{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:39:07Z","timestamp":1768819147973,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2012,7,11]],"date-time":"2012-07-11T00:00:00Z","timestamp":1341964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can be used as promising candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer screening protocol has been conducted with microfluidic-based devices. Furthermore, aptamer affinity screening by a microfluidic-based method has demonstrated remarkable advantages over competing traditional methods. In this paper, we first reviewed microfluidic systems which demonstrated efficient and rapid screening of a specific aptamer. Then, the clinical applications of screened aptamers, also performed by microfluidic systems, are further reviewed. These automated microfluidic systems can provide advantages over their conventional counterparts including more compactness, faster analysis, less sample\/reagent consumption and automation. An aptamer-based compact microfluidic system for diagnosis may even lead to a point-of-care device. The use of microfluidic systems for aptamer screening and diagnosis is expected to continue growing in the near future and may make a substantial impact on biomedical applications.<\/jats:p>","DOI":"10.3390\/s120709514","type":"journal-article","created":{"date-parts":[[2012,7,11]],"date-time":"2012-07-11T11:03:00Z","timestamp":1342004580000},"page":"9514-9529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Screening of Aptamers on Microfluidic Systems for Clinical Applications"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5553-5833","authenticated-orcid":false,"given":"Chen-Hsun","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, National Cheng Kung University, Tainan 70101, Taiwan"}]},{"given":"Chao-Jyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, National Taiwan University, Taipei 10617, Taiwan"}]},{"given":"Gwo-Bin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan"}]}],"member":"1968","published-online":{"date-parts":[[2012,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1093\/clinchem\/45.9.1628","article-title":"Aptamers: An emerging class of molecules that rival antibodies in diagnostics","volume":"45","author":"Jayasena","year":"1999","journal-title":"Clin. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment-RNA ligands to bacteriophage-t4 DNA-polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/35070613","article-title":"Functional proteins from a random-sequence library","volume":"410","author":"Keefe","year":"2001","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1016\/j.bbrc.2005.10.172","article-title":"In vitro selection of DNA aptamers binding ethanolamine","volume":"338","author":"Mann","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.bioeng.2007.06.003","article-title":"Advances in SELEX and application of aptamers in the central nervous system","volume":"24","author":"Yang","year":"2007","journal-title":"Biomol. Eng."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1016\/j.bios.2004.11.006","article-title":"Analytical applications of aptamers","volume":"20","author":"Tombelli","year":"2005","journal-title":"Biosens. Bioelectron."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/138161211795049769","article-title":"Advances and perspectives in cell-specific aptamers","volume":"17","author":"Sun","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3390\/s120100612","article-title":"Aptamers and their biological applications","volume":"12","author":"Song","year":"2012","journal-title":"Sensors"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.bioeng.2007.06.001","article-title":"SELEX-A (r)evolutionary method to generate high-affinity nucleic acid ligands","volume":"24","author":"Stoltenburg","year":"2007","journal-title":"Biomol. Eng."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/S1872-2040(11)60542-2","article-title":"Application of aptamer based biosensors for detection of pathogenic microorganisms","volume":"40","author":"Wang","year":"2012","journal-title":"Chin. J. Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e27862","DOI":"10.1371\/journal.pone.0027862","article-title":"A SELEX-screened aptamer of human hepatitis B virus RNA encapsulation signal suppresses viral replication","volume":"6","author":"Feng","year":"2011","journal-title":"PLoS One"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1093\/nar\/gkr1098","article-title":"5\u2032-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity","volume":"40","author":"Hwang","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.mimet.2012.01.014","article-title":"Development of RNA aptamers for detection of Salmonella Enteritidis","volume":"89","author":"Hyeon","year":"2012","journal-title":"J. Microbiol. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1006\/bbrc.2002.6354","article-title":"Selection of RNA aptamers to the Alzheimer's disease amyloid peptide","volume":"290","author":"Ylera","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00216-005-0089-3","article-title":"A microfluidic SELEX prototype","volume":"384","author":"Hybarger","year":"2006","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1073\/pnas.0813135106","article-title":"Micromagnetic selection of aptamers in microfluidic channels","volume":"106","author":"Lou","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/jssc.200600483","article-title":"Microfluidic selection and applications of aptamers","volume":"30","author":"Mosing","year":"2007","journal-title":"J. Sep. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1039\/b814993c","article-title":"Selection and elution of aptamers using nanoporous sol-gel arrays with integrated microheaters","volume":"9","author":"Park","year":"2009","journal-title":"Lab Chip"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.1021\/ac900759k","article-title":"Generation of highly specific aptamers via micromagnetic selection","volume":"81","author":"Qian","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15373","DOI":"10.1073\/pnas.1009331107","article-title":"Quantitative selection of DNA aptamers through microfluidic selection and high-throughput sequencing","volume":"107","author":"Cho","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6107","DOI":"10.1021\/ac050836q","article-title":"Capillary electrophoresis-SELEX selection of aptamers with affinity for HIV-1 reverse transcriptase","volume":"77","author":"Mosing","year":"2005","journal-title":"Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1089\/oli.2010.0263","article-title":"A sol-gel-based microfluidics system enhances the efficiency of RNA aptamer selection","volume":"21","author":"Ahn","year":"2011","journal-title":"Oligonucleotides"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1073\/pnas.0813135106","article-title":"Micromagnetic selection of aptamers in microfluidic channels","volume":"106","author":"Xinhui","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","first-page":"U139","article-title":"CE-SELEX: In vitro selection of DNA aptamer using capillary electrophoresis","volume":"229","author":"Bowser","year":"2005","journal-title":"Abstr. Paper Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1002\/elps.200900543","article-title":"Selection of aptamers for signal transduction proteins by capillary electrophoresis","volume":"31","author":"Tok","year":"2010","journal-title":"Electrophoresis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.aca.2008.10.027","article-title":"Kinetic capillary electrophoresis-based affinity screening of aptamer clones","volume":"631","author":"Yunusov","year":"2009","journal-title":"Anal. Chim. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9382","DOI":"10.1021\/ja052406n","article-title":"In vitro selection of aptamers with affinity for neuropeptide Y using capillary electrophoresis","volume":"127","author":"Mendonsa","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1021\/ac202559w","article-title":"Sol-gel derived nanoporous compositions for entrapping small molecules and their outlook toward aptamer screening","volume":"84","author":"Ahn","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1039\/b814993c","article-title":"Selection and elution of aptamers using nanoporous sol-gel arrays with integrated microheaters","volume":"9","author":"Park","year":"2009","journal-title":"Lab Chip"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.bios.2009.12.029","article-title":"Integrated microfluidic system for rapid screening of CRP aptamers utilizing systematic evolution of ligands by exponential enrichment (SELEX)","volume":"25","author":"Huang","year":"2010","journal-title":"Biosens. Bioelectron."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bios.2012.02.024","article-title":"An integrated microfluidic system for rapid screening of alpha-fetoprotein-specific aptamers","volume":"35","author":"Huang","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S0006-291X(02)02490-7","article-title":"In vitro selection of specific RNA inhibitors of NFATc","volume":"298","author":"Bae","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1371\/journal.pbio.0030123","article-title":"Neutralizing aptamers from whole-cell SELEX inhibit the RET receptor tyrosine kinase","volume":"3","author":"Cerchia","year":"2005","journal-title":"PLoS Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15416","DOI":"10.1073\/pnas.2136683100","article-title":"A tenascin-C aptamer identified by tumor cell SELEX: Systematic evolution of ligands by exponential enrichment","volume":"100","author":"Daniels","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/nprot.2010.66","article-title":"Development of DNA aptamers using Cell-SELEX","volume":"5","author":"Sefah","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3390\/ijms9040668","article-title":"Cell-SELEX: Novel perspectives of aptamer-based therapeutics","volume":"9","author":"Guo","year":"2008","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.aca.2008.05.031","article-title":"Applications of aptamers in cancer cell biology","volume":"621","author":"Phillips","year":"2008","journal-title":"Anal. Chim. Acta"},{"key":"ref_39","unstructured":"Weng, C.H., Hung, L.Y., Lin, H.I., Hsieh, I.S., Shieh, S.C., Chen, Y.L., and Lee, G.B. (2011, January 2\u20136). An Integrated Microfluidic System For Automating On-Chip Selex Process To Screen Tumor Cell-Specific Aptamers. Seattle, WA, USA."