at Pacific Northwest National Laboratory, building Structures for Loss Ion Manipulations (SLIM) ion mobility instrumentation for application in metabolomics and proteomics. In 2018, I began my independent career as an Assistant Professor at Florida Institute of Technology. I have since moved to Clemson University in August 2022. Work in my research group focuses on ion mobility-mass spectrometry (IM-MS)-based methods and technology, including structurally selective reactions for improved characterization of steroids and other controlled substances.

Robin Kemperman, PhD Children’s Hospital of Philadelphia Robin Kemperman received his Bachelor's in chemistry from the HAN University of Applied Sciences in The Netherlands. Thereafter, he fulfilled his MSc and PhD in analytical chemistry at the University of Florida under the direction of Dr. Richard Yost. Currently, he works at the Children's Hospital of Philadelphia as Sr. Mass Spectrometrist in the Metabolic and Advanced Diagnostics Lab. Dr. Kemperman's work has covered a variety of aspects in mass spectrometry, including targeted analysis of steroids and ketone bodies using LC-MS/MS, bile acid, opioid, and glycan isomer separations using ion mobility spectrometry, and metabolomics High-Resolution MS. Dr. Kemperman is experienced in clinical MS-based validations and has presented his work at a variety of national and international meetings. Focusing on the future, he is interested in working on novel innovations for biomedical and clinical applications.

Objectives

Attendees will learn the basic principles of ion mobility, benefits and challenges to routine implementation in the clinical lab, method development, and current applications.

Objective 1: Understand the basic operating principles of IMS and the differences between the different techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.)

Objective 2: Recognize the benefits and limitations to incorporating IMS into conventional LC-MS/MS workflows in the clinic.

Objective 3: Become familiar with method design and development and current/future applications.

Summary

Ion mobility-mass spectrometry (IM-MS) has become a cornerstone of biomedical analysis, with applications ranging from isomeric small molecule differentiation to the study of protein structure. Despite its advantages, IM-MS has yet to see routine implementation in the clinical lab due to challenges in quantitation, limited universal standards, data processing software, and reproducibility across different IM techniques/vendor platforms. This workshop will introduce common IM techniques and their operating principles, expanding upon the benefits of incorporating IM into conventional LC-MS/MS workflows and discussing its challenges. More importantly, recent advances in hardware, software, and data processing approaches will be highlighted. Finally, an overview of current applications (including metabolomics, lipidomics, and proteomics examples) will be provided.

Syllabus

1. Basic Operating Conditions of IMS: Electric field application, experimental conditions (temperature, pressure, gas composition)
2. Different IMS techniques: Drift tube/traveling wave, field asymmetric/differential mobility, emerging techniques (i.e., TIMS, SLIM, cIMS, etc.)
3. Applications: Current examples from metabolomics, lipidomics, and proteomics

Location: Colton (Conference Ctr > 2nd Floor)

Cajetan Neubauer University of Colorado, Boulder My research is focused on two small molecules that shape the Earth system and whose roles are profoundly changing due to human activity. Nitrate – the chemical form in which plants assimilate nitrogen – impacts the structure, productivity and biodiversity of ecosystems via a complex cycle of microbially-mediated reactions. Methionine – the initiating amino acid in protein synthesis – is fundamental to all cells and has been a regulator for the growth of organisms throughout evolution. Since the beginning of science, improvements in measurements have led to discoveries. We are developing a new generation of isotope analytics that is based on ESI-Orbitrap mass spectrometry. This technique is opening detailed new views into natural processes. In particular it can reveal the history of a chemical compound, for example the origins of building blocks and the process by which they have been combined. The overarching aim of my research program is to reveal detailed biological information that is stored within molecules. This aspect of biology is called "intramolecular biology."

Alan Rockwood, PhD, DABCC University of Utah, School of Medicine Alan Rockwood, PhD, DABCC is Professor (Clinical) Emeritus of Pathology at the University of Utah School of Medicine in Salt Lake City, Utah, USA. Originally trained in Physical Chemistry, he performed research on the fundamentals of mass spectrometry and instrumentation development before focusing his career on Clinical Chemistry. He is certified by the American Board of Clinical Chemistry and has held a Certificate of Qualification in Clinical Chemistry from the New York State Board of Health. Currently, his primary area of research is the development of mass spectrometry-based quantitative assays for targeted analytes of clinical interest, including small molecules and more recently proteins and peptides. Additionally, he maintains a smaller research effort on fundamentals of mass spectrometry, particularly novel approaches for isotopic profile calculations. He has published >150 papers in peer reviewed journals.

