[11] Real-time measurements of receptor activity: Applications of microphysiometric techniques to receptor biology

Publisher Summary This chapter discusses the use of a silicon-based biosensor that can detect the activation of cellular receptors by monitoring changes in metabolism that occur secondary to receptor activation. The method does not depend on a specific transduction pathway and can, therefore, be used to monitor a wide variety of receptor types in assorted cellular environments. Functional assays are generally more complicated and difficult to perform than binding assays. The selection of an appropriate functional assay requires prior knowledge of the signal–transduction pathway or physiological response implicated with the receptor in question. Unfortunately, the specific requirements of a given receptor's coupling and the compatibility of a host cell's transduction mechanisms are not always known. It, therefore, may be necessary to examine a considerable variety of possible responses to any given test ligand. As a matter of practice, one must focus on each system, one at a time, assaying for the anticipated effect. This approach can be compromised by the real possibility that a cloned and heterologously expressed receptor does not couple effectively to the expected effector system in the transfected host cell.