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"235105","DOI":"10.1088\/0957-4484\/19\/23\/235105","article-title":"Quantum dot-labeled aptamer nanoprobes specifically targeting glioma cells","volume":"19","author":"Chen","year":"2008","journal-title":"Nanotechnology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1021\/nl062998n","article-title":"Self-assembled combinatorial encoding nanoarrays for multiplexed biosensing","volume":"7","author":"Lin","year":"2007","journal-title":"Nano Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/oli.2010.0234","article-title":"Advances in aptamers","volume":"20","author":"Syed","year":"2010","journal-title":"Oligonucleotides"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.elecom.2009.12.008","article-title":"Microfluidic chip-based aptasensor for amplified electrochemical detection of human thrombin","volume":"12","author":"Huixiang","year":"2010","journal-title":"Electrochem. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1016\/j.bios.2008.10.003","article-title":"Status of biomolecular recognition using electrochemical techniques","volume":"24","author":"Sadik","year":"2009","journal-title":"Biosens. Bioelectron."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1021\/ja806531z","article-title":"Continuous, real-time monitoring of cocaine in undiluted blood serum via a microfluidic, electrochemical aptamer-based sensor","volume":"131","author":"Swensen","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.elecom.2009.12.008","article-title":"Microfluidic chip-based aptasensor for amplified electrochemical detection of human thrombin","volume":"12","author":"Wang","year":"2010","journal-title":"Electrochem. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1002\/asia.200900660","article-title":"Homogeneous analysis: Label-free and substrate-free aptasensors","volume":"5","author":"Li","year":"2010","journal-title":"Chem.-Asian J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15352","DOI":"10.1021\/ja905854a","article-title":"A basic site-containing DNAzyme and aptamer for label-free fluorescent detection of Pb2+ and adenosine with high sensitivity, selectivity, and tunable dynamic range","volume":"131","author":"Xiang","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6534","DOI":"10.1021\/la200649n","article-title":"Rapid microarray detection of DNA and proteins in microliter volumes with surface plasmon resonance imaging measurements","volume":"27","author":"Seefeld","year":"2011","journal-title":"Langmuir"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00216-007-1510-x","article-title":"Surface plasmon resonance imaging for affinity analysis of aptamer-protein interactions with PDMS microfluidic chips","volume":"389","author":"Wang","year":"2007","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1021\/ac061879p","article-title":"Aptamer-based detection of plasma proteins by an electrochemical assay coupled to magnetic beads","volume":"79","author":"Centi","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"034101","DOI":"10.1063\/1.3194283","article-title":"Rapid detection of natriuretic peptides by a microfluidic LabChip analyzer with DNA aptamers: Application of natriuretic peptide detection","volume":"3","author":"Lin","year":"2009","journal-title":"Biomicrofluidics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.snb.2011.04.087","article-title":"An integrated microfluidic system for fast, automatic detection of C-reactive protein","volume":"157","author":"Lee","year":"2011","journal-title":"Sens Actuators B"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1002\/elps.200700854","article-title":"Poly(methyl methacrylate) microchip affinity capillary gel electrophoresis of aptamer-protein complexes for the analysis of thrombin in plasma","volume":"29","author":"Obubuafo","year":"2008","journal-title":"Electrophoresis"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1002\/elps.200406103","article-title":"Microbead-based affinity chromatography chip using RNA aptamer modified with photocleavable linker","volume":"25","author":"Cho","year":"2004","journal-title":"Electrophoresis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1021\/ac101269u","article-title":"On-chip aptamer-based Sandwich assay for thrombin detection employing magnetic beads and quantum dots","volume":"82","author":"Tennico","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7436","DOI":"10.1021\/ac9012072","article-title":"Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells","volume":"81","author":"Xu","year":"2009","journal-title":"Anal. Chem."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/12\/7\/9514\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:51:14Z","timestamp":1760219474000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/12\/7\/9514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,11]]},"references-count":57,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2012,7]]}},"alternative-id":["s120709514"],"URL":"https:\/\/doi.org\/10.3390\/s120709514","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,11]]}}}