基于功能化纳米材料的生物传感器设计及在生物医学中的应用
|
摘要
随着全世界癌症病人患者的不断增多以及晚期疾病诊断导致的死亡人数的增加，生物传感器在早起癌症诊断中扮演了重要的作用。对生物医学领域的超灵敏甚至单分子检测变得越来越重要，如血液中的某些蛋白质含量的增加可能意味着肿瘤的发生，microRNA含量的增加或减少可能导致多种疾病的发生。近年来，科学家探索了纳米材料的很多优良的物理和化学性质，纳米材料在疾病标记物检测方面的应用催生了一系列超灵敏检测方法。纳米技术的产生为超灵敏生物传感器打开了新的途径，见证了基于纳米材料的生物传感器的快速发展及新的优势。纳米金，石墨烯，碳纳米管和DNA纳米结构在生物传感器的设计与发展产生了重要影响。一系列基于功能化纳米材料的生物传感器为临床诊断，环境检测，食品安全做出重要贡献。
本论文将纳米材料与DNA纳米技术相结合，分别制备了基于纳米金和纳米银SERS探针，石墨烯，DNA Origami的生物传感器，实现对多种生物分子的高灵敏和多元分析。主要内容如下：
1.基于DNA Origami的逻辑门设计及在RNA诊断中的应用
以DNA Origami为构架，设计了用于分析microRNA的逻辑门。逻辑门有三个组成部分：输入模块，计算模块和输出模块。输入模块将microRNA作为输入信号，计算模块分析输入信号并将结果传递给输出模块，输出模块将计算结果显示出来。使用原子力显微镜实现了对逻辑门计算结果和microRNA诊断结果的可视化检测。
2.基于Au-Ag SERS探针的制备用于病毒DNA的高灵敏度和多元检测
制备了具有nanogap的双金属Au-Ag SERS探针，用于病毒DNA的高灵敏度检测和多元DNA分析。另外，这种探针可以分别使用荧光分子和巯基小分子作为拉曼分子，增加了多元检测和成像的应用前景。
3.基于氧化石墨烯的纳米探针制备及用于癌症标志物AFP的检测。制备了酶-GO复合物，得到高吸附量的酶-GO复合物探针。GO表面的高吸附量酶可以通过标准动力学实验和CD光谱测定。证明了酶在吸附GO后仍然保持原有的活性和三维结构。另外，证明了基于GO的纳米探针用于高灵敏度的检测AFP。
With the growing number of cancer cases being diagnosed worldwide and theincreased number of fatalities due to late disease detection, biosensors can play animportant role in the early diagnosis of cancer.It has become more and moreimportant for highly sensitive and quantitative detection of biomolecules associatedwith human diseases. For example, the increase concentration of some proteins inblood may indicate cancer disease; the decrease or increase of microRNAconcentration may lead to many diseases. Recently, the application of nanomaterialsto detect disease biomarkers is giving rise to ultrasensitive assays, with scientistsexploiting the many advantageous physical and chemical properties ofnanomaterials. The emergence of nanotechnology is opening new horizons forbiosensor, with recent years witnessing the development and advantages of avariety of nanomaterial-based biosensors.These biosensors based nanoparticles,graphene oxide, carbon nanotubes and DNA nanostructures have already made amajor impact on clinical diagnostics, environment monitoring and food safety.
Here, by combining DNA nanotechnology and functionalized nanomaterials, wedesigned several biosensor based on DNA Origami, graphene oxide, AuNPs andAgNPs SERS probes for highly sensitive and multiplexing detection of variousbiomolecules.
1． Design of logic gates based on DNA Origami for microRNA diagnostics.
We designed logic gates based on DNA Origami nanostructures formicroRNA diagnostics. The logic gates are composed of three modules:input module, computation module and output module. The inputmodule use microRNAs as the inputs of logic gates. The computationmodule analyzes the input signal and transduces the results to the output module. The output module will display the results of the logic gates. Weuse atomic force microscope to observe the computation results andmicroRNA diagnostics visually.
2． Highly sensitive and multiplex detection of virus DNAs using Au-Ag SERSprobes.
