On-chip assembly of electrically functional structures from biological and colloidal particles

We study the assembly of electrically functional and miniaturized biosensors from colloidal systems ranging from synthetic organic/inorganic micro- and nanoparticles to naturally existing live cells. The unique combination of highly specific biological interactions and different assembly schemes -- (1) controlled manipulation in externally applied electric fields, and (2) free diffusion in bulk suspensions are investigated as a versatile tool for fabricating simple, rapid and inexpensive sensing devices that can potentially be interfaced with electrical circuits on a chip. For each system, a detailed modeling is carried out with the aim to acquire fundamental understanding of the operating parameters involved in the assembly process.; Gold nanoparticle-tagged silver enhanced immunoassays are designed for detecting low concentrations of target antigens and their performance is optimized by developing a simple adsorption-controlled kinetic model. Antigens in solution are allowed to diffuse toward and bind with primary antibodies immobilized on a glass substrate. Secondary labeling of antigens with gold nanoparticles and their subsequent silver enhancement enables visual detection of the antigens with bare eyes. The results are quantified by measuring the darkness of the spots using densitometry technique. In order to systematically probe the influence of the operating parameters on the assay performance, the concentration and incubation time of each reagent are varied individually and the role of mass transfer is explored in each case. Since the electroless deposition of silver metal on the bound nanoparticles makes a conductive patch on the substrate, these assays could allow direct interfacing to on-chip electrodes for electrical readout of the results.; The co-assembly of live cells and synthetic microparticles on electrically controlled chips is demonstrated as a simple and facile route to making novel biocomposite materials, in which the biological functionality of the cells is augmented by the physical functionality of the particles. One-dimensional chains and planar membranes from live cells and colloidal particles are assembled by dielectrophoresis. The experimental results and numerical simulations of the assembly dynamics indicate that the electric field draws the particles into the interstitial junctions between the cells, where the field strength is greatest. This allows using the particles as binding elements. Permanent cell-particle chains and membranes are assembled dielectrophoretically by biospecifically binding yeast and mouse fibroblast cells with lectin-conjugated magnetic microparticles. Such biomagnetic cell-particle assemblies may find application in sensors, microassays, microsurgery, or as responsive biomaterials.; A novel method for direct electrical detection of antigens is described in which the results of latex agglutination test are measured using electrochemical impedance spectroscopy (EIS). Antibody-conjugated latex microspheres are agglutinated in the presence of complementary antigens above interdigitated microelectrodes. As the particles sediment on top of the electrodes, a reproducible impedance spectrum is generated in the 0.1--1 MHz frequency range in 10 min that depends strongly on the morphology and the sedimentation rate of the agglutinates. The performance of the sensor is interpreted by fitting the experimental data to an equivalent circuit model. The effects of the various operating parameters are also characterized in detail.