Methods of labeling or barcoding molecules within one or more portions of a plurality of cells are provided. Kits and systems for labeling or barcoding molecules within one or more portions of a plurality of cells are also provided. The methods, kits, and systems may utilize photo-controlled adapter sequences, nucleic acids tags, and/or linkers.

Disclosed herein are methods and compositions for corresponding positions on an array with differently labeled affinity reagents immobilized at the positions. A first and a second affinity reagents are immobilized on at least some of the first and second positions, respectively. The first affinity reagent and the second affinity reagent are associated with a first luciferase polypeptide and a second luciferase polypeptide, respectively. The first luciferase polypeptide does not cross react with the second substrate and the second luciferase polypeptide does not cross react with the first substrate. The method further comprises contacting the array with the first substrate, which reacts with the first luciferase polypeptide and detecting the first luminescent signal and detecting the second luminescent signal at positions, thereby corresponding positions on an array with the first affinity reagent or the second affinity reagent immobilized at the positions.

Disclosed herein are methods and compositions for corresponding positions on an array with differently labeled affinity reagents immobilized at the positions. A first and a second affinity reagents are immobilized on at least some of the first and second positions, respectively. The first affinity reagent and the second affinity reagent are associated with a first luciferase polypeptide and a second luciferase polypeptide, respectively. The first luciferase polypeptide does not cross react with the second substrate and the second luciferase polypeptide does not cross react with the first substrate. The method further comprises contacting the array with the first substrate, which reacts with the first luciferase polypeptide and detecting the first luminescent signal and detecting the second luminescent signal at positions, thereby corresponding positions on an array with the first affinity reagent or the second affinity reagent immobilized at the positions.

Methods of labeling or barcoding molecules within one or more portions of a plurality of cells are provided. Kits and systems for labeling or barcoding molecules within one or more portions of a plurality of cells are also provided. The methods, kits, and systems may utilize photo-controlled adapter sequences, nucleic acids tags, and/or linkers.

Methods of labeling or barcoding molecules within one or more portions of a plurality of cells are provided. Kits and systems for labeling or barcoding molecules within one or more portions of a plurality of cells are also provided. The methods, kits, and systems may utilize photo-controlled adapter sequences, nucleic acids tags, and/or linkers.

A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.

A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.

A method for optically detecting mutations in a sequence of DNA is disclosed. The method includes generating an optically coded input sequence by optically coding an input sequence, generating an optically coded reference sequence by optically coding a reference sequence, generating an aligned sequence by overlapping the optically coded input sequence with the optically coded reference sequence, and determining a mutation in the input sequence with respect to the reference sequence. The input sequence includes an input arrangement of a plurality of elements. Each of the plurality of elements includes an element value of a plurality of element values. The reference sequence includes a reference arrangement of the plurality of elements. Each element of the aligned sequence includes one of a low-value element or a high-value element. The mutation is determined responsive to detecting the low-value element in the aligned sequence.

A method for optically detecting mutations in a sequence of DNA is disclosed. The method includes generating an optically coded input sequence by optically coding an input sequence, generating an optically coded reference sequence by optically coding a reference sequence, generating an aligned sequence by overlapping the optically coded input sequence with the optically coded reference sequence, and determining a mutation in the input sequence with respect to the reference sequence. The input sequence includes an input arrangement of a plurality of elements. Each of the plurality of elements includes an element value of a plurality of element values. The reference sequence includes a reference arrangement of the plurality of elements. Each element of the aligned sequence includes one of a low-value element or a high-value element. The mutation is determined responsive to detecting the low-value element in the aligned sequence.

Bistable devices are constructed using a polynucleotide platform for sensing molecular events such as binding or conformational changes of target molecules. Uses include measurement of target concentration, measuring the effect of environmental condition (such as heat, light, or pH) on the target, or screening a library for molecules that bind the target or modulate its biological function. Devices comprise three regions: a top lid, bottom lid, and flexible linker or hinge between them. A device has an open configuration in which the top and bottom lid are separated, and a closed configuration they are bound close together. Binding domains or variations of the target molecule are fixed to a device so that when the molecular event occurs, the device switches from open to closed, or vice versa, which generates a signal. Optimal device design is determined by the signal modality (optical or electronic) used to measure closure of surface-immobilized devices.