Quality Is Key
As SPR instrument suppliers acknowledge, throughput cannot come at the expense of information quality.
“Researchers see value in SPR because it yields richer kinetic data earlier on in the process than with traditional end-point assays,” says Ariel Notcovich, R&D manager for Bio-Rad Laboratories’ protein function and lab separations divisions. “The further upstream that researchers can get this information from a technology, the earlier they can make good decisions regarding their molecules of interest.”
To this end, Bio-Rad is developing new chemistries to improve existing workflows on its ProteOn™ XPR36 protein-interaction array system. The instrument’s 6-x-6 fluidics are designed to enable 36 interactions to be measured simultaneously, “which opens up new possibilities to SPR users in terms of assay design,” Notcovich says.
With software and hardware improvements in the works to target higher throughput and new applications, Bio-Rad intends that these new workflows will facilitate the use of SPR technology, with “faster experiment setup and protocol validation, improved back-end speeds, and simplified navigation and use of analysis tools and reporting.”
“A move toward high-throughput instrumentation and software platforms that can perform multiple types of analyses from a single sample is where SPR is headed. The major advantage will be good-quality results that allow reliable quantitative validations, ranking, and screening of molecules without compromising throughput.”
Plexera’s approach to throughput incorporates high-density arrays “theoretically designed to accept up to 5,000 spots in an active window of 14 mm by 14 mm,” explains the company’s president, Jay Smith. “We are routinely achieving 1,000 or 2,000 spots in that window and have requests from some of our big pharma customers for 10,000 spots, for DNA-based label-free detection applications.” Between 1 and 36 spots is common for typical SPR platforms.
Plexera has achieved these throughput gains by means of a planar array, in its PlexArray™ HT SPR system, which the company will officially launch at the Society for Biomolecular Screening meeting in Orlando next month.
“We don’t use cartridges, per se, but an off-the-shelf microscope-slide format that end-users can manipulate as they require with the addition of a protein printer. With our platform, researchers have full flexibility to print whatever they want to print onto a gold slide. Plexera then has a patented device that creates a liquid flow cell over the printed area,” Smith explains.
“The slide array is inserted into a special holder in the instrument with an inlet and outlet; we have essentially created a flow cell that works on a planar array. This differs from the network of capillaries in a typical SPR cartridge and affords many-fold gains in throughput. In addition, Plexera’s chip and instrument combination affords broad flexibility in assay and experiment design, which open new avenues to research and assay development. We are developing additional slide technology to further expand the applications for the system.”
Plexera acknowledges the applicability of SPR across the drug development process and aims to offer technologies for applications from “target selection/biomarker identification, target characterization and validation, proof of concept, and clinical safety and efficacy,” Smith notes.
“In the U.S. marketplace, at least, drug discovery and development companies are starting to use SPR in all of the steps of their processes. Even drug manufacturers are starting to use SPR to identify biologically active ingredients, such as oxidative states of certain proteins, that are unwanted in the manufacturing process.”