Biosensors: from detectors to analytic instruments

Byron Goldstein
Los Alamos National Laboratory

Biosensors detect biomolecules by using a biological recognition mechanism coupled with a physical transduction technique. Some biosensors are used purely as detection devices to indicate when a specific biomolecule is present above some threshold concentration, the limit of the detector's sensitivity. Other biosensors are used as analytical instruments in basic research to obtain detailed quantitative information about a biological interaction. The most popular such instrument is an optical biosensor called a BIACORE that is now in wide use as a tool for extracting reaction rates from the observed time course of a biomolecular reaction. In the BIACORE, one reactant in solution, the analyte, flows past a second reactant attached to a sensor surface. Reliable interpretation of the resulting binding data depends on understanding the roles of flow, diffusion, surface attachment, and reaction. We have derived conditions under which simple models, consisting of ordinary differential equations for binding at the sensor surface, can be used to separate information about the chemical reaction from confounding factors inherent in the biosensor design. To test these models we have developed a computer model that can simulate BIACORE experiments. This model accounts for the flow and diffusion of the analyte in solution, the chemical reaction at the sensor surface and the geometry of the BIACORE. Our approach is to use the computer model to simulate BIACORE experiments and then see if the simple models can fit the simulated data and yield the correct chemical rate constants.