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Single Molecule Filter, and Single Molecule Electrograph, and Process for Making and using Same

Nanometer-scale pores are common in biological systems and are critical for regulating biochemical processes in living systems, like the passage of ions and macromolecules through cell membranes. Biological pores can be exploited to detect small biomolecules like DNA by measuring transient changes in the pore’s ionic current. Small molecules will interrupt the flow of ions as they interact and translocate through the pore. Several manufactures are now introducing products based on this concept to sequence genes and DNA for medical applications. Reports have also shown other biomolecules like proteins may be able to be characterized using nanopores. There have been a number of attempts to fabricate nanopores using solid-state materials such as silicon nitride and two-dimensional materials such as graphene. In all cases, an electron or helium ion beam is used to ablate a hole through a membrane of the material. The diameter of the pore is generally not well controlled and the surface is amorphous because the ablation process is stochastic. Materials such as silicon nitride and graphene also tend to be electrically noisy, thereby diminishing the signal to noise ratio during the translocation measurements.

A number of problems associated with previous reports for fabricating nanopores in solid-state materials and using them for single molecule detection and characterization are remedied by this invention: 1. The invention uses a silicon dioxide tube as the pore with a well-defined inner diameter determined by controlled etching and oxidation processes. 2. Silicon dioxide is hydrophilic, and thus has superior wetting properties that are required to detect and characterize molecules in aqueous solution. 3. With previous techniques, the pore is formed through electron, gallium or helium ion ablation leaving physical damage, which could cause excessive electronic noise. In contrast, the well-controlled and precisely defined interfaces to the biomolecules made possible because of this invention could mitigate electronic noise. 4. The structure of the invention is compatible with batch fabrication processes typically used by the semiconductor industry allowing the device to be manufactured in large massive parallel arrays.

Figure 35 below illustrate calculation of electrostatic profile of biomolecules passing through a nanotube. Poisson-Boltzmann calculations are used to estimate a surface charge on two protein biomarkers (a first protein biomarker 200 (shown in figure 35) that is indicative of an ischemic stroke and a second protein biomarker 202 (shown in figure 35) that is indicative of hemorrhagic strokes) disposed in 150 mM NaCl and subjected to communication through a 6-nm inner diameter nanotube of a single molecule filter. Hydrophilic residues on the surface of the protein biomarkers (200, 202) include amino acid side chains that are charged or neutral. In some cases, the charge on protein biomarkers (200, 202) may be influenced by a local environment such as a concentration of protein biomarkers (200, 202) in the fluid. Furthermore, the surface charge may be influenced by confinement, e.g., from passing protein biomarkers (200, 202) through the nanotube that has a certain dimension or size. The calculations yield the surface charge on protein biomarkers (200, 202) as protein biomarkers (200, 202) is communicated through the 6-nm inner diameter nanotube. Magnitudes or profiles of surface charge along a long axis of protein biomarkers (200, 202) are substantially different such that protein biomarkers (200, 202) can be unique identified or characterized.


A single molecule filter includes: a membrane including: a first surface; a second surface; and a membrane aperture disposed in the membrane and traversing the membrane from the first surface to the second surface, the membrane aperture provided to communicate a single molecule across the membrane; and a nanotube disposed on the membrane and including: a first end disposed on the first surface of the membrane; a second end disposed distal to the first surface; and a tubular aperture extending along the nanotube from the first end to the second end, the tubular aperture provided to communicate the single molecule from the second end of the nanotube to the membrane aperture.


John Suehle, John Kasianowicz, Arvind Balijepalli, Joseph Robertson, and Jessica Benjamini

Patent Number: 
Technology Type(s): 
Analytical Chemistry, Biochemical Science, Chemical Sciences, Physical and Chemical Properties,
Internal Laboratory Ref #: 
Patent Issue Date: 
September 4, 2018
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