Provided are methods, compositions and devices for high sensitivity detection of biomolecules such as nucleic acids in biological samples. The methods rely on target detection, nucleic acid amplification, and sensitive detection to provide a signal which can be conveniently measured in a lab assay or device, including with portable and point-of-care instrumentation.

The present application provides for systems and methods for detecting and estimating signals corresponding to one or more biomarkers in biological samples stained for the presence of protein and/or nucleic acid biomarkers. On particular aspect is directed to a method of estimating an amount of signal corresponding to at least one biomarker in an image of a biological sample. The method includes detecting isolated spots in a first image, deriving an optical density value of a representative isolated spot based on signal features from the detected isolated spots, estimating a number of predictive spots in signal aggregates in each of a plurality of sub-regions based on the derived optical density value of the representative isolated spot, and storing the estimated number of predictive spots and detected isolated spots in each of the plurality of generated sub-regions in a database.

The present application provides for systems and methods for detecting and estimating signals corresponding to one or more biomarkers in biological samples stained for the presence of protein and/or nucleic acid biomarkers. On particular aspect is directed to a method of estimating an amount of signal corresponding to at least one biomarker in an image of a biological sample. The method includes detecting isolated spots in a first image, deriving an optical density value of a representative isolated spot based on signal features from the detected isolated spots, estimating a number of predictive spots in signal aggregates in each of a plurality of sub-regions based on the derived optical density value of the representative isolated spot, and storing the estimated number of predictive spots and detected isolated spots in each of the plurality of generated sub-regions in a database.

The present application relates to methods of detecting a target nucleic acid molecule in a sample. The method includes providing a sample containing a target nucleic acid molecule and a capture oligonucleotide molecule. In one embodiment, the capture oligonucleotide molecule has (i) a length of 30-60 base pairs, (ii) a 4-8 base pair overhang on its 3′ end, (iii) a 5′ tail, (iv) a target-specific portion between the 3′ end and the 5′ tail, (v) a deoxy-adenosine diphosphate content of 40-50%, (vi) no deoxy thymidine phosphate in the 3′ end or the 5′ tail, and (vii) the 3′ end and the 5′ tail having an ATP content which is 40-50% of that of the capture oligonucleotide molecule. In another aspect of the method of detecting, certain reagents are coupled to a solid support. The present application also relates to compositions and kits useful in carrying out the methods of the present application.

The present application relates to methods of detecting a target nucleic acid molecule in a sample. The method includes providing a sample containing a target nucleic acid molecule and a capture oligonucleotide molecule. In one embodiment, the capture oligonucleotide molecule has (i) a length of 30-60 base pairs, (ii) a 4-8 base pair overhang on its 3′ end, (iii) a 5′ tail, (iv) a target-specific portion between the 3′ end and the 5′ tail, (v) a deoxy-adenosine diphosphate content of 40-50%, (vi) no deoxy thymidine phosphate in the 3′ end or the 5′ tail, and (vii) the 3′ end and the 5′ tail having an ATP content which is 40-50% of that of the capture oligonucleotide molecule. In another aspect of the method of detecting, certain reagents are coupled to a solid support. The present application also relates to compositions and kits useful in carrying out the methods of the present application.

Provided are a method for sequencing polynucleotides based on optical signal kinetics of luminescent labels and secondary luminescent signals, in which different luminescence forms and luminescence timings are applied to distinguish the sequential incorporation of different nucleotides, so as to realize the sequencing of the polynucleotides.

Provided are a method for sequencing polynucleotides based on optical signal kinetics of luminescent labels and secondary luminescent signals, in which different luminescence forms and luminescence timings are applied to distinguish the sequential incorporation of different nucleotides, so as to realize the sequencing of the polynucleotides.

The present invention relates to a method of detecting a target at least partially single-stranded viral genome in a sample. Also disclosed are kits and reaction mixtures.

The present invention relates to a method of detecting a target at least partially single-stranded viral genome in a sample. Also disclosed are kits and reaction mixtures.

A method for testing a sample for the presence of one or more targets comprises multiplexed catalyzed reporter deposition (CARD) is provided.