# US 11,994,455 B2 · Analyte quantitation using Raman spectroscopy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,994,455 B2 - Document ID: US11994455B2 - Status: Granted - Kind: B2 - Application number: 17/710,244 - Filed: 2022-03-31 - Published: 2022-10-06 - Granted: 2024-05-28 - Earliest claimed: 2021-04-01 - Assignees: OndaVia, Inc. - Applicants: OndaVia, Inc. - Inventors: Mark Charles Peterman; Merwan Benhabib - Web page: https://patentgrep.com/patent/US11994455B2 ## CPC - G01N 15/06: Investigating concentration of particle suspensions (by weighing G01N5/00; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10) - G01N 21/274: {Calibration, base line adjustment, drift correction} - G01J 3/4406: {Fluorescence spectrometry} - G01N 21/658: {enhancement Raman, e.g. surface plasmons} - G01J 3/44: Raman spectrometry; Scattering spectrometry {; Fluorescence spectrometry} - G01N 15/075: by optical means - G01N 2201/129: Using chemometrical methods - 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) - G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N) ## Abstract An analyte in water is quantified by mixing an internal standard with a water sample. The sample is analyzed with a Raman spectrometer. The analysis includes mapping the signal from the Raman spectrometer to the quantity of said analyte. The mapping can include using a calibration curve, for example a multivariate calibration curve, that was previously prepared with the internal standard. In other examples, a sample is measured after addition of a known amount of the analyte. ## Claims ### Claim 1 A method to measure an analyte in water comprising the steps of: providing a sample containing a quantity of said analyte; mixing an internal standard with the sample, wherein the internal standard comprises an isotope; analyzing the sample with a Raman spectrometer to produce a measured spectrum of the sample; and, determining a concentration of the analyte using the measured spectrum and a calibration curve wherein the calibration curve is one or more of a) a multivariate calibration curve and b) a calibration curve prepared with samples containing the analyte and the internal standard; wherein determining a concentration of the analyte using the measured spectrum comprises: collecting multiple spectra of the sample at multiple excitation wavelengths, obtaining variant and invariant spectra, and determining concentration of the analyte using the variant spectrum. ### Claim 2 (depends on 1) The method of claim 1 wherein determining the concentration comprises a multivariate adaptive regressive splines technique, a partial least squares technique, or a polynomial fit. ### Claim 3 (depends on 1) The method of claim 1 wherein the calibration curve is determined considering spectra of the analyte at different known concentrations and the internal standard at a known concentration, wherein the internal standard is added in the same amount or concentration as will be used to make the measurement, wherein the spectra are scaled to a peak of the internal standard. ### Claim 4 (depends on 1) The method of claim 1 comprising the steps of producing at least one dark spectrum without laser excitation, and subtracting the dark spectrum from the measured spectrum. ### Claim 5 (depends on 1) The method of claim 1 comprising shifting the measured spectrum such that the measured spectrum has a peak in a known location for the isotope. ### Claim 6 (depends on 1) The method of claim 1 comprising scaling the measured spectrum using a peak for the isotope and a known concentration of the isotope in the sample. ### Claim 7 (depends on 1) The method of claim 1 comprising subtracting spectra for one or more interfering compounds in the sample. ### Claim 8 (depends on 7) The method of claim 7 wherein the analyte is monoethanolamine and the interfering compounds are one or more of dimethylethanolamine, methylamine, and 3-methoxypropylamine. ### Claim 9 (depends on 7) The method of claim 7 comprising comparing minimization coefficients for an interfering compounds to the isotope to determine a concentration of the interfering compound. ### Claim 10 (depends on 1) The method of claim 1 wherein collecting multiple spectra of the sample at multiple excitation wavelengths comprises at least one of: using an array of lasers or adjusting the temperature of a single laser. ### Claim 11 (depends on 1) The method of claim 1 comprising calculating a detection limit for the sample. ### Claim 12 (depends on 1) The method of claim 1 wherein the analyte is MEA and the isotope is MEA-d4. ### Claim 13 (depends on 1) The method of claim 1 wherein the analyte is MMA and the isotope is MMA-d3. ### Claim 14 (depends on 1) The method of claim 1 comprising treating the sample by way of anion-exchange based solid phase extraction. ### Claim 15 (depends on 14) The method of claim 14 wherein the analyte is an amine and the sample is acidic during the sample phase extraction. ### Claim 16 (depends on 1) The method of any claim 1 wherein the sample has a pH of at least 2 greater than the pKa of the analyte while analyzing the sample with the Raman spectrometer. ### Claim 17 A method to measure an analyte in water comprising the steps of: providing an original sample containing a quantity of said analyte; mixing one or more known amounts of the analyte with the sample to produce at least one additional sample; analyzing the original sample and the at least one additional sample with a Raman spectrometer to produce measured spectra of the samples; and, determining a concentration of the analyte using the measured spectra wherein determining a concentration of the analyte using the measured spectra comprises: collecting multiple spectra of the sample at multiple excitation wavelengths, obtaining variant and invariant spectra, and determining concentration of the analyte using the variant spectrum. ### Claim 18 (depends on 17) The method of claim 17 wherein the analyte is a metal such as lead, copper, zinc, mercury, iron, cobalt, nickel or a colorimetric method for calcium magnesium or ammonia. ### Claim 19 A method of measuring the concentration of MEA-triazine in a sample comprising adding a Raman-active compound containing a phenyl group to the sample and producing a Raman spectra of the sample. ### Claim 20 (depends on 19) The method of claim 19 wherein concentration of the MEA-triazine is in the range of 30-80% by mass.