Oxford Nanopore Technologies PLC

A method of controlling a biochemical analysis system for analysing polymers comprising a sequence of polymer units is provided. The system is operable to take successive measurements of a polymer from a sensor element during translocation of the polymer with respect to a nanopore of the sensor element. The method comprises, when a polymer has partially translocated through the nanopore, analysing the measurements taken from the polymer during the partial translocation thereof to determine modification information in respect of a portion of the sequence of the polymer units. The polymer is classified as belonging to one of a set of classes based on the modification information; and the system is operated to reject the polymer or continue taking measurements from the polymer based on the class to which the polymer unit is classified as belonging.

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

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. The predetermined sequence of the clock nucleotides comprises a restriction site for a restriction enzyme and at least one further nucleotide that extends the predetermined sequence.

The invention provides methods of selecting polynucleotides based on their size in globular form. The polynucleotides may be treated with a condensation medium. e.g. comprising polyethylene glycol. e.g. PEG8000, and salt, in order to adopt a globular form. The method may employing filtering in order to retain the larger nucleic acids and make the larger nucleic acids available for sequencing applications, such as nanopore sequencing. The invention also relates to kits for selecting polynucleotides.

The invention relates to a novel method of producing hetero-oligomeric pores. The invention also relates to hetero-oligomeric pores produced using the method and polynucleotide characterisation using the hetero-oligomeric pores.

A nanopore sensing device comprises a planar structure provided with plural fluidic passages extending between the first and second chambers. The planar structure supports nanopores in membranes across respective passages and sensor electrodes are arranged to sensea fluidic electrical potential in respective passages between the nanopores and the second chamber. The passages comprise planar fluidic resistor portions between the sensor electrode and the second chamber, the planar fluidic resistor portions extending in a planar direction of the planar structure and being configured to form a fluidic resistor.

The disclosure provides a nanopore system assembled with non-membrane proteins for detecting analytes. Also disclosed are the methods, kits, and detection devices employing the disclosed nanopore system. The nanopore system has a wide variety of applications, including single molecule detection, DNA/RNA/peptide sequencing, sensing of chemicals, biological reagents, and polymers, and disease diagnosis.

A biochemical sensing system senses interactions between molecular entities and nanopores using a sensor device comprising an array of sensor elements that support the nanopores. A switch arrangement selectively connects detection channels for amplifying sensed electrical signals to respective sensor elements. On the basis of an analysis of the amplified electrical signal output from the detection channels, detection of completion of interactions at sensor elements occurs. In response thereto, the switch arrangement is controlled to connect the detection channel connected to a sensor element at which completion of an interaction has been detected to a further sensor element.

The invention relates to a method for modifying a template double stranded polynucleotide, especially for characterisation using nanopore sequencing. The method produces from the template a plurality of modified double stranded polynucleotides. These modified polynucleotides can then be characterised.

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.