Report of the 23rd Asilomar Conference on Mass Spectrometry

Sponsored by ASMS, the 2007 Asilomar conference “Mass Spectrometry in Clinical Chemistry and Molecular Diagnostics” included 120 participants from backgrounds as diverse as industry, instrumentation companies, hospitals, governmental laboratories, reference laboratories, medical schools, and other academic institutions. The American Association for Clinical Chemistry accredited this conference for ACCENT continuing education credits. Following opening comments by organizers Alan Rockwood and Ravinder Singh, Jack Henion from Advion Biosciences presented “Can Mass Spectrometry Add Value to Modern Clinical Chemistry?” which overviewed the merits and issues pertaining to implementing mass spectrometry (especially LC/MS) into the modern clinical laboratory. Strengths and limitations of mass spectrometry were described, emphasizing the value provided by LC/MS in clinical tests that have historically employed immunoassay techniques. Ambient ionization techniques, ion mobility, chipbased nanospray, and others were also discussed. Charles Cantor from SEQUENOM, Inc. and Boston University School of Medicine then presented “SNP Detection by Mass Spectrometry,” focusing on genetic applications of mass spectrometry. The session on Biomarker Applications and Genetic Testing, chaired by Leigh Anderson, Plasma Proteome Institute, led off with Anderson’s lecture, “Specific MS Assays for Peptides and Proteins Using Selected Reaction Monitoring and SISCAPA.” This described the technique of “Standards and Capture by Anti-Peptide Antibodies” (SISCAPA), essentially an immunoassay with a mass spectrometer replacing the second (capture) antibody of a conventional immunoassay. Robert Plumb from Imperial College, London, described “The Application of High Resolution Liquid Chromatography and High Resolution Exact Mass Spectrometry to Investigate the Effects of Gut Microflora on Metabolism and Toxicity.” Andrew Hoofnagle from the Department of Laboratory Medicine, University of Washington, described in “Clinical Tumor Marker Quantitation with LC/MS/ MS: Is There Hope?” thyroglobulin (an important tumor marker) as a model of immunoassay imperfection. Immunoassays are unreliable in some patients due to the presence of auto-antibodies that interfere with the test. Hoofnagle’s approach solves the problems of endogenous interfering antibodies (digest the sample into peptides) and the lack of standardization between different commercial immunoassays (include an internal standard peptide). Christie Hunter from Applied Biosystems described in “Peptide MRM-Based Assays in Plasma for Biomarker Verification Studies,” the use of a triple quadrupole linear ion trap mass spectrometer to create more than 1000 high quality, specific MRM transitions for multiple peptides to many human plasma proteins. A nonisobaric chemical labeling strategy was employed to create global reference standards to enable quantitative analysis. The session concluded with “Automated Nucleic Acid Based Signature Sequence Analysis by MALDI-TOF Mass Spectrometry—a Comparative Sequence Analysis Tool” by Christiane Honisch, Ph.D., SEQUENOM, Inc. Russell Grant from Labcorp, Inc./Esoterix, chair of the session “Instrumentation and Automation,” presented “Application of Automation Tools in LC-MS/MS Assays for Clinical Diagnostics.” He discussed a number of automation tools employed at LabCorp in development and application of LC-MS/MS workflows, including smart automation tools in optimization of method development. The application of automation in the various components of sample analysis were also discussed, including staggered parallel multidimension LC systems. The goal of automation in clinical testing was highlighted by comparison to the existing autoanalyzer workflows utilized in modern clinical diagnostics. Scott Kuzdzal from Perkin Elmer, Life and Analytical Sciences, then presented “Better Biomarkers by Bacon’s Bees.” Donald H. Chace from Pediatrix Analytical chaired the evening session “Metabolic Disorders” and presented “Beyond Newborn Screening: Clinical Mass Spectrometry Application Expansion in the Next Ten Years.” Newborn screening by mass spectrometry may serve as a model for overall expansion of MS in the clinical lab. The use of MS/MS in newborn screening