Nautilus Subsidiary, Inc.

Nautilus Biotechnology, Inc.

Leland Stanford Junior University

Parag Mallick

Sujal M Patel

Jarrett D Egertson

Pierre F Indermuhle

Stephen P Hendricks

Torri Elise Rinker

Elvis Ikwa

Tural Aksel

Sadie Ingle

Steven Tan

David Stern

Dmitriy Gremyachinskiy

Rachel Galimidi

Christina Inman

Gregory Kapp

Sonal Tonapi

Joshua Simon Klein

Elliott Sorelle

Michael Dorwart

Vadim Lobanov

Ryan Kempston Seghers

Markus Burns

Julia Robinson

Cassandra Stawicki

Sanjiv Sam Gambhir

Christina E Inman

Edwin Chang

Arutselvan Natarajan

Pengyu Hao

Abdullah Ozer

Minyong Chung

Tracy Chan

Lingyun Xu

Nick Hughes

Carsten H Nielsen

The present disclosure provides systems and methods for detecting components of an array of biological, chemical, or physical entities. In an aspect, the present disclosure provides a method for detecting an array of biological, chemical, or physical entities, comprising: (a) using one or more light sensing devices, acquiring pixel information from sites in an array, wherein the sites comprise biological, chemical, or physical entities that produce light; (b) processing the pixel information to identify a set of regions of interest (ROIs) corresponding to the sites in the array that produce the light; (c) classifying the pixel information for the ROIs into a categorical classification from among a plurality of distinct categorical classifications, thereby producing a plurality of pixel classifications; and (d) identifying one or more components of the array of biological, chemical, or physical entities based at least in part on the plurality of pixel classifications.

Methods and systems for computational decoding of biological, chemical, and physical entities

Systems and methods for flow cells are provided. Flow cells may encompass a range of fluidic devices for various applications ranging from microfluidic systems to bulk phase flow systems. Flow cells may comprise one or more components for passive or active fluid transfer. Descriptions are provided for advantageous methods of fabricating flow cells for particular applications such as biological assays. Provided is a composition, comprising a first substrate comprising a first covalently-bound ligand; and a second substrate comprising a second covalently-bound ligand; wherein the first covalently-bound ligand and the second covalently-bound ligand are covalently bonded to form a heterocyclic compound. Also provided is a flow cell device, comprising: a first substrate comprising a microfabricated surface; and a second substrate comprising a non-patterned surface; wherein the first substrate is joined to the second substrate to form an enclosure; and wherein the microfabricated surface comprises at least one chamber, wherein the chamber comprises a microarray of active sites with specific functionalization separated by an optically resolvable distance and a functionalized surface comprising a passivating group or a blocking group; and wherein each active site of the microarray of active sites comprises a capture agent.

Flow cell systems and methods

The present disclosure provides methods and systems for performing single-molecule detection using fabricated integrated on-chip devices. Provided herein is a composition, comprising: (a) a substrate; (b) a structured nucleic acid particle coupled to the substrate, wherein a biological entity is coupled to the structured nucleic acid particle; and (c) a fluorescent detection agent, wherein the fluorescent detection agent comprises an affinity reagent attached to another structured nucleic acid particle, wherein the affinity reagent is bound to the biological entity.

Methods and systems for integrated on-chip single-molecule detection

Compositions, systems, and methods for the display of analytes such as biomolecules are described. Display of analytes is achieved by coupling of the analytes to displaying molecules that are configured to associate with surfaces or interfaces. Arrays of analytes may be formed from the described systems for utilization in assays and other methods.

Systems and methods for biomolecule retention

Methods and systems are provided for accurate and efficient identification and quantification of proteins. In an aspect, disclosed herein is a method for identifying a protein in a sample of unknown proteins, comprising receiving information of a plurality of empirical measurements performed on the unknown proteins; comparing the information of empirical measurements against a database comprising a plurality of protein sequences, each protein sequence corresponding to a candidate protein among a plurality of candidate proteins; and for each of one or more of the plurality of candidate proteins, generating a probability that the candidate protein generates the information of empirical measurements, a probability that the plurality of empirical measurements is not observed given that the candidate protein is present in the sample, or a probability that the candidate protein is present in the sample; based on the comparison of the information of empirical measurements against the database.

Decoding approaches for protein identification

Systems and methods for obtaining qualitative or quantitative measurements of proteoforms of polypeptides are described. The described methods include measurements of affinity reagent binding on single-molecule polypeptide arrays to distinguish between polypeptide isoforms. The described methods may provide high resolution quantitative comparisons of proteoforms with very low copy numbers.

Systems and methods for biomolecule quantitation

An affinity reagent, having: (a) a retaining component such as a structured nucleic acid particle; and (b) one or both of (i) one or more label components attached to the retaining component, and (ii) one or more binding components attached to the retaining component.

Affinity reagents having enhanced binding and detection characteristics

Methods and systems are provided herein for selecting an affinity reagent which binds a desired peptide epitope in a plurality of sequence contexts. The method relies on obtaining a peptide library, each peptide having the sequence αXβ, wherein X is the desired peptide epitope, wherein each of α and β comprise an amino acid, using the peptide library to select an affinity reagent.

Selection of affinity reagents

Methods of selecting binding reagents

Methods and systems for identifying a protein within a sample are provided herein. A panel of antibodies are acquired, none of which are specific for a single protein or family of proteins. Additionally, the binding properties of the antibodies in the panel are determined. Further, the protein is iteratively exposed to a panel of antibodies. Additionally, a set of antibodies which bind the protein are determined. The identity of the protein is determined using one or more deconvolution methods based on the known binding properties of the antibodies to match the set of antibodies to a sequence of a protein.

Methods of assaying proteins

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San Mateo, CA, United States of America

Parag Mallick