When ligands and receptors are both attached on surfaces, because of the restriction of configurational freedom, their recognition kinetics may be substantially reduced as compared with freely diffusing species. In nature, this reduction may influence the efficiency of the capture and adhesion of circulating cells. Here we show that similar consequences are observed for colloids grafted with biomolecules that are used as probes for diagnostics. We exploit Brownian magnetic colloids that self-assemble into linear chains to show also that the resulting one-dimensional confinement considerably accelerates the recognition rate between grafted receptors and their ligands. We propose that because confinement significantly augments the colliding frequency, it also causes a large increase in the attempt frequency of the recognition. This work gives the basis of a rapid, homogeneous, and highly sensitive bioanalysis method.association rate ͉ bioassay ͉ magnetic colloids ͉ specific adhesion D iagnostics techniques are generally based on building a specific immunocomplex structure in which the antigen to be detected is recognized by two antibodies (1-8). Early immunochemistry was based on precipitation of large complexes made of antibodies and antigens. Following the same track, the use of Brownian particles significantly improved the detection sensitivity, because of the increase in scattered light when aggregation between grafted colloids takes place. As the most simple but very generic example, let us consider an antigen Ag having two different epitopes for two antibodies, A and B. To reveal the presence of such antigen, particles grafted with A and B antibodies are mixed with the sample to be analyzed. The formation of small clusters is then expected, at a rate depending on many factors. Change in light scattering due to the presence of these small clusters will reveal the existence of sandwich-like structures: A-Ag-B (latex agglutination immunoassay). These homogeneous assays, as opposed to heterogeneous assays in which washing steps are necessary before detection, are today by far the most simple and straightforward assays. They were introduced Ͼ40 years ago (2), and today several hundred different tests based on this principle can be found on the market, mainly for infectious disease detection and protein quantification, as long as the antigen concentration to be detected is տ1 nmol͞liter (1). Meanwhile, many diagnostic assays require sensitivity in the picomolar range. They are presently performed by using a heterogeneous approach (such as ELISA) (1). For that range of concentration, if we were still to consider the same homogeneous approach, it would in principle take too long. Indeed, decreasing the number of antigens to be detected implies also decreasing the number of particles in solution, † and thus the particles' colliding frequency. Therefore, at these very low antigen concentrations, the encounter frequency between species becomes a critical issue to consider.In this work, we demonstrate conditions that ac...
We have studied the effect of shear on the stability of suspensions made of non-Brownian solid particles. We demonstrate the existence of an irreversible transition where the solid particles aggregate at remarkably low volume fractions (phi approximately 0.1). This shear-induced aggregation is dramatic and exhibits a very sudden change in the viscosity, which increases sharply after a shear-dependent induction time. We show that this induction time is related exponentially to the shear rate, reflecting the importance of the hydrodynamic forces in reducing the repulsive energy barrier that prevents the particles from aggregating.
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