Oxford Nanopore Technologies Limited

Vib Vzw

Vrije Universiteit Brussel

Sony Deutschland Gmbh

Other

Sharp Life Science (Eu) Limited

James Anthony Clarke

James White

Andrew John Heron

Lakmal Nishantha Jayasinghe

Clive Gavin Brown

Elizabeth Jayne Wallace

Stuart William Reid

John Milton

Mark Bruce

Gavin Harper

Graham Hall

Marion Louise Crawford

Domenico Caprotti

John Hagan Pryce Bayley

Daniel John Turner

Rebecca Victoria Bowen

Jason Robert Hyde

Steven Paul White

Gurdial Singh Sanghera

Terence Alan Reid

Ruth Moysey

Richard George Hambley

David Jackson Stoddart

Luke McNeill

Brian McKeown

Jonathan Bankes Pugh

David Alves

Stephen Cheley

Szabolcs Soeroes

Han Karel Remaut

Ramiz Iqbal Nathani

Stefan Howorka

Gaëlle Anne-Leonie Andreatta

Richard Muscat

Paul Richard Moody

Akio Yasuda

Benjamin James Hadwen

Jurina Wessels

Christopher James Wright

Sally Anderson

Oliver Harnack

Daniel Ryan Garalde

Daniel George Fordham

Matthew Holden

Roger Charles Gill

Terry Reid

Mike Jennison

Mihaela Misca

Jessica Mary May Knott

Jessica Mary May Johnson

Apparatus and methods for controlling the insertion of a membrane channel into a membrane are disclosed. The membrane separates first and second liquids. A driving unit applies a potential difference across the membrane via first and second electrodes to promote insertion of a membrane channel into the membrane. 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 membrane voltage reduction unit is configured such that a reduction in resistance through the membrane caused by insertion of a membrane channel intrinsically increases a potential difference across the membrane voltage reduction unit thereby lowering the potential difference across the membrane, the lowering sufficient to prevent or reduce promotion of insertion of a further membrane channel.

Apparatus and methods for controlling insertion of a membrane channel into a membrane

METHODS AND SYSTEMS FOR CHARACTERIZING ANALYTES USING NANOPORES

COUPLING METHOD

Nanopore Arrays for Sequencing Nucleic Acids

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.

Droplet interfaces in electro-wetting devices

The invention relates to mutant forms of CsgG. The invention also related to analyte detection and characterisation using CsgG.

Mutant CsgG pores

The invention relates to mutant forms of lysenin. The invention also relates to analyte characterisation using lysenin.

Mutant lysenin pores

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.

Modified helicases

A sequence of polymer units in a polymer (), eg. DNA, is estimated from at least one series of measurements related to the polymer, eg. ion current as a function of translocation through a nanopore (), wherein the value of each measurement is dependent on a k-mer being a group of k polymer units (). A probabilistic model, especially a hidden Markov model (HMM), is provided, comprising, for a set of possible k-mers: transition weightings representing the chances of transitions from origin k-mers to destination k-mers; and emission weightings in respect of each k-mer that represent the chances of observing given values of measurements for that k-mer. The series of measurements is analysed using an analytical technique, eg. Viterbi decoding, that refers to the model and estimates at least one estimated sequence of polymer units in the polymer based on the likelihood predicted by the model of the series of measurements being produced by sequences of polymer units. In a further embodiment, different voltages are applied across the nanopore during translocation in order to improve the resolution of polymer units.

Method and system of estimating a sequence of polymer units

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.

Hairpin loop method for double strand polynucleotide sequencing using transmembrane pores

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.

Coupling method

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.

Formation of layers of amphiphilic molecules

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. The membrane voltage reduction unit is configured such that a reduction in resistance through the membrane caused by insertion of a membrane channel intrinsically increases a potential difference across the membrane voltage reduction unit thereby lowering the potential difference across the membrane. The lowering of the potential difference across the membrane is sufficient to prevent or reduce promotion of insertion of a further membrane channel.

A time-ordered series of measurements of a polymer made during translocation of the polymer through a Nanopore are analysed. The measurements are dependent on the identity of k-mers in the Nanopore, a k-mer bring k polymer units of the polymer, where k is a positive integer. The method involves deriving, from the series of measurements, a feature vector of time-ordered features representing characteristics of the measurements; and determining similarity between the derived feature vector and at least one other feature vector.

Analysis of measurements of a polymer

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Oxford, United Kingdom

James Anthony Clarke