We prepared Au-Ag SERS probes with interior nanogaps for highlysensitive and multiplex detection of virus DNAs. Fluorescence dyes andsmall organic molecules with thiol could be used raman tags for the SERSprobes, which could be applied in multiplex detection and imaging.
3． Graphene-based nanoprobes and a prototype optical biosensing platform.
We have demonstrated that GO can be used for the preparation ofenzyme conjugates with high active-enzyme loadings per unit weight ofthe material. High-efficiency loading of enzymes onto the GO surface wasconfirmed by the characterization using standard kinetic assays and CDspectroscopy, demonstrating that the enzymes retained their nativeactivity and3D structure after adsorbing onto GO. Furthermore, we havedemonstrated the fabrication of GO-based probes and their use for ahighly sensitive detection of AFP.
本论文将纳米材料与DNA纳米技术相结合，分别制备了基于纳米金和纳米银SERS探针，石墨烯，DNA Origami的生物传感器，实现对多种生物分子的高灵敏和多元分析。主要内容如下：
1.基于DNA Origami的逻辑门设计及在RNA诊断中的应用
以DNA Origami为构架，设计了用于分析microRNA的逻辑门。逻辑门有三个组成部分：输入模块，计算模块和输出模块。输入模块将microRNA作为输入信号，计算模块分析输入信号并将结果传递给输出模块，输出模块将计算结果显示出来。使用原子力显微镜实现了对逻辑门计算结果和microRNA诊断结果的可视化检测。
2.基于Au-Ag SERS探针的制备用于病毒DNA的高灵敏度和多元检测
制备了具有nanogap的双金属Au-Ag SERS探针，用于病毒DNA的高灵敏度检测和多元DNA分析。另外，这种探针可以分别使用荧光分子和巯基小分子作为拉曼分子，增加了多元检测和成像的应用前景。
3.基于氧化石墨烯的纳米探针制备及用于癌症标志物AFP的检测。制备了酶-GO复合物，得到高吸附量的酶-GO复合物探针。GO表面的高吸附量酶可以通过标准动力学实验和CD光谱测定。证明了酶在吸附GO后仍然保持原有的活性和三维结构。另外，证明了基于GO的纳米探针用于高灵敏度的检测AFP。
With the growing number of cancer cases being diagnosed worldwide and theincreased number of fatalities due to late disease detection, biosensors can play animportant role in the early diagnosis of cancer.It has become more and moreimportant for highly sensitive and quantitative detection of biomolecules associatedwith human diseases. For example, the increase concentration of some proteins inblood may indicate cancer disease; the decrease or increase of microRNAconcentration may lead to many diseases. Recently, the application of nanomaterialsto detect disease biomarkers is giving rise to ultrasensitive assays, with scientistsexploiting the many advantageous physical and chemical properties ofnanomaterials. The emergence of nanotechnology is opening new horizons forbiosensor, with recent years witnessing the development and advantages of avariety of nanomaterial-based biosensors.These biosensors based nanoparticles,graphene oxide, carbon nanotubes and DNA nanostructures have already made amajor impact on clinical diagnostics, environment monitoring and food safety.
Here, by combining DNA nanotechnology and functionalized nanomaterials, wedesigned several biosensor based on DNA Origami, graphene oxide, AuNPs andAgNPs SERS probes for highly sensitive and multiplexing detection of variousbiomolecules.
1． Design of logic gates based on DNA Origami for microRNA diagnostics.
We designed logic gates based on DNA Origami nanostructures formicroRNA diagnostics. The logic gates are composed of three modules:input module, computation module and output module. The inputmodule use microRNAs as the inputs of logic gates. The computationmodule analyzes the input signal and transduces the results to the output module. The output module will display the results of the logic gates. Weuse atomic force microscope to observe the computation results andmicroRNA diagnostics visually.
2． Highly sensitive and multiplex detection of virus DNAs using Au-Ag SERSprobes.
We prepared Au-Ag SERS probes with interior nanogaps for highlysensitive and multiplex detection of virus DNAs. Fluorescence dyes andsmall organic molecules with thiol could be used raman tags for the SERSprobes, which could be applied in multiplex detection and imaging.
