The disclosure provides a nanopore system assembled with non-membrane proteins for detecting analytes. Also disclosed are the methods, kits, and detection devices employing the disclosed nanopore system. The nanopore system has a wide variety of applications, including single molecule detection, DNA/RNA/peptide sequencing, sensing of chemicals, biological reagents, and polymers, and disease diagnosis.

A system and method for providing sequencing of biomolecules, which can be used for differential analysis of a test sample from a normal sample. Methods can involve steps of providing a mapped sequence file of each of a pilot test sample and a pilot normal sample, wherein each sequence file has a pilot number of reads; calculating, by a processor, a first test-normal genomic comparison pilot view from the sequence files of the pilot test sample and the pilot normal sample, wherein the first pilot view distinguishes pilot test sample data from pilot normal sample data based on at least one genomic parameter; calculating, by the processor, for each sequence file a downsampled sequence file having a reduced pilot number of reads; calculating, by the processor, a second test-normal genomic comparison pilot view from the downsampled sequence files of the pilot test sample and the pilot normal sample, wherein the second pilot view distinguishes the pilot test sample data from the pilot normal sample data based on the at least one genomic parameter; repeating the downsampling steps for determining the fewest pilot number of reads required for calculating a test-normal genomic comparison view that distinguishes the pilot test sample data from the pilot normal sample data based on the at least one genomic parameter; sequencing biomolecules of the test sample and the normal sample using a number of reads equal to the fewest pilot number of reads; calculating, by the processor, a test-normal genomic comparison view for displaying the differential analysis based on the at least one genomic parameter.

An amino acid-specific binder selectively binds to a binding amino acid. A binder complex selectively identifies the binding amino acid and includes an adjunct attached to the amino acid-specific binder. The adjunct includes a taggant, protein, substrate, or chemical modifier. Selectively identifying an N-terminal amino acid includes anchoring a C-terminal end; contacting an N-terminal amino acid of the anchored analyte with the binder complex; selectively binding when the N-terminal amino acid includes the binding amino acid; producing, by the taggant of the tagged complex, a taggant signal; detecting the taggant signal; and identifying the N-terminal amino acid based on the taggant signal.

The invention relates to peptide mass fingerprinting technique for the proteins such as Human insulin and insulin analogs. The insulin analogues can vary at least by one amino acid, which is elusive to distinguish by currently available analytical methods. The invention further allows sequence confirmation of the peptide wherein the run time of the method is forty minutes. This method could be applied for molecules up to 50 kDa.

An amino acid-specific binder selectively binds to a binding amino acid. A binder complex selectively identifies the binding amino acid and includes an adjunct attached to the amino acid-specific binder. The adjunct includes a taggant, protein, substrate, or chemical modifier. Selectively identifying an N-terminal amino acid includes anchoring a C-terminal end; contacting an N-terminal amino acid of the anchored analyte with the binder complex; selectively binding when the N-terminal amino acid includes the binding amino acid; producing, by the taggant of the tagged complex, a taggant signal; detecting the taggant signal; and identifying the N-terminal amino acid based on the taggant signal.

Provided herein are methods to identify TCR-recognizing cancer-specific antigens, and TCR-engineered T cells having antigen-specific cytotoxic activity. Provided herein are engineered T lymphocytes produced by the methods described herein. Provided herein are methods of treating cancer in a subject comprising administering the engineered T lymphocytes described herein. Provided herein are antibodies, or fragments thereof, produced by the methods described herein. Provided herein are methods of treating cancer in a subject comprising administering the antibodies described herein to a subject. In some embodiments, the therapeutic compositions (e.g., engineered lymphocytes, antibodies, etc.) and methods herein are provided as part of a kit or system.

There is provided a simple and minimally invasive adenocarcinoma detection method. The adenocarcinoma detection method of the present invention includes a step of detecting in vitro a presence or absence of an abnormal cleavage in a specific protein in a test subject-derived sample. The abnormal cleavage in the specific protein is, for example, a cleavage resulting in one or more breaks in a peptide bond in the specific protein and/or a cleavage resulting in a deletion of one or two more amino acid residues at one or more sites of the specific protein. The adenocarcinoma detection method of the present invention includes a step of detecting a presence or amount of a protein having the abnormal cleavage or a decrease in an amount of a normal protein.

The present invention relates to, in part, methods of improved healthcare in female subjects that, for example, rely on menstrual fluid sampling for applying selection biomarkers.

The present invention relates generally to the field of immune binding proteins and method for obtaining immune binding proteins from genomic or other sources. The present invention also relates to methods and apparati for obtaining single cells that express immune binding proteins. The single cells expressing the immune binding proteins can be obtained from a patient that has had an effective immune response to a disease state (e.g., cancer or an infectious agent). The methods and apparati of the disclosure can be used to obtain immune cells that produce immune binding proteins responsible for the effective immune response. The methods and apparati of the disclosure can also be used to obtain cells that express a polypeptide (e.g., a receptor, a secreted protein, a cytokine, or a recombinant protein) or other factor of interest.

The present invention describes a method for chemical sensing and biomolecular diagnostics with a microelectronic sensor based on the combination of an open-gate pseudo-conductive high-electron mobility transistor and a Vivaldi antenna installed in the open gate area of the transistor and operated in the sub-THz and THz frequency range.