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MSACL 2017 US: Preliminary Conference Program

Palm Springs, CA • January 22 - 26, 2017

With Thanks to Our Corporate Conference Sponsors:

And Special Thanks to Our Travel Grant Sponsors:

Sunday

How do I Modify My Conference Registration?
Answer: You should have received a confirmation email from RegOnline when you registered. Its subject will be MSACL Registration Confirmation. Within this email there is the option to Review your registration. Click on this and then Click on Manage your registration. Here you will need to enter the password that you created when you initiated your registration. Once in, you will be able to modify your registration.

(1) Daniel Holmes, MD
The Importance of Providing an Interface between Labs Results and Clinicians

(2) Thomas Annesley, PhD
Why be a reviewer? What to look for, and how to write an effective review.

(3) Rainer Vollmerhaus, PhD
Effective Results Management

(4) Karen Mahooti, MBA
Creating Compelling Presentations

SHORT COURSES

PRIVATE DISCUSSION GROUP
for Short Course Instructors
@ Chino

Monday

SHORT COURSES: Group A
10 minute Coffee Breaks at every :50, except before lunch and last hour of class.
Lunch 12:00 - 1:00 PM at Date Restaurant.

SHORT COURSES: Group B
10 minute Coffee Breaks at every :20, except before lunch and last hour of class.
Lunch 12:30 - 1:30 PM at Date Restaurant.

SHORT COURSES: Group C
10 minute Coffee Breaks at every :50, except before lunch and last hour of class.
Lunch 1:00 - 2:00 PM at Date Restaurant.

SHORT COURSES: Group A
10 minute Coffee Breaks at every :50, except last hour of class.

SHORT COURSES: Group B
10 minute Coffee Breaks at every :20, except last hour of class.

SHORT COURSES: Group C
10 minute Coffee Breaks at every :50, except last hour of class.

Tuesday

SHORT COURSES
10 minute Coffee Breaks at every :50, except last hour.

CMS JOURNAL DISCUSSION GROUP
@ Room 1 (Mojave)

Wednesday

CORPORATE WORKSHOPS (Early AM)

Ensuring the future of innovation in laboratory medicine
Chair: Stephen Master
Panel: Drs. Michael Bennett (President, AACC), Richard Friedberg (President, CAP), Steve Gonias (Chair of Pathology, UCSD)

The development of clinical laboratory medicine over the past century has been driven by advancements in the range of analytes measured and the analytical performance provided by novel technologies. The discipline has continued to create and implement new diagnostic modalities, with mass spectrometry being the most recent example of a technology that provides fundamental improvements in clinical testing capabilities. This historical success in clinical translation has depended on an adequately trained group of clinical laboratorians (both MD and PhD-level leadership as well as technologists) with the resources to perform assay development and optimization. However, the need for trained personnel has also spurred commercial development of turnkey (or even Point-of-Care) versions of these technologies. Paradoxically, this may reduce the willingness of medical centers to support trained personnel and the development infrastructure that is required for the further advancement of diagnostics through advanced mass spectrometry, informatics, and other emerging technologies.

In light of this issue, it will be important for professional societies and organizations dedicated to clinical chemistry and laboratory medicine to develop effective and cooperative strategies to ensure the ongoing intellectual vitality of the field. Specifically, a number of questions will need to be addressed: How do we provide adequate training in novel assay development for laboratorians? How do we identify and strategically support emerging technologies? What are the roles of academic medical centers, large reference labs, and IVD companies in technology development pipelines? How do we effectively advocate for funding sources that can encourage translational diagnostic development? How do we ensure that test development addresses significant medical needs? How do we communicate this value to health care payers? If technology development is centralized at a small number of centers, is this adequate for robust and creative development of technology?