3． Graphene-based nanoprobes and a prototype optical biosensing platform.
We have demonstrated that GO can be used for the preparation ofenzyme conjugates with high active-enzyme loadings per unit weight ofthe material. High-efficiency loading of enzymes onto the GO surface wasconfirmed by the characterization using standard kinetic assays and CDspectroscopy, demonstrating that the enzymes retained their nativeactivity and3D structure after adsorbing onto GO. Furthermore, we havedemonstrated the fabrication of GO-based probes and their use for ahighly sensitive detection of AFP.
引文
1. Pelaz, B., et al., The State of Nanoparticle-Based Nanoscience andBiotechnology: Progress, Promises, and Challenges. ACS Nano,2012.6(10):p.8468-8483.
2. Wang, J. and X. Qu, Recent progress in nanosensors for sensitive detection ofbiomolecules. Nanoscale,2013.5(9): p.3589-3600.
3. Kumar, P.S., et al., High-yield synthesis and optical response of goldnanostars. Nanotechnology,2008.19(1): p.015606.
4. Aili, D., et al., Hybrid Nanoparticle Liposome Detection of PhospholipaseActivity. Nano Letters,2010.11(4): p.1401-1405.
5. Gupta, S., et al., Kinase-Actuated Immunoaggregation of Peptide-ConjugatedGold Nanoparticles. Small,2010.6(14): p.1509-1513.
6. Giljohann, D.A., et al., Gold Nanoparticles for Biology and Medicine.Angewandte Chemie International Edition,2010.49(19): p.3280-3294.
7. Medley, C.D., et al., Gold Nanoparticle-Based Colorimetric Assay for theDirect Detection of Cancerous Cells. Analytical Chemistry,2008.80(4): p.1067-1072.
8. Wang, X., et al., The gold-nanoparticle-based surface plasmon resonancelight scattering and visual DNA aptasensor for lysozyme. Analytical andBioanalytical Chemistry,2011.400(7): p.2085-2091.
9. Rodríguez-Lorenzo, L., et al., Plasmonic nanosensors with inverse sensitivityby means of enzyme-guided crystal growth. Nat Mater,2012.11(7): p.604-607.
10. de la Rica, R. and M.M. Stevens, Plasmonic ELISA for the ultrasensitivedetection of disease biomarkers with the naked eye. Nat Nano,2012.7(12):p.821-824.
11. Yamamichi, J., et al., Single-step, label-free quantification of antibody inhuman serum for clinical applications based on localized surface plasmonresonance. Nanomedicine: Nanotechnology, Biology and Medicine,2011.7(6): p.889-895.
12. Guo, L. and D.-H. Kim, LSPR biomolecular assay with high sensitivityinduced by aptamer–antigen–antibody sandwich complex. Biosensors andBioelectronics,2012.31(1): p.567-570.
13. Inci, F., et al., Nanoplasmonic Quantitative Detection of Intact Viruses fromUnprocessed Whole Blood. ACS Nano,2013.7(6): p.4733-4745.
14. Otte, M.A., et al., Improved Biosensing Capability with Novel SuspendedNanodisks. The Journal of Physical Chemistry C,2011.115(13): p.5344-5351.
15. Polavarapu, L. and L.M. Liz-Marzan, Towards low-cost flexible substrates fornanoplasmonic sensing. Physical Chemistry Chemical Physics,2013.15(15): p.5288-5300.
16. DuVal, D. and L.M. Lechuga, Breakthroughs in Photonics2012:2012Breakthroughs in Lab-on-a-Chip and Optical Biosensors. Photonics Journal,IEEE,2013.5(2): p.0700906-0700906.
17. Tang, L., J. Casas, and M. Venkataramasubramani, Magnetic NanoparticleMediated Enhancement of Localized Surface Plasmon Resonance forUltrasensitive Bioanalytical Assay in Human Blood Plasma. AnalyticalChemistry,2012.85(3): p.1431-1439.
18. Chen, J.-Y. and Y.-C. Chen, A label-free sensing method for phosphopeptidesusing two-layer gold nanoparticle-based localized surface plasma resonancespectroscopy. Analytical and Bioanalytical Chemistry,2011.399(3): p.1173-1180.
