Single Microbead Floating/Sinking-Enabled Digital Biosensing

Digital bioassays have emerged as cutting-edge techniques for highly sensitive biomarker analysis. However, the requirement of sophisticated operation and equipment, fully sealed microchambers, and well-trained professionals confines its application to central laboratories. Herein, we present dMSink, a new conceptual mix-and-read <u><b>d</b></u>igital biosensing platform based on the single microbead (<u><b>M</b></u>B) floating/<u><b>sink</b></u>ing mechanism that is compatible in general biolabs and even in-field testing. Specifically, MBs will float on the surface of a liquid with a finely tuned critical density to ensure that even a single target molecule binding event-introduced extra tiny force (e.g., magnetic force) on the MB is sufficient to induce its sinking. Therefore, only by digitally counting the number of sunken MBs with a conventional microscope can ultrasensitive quantification of diverse biomarkers be facilely achieved. The dMSink empowers the digital bioassay for both speed and sensitivity, significantly simplifying its implementation to in-field multiplexed diagnosis.