1. A Dried Plasma Spot Device for the Collection and Automated On-Line LC/MS/MS Bioanalysis of Micro Blood Samples, 2. The Hematocrit Issue in Dried Blood Spot Analysis: Still an Issue?
1. Jack Henion, Ph.D. Emeritus Professor, Cornell University,
2. Christophe Stove, Ph.D. Professor, Ghent University

Major Dried Blood Spot (DBS) uses include screening for inborn metabolomic errors, epidemiological surveys (e.g. HIV monitoring), TDM, and toxicology. Implementing dried blood microsamples in an analytical workflow offers advantages, including simplification of sample collection, transport, storage and processing, as well as automation. Furthermore, it enables collection by non-medically trained persons in remote areas or at home. However, DBS also introduces challenges, such as a need for sensitivity and extensive method validation. Quantitative DBS analysis suffers from issues that continue to limit its breakthrough into routine bioanalysis. Amongst these are spot volume, spot inhomogeneity, and influence of hematocrit. The latter has proven especially problematic for widespread DBS acceptance. Recently, several approaches to accommodate the hematocrit issue have been developed, the pros and cons of which will be discussed in these presentations.

Practical Considerations for LC/MS Method Development of a Comprehensive Urine Pain Panel
Stephanie J. Marin, Ph.D.

Pre-Register

There has been increased interest in the clinical laboratory to develop comprehensive LC-MS/MS assays for urine drug testing, with 50 or more drugs and metabolites from multiple drug classes in a single method. These panels can increase throughout and improve laboratory efficiency, but create many challenges. Considerations for developing robust sample preparation methods for acidic, basic and neutral drugs for pain management and compliance testing in hydrolyzed urine specimens will be discussed. Method development strategies depending upon the compounds of interest will be presented.

CORPORATE WORKSHOPS (AM)

(1) Rapid Response: Precision Microbiome Detection, (2) Implementing the MicroFlex in the Clinical Laboratory to Identify Monoclonal Proteins in Serum
(1) Alexander A. Aksenov, PhD, Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD, (2) David Barnidge, PhD, Mayo Clinic

(1) The goal of the Rapid Response Precision Microbiome (RRPM) initiative at UCSD is to enable under 48-hour integrated "-omics" reporting to the physician. We will highlight what it takes to achieve such rapid turn-around on microbial molecules, host status, antibiotic resistance and/or drug metabolism, but also demonstrate points for optimization. (2) Introduction of a mass spectrometer into a clinical lab unfamiliar with the platform can be challenging. Here we discuss implementation of the Bruker MicroFlex MALDI-TOF into a protein immunology lab where the results obtained by mass spectrometry are compared to gel electrophoresis for specific clinical tests. The talk will present results observed using the MicroFlex in combination with automated liquid sample handling and matrix spotting for samples taken from a serum tube.

Can you reduce drug testing reimbursement challenges? A case study using HRMS for simultaneous analyte screening and quantitation.
Ana Grenier, Ph.D.

Continuing to manage healthcare cost constraints and monitoring therapy adherence and abstinence from non-prescribed drugs are important aspects to consider when physicians prescribe drugs with the potential of misuse, abuse, and addiction. Typically, drug monitoring is performed by screening urine using an immunoassay technique, and confirmed by mass spectrometry methodologies (GC/MS or LC MS/MS). Innovations in mass spectrometry technologies, such as resolution power, have made possible to improve the accuracy of testing in the clinical research market. Here, we present the clinical research evaluation for the simultaneous screening for analytes of interest and to quantify 47 drugs in urine by Liquid Chromatography-High Resolution Mass Spectrometry utilizing the Q Exactive™ instrument.

Low-flow Immunoaffinity Mass Spectrometry for the Masses and Implications for Biomedical Research
Michael Lassman, Principle Scientist, Merck

Only 4-5 years ago, neither low-flow mass spectrometry, nor immunoaffinity mass spectrometry (IA-LC/MS) could be considered routine platforms. These techniques, championed by specialized laboratories were only applied within a small number of academic research groups. High sensitivity platforms such as nanoflow mass spectrometry which measured proteins and peptides in in vitro cell lines, could not be easily incorporated into translational or clinical research. Leap forward half a decade, and IA-LC/MS is not simple, but is applied in many academic, research, government and hospital laboratories, allowing specific and robust quantitation of proteins and peptides in complex matrices that could only be measured previously using immunoassays. The value of IA-LC/MS in biomedical research will be explored as will implications on how IA-LC/MS may enable improved clinical research and patient care.