19. Jeanmaire, D.L. and R.P. Van Duyne, Surface raman spectroelectrochemistry:Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on theanodized silver electrode. Journal of Electroanalytical Chemistry andInterfacial Electrochemistry,1977.84(1): p.1-20.
20. Rodríguez-Lorenzo, L., et al., Zeptomol Detection Through ControlledUltrasensitive Surface-Enhanced Raman Scattering. Journal of theAmerican Chemical Society,2009.131(13): p.4616-4618.
21. Shafer-Peltier, K.E., et al., Toward a Glucose Biosensor Based onSurface-Enhanced Raman Scattering. Journal of the American ChemicalSociety,2002.125(2): p.588-593.
22. Stuart, D.A., et al., In Vivo Glucose Measurement by Surface-EnhancedRaman Spectroscopy. Analytical Chemistry,2006.78(20): p.7211-7215.
23. Ma, K., et al., In Vivo, Transcutaneous Glucose Sensing UsingSurface-Enhanced Spatially Offset Raman Spectroscopy: Multiple Rats,Improved Hypoglycemic Accuracy, Low Incident Power, and ContinuousMonitoring for Greater than17Days. Analytical Chemistry,2011.83(23): p.9146-9152.
24. Barhoumi, A., et al., Surface-Enhanced Raman Spectroscopy of DNA. Journalof the American Chemical Society,2008.130(16): p.5523-5529.
25. Cho, H., et al., Label-free and highly sensitive biomolecular detection usingSERS and electrokinetic preconcentration. Lab on a Chip,2009.9(23): p.3360-3363.
26. Papadopoulou, E. and S.E.J. Bell, Label-Free Detection of Single-BaseMismatches in DNA by Surface-Enhanced Raman Spectroscopy. AngewandteChemie International Edition,2011.50(39): p.9058-9061.
27. Ock, K., et al., Real-Time Monitoring of Glutathione-Triggered ThiopurineAnticancer Drug Release in Live Cells Investigated by Surface-EnhancedRaman Scattering. Analytical Chemistry,2012.84(5): p.2172-2178.
28. Kang, B., et al., Exploiting the Nanoparticle Plasmon Effect: Observing DrugDelivery Dynamics in Single Cells via Raman/Fluorescence ImagingSpectroscopy. ACS Nano,2013.7(8): p.7420-7427.
29. Jin, R., et al., Glass-Bead-Based Parallel Detection of DNA Using CompositeRaman Labels. Small,2006.2(3): p.375-380.
30. Faulds, K., et al., Quantitative Simultaneous Multianalyte Detection of DNAby Dual-Wavelength Surface-Enhanced Resonance Raman Scattering.Angewandte Chemie International Edition,2007.46(11): p.1829-1831.
31. Kang, T., et al., Patterned Multiplex Pathogen DNA Detection by AuParticle-on-Wire SERS Sensor. Nano Letters,2010.10(4): p.1189-1193.
32. Xu, S., et al., Immunoassay using probe-labelling immunogold nanoparticleswith silver staining enhancement via surface-enhanced Raman scattering.Analyst,2004.129(1): p.63-68.
33. Wang, G., et al., Detection of the Potential Pancreatic Cancer Marker MUC4in Serum Using Surface-Enhanced Raman Scattering. Analytical Chemistry,2011.83(7): p.2554-2561.
34. Chen, Z., et al., Protein microarrays with carbon nanotubes as multicolorRaman labels. Nat Biotech,2008.26(11): p.1285-1292.
35. Hwang, H., et al., Optoelectrofluidic Sandwich Immunoassays for Detectionof Human Tumor Marker Using Surface-Enhanced Raman Scattering.Analytical Chemistry,2010.82(18): p.7603-7610.
36. Sha, M.Y., et al., Surface-Enhanced Raman Scattering Tags for Rapid andHomogeneous Detection of Circulating Tumor Cells in the Presence ofHuman Whole Blood. Journal of the American Chemical Society,2008.130(51): p.17214-17215.
