Example nanopore sequencers include a cis well, a trans well, and a nanopore fluidically connecting the cis and trans wells. In one example sequencer, a modified electrolyte (including an electrolyte and a cation complexing agent) is present in the cis well, or the trans well, or in the cis and the trans wells. In another example sequencer, a gel state polyelectrolyte is present in the cis well, or the trans well, or in the cis and the trans wells.

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.

An apparatus for supporting an array of layers of amphiphilic molecules, the apparatus comprising: a body, formed in a surface of the body, an array of sensor wells capable of supporting a layer of amphiphilic molecules across the sensor wells, the sensor wells each containing an electrode for connection to an electrical circuit, and formed in the surface of the body between the sensor wells, flow control wells capable of smoothing the flow of a fluid across the surface.

The invention relates to new methods of moving helicases past spacers on polynucleotides and controlling the loading of helicases on polynucleotides. The invention also relates to new methods of characterising target polynucleotides using helicases.

An apparatus for supporting an array of layers of amphiphilic molecules, the apparatus comprising: a body, formed in a surface of the body, an array of sensor wells capable of supporting a layer of amphiphilic molecules across the sensor wells, the sensor wells each containing an electrode for connection to an electrical circuit, and formed in the surface of the body between the sensor wells, flow control wells capable of smoothing the flow of a fluid across the surface.

A method of synthesizing an oligonucleotide using a nanofluidic device including a plurality of nanopore channels, a plurality of electrodes, and an electrolyte solution, includes coupling a primer to an inner wall of a nanopore channel of the plurality of nanopore channels, the primer having a protecting group. The method also includes applying a voltage to an electrode of the plurality of electrodes that corresponds to the nanopore channel to produce an acid from the electrolyte solution at the electrode. The electrode includes an anode and a cathode disposed at opposite sides of the nanopore channel. The method further includes the acid removing the protecting group from the primer. Moreover, the method includes coupling a nucleotide to the primer with the protecting group removed to form an intermediate product. In addition, the method includes repeating the steps on the intermediate product until the oligonucleotide is synthesized.

An integrated semiconductor device for manipulating and processing bio-entity samples and methods are described. The device includes a lower substrate, at least one optical signal conduit disposed on the lower substrate, at least one cap bonding pad disposed on the lower substrate, a cap configured to form a capped area, and disposed on the at least one cap bonding pad, a fluidic channel, wherein a first side of the fluidic channel is formed on the lower substrate and a second side of the fluidic channel is formed on the cap, a photosensor array coupled to sensor control circuitry, and logic circuitry coupled to the fluidic control circuitry, and the sensor control circuitry.

The present invention provides a method of detecting one or more analytes in a target sample, the method comprising: a. providing a nanoparticle dimer adapted to bind the analyte; b. causing the dimer to pass through a nanopore by voltage-driven translocation; c. observing changes in the translocation current; and d. comparing the translocation current profile of the target sample to the translocation current profile of a control sample; wherein a change in the translocation current profile of the target sample versus the control sample indicates the presence of the analyte in the target sample. Also provided is a method of detecting one or more analytes in a target sample, the method comprising: a. providing a nanoparticle adapted to bind the analyte; b. providing a carrier nucleic acid molecule with at least one single-stranded region; c. contacting the carrier nucleic acid molecule and nanoparticle with the target sample, forming a carrier nucleic acid/analyte/nanoparticle complex; b. causing the carrier nucleic acid/analyte/nanoparticle complex to pass through a biological nanopore by voltage-driven translocation; c. observing changes in the translocation current; and d. comparing the translocation current profile of the target sample to the translocation current profile of a control sample; wherein a change in the translocation current profile of the target sample versus the control sample indicates the presence of the analyte in the target sample.

A detection method includes forming a complex by binding a target substance and a dielectric particle modified by a single-domain antibody that is bindable to the target substance, separating the complex and an unbound particle in a fluid with dielectrophoresis, the unbound particle being the dielectric particle not forming the complex, and detecting the target substance contained in the separated complex with an imaging element.

A biomolecule is more easily and reliably reciprocated in a nanopore. An adapter molecule that directly or indirectly binds to a biomolecule to be analyzed comprises a three-dimensional structure formation domain consisting of a single-stranded nucleotide.