Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis

TLDR

High‑throughput screening in genetics, chemistry, and diagnostics relies on multiplexing, which requires an encoding scheme, yet existing methods are complex, costly, and provide few unique codes. The authors develop a continuous‑flow lithography method that simultaneously synthesizes, encodes, and functionalizes particles, producing multifunctional particles with over a million unique codes. The method uses continuous‑flow lithography to integrate particle synthesis, encoding, and probe incorporation in one step. The particles enable rapid, single‑fluorescence multiplexed detection of DNA oligomers in a flow‑through microfluidic channel, and high‑specificity detection is also achieved with individual multiprobe particles.

Abstract

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 that combines particle synthesis and 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. Furthermore, we demonstrate with high specificity the same multiplexed detection using individual multiprobe particles.