(5cg) Deterministic Arraying of Microbeads for Point-of-Care Diagnostics and Environmental Sensors

Bead based microarrays are promising platforms for implementing the high throughput, multiplexed assaying of the binding interactions of biomolecules (for example the binding of antigens and antibodies, or the conjugation of membrane receptors with small molecule ligands). In these arrays, each bead contains a particular probe molecule on its surface, and a code to identify this probe. Particles with different probes are mixed and subsequently bound onto a surface in a regular array. The array is then incubated with a target, and the binding of the target to particular probe molecules is identified (usually by fluorescently labeling the targets and scanning to find luminescent beads). The bead code is then read to identify the probe and complete the multiplexed assay. The promise of this platform lies in the fact that by decreasing the size of the beads, ulra-mininaturized platforms capable of an increased number of binding assays can be constructed. Bead arraying is essential to the formation of these bead based microarrays, and most research has focused on using the covalent binding of functional groups on the bead surface to functionalized sites on the platform surface. Arraying paradigms which sequester particles without reaction have the distinct advantage that they avoid chemical reaction conjugation.

Conventional microarrays for drug discovery operate based on diffusion-controlled molecular recognition events. Bead-based arrays offer several advantages over conventional ones as microbeads have a high surface-to-volume ratio thus reducing the required volume of the clinical sample and allow multiplexing (simultaneously looking for several target molecules in one sample). There is a great interest in combining bead-based arrays and microfluidic technologies to reduce analysis time (convection vs. diffusion) and more importantly to bring point-of-care diagnostics closer to the patient. This integration requires development of technologies to manipulate, decode, and analyze microbeads, one at a time, in a single device and is still in its early stage. Commercial flow cytometers are bulky, expensive, and are not suitable for point-of-care. The difficulties of this integration are twofold: deterministic arraying of microbeads for decoding, and the implementation of detection systems into these devices. The ability to accurately array microbeads using flow fields will overcome one of the difficulties in integrating bead-based arrays with microfluidic devices. As the result of this research, point-of-care systems for identifying common infectious diseases could be in every doctor's office in the near future. It could also bring low cost integrated sensors, such as pathogen detection sensors, into environmental monitoring systems.