Abstract: Apparatus and methods for controlling the insertion of a membrane channel into a membrane are disclosed. In one arrangement a first bath holds a first liquid in contact with a first surface of a membrane. A second bath holds a second liquid in contact with a second surface of the membrane. The membrane separates the first and second liquids. A first electrode contacts the first liquid. A second electrode contacts the second liquid. A driving unit applies a potential difference across the membrane via the first and second electrodes to promote insertion of a membrane channel into the membrane from the first liquid or the second liquid. A membrane voltage reduction unit is connected in series with the membrane. The driving unit applies a driving voltage across the membrane voltage reduction unit and the membrane, the driving voltage providing the potential difference across the membrane.

Abstract: The invention relates to new in vitro methods for synthesising a polymer, particularly a polynucleotide molecule, having a pre-defined sequence of units such as nucleotides. For synthesising a polynucleotide molecule the methods involve a process of extending a polynucleotide synthesis molecule with a transfer nucleotide. The methods additionally involve repeating the extension process multiple times to iteratively extend the polynucleotide molecule with multiple transfer nucleotides to generate a new polynucleotide molecule having a pre-defined nucleotide sequence. The invention also relates to in vitro methods of joining multiple synthetic polynucleotides following synthesis to form larger synthetic polynucleotides, as well as devices and systems for performing the extension, synthesis and assembly methods of the invention.

Abstract: The invention relates to compositions, methods, devices, systems, and kits for detecting and characterizing molecules using a nanopore device.

Abstract: A fluidic device, such as an electrowetting-on-dielectric device, is provided. The device comprises a fluid chamber containing apolar fluid. The fluid chamber comprises an input port and a channel fluidly connected to the input port. The input port is formed with an opening to receive a pipette tip and impart a droplet of polar fluid into the channel. The insertion of the pipette tip into the fluid chamber causes displacement of the apolar fluid in the fluid chamber such that when the pipette tip is retracted from the fluid chamber, apolar fluid displaces the polar fluid from the surface of the pipette tip to form a droplet of polar fluid surrounded by apolar fluid in the channel of the fluid chamber.

Abstract: A measurement signal measured from a polymer during translocation of the polymer with respect to a nanopore is analysed using an input sequence estimate of the sequence of polymer units of the polymer, and a mapping between the measurement signal and the input sequence estimate. In particular, a sequence slice derived from a slice of the input sequence estimate around a subject polymer unit in the sequence of polymer units, and a signal slice of the measurement signal mapped to the sequence slice by the mapping, are supplied as inputs to a slice machine learning system that provides an output representing an estimate of the identity of the subject polymer unit.

Abstract: Methods and apparatus for measuring current are provided. In one arrangement, a first charge amplifier integrates a current to be measured. A processing circuit filters an output from the first charge amplifier using a first low pass filter module and a second low pass filter module. A second charge amplifier integrates a current derived from the filtered output from the first charge amplifier. The apparatus is configured to reset the first charge amplifier at the start of each of a plurality of sensing frames. The processing circuit obtains at least a first sample of the output from the first charge amplifier in each sensing frame. The sampling of the first sample alternates from one sensing frame to the next sensing frame between sampling via the first low pass filter module and sampling via the second low pass filter module.

Abstract: The invention relates to modified helicases with reduced unbinding from polynucleotides. The helicases can be used to control the movement of polynucleotides and are particularly useful for sequencing polynucleotides.

Abstract: The invention relates to a new method of sequencing a double stranded target polynucleotide. The two strands of the double stranded target polynucleotide are linked by a bridging moiety. The two strands of the target polynucleotide are separated using a polynucleotide binding protein and the target polynucleotide is sequenced using a transmembrane pore.

Abstract: The invention relates generally to a method of detecting and/or analysing target polymers, especially target polynucleotides, using a biological pore. The invention also relates to a novel system for carrying out the method. The method has many uses. In particular, the method may be used for diagnosis, detection of polymorphisms and V(D)J repertoire analysis.

Abstract: Methods and apparatus for measuring current are provided. In one arrangement, a first charge amplifier integrates a current to be measured. A processing circuit filters an output from the first charge amplifier using a first low pass filter module and a second low pass filter module. A second charge amplifier integrates a current derived from the filtered output from the first charge amplifier. The apparatus is configured to reset the first charge amplifier at the start of each of a plurality of sensing frames. The processing circuit obtains at least a first sample of the output from the first charge amplifier in each sensing frame. The sampling of the first sample alternates from one sensing frame to the next sensing frame between sampling via the first low pass filter module and sampling via the second low pass filter module.