The Batch and Beyond - LCMS Result Automation Strategies and Analytics
Jim Edwards

The utilization of self-aware peak processing algorithms, a comprehensive quality architecture, and a streamlined, exception-based data/result review process have proven to be a successful strategy for improving both quality and throughput of LCMS analysis. The positive impacts of these batch-oriented optimizations can be significantly magnified by an additional layer of analytics and visualization which provide comprehensive information across instruments, assays, and batches over time. Please join us for a discussion on how these analytics are used to diagnose and prevent issues, target quality improvement efforts where they will be most effective, improve the quality and speed of automated result release, and align both the business and science aspects of the laboratory for an elevation in the efficiency and effectiveness of both.

The Evolution of SelexION® ION Mobility Technology: Past, Present and Future
Michael Jarvis

Pre-Register

Since its introduction in 2011, a growing list of LC-MS/MS applications in Clinical Research, Lipidomics, and Forensics have benefited from the use of SelexION(R) ion mobility technology. In this workshop we will present an overview of the technology, a history of the evolution of the product, and key examples of applications that have benefited from the use of this unique technology. We will also offer an exciting glimpse into the future, with a sneak peek at enhanced capabilities currently under development. Please join us for this exciting presentation!

CORPORATE WORKSHOPS (PM)

Detection of THC in oral fluid: the bane of a toxicologist’s existence.
Jill Yeakel, Lehigh Valley Toxicology

Pre-Register

This presentation will review the comparison of two sample preparation techniques used for the analysis of THC in oral fluid samples. Due to the chemical composition of THC, many scientists struggle to achieve both clean extractions and sensitive detection. The difference between solid phase extraction and filter vial preparations will be discussed to determine the optimal procedure prior to injection on a liquid chromatograph tandem mass spectrometer (LC-MS/MS). The instrumental parameters for analysis on the LC-MS/MS will also be provided to illustrate the most advantageous process for sensitively detecting THC along with a multitude of other drugs in a single method.

Paperspray MS in clinical research: early experiences in a U.K.  clinical laboratory
Lewis Couchman, Viapath Analytics, Kings College Hospital, London, UK

Paperspray MS offers a unique opportunity for clinical laboratories in which dried samples collected onto filter papers are analysed directly, and rapidly, without any prior sample extraction or preparation.In this workshop, our early experiences using Paperspray MS in conjunction with high-resolution, accurate mass detection (Q Exactive MS) will be discussed.  Considerations for the development of targeted quantitative applications from dried blood samples will be covered, including possible approaches to calibrate and add internal standards to account for paperspray and 'extraction' variability.  Secondly, the use of Paperspray MS as an analytical screening tool for drugs of abuse in dried urine samples will be discussed. Approaches for MS data acquisition to maximize the possibility of compound identification will be covered.

Demystifying a Couple of Challenging Assays
Seyed Sadjadi

In this workshop we discuss the use of stationary and mobile phase modifications to overcome chromatographic challenges in two quantitative assays: EtS/EtG and Chiral Amphetamines. First, we discuss the use of new LC stationary phases and mobile phases to solve the issues of polarity, isobaric urine interference, and retention in Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS). Next we will discuss the role of mobile phase pH in the chiral separation of methamphetamine and related compounds. The result of this investigation will be better understanding of how minor adjustments can make major improvements in assay performance.

Integration & Implementation of Fully Automated Sample Preparation for Mass Spectrometry
Isabel Cabruja (CEO, Shimadzu Italy) and Manoj Tyagi, PhD. FACB, NRCC -CC (Medical Lab Director, Captiva LLC)

The direct detection of disease related biological compounds and drugs in blood, urine, or other biological samples are possible thanks to mass spectrometry. The bottleneck, however, remains sample preparation, which is often tedious, increases contamination and introduces errors. This interactive workshop will take a closer look at the implementation of full sample preparation automation for triple quadrupole mass spectrometry. The Shimadzu CLAM-2000 is the first system in the world able to perform all steps fully automated from pretreatment of the sample to LCMS analysis We will demonstrate successful integration of sample prep automation for several assays, and Dr. Manoj Tyagi (Captiva Labs) will join us to present a fully automated approach to quantitative clinical toxicology and drug analysis from oral fluid matrix.

