Held July 15–19 in Los Angeles, California, the annual American Association for Clinical Chemistry (AACC) conference hosted tens of thousands of attendees. The conference presentations and exhibits encompassed both traditional clinical chemistry technologies, such as clinical analyzers, as well as molecular diagnostics techniques, including DNA sequencing and PCR. The conference was held at an interesting time, as two traditional laboratory research supply companies, Agilent Technologies (see IBO 5/31/12) and Life Technologies (see page 2), recently announced diagnostic company acquisitions.

The utilization of research technologies to develop clinical solutions was the subject of a talk that was part of the Tuesday symposia “Strengthening and Expanding the Framework of Clinical Proteomics.” Dr. Henry Rodriguez, director of the National Cancer Institute’s (NCI) Office of Cancer Clinical Proteomics Research, discussed the partnership between the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the AACC to advance clinical proteomics research into the clinic. CPTAC addresses clinical proteomics by seeking to correlate genes to proteins and, subsequently, to phenotype. The first stage of CPTAC ran from 2006 to 2011 and optimized proteomic research techniques utilizing a network of labs to conduct round robin studies. CPTAC achievements include the development of MassQC software for monitoring 46 analytical performance metrics of MS systems in proteomic research. Launched last year, the so-called “CPTAC II” program will run through 2016. Dr. Rodriguez noted new to these phase was the requirement that participating labs document their expertise in laboratory clinical chemistry. The program will span discovery, verification, creation of a tumor proteomic library, assessment of new therapeutic targets and biomarker candidates, and clinical implementation. Building on an informal partnership that began in 2008, CPTAC and AACC formalized their cooperation in 2009 with a memorandum of understanding. Last year, CPTAC and AACC held a workshop entitled “Statistical Experimental Design Considerations in Research Studies Using Proteomic Technologies.” A paper on the workshop is expected to be published in a few months.

As part of the same symposia, Dr. Stephen Master of the Perelman School of Medicine at the University of Pennsylvania discussed the integration of multiple “omics” to create a detailed molecular phenotype. He examined two models of integration: a “super-biomarker,” which could combine information from genomics, proteomics, metabolomics, histology and MRI; or to consolidate biomarkers, which would relate traditional markers to something that is easily measured. In his work addressing the stratification of prostate cancer tumors based on risk, he utilized label-free MS quantitation to identify proteomic biomarkers, statistical analysis of protein microarrays to identify a protein that is a known predictor of a risk of recurrence and a protein that is a known suppressor. He also extracted image parameters using computational histology. To create a composite proteomic biomarker, he mapped the high-dimensional data to an alternative space, but the huge dimensional space of the data resulted in the unequal weighting of modalities. The study suggested that the future of clinical proteomics will require a single testing modality to cover all data or multiple testing modalities that require integration.

In Wednesday’s plenary session, Elaine Mardis, PhD, of the Washington University School of Medicine described her whole-genome sequencing work addressing tumor heterogeneity. She utilized deep digital sequencing, which sequences variant sites and structural variation assemblies at around one thousand-fold depth to produce data that she called highly digital and quantitative and that can be used for validation. Digital readouts enable the calculation of the allele frequency of each mutation in the tumor cell population. Her work on acute myeloid leukemia studies why most patients die of a relapse of the disease, identifying new mutations in some patients but not all.

Many other research instrument and lab product companies exhibited their clinical products at the show, including MS companies. All major MS companies were at the show with the exception of Shimadzu. Waters launched the in vitro diagnostic (IVD) (class I medical device) version of its MassTrak Online SPE (solid phase extraction) Analyzer, with an average run time of three minutes from injection to injection. The fully automated system holds two SPE cartridge trays and can use up to 23 solvents. It is designed for SPE sample preparation or SPE method development. Waters also displayed the IVD version of its Xevo TQD MS (see IBO 6/15/11). The company previewed but did not display an IVD version of a liquid handler for SPE developed with Tecan for use with its SPE microplates that has a typical throughput of 200 samples per day.

Agilent also displayed its LC/MS systems for clinical research as well as its RapidFire 300 High-throughput MS System for online sample preparation using SPE. The system has a sample preparation processing time of 6-8 seconds and run time of 14 seconds. Among the applications for the system are detection of unknown synthetic drug blends.

Continuing the automation trend, Thermo Fisher Scientific displayed a fully automated clinical research workflow, which included Matrix PlateMate 2×3 automated pipetting workstation, multiplex Transcent HPLC system and the Orbitrap QExactive MS. The company also displayed products from its Phadia division, including the ImmunoCap line of allergy blood tests. In the US, Phadia is focused on improving educational efforts targeting physicians.

New multiplex PCR tests were also on display. Idaho Technology showed its FilmArray technology. The FilmArray Respiratory Panel was launched last year, and this spring, the firm won FDA approval for five additional bacterial respiratory pathogens, for the testing of 20 viral and bacterial respiratory pathogens in total. A sealed pouch contains the 12 premixed vials of reagents for nested multiplex PCR and a microarray for second-stage individual singleplex PCR. The pouch is inserted into a loading station and then into the FilmArray Instrument. The RP panel is priced at $129 and the FilmArray Instrument at $49,500. FilmArray panels under development include a blood culture ID panel, which will be submitted to the FDA later this year, and a BioTheat panel.

Seegene introduced its TOCE-CCMTA (Tagging Oligonucleotide Capture and Extension-Cyclic Catcher Melting Temperature Analysis) technology. In contrast to other multiplex quantitative real-time PCR technologies, qTOCE enables the measurement of up to five target analytes per channel. The technology runs on any four-channel real-time PCR system and allows for detection of single point mutation. Assays based on the technology include the QuantPlex RV-16 Assay for 21 respiratory viral pathogens; the QuantPlex HPV 28 Genotyping Assay for 19 high-risk and 9 low-risk HPV genotypes; and the QuantPlex STI-7 Assay for seven sexually transmitted pathogens.