The present invention provides new polypeptide derivatives binding to Human Epidermal Growth Factor Receptor 2 (HER2) and their conjugates thereof, and to their use as a diagnostic agent, particularly for early detection, patient stratification and treatment monitoring of forms of cancer characterized by over-expression of HER2.

An observation method of a sample containing a target substance, the observation method including an imaging step in which a step of obtaining a speckle image including, as a speckle, light emitted from a luminescent substance in which a medium is brought into contact with the sample is performed a plurality of times so as to obtain a plurality of speckle images, the medium containing a probe that contains the luminescent substance emitting light and that repeatedly binds to and dissociates from the target substance directly and specifically, and an observation image generation step of generating an observation image of the target substance in the sample from the plurality of speckle images, wherein a half-life of a probe-target complex formed by binding between the probe and the target substance is equal to or more than 10 milliseconds and equal to or less than 3 seconds.

An observation method of a sample containing a target substance, the observation method including an imaging step in which a step of obtaining a speckle image including, as a speckle, light emitted from a luminescent substance in which a medium is brought into contact with the sample is performed a plurality of times so as to obtain a plurality of speckle images, the medium containing a probe that contains the luminescent substance emitting light and that repeatedly binds to and dissociates from the target substance directly and specifically, and an observation image generation step of generating an observation image of the target substance in the sample from the plurality of speckle images, wherein a half-life of a probe-target complex formed by binding between the probe and the target substance is equal to or more than 10 milliseconds and equal to or less than 3 seconds.

Disclosed is a solid phase method of synthesising biomolecule-effector-conjugates and biomolecule-reporter-conjugates. In particular, this invention relates to a solid phase method of synthesising antibody-effector-conjugates and antibody-reporter conjugates. This invention also relates to intermediate methods of producing immobilised, chemically modified biomolecules, e.g., antibodies.

Disclosed is a solid phase method of synthesising biomolecule-effector-conjugates and biomolecule-reporter-conjugates. In particular, this invention relates to a solid phase method of synthesising antibody-effector-conjugates and antibody-reporter conjugates. This invention also relates to intermediate methods of producing immobilised, chemically modified biomolecules, e.g., antibodies.

Methods for labeling and imaging the accessible genome using a transposase are disclosed. In some embodiments, a bifunctional transposase complex or transposome is used to insert adaptors comprising chemical tags selectively at accessible sites in the genome where active regulatory DNA is located. Various chemical tags can be used for labeling DNA at insertion sites, including, for example, fluorescent dyes for fluorescence imaging, metal particles for electron microscopy or magnetic manipulation of DNA, isotopic labels, or biotin or other ligands, haptens, substrates, or inhibitors that are recognized by streptavidin, antibodies, enzymes, or receptors. Labeling DNA in this manner can be used to provide spatial information regarding the positioning of regulatory DNA in the genome and makes possible the imaging and sorting of cells based on the status of their regulatory DNA.

Methods for labeling and imaging the accessible genome using a transposase are disclosed. In some embodiments, a bifunctional transposase complex or transposome is used to insert adaptors comprising chemical tags selectively at accessible sites in the genome where active regulatory DNA is located. Various chemical tags can be used for labeling DNA at insertion sites, including, for example, fluorescent dyes for fluorescence imaging, metal particles for electron microscopy or magnetic manipulation of DNA, isotopic labels, or biotin or other ligands, haptens, substrates, or inhibitors that are recognized by streptavidin, antibodies, enzymes, or receptors. Labeling DNA in this manner can be used to provide spatial information regarding the positioning of regulatory DNA in the genome and makes possible the imaging and sorting of cells based on the status of their regulatory DNA.

According to one aspect, the present disclosure provides a method of identifying a substrate of a transglutaminase using a peptide array comprising a plurality of peptides. The method includes the steps of contacting the peptides in the peptide array with the transglutaminase, allowing the transglutaminase to bind to the peptides, and identifying the substrate of the transglutaminase.

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.