{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:04:24Z","timestamp":1784696664482,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Modern methods for preparing biological samples prior to chromatography\u2013mass spectrometry analysis are rapidly developing and include both commercial platforms and in-house devices designed for specific sample-preparation conditions. Here, we demonstrate the feasibility of using hypercrosslinked polystyrene, packed into disposable plastic pipette tips, as a sorbent for micro-solid-phase extraction. This approach was combined with a custom 3D-printed device designed to perform sample preparation similar to that of commercial microextraction by packed sorbent (MEPS) systems. Extraction conditions were developed for aromatic metabolites of tyrosine and phenylalanine in human blood serum, followed by gas chromatography\u2013mass spectrometry analysis of their silyl derivatives. The proposed method was evaluated using serum samples from healthy donors. Two types of hypercrosslinked polystyrene with nominal particle sizes of 40 and 60 \u00b5m were used. Under the optimized conditions, the mean normalized recoveries reached 90% for benzoic acid and 60\u201380% for most analytes, whereas phenyllactic and 4-hydroxyphenyllactic acids, the two most polar analytes, remained at lower recoveries. Moreover, the 3D-printed device achieved reproducibility comparable to that of a commercial MEPS system, with relative standard deviations below 10% under optimized conditions. The proposed in-house device also offers a fast and efficient strategy for evaluating custom sorbents in various sample-preparation applications.<\/jats:p>","DOI":"10.3390\/ijms27146443","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"6443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 3D-Printed Micro-Solid-Phase Extraction Device with Hypercrosslinked Polystyrene Sorbents for Highly Reproducible Aromatic Acid Analysis in Blood Serum"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-0485","authenticated-orcid":false,"given":"Alisa K.","family":"Pautova","sequence":"first","affiliation":[{"name":"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Petrovka str., 25-2, 107031 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5737-3700","authenticated-orcid":false,"given":"Alexander Y.","family":"Popov","sequence":"additional","affiliation":[{"name":"Efferon JSC, Leninskie Gory 1\/75G, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-6087","authenticated-orcid":false,"given":"Andrey S.","family":"Samokhin","sequence":"additional","affiliation":[{"name":"Chemistry Department, Lomonosov Moscow State University, GSP-1, Leninskie Gory, 1-3, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia V.","family":"Beloborodova","sequence":"additional","affiliation":[{"name":"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Petrovka str., 25-2, 107031 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander I.","family":"Revelsky","sequence":"additional","affiliation":[{"name":"Chemistry Department, Lomonosov Moscow State University, GSP-1, Leninskie Gory, 1-3, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115475","DOI":"10.1016\/j.trac.2019.04.007","article-title":"Capillary Gas Chromatography-Mass Spectrometry: Current Trends and Perspectives","volume":"124","author":"Gruber","year":"2020","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118244","DOI":"10.1016\/j.trac.2025.118244","article-title":"Sample Preparation of Polar Metabolites in Biological Samples: Methodologies and Technological Insights","volume":"189","author":"Dong","year":"2025","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e5105","DOI":"10.1002\/bmc.5105","article-title":"Recent Applications of Microextraction Sample Preparation Techniques in Biological Samples Analysis","volume":"35","author":"Daryanavard","year":"2021","journal-title":"Biomed. Chromatogr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115757","DOI":"10.1016\/j.jpba.2023.115757","article-title":"Targeted Quantitative Metabolic Profiling of Brain-Derived Cell Cultures by Semi-Automated MEPS and LC-MS\/MS","volume":"236","author":"Protti","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rosendo, L.M., Rosado, T., Oliveira, P., Sim\u00e3o, A.Y., Margalho, C., Costa, S., Passarinha, L.A., Barroso, M., and