The disclosure relates to methods and systems for ultrahigh throughput protein synthesis and analysis.

The present invention provides methods, compositions, and systems for distributing single polymerase molecules into array regions. In particular, the methods, compositions, and systems of the present invention result in a distribution of single polymerase molecules into array regions at a percentage that is larger than the percentage expected to be occupied under a Poisson distribution.

A method of preparing a discrete polymer network array include mixing a plurality of nucleic acid polymer networks with a plurality of color-activated polymer networks to form a dispersion, applying the dispersion to an array of wells, the nucleic acid polymer networks selectively depositing into wells of the array of wells, and rinsing the array of wells to selectively remove the plurality of color-activated polymer networks.

Methods are disclosed of making and using platforms for peptide synthesis and compositions thereof, such peptide-anchored resins or beads for use in solid-phase peptide synthesis. The platform includes a plurality of platform particles, which particles are insoluble carrier material particles (microparticles/nanoparticles) having a plurality of different linkers coupled to them. The plurality of linkers includes, in various combinations and combinations, (a) Fmoc-2,4-dimethoxy-4-(carboxymethyloxy)-benzhydrylamine (Rink amide linker); (b) 4-Formyl-3-methoxy-phenoxyacetic acid; (c) 2-Hydroxy-5-dibenzosuberone; (d) 4-Hydroxymethylbenzoic acid (HMBA); (e) 4-Hydroxymethyl-phenoxyacetic acid (HMP linker); (f) 4-(Fmoc-hydrazino)-benzoic acid; (g) 4(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)-butyric acid; and (h) Fmoc-Suberol (5-Fmoc-amino-2-carboxymethoxy-10,11-dihydro-5H-dibenzo[a,d] cycloheptene). In some embodiments, the insoluble carrier material particles have a plurality of linkers that are each a different type from one another. Such platforms can be used in solid-phase peptide synthesis processes.

A fluidic device includes a plurality of reaction wells, typically in a dense array, with at least one bead retention segment in fluid communication with and spatially separated from at least one signal detection segment. A respective bead retention segment can be configured to hold a single bead, which can have a reagent attached thereto.

Methods, compositions, and systems for distributing nucleic acids into array regions are provided. The methods, compositions, and systems utilize nucleic acid condensing agents to increase efficiency of distribution of the nucleic acids into the array regions. Various methods for facilitating distribution of the nucleic acids to the array regions are provided.

Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate. The open substrate may be configured to rotate or otherwise move. The open substrate can comprise an array of individually addressable locations, with analytes immobilized thereto. The substrate may be spatially indexed to identify nucleic acid molecules from one or more sources, and/or sequences thereof, with the respective one or more sources. A solution comprising a plurality of probes may be directed across the array to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via scanning of the substrate while minimizing temperature fluctuations of the substrate or optical aberrations caused by bubbles.

The present invention provides methods for increasing polymerase processivity. In some aspects the invention includes providing a polymerase-nucleic acid complex having a nucleic acid comprising a template strand, and the template strand is entrapped in the polymerase through anchors that are covalently connected to each other across the nucleic acid binding cleft of the polymerase. In some cases the anchors comprise cysteines.

An example of a flow cell includes a substrate, a plurality of chambers defined on or in the substrate, and a plurality of depressions defined in the substrate and within a perimeter of each of the plurality of chambers. The depressions are separated by interstitial regions. Primers are attached within each of the plurality of depressions, and a capture site is located within each of the plurality of chambers.

Provided herein are methods that comprise providing polymer chains comprising a plurality of reactive groups onto the surface of beads and covalent attachment of functionalized biomolecules, such as primers.