An apparatus for label-free analysis of molecules, including interactions and reactions of the molecules, is disclosed. The apparatus is based on detecting molecule movement under the influence of an external electric field. The apparatus is able to achieve sensitive detection of molecular binding to proteins or other molecules, and conformational changes of proteins or other molecules and biochemical reactions of the proteins or other molecules. Applications of the apparatus include screening of drug molecules, kinetic analysis of posttranslational modification of proteins, and small molecule-protein interactions.

An apparatus for label-free analysis of molecules, including interactions and reactions of the molecules, is disclosed. The apparatus is based on detecting molecule movement under the influence of an external electric field. The apparatus is able to achieve sensitive detection of molecular binding to proteins or other molecules, and conformational changes of proteins or other molecules and biochemical reactions of the proteins or other molecules. Applications of the apparatus include screening of drug molecules, kinetic analysis of posttranslational modification of proteins, and small molecule-protein interactions.

Provided herein are methods for preparing biological samples for spatial proteomic analysis, methods of determining a location of a protein analyte in a biological sample, and methods of determining a location of a protein analyte and a nucleic acid analyte in a biological sample.

Provided herein are methods for preparing biological samples for spatial proteomic analysis, methods of determining a location of a protein analyte in a biological sample, and methods of determining a location of a protein analyte and a nucleic acid analyte in a biological sample.

A flow-through electrochemical detection system determines if a target nucleic acid polymer is present in a sample. This system contains, at a minimum, an assay reaction chamber that contains a porous working electrode to which target nucleic acid polymer capturing molecules are bound. As a sample passes through the working electrode, any target nucleic acid polymer present in the sample binds to the target nucleic acid polymer capturing molecules. After the sample passes through the flow-through electrochemical detection system, target nucleic acid polymer detectors are placed inside the assay reaction chamber and bind to any target nucleic acid polymer present. The target nucleic acid polymer detectors contain a means for generating an electric current when exposed to a chemical or an enzyme. A potentiostat connected to the working electrode measures the generated current, thereby detecting the presence and quantity of the target nucleic acid polymer in the sample.

A flow-through electrochemical detection system determines if a target nucleic acid polymer is present in a sample. This system contains, at a minimum, an assay reaction chamber that contains a porous working electrode to which target nucleic acid polymer capturing molecules are bound. As a sample passes through the working electrode, any target nucleic acid polymer present in the sample binds to the target nucleic acid polymer capturing molecules. After the sample passes through the flow-through electrochemical detection system, target nucleic acid polymer detectors are placed inside the assay reaction chamber and bind to any target nucleic acid polymer present. The target nucleic acid polymer detectors contain a means for generating an electric current when exposed to a chemical or an enzyme. A potentiostat connected to the working electrode measures the generated current, thereby detecting the presence and quantity of the target nucleic acid polymer in the sample.

Provided is a gene target region enrichment method and a kit. The method comprises (1) amplifying fragmented DNA comprising a target region by means of a specific probe so as to obtain a captured-extension product, wherein the specific probe comprises a sequence complementary to the target region of the fragmented DNA, and the 3′ terminal nucleotide of the specific probe is modified to prevent a ligation reaction at the 3′ terminal of the specific probe; and (2) linking the 3′ terminal of the captured-extension product obtained in step (1) to linker DNA to obtain a ligation product.

Provided is a gene target region enrichment method and a kit. The method comprises (1) amplifying fragmented DNA comprising a target region by means of a specific probe so as to obtain a captured-extension product, wherein the specific probe comprises a sequence complementary to the target region of the fragmented DNA, and the 3′ terminal nucleotide of the specific probe is modified to prevent a ligation reaction at the 3′ terminal of the specific probe; and (2) linking the 3′ terminal of the captured-extension product obtained in step (1) to linker DNA to obtain a ligation product.

The present invention features methods for manufacturing an electrochemical sensor for detecting a diagnostic target oligonucleotide. The methods described herein provide for an electrochemical sensor with a higher level of coverage of the probes on its surface, thus allowing for more sensitive detection of a target oligonucleotide. The methods may feature first mixing disulfide terminated oligonucleotides having a free thiol moiety at the 3′ end with a gold substrate and subsequently introducing to the gold substrate a composition for reducing thiol moieties to cause the oligonucleotides to bind to the surface of the gold substrate. In some embodiments, the method comprises removing excess thiol and oligonucleotides, which may help with non-competitive binding. In some embodiments, the method comprises rinsing the gold substrate with water and drying with nitrogen.

The present invention features methods for manufacturing an electrochemical sensor for detecting a diagnostic target oligonucleotide. The methods described herein provide for an electrochemical sensor with a higher level of coverage of the probes on its surface, thus allowing for more sensitive detection of a target oligonucleotide. The methods may feature first mixing disulfide terminated oligonucleotides having a free thiol moiety at the 3′ end with a gold substrate and subsequently introducing to the gold substrate a composition for reducing thiol moieties to cause the oligonucleotides to bind to the surface of the gold substrate. In some embodiments, the method comprises removing excess thiol and oligonucleotides, which may help with non-competitive binding. In some embodiments, the method comprises rinsing the gold substrate with water and drying with nitrogen.