Microfluidic Technology for Nucleic Acid Aptamer Evolution and Application

The intersection of microfluidics and aptamer technologies holds particular promise for rapid progress in a plethora of applications across biomedical science and other areas. Here, the influence of microfluidics on the field of aptamers, from traditional capillary electrophoresis approaches through innovative modern‐day approaches using micromagnetic beads and emulsion droplets, is reviewed. Miniaturizing aptamer‐based bioassays through microfluidics has the potential to transform diagnostics and embedded biosensing in the coming years.

[1]  Zhi Zhu,et al.  Bioinspired Engineering of a Multivalent Aptamer-Functionalized Nanointerface to Enhance the Capture and Release of Circulating Tumor Cells. , 2018, Angewandte Chemie.

[2]  Tian Jian Lu,et al.  Lateral flow aptamer assay integrated smartphone-based portable device for simultaneous detection of multiple targets using upconversion nanoparticles , 2018, Sensors and Actuators B: Chemical.

[3]  M. Berezovski,et al.  Selection of aptamers for a protein target in cell lysate and their application to protein purification , 2009, Nucleic acids research.

[4]  A. Abate,et al.  SiC-Seq: Single-cell genome sequencing at ultra high-throughput with microfluidic droplet barcoding , 2017, Nature Biotechnology.

[5]  Juewen Liu,et al.  Metal Sensing by DNA. , 2017, Chemical reviews.

[6]  He Zhang,et al.  Aptamer-based microfluidic beads array sensor for simultaneous detection of multiple analytes employing multienzyme-linked nanoparticle amplification and quantum dots labels. , 2014, Biosensors & bioelectronics.

[7]  Paul A. Wiggins,et al.  RNA mango aptamer-fluorophore: a bright, high-affinity complex for RNA labeling and tracking. , 2014, ACS chemical biology.

[8]  Xiaochun Xu,et al.  Specific Capture and Release of Circulating Tumor Cells Using Aptamer‐Modified Nanosubstrates , 2013, Advanced materials.

[9]  Alar Ainla,et al.  A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate. , 2016, Analytical chemistry.

[10]  M. Bowser,et al.  In vitro evolution of functional DNA using capillary electrophoresis. , 2004, Journal of the American Chemical Society.

[11]  G. Whitesides,et al.  Microfluidic devices fabricated in Poly(dimethylsiloxane) for biological studies , 2003, Electrophoresis.

[12]  Ning Gan,et al.  Microfluidic electrophoretic non-enzymatic kanamycin assay making use of a stirring bar functionalized with gold-labeled aptamer, of a fluorescent DNA probe, and of signal amplification via hybridization chain reaction , 2018, Microchimica Acta.

[13]  J. Kjems,et al.  Self-assembly of a nanoscale DNA box with a controllable lid , 2009, Nature.

[14]  Yi Xiao,et al.  Improving aptamer selection efficiency through volume dilution, magnetic concentration, and continuous washing in microfluidic channels. , 2011, Analytical chemistry.

[15]  E. Westhof,et al.  iSpinach: a fluorogenic RNA aptamer optimized for in vitro applications , 2016, Nucleic acids research.

[16]  D. Kent,et al.  High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays , 2011, Nature Methods.

[17]  Nancy Kelley-Loughnane,et al.  Aptamer-functionalized nanoparticles for surface immobilization-free electrochemical detection of cortisol in a microfluidic device. , 2016, Biosensors & bioelectronics.

[18]  Ying Wang,et al.  Analogic China map constructed by DNA , 2006 .

[19]  J. Sturm,et al.  Continuous Particle Separation Through Deterministic Lateral Displacement , 2004, Science.

[20]  Leslie Y Yeo,et al.  Microfluidic devices for bioapplications. , 2011, Small.

[21]  P. Yin,et al.  Complex shapes self-assembled from single-stranded DNA tiles , 2012, Nature.

[22]  Simon Chi-Chin Shiu,et al.  Aptamer-based electrochemical biosensor for highly sensitive and selective malaria detection with adjustable dynamic response range and reusability , 2018 .

[23]  Simon Chi-Chin Shiu,et al.  A portable microfluidic Aptamer-Tethered Enzyme Capture (APTEC) biosensor for malaria diagnosis. , 2018, Biosensors & bioelectronics.

