SPR Leads the Market
According to Gerry Ronan, CEO of Farfield Sensors (www.farfield-sensors.co.uk), "The BIA market is dominated by Biacore (www.biacore.com) whose surface plasmon resonance (SPR) systems use optical sensors to measure the rate of mass addition and removal from which kinetic and affinity parameters can be calculated."
Stefan Lfs, vp and CSO at Biacore, claims, "We established the market for label-free, real-time investigation of protein interactions. There are now over 4,000 peer-reviewed publications describing work based on Biacore's systems, and these are being added to at the rate of 700800 every year."
Central to an SPR biosensor is a glass-surfaced chip that supports a thin layer of gold, providing both the means to immobilize or covalently link the test protein and to generate the physical conditions for SPR.
Surface plasmons are collective oscillations of free electrons constrained in the metal film. Polarized light from a prism excites the electrons resonantly.
As molecules are immobilized on a sensor surface, the refractive index at the interface between the surface and a solution flowing over the surface changes, altering the angle at which the reduced-intensity light is reflected from the glass. The change in angle, caused by binding or dissociation of molecules from the sensor surface, is proportional to the mass of bound material.
"SPR has no lower resolution limit. We can detect down to 200 daltons, maybe lower, depending on the density of target molecules on the chip surface," Lfs maintains. "Low sample concentration can be a problem, but with a sufficiently high binding affinity, even this can be managed. Sample protein preparation and processing remain as the key issues curtailing broader technology adoption."
"In the early years, Biacore's customers within the pharmaceutical and biotechnology industries used their instruments in the same way as academics, and later on for target identification and validation.
"As different systems and applications have developed, it has become possible to address later stages in the development process including lead optimization and secondary screening.
"Our instruments are also suitable for process control, in particular of biopharmaceutical drugs like antibodies and therapeutic proteins and also immunogenic studies. The newly launched Biacore T100 system now meets the regulatory demands made when working in the GLP and GMP environment."
Biacore acknowledges the contribution made by customers in developing new applications. "The majority of these involve proteins, although a significant number are now DNA-protein," Lfs comments.
"Some customers investigate more fundamental surface interactions to develop new surfaces minimizing nonspecific binding for different types of medical devices. Compared with five years ago, we can now measure the direct binding of small molecule drugs with target proteins."
Kinomic's Trutnau identifies two potential bottlenecks to the increased usage of biosensorssoftware and hardware. "Data analysis to produce a kinetic profile still takes time. Kinetic analysis is important, for example, when selecting a therapeutic antibody to treat a particular cancer.
"Rapid binding may not be so critical as knowing that an antibody sticks to its targeted tumor cell long enough to do the job. Our software produces results two- to tenfold faster than other systems. A single button click sets off the automated data analysis. Users love the on-screen traffic light system that shows whether measurements are consistent."