The resurgence of Coulter counting for analyzing nanoscale objects

Abstract

This review discusses recent advances in the science and technology of Coulter counting. The Coulter counting principle has been used to determine the size, concentration, and in favorable cases the surface charge, of nanometer-scale colloidal particles, viruses, DNA and other polymers, and metal ions. A resurgence of interest in the field of COulter counting is occurring because of the advent of new technologies that permit fabrication of membranes containing single, robust, and chemically well-defined channels having smaller and more uniform sizes than could be prepared in the past. These channels are prepared from biological materials, such as self-assembling membrane proteins, and from synthetic materials such as polymers, carbon nanotubes, and silicon-based inorganic materials. In addition to particle characterization, there have been a few recent examples of using Coulter counters to study chemical processes, such as the dehybridization of DNA.

Localized Functionalization of Single Nanopores

“…We used pores with a starting diameter of 1000 nm to build the large apertures, and pores with starting diameters of 500 nm to build the smaller apertures. While equation (1), which describes a cylindrical pore, fits the pores with 1000 nm starting diameter quite well it was discovered that the pores with 500 nm starting diameter could not be fitted with this model without modifications to (1). While both pore types were perfectly cylindrical after initial drilling, SEM cross sections recorded after FIB cuts showed that after oxide deposition, the 1000 nm pores remained cylindrical but that the 500 nm pores were slightly conical, with a smaller top diameter.…”

“…[1][2] Although much work has been devoted to the reduction of aperture diameters to count smaller and smaller biological objects, [3][4][5][6][7][8][9][10] the next challenge remains to combine size control with local chemical functionality to achieve specific counting and detection. The initial solution to this problem was provided by the use of α-hemolysin, a cellular membrane protein that self-assembles in lipid bilayers to form a 1.5 nm diameter pore.…”

Integrated optical waveguides and inertial focussing microfluidics in silica for microflow cytometry applications

“…The particle lagging behind the flow causes the fluid streamlines to be directed around the particle. The fluid passing over the particle on the side facing the centre of the channel is accelerated around the particle resulting in a lower pressure compared to the fluid passing by the more direct route between the particle and the wall producing a net force acting away from the wall [2]. Lift forces become significant when the particle Reynolds number, which describes the ratio of inertial to viscous forces on the particle length scale, is of order 1 causing particle migration to the equilibrium positions where the forces are balanced [20].…”

“…The electrical impedance of a particle can be used to sensitively determine particle size down to submicron diameters [2] and impedance spectroscopy can be used for label free cell differentiation to a limited extent [3]. Optical analysis can also be used to measure the size and morphology from the angular scatter of particles and offers more information on phenotype than impedance sensing as a range of fluorescently tagged antibodies with different emission peaks can be used to discriminate between cell types.…”

Fabrication of 10 nm diameter hydrocarbon nanopores

“…One such method is ion beam sculpting, where relatively large focused ion beam ͑FIB͒ holes are closed down to 2-10 nm using a defocused argon ion beam. 7 Other methods include electron beam-induced pore closing, 8 electron beam stimulated decomposition and sputtering, 9,10 film embedding of carbon nanotubes, 11 soft lithography, 12 and chemical etching. 13,14 Once created, nanopores must be measured.…”