Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores

Abstract

Solid-state nanopores have emerged as a versatile tool for the characterization of single biomolecules such as nucleic acids and proteins 1 . However, the creation of a nanopore in a thin insulating membrane remains challenging. Fabrication methods involving specialized focused electron beam systems can produce well-defined nanopores, but yield of reliable and low-noise nanopores in commercially available membranes remains low 2,3 and size control is nontrivial 4,5 . Here, the application of high electric fields to fine-tune the size of the nanopore while ensuring optimal low-noise performance is demonstrated. These short pulses of high electric field are used to produce a pristine electrical signal and allow for enlarging of nanopores with subnanometer precision upon prolonged exposure. This method is performed in situ in an aqueous environment using standard laboratory equipment, improving the yield and reproducibility of solid-state nanopore fabrication.

Fabrication of Low Noise Borosilicate Glass Nanopores for Single Molecule Sensing

“…Its possible that electron deposition during pore shrinking might play a role in this. It is important to note here that the I RMS noise of borosilicate nanopores are lower than silicon nitride, silicon oxide [ 36 , 37 ], graphene [ 38 ], MoS 2 [ 20 ] nanopores by about a factor of 5 and comparable to quartz nanopores [ 39 ]. I RMS noise plays a major role in deciding the resolving power of nanopores for molecular detection.…”

Increased dwell time and occurrence of dsDNA translocation events through solid state nanopores by LiCl concentration gradients

“…Air bubbles in the nanopore can “dewet” the pore and prevent passage of ionic solution and molecules . Such a phenomenon is reversible through various techniques including electrowetting, which employs a cyclic voltage pulse to enhance the hydrophilicity of the pore albeit while also marginally increasing your pore diameter in the process . Electrowetting allows for continued data acquisition, although introduces the need for constant monitoring of the data acquisition session to interfere when a hydrophobic blockage occurs.…”

“…Nanopore technology has the potential for detecting and characterizing biomolecules including DNA , RNA and proteins , viruses , and polysaccharides . As biomolecules pass through the nanopore, they cause ionic current blockages, which can be analyzed to characterize physical and chemical properties of the biomolecule . Although both biological and solid‐state nanopores are effective in biomolecular detection, solid‐state nanopores have the added benefit of increased durability and size tuning …”

Fabrication of Low Noise Borosilicate Glass Nanopores for Single Molecule Sensing

“…When comparing shrunk and unshrunk pores with similar taper lengths, we find that unshrunk pores have~31% larger open pore current and~12% lower I RMS noise as can be seen in Fig 2F. Its possible that electron deposition during pore shrinking might play a role in this. It is important to note here that the I RMS noise of borosilicate nanopores are lower than silicon nitride, silicon oxide [36,37], graphene [38], MoS 2 [20] nanopores by about a factor of 5 and comparable to quartz nanopores [39]. I RMS noise plays a major role in deciding the resolving power of nanopores for molecular detection.…”