The appeal of using arrays free from fancy adornments — fluorescent, radioactive or otherwise — is fairly obvious. Such arrays could eliminate extra work and reduce errors in detection and analysis.

Surface plasmon resonance (SPR) is a promising technology for this approach. In SPR the interactants are fixed to a gold-coated substrate, and sample binding is detected as mass concentration-dependent changes in refractive index at that spot, which makes it possible to monitor binding in real time. “You can look at specificity, affinity, kinetics, make concentration measurements, and work in a range of different sample environments,” says Gary Franklin, industrial-sector specialist at Biacore.

Recently acquired by GE Healthcare in Little Chalfont, UK, Biacore has pioneered the development of SPR platforms for a wide variety of proteomics applications. It has two main options for array users. In the Flexchip platform, 400 interactants can be spotted on a slide and then screened against a single sample. In contrast, the A100 is limited to 20 immobilized interactants but, thanks to parallel flow systems, it can perform up to four simultaneous screens with large numbers of samples. “The A100 can look at up to 3,800 interactions per day in a variety of different, multiplexed ways,” says Franklin.

The ProteomicProcessor from Lumera will offer high-throughput label-free analysis.

Lumera of Bothell, Washington, is a relative newcomer to the market. It takes advantage of extremely rapid optical-switching technology, originally developed for telecommunications, in its ProteomicProcessor SPR instrument. Throughput was a key limitation of early SPR array experiments, and Lumera says its switching technology has reduced the problem. “We're basically limited by the size of the slide and how small you can print your spots,” says Tim Londergan, director of the company's bioscience business unit. “You can really see this tracking to DNA microarray scale.” Lumera has nearly finished testing its 'beta' instrument and plans to launch its first commercial system in January 2007.

But SPR is not without limitations, and reduced sensitivity remains a common complaint. “My feeling is that there may be a somewhat limited dynamic range,” says Joshua LaBaer, director of the Harvard Institute of Proteomics. “It's a fairly narrow window, and you have to be able to figure out how to get your chemistry within that window.”

Other technologies are also emerging, such as the arrays based on microcantilevers made by Protiveris of Rockville, Maryland, or the atomic-force microscopy system from BioForce Nanosciences of Ames, Iowa. Most of these platforms are in their infancy, but technology development is under way and many microarray users foresee a label-free future — one way or another. “It's going to revolutionize the way we think about things,” says LaBaer. “It won't happen in ten days or a year, but it's going to happen.”

Michael Eisentein