# US 10,768,157 B2 · Materials and methods for the detection of trace amounts of substances in biological and environmental samples > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,768,157 B2 - Document ID: US10768157B2 - Status: Granted - Kind: B2 - Application number: 15/714,349 - Filed: 2017-09-25 - Published: 2018-03-01 - Granted: 2020-09-08 - Earliest claimed: 2015-10-20 - Assignees: The Florida International University Board of Trustees - Applicants: Abuzar Kabir; Kenneth G. Furton - Inventors: Abuzar Kabir; Kenneth G. Furton - Web page: https://patentgrep.com/patent/US10768157B2 ## CPC - G01N 33/04: Dairy products - B01J 20/268: {Polymers created by use of a template, e.g. molecularly imprinted polymers} - B01J 20/28047: {Gels} - B01J 20/291: Gel sorbents - B01J 20/3085: {Chemical treatments not covered by groups B01J20/3007 - B01J20/3078} - C08G 77/06: Preparatory processes - C08G 77/26: nitrogen-containing groups - C08G 77/80: {Siloxanes having aromatic substituents, e.g. phenyl side groups} - C08J 9/26: by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out - G01N 33/94: involving narcotics {or drugs or pharmaceuticals, neurotransmitters or associated receptors} - G01N 33/9446: {Antibacterials} - B01J 2220/54: Sorbents specially adapted for analytical or investigative chromatography - C08J 2201/0462: using organic solvents - C08J 2205/02: the finished foam itself being a gel or a gel being temporarily formed when processing the foamable composition - C08J 2383/08: containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen - G01N 2600/00: Assays involving molecular imprinted polymers/polymers created around a molecular template - 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) - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS - C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29) ## Abstract The subject invention provides chemical compositions and synthesis strategies to create molecularly imprinted polymers (MIPs) via sol-gel processes. In a specific embodiment, the subject invention utilizes a(n) organic, inorganic, or metallic template analyte to create a hybrid organic-inorganic or inorganic three-dimensional network possessing cavities complementary to the shape, size, and functional orientation of the template molecule or ions. The subject invention further pertains to the use of the novel MIPs as selective solid phase extraction (SPE) sorbents for pre-concentration and clean-up of trace substances in biological and environmental samples. Synthesis of other molecularly imprinted polymers with environmental, pharmaceutical, chemical, clinical, toxicological, and national security implications can be conducted in accordance with the teachings of the subject invention. ## Claims ### Claim 1 A method of synthesizing a molecularly imprinted polymer (MIP) matrix, comprising: mixing a template analyte with more than one sol-gel precursor to form a template-precursor complex, the sol-gel precursors comprising silane groups; hydrolyzing the sol-gel precursors of the template-precursor complex and a cross-linking agent with a hydrolytic agent in the presence of a reaction catalyst; combining the hydrolyzed cross-linking agent with the template-precursor complex having hydrolyzed sol-gel precursors; adding a basic solution to the combination of the hydrolyzed cross-linking agent and the template-precursor complex to form a sol-gel polymer network surrounding the template analyte; and extracting the template analyte using a solvent, leaving behind molecular cavities in the sol-gel polymer network that are complementary in size, shape, and functionality to the template analyte. ### Claim 2 (depends on 1) The method according to claim 1, the template analyte being selected from drugs, cells, proteins, amino acids, toxins, and viruses. ### Claim 3 (depends on 1) The method according to claim 1, the template analyte being an antibiotic drug selected from chloramphenicol, thiamphnicol, florfenicol, ceftiofur, cefaclor, oxytetracycline, tetracycline, sulfamethazine, sulfanilamide, sulfacetamide, sulfadiazine, sulfathiazole, sulfamerazine, sulfamethizole, sulfadimethoxine, amoxicillin, ampicillin, ciprofloxacin, enrofloxacin, and analogous compounds thereof. ### Claim 4 (depends on 1) The method according to claim 1, the sol-gel precursors being 3-aminopropyltriethoxysilane and triethoxyphenylsilane. ### Claim 5 (depends on 1) The method according to claim 1, the cross-linking agent