[24]  Nicolas H Voelcker,et al.  Aptamer sensor for cocaine using minor groove binder based energy transfer. , 2012, Analytica chimica acta.

[25]  T. Laurell,et al.  Review of cell and particle trapping in microfluidic systems. , 2009, Analytica chimica acta.

[26]  Kevin W Plaxco,et al.  Real-Time, Aptamer-Based Tracking of Circulating Therapeutic Agents in Living Animals , 2013, Science Translational Medicine.

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

[28]  Zhi Zhu,et al.  Integration of target responsive hydrogel with cascaded enzymatic reactions and microfluidic paper-based analytic devices (µPADs) for point-of-care testing (POCT). , 2016, Biosensors & bioelectronics.

[29]  Alexis Autour,et al.  Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells , 2018, Nature Communications.

[30]  Ying Liu,et al.  Simultaneous detection of cell-secreted TNF-α and IFN-γ using micropatterned aptamer-modified electrodes. , 2012, Biomaterials.

[31]  D. Pang,et al.  Ebola Virus Aptamers: From Highly Efficient Selection to Application on Magnetism-Controlled Chips. , 2019, Analytical chemistry.

[32]  Dongsheng Liu,et al.  Regulation of an enzyme cascade reaction by a DNA machine. , 2013, Small.

[33]  Mette D. E. Jepsen,et al.  Construction of a fuzzy and Boolean logic gates based on DNA. , 2015, Small.

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

[35]  Atefeh Sarafan Sadeghi,et al.  Development and characterization of DNA aptamers against florfenicol: Fabrication of a sensitive fluorescent aptasensor for specific detection of florfenicol in milk. , 2018, Talanta.

[36]  S. Liang,et al.  Development of Aptamer-Based Point-of-Care Diagnostic Devices for Malaria Using Three-Dimensional Printing Rapid Prototyping , 2016 .

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

[38]  Shenshan Zhan,et al.  A mini-review on functional nucleic acids-based heavy metal ion detection. , 2016, Biosensors & bioelectronics.

[39]  R. Mathies,et al.  Integration of programmable microfluidics and on-chip fluorescence detection for biosensing applications. , 2014, Biomicrofluidics.

[40]  Chao Ma,et al.  Self-powered sensor for Hg2+ detection based on hollow-channel paper analytical devices , 2015 .

[41]  S. Jaffrey,et al.  RNA Mimics of Green Fluorescent Protein , 2011, Science.

[42]  S. Cosnier,et al.  Label-free impedimetric thrombin sensor based on poly(pyrrole-nitrilotriacetic acid)-aptamer film. , 2013, Biosensors & bioelectronics.

[43]  Y. Liu,et al.  Micropatterned aptasensors for continuous monitoring of cytokine release from human leukocytes. , 2011, Analytical chemistry.

[44]  Jonathan G Heddle,et al.  An aptamer-enabled DNA nanobox for protein sensing. , 2018, Nanomedicine : nanotechnology, biology, and medicine.

[45]  Ming Zhou,et al.  Microfluidic electrochemical aptameric assay integrated on-chip: a potentially convenient sensing platform for the amplified and multiplex analysis of small molecules. , 2011, Analytical chemistry.

[46]  Kemin Wang,et al.  Screening of DNA aptamers against myoglobin using a positive and negative selection units integrated microfluidic chip and its biosensing application. , 2014, Analytical chemistry.

[47]  Jungkyu Kim,et al.  Microfluidic sample preparation: cell lysis and nucleic acid purification. , 2009, Integrative biology : quantitative biosciences from nano to macro.

[48]  Dai-Wen Pang,et al.  Multifunctional Screening Platform for the Highly Efficient Discovery of Aptamers with High Affinity and Specificity. , 2017, Analytical chemistry.

[49]  Feng Xu,et al.  Multiplexed Instrument-Free Bar-Chart SpinChip Integrated with Nanoparticle-Mediated Magnetic Aptasensors for Visual Quantitative Detection of Multiple Pathogens. , 2018, Analytical chemistry.

[50]  Zhi Zhu,et al.  Microfluidic Distance Readout Sweet Hydrogel Integrated Paper-Based Analytical Device (μDiSH-PAD) for Visual Quantitative Point-of-Care Testing. , 2016, Analytical chemistry.

