We report a scalable method to fabricate high-quality graphene nanopores for biomolecule detection using a helium ion microscope (HIM). HIM milling shows promising capabilities for precisely controlling the size and shape, and may allow for the potential production of nanopores at wafer scale. Nanopores could be fabricated at different sizes ranging from 5 to 30 nm in diameter in few minutes. Compared with the current solid-state nanopore fabrication techniques, e.g. transmission electron microscopy, HIM is fast. Furthermore, we investigated the exposure-time dependence of graphene nanopore formation: the rate of pore expansion did not follow a simple linear relationship with exposure time, but a fast expansion rate at short exposure time and a slow rate at long exposure time. In addition, we performed biomolecule detection with our patterned graphene nanopore. The ionic current signals induced by 20-base single-stranded DNA homopolymers could be used as a basis for homopolymer differentiation. However, the charge interaction of homopolymer chains with graphene nanopores, and the conformations of homopolymer chains need to be further considered to improve the accuracy of discrimination.

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Antibiotics as emerging environmental contaminants, are widely used in both human and veterinary medicines. A solid-state nanopore sensing method is reported in this article to detect Tetracycline, which is based on Tet-off and Tet-on systems. rtTA (reverse tetracycline-controlled trans-activator) and TRE (Tetracycline Responsive Element) could bind each other under the action of Tetracycline to form one complex. When the complex passes through nanopores with 8 ~ 9 nanometers in diameter, we could detect the concentrations of Tet from 2 ng/mL to 2000 ng/mL. According to the Logistic model, we could define three growth zones of Tetracycline for rtTA and TRE. The slow growth zone is 0–39.5 ng/mL. The rapid growth zone is 39.5−529.7 ng/mL. The saturated zone is > 529.7 ng/mL. Compared to the previous methods, the nanopore sensor could detect and quantify these different kinds of molecule at the single-molecule level.

We provide a way to precisely control the geometry of a SiNx nanopore by adjusting the applied electric pulse. The pore is generated by applying the current pulse across a SiNx membrane, which is immersed in potassium chloride solution. We can generate single conical and cylindrical pores with different electric pulses. A theoretical model based on the Poisson and Nernst—Planck equations is employed to simulate the ion transport properties in the channel. In turn, we can analyze pore geometries by fitting the experimental current-voltage (I–V) curves. For the conical pores with a pore size of 0.5–2nm in diameter, the slope angles are around −2.5° to −10°. Moreover, the pore orifice can be enlarged slightly by additional repeating pulses. The conic pore lumen becomes close to a cylindrical channel, resulting in a symmetry I–V transport under positive and negative biases. A qualitative understanding of these effects will help us to prepare useful solid-nanopores as demanded.

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success depends on nanopore diameter, geometry, and surface chemistry. This work explores the possibility of using the detergent Tween-20 for nanopore surface coating [2] combined with high bandwidth recording electronics to characterize freely translocating, untethered proteins on a single molecule level. Here, we utilize the dependence of DI on the orientation of non-spherical proteins transiting a nanopore to determine their intrinsic shapes, volumes, and dipole moments in solution. The ability to thoroughly examine unlabeled, natively-folded proteins in an aqueous sample on a single molecule level signifies an important step toward the use of nanopores for proteomic and diagnostic applications. [1] Yusko, E.C., et al., Real-time shape approximation and 5-D fingerprinting of single proteins. arXiv preprint arXiv:1510.01935, 2015. [2] Hu, Rui, et al. Intrinsic and membrane-facilitated a-synuclein oligomerization revealed by label-free detection through solid-state nanopores. Scientific reports 6, 2016.

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