Improving patient outcomes by overcoming the challenges
of implementing high value tests in the clinical lab

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Educational Grantee Partners:

Brian Kelly, Dustin Bunch, Tim Collier, Joshua Hayden, Joyce Liao, Amanda Paulovich, Heather Stieglitz, Jenny Van Eyk


Agenda (Preliminary) - View Program

Wednesday, April 5

Time

Sessions

Morning Sunrise Activity

Location: Ferrantes

Industry Workshop : Thermo Fisher Scientific

Location: Steinbeck 1

Industry Workshop : Indigo BioAutomation

Location: Steinbeck 2

Industry Workshop : Waters

Location: Steinbeck 3

Coffee Hour

Location: Exhibit Hall - Serra

Visit the Exhibit Hall for a relaxed tour of the posters and Exhibits while enjoying your morning coffee.

Coffee Roundtables

Location: Steinbeck Foyer

Mark Kushnir, PhD

ARUP Institute for Clinical & Experimental Pathology

Hsuan-Chieh (Joyce) Liao, PhD, NRCC, DABCC

University of Washington

Liang Li, PhD

Metabolomics Innovation Centre of Canada & University of Alberta

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.

Molecular Phenomics in Systems, Synthetic, and Chemical Biology

Location: Steinbeck

John A. McLean, Ph.D.

Department of Chemistry, Vanderbilt University

Intermission

Location: Steinbeck Foyer

Plenary Keynote : Advancing Neuroscience Research via Novel Application of Ion Mobility Mass Spectrometry (IM-MS)

Location: Steinbeck

Lingjun Li, PhD

School of Pharmacy and Department of Chemistry, University of Wisconsin - Madison

Naturally occurring D-amino acid substitution, also known as amino acid D-isomerization, has been observed in many disease-associated peptides and proteins, including amyloid beta (Aβ), one of the putative biomarkers and drug targets for Alzheimer’s disease. Aβ is of significant interest due to the prevalence of post-translational D-isomerization in AD brain samples. While many prior reports have described technical advancements associated with the chiral discrimination and separation of D-amino acid containing peptides, there remains a dearth of tools capable of targeting Aβ42 stereochemistry. Ion mobility-mass spectrometry (IM-MS) has increasingly become an important alternative for the chiral separation of Aβ stereoisomers. IM-MS offers high analytical speed, low sample consumption and the ability to resolve small structural differences in peptide analytes, driven by recent technological advancements in IM-MS. In this talk, I will present a multi-dimensional IM-MS-based structural analysis strategy to facilitate the study of the chiral effects on monomer structure, oligomeric propensity, and receptor binding for Aβ peptides. Furthermore, analytical strategies to enhance peptide epimer differentiation and for site-specific localization of D-amino acid containing peptides will be presented. Finally, I will discuss our recent efforts in developing a high-resolution ion mobility-enabled sn-position resolved lipidomics strategy for probing phospholipid dysregulation in the brain of a mouse model for Alzheimer’s disease.

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

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.

Poster Session 1

Location: Exhibit Hall - Serra

Lunch Buffet

Location: Exhibit Hall - Serra

Poster Session 2

Location: Exhibit Hall - Serra

Scientific Session 1
Adding Value in Standardization of Proteomics Assays

Location: Steinbeck 1

Scientific Session 1
Lipidomics Biomarkers

Location: Steinbeck 2

Scientific Session 1
Toxicology/TDM

Location: Steinbeck 3

Scientific Session 1
TBA

Location: Colton

Coffee Break

Location: Exhibit Hall - Serra

Scientific Session 2
Emerging Technologies for PoC Dx

Location: Steinbeck 1

Scientific Session 2
Strategies in Lipidomic Assay Design

Location: Steinbeck 2

Scientific Session 2
Immunology

Location: Steinbeck 3

Scientific Session 2
TBA

Location: Colton

Intermission

Location: Steinbeck Foyer

Discussion : Tackling Tough Issues in Toxicology LC-MS/MS Method Development

Location: Steinbeck 1

Hsuan-Chieh (Joyce) Liao, PhD, NRCC, DABCC

University of Washington

Joshua Hayden, PhD, DABCC, FACB

Norton Healthcare

Heather Stieglitz, PhD, DABCC

The Ohio State University Wexner Medical Center

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.

Discussion : Job Fair

Location: Steinbeck 2

Discussion : Use of Reference Materials for Calibration and Validation in Clinical Mass Spectrometry Applications

Location: Colton

Johanna Camara, PhD

NIST

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.

Discussion : Clinical LC-MS/MS User Training is Lacking : Moving Towards Training and Certification

Location: Stevenson 1

Judy Stone, MT (ASCP), PhD, DABCC

UCSF

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.

MSACL Hospitality Lounge

Location: Club Room