<title>Optically controlled collisions of biological objects</title>

We have developed a new assay in which two mesoscale particles are caused to collide using two independently controlled optical tweezers. This assay involves the measurement of the adhesion probability following a collision. Since the relative orientation, impact parameter (i.e., distance of closest approach), and collision velocity of the particles, as well as the components of the solution, are all under the user's control, this assay can mimic a wide range of biologically relevant collisions. We illustrate the utility of our assay by evaluating the adhesion probability of a single erythrocyte (red blood cell) to an influenza virus-coated microsphere, in the presence of sialic acid-bearing inhibitors of adhesion. This probability as a function of inhibitor concentration yields a measure of the effectiveness of the inhibitor for blocking viral adhesion. Most of the inhibition constants obtained using the tweezers agree well with those obtained from other techniques, although the inhibition constants for the best of the inhibitors were beyond the limited resolution of conventional assays. They were readily evaluated using our tweezers-based assay, however, and prove to be the most potent inhibitors of adhesion between influenza virus and erythrocytes ever measured. Further studies are underway to investigate the effect of collision velocity on the adhesion probability, with the eventual goal of understanding the various mechanisms of inhibition (direct competition for viral binding sites versus steric stabilization). Analysis of these data also provide evidence that the density of binding sites may be a crucial parameter in the application of this assay and polymeric inhibition in general.