In the 1940s Wallace Coulter set about finding a way to quickly count blood cells, which at the time was a slow and inefficient process. His approach was to pass cells, one by one, through a small hole connecting two compartments filled with electrolyte solution. Simultaneously, he applied a voltage across the compartments and measured the ionic current through the hole. As a cell passed through the hole, it would partially block the flow of electric charges, and the current would drop by an amount proportional to the volume of the cell.

Coulter’s technique worked out wonderfully and revolutionized cell counting. The holes in Coulter’s devices were roughly 10 μm in diameter, slightly larger than the size of the cells being probed. But as time passed, improved fabrication techniques led to smaller holes, which allowed smaller analytes to be investigated.

The last two decades have seen a renaissance of the Coulter counter concept. The principle remains essentially the same, but nanopores—holes with a diameter of merely a few nanometers—have shrunk the length scale from that of single cells to that of single molecules. For further reading, click here.