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: 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 utilisation of the detection channels, due to inefficiency in the utilisation 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: The invention relates to constructs comprising a nucleic acid binding protein and a surface. At least one native accessible cysteine residue is removed from the binding protein. The binding protein is attached to the surface via one or more accessible cysteine residues. The removal of other accessible cysteine residues from the protein allows control attachment to the surface. The constructs can be used to generate transmembrane pores having a nucleic acid binding protein 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 each of its component nucleotides by stochastic sensing.

Abstract: A method of fabricating a membrane having a tapered 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 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: 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: 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.