Described herein are systems and methods for analyzing biological samples. Including a method for processing an analyte, comprising providing a fluidic device comprising the analyte and one or more polymer precursors; selecting a discrete area within said fluidic device; providing an energy source in optical communication with fluidic device; and selectively supplying a unit of energy generated from the energy source to the fluidic device to generate a polymer matrix within the fluidic device, wherein the polymer matrix is within the discrete area or adjacent to the discrete area.

The present invention relates to a method for labeling a cell with a barcode. The method for labeling a cell with a barcode of the invention includes (1) for a cell group containing a plurality of single cells, directly or indirectly bringing a cell surface protein of the cell into contact with a modified barcode; or (2) directly or indirectly bringing a cell surface protein of a single cell into contact with a modified barcode.

The present invention provides compositions and methods that can be used to determine a peptide signature for an antibody repertoire in a sample comprising multiple antibodies. The method can be used to characterize a phenotype in a sample, such as providing a diagnosis, prognosis or theranosis of a medical condition.

The present disclosure relates to a metalloprotein binder that specifically binds to a N-terminally modified peptide. Also provided herein is methods and related kits for treating or analyzing a peptide using the metalloprotein binder. The methods and compositions provided herein are useful for high-throughput peptide analysis and/or sequencing.

Kits and methods of using the kits for analyzing macromolecules, including peptides, polypeptides, and proteins, employing nucleic acid encoding are disclosed. The sample analysis kits employ nucleic acid encoding and/or nucleic acid recording of a molecular interaction and/or reaction, such as recognition events (e.g., between an antigen and an antibody, between a modified terminal amino acid residue, or between a small molecule or peptide therapeutic and a target, etc.). Additional barcoding reagents, such as those for cycle-specific barcoding (e.g., clocking), compartment barcoding, combinatorial barcoding, spatial barcoding, or any combination thereof, may be included in the kits. The sample may comprise macromolecules, including peptides, polypeptides, and proteins, and the recording may generate molecular interaction and/or reaction information, and/or polypeptide sequence information. The kits may be used in high-throughput, multiplexed, and/or automated analysis, and are suitable for analysis of a proteome or subset thereof.

Disclosed are compositions and methods for the multiplexed analysis of one or more intracellular targets of a single cell. Exemplary compositions of the disclosure comprise a surface comprising a plurality of capture agents operatively-linked thereto, wherein each capture agent specifically binds to a distinct intracellular target and wherein the plurality of capture agents form a repeating pattern; a substrate comprising a plurality of chambers, wherein the substrate releasably couples with the surface and wherein each chamber of the plurality of chambers comprises at least one repeat of the repeating pattern of the plurality of capture agents of the surface; a coating composition comprising a cell lysis composition; and a linker composition comprising a functionalization component and an extension component.

Described herein are systems and methods for analyzing biological samples. Including a method for processing an analyte, comprising providing a fluidic device comprising the analyte and one or more polymer precursors; selecting a discrete area within said fluidic device; providing an energy source in optical communication with fluidic device; and selectively supplying a unit of energy generated from the energy source to the fluidic device to generate a polymer matrix within the fluidic device, wherein the polymer matrix is within the discrete area or adjacent to the discrete area.

Systems and methods for determining amino acid sequences of peptides that bind to MHC-I or HLA-I complex or MHC-II or HLA-II complex are provided. One embodiment includes isolating peptides from MHC or HLA class I or class II-peptide complexes and adding one or more known labeled peptides of interest to form a sample containing labeled peptides and unlabeled isolated peptides. The method also includes analyzing the sample with an LC-MS/MS system to obtain sequence data of the peptides, and increasing the sensitivity of the LC-MS/MS system when the labeled peptide is detected by the LC-MS/MS system. The method then concludes with determining the amino acid sequence of the unlabeled peptides in an m/z range that includes the m/z of the labeled peptide. The system can be triggered to increase the sensitivity in or near the m/z of the labeled peptide using an algorithm or computer program.

Disclosed are methods of quantifying multiple quality attributes, such as post translational modifications, of multiple samples in a single mass spectrometry (MS) run, including contacting two or more samples with a digesting solution under conditions sufficient to digest samples, wherein each sample is digested separately and the digesting solution is a Tris-free buffer solution; contacting each of the two or more digested samples with a specific Tandem Mass Tag (TMT) labeling reagent under conditions sufficient to label peptides within each of the digested samples with the specific TMT labeling reagent; quenching labeling of peptides within each of the two or more digested samples; combining equal volumes of the two or more labeled, digested samples into a single combined sample solution; and analyzing the single combined sample solution by targeted mass spectral analysis, thereby allowing multiple quality attributes of the two or more samples to be quantified in a single mass spectrometry (MS) run.

Provided herein are several methods for selecting agents that bind to transmembrane receptors in a conformationally-selective way. In some embodiments, the method may comprise producing: a transmembrane receptor in an active conformation; and said transmembrane receptor in an inactive conformation and using cell sorting to select, from a population of cells comprising a library of cell surface-tethered extracellular capture agents, cells that are specifically bound to either the transmembrane receptor in its active conformation or the transmembrane receptor in its inactive conformation, but not both. In other embodiments, the method may comprise: contacting a GPCR with a population of cells that comprise a library of surface-tethered extracellular proteins; labeling the cell population with a conformationally-specific binding agent, e.g., a G-protein or mimetic thereof; and using cell sorting to select from the cell population cells that bind to the agent.