Abstract: The invention resides in a method of determining a sequence of a target polymer, or part thereof, comprising polymer units comprising canonical and non-canonical polymer units. The method comprises taking a series of measurements of a signal relating to the target polymer wherein a measurement of the signal is dependent upon a plurality of polymer units, and wherein the polymer units of the target polymer modulate the signal, and wherein a non-canonical polymer unit modulates the signal differently from a corresponding canonical polymer unit. The series of measurements are analysed using a machine learning technique that attributes a measurement of a non-canonical polymer unit to being a measurement of a respective corresponding canonical polymer unit. The sequence of the target polymer, or part thereof, is determined from the analysed series of measurements. A non-canonical polymer unit identified from the analysis can be additionally or alternatively determined.

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.

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.

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 present invention relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore. The invention further relates to a transmembrane pore complex and methods for production of the pore complex and for use in molecular sensing and nucleic acid sequencing applications.

Abstract: A modified portal protein of a bacteriophage DNA packaging motor, wherein the modified portal protein is capable of direct insertion into a membrane and wherein the portal protein is modified compared to the wild type portal protein such that one or more amino acid residues on the outer surface of the portal protein is substituted by one or more other amino acid residue, and/or wherein a one or more amino acid residue is inserted on the outer surface of the portal protein so as to alter the outer surface hydrophobicity of the modified portal protein compared to the wild type portal protein.

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 a method of characterising a target polynucleotide using a single-stranded binding protein (SSB). The SSB is either an SSB comprising a carboxy-terminal (C-terminal) region which does not have a net negative charge or a modified SSB comprising one or more modifications in its C-terminal region which decreases the net negative charge of the C-terminal region.

Abstract: The invention provides a method of detecting a target polynucleotide in a sample comprising: (a) contacting the sample with a guide polynucleotide that binds to a sequence in the target polynucleotide and a polynucleotide-guided effector protein, wherein the guide polynucleotide and polynucleotide-guided effector protein form a complex with any target polynucleotide present in the sample; (b) contacting the sample with a membrane comprising a transmembrane pore; (c) applying a potential to the membrane; and (d) monitoring for the presence or absence of an effect resulting from the interaction of the complex with the transmembrane pore to determine the presence or absence of the complex, thereby detecting the target polynucleotide in the sample.

Abstract: Provided herein, in some embodiments, are methods of determining whether a target nucleic acid comprises a particular barcode sequence.

Abstract: A system for characterising a target polynucleotide, the system comprising a membrane and a pore complex; wherein the pore complex comprises: (i) a nanopore located in the membrane, and (ii) an auxiliary protein or peptide attached to the nanopore; wherein the nanopore and the auxiliary protein or peptide together form a continuous channel across the membrane, the channel comprising a first constriction region and a second constriction region; wherein the first constriction region is formed by a portion of the nanopore, and wherein the second constriction region is formed by at least a portion of the auxiliary protein or peptide.

Abstract: Provided herein are methods of encoding data on a polymer. Also provided are methods of reading data encoded on a polymer. Also provided are systems for encoding data on a polymer; systems for reading data encoded on a polymer; and data encoding/data reading platforms.

Abstract: The present invention relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore. The invention further relates to a transmembrane pore complex and methods for production of the pore complex and for use in molecular sensing and nucleic acid sequencing applications.

Abstract: Provided is a method of characterising a polynucleotide using a transmembrane pore, wherein the pore is a double pore comprising a first Csg G pore, or a homologue thereof, and a second CsgG pore, or a homologue thereof.

Abstract: The invention relates to a sensing system comprising an electrowetting device, which electrowetting device comprises an array of actuation electrodes, and a control system configures to perform droplet operations on a system of droplets present in the sensing system. The invention also relates to a method of operating the sensing system of the invention. The invention also provides novel droplet constructs which can be made and manipulated in the sensing system of the invention.

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.

Abstract: Methods of characterizing an analyte using a detector such as a nanopore and an enzyme are provided. One aspect features methods for characterizing a double-stranded polynucleotide using a detector, e.g., without using a hairpin connecting a template and a complement of the double-stranded polynucleotide. Another aspect features methods for characterizing an analyte using a tag-modified nanopore with increased sensitivity and/or higher throughput. Compositions and systems including, e.g., adaptors for attachment to double-stranded polynucleotides and tag-modified nanopores, which can be used in the methods are also provided.

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

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