Microflow LC: Improving sensitivity for the quantitation of biopharmaceuticals with LC-MS
Remco Van Soest

Pre-Register

The utilization of Microflow LC is increasing in LC-MS due to the potential to increase sensitivity in comparison to traditional flow LC-MS. This workshop will focus on the successful application of MicroLC in the quantitation of peptide and protein drugs in plasma.

DISCUSSION GROUPS
@ Rooms around Ballroom Foyer

Participants will discuss how CDC Standardization Programs support laboratories with improving measurements for key hormones such as 25-hydroxyvitamin D, estradiol, and testosterone. Included will be additional discussions about new projects and tools available in CDC Standardization Programs.

Exhibitors, let MSACL know your thoughts on the way the conference is working for you and what we can do to make the experience better in the long run.

Feedback on the Practical Training track. How is it going? What can be improved?

1) Why be a reviewer? and 2) what to look for and how to write up an effective review.

Panel Discussion with: a practicing physican (Alyssa Burgart, Pediatric Anaesthesiology, Stanford), an MD clinical chemist (Dan Holmes, University of British Columbia), and a pediatric metabolism specialist (Mike Bennett, Children’s Hospital of Philadelphia).

Even the most advanced MS-based assay will fail if it cannot be translated into a clinical decision. A successful diagnostic should answer an important clinical question, provide adequate performance to support a clinical management decision, be delivered within a clinically relevant time-frame, and be understood by the clinician. Complex biomarker discovery efforts based on sensitive emerging technologies and improved biological understanding must still meet these basic criteria if we want our work to matter for patients. One key is ensuring that the clinical laboratory is adequately integrated with clinicians on a regular basis to understand the true clinical needs and ensure that the strengths and weaknesses of assays are clearly understood.

We will discuss the nature of clinical decision-making, important gaps in current testing capabilities, and paradigms for effective collaboration between the lab and the clinician. Our questions will include: What tests do physicians need, and why? How do assay performance and turnaround time influence the utility of a clinical test? What programs have been successful in ensuring that the lab develops tests that meet clinical need? How can the lab effectively communicate the interpretation of complex, emerging tests? What are the ethical considerations for determining when a test is “useful enough” to justify the cost of its development?

Protein MS assays are assured to be the next-generation tests for precise and enabling measurement of clinical protein biomarkers. Or are they? In the 30 years after the MALDI and ESI invention, only a dozen or so protein MS tests have been translated into clinical laboratories. Analytical performance requirements have been in place for some time, along with small molecules MS clinical tests precedents, so why haven’t more protein MS assays found their ways into clinical labs? Is there anything else missing? What about the clinical and economic drivers? If some of these key drivers have not been met yet, are we to proceed with the protein MS tests translation anyway, anticipating near-term clinical adoption? How do we then pick the biomarker targets for these tests? Many players have a stake in the clinical protein MS tests– from reagents and instruments manufacturers, to clinical labs and diagnostic companies. So please join us for a lively discussion and confessions of the culpable that may help us answer the ultimate question: Are clinical protein MS tests prophetic or just rhetoric?

Thursday

CORPORATE WORKSHOPS (AM)

Automated Extraction of Catecholamines and Metabolites in Urine and Novel Methods for the Isolation of Steroids in Serum using Hamilton MICROLAB® NIMBUS96 and LC-MS/MS
Kaylee Mastrianni, PhD., Applications Chemist, DPX Technologies, LLC, Columbia, SC; Daniel B. Kassel, PhD., Founder & CEO, SciAnalytical Strategies, Inc., La Jolla, CA

Pre-Register

A simple diphenylboronic acid (DPBA) complexation prior to dispersive pipette extraction (DPX) minimizes oxidation and maximizes selectivity and recovery of bioamines from urine. Automation of the DPX extraction using the Hamilton NIMBUS96 facilitates higher throughput of 96 samples making this method ideal for clinical laboratories experiencing increased demand for epinephrine, norepinephrine, dopamine, metanephrine and normetanephrine testing in urine. Analyses of steroids includes a patent pending protein crash method based on DPX extraction that streamlines the entire process from serum extraction to LC-MS/MS analysis without the need for centrifugation and vortex mixing. Up to 96 serum samples are processed simultaneously in ~10 minutes on an automated liquid handler, providing clean extracts, immediately ready for analysis.