[51]  A. Varenne,et al.  Aptamer entrapment in microfluidic channel using one‐step sol‐gel process, in view of the integration of a new selective extraction phase for lab‐on‐a‐chip , 2017, Electrophoresis.

[52]  K. Tsaneva-Atanasova,et al.  Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader , 2019, Nature Communications.

[53]  John G. Bruno,et al.  In VitroSelection of DNA to Chloroaromatics Using Magnetic Microbead-Based Affinity Separation and Fluorescence Detection , 1997 .

[54]  Robert Langer,et al.  Microfluidic system for studying the interaction of nanoparticles and microparticles with cells. , 2005, Analytical chemistry.

[55]  P. Yager,et al.  Microfluidic Diffusion-Based Separation and Detection , 1999, Science.

[56]  R. Kennedy,et al.  Aptamers as ligands in affinity probe capillary electrophoresis. , 1998, Analytical chemistry.

[57]  N. Seeman,et al.  An immobile nucleic acid junction constructed from oligonucleotides , 1983, Nature.

[58]  Robert Langer,et al.  Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy , 2010, Proceedings of the National Academy of Sciences.

[59]  Fumihito Arai,et al.  Cellular Force Measurement Using a Nanometric-Probe-Integrated Microfluidic Chip with a Displacement Reduction Mechanism , 2013, J. Robotics Mechatronics.

[60]  Liang Huang,et al.  Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture. , 2017, Biomicrofluidics.

[61]  Jae Hee Jung,et al.  Fast and continuous microorganism detection using aptamer-conjugated fluorescent nanoparticles on an optofluidic platform. , 2015, Biosensors & bioelectronics.

[62]  Andrew D Griffiths,et al.  Using droplet-based microfluidics to improve the catalytic properties of RNA under multiple-turnover conditions , 2015, RNA.

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

[64]  F. Ceroni,et al.  The spinach RNA aptamer as a characterization tool for synthetic biology. , 2014, ACS synthetic biology.

[65]  Yuanjin Zhao,et al.  Emerging Droplet Microfluidics. , 2017, Chemical reviews.

[66]  M. Stojanović,et al.  Integrated Microfluidic Isolation of Aptamers Using Electrophoretic Oligonucleotide Manipulation , 2016, Scientific Reports.

[67]  Gwo-Bin Lee,et al.  Selection of aptamers specific for glycated hemoglobin and total hemoglobin using on-chip SELEX. , 2015, Lab on a chip.

[68]  Jin-Woo Choi,et al.  A novel in-plane passive microfluidic mixer with modified Tesla structures. , 2004, Lab on a chip.

[69]  Ilaria Palchetti,et al.  Nucleic acid and peptide aptamers: fundamentals and bioanalytical aspects. , 2012, Angewandte Chemie.

[70]  I. Ges,et al.  Electrochemical detection of catecholamine release using planar iridium oxide electrodes in nanoliter microfluidic cell culture volumes. , 2012, Biosensors & bioelectronics.

[71]  Hsin I. Lin,et al.  An integrated microfluidic system for C-reactive protein measurement. , 2009, Biosensors & bioelectronics.

[72]  Yee-Wai Cheung,et al.  Aptamer-mediated Plasmodium-specific diagnosis of malaria. , 2017, Biochimie.

[73]  Samie R Jaffrey,et al.  Fluorescent RNA Aptamers as a Tool to Study RNA-Modifying Enzymes. , 2016, Cell chemical biology.

[74]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[75]  H. T. Soh,et al.  Closed-loop control of circulating drug levels in live animals , 2017, Nature Biomedical Engineering.

[76]  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.

[77]  Chih-Ming Ho,et al.  A self-pumping lab-on-a-chip for rapid detection of botulinum toxin. , 2010, Lab on a chip.

[78]  Alex Toftgaard Nielsen,et al.  Comparative study on aptamers as recognition elements for antibiotics in a label-free all-polymer biosensor. , 2013, Biosensors & bioelectronics.

[79]  Yanling Song,et al.  Portable visual quantitative detection of aflatoxin B1 using a target-responsive hydrogel and a distance-readout microfluidic chip. , 2016, Lab on a chip.