Gallardo, E. (2022). The Determination of Cannabinoids in Urine Samples Using Microextraction by Packed Sorbent and Gas Chromatography-Mass Spectrometry. Molecules, 27.","DOI":"10.3390\/molecules27175503"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ntorkou, M., and Zacharis, C.K. (2025). Sorbent-Based Microextraction Combined with GC-MS: A Valuable Tool in Bioanalysis. Chemosensors, 13.","DOI":"10.3390\/chemosensors13020071"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"937","DOI":"10.4155\/bio-2023-0121","article-title":"A Review of Bioanalytical Applications of Microextraction Techniques Combined with Derivatization","volume":"15","author":"Manousi","year":"2023","journal-title":"Bioanalysis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1016\/j.chroma.2009.09.053","article-title":"Recent Advances in Microextraction by Packed Sorbent for Bioanalysis","volume":"1217","year":"2010","journal-title":"J. Chromatogr. A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.chroma.2011.11.063","article-title":"Reinforced Polydiphenylamine Nanocomposite for Microextraction in Packed Syringe of Various Pesticides","volume":"1222","author":"Bagheri","year":"2012","journal-title":"J. Chromatogr. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jpba.2013.12.022","article-title":"Determination of Clenbuterol from Pork Samples Using Surface Molecularly Imprinted Polymers as the Selective Sorbents for Microextraction in Packed Syringe","volume":"91","author":"Du","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104832","DOI":"10.1016\/j.jfca.2022.104832","article-title":"Microextraction by Packed Sorbent of Polycyclic Aromatic Hydrocarbons in Brewed Coffee Samples with a New Zwitterionic Ionic Liquid-Modified Silica Sorbent","volume":"114","year":"2022","journal-title":"J. Food Compos. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/jssc.201100509","article-title":"Polypyrrole\/Polyamide Electrospun-based Sorbent for Microextraction in Packed Syringe of Organophosphorous Pesticides from Aquatic Samples","volume":"35","author":"Bagheri","year":"2012","journal-title":"J. Sep. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121185","DOI":"10.1016\/j.talanta.2020.121185","article-title":"Automated Microextraction by Packed Sorbent of Cannabinoids from Human Urine Using a Lab-Made Device Packed with Molecularly Imprinted Polymer","volume":"219","author":"Sartore","year":"2020","journal-title":"Talanta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105388","DOI":"10.1016\/j.jfca.2023.105388","article-title":"A Molecularly Imprinted Polymer for Microextraction by Packed Sorbent of Sulfonylureas Herbicides from Corn Samples","volume":"121","author":"Andrade","year":"2023","journal-title":"J. Food Compos. Anal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1002\/jssc.201400616","article-title":"Microextraction by Packed Sorbent Liquid Chromatography with Time-of-flight Mass Spectrometry of Triazines Employing a Molecularly Imprinted Polymer\u2020","volume":"37","author":"Andrade","year":"2014","journal-title":"J. Sep. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.trac.2019.06.036","article-title":"Micro Solid-Phase Extraction (Pipette Tip and Spin Column) and Thin Film Solid-Phase Microextraction: Miniaturized Concepts for Chromatographic Analysis","volume":"118","author":"Seidi","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339383","DOI":"10.1016\/j.aca.2021.339383","article-title":"Disposable Pipette Extraction: A Critical Review of Concepts, Applications, and Directions","volume":"1192","author":"Carasek","year":"2022","journal-title":"Anal. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.talanta.2015.03.032","article-title":"Hybrid Silica Monolith for Microextraction by Packed Sorbent to Determine Drugs from Plasma Samples by Liquid Chromatography\u2013Tandem Mass Spectrometry","volume":"140","author":"Domingues","year":"2015","journal-title":"Talanta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"460547","DOI":"10.1016\/j.chroma.2019.460547","article-title":"On-Site Rapid Screening of Benzodiazepines in Dietary Supplements Using Pipette-Tip Micro-Solid Phase Extraction Coupled to Ion Mobility Spectrometry","volume":"1610","author":"Sun","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1002\/jssc.202000906","article-title":"Pipette Tip Micro-solid Phase Extraction (Octyl-functionalized Hybrid Silica Monolith) and Ultra-high-performance Liquid Chromatography-tandem Mass Spectrometry to Determine Cannabidiol and Tetrahydrocannabinol in Plasma Samples","volume":"44","author":"Cruz","year":"2021","journal-title":"J. Sep. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00056","DOI":"10.1016\/j.ohx.2019.e00056","article-title":"Sample Treatment Platform for Automated Integration of Microextraction Techniques and Liquid Chromatography Analysis","volume":"5","author":"Medina","year":"2019","journal-title":"HardwareX"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Brennan, M., Bokhari, F., and Eddington, D. (2018). Open Design 3D-Printable Adjustable Micropipette That Meets the ISO Standard for Accuracy. Micromachines, 9.","DOI":"10.3390\/mi9040191"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.slast.2022.01.003","article-title":"Rapid Deployment of Inexpensive Open-Source Orbital Shakers in Support of High-Throughput Screening","volume":"27","author":"Baillargeon","year":"2022","journal-title":"SLAS Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wijnen, B., Hunt, E.J., Anzalone, G.C., and Pearce, J.M. (2014). Open-Source Syringe Pump Library. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107216"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1038\/s41598-020-58246-6","article-title":"Open-Source, 3D-Printed Peristaltic Pumps for Small Volume Point-of-Care Liquid Handling","volume":"10","author":"Behrens","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"341832","DOI":"10.1016\/j.aca.2023.341832","article-title":"An Open Source 3D Printed Autosampler for Capillary Electrophoresis","volume":"1279","year":"2023","journal-title":"Anal. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.reactfunctpolym.2005.11.004","article-title":"Porous Structure of Hypercrosslinked Polystyrene: State-of-the-Art Mini-Review","volume":"66","author":"Tsyurupa","year":"2006","journal-title":"React. Funct. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"132527","DOI":"10.1016\/j.cej.2021.132527","article-title":"Polystyrene-Based Nanospheres with Controllable Microstructures for Exceptional Solid Phase Microextraction of Organic Pollutants","volume":"428","author":"Chen","year":"2022","journal-title":"Chem. Eng. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s12161-024-02570-4","article-title":"Effervescence-Assisted Magnetic Solid-Phase Extraction of Nitroimidazoles and Their Metabolites Using Magnetic Hypercrosslinked Polystyrene","volume":"17","author":"Goncharov","year":"2024","journal-title":"Food Anal. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s13726-023-01177-6","article-title":"Hypercrosslinked Polystyrene-Based Adsorbents for the Removal of Lead Ions from Aqueous Effluents: Experimental and RSM Modeling","volume":"32","author":"Nasiri","year":"2023","journal-title":"Iran. Polym. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113360","DOI":"10.1016\/j.micromeso.2024.113360","article-title":"Synthesis of Porous Hypercrosslinked Polymers from Waste Polystyrene for Efficient CO2 Separation","volume":"381","author":"Wang","year":"2025","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106265","DOI":"10.1016\/j.reactfunctpolym.2025.106265","article-title":"Simultaneous Hypercrosslinking and Functionalization of Porous Polystyrene Adsorbent for Protein-Bound Uraemic Toxins Removal","volume":"214","author":"Chen","year":"2025","journal-title":"React. Funct. Polym."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.15360\/1813-9779-2025-6-2578","article-title":"Multimodal LPS-Selective Hemoadsorption and Hemodiafiltration in the Intensive Care of Gram-Negative Sepsis Patients: A Multicenter Observational Study","volume":"21","author":"Ismailov","year":"2025","journal-title":"Gen. Reanimatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Liu, Y., and Peng, X. (2022). Multi-Functional Hypercrosslinked Polystyrene as High-Performance Adsorbents for Artificial Liver Blood Purification. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.789814"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"RCR5119","DOI":"10.59761\/RCR5119","article-title":"Methodology for the Determining Aromatic Monocarboxylic Acids as Products of Phenylalanine and Tyrosine Metabolism: Current Advances and Trends","volume":"93","author":"Zhizhin","year":"2024","journal-title":"Russ. Chem. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.clinms.2019.05.005","article-title":"Analysis of Phenylcarboxylic Acid-Type Microbial Metabolites by Microextraction by Packed Sorbent from Blood Serum Followed by GC\u2013MS Detection","volume":"14","author":"Pautova","year":"2019","journal-title":"Clin. Mass Spectrom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1134\/S1061934823140058","article-title":"Simultaneous Determination of Aromatic, Short-Chain Fatty and Dicarboxylic Acids in Blood Serum and Cerebrospinal Fluid by Gas Chromatography\u2013Mass Spectrometry","volume":"78","author":"Pautova","year":"2023","journal-title":"J. Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112883","DOI":"10.1016\/j.jpba.2019.112883","article-title":"Microextraction of Aromatic Microbial Metabolites by Packed Hypercrosslinked Polystyrene from Blood Serum","volume":"177","author":"Pautova","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1007\/s00216-020-02464-4","article-title":"Restricted Access Carbon Nanotube for Microextraction by Packed Sorbent to Determine Antipsychotics in Plasma Samples by High-Performance Liquid Chromatography-Tandem Mass Spectrometry","volume":"412","author":"Cruz","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1039\/D3AY00238A","article-title":"Restricted Access Polypyrrole Employed in Pipette-Tip Solid-Phase Extraction for Determination of Nimodipine and Nicardipine in Breast Milk","volume":"15","author":"Silva","year":"2023","journal-title":"Anal. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104162","DOI":"10.1016\/j.microc.2019.104162","article-title":"Microextraction by Packed Sorbent Using a New Restricted Molecularly Imprinted Polymer for the Determination of Estrogens from Human Urine Samples","volume":"150","author":"Teixeira","year":"2019","journal-title":"Microchem. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1002\/jssc.201800528","article-title":"Hypercrosslinked Polymeric Restricted Access Materials for Analysis of Biological Fluids","volume":"41","author":"Popov","year":"2018","journal-title":"J. Sep. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0167-2991(02)80175-6","article-title":"Adsorption of Inflammatory Cytokines and Endotoxin by Mesoporous Polymers and Activated Carbons","volume":"144","author":"Murphy","year":"2002","journal-title":"Stud. Surf. Sci. Catal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1134\/S0036023621020030","article-title":"Integrated Approach to Monitoring Volatile Organic Compounds by Photonic-Crystal Sensor Matrices","volume":"66","author":"Ivanov","year":"2021","journal-title":"Russ. J. Inorg. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1007\/s10570-020-03652-2","article-title":"Direct Determination of Cellulosic Glucan Content in Starch-Containing Samples","volume":"28","author":"Sluiter","year":"2021","journal-title":"Cellulose"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10511","DOI":"10.1021\/acs.analchem.5c07147","article-title":"Toward Accurate Estimation of Extractable Organic Fluorine by Analysis of Fluoride Contamination in Extracts Using Gas Chromatography","volume":"98","author":"Montelius","year":"2026","journal-title":"Anal. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"378","DOI":"10.32614\/RJ-2017-066","article-title":"GlmmTMB Balances Speed and Flexibility Among Packages for Zero-Inflated Generalized Linear Mixed Modeling","volume":"9","author":"Brooks","year":"2017","journal-title":"R J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1134\/S1061934820030156","article-title":"Syringe Pump Created Using 3D Printing Technology and Arduino Platform","volume":"75","author":"Samokhin","year":"2020","journal-title":"J. Anal. Chem."},{"key":"ref_49","unstructured":"(2002). Piston-Operated Volumetric Apparatus\u2014Part 6: Gravimetric Methods for the Determination of Measurement Error (Standard No. ISO 8655-6:2002)."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:33:00Z","timestamp":1784694780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":49,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146443"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146443","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}