Abstract: The invention relates to a mutant ?-hemolysin (?-HL) pore which is useful for detecting one or more nucleotides by stochastic sensing. The pore is particularly useful for sequencing DNA or RNA. A molecular adaptor that allows detection of the nucleotide(s) is covalently attached to the pore. The pore is specifically modified to facilitate positioning of the adaptor and may be modified to facilitate covalent attachment.

Abstract: A sequence of polymer units in a polymer (3), 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 (1), wherein the value of each measurement is dependent on a k-mer being a group of k polymer units (4). 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.

Abstract: 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.

Abstract: The invention provides method of covalently coupling two or more moieties, the method comprising: (a) providing a first moiety having covalently attached thereto (i) at least one first linker comprising a first hybridizable region and (ii) at least one first group capable of forming a covalent bond; (b) providing a second moiety having covalently attached thereto (i) at least one second linker comprising a second hybridizable region capable of hybridizing to the first hybridizable region and (ii) at least a second group capable of forming a covalent bond with the first group; (c) contacting the first and second moieties under conditions that allow the first and second hybridizable regions to hybridize and link the moieties; and (d) exposing the linked moieties to conditions that allow the formation of a covalent bond between the first and second groups.

Abstract: A target polynucleotide is expanded. In respect of each nucleotide in the target polynucleotide, the target polynucleotide comprises clock nucleotides and at least one signal nucleotide in a predetermined order. The clock nucleotides have a predetermined sequence common to each nucleotide in the target polynucleotide. The at least one signal nucleotide is characteristic of the identity of the respective nucleotide in the target polynucleotide. During translocation of the expanded polynucleotide through a nanopore, electrical measurements dependent on the polynucleotide within the pore are made, to derive an analysis signal. Clock signals derived from the clock nucleotides are identified. Relative to the positions of the identified clock signals, nucleotide signals derived from the least one signal nucleotide are derived to analyse the target polynucleotide.

Abstract: An analysis instrument comprises plural modules connected together over a data network, each module comprising an analysis apparatus operable to perform biochemical analysis of a sample. Each module comprises a control unit that controls the operation of the analysis apparatus. The control units are addressable to select an arbitrary number of modules to operate as a cluster for performing a common biochemical analysis. The control units communicate over the data network, repeatedly during the performance of the common biochemical analysis, to determine the operation of the analysis apparatus of each module required to meet the global performance targets, on the basis of measures of performance derived from the output data produced by the modules. The arrangement of the instrument as modules interacting in this manner provides a scalable analysis instrument.

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

Abstract: The invention relates to a new method of characterising a target polynucleotide. The method uses a pore and an XPD helicase. The helicase controls the movement of the target polynucleotide through the pore.

Abstract: An apparatus for supporting an array of layers of amphiphilic molecules, the apparatus comprising: a body (11), formed in a surface of the body, an array of sensor wells (10) capable of supporting a layer of amphiphilic molecules (30) across the sensor wells, the sensor wells each containing an electrode (12) 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: A piston head for a syringe pump comprises a barrier portion (11) for driving fluid through a syringe pump barrel (30), wherein a peripheral section (13,14) of the barrier portion (11) is shaped to seal against the syringe pump barrel (30); and a re-silent member (15) arranged to resist deformation of the shaped peripheral section (13,14) of the barrier portion (11).

Abstract: A pump for use in low-profile applications comprises a barrel for holding fluid; and a piston that converts a rotational driving force into a longitudinal driving motion within the barrel. The pump provides space saving advantages by reducing the need for external equipment and mechanisms around the pump for providing actuation or moving the actuating mechanism.

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: The invention relates to a new method of characterising a target polynucleotide. The method uses a pore and a Hel308 helicase or amolecular motor which is capable of binding to the target polynucleotide at an internal nucleotide. The helicase or molecular motor controls the movement of the target polynucleotide through the pore.

Abstract: An apparatus for sensing of an interaction of a molecular entity with a membrane protein in a lipid bilayer comprises an array of sensor elements (21) arranged to output an electrical signal that is dependant on occurrences of the interaction. A detection circuit (3) comprised detection channels (30) capable of amplifying an electrical signal from a sensor element. More sensor elements (21) are provided than detection channels (30), and detection channels (30) are selectively connected to sensor elements (21) that have acceptable quality of performance in that a lipid bilayer is formed and that an acceptable number of membrane proteins are inserted, on the basis of the amplified electrical signals that are output from the detection channels. This improves the efficiency of utilization of the detection channels, due to inefficiency in the utilization of the sensor elements, resulting in a reduction in the cost of the apparatus and the ability to perform sensing using relatively small samples.

Abstract: A one-way valve, comprises a valve housing; a valve member provided within the valve housing, the valve member being operative to open and close the valve and comprising a diaphragm with a central orifice to allow fluid to pass from one side of the diaphragm to the other; a valve inlet provided on a first side of the diaphragm; and a valve outlet provided on a second side of the diaphragm; wherein the configuration of the diaphragm and the valve housing biases the diaphragm to seal the inlet at rest.

Abstract: The invention relates to mutant forms of Msp. The invention also relates to nucleic acid characterisation using Msp.

Abstract: A method of fabricating a membrane having a tampered pore, a polymeric membrane having a tapered pore, and uses of such polymeric membrane are disclosed. The membrane includes apertures of increasing diameter which are aligned with each other to form the tapered pore.

Abstract: The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.

Abstract: An analysis apparatus for performing biochemical analysis of a sample using nanopores comprises: a sensor device that supports plural nanopores, reservoirs holding material for performing the analysis; a fluidics system; and plural containers for receiving respective samples, all arranged in a cartridge that is removably attachable to an electronics unit arranged to generate drive signals to perform signal processing circuit to generate output data representing the results of the analysis. The fluidics system supplies samples selectively from the containers to the sensor device using a rotary valve.