Single-Cell Biopsy using Nanopipettes

Abstract

To fully understand cell functioning and stochastic gene expression patterns, it necessary to measure molecular interactions at the single cell level. Advances in microscopy as well as genomics technology have enabled detailed analysis of gene expression at the single-cell level, but the means to manipulate individual cells are still limited. Nanotechnology-based tools having high sensitivity and low invasiveness are holding great promises as new biomedical devices for single cell manipulation. The fully electrical read-out as well as the ease and low cost of fabrication are unique features that give nanopipette technology enormous potential. We developed a single-cell manipulation platform based on nanopipettes. The system uses scanning microscopy techniques to position the nanopipette with nanoscale precision, and electro-wetting to aspirate minute amount of cytoplasmic material from individual cells without comprising cell viability. It is well documented that the application of a voltage at the interface across two immiscible liquids changes their surface tension. The resulting force is sufficient to cause liquid to flow into/out of the nanopipette, with displacement volumes much smaller than a typical mammalian cell. Multiple biopsies can be taken from the same cell to study gene expression patterns. We will present preliminary RNA-seq data of material biopsied from a single cell. We envision that this technology will allow biological analysis with unprecedented level of detail, allowing a better understanding of single cell dynamics.