Vol. 23 • Issue 15 • Page 15

Automation has been steadily making its way into MDx. In this field, fully automated is defined as including nucleic acid isolation, signal or target amplification and detection, and data analysis. Although each of these phases has been automated in the past, they were usually disconnected, with the isolation step frequently separate from and independent of the downstream application. Now there is a growing number of fully automated platforms for MDx, with systems to fit almost every lab's testing volumes and price range.

High-to-Medium Volume Testing

The Gen-Probe Tigris system offers truly hands-free processing of samples with direct tube sampling, automated sample preparation, amplification and detection, with results being automatically sent to a laboratory information system. The instrument can process as many as 1,000 samples in 13.5 hours. Gen-Probe has just released the Panther system in Europe, which has a smaller footprint and lower throughput (500 samples in 12 hours) than the Tigris; the Panther is not expected to launch in the U.S. for at least another year.

The Roche COBAS system is a fully automated system comprised of the COBAS Ampliprep instrument, which isolates nucleic acids and prepares the real-time PCR samples, and the COBAS TaqMan Analyzer, which performs the real-time PCR. Currently available IVD offerings include HBV, HCV and HIV quantitative assays.

Medium-to-Low Volume Testing

The BD Max system from BD Diagnostics is based on microfluidics and real-time PCR. A GBS detection assay is available as an IVD test, with IVD tests for MRSA and C. difficile under development. It can be used as an open system to fully automate user-defined protocols from extraction to detection. It also can run extraction-only or PCR-only protocols.

Cepheid is continuing to expand the testing menu for its GeneXpert real-time PCR platform. The instrument can run a number of infectious disease assays, including MRSA, GBS and C. difficile, to name a few. The company also has a HemosIL test for Factor V Leiden and Factor II gene mutations.

Nanosphere's Verigene platform uses gold nanoparticle probes for signal amplification. The Respiratory Virus Plus Nucleic acid test, unlike other assays available on this platform that require an up-front extraction step, has "sample-to-result automation."

Focus Diagnostics' Simplexa assays, run on 3M's Integrated Cycler, use real-time PCR for detecting various infectious diseases. These assays require an up-front extraction step; however, the company is developing a direct amplification disc that includes extraction reagents on board, which will bring this platform into the fully automated category.

The Enigma ML is a portable, modular, PCR-based system. The company recently announced clinical trials for its first diagnostic assay, a test for influenza A and B.

Single-Sample Testing

The Liat Analyzer system offered by IQuum is based on a segmented, single-use, flexible tube. The separate compartments of the Liat tube can be customized to contain various reagents for nucleic acid extraction and rapid real-time PCR amplification, creating a lab-in-a tube system. This technology was temporarily given emergency use authorization by the FDA in 2009 for H1N1 detection.

The Idaho Technologies FilmArray processes a single sample in about 1 hour. The system uses nested PCR and melting curve analysis to generate results. The FDA recently approved its FilmArray Respiratory Panel, a multiplex assay that detects 15 respiratory viruses simultaneously. With the rapid advances in MDx automation, it won't be long before the automation available for molecular testing, despite its complexity, matches the other applications in laboratory medicine.

Dr. Lefferts is supervisor, Molecular Pathology, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.