Abstract

Ultrasensitive biological sensors for low-abundant DNA and protein detection have emerged as an important tool for improving biomedical diagnostics, drug discovery and advanced bioanalytical assays in fundamental research. We report on a single-molecule readout scheme based on total internal reflection fluorescence microscopy (TIRFM) demonstrating a detection limit in the low fM regime for short (30 mer) unlabeled DNA strands1. Detection of target-DNA is accomplished by mediating the binding of suspended fluorescently labeled DNA-modified small unilamellar vesicles (O∼100) to a DNA-modified substrate by unlabeled complementary single-stranded DNA.

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