[80]  Yair Glick,et al.  DNA Bipedal Motor Achieves a Large Number of Steps Due to Operation Using Microfluidics-Based Interface. , 2017, ACS nano.

[81]  L. Fu,et al.  Microfluidic Mixing: A Review , 2011, International journal of molecular sciences.

[82]  D. Weitz,et al.  Convection-Driven Pull-Down Assays in Nanoliter Droplets Using Scaffolded Aptamers. , 2017, Analytical chemistry.

[83]  Gabriel P López,et al.  Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation. , 2015, Lab on a chip.

[84]  Seung Soo Oh,et al.  In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release. , 2013, ACS nano.

[85]  Vitor B. Pinheiro,et al.  Catalysts from synthetic genetic polymers , 2014, Nature.

[86]  Baoquan Ding,et al.  A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo , 2018, Nature Biotechnology.

[87]  J. Goodchild Conjugates of oligonucleotides and modified oligonucleotides: a review of their synthesis and properties. , 1990, Bioconjugate chemistry.

[88]  I M Sokolov,et al.  Directed particle diffusion under "burnt bridges" conditions. , 2001, Physical review. E, Statistical, nonlinear, and soft matter physics.

[89]  Simon Chi-Chin Shiu,et al.  Aptamer Display on Diverse DNA Polyhedron Supports , 2018, Molecules.

[90]  A. Abate,et al.  Ultrahigh-throughput screening in drop-based microfluidics for directed evolution , 2010, Proceedings of the National Academy of Sciences.

[91]  A. Kinghorn,et al.  Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection , 2015, Molecules.

[92]  Qiao Lin,et al.  microfluidic affinity sensor for the detection of cocaine , 2009 .

[93]  A. Griffiths,et al.  Selection of ribozymes that catalyse multiple-turnover Diels-Alder cycloadditions by using in vitro compartmentalization. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Weihong Tan,et al.  Enrichment of cancer cells using aptamers immobilized on a microfluidic channel. , 2009, Analytical chemistry.

[95]  Ronald A. Li,et al.  Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers. , 2016, Analytical chemistry.

[96]  Jeong-Suong Yang,et al.  Microfluidic biochips for simple impedimetric detection of thrombin based on label-free DNA aptamers , 2016, BioChip Journal.

[97]  A. Mirzabekov,et al.  Chemical methods of DNA and RNA fluorescent labeling. , 1996, Nucleic acids research.

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

[99]  A. Turberfield,et al.  A DNA-fuelled molecular machine made of DNA , 2022 .

[100]  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.

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

[102]  S. Lunte,et al.  Chapter 1 Principles of capillary electrophoresis , 1996 .

[103]  Maria Minunni,et al.  Non-SELEX isolation of DNA aptamers for the homogeneous-phase fluorescence anisotropy sensing of tau Proteins. , 2018, Analytica chimica acta.

[104]  P. Yager,et al.  Diffusion-based extraction in a microfabricated device , 1997 .

[105]  Yun Zhang,et al.  Using the Rubik's Cube to directly produce paper analytical devices for quantitative point-of-care aptamer-based assays. , 2017, Biosensors & bioelectronics.

[106]  Lixue Wang,et al.  Detection of single tumor cell resistance with aptamer biochip. , 2012, Oncology letters.

[107]  David G. Gorenstein,et al.  Aptamers and the next generation of diagnostic reagents , 2012, Proteomics. Clinical applications.

[108]  Shenguang Ge,et al.  Photoelectrochemical lab-on-paper device based on an integrated paper supercapacitor and internal light source. , 2013, Analytical chemistry.

[109]  Homayoun Najjaran,et al.  Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications , 2015, Sensors.

[110]  Jie Chao,et al.  DNA Hydrogel with Aptamer-Toehold-Based Recognition, Cloaking, and Decloaking of Circulating Tumor Cells for Live Cell Analysis. , 2017, Nano letters.

[111]  Weihong Tan,et al.  Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. , 2012, Analytical chemistry.

[112]  W. Duan,et al.  Selection of DNA aptamers against epithelial cell adhesion molecule for cancer cell imaging and circulating tumor cell capture. , 2013, Analytical chemistry.

[113]  S. Quake,et al.  Microfluidics: Fluid physics at the nanoliter scale , 2005 .

