Abstract: Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.

Abstract: A method is provided for deterministically translocating through a nanopore a target polymer molecule of a nucleic acid polymer molecule or a protein polymer molecule. In the method, an enzyme clamp is reversibly bound to a plurality of sequential polymer subunits of the target polymer molecule. The target polymer molecule and the enzyme clamp are disposed at the nanopore. In the method, there is applied a pulse of force operative to deterministically advance the enzyme clamp along the target polymer molecule by no more than one polymer subunit. The pulse of force is then repeatedly applied to cause deterministic translocation of a sequential plurality of polymer subunits of the target polymer molecule through the nanopore.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a voltage between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a voltage between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: A nanopore system provided herein includes first and second fluidic reservoirs in fluidic communication with a nanopore forming a fluidic path between the reservoirs. An enzyme clamp, provided in the first fluidic reservoir, abuts the nanopore and is reversibly bound to a sequential plurality of polymer subunits of a target polymer molecule in ionic solution. The clamp has an outer clamp diameter that is greater than the nanopore diameter. An electrical circuit includes an electrode in each of the reservoirs for applying a voltage bias across the nanopore. A pulse generator is connected in the electrical circuit to apply control pulses across the nanopore to step the clamp along sequential polymer subunits of the target polymer molecule. The system includes no fuel or source of fuel for the clamp. A controller is connected in the electrical circuit for controlling the collection of electrical indications of polymer subunits.

Abstract: Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a voltage between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a voltage between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.

Abstract: A nanopore system provided herein includes first and second fluidic reservoirs in fluidic communication with a nanopore forming a fluidic path between the reservoirs. An enzyme clamp, provided in the first fluidic reservoir, abuts the nanopore and is reversibly bound to a sequential plurality of polymer subunits of a target polymer molecule in ionic solution. The clamp has an outer clamp diameter that is greater than the nanopore diameter. An electrical circuit includes an electrode in each of the reservoirs for applying a voltage bias across the nanopore. A pulse generator is connected in the electrical circuit to apply control pulses across the nanopore to step the clamp along sequential polymer subunits of the target polymer molecule. The system includes no fuel or source of fuel for the clamp. A controller is connected in the electrical circuit for controlling the collection of electrical indications of polymer subunits.

Abstract: In a method p for controlling translocation of a target polymer molecule through a nanopore, a clamp is reversibly bound to a sequential plurality of polymer subunits along the target polymer molecule length and the molecule and clamp are disposed in an ionic solution that is in fluidic communication with the nanopore. A constant translocation force is applied across the nanopore to induce travel of the target polymer molecule into the nanopore, until the clamp abuts the nanopore aperture and stops further travel of the target polymer molecule into the nanopore. Then a voltage control pulse is applied across the nanopore and/or a thermal control pulse is applied at the nanopore, with a pulse duration that steps the clamp along the target polymer molecule by no more than one polymer subunit in a direction opposite that of travel into the nanopore. No fuel is provided to the clamp.

Abstract: Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.

Abstract: There is provided a nanometric structure that includes a self-supporting nanometric material having a thickness of no more than about 5 nm. A plurality of nanopores is provided in the nanometric material, and the nanopore plurality has a density of at least about 1000 nanopores/cm2. Each nanopore in the plurality of nanopores has a diameter that is no greater than about 10 nm. The plurality of nanopores is monodisperse in diameter with a variation of about ±30%. In a further nanometric structure provided herein there is included a self-supporting nanometric material having a thickness of no more than about 5 nm. A plurality of nanopores in the nanometric material includes at least about 50 nanopores. Each nanopore in the plurality of nanopores has a diameter that is no greater than about 10 nm. The plurality of nanopores is monodisperse in diameter with a variation of about ±30%.

Abstract: Provided herein is a nanopore sensor, including a self-supported solid state material selected from hexagonal-BN, a mono-atomic glass, MoS2, WS2, MoSe2, MoTe2, TaSe2, NbSe2, NiTe2, Bi2Sr2CaCu2Ox, and Bi2Te3, having a thickness less than about 5 nm. A nanopore extends through the material thickness. A connection from the first material surface to a first reservoir provides, at the first material surface, a species in an ionic solution from the first reservoir to the nanopore, and a connection from the second material surface to a second reservoir collects in the second reservoir the species and ionic solution after translocation of the species and ionic solution through the nanopore. An electrical circuit is connected with the nanopore, through the material thickness, from the first reservoir to the second reservoir, to monitor translocation of species in the ionic solution through the nanopore in the solid state material.

Abstract: There is provided a substantially bare, self-supported single-layer graphene membrane including a nanopore extending through a thickness of the graphene membrane from a first to a second membrane surface opposite the first graphene membrane surface. A connection from the first graphene membrane surface to a first reservoir provides, at the first graphene membrane surface, a species in an ionic solution to the nanopore, and a connection from the second graphene membrane surface to a second reservoir is provided to collect the species and ionic solution after translocation of the species and ionic solution through the nanopore from the first graphene membrane surface to the second graphene membrane surface. An electrical circuit is connected on opposite sides of the nanopore to measure flow of ionic current through the nanopore in the graphene membrane.

Abstract: Provided is a solid state support structure including an aperture having a molecular entrance and a molecular exit. A first reservoir is in fluidic communication with the molecular entrance of the aperture and contains a molecule-bearing liquid solution. A second reservoir is in fluidic communication with the molecular exit of the aperture for containing a molecule-bearing liquid solution. A first liquid channel is connected to the first reservoir within less than about 300 microns of the aperture in the support structure and includes molecule-bearing liquid solution for delivery to the first reservoir. A second liquid channel is connected to the second reservoir for accepting molecule-bearing liquid solution from the second reservoir. An electrical connection between the first reservoir and the second reservoir imposes an electrical bias between the first reservoir and the second reservoir for driving the molecule-bearing liquid solution through the aperture in the solid state support structure.

Abstract: In a method p for controlling translocation of a target polymer molecule through a nanopore, a clamp is reversibly bound to a sequential plurality of polymer subunits along the target polymer molecule length and the molecule and clamp are disposed in an ionic solution that is in fluidic communication with the nanopore. A constant translocation force is applied across the nanopore to induce travel of the target polymer molecule into the nanopore, until the clamp abuts the nanopore aperture and stops further travel of the target polymer molecule into the nanopore. Then a voltage control pulse is applied across the nanopore and/or a thermal control pulse is applied at the nanopore, with a pulse duration that steps the clamp along the target polymer molecule by no more than one polymer subunit in a direction opposite that of travel into the nanopore. No fuel is provided to the clamp.