being tetramethyl orthosilicate. ### Claim 6 (depends on 1) The method according to claim 1, the reaction catalyst being an acid. ### Claim 7 (depends on 6) The method according to claim 6, the reaction catalyst being hydrochloric acid. ### Claim 8 (depends on 1) The method according to claim 1, the hydrolytic agent being water. ### Claim 9 (depends on 1) The method according to claim 1, the solvent being selected from methanol, ethanol, isopropanol, formic acid, acetonitrile, acetone, and mixtures thereof. ### Claim 10 (depends on 1) A sol-gel MIP sorbent material prepared using the method according to claim 1. ### Claim 11 (depends on 10) The material according to claim 10, said material being capable of detecting the template analyte in a sample but is indifferent to other species present in the same sample. ### Claim 12 (depends on 1) A method of detecting a template analyte in a fluid sample, comprising: providing a sol-gel polymer sorbent material imprinted molecularly with the template analyte, the sorbent material being prepared according to claim 1, dried, and packaged in an apparatus capable of performing solid-phase extraction; passing the fluid sample through the sorbent material; and quantifying the concentration of the template analyte in the eluent of the sorbent material. ### Claim 13 (depends on 12) The method according to claim 12, the apparatus capable of performing solid-phase extraction being selected from a syringe and a solid-phase extraction cartridge. ### Claim 14 (depends on 12) The method according to claim 12, the sample being selected from physiological fluids, forensic specimens, environmental pollutants, food samples, beverage samples, pharmaceutical samples, chemical samples, drug residues and metabolites thereof, and poison residues and metabolites thereof. ### Claim 15 (depends on 12) The method according to claim 12, the quantification of the concentration of the template analyte in the eluent being obtained using liquid chromatography. ### Claim 16 A method of detecting one or more template analytes in a sample, comprising: providing a molecularly imprinted polymer (MIP) sorbent material, the sorbent material being prepared via a sol-gel process employing one or more sulfonamide drugs as the template analyte(s), 3-aminopropyltriethoxysilane and triethoxyphenylsilane as sol-gel precursors, tetramethyl orthosilicate as a cross-linking agent, hydrochloric acid as a reaction catalyst, water as a hydrolytic agent, and isopropanol and methanol as solvents; packaging dried MIP sorbent material in an extraction apparatus selected from a syringe and a solid-phase extraction cartridge; providing a fluid sample; passing the fluid sample through the extraction apparatus; and quantifying the concentration of the template analyte(s) in the eluent of the MIP sorbent material. ### Claim 17 (depends on 16) The method according to claim 16, the eluent of the sorbent material being obtained using a solvent selected from methanol, ethanol, isopropanol, formic acid, acetonitrile, acetone, and a mixture thereof. ### Claim 18 (depends on 16) The method according to claim 16, the sample being selected from physiological fluids, forensic specimens, environmental pollutants, food samples, beverage samples, pharmaceutical samples, chemical samples, drug residues and metabolites thereof, and poison residues and metabolites thereof. ### Claim 19 (depends on 16) The method according to claim 16, the one or more sulfonamide drugs being selected from sulfanilamide, sulfacetamide, sulfadiazine, sulfathiazole, sulfamerazine, sulfamethizole, and analogous compounds thereof. ### Claim 20 A method of synthesizing a molecularly imprinted polymer (MIP) matrix, comprising: mixing a template analyte with a mixture of sol-gel precursors to form a template-precursor complex, the mixture of sol-gel precursors comprising 3-aminopropyltriethoxysilane and triethoxyphenylsilane; hydrolyzing the sol-gel precursors of the template-precursor complex and a cross-linking agent with a hydrolytic agent in the presence of a reaction catalyst; combining the hydrolyzed cross-linking agent with the template-precursor complex having hydrolyzed sol-gel precursors; allowing a sol-gel polymer network to form surrounding the template analyte; and extracting the template analyte using a solvent, leaving behind molecular cavities in the sol-gel polymer network that are complementary in size, shape, and functionality to the template analyte.