# US 12,007,397 B2 · Enhanced detection and quantitation of biomolecules > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,007,397 B2 - Document ID: US12007397B2 - Status: Granted - Kind: B2 - Application number: 17/931,469 - Filed: 2022-09-12 - Published: 2023-03-23 - Granted: 2024-06-11 - Earliest claimed: 2021-09-13 - Assignees: PrognomIQ, Inc. - Applicants: PrognomiQ, Inc. - Inventors: Bruce Wilcox; Kavya Swaminathan; Preston B. Williams; Jared Deyarmin; Mi Yang - Web page: https://patentgrep.com/patent/US12007397B2 ## CPC - G01N 33/6848: {Methods of protein analysis involving mass spectrometry} - G01N 33/5752: of the lungs - G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease} - G01N 2458/15: Non-radioactive isotope labels, e.g. for detection by mass spectrometry - G01N 2570/00: Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Described herein are methods for screening for a disease state. The method may include obtaining multiple data sets, and identifying the disease state based on a combination of the data sets. The data sets may include biomolecule measurements obtained by multiple methods, such as through the use of particles and reference biomolecules. ## Claims ### Claim 1 A method for measuring endogenous biomolecules in a biological sample, comprising: (a) contacting a first aliquot of the biological sample with nanoparticles, thereby forming biomolecule coronas comprising the endogenous biomolecules of the biological sample adsorbed directly to the nanoparticles; (b) measuring the contacted sample of (a) to obtain a first set of measurements; (c) contacting a second aliquot of the biological sample with a plurality of reference biomolecules; (d) measuring the contacted sample of (c) to obtain a second set of measurements; and (e) combining the first and second sets of measurements, wherein the plurality of reference biomolecules comprises an isotopic label, a mass tag, a barcode, a post-translation modification, or a biomolecule from a species different than a species of a subject from whom the biological sample was taken. ### Claim 2 (depends on 1) The method of claim 1, further comprising identifying concentrations of the endogenous biomolecules based on the combination of measurements from (e). ### Claim 3 (depends on 1) The method of claim 1, further comprising determining a quality control aspect of the endogenous biomolecule measurements based on the combination of measurements from (e). ### Claim 4 (depends on 3) The method of claim 3, wherein the biological sample comprises a group of biological samples, and wherein measuring the endogenous biomolecules comprises measuring the endogenous biomolecules of the group of biological samples and the quality control aspect is in relation to the endogenous biomolecules of the group of biological samples. ### Claim 5 (depends on 1) The method of claim 1, wherein obtaining the first set of measurements or the second set of measurements comprises using a mass spectrometer. ### Claim 6 (depends on 1) The method of claim 1, further comprising normalizing or adjusting the first set of measurements based on the plurality of reference biomolecules. ### Claim 7 (depends on 1) The method of claim 1, wherein the first set of measurements comprises an amount of the endogenous biomolecules in the biological sample. ### Claim 8 (depends on 7) The method of claim 7, further comprising determining an amount of the endogenous biomolecules adsorbed to the nanoparticles relative to the amount of the endogenous biomolecules in the biological sample. ### Claim 9 (depends on 1) The method of claim 1, further comprising identifying a source of variability in the first set of measurements based on the plurality of reference biomolecules. ### Claim 10 (depends on 1) The method of claim 1, further comprising using the plurality of reference biomolecules to identify or measure additional endogenous biomolecules. ### Claim 11 (depends on 1) The method of claim 1, further comprising evaluating a biological state of a subject from whom the biological sample was taken, based on the combination of measurements from (e). ### Claim 12 (depends on 1) The method of claim 1, wherein the endogenous biomolecules comprise proteins, lipids, metabolites, sugars, or nucleic acids. ### Claim 13 (depends on 1) The method of claim 1, wherein the nanoparticles comprise a metal, polymer, or lipid. ### Claim 14 (depends on 1) The method of claim 1, wherein the biological sample comprises a biofluid. ### Claim 15 (depends on 1) The method of claim 1, wherein the adsorbed endogenous biomolecules comprise at least 100 distinct biomolecules. ### Claim 16 (depends on 1) The method of claim 1, wherein the plurality of reference biomolecules is combined with the second aliquot of the biological sample before contacting the second aliquot with nanoparticles resulting in formation of biomolecule coronas. ### Claim 17 (depends on 1) The method of claim 1, wherein the plurality of the reference biomolecules is combined with the second aliquot of the biological sample after contacting the second aliquot with nanoparticles resulting in formation of biomolecule coronas. ### Claim 18 (depends on 1) The method of claim 1, further comprising identifying or measuring a plurality of low abundance biomolecules in the biological sample based on the combination of measurements from (e). ### Claim 19 (depends on 1) The method of claim 1, further comprising recovering a false negative or ruling out a false positive from among the endogenous biomolecules based on the combination of measurements from (e). ### Claim 20 (depends on 1) The method of claim 1, wherein the plurality of reference biomolecules comprises an isotopic label. ### Claim 21 (depends on 1) The method of claim 1, wherein the plurality of reference biomolecules comprises a mass tag. ### Claim 22 (depends on 1) The method of claim 1, wherein the plurality of reference biomolecules comprises a barcode. ### Claim 23 (depends on 1) The method of claim 1, wherein the plurality of reference biomolecules comprises a post-translation modification. ### Claim 24 (depends on 1) The method of claim 1, wherein the plurality of reference biomolecules comprises a biomolecule from a species different than a species of a subject from whom the biological sample was taken.