DIGITAL CHEMICAL-ANALYSIS OF DILUTE MICRODROPLETS

The concept of digital molecular detection, the ability to count individual molecules, is described and the mathematical framework for defining detection limits under various experimental constraints presented. We shoe that with modest signal-to-noise ratio for detection of single molecules, significant advantages accrue when using a digital detection strategy versus a conventional approach. Concentration detection limits decrease inversely with total sample volume for digital detection versus reduction as the inverse square root for conventional measurements. This advantage could yield detection limits that are reduced by orders of magnitude if sample volume is limited. In addition, we present experimental results demonstrating the concept of digital molecular detection using beta-phycoerythrin molecules and levitated microdroplet fluorimetry. Single beta-phycoerythrin molecules are detected with a signal-to-noise ratio greater than 4.