Nanoscale Tweezers for Single Cell Biopsies

Much of the functionality of multi-cellular systems arises from the spatial organisation and dynamic behaviours, both within and between cells. Current single-cell genomic methods only provide a transcriptional “snapshot” of individual cells. The real-time analysis and perturbation of living cells would generate a step-change in the way single-cell analysis is approached. To address this challenge, we report on the development of minimally invasive nanotweezers that can be spatially controlled to extract and manipulate samples from living cells with single-molecule precision. These nanotweezers consists of two closely spaced electrodes with gaps as small as 10-20 nm, which can be used for the dielectrophoretic trapping of DNA and proteins under physiological conditions. This is in part due to the high electric field gradients being generated and the low operating voltages. Aside from trapping single molecules, we show that it is possible to extract nucleic acids from living cells including the nucleus and cytoplasm for gene expression analysis without affecting cell viability. We also report on the trapping, manipulation and extraction of a single mitochondrion. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.