Digital enzyme-linked immunosorbent assay (ELISA) technologies such as Single Molecule Arrays (Simoa) have enabled 1000-fold increases in sensitivity over conventional protein detection methods. However, the analytical sensitivities of current digital ELISA technologies remain insufficient for many rare protein biomarker candidates. In addition, many existing ultrasensitive protein detection methods require specialized instrumentation or time-consuming workflows that have limited their widespread implementation. To address these challenges, we have recently developed a more sensitive and highly accessible digital ELISA platform, Molecular On-bead Signal Amplification for Individual Counting (MOSAIC), that democratizes ultrasensitive protein detection. By using a localized signal amplification strategy and a rapid flow cytometric readout, MOSAIC achieves simultaneous advancements over current digital ELISA technologies: (1) attomolar sensitivities, with an order of magnitude enhancement over Simoa; (2) a high-throughput readout and workflow that can be easily integrated into existing laboratory infrastructure; and (3) expanded multiplexing capabilities for digital protein detection. Our current work focuses on further improving the workflow and analytical capabilities of MOSAIC, as well as translating MOSAIC towards the detection and discovery of rare biomarkers for diverse disease applications.
Funding: Good Ventures Open Philanthropy