A method for identifying and quantifying organic or biochemical substances in a fluid medium using a nanogap sensor is disclosed. A nanogap sensor with two electrodes of different materials is used, a respective probe molecule is bonded to each electrode and the free remainder of the probe molecules have at least one bondable group with specificity to a substance or analyte. The analyte has at least two binding sites and passes selectively out of the fluid medium, binds to the free ends of the probe molecules to form a bridge, modifying the impedance between the electrodes.

A method for identifying and quantifying organic or biochemical substances in a fluid medium using a nanogap sensor is disclosed. A nanogap sensor with two electrodes of different materials is used, a respective probe molecule is bonded to each electrode and the free remainder of the probe molecules have at least one bondable group with specificity to a substance or analyte. The analyte has at least two binding sites and passes selectively out of the fluid medium, binds to the free ends of the probe molecules to form a bridge, modifying the impedance between the electrodes.

An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.

An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.

Reagents and methods for the analysis of cell free biomolecules (e.g. cell free nucleic acid molecules and cell free polypeptides) of microparticles (e.g. cell-free microparticles originating from blood, or cell-free microparticles originating from an embryo generated by in vitro fertilisation) are provided. Also provided are reagents and methods for the analysis of biomolecules (e.g. nucleic acid molecules and polypeptides) of cells (e.g. cells originating from blood, or cells originating from an embryo generated by in vitro fertilisation). The methods comprise analysing a sample that comprises a microparticle (or cell) or a sample derived from a microparticle (or cell). The methods include methods of measuring at least two linked signals, each signal corresponding to the presence, absence and/or level of a biomolecule of a microparticle (or cell). The methods also include methods of determining the presence, absence and/or level of a biomolecule of a microparticle (or cell) using a barcoded affinity probe. In certain methods both nucleic acid biomolecules and non-nucleic acid biomolecules of a microparticle (or cell) are analysed together. Reagents for use in the methods are also provided.

Reagents and methods for the analysis of cell free biomolecules (e.g. cell free nucleic acid molecules and cell free polypeptides) of microparticles (e.g. cell-free microparticles originating from blood, or cell-free microparticles originating from an embryo generated by in vitro fertilisation) are provided. Also provided are reagents and methods for the analysis of biomolecules (e.g. nucleic acid molecules and polypeptides) of cells (e.g. cells originating from blood, or cells originating from an embryo generated by in vitro fertilisation). The methods comprise analysing a sample that comprises a microparticle (or cell) or a sample derived from a microparticle (or cell). The methods include methods of measuring at least two linked signals, each signal corresponding to the presence, absence and/or level of a biomolecule of a microparticle (or cell). The methods also include methods of determining the presence, absence and/or level of a biomolecule of a microparticle (or cell) using a barcoded affinity probe. In certain methods both nucleic acid biomolecules and non-nucleic acid biomolecules of a microparticle (or cell) are analysed together. Reagents for use in the methods are also provided.

Embodiments relate to the preparation of nucleic acid libraries. Some embodiments relate to the preparation of normalized nucleic acid libraries, such as libraries in which the amounts of amplified nucleic acids are substantially the same for different amounts of input nucleic acids. Some embodiments relate to preparation of indexed nucleic acid libraries with certain adaptors.

Embodiments relate to the preparation of nucleic acid libraries. Some embodiments relate to the preparation of normalized nucleic acid libraries, such as libraries in which the amounts of amplified nucleic acids are substantially the same for different amounts of input nucleic acids. Some embodiments relate to preparation of indexed nucleic acid libraries with certain adaptors.

The present invention provides assay systems and methods for detection of copy number variation at one or more loci and polymorphism detection at one or more loci in a mixed sample from an individual.

The present invention provides assay systems and methods for detection of copy number variation at one or more loci and polymorphism detection at one or more loci in a mixed sample from an individual.