Micro- and Nanopore Technologies for Single-Cell Analysis

Coulter counter is a sensor widely used for counting small objects in a sample suspension by simple impedance measurements. Advances in MEMS technology have led to resurgence of this powerful analytical tool for single-cell analyses. Extensive efforts have been devoted to make use of ultrathin membranes for achieving better spatial resolution of micropore sensors to discriminate cells from their multiple physical features including size, shape, and surface charge. Bio-recognition pores were also developed by functionalizing pore wall surface with molecular probes, which were found useful in rendering bio-specificity to the sensor for selectively detecting cells of certain biological structures. There are also increasing biological and medical interests in exploiting the sensing mechanism for studying functions of individual cells by detecting intracellular as well as extracellular particles and molecules from exosomes to polynucleotides. The chapter reviews the recent progress in this field. It begins with an explanation of a Coulter counter principle followed by a description of the historical use of the technique for counting cells. The following sections summarize reports on research and development of functional micropores and nanopores for single-cell analyses. There, cutting-edge studies that aim to incorporate machine learning in resistive pulse analyses are also presented. Finally, potential and challenge for a total cell analysis are discussed.