Abstract: Methods for determining molecular concentration using solid-state nanopores are provided. The methods include measuring a current signal and using the signal to identify first and second electrical signatures. A first set is used to determine a first rate of a target having an unknown concentration, and a second set is used to determine a second rate of a control having a known concentration. The first and second rates are each a function of a pore property factor that represents physical properties of the solid-state nanopore and operating conditions. The first rate is further a function of a first property factor that represents physical properties of the target and the unknown concentration. The second rate is further a function of a second property factor that represents physical properties of the control and the known concentration. Ratios of the first rate to the second rate are used to determine the unknown concentration.

Abstract: A method for fabricating a nanopore at a particular location in a membrane includes controlling a dielectric strength of the membrane at a particular location on the membrane while applying one of an electric potential or an electric current to the membrane, monitoring an electrical property across the membrane while one of the electric potential or the electric current is being applied across the membrane, detecting an abrupt change in the electrical property across the membrane while one of the electric potential or the electric current is being applied across the membrane; and removing the electric potential or the electric current from the membrane in response to detecting the abrupt change in the electrical property.

Abstract: To reduce unwanted variation in the speed of DNA translocating solid-state nanopores, a nanoscale pre-confinement of translocating molecules is demonstrated using an ultra-thin nanoporous silicon nitride (NPN) membrane separated from a single sensing nanopore by a nanoscale cavity. Comprehensive experimental results demonstrate that the presence of this nanofilter results in a global minimum in the coefficient of variation of passage times in the sensing pore over a range of DNA sizes which depends on the height of the cavity. Such advanced nanopore devices minimize the standard deviation of the passage time distribution independently of its diameter and stability. These results also represents the first experimental verification that the inter- and intra-molecular passage time variation depends on the conformational entropy of such molecule prior to translocation, while providing a practical strategy for controlling transport across solid-state nanopores.

Abstract: A method for fabricating a nanopore at a particular location in a membrane includes controlling a dielectric strength of the membrane at a particular location on the membrane while applying one of an electric potential or an electric current to the membrane, monitoring an electrical property across the membrane while one of the electric potential or the electric current is being applied across the membrane, detecting an abrupt change in the electrical property across the membrane while one of the electric potential or the electric current is being applied across the membrane; and removing the electric potential or the electric current from the membrane in response to detecting the abrupt change in the electrical property.