37. Zavaleta, C.L., et al., Multiplexed imaging of surface enhanced Ramanscattering nanotags in living mice using noninvasive Raman spectroscopy.Proceedings of the National Academy of Sciences,2009.106(32): p.13511-13516.
38. Qian, X., et al., In vivo tumor targeting and spectroscopic detection withsurface-enhanced Raman nanoparticle tags. Nat Biotech,2008.26(1): p.83-90.
39. Stone, N., et al., Surface enhanced spatially offset Raman spectroscopic(SESORS) imaging-the next dimension. Chemical Science,2011.2(4): p.776-780.
40. Kircher, M.F., et al., A brain tumor molecular imaging strategy using a newtriple-modality MRI-photoacoustic-Raman nanoparticle. Nat Med,2012.18(5): p.829-834.
41. Samanta, A., et al., Ultrasensitive Near-Infrared Raman Reporters forSERS-Based In Vivo Cancer Detection. Angewandte Chemie InternationalEdition,2011.50(27): p.6089-6092.
42. Mirkin, C.A., et al., A DNA-based method for rationally assemblingnanoparticles into macroscopic materials. Nature,1996.382(6592): p.607-609.
43. Taton, T.A., C.A. Mirkin, and R.L. Letsinger, Scanometric DNA ArrayDetection with Nanoparticle Probes. Science,2000.289(5485): p.1757-1760.
44. Kim, D., W.L. Daniel, and C.A. Mirkin, Microarray-Based MultiplexedScanometric Immunoassay for Protein Cancer Markers Using GoldNanoparticle Probes. Analytical Chemistry,2009.81(21): p.9183-9187.
45. Alhasan, A.H., et al., Scanometric MicroRNA Array Profiling of ProstateCancer Markers Using Spherical Nucleic Acid–Gold Nanoparticle Conjugates.Analytical Chemistry,2012.84(9): p.4153-4160.
46. Seeman, N.C., DNA in a material world. Nature,2003.421(6921): p.427-431.
47. Seeman, N.C., Nucleic acid junctions and lattices. Journal of TheoreticalBiology,1982.99(2): p.237-247.
48. Mao, C., W. Sun, and N.C. Seeman, Designed Two-Dimensional DNA HollidayJunction Arrays Visualized by Atomic Force Microscopy. Journal of theAmerican Chemical Society,1999.121(23): p.5437-5443.
49. Yan, H., et al., A robust DNA mechanical device controlled by hybridizationtopology. Nature,2002.415(6867): p.62-65.
50. Dietz, H., S.M. Douglas, and W.M. Shih, Folding DNA into Twisted andCurved Nanoscale Shapes. Science,2009.325(5941): p.725-730.
51. Voigt, N.V., et al., Single-molecule chemical reactions on DNA origami. NatNano,2010.5(3): p.200-203.
52. Song, S., et al., Gold-Nanoparticle-Based Multicolor Nanobeacons forSequence-Specific DNA Analysis. Angewandte Chemie International Edition,2009.48(46): p.8670-8674.
53. Pei, H., et al., Designed Diblock Oligonucleotide for the Synthesis of SpatiallyIsolated and Highly Hybridizable Functionalization of DNA–GoldNanoparticle Nanoconjugates. Journal of the American Chemical Society,2012.134(29): p.11876-11879.
54. Suzuki, K., K. Hosokawa, and M. Maeda, Controlling the Number andPositions of Oligonucleotides on Gold Nanoparticle Surfaces. Journal of theAmerican Chemical Society,2009.131(22): p.7518-7519.
55. Josephs, E.A. and T. Ye, A Single-Molecule View of Conformational Switchingof DNA Tethered to a Gold Electrode. Journal of the American ChemicalSociety,2012.134(24): p.10021-10030.
56. Kimura-Suda, H., et al., Base-Dependent Competitive Adsorption ofSingle-Stranded DNA on Gold. Journal of the American Chemical Society,2003.125(30): p.9014-9015.
57. Herne, T.M. and M.J. Tarlov, Characterization of DNA Probes Immobilized onGold Surfaces. Journal of the American Chemical Society,1997.119(38): p.8916-8920.
