Single Cell Sensing and Manipulation by Scanning Nanopore Microscopy

Abstract

Signal Transduction by Ion Nano-Gating (STING) technology is a label-free biosensor based on quartz nanopipettes capable of detecting DNA and proteins. Using conical quartz nanopipettes a Scanning Ion Conductance Microscope (SICM) was developed and used for single cell imaging, sensing and manipulation. The height of the nanopore above a surface can be accurately controlled by measuring the ionic current through the pore as it approaches a surface. By maintaining a predefined distance from a surface and raster scanning the pore, a topographical image can be acquired. Additionally, material can be ejected through nanopipette using electrophoretic and electroosmotic properties. The cost of fabrication and ease of use of nanopipettes provides an ideal system for developing cellular systems for both cell detection and control. We demonstrate the capability of this sensor to image living cells, deposit material for controlled single cell growth on a substrate, and a platform for single cell injection and detection using an integrated microfluidic chip. The combination of STING technology with traditional SICM technology can be leveraged to acquire both topographical data and functional data, such as local ion concentration. This form of complementary microscopy is henceforth termed functional Scanning Ion Conductance Microscopy (fSICM). Preliminary fSICM results will be presented. This work illustrates the applicability of the STING sensor to a variety of applications, from single cell detection to definition of cellular circuits.