Daniel C. Pregibon, Chemical Engineering, MIT, 66-053, 77 Massachusetts Ave., Cambridge, MA 02139, Mehmet Toner, Massachusetts General Hospital/Shriners Burn Hospital/Harvard Medical School, 51 Blossom Street, Boston, MA 02114, and Patrick S. Doyle, Department of Chemical Engineering, MIT, 66-053, 77 Massachusetts Ave., Cambridge, MA 02139.
High-throughput screening for genetic analysis, combinatorial chemistry, and clinical diagnostics benefits from multiplexing, which allows for the simultaneous assay of several analytes but necessitates an encoding scheme for molecular identification. Current approaches for multiplexed analysis involve complicated or expensive processes for encoding, functionalizing, or decoding active substrates (particles or surfaces) and often yield a very limited number of analyte-specific codes. We present a method based on continuous-flow lithography (Dendukuri et al. Nat. Mat. 2006) that combines particle synthesis, encoding, and probe incorporation into a single process to generate multifunctional particles bearing over a million unique codes. By using such particles, we demonstrate a multiplexed, single-fluorescence detection of DNA oligomers with encoded particle libraries that can be scanned rapidly in a flow-through microfluidic channel (Pregibon et al. Science 2007). Furthermore, we demonstrate with high specificity the same multiplexed detection using single, multiprobe particles.
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