Abstract: Stand-alone microsystems adapted for performing combinatorial detection of bioagents at single molecule level wherein the microsystems are featured with three-dimensional microarray and multi-layer microfluidics to thereby provide high throughput screening and high content screening sufficient to allow for substantially real-time performance of the microsystem. Methods for detection of bioagents at a single molecule level or single organism level include providing a reconfigurable microsystem adapted for performing combinatorial detection of bioagents at a single molecule level and reconfiguring the reconfigurable microsystem for various environments.