"Thus, biochips make a perfect match for the new wave of tests that rely on gene and protein expression patterns," Rosen notes, saying that for the purposes of the Kalorama report, "biochip" is meant to refer to all testing devices that involve multiplexed biosensors, microfluidics and microarrays. "The devices have evolved and have been developed to miniaturize a variety of diagnostic technologies—nucleic acid amplification and detection, chromosome analysis, immunoassays, mass spectrometry, flow cytometry and sequencing. Biochip technology is expected to have a significant impact on molecular diagnostics, especially since several biochip instruments have been cleared for use for IVDs."  

 

Some of those instruments include Affymetrix's GeneChip System 3000Dx v.2 and Transgenomic's WAVE Microchip Electrophoresis system. Several chip-based tests have come to market, Rosen adds, and several are used in lab services for cancer detection and therapy selection, with still more in development.  

 

"There are only five FDA-cleared molecular diagnostic products, of which three are for cancer diagnostics," Rosen notes. "Roche's AmpliChip, Agendia's Mammaprint, Osmetech's cystic fibrosis test, Vermillion's OVA1 ovarian-cancer test and Pathwork Diagnostics' Tissue of Origin test."

 

It should be noted that since the gathering of data for the Kalorama report, Pathwork now seems to be defunct, and market-watchers note that the future of the Tissue of Origin test is unclear.   Rosen also noted that Ipsogen SA (now known as QIAGEN Marseille) is leading the way in CE-marked DNA microarrays for clinical diagnostics.  

Ipsogen has built a portfolio 21 kits, of which 10 are CE-marked, Rosen says, since its founding in 1999, and it has developed and commercialized "unique molecular tools for patient risk stratification, to predict patient response to treatment and to monitor minimal residual disease for hematological malignancies." From this proof of concept, she says, Ipsogen is now leveraging its expertise to address molecular diagnosis of solid tumors, such as breast and colon cancer.  

 

Rosen also thinks the digital PCR (dPCR) space is interesting right now, in part because dPCR has been shown to be better than many existing technologies at detecting subtle differences between samples with similar genomic structures.  

 

"This is especially important in determining drug targets for pharmacodiagnostic testing and stratifying disease," Rosen says. "At this time, no dPCR systems have been cleared for clinical diagnostics; they are used in cancer research."

 

In 2006, she notes, Fluidigm introduced the first commercial system for dPCR based on integrated fluidic circuits, and in November 2010, Life Technologies commercialized a dPCR product line for the OpenArray system. In March 2010, QuantaLife—which was acquired by Bio-Rad Laboratories in October 2011—was issued a patent for dPCR based on emulsions, leading to its droplet digital PCR technology to convert a DNA sample into 20,000 1-nL droplets. TaqMan-based amplification takes place in each droplet, Rosen explains, followed by absolute quantitation of the number of copies of a gene target as the individual droplets stream past a fluorescence detector.

 

"QuantaLife reported that its system is capable of detecting DNA targets with absolute quantitation," Rosen says. "Droplet digital PCR can achieve 10 times higher resolution and 25 times greater sensitivity than conventional real-time PCR techniques, without the need for standards. According to QuantaLife, the system is the first cost-effective, high-resolution platform available for the validation of next-generation sequencing discoveries. It is easy to use, easy to automate and easy to integrate into existing workflows in both life-science and clinical research labs."

 

The QuantLife products joined Bio-Rad's life-science research product line. But more than that, Rosen notes, in August 2012, Bio-Rad Laboratories launched a Digital Biology Center to focus on the development of new products based on QuantaLife's droplet partitioning technology, with the first product based on this technology being the Bio- Rad QX100 Droplet Digital PCR.

 

"In January 2011, RainDance Technologies announced that it, too, is developing a digital PCR system," Rosen relates. "RainDance's microdroplet-based RainStorm technology enables researchers to perform fully automated biological analysis in disease areas including cancer, infectious disease, immunology and genetic screening."