Speeding up the cancer biomarker discovery: Advanced Clinical Proteomics workflow with High Resolution MS
Sebastien Gallien, Ph.D., Former researcher at CRP-Santé LIH Luxembourg Institute of Health

Adoption of cancer biomarkers in clinical labs has been plagued by the speed with which these biomarkers are discovered and validated for clinical use. Clinical proteomics approaches where the use of predefined set of surrogate peptides for proteins has been helpful in systematically identifying these markers. Targeted analyses using parallel reaction monitoring (PRM), performed on high resolution and accurate-mass (HRAM) quadrupole-orbitrap mass spectrometers, present the selectivity and sensitivity to confidently quantify peptides in complex samples. The internal standards (IS) used for isotope dilution quantification were recently leveraged to actually drive the acquisition (“internal standard triggered-parallel reaction monitoring”, IS-PRM), thus improving the acquisition efficiency. Leatn how to uncover biomarkers faster.

Ultra-rapid LC-MS/MS analysis
Lewis Couchman, Toxicology Unit, Department of Clinical Biochemistry, Viapath Analytics, King’s College Hospital, London, UK.

Typically, targeted quantitative LC-MS/MS analyses using gradient elution are carried out at the rate of a few minutes per injection. In this workshop, an approach to ultra-rapid LC-MS/MS analysis using Raptor biphenyl columns will be demonstrated in which complete injection-to-injection cycle-times are approximately 30 seconds without the requirement for LC multi-plexing. Despite such short analysis times, chromatographic efficiency is typically maintained (e.g. for drugs and metabolites), and the approach has been shown to be applicable to a range of compounds. Retention time reproducibility of more than 1,500 injections on a single short column has been shown to be excellent. Practical considerations and requirements for this approach will be demonstrated using a range of analytes for which therapeutic drug monitoring is advocated.

Advances in Human Microbiome Science: Metabolic Disease
Stanley L Hazen, MD, PhD (Chair of the Department of Cellular & Molecular Medicine at the Cleveland Clinic’s Lerner Research Institute, Section Head of Preventive Cardiology & Rehabilitation at the Cleveland Clinic, Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis, and the Leonard Krieger Chair in Preventive Cardiology)

Dr. Hazen’s laboratory focuses on understanding mechanisms through which inflammation contributes to diseases such as atherosclerosis. His work has led to numerous discoveries in multiple areas of cardiovascular disease research. His discovery of a mechanistic link between gut microbes and cardiovascular disease was awarded as an Inaugural recipient of a “Top 10 Clinical Discovery of the Year (2011)” award by the Clinical Research Forum (April, 2012), which is comprised of leadership at NHLBI, academia and industry. His further studies on the gut microbe – cardiovascular disease connection were recognized by the American Heart Association and the American Stroke Association in 2014 as a “2013 top 10 advances in heart disease and stroke science”. Dr. Hazen will present on mass spectrometry based applications to human microbiome analysis.

Facilitating LC/MS Method Development: Impact of Stationary Phase Chemistry
David S. Bell, PhD

Problems encountered executing LC/MS methods are often a result of the choice of column chemistry employed. Many analysts will reach for their C18 upon commencement of method development; however C18s are often not the best tool for a given separation. There are many choices of alternative stationary phase chemistries that render the phase decision difficult. In this work stationary phase classes and chromatographic modes which are highly complementary to alkyl phases are discussed. An understanding of the contrasting interactions that these classes of stationary phase chemistries provides guidance regarding the choice of phase that may be most appropriate for a given task. This critical information promises to facilitate LC/MS method development and generate simpler, more reliable separations

Chat with the Exhibitors and get ready for the Plenary in the Exhibit Hall at 11:00 AM.

