Report of the 23Rd Asilomar Conference on Mass Spectrometry
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Report of the 23rd Asilomar Conference on Mass Spectrometry Alan L. Rockwood ARUP Laboratories and Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA Ravinder J. Singh Mayo Clinic and Mayo Medical School, Rochester, Minnesota, USA ponsored by ASMS, the 2007 Asilomar conference mor marker) as a model of immunoassay imperfection. “Mass Spectrometry in Clinical Chemistry and Immunoassays are unreliable in some patients due to SMolecular Diagnostics” included 120 participants the presence of auto-antibodies that interfere with the from backgrounds as diverse as industry, instrumenta- test. Hoofnagle’s approach solves the problems of en- tion companies, hospitals, governmental laboratories, dogenous interfering antibodies (digest the sample into reference laboratories, medical schools, and other aca- peptides) and the lack of standardization between dif- demic institutions. The American Association for Clin- ferent commercial immunoassays (include an internal ical Chemistry accredited this conference for ACCENT standard peptide). continuing education credits. Christie Hunter from Applied Biosystems described Following opening comments by organizers Alan in “Peptide MRM-Based Assays in Plasma for Biomar- Rockwood and Ravinder Singh, Jack Henion from Ad- ker Verification Studies,” the use of a triple quadrupole vion Biosciences presented “Can Mass Spectrometry linear ion trap mass spectrometer to create more than Add Value to Modern Clinical Chemistry?” which 1000 high quality, specific MRM transitions for multiple overviewed the merits and issues pertaining to imple- peptides to many human plasma proteins. A non- menting mass spectrometry (especially LC/MS) into isobaric chemical labeling strategy was employed to the modern clinical laboratory. Strengths and limita- create global reference standards to enable quantitative tions of mass spectrometry were described, emphasiz- analysis. The session concluded with “Automated Nu- ing the value provided by LC/MS in clinical tests that cleic Acid Based Signature Sequence Analysis by have historically employed immunoassay techniques. MALDI-TOF Mass Spectrometry—a Comparative Se- Ambient ionization techniques, ion mobility, chip- quence Analysis Tool” by Christiane Honisch, Ph.D., based nanospray, and others were also discussed. SEQUENOM, Inc. Charles Cantor from SEQUENOM, Inc. and Boston Russell Grant from Labcorp, Inc./Esoterix, chair of the University School of Medicine then presented “SNP session “Instrumentation and Automation,” presented Detection by Mass Spectrometry,” focusing on genetic “Application of Automation Tools in LC-MS/MS Assays applications of mass spectrometry. for Clinical Diagnostics.” He discussed a number of auto- The session on Biomarker Applications and Genetic mation tools employed at LabCorp in development and Testing, chaired by Leigh Anderson, Plasma Proteome application of LC-MS/MS workflows, including smart Institute, led off with Anderson’s lecture, “Specific MS automation tools in optimization of method development. Assays for Peptides and Proteins Using Selected Reac- The application of automation in the various components tion Monitoring and SISCAPA.” This described the of sample analysis were also discussed, including stag- technique of “Standards and Capture by Anti-Peptide gered parallel multidimension LC systems. The goal of Antibodies” (SISCAPA), essentially an immunoassay automation in clinical testing was highlighted by compar- with a mass spectrometer replacing the second (cap- ison to the existing autoanalyzer workflows utilized in ture) antibody of a conventional immunoassay. Robert modern clinical diagnostics. Scott Kuzdzal from Perkin Plumb from Imperial College, London, described “The Elmer, Life and Analytical Sciences, then presented Application of High Resolution Liquid Chromatogra- “Better Biomarkers by Bacon’s Bees.” phy and High Resolution Exact Mass Spectrometry to Donald H. Chace from Pediatrix Analytical chaired Investigate the Effects of Gut Microflora on Metabolism the evening session “Metabolic Disorders” and pre- and Toxicity.” sented “Beyond Newborn Screening: Clinical Mass Andrew Hoofnagle from the Department of Labora- Spectrometry Application Expansion in the Next Ten tory Medicine, University of Washington, described in Years.” Newborn screening by mass spectrometry may “Clinical Tumor Marker Quantitation with LC/MS/ serve as a model for overall expansion of MS in the MS: Is There Hope?” thyroglobulin (an important tu- clinical lab. The use of MS/MS in newborn screening © 2008 American Society for Mass Spectrometry. Published by Elsevier Inc. 1044-0305/08/$32.00 doi:10.1016/j.jasms.2008.04.022 R2 ROCKWOOD AND SINGH J Am Soc Mass Spectrom 