Recent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top-down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore technology is exquisitely sensitive to single intact molecules, but it has only been successfully applied to DNA sequencing, so far. Here, we explore the potential of sub-nanopores for single-molecule protein identification (SMPI) and describe an algorithm for identification of the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. The analysis of identification p-values suggests that the current technology is already sufficient for matching nanospectra against small protein databases, e.g., protein identification in bacterial proteomes.

The authors discuss some of the effects quantum mechanics has on the performance of nanometer-scale devices. At low temperature, the confinement and the coherence of the electronic motion on the scale of the electron wavelength give rise to gross deviations from classical charge transport that describes the resistance found in large conventional devices. The authors examine three examples of the quantum mechanical nature of the resistance of a split-gate MODFET, that are not accounted for in conventional classical models of a FET, and yet may influence device speed, noise performance and device isolation. The authors consider the temperature and electric field ranges where quantum mechanical effects are manifested in the charge transport, and speculate about the conditions in which parasitic quantum mechanical effects might be found in a conventional device.>