Methods and apparatus providing for the isolation of an unknown mutation from a sample comprising wild type nucleic acids and mutated nucleic acids through the application of time-varying driving fields and periodically varying mobility-altering fields to the sample within in an affinity matrix.

The present disclosure relates to fluidic systems and devices for processing, extracting, or purifying one or more analytes. These systems and devices can be used for processing samples and extracting nucleic acids, for example by isotachophoresis. In particular, the systems and related methods can allow for extraction of nucleic acids, including non-crosslinked nucleic acids, from samples such as tissue or cells. The systems and devices can also be used for multiplex parallel sample processing.

The present invention relates to a method for the preparation of nanoscale nucleic acid-encircled lipid bilayers, the nanoscale nucleic acid-encircled lipid bilayers and their use.

The present disclosure discusses a method of separating a sample including oligonucleotides including coating a flow path of a chromatographic system; injecting the sample comprising oligonucleotides into the chromatographic system; flowing the sample through the chromatographic system; and separating the oligonucleotides. In some examples, the coating of the flow path is non-binding with respect to the analyte, such as oligonucleotides. Consequently, the analyte does not bind to the coating of the flow path. The non-binding coating eliminates the need for passivation, which can eliminate the formerly needed time to passivate as well. In addition, analyte can be recovered with a first injection in a system, such as chromatographic system.

A method of eluting biomolecules, such as nucleic acids from a biological sample by electroelution is provided. An example of a method includes various steps, such as loading the biological sample to a device comprising a housing, at least two conductive redox polymer electrodes operationally coupled to the housing and a biomolecule impermeable layer disposed on at least one of the electrodes. The loading of sample is followed by initiating an electrical connection to generate an electric field strength sufficient to elute biomolecules from the biological sample; and eluting the biomolecules from the biological sample.

The present disclosure relates to fluidic systems and devices for processing, extracting, or purifying one or more analytes. These systems and devices can be used for processing samples and extracting nucleic acids, for example by isotachophoresis. In particular, the systems and related methods can allow for extraction of nucleic acids, including non-crosslinked nucleic acids, from samples such as tissue or cells. The systems and devices can also be used for multiplex parallel sample processing.

The present disclosure relates generally to novel methods for nucleic acid sequencing. Specifically, the invention relates to a liquid chromatography-mass-spectrometry (LC-MS) based technique for direct sequencing of RNA without cDNA. The technique allows one to simultaneously read an RNA sequence with single nucleotide resolution while determining the presence, type and location of a wide spectrum of RNA modifications.

Methods of purifying targeted oligonucleotides within a reaction mixture using hydrophilic interaction liquid chromatography (HILIC) is disclosed. One of the methods in accordance with the present disclosure includes screening the targeted oligonucleotides within the reaction mixture with HILIC to create an initial reaction mixture profile; determining an elution percentage for the targeted oligonucleotides; focusing a HILIC elution gradient around the elution percentage of the targeted oligonucleotides; and purifying the targeted oligonucleotides with HILIC using the focused elution gradient at room temperature. Some embodiments can utilize mass triggering for fraction collection of the targeted oligonucleotides. Some embodiments can utilize UV triggering when the mass falls outside of the mass range of the MS detector.

Methods of purifying targeted oligonucleotides within a reaction mixture using hydrophilic interaction liquid chromatography (HILIC) is disclosed. One of the methods in accordance with the present disclosure includes screening the targeted oligonucleotides within the reaction mixture with HILIC to create an initial reaction mixture profile; determining an elution percentage for the targeted oligonucleotides; focusing a HILIC elution gradient around the elution percentage of the targeted oligonucleotides; and purifying the targeted oligonucleotides with HILIC using the focused elution gradient at room temperature. Some embodiments can utilize mass triggering for fraction collection of the targeted oligonucleotides. Some embodiments can utilize UV triggering when the mass falls outside of the mass range of the MS detector.

The present technology relates to a method of separating a sample comprising oligonucleotides. The method includes injecting a polyphosphonic acid at a concentration of between about 0.01 M to about 1 M into the sample comprising oligonucleotides. The method also includes flowing the sample and polyphosphonic acid through a liquid chromatography column and separating the oligonucleotides.