Abstract: Droplet interfaces are formed between droplets in an electro-wetting device comprising an array of actuation electrodes. Actuation signals are applied to selected actuation electrodes to place the droplets into an energised state in which the shape of the droplets is modified compared to a shape of the droplets in a lower energy state and to bring the two droplets into proximity. The actuation signals are then changed to lower the energy of the droplets into the lower energy state so that the droplets relax into the gap and the two droplets contact each other thereby forming a droplet interface. The use of sensing electrodes in the device permit electrical current measurements across the droplet interface. The sensing electrodes can be used for either (i) applying a reference signal during droplet actuation or (ii) recording electrical current measurements. Two or more electrodes are configurable to lyse cells within a droplet positioned over said electrodes.

Abstract: The invention relates to a new method of determining the presence, absence or characteristics of an analyte. The analyte is coupled to a membrane. The invention also relates to nucleic acid sequencing.

Abstract: To form a layer separating two volumes of aqueous solution, there is used an apparatus comprising elements defining a chamber, the elements including a body of non-conductive material having formed therein at least one recess opening into the chamber, the recess containing an electrode. A pre-treatment coating of a hydrophobic fluid is applied to the body across the recess. Aqueous solution, having amphiphilic molecules added thereto, is flowed across the body to cover the recess so that aqueous solution is introduced into the recess from the chamber and a layer of the amphiphilic molecules forms across the recess separating a volume of aqueous solution introduced into the recess from the remaining volume of aqueous solution.

Abstract: The invention relates to mutant forms of CsgG. The invention also relates to analyte detection and characterization using CsgG.

Abstract: 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.

Abstract: The invention relates to a new method of characterising a target RNA polynucleotide by taking one or more measurements as the target RNA polynucleotide moves with respect to a transmembrane pore. The movement is controlled by a DNA helicase. The invention also relates to a modified RNA construct wherein the RNA polynucleotide has been modified to increase DNA helicase binding thereto.

Abstract: A microfluidic device for analysing a test liquid comprises: a sensor (235), such as a membrane provided with nanopores, provided in a sensing chamber (237); a sensing chamber inlet channel (261) and a sensing chamber outlet channel (262), each connecting to the sensing chamber for respectively passing liquid into and out of the sensing chamber, and a reservoir (233) forming a sample input port to the microfluidic device, the reservoir being in fluid communication with the sensing chamber inlet channel (261); a liquid collection channel (232); a barrier (231) between an end of the sensing chamber outlet channel (262) and the liquid collection channel (232); a first seal (251), covering the sample input port: a second seal (252), covering the end of the sensing chamber outlet channel (262), thereby preventing liquid from flowing from the sensing chamber (237), over the barrier (231), into the liquid collection channel (232); wherein the microfluidic device is filled with a liquid from the first seal (251) at t

Abstract: The present disclosure relates to a computer-implemented method for cancer diagnosis, comprising: a) selectively sequencing polymers of a biological sample according to at least one target gene site by translocating the polymers through nanopores of a nanopore sequencing system, including: (i) analyzing an initial nucleotide sequence of a first polymer of the biological sample while the first polymer is translocating through a nanopore of the nanopore sequencing system to determine whether the initial nucleotide sequence corresponds to the at least one target gene site; and (ii) continuing the sequencing of the first polymer to obtain measurement data of the first polymer only if the initial nucleotide sequence of the first polymer corresponds to the at least one target gene site: b) determining, based on the measurement data, a biological state of a nucleotide sequence of the first polymer corresponding to the at least one target gene site; and c) classifying a cancer using a classification algorithm based o

Abstract: Described herein, among other things, is a method of sequencing, comprising: concatenating a plurality of fragments of genomic DNA to produce concatenated DNA; sequencing the concatenated DNA to produce a plurality of sequence reads, wherein at least some of the sequence reads comprise: at least the sequence of the 3? and/or 5? ends of a fragment that corresponds to the locus of interest and sequence of one or both of the fragments that flank the fragment in the concatenated DNA; and grouping the sequence reads that corresponds to the locus of interest using, for each of the grouped sequence reads: the 3? and/or 5? end sequences; and/or the flanking sequence.

Abstract: The invention relates to new methods for synthesising polynucleotide molecules according to a predefined nucleotide sequence. The invention also relates to methods for the assembly of synthetic polynucleotides following synthesis, as well as systems and kits for performing the synthesis and/or assembly methods.