Objectives

Participants will 1) learn the basic principles of isotopic effects and be able to explain how they can be used to study human metabolism, including drug metabolism, and 2) be able to explain how emerging measurements on bioanalytical mass spectrometers such as ESI-Orbitrap systems can perform accurate isotope ratios on molecular species.

Summary

Isotope ratio mass spectrometry (IRMS) measures the relative abundance of different isotopes of an element, providing valuable insights into the molecular mechanism of metabolic diseases, drug metabolism, and links between nutrition and health. In classical IRMS complex molecules are converted to low molecular weight gases, thus losing important intramolecular isotopic information. IRMS is now becoming possible on bioanalytical mass spectrometers such as ESI-Orbitrap systems.These recent advances give access to isotopic information in intact biomolecules, drugs, and metabolites. This workshop will introduce the principles that cause isotopic effects in the human body, introduce the technologies used to make highly precise measurements of isotope ratios in metals and biomolecules, and illustrate how recent advanced on doing IRMS using ESI-MS instrument can open new avenues of IRMS for biomedical and clinical research application. Methods and studies we highlight will help stimulate thought on new application areas for IRMS in biomedical research and eventual clinical diagnostics.

Topics Covered

* Principles that cause isotope effects in the human body
* IRMS technologies and current advances
* Applications of IRMS for biomedical and clinical research

Location: De Anza 1 (Portola Hotel > Ground Floor)

Zoltan Takats, PhD Imperial College Professor Takats has obtained his PhD from Eötvös Loránd University, Budapest, Hungary. He has worked as a post-doctoral research associate at Purdue University, Indiana, USA. After returning to Hungary, he served as Director of Cell Screen Research Centre and also as Head of Newborn Screening and Metabolic Diagnostic Laboratory at Semmelweis University, Budapest. Professor Takats was awarded the Starting Grant by the European Research Council in 2008 and he subsequently, became a Junior Research Group Leader at Justus Liebig University, Gießen, Germany. He moved to the United Kingdom in 2012 and currently works as a Professor of Analytical Chemistry at Imperial College London. Professor Takats has pursued pioneering research in mass spectrometry and he is one of the founders of the field of ‘Ambient Mass Spectrometry’. He is the primary inventor of six mass spectrometric ionization techniques and author of 78 peer reviewed publications. He was the recipient of the prestigious Mattauch-Herzog Award of the German Mass Spectrometry Society and the Hungarian Star Award for Outstanding Innovators. He is the founder of Prosolia Inc, Medimass Ltd and Massprom Ltd, all companies pursuing analytical and medical device development.

Lauren Ford, BSc (Hons), PhD Imperial College London I am an early career researcher and have a background in materials chemistry, having studied for a PhD between the School of Chemistry and the School of Design at the University of Leeds I have experience in polymer technology, physical adsorption theory and purification. I am interested in using these skills to aid detection of disease using mass spectrometry detection. Since joining Imperial in 2019 I have been working as a post-doctoral research associate in the department of Surgery and Cancer, working on the iEndoscope project. This project utilised ambient ionisation mass spectrometry and allowed me to gain critical experience of ambient MS for early cancer detection.

Objectives

To identify methods to deliver mass spectrometry guided surgery to become routinely used in the clinical interventional world. The workshop will focus on the interpretation of clinical information/data and how this should be fed back to healthcare professionals and ultimately patients. The workshop will highlight the limitations of current technologies and developments enabling clinical adoption.