58. Fan, C., K.W. Plaxco, and A.J. Heeger, Electrochemical interrogation ofconformational changes as a reagentless method for the sequence-specificdetection of DNA. Proceedings of the National Academy of Sciences,2003.100(16): p.9134-9137.
59. Liu, G., et al., An Enzyme-Based E-DNA Sensor for Sequence-SpecificDetection of Femtomolar DNA Targets. Journal of the American ChemicalSociety,2008.130(21): p.6820-6825.
60. Wei, F., et al., Electrochemical detection of low-copy number salivary RNAbased on specific signal amplification with a hairpin probe. Nucleic AcidsResearch,2008.36(11): p. e65.
61. Wen, Y., et al., DNA Nanostructure-based Interfacial engineering forPCR-free ultrasensitive electrochemical analysis of microRNA. Sci. Rep.,2012.2.
62. Wen, Y., et al., DNA Nanostructure-Decorated Surfaces for EnhancedAptamer-Target Binding and Electrochemical Cocaine Sensors. AnalyticalChemistry,2011.83(19): p.7418-7423.
63. Pei, H., et al., Regenerable electrochemical immunological sensing at DNAnanostructure-decorated gold surfaces. Chemical Communications,2011.47(22): p.6254-6256.
64. Ge, Z., et al., Electrochemical single nucleotide polymorphisms genotypingon surface immobilized three-dimensional branched DNA nanostructure.Science China Chemistry,2011.54(8): p.1273-1276.
65. Bu, N.-N., et al., Tetrahedron-structured DNA and functional oligonucleotidefor construction of an electrochemical DNA-based biosensor. ChemicalCommunications,2011.47(27): p.7689-7691.
66. Bu, N.-N., et al., Electrochemiluminescent biosensor of ATP usingtetrahedron structured DNA and a functional oligonucleotide forRu(phen)3 2+intercalation and target identification. Biosensors andBioelectronics,2013.43(0): p.200-204.
67. Zhao, Z., et al., Encapsulation of Gold Nanoparticles in a DNA Origami Cage.Angewandte Chemie International Edition,2011.50(9): p.2041-2044.
68. Ke, Y., et al., Self-Assembled Water-Soluble Nucleic Acid Probe Tiles forLabel-Free RNA Hybridization Assays. Science,2008.319(5860): p.180-183.
69. Qian, L., et al., Analogic China map constructed by DNA. Chinese ScienceBulletin,2006.51(24): p.2973-2976.
70. Zhang, Z., et al., Asymmetric DNA Origami for Spatially Addressable andIndex-Free Solution-Phase DNA Chips. Advanced Materials,2010.22(24): p.2672-2675.
71. Zhang, Z., et al., A DNA-Origami Chip Platform for Label-Free SNPGenotyping Using Toehold-Mediated Strand Displacement. Small,2010.6(17): p.1854-1858.
72. Subramanian, H.K.K., et al., The Label-Free Unambiguous Detection andSymbolic Display of Single Nucleotide Polymorphisms on DNA Origami.Nano Letters,2011.11(2): p.910-913.
73. Goodman, R.P., et al., Reconfigurable, braced, three-dimensional DNAnanostructures. Nat Nano,2008.3(2): p.93-96.
74. Pei, H., et al., Reconfigurable Three-Dimensional DNA Nanostructures forthe Construction of Intracellular Logic Sensors. Angewandte ChemieInternational Edition,2012.51(36): p.9020-9024.
75. Kuzuya, A., et al., Nanomechanical DNA origami 'single-molecule beacons'directly imaged by atomic force microscopy. Nat Commun,2011.2: p.449.
76. Mei, Q., et al., Stability of DNA Origami Nanoarrays in Cell Lysate. NanoLetters,2011.11(4): p.1477-1482.
77. Li, J., et al., Self-Assembled Multivalent DNA Nanostructures for NoninvasiveIntracellular Delivery of Immunostimulatory CpG Oligonucleotides. ACSNano,2011.5(11): p.8783-8789.
