Label-free detection of single molecules
The detection limit for the resistive-pulse technique critically depends on the diameter and length of the sensing orifice. Classically the pores used in Coulter counters have diameters well above 10 microns. Macromolecules can only be detected using this technique with a pore with typical dimensions in the nanometre length scale. Nanopores, as we define them, are small holes in membranes that are less than 100 nm thick and have diameters well below 100 nm.
Today, there are two sources of nanopores. The ‘bottom-up’ method uses natural nanopores extracted from bacteria. The second approach is ‘top-down’ – using modern nanotechnology to fabricate nanpores in thin engineered membranes.
A very good description of model biological nanopores can be found on the nanoSEQ page.
A video describing the DNA sequencing method developed by Oxford Nanopore Technologies can be see here.
Descriptions of the so-called solid-state nanopores, how they are made, and what they are used for, can be found on the pages of the following reseach groups:
Cees Dekker Lab
Nynke Dekker Lab
Golovchencko and Branton Lab