Summary

The need for in-situ, real time tissue identification has been dramatically increasing with the development and deployment of robotic and other high-precision surgical approaches. While surgical mass spectrometry techniques have been continuously developed, published, and demonstrated in human surgical theatres, none of these approaches have reached regulatory approval and routine application in surgery. We will use this interactive setting to discuss overcoming current roadblocks to delivering technology for patients and healthcare professionals. The workshop will give an overview of the current mass spectrometry technology developed and the strengths and weaknesses in each approach. This will be followed by discussing the embedding of the approach both into existing oncology and clinical diagnostic systems. Using Mass Spectrometry in surgery will change how interventional cancer care is delivered, hence it is important to ensure data tools are developed which can be relied on. Delivery of the obtained clinical information in the operating theatre is also important to explore. As part of this workshop, we will discuss data visualisation strategies such as in the virtual reality space, delivery of feedback to the clinical healthcare professionals and tools developed to advance usability, such as navigation. Data interpretation in the wider context of clinical oncology will also be explored.

Syllabus/Topics

• Surgical mass spectrometry methods – strengths, weaknesses, applications and future perspectives
• Embedding of technology into healthcare systems. How to deliver clinical information, data interpretation, navigation guidance and feedback.
• Regulatory and health economics aspects.

Location: De Anza 2 (Portola Hotel > Ground Floor)

Annie Moradian, PhD Precision Biomarker Laboratories Annie Moradian is a Lead Biomedical Scientist at Precision Biomarker Laboratories at Cedars-Sinai Medical Center. Annie obtained her PhD in Analytical Chemistry from University of British Columbia. She has extensive background in both quantitative and discovery proteomics. Currently her focus is on development and optimization of new high-throughput LC-MS methods for biomarker candidate discovery and verification.

Chi Nguyen, PhD Precision Biomarker Laboratories Cedars-Sinai Medical Center Los Angeles

Objectives

A case study approach will be used to demonstrate the following:
- Introduce tools used for unbiased biomarker identification and discuss recent discovery proteomics techniques
- How to utilize and mine discovery proteomics data to create targeted proteomics methods
- Demonstrate software tools and applications used to develop targeted methods

Summary

In this workshop, we will describe in detail the path from collecting and utilizing comprehensive information from various sources of discovery proteomics analyses to the creation of targeted proteomics methods for the verification of protein biomarkers. This workshop will be divided in two sections. In the first section, a discovery proteomics strategy will be discussed with a focus on the study design, the data acquisition approach, and the data analysis pipeline for biomarker selection. An example case study will be presented and discussed. In the second section, the attendees will be guided through a step-by-step instruction on how to utilize pertinent information acquired from the discovery approach to develop a targeted proteomics method. A brief introduction on Skyline and instructions on working with spectral libraries in Skyline will be included. Furthermore, technical aspects such as the choice of instrument, flowrate and acquisition strategy at every step of the targeted proteomics assay development will be tackled and discussed.

Location: De Anza 3 (Portola Hotel > Ground Floor)

Judy Stone, MT (ASCP), PhD, DABCC Clinical Chemist (retired) 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 was 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).

Prof. Dr. med. Michael Vogeser University Hospital, LMU Munich Dr. Michael Vogeser, MD, is specialist in Laboratory Medicine and senior physician at the Hospital of the University of the Ludwig-Maximilians-University Munich, Germany (LMU; Institute of Laboratory Medicine). As an Associate Professor he is teaching Clinical Chemistry and Laboratory Medicine. The main scope of his scientific work is the application of mass spectrometric technologies in routine clinical laboratory testing as translational diagnostics. Besides method development in therapeutic drug monitoring and endocrinology a further particular field of his work is quality and risk management in mass spectrometry and in clinical testing in general. Michael has published >240 articles in peer reviewed medical journals. Michael heads the Commission for In Vitro Diagnostics in the German Association of Scientific Medical Societies (AWMF).)

Objective

To explain the basic principles, requirements, and processes of laboratory accreditation; with examples and a focus on laboratories that are in transition from research to patient care.

Summary

Many more countries are now requiring clinical laboratory accreditation to ISO 15189 or alternative standards. Accreditation presents a particular challenge for highly complex in-house testing such as mass spectrometry, but can also offer significant potential for improving processes and overall performance. Advantages and disadvantages of accreditation, risks, opportunities, and preparation strategies will be discussed. Extensive experience from both the perspective of the client and the assessor (inspector) will be shared. Our personal experience is with laboratory accreditation in the United States and the EU, but we will attempt to present these concepts from a global perspective.

Some Useful Documents