CORPORATE WORKSHOPS (PM)

Microsampling Workshop | A Look at the Implementation of Dried Blood Microsampling from Convenient Patient Collection to Reliable, Automated Specimen Processing
Thierry Dervieux, PharmD., PhD., DABCC, CSO & Medical Director, Exagen Diagnostics & Julia Colletti, Scientist, Mass Spectrometry R&D, Quest Diagnostics

Pre-Register

Examine how two clinical diagnostic organizations have implemented volumetric absorptive microsampling (VAMS™) to capitalize on patient benefits of improved comfort from a fingerstick and increased convenience of at-home collection. Furthermore, the presenters will share how they generate results similar to those from venous blood, resolve the volumetric hematocrit assay bias, and fully automate the assay on a Hamilton® STAR™ workstation.

(1) Therapeutic Drug Monitoring of Disease Modifiers in Rheumatic Diseases: Implementation Using VAMS Collection Method | Exagen Diagnostics

(2) Automated Method for the Sample Preparation and LC-MS/MS Analysis of Steroids in Dried Blood using Mitra Microsampling Devices | Quest Diagnostics

A robust triple-quadrupole ion-paired reverse-phase metabolomics workflow for turn-key analysis of central metabolic pathways.
Adam Rosebrock

Pre-Register

Mass-spectrometry analysis of endogenous metabolites, metabolomics, has emerged as a powerful tool to directly examine biochemical state. Advances in LC separation and mass spectrometry instrumentation permit efficient and sensitive separation and detection, enabling the parallel analysis of hundreds of compounds in a single run. Despite the promise of metabolomic analysis, the wide chemical diversity of analytes presents many challenges for method development and a resulting hurdle for setting up metabolic assays. For Research Use Only. Not for use in diagnostic procedures.

Matrix Effects and Matrix Affects: The Impact of Different Sample Matrices on Sample Preparation and Chromatographic Analysis
Jonathan Danaceau, Ph.D, Principal Applications Chemist, Waters Corporation

This workshop will discuss many challenges that analysts face when working with a variety of complex sample matrices. The analysis of 3 compounds will be described with an emphasis on how the sample pre-treatment, SPE protocols and chromatographic methods must change depending on the sample matrix. Four different sample matrices will be used including urine, whole blood, plasma and oral fluids. Suggestions will also be provided for method developers concerned with these types of matrices.

Best of both worlds: combining quantitative targeted proteomics with high-content discovery proteomics
Fadi Abdi, Florian Marty

Biognosys is the leading next generation proteomics company. Using our proprietary HRM-MS approach we have recently identified over 9`000 proteins in a single shot DIA measurement of mouse cerebellum tissue. Here, we present a workflow that combines the quantitative power of stable isotope-labelled reference peptides with the discovery potential of HRM-MS. Using the reference peptides from our PlasmaDive and PlasmaDeepDive panels we have obtained absolute quantitative information of 173 proteins in un-depleted plasma. Additionally, over 400 plasma proteins were identified in a single shot experiment and can be quantified over a large cohort with high reproducibility. Further, the quantification values obtained for the SIS peptides can be used to extrapolate the absolute quantitative values of all proteins identified.

Quantitation of Proteins and Antibodies In Serum by LC-MS/MS Using Full-Length Stable Isotope Labeled Internal Standards and Certified Reference Materials
Kevin Ray and Uma Sreenivasan

LC-MS/MS is becoming a powerful tool for the quantitation of proteins in plasma. Such methods typically utilize stable isotope labeled (SIL) peptide internal standards. For more accurate quantitation, a full-length SIL protein can be added to the sample at the initial stage of the assay workflow. To enable this approach, we have developed SIL monoclonal antibodies, including SIL-Infliximab, as well as SIL versions of clinically-relevant human proteins, such as Thyroglobulin. We will demonstrate that the use of a SIL proteins and SILuMAB internal standards allows for more accurate and rapid quantitation of therapeutic antibodies and human protein biomarkers in plasma by LC-MS/MS. We will also discuss development and certification of proteins as Certified Reference Materials for accurate quantitation in clinical applications.