[114]  Andrew D Griffiths,et al.  A completely in vitro ultrahigh-throughput droplet-based microfluidic screening system for protein engineering and directed evolution. , 2012, Lab on a chip.

[115]  Xuexia Lin,et al.  Oxygen-induced cell migration and on-line monitoring biomarkers modulation of cervical cancers on a microfluidic system , 2015, Scientific Reports.

[116]  Lei Zheng,et al.  Aptamer-Based Technologies in Foodborne Pathogen Detection , 2016, Front. Microbiol..

[117]  N. Seeman Nucleic acid junctions and lattices. , 1982, Journal of theoretical biology.

[118]  Eleanor A. L. Bagg,et al.  Emulsion PCR significantly improves nonequilibrium capillary electrophoresis of equilibrium mixtures-based aptamer selection: allowing for efficient and rapid selection of aptamer to unmodified ABH2 protein. , 2015, Analytical chemistry.

[119]  A dual-functional microfluidic chip for on-line detection of interleukin-8 based on rolling circle amplification. , 2018, Biosensors & bioelectronics.

[120]  Paul I. Okagbare,et al.  Highly efficient capture and enumeration of low abundance prostate cancer cells using prostate‐specific membrane antigen aptamers immobilized to a polymeric microfluidic device , 2009, Electrophoresis.

[121]  A. Ferré-D’Amaré,et al.  Structural basis for activity of highly efficient RNA mimics of green fluorescent protein , 2014, Nature Structural &Molecular Biology.

[122]  Wei-Hua Huang,et al.  A micropillar‐integrated smart microfluidic device for specific capture and sorting of cells , 2007, Electrophoresis.

[123]  Wenjiao Song,et al.  Using Spinach-based sensors for fluorescence imaging of intracellular metabolites and proteins in living bacteria , 2013, Nature Protocols.

[124]  Nicholas O Fischer,et al.  Single microbead SELEX for efficient ssDNA aptamer generation against botulinum neurotoxin. , 2008, Chemical communications.

[125]  François Lagugné-Labarthet,et al.  Microfluidic channel with embedded SERS 2D platform for the aptamer detection of ochratoxin A , 2013, Analytical and Bioanalytical Chemistry.

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

[127]  H. Craighead,et al.  Microfluidic Device for Aptamer-Based Cancer Cell Capture and Genetic Mutation Detection. , 2018, Analytical chemistry.

[128]  Giacomo Musile,et al.  An aptamer‐based paper microfluidic device for the colorimetric determination of cocaine , 2018, Electrophoresis.

[129]  Sergey N Krylov,et al.  Non-SELEX: selection of aptamers without intermediate amplification of candidate oligonucleotides , 2006, Nature Protocols.

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

[131]  D. Hayes,et al.  The measurement and therapeutic implications of circulating tumour cells in breast cancer , 2005, British Journal of Cancer.

[132]  M. Koupenova,et al.  Adenosine, Adenosine Receptors and Their Role in Glucose Homeostasis and Lipid Metabolism , 2013, Journal of cellular physiology.

[133]  Zhengbo Chen,et al.  Aptamer biosensor for label-free impedance spectroscopy detection of thrombin based on gold nanoparticles , 2011 .

[134]  A. Turberfield,et al.  A free-running DNA motor powered by a nicking enzyme. , 2005, Angewandte Chemie.

[135]  Simon Chi-Chin Shiu,et al.  Aptamer‐Mediated Protein Molecular Recognition Driving a DNA Tweezer Nanomachine , 2017, Advanced biosystems.

[136]  Shuping Xu,et al.  Aptamer-based surface-enhanced Raman scattering-microfluidic sensor for sensitive and selective polychlorinated biphenyls detection. , 2015, Analytical chemistry.

[137]  Yun Zhang,et al.  Naked-eye quantitative aptamer-based assay on paper device. , 2016, Biosensors & bioelectronics.

[138]  A. A. Modestov,et al.  Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood , 2015, Molecular therapy : the journal of the American Society of Gene Therapy.

[139]  James W. Jorgenson,et al.  Zone electrophoresis in open-tubular glass capillaries , 1981 .

[140]  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.

[141]  L. Millner,et al.  Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes. , 2013, Annals of clinical and laboratory science.

