Screening of Aptamers on Microfluidic Systems for Clinical Applications

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.

[1]  Sam F. Y. Li,et al.  Selection of aptamers for signal transduction proteins by capillary electrophoresis , 2010, Electrophoresis.

[2]  R. Corn,et al.  Rapid microarray detection of DNA and proteins in microliter volumes with surface plasmon resonance imaging measurements. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[3]  Gwo-Bin Lee,et al.  An integrated microfluidic system for fast, automatic detection of C-reactive protein , 2011 .

[4]  Gerhard Ziemer,et al.  CELL-SELEX: Novel Perspectives of Aptamer-Based Therapeutics , 2008, International journal of molecular sciences.

[5]  R. Stoltenburg,et al.  SELEX--a (r)evolutionary method to generate high-affinity nucleic acid ligands. , 2007, Biomolecular engineering.

[6]  Dongliang Yang,et al.  Advances in SELEX and application of aptamers in the central nervous system. , 2007, Biomolecular engineering.

[7]  Quan Cheng,et al.  Surface plasmon resonance imaging for affinity analysis of aptamer–protein interactions with PDMS microfluidic chips , 2007, Analytical and bioanalytical chemistry.

[8]  M. Bowser,et al.  Capillary electrophoresis-SELEX selection of aptamers with affinity for HIV-1 reverse transcriptase. , 2005, Analytical chemistry.

[9]  Gwo-Bin Lee,et al.  AN INTEGRATED MICROFLUIDIC SYSTEM FOR AUTOMATING ON-CHIP SELEX PROCESS TO SCREEN TUMOR CELL-SPECIFIC APTAMERS , 2011 .

[10]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[11]  R. Stoltenburg,et al.  In vitro selection of DNA aptamers binding ethanolamine. , 2005, Biochemical and biophysical research communications.

[12]  Seong-Wook Lee,et al.  In vitro selection of specific RNA inhibitors of NFATc. , 2002, Biochemical and biophysical research communications.

[13]  Chankyu Park,et al.  Development of RNA aptamers for detection of Salmonella Enteritidis. , 2012, Journal of microbiological methods.

[14]  Sergey N. Krylov,et al.  Kinetic capillary electrophoresis-based affinity screening of aptamer clones. , 2009, Analytica chimica acta.

[15]  Volker A Erdmann,et al.  Selection of RNA aptamers to the Alzheimer's disease amyloid peptide. , 2002, Biochemical and biophysical research communications.

[16]  Wei Sun,et al.  Advances and perspectives in cell-specific aptamers. , 2011, Current pharmaceutical design.

[17]  Dong-Ki Lee,et al.  A sol-gel-based microfluidics system enhances the efficiency of RNA aptamer selection. , 2011, Oligonucleotides.

[18]  Glen Hybarger,et al.  A microfluidic SELEX prototype , 2006, Analytical and bioanalytical chemistry.

[19]  Steven A Soper,et al.  Poly(methyl methacrylate) microchip affinity capillary gel electrophoresis of aptamer–protein complexes for the analysis of thrombin in plasma , 2008, Electrophoresis.

[20]  M. Bowser,et al.  Microfluidic selection and applications of aptamers. , 2007, Journal of separation science.

[21]  Gwo-Bin Lee,et al.  An integrated microfluidic system for rapid screening of alpha-fetoprotein-specific aptamers. , 2012, Biosensors & bioelectronics.

[22]  Omowunmi A Sadik,et al.  Status of biomolecular recognition using electrochemical techniques. , 2009, Biosensors & bioelectronics.

[23]  Cheryl Moody Bartel,et al.  On-chip aptamer-based sandwich assay for thrombin detection employing magnetic beads and quantum dots. , 2010, Analytical chemistry.

[24]  A. Heeger,et al.  Micromagnetic selection of aptamers in microfluidic channels , 2009, Proceedings of the National Academy of Sciences.

[25]  M. Mascini,et al.  Analytical applications of aptamers. , 2005, Biosensors & bioelectronics.

[26]  M. Bowser,et al.  In vitro selection of aptamers with affinity for neuropeptide Y using capillary electrophoresis. , 2005, Journal of the American Chemical Society.