78. Walsh, A.S., et al., DNA Cage Delivery to Mammalian Cells. ACS Nano,2011.5(7): p.5427-5432.
79. Modi, S., et al., A DNA nanomachine that maps spatial and temporal pHchanges inside living cells. Nat Nano,2009.4(5): p.325-330.
80. Surana, S., et al., An autonomous DNA nanomachine maps spatiotemporalpH changes in a multicellular living organism. Nat Commun,2011.2: p.340.
81. Moshe, M., J. Elbaz, and I. Willner, Sensing of UO22+and Design of LogicGates by the Application of Supramolecular Constructs of Ion-DependentDNAzymes. Nano Letters,2009.9(3): p.1196-1200.
82. Elbaz, J., et al., pH-Programmable DNA Logic Arrays Powered by ModularDNAzyme Libraries. Nano Letters,2012.12(12): p.6049-6054.
83. Weizmann, Y., et al., Autonomous Fueled Mechanical Replication of NucleicAcid Templates for the Amplified Optical Detection of DNA. AngewandteChemie International Edition,2006.45(14): p.2238-2242.
84. Hemphill, J. and A. Deiters, DNA Computation in Mammalian Cells:MicroRNA Logic Operations. Journal of the American Chemical Society,2013.135(28): p.10512-10518.
85. Bennett, C., The thermodynamics of computation—a review. InternationalJournal of Theoretical Physics,1982.21(12): p.905-940.
86. Adleman, L.M., Molecular Computation Of Solutions To CombinatorialProblems. Science,1994.266(5187): p.1021-1024.
87. Lipton, R.J., DNA Solution Of Hard Computational Problems. Science,1995.268(5210): p.542-545.
88. Benenson, Y., et al., Programmable and autonomous computing machinemade of biomolecules. Nature,2001.414(6862): p.430-434.
89. Braich, R.S., et al., Solution of a20-variable3-SAT problem on a DNAcomputer. Science,2002.296(5567): p.499-502.
90. Benenson, Y., et al., DNA molecule provides a computing machine with bothdata and fuel. Proceedings of the National Academy of Sciences of theUnited States of America,2003.100(5): p.2191-2196.
91. Adar, R., et al., Stochastic computing with biomolecular automata.Proceedings of the National Academy of Sciences of the United States ofAmerica,2004.101(27): p.9960-9965.
92. Macdonald, J., et al., Medium scale integration of molecular logic gates in anautomaton. Nano Letters,2006.6(11): p.2598-2603.
93. Benenson, Y., et al., An autonomous molecular computer for logical controlof gene expression. Nature,2004.429(6990): p.423-429.
94. Seelig, G., et al., Enzyme-free nucleic acid logic circuits. Science,2006.314(5805): p.1585-1588.
95. Wang, J., Electrochemical biosensors: Towards point-of-care cancerdiagnostics. Biosensors&Bioelectronics,2006.21(10): p.1887-1892.
96. Rinaudo, K., et al., A universal RNAi-based logic evaluator that operates inmammalian cells. Nature Biotechnology,2007.25(7): p.795-801.
97. Win, M.N. and C.D. Smolke, Higher-Order Cellular Information Processingwith Synthetic RNA Devices. Science,2008.322(5900): p.456-460.
98. Benenson, Y., Biocomputers: from test tubes to live cells. MolecularBiosystems,2009.5(7): p.675-685.
99. Xie, Z., et al., Logic integration of mRNA signals by an RNAi-based molecularcomputer. Nucleic Acids Research,2010.38(8): p.2692-2701.
100. de Silva, A.P. and N.D. McClenaghan, Molecular-scale logic gates.Chemistry-a European Journal,2004.10(3): p.574-586.
101. Penchovsky, R. and R.R. Breaker, Computational design and experimentalvalidation of oligonucleotide-sensing allosteric ribozymes. NatureBiotechnology,2005.23(11): p.1424-1433.
102. Baron, R., et al., Elementary arithmetic operations by enzymes: A model formetabolic pathway based computing. Angewandte Chemie-InternationalEdition,2006.45(10): p.1572-1576.
103. Baron, R., et al., Logic gates and elementary computing by enzymes. Journalof Physical Chemistry A,2006.110(27): p.8548-8553.