2008, 19, R1–R4 increased from a few hundreds of samples in the early of Michigan Medical School, described “Biomarker Dis- 1990s to several million specimens analyzed in year covery from Tumor Tissues and Plasma” and demon- 2008. The success was based on several factors, one of strated the strategy of starting with evidence for tumori- which is that tandem mass spectrometers have the genic pathway mechanisms in the tumor and tracking the ability to measure complex profiles from a single small corresponding protein biomarker candidates through sample. proximal biofluids to the plasma, using the Her2/neu Michael Morris, Clinical Operations Group, Waters mouse model of human breast cancers and the androgen- Corporation, presented “The Role of Time-of-Flight driven fusion gene TMPRSS2/ETS in human prostate Technology in Routine Clinical Applications.” Morris cancers. He also discussed the detection of autoantibod- reviewed clinical screening applications, including as- ies. This was followed by lecture by Dean Hafeman, pects of neonatal screening for inborn errors of metab- Protein Discovery Inc., “High Throughput Biomarker olism. The criteria for identification of compounds by Discovery and Small Molecule Quantification in Biolog- mass spectrometry from a number of agencies (FDA, ical Tissues using Parallel Electrochromatographic EU, CAP, CLSI) were also reviewed, and ways of Preparation.” meeting the criteria were discussed, including multiple Pierre Chaurand in “Molecular Imaging of Tissue MRM transitions and exact mass measurement, and Sections by MALDI Mass Spectrometry” described a theoretical versus experimental isotope ratio compari- relatively new technology that can be used to locate sons. The application of LC-TOF to the screening of a drugs, lipids, peptides, and proteins directly from the panel of drugs implicated in drug-facilitated crime was surface of fresh frozen tissue sections. When analyzing presented. The session concluded with “Tandem Mass tissue sections for proteins, the profiles recovered typ- Spectrometry in Biochemical Genetics” by Dietrich Ma- ically contain about 500 distinct signals in the m/z range tern from Mayo Clinic College of Medicine. up to 100,000. Thousands of proteomic profiles of Shalender Bhasin, Boston Medical Center, chaired tissues sections can now be acquired from large sample Sunday morning’s session “Quality, Clinical and Client sets in very short periods of time. Perspectives, and Unmet Needs,” which highlighted The Monday morning session chaired by Steven the challenges of making accurate sex steroid measure- Soldin, Georgetown University, focused on Endocrine, ments with the existing methodologies, and how mass Drugs, and Toxicology. Soldin described “Tandem spectrometry can address current problems in patient Mass Spectrometry for Thyroid and Steroid Hormone care. Also presented were perspectives on standardiza- Replacement.” Following were Mary F. Lopez, Thermo tion of test results and a summary of approaches for Fisher Scientific, “Targeted MS Quantitation of the rigorous method validation. William Rosner, St. Luke’s- Anti-aging Hormone Klotho,” and Robert A. Middle- Roosevelt Hospital Center and College of Physicians berg, NMS Laboratories, “The Role of Mass Spectrom- and Surgeons, Columbia University, presented “Assays etry in TDM/Toxicology.” for Plasma Testosterone: What’s the Problem?” Maria In his talk “Toxic Trace Elements and the Role of Ospina, Centers for Disease Control and Prevention ICPMS,” Sum Chan, Quest Diagnostics, discussed discussed “Harmonizing Testosterone Measurements— symptoms, and the physiological and molecular basis of CDC Perspective a.k.a. the CDC Sex Steroid Harmoni- trace element toxicity, illustrating this with arsenic, zation Project.” Steroid hormones measurements, espe- cadmium, lead, and mercury examples using induc- cially of testosterone and estradiol, are increasingly tively coupled plasma-mass spectrometry (ICP-MS). used in patient care at research. However, there are The principles and the variations of available hardware problems with comparability and reliability of these such as nebulizers, RF generators, and collision/reaction measurements. CDC’s steroid hormone standardization cells were given, as well as various strategies to deal with project includes preanalytical, analytical, and postana- interferences. lytical issues. Bhasin’s talk described “Population- Steven Hofstadler, Ibis Biosciences, chaired the Mon- Based Reference Ranges for Sex Steroid Assays: The day afternoon “Infectious Disease” session. In his talk Impact of Assay CV and Quality on Clinical Decision “High Throughput Analysis of Nucleic Acids for the Making.” Identification and High Resolution Strain Typing of Russell Grant’s talk “Validation of Endogenous Bacterial and Viral Pathogen,”