# US 9,040,672 B2 · Devices and methods for reducing matrix effects > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,672 B2 - Document ID: US9040672B2 - Status: Granted - Kind: B2 - Application number: 13/175,161 - Filed: 2011-07-01 - Published: 2011-10-27 - Granted: 2015-05-26 - Earliest claimed: 2007-05-16 - Assignees: Agilent Technologies, Inc. - Applicants: David C. Jones - Inventors: David C. Jones - Web page: https://patentgrep.com/patent/US9040672B2 ## CPC - G01N 1/405: {by adsorption or absorption} - B01L 3/0275: {Interchangeable or disposable dispensing tips} - B01L 3/5085: {for multiple samples, e.g. microtitration plates} - B01L 2300/0681: Filter - G01N 35/1074: {arranged in a two-dimensional array} - G01N 2035/1053: {for separating part of the liquid, e.g. filters, extraction phase} - Y10T 436/107497: Preparation composition [e.g., lysing or precipitation, etc.] - Y10T 436/25125: Digestion or removing interfering materials - 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) - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract Devices and methods are provided for reducing matrix effects in protein precipitated bioanalytical samples comprising: a support, and a sorbent associated with the support capable of binding matrix interfering agents present in the bioanalytical sample, wherein the device further comprises filtering means for removing precipitated protein particles. The filtering means is a size exclusion filter or a polymeric or inorganic monolith having a maximum pore size less than or equal to the diameter of the particles to be removed from the sample, and can be integral with the sorbent or associated with the sorbent. The sorbent is characterized by sufficient selectivity between the matrix interfering agents and analytes of interest to provide retention of the matrix interfering agents while providing elution of the analytes of interest (e.g., a reversed phase or a polar modified reversed phase). Typical devices incorporating these features include luer syringe filters, individual filter cartridges, multiwell plates, pipette tips, or inline columns for multiple or single use. ## Claims ### Claim 1 A device for reducing matrix effects in a protein precipitated bioanalytical sample comprising: a) a support, b) a sorbent associated with the support capable of binding matrix interfering agents present in the bioanalytical sample; and c) a filtering means for removing precipitated protein particles, wherein the filtering means is characterized in having pore sizes between about 0.05 μm and about 0.5 μm in diameter. ### Claim 2 (depends on 1) The device of claim 1, wherein the filtering means is selected from a size exclusion filter or a polymeric or inorganic monolith having a maximum pore size less than or equal to the diameter of the particles to be removed from the sample. ### Claim 3 (depends on 1) The device of claim 1, wherein the filtering means is integral with the sorbent or associated with the sorbent. ### Claim 4 (depends on 1) The device of claim 1, wherein the filtering means is a porous monolith having macropores of a diameter sufficiently small so as to exclude particles from the sample, and the sorbent is a reversed phase or polar modified reversed phase bonded to the porous monolith. ### Claim 5 (depends on 1) The device of claim 1, wherein the sorbent is characterized by sufficient selectivity between the matrix interfering agents and analytes of interest to provide retention of the matrix interfering agents while providing elution of the analytes of interest. ### Claim 6 (depends on 5) The device of claim 5, wherein the sorbent is characterized by a selectivity greater than 1 between matrix interfering agents and analytes of interest. ### Claim 7 (depends on 1) The device of claim 1, wherein the sorbent comprises a reversed phase or a polar modified reversed phase. ### Claim 8 (depends on 7) The device of claim 7, wherein the polar modified reversed phase is an amide modified reversed phase. ### Claim 9 (depends on 1) The device of claim 1, wherein the matrix interfering agent is a surfactant, lipid, excipient, or dosing agent. ### Claim 10 (depends on 1) The device of claim 1, adapted for use as a luer syringe filter, individual filter cartridge, a multiwall plate, pipette tip, or an inline column for multiple or single use. ### Claim 11 (depends on 1) The device of claim 1, wherein the support further comprises reservoir means for performing protein precipitation within the device. ### Claim 12 (depends on 1) A method for reducing matrix effects and removing protein precipitates in a bioanalytical sample, said method comprising: a) providing the device of claim 1; b) contacting the bioanalytical sample with the sorbent; and c) eluting analytes from the sorbent while retaining the matrix interfering agents and precipitated proteins, wherein the amount of matrix interfering agents and proteins in the resulting treated sample is reduced. ### Claim 13 (depends on 12) The method of claim 12, further comprising precipitating the proteins in the bioanalytical sample in the device prior to or simultaneously with the step of contacting the bioanalytical sample with the sorbent. ### Claim 14 (depends on 12) The method of claim 12, wherein step c) is performed using vacuum, centrifugal or electrokinetic force, gravity or capillary forces, or positive pressure. ### Claim 15 (depends on 12) The method of claim 12, wherein the matrix interfering agents are surfactants, lipids, excipients, or dosing agents. ### Claim 16 (depends on 12) The method of claim 12, wherein the sorbent is characterized by sufficient selectivity between the matrix interfering agents and analytes of interest to provide retention of the matrix interfering agents while providing elution of the analytes of interest. ### Claim 17 (depends on 1) A method for reducing matrix effects and removing precipitated proteins in a protein precipitated bioanalytical sample, the method comprising passing the sample through the device of claim 1. ### Claim 18 (depends on 1) A method for preparing the device of claim 1 comprising the following steps: a) providing a support capable of containing a quantity of sorbent and a filtering means; b) providing an amount of sorbent effective to retain matrix interfering agents and filtering means effective to remove precipitated proteins; and c) assembling the filtering means and the sorbent within the support.