[142]  D. Shangguan,et al.  Aptamers evolved from live cells as effective molecular probes for cancer study , 2006, Proceedings of the National Academy of Sciences.

[143]  Eric P. Hoffman,et al.  Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy , 2015, Proceedings of the National Academy of Sciences.

[144]  A. Roget,et al.  Synthesis and use of labelled nucleoside phosphoramidite building blocks bearing a reporter group: biotinyl, dinitrophenyl, pyrenyl and dansyl. , 1989, Nucleic acids research.

[145]  Shawn M. Douglas,et al.  A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads , 2012, Science.

[146]  Julian A. Tanner,et al.  Structural basis for discriminatory recognition of Plasmodium lactate dehydrogenase by a DNA aptamer , 2013, Proceedings of the National Academy of Sciences.

[147]  Jinghua Yu,et al.  A microfluidic origami electrochemiluminescence aptamer-device based on a porous Au-paper electrode and a phenyleneethynylene derivative. , 2013, Chemical communications.

[148]  Zeynep Altintas,et al.  A fully automated microfluidic-based electrochemical sensor for real-time bacteria detection. , 2018, Biosensors & bioelectronics.

[149]  M. Gu,et al.  High‐sensitivity detection of oxytetracycline using light scattering agglutination assay with aptasensor , 2010, Electrophoresis.

[150]  Muhammad H. Zaman,et al.  Continuous flow microfluidic solution for quantitative analysis of active pharmaceutical ingredient content and kinetic release , 2015 .

[151]  D. Meldrum,et al.  On-chip isotachophoresis separation of functional DNA origami capture nanoarrays from cell lysate , 2013, Nano Research.

[152]  E. Gragoudas,et al.  Pegaptanib for neovascular age-related macular degeneration. , 2004, The New England journal of medicine.

[153]  Andrew B Kinghorn,et al.  APTEC: aptamer-tethered enzyme capture as a novel rapid diagnostic test for malaria. , 2015, Chemical communications.

[154]  Wade W Grabow,et al.  Fluorescent monitoring of RNA assembly and processing using the split-spinach aptamer. , 2015, ACS synthetic biology.

[155]  R. Hanson The Role of ATP in Metabolism , 1989 .

[156]  G. Mayer The chemical biology of aptamers. , 2009, Angewandte Chemie.

[157]  Yuejun Kang,et al.  Multiplexed Biomolecular Detection Based on Single Nanoparticles Immobilized on Pneumatically Controlled Microfluidic Chip , 2014, Plasmonics.

[158]  D C Ward,et al.  Enzymatic synthesis of biotin-labeled polynucleotides: novel nucleic acid affinity probes. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[159]  Yi Liu,et al.  Enhanced and Differential Capture of Circulating Tumor Cells from Lung Cancer Patients by Microfluidic Assays Using Aptamer Cocktail. , 2016, Small.

[160]  Andrew D. Ellington,et al.  Surface-immobilized aptamers for cancer cell isolation and microscopic cytology. , 2010, Cancer research.

[161]  Hong Shen,et al.  Study on sensing strategy and performance of a microfluidic chemiluminescence aptazyme sensor. , 2016, Talanta.

[162]  Marwa Selmi,et al.  Optimization of microfluidic biosensor efficiency by means of fluid flow engineering , 2017, Scientific Reports.

[163]  Zhi Zhu,et al.  Design and synthesis of target-responsive aptamer-cross-linked hydrogel for visual quantitative detection of ochratoxin A. , 2015, ACS applied materials & interfaces.

[164]  L. Pavesi,et al.  Sensitivity and Limit of detection of biosensors based on ring resonators , 2015, 2015 XVIII AISEM Annual Conference.

[165]  Michael Musheev,et al.  Nonequilibrium capillary electrophoresis of equilibrium mixtures: a universal tool for development of aptamers. , 2005, Journal of the American Chemical Society.

[166]  P. Rothemund Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[167]  Jon Ashley,et al.  Selection of bovine catalase aptamers using non‐SELEX , 2012, Electrophoresis.

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

[169]  R. Veedu,et al.  Nucleic acid aptamers against biotoxins: a new paradigm toward the treatment and diagnostic approach. , 2012, Nucleic acid therapeutics.