We introduce a two-dimensional method for mass spectrometry in solution that is based on the interaction between a nanometer-scale pore and analytes. As an example, poly(ethylene glycol) molecules that enter a single ␣-hemolysin pore cause distinct mass-dependent conductance states with characteristic mean residence times. The conductance-based mass spectrum clearly resolves the repeat unit of ethylene glycol, and the mean residence time increases monotonically with the poly(ethylene glycol) mass. This technique could prove useful for the real-time characterization of molecules in solution.Gaussian mixture model ͉ poly(ethylene glycol) ͉ ␣-hemolysin ͉ ion channel ͉ maximum likelihood signal classification

There are thousands of different nanometer-scale pores in biology, many of which act as sensors for specific chemical agents. Recent work suggests that protein and solid-state nanopores have many potential uses in a wide variety of analytical applications. In this review we survey this field of research and discuss the prospects for advances that could be made in the near future.

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