[27]  Bingling Li,et al.  Homogeneous analysis: label-free and substrate-free aptasensors. , 2010, Chemistry, an Asian journal.

[28]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[29]  Anthony D. Keefe,et al.  Functional proteins from a random-sequence library , 2001, Nature.

[30]  Yixian Wang,et al.  Application of Aptamer Based Biosensors for Detection of Pathogenic Microorganisms , 2012, Chinese Journal of Analytical Chemistry.

[31]  Weihong Tan,et al.  Applications of aptamers in cancer cell biology. , 2008, Analytica chimica acta.

[32]  Seonghwan Lee,et al.  Aptamers and Their Biological Applications , 2012, Sensors.

[33]  Jürgen Beck,et al.  A SELEX-Screened Aptamer of Human Hepatitis B Virus RNA Encapsidation Signal Suppresses Viral Replication , 2011, PloS one.

[34]  Chengcheng Liu,et al.  Microfluidic chip-based aptasensor for amplified electrochemical detection of human thrombin , 2010 .

[35]  S. Jayasena Aptamers: an emerging class of molecules that rival antibodies in diagnostics. , 1999, Clinical chemistry.

[36]  Dong-Ki Lee,et al.  Selection and elution of aptamers using nanoporous sol-gel arrays with integrated microheaters. , 2009, Lab on a chip.

[37]  Weihong Tan,et al.  Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. , 2009, Analytical chemistry.

[38]  D. Shangguan,et al.  Development of DNA aptamers using Cell-SELEX , 2010, Nature Protocols.

[39]  Seung Soo Oh,et al.  Quantitative selection of DNA aptamers through microfluidic selection and high-throughput sequencing , 2010, Proceedings of the National Academy of Sciences.

[40]  Tai-Yuan Chen,et al.  Rapid detection of natriuretic peptides by a microfluidic LabChip analyzer with DNA aptamers: Application of natriuretic peptide detection. , 2009, Biomicrofluidics.

[41]  Hong Qing,et al.  Quantum dot-labeled aptamer nanoprobes specifically targeting glioma cells , 2008, Nanotechnology.

[42]  Muhammad Ali Syed,et al.  Advances in aptamers. , 2010, Oligonucleotides.

[43]  Bertrand Tavitian,et al.  Neutralizing Aptamers from Whole-Cell SELEX Inhibit the RET Receptor Tyrosine Kinase , 2005, PLoS biology.

[44]  L. Gold,et al.  A tenascin-C aptamer identified by tumor cell SELEX: Systematic evolution of ligands by exponential enrichment , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Yi Lu,et al.  Abasic site-containing DNAzyme and aptamer for label-free fluorescent detection of Pb(2+) and adenosine with high sensitivity, selectivity, and tunable dynamic range. , 2009, Journal of the American Chemical Society.

[46]  Arica A Lubin,et al.  Continuous, real-time monitoring of cocaine in undiluted blood serum via a microfluidic, electrochemical aptamer-based sensor. , 2009, Journal of the American Chemical Society.

[47]  Thomas Laurell,et al.  Sol-gel derived nanoporous compositions for entrapping small molecules and their outlook toward aptamer screening. , 2012, Analytical chemistry.

[48]  M. Mascini,et al.  Aptamer-based detection of plasma proteins by an electrochemical assay coupled to magnetic beads. , 2007, Analytical chemistry.

[49]  Yong-Kweon Kim,et al.  Microbead‐based affinity chromatography chip using RNA aptamer modified with photocleavable linker , 2004, Electrophoresis.

[50]  Seung Soo Oh,et al.  Generation of highly specific aptamers via micromagnetic selection. , 2009, Analytical chemistry.

[51]  Hao Yan,et al.  Self-assembled combinatorial encoding nanoarrays for multiplexed biosensing. , 2007, Nano letters.

[52]  Gwo-Bin Lee,et al.  Integrated microfluidic system for rapid screening of CRP aptamers utilizing systematic evolution of ligands by exponential enrichment (SELEX). , 2010, Biosensors & bioelectronics.