The present invention provides methods for immobilizing target nucleic acids on a solid support utilizing combinatorial capture probe pairs. These pairs contain first and second capture oligonucleotides that each comprise a target binding region, a capture region and a stem region positioned between the target binding and capture regions. The target binding regions comprise nucleic acid sequences that allow them to hybridize to adjacent regions on the target nucleic acid. The stem regions have nucleic acid sequences that are complementary to each other and the capture regions each comprise a sequence that when positioned adjacent to one another produce a combined nucleic acid sequence that is complementary to a portion of an oligonucleotide bound to a solid support. When the first and second capture oligonucleotides are annealed to the target nucleic acid, the stem regions are brought together allowing them to hybridize, which in turn brings the capture regions together to produce a combined nucleic acid sequence. This combined nucleic acid sequence is then able to hybridize to the oligonucleotide bound to the solid support thereby immobilizing the target nucleic acid.

The present invention provides methods for immobilizing target nucleic acids on a solid support utilizing combinatorial capture probe pairs. These pairs contain first and second capture oligonucleotides that each comprise a target binding region, a capture region and a stem region positioned between the target binding and capture regions. The target binding regions comprise nucleic acid sequences that allow them to hybridize to adjacent regions on the target nucleic acid. The stem regions have nucleic acid sequences that are complementary to each other and the capture regions each comprise a sequence that when positioned adjacent to one another produce a combined nucleic acid sequence that is complementary to a portion of an oligonucleotide bound to a solid support. When the first and second capture oligonucleotides are annealed to the target nucleic acid, the stem regions are brought together allowing them to hybridize, which in turn brings the capture regions together to produce a combined nucleic acid sequence. This combined nucleic acid sequence is then able to hybridize to the oligonucleotide bound to the solid support thereby immobilizing the target nucleic acid.

Disclosed herein are oligonucleotides and methods for detecting a target nucleic acid, as well as methods of diagnosing a subject with a disease or a disorder by detecting a target nucleic acid using the oligonucleotides and methods disclosed herein. The oligonucleotides include a quadruplex-forming sequence. Prior to binding the target nucleic acid, the quadruplex-forming sequence is in a non-quadruplex conformation. Upon binding the target nucleic acid, the sequence transforms to the quadruplex conformation, which can be detected, for example, using optical methods. The methods are based on thermodynamic properties and do not require the use of enzymes. The methods can be used to diagnose a subject with a disease or a disorder, prognose the outcome of a disease or disorder, or predict the development of a future disease or disorder.

Disclosed herein are oligonucleotides and methods for detecting a target nucleic acid, as well as methods of diagnosing a subject with a disease or a disorder by detecting a target nucleic acid using the oligonucleotides and methods disclosed herein. The oligonucleotides include a quadruplex-forming sequence. Prior to binding the target nucleic acid, the quadruplex-forming sequence is in a non-quadruplex conformation. Upon binding the target nucleic acid, the sequence transforms to the quadruplex conformation, which can be detected, for example, using optical methods. The methods are based on thermodynamic properties and do not require the use of enzymes. The methods can be used to diagnose a subject with a disease or a disorder, prognose the outcome of a disease or disorder, or predict the development of a future disease or disorder.

Fluorescence resonance energy transfer (FRET)-based nucleic acid sensors and methods of their use for detecting nucleic acids are provided. The sensors are highly sensitive and detect nucleic acids at the femtomolar (fM) level, without the need for labeling and amplification.

Fluorescence resonance energy transfer (FRET)-based nucleic acid sensors and methods of their use for detecting nucleic acids are provided. The sensors are highly sensitive and detect nucleic acids at the femtomolar (fM) level, without the need for labeling and amplification.

Methods, compositions and apparatus useful for individually manipulating and individually detecting analytes such as proteins. Analytes can be attached to particles to facilitate individual manipulation or detection of the particle-attached analytes. The particle-attached analytes can be composed of a single analyte attached to a single particle, such that no more than one analyte is attached per particle and no more than one particle is attached per analyte.

Provided herein are compositions, kits and methods for synthesis of nucleic acids. Also provided herein are compositions and methods for synthesizing strands of nucleic acid across different nucleic acid back-bones hybridized together using a strand displacing polymerase.

Provided herein are compositions, kits and methods for synthesis of nucleic acids. Also provided herein are compositions and methods for synthesizing strands of nucleic acid across different nucleic acid back-bones hybridized together using a strand displacing polymerase.

Temperature sensitive transcriptional bioswitches and related genetic circuits and in particular bandpass and/or multiplex genetic circuits, vectors, cells, compositions methods and systems are described.