104. Macdonald, J., D. Stefanovic, and M.N. Stojanovic, Solution-phasemolecular-scale computation with deoxyribozyme-based logic gates andfluorescent readouts, in Methods in Molecular Biology, V.V. Didenko, Editor.2006. p.343-363.
105. Strack, G., et al., Boolean logic gates that use enzymes as input signals.Chembiochem,2008.9(8): p.1260-1266.
106. Zhou, J., et al., Enzyme-Based NAND and NOR Logic Gates with ModularDesign. Journal of Physical Chemistry B,2009.113(49): p.16065-16070.
107. Parker, J., Computing with DNA-Although DNA clearly outclasses anysilicon-based computer when it comes to information storage andprocessing speed, a DNA-based PC is still a long way off. Embo Reports,2003.4(1): p.7-10.
108. Mao, C.D., et al., Logical computation using algorithmic self-assembly ofDNA triple-crossover molecules. Nature,2000.407(6803): p.493-496.
109. Rothemund, P.W.K., N. Papadakis, and E. Winfree, Algorithmic self-assemblyof DNA Sierpinski triangles. Plos Biology,2004.2(12): p.2041-2053.
110. An, C.I., V.B. Trinh, and Y. Yokobayashi, Artificial control of gene expressionin mammalian cells by modulating RNA interference through aptamer-smallmolecule interaction. Rna-a Publication of the Rna Society,2006.12(5): p.710-716.
111. Simmel, F.C., Towards biomedical applications for nucleic acid nanodevices.Nanomedicine,2007.2(6): p.817-830.
112. Teller, C., S. Shimron, and I. Willner, Aptamer-DNAzyme Hairpins forAmplified Biosensing. Analytical Chemistry,2009.81(21): p.9114-9119.
113. Culler, S.J., K.G. Hoff, and C.D. Smolke, Reprogramming Cellular Behaviorwith RNA Controllers Responsive to Endogenous Proteins. Science,2010.330(6008): p.1251-1255.
114. Shi, J., et al., Nanotechnology in Drug Delivery and Tissue Engineering: FromDiscovery to Applications. Nano Letters,2010.10(9): p.3223-3230.
115. Zhou, M., et al., Aptamer-Controlled Biofuel Cells in Logic Systems and Usedas Self-Powered and Intelligent Logic Aptasensors. Journal of the AmericanChemical Society,2010.132(7): p.2172-+.
116. Gil, B., et al., Detection of Multiple Disease Indicators by an AutonomousBiomolecular Computer. Nano Letters,2011.11(7): p.2989-2996.
1. Adleman, L.M., Molecular computation of solutions to combinatorial problems. Science,1994.266(5187): p.1021-4.
2. Lipton, R.J., DNA Solution Of Hard Computational Problems. Science,1995.268(5210):p.542-545.
3. Ouyang, Q., et al., DNA solution of the maximal clique problem. Science,1997.278(5337): p.446-449.
4. Gil, B., et al., Detection of Multiple Disease Indicators by an Autonomous BiomolecularComputer. Nano Letters,2011.11(7): p.2989-2996.
5. Chen, J.H. and D.H. Wood, Computation with biomolecules. Proceedings of theNational Academy of Sciences of the United States of America,2000.97(4): p.1328-1330.
6. Benenson, Y., et al., Programmable and autonomous computing machine made ofbiomolecules. Nature,2001.414(6862): p.430-434.
7. Adar, R., et al., Stochastic computing with biomolecular automata. Proceedings of theNational Academy of Sciences of the United States of America,2004.101(27): p.9960-9965.
8. Benenson, Y., et al., An autonomous molecular computer for logical control of geneexpression. Nature,2004.429(6990): p.423-429.
9. Rinaudo, K., et al., A universal RNAi-based logic evaluator that operates in mammaliancells. Nature Biotechnology,2007.25(7): p.795-801.
10. Konry, T. and D.R. Walt, Intelligent Medical Diagnostics via Molecular Logic. Journal ofthe American Chemical Society,2009.131(37): p.13232-+.
11. Hemphill, J. and A. Deiters, DNA Computation in Mammalian Cells: MicroRNA