Switchable ion channels that are made of membrane proteins play different roles in cellular circuits. Since gating nanopore channels made of proteins can only work in the environment of lipid membrane, they are not fully compatible to the application requirement as a component of those nanodevice systems in which lipid membranes are hard to establish. Here we report a synthetic nanopore-DNA system where single solid-state conical nanopores can be reversibly gated by switching DNA motors immobilized inside the nanopores. High- (on-state) and low- (off-state) conductance states were found within this nanopore-DNA system corresponding to the single-stranded and i-motif structures of the attached DNA motors. The highest gating efficiency indicated as current ratio of on-state versus off-state was found when the length of the attached DNA molecule matched the tip diameter of the nanopore well. This novel nanopore-DNA system, which was gated by collective folding of structured DNA molecules responding to the external stimulus, provided an artificial counterpart of switchable protein-made nanopore channels. The concept of this DNA motor-driven nanopore switch can be used to build novel, biologically inspired nanopore machines with more precisely controlled functions in the near future by replacing the DNA molecules with other functional biomolecules, such as polypeptides or protein enzymes.

Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise quantification based on unique interactions between proteins and NPs engineered for deep and scalable quantitative proteomic studies.