Detecting Single Molecule Deoxyribonucleic Acid in a Cell Using a Three-Dimensionally Integrated Nanopore.

Amplification-free genome analysis can revolutionize biology and medicine by uncovering genetic variations among individuals. Here, the authors report on a 3D-integrated nanopore for electrolysis to in situ detection of single-molecule DNA in a cell by ionic current measurements. It consists of a SiO multipore sheet and a SiN nanopore membrane stacked vertically on a Si wafer. Single cell lysis is demonstrated by 10  V m -level electrostatic field focused at the multinanopore. The intracellular molecules are then directly detected as they move through a sensing zone, wherein the authors find telegraphic current signatures reflecting folding degrees of freedom of the millimeter-long polynucleotides threaded through the SiN nanopore. The present device concept may enable on-chip single-molecule sequencing to multi-omics analyses at a single-cell level.