Abstract: Provided herein is a circular proximity ligation assay in which proximity-probes are employed as bridges to connect two free oligonucleotides via a dual ligation event, resulting in the formation of a circle. The circles are then quantified by, e.g., qPCR. The addition of an extra oligonucleotide is believed to enhance specificity by decreasing the probability of random background ligation events. In addition, circle formation may have selective advantages, as uncircularized DNA can be removed by a simple exonuclease treatment and it has streamlined the workflow by eliminating preamplification prior to qPCR.

Abstract: Provided herein is a circular proximity ligation assay in which proximity-probes are employed as bridges to connect two free oligonucleotides via a dual ligation event, resulting in the formation of a circle. The circles are then quantified by, e.g., qPCR. The addition of an extra oligonucleotide is believed to enhance specificity by decreasing the probability of random background ligation events. In addition, circle formation may have selective advantages, as uncircularized DNA can be removed by a simple exonuclease treatment and it has streamlined the workflow by eliminating preamplification prior to qPCR.

Abstract: The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.

Abstract: Provided herein is a circular proximity ligation assay in which proximity-probes are employed as bridges to connect two free oligonucleotides via a dual ligation event, resulting in the formation of a circle. The circles are then quantified by, e.g., qPCR. The addition of an extra oligonucleotide is believed to enhance specificity by decreasing the probability of random background ligation events. In addition, circle formation may have selective advantages, as uncircularized DNA can be removed by a simple exonuclease treatment and it has streamlined the workflow by eliminating preamplification prior to qPCR.

Abstract: The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.

Abstract: The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.

Abstract: Method and apparatus which uses harmonic cantilevers, such as used in atomic force microscopy, to detect variations in the attractive and repulsive forces on a solid surface as a result of macromolecular binding, for example, hybridization of a single stranded DNA molecule attached to the surface with another DNA molecule. The complexed macromolecule is less flexible than an uncomplexed molecule. It will typically have more negative charge due to amino acids or DNA monomers. Both stiffness of the surface and the attractive capillary forces will change after binding and may be detected. The present methods and materials enable ultraflat surfaces for the macromolecule deposition, and may include the use of a gold-coated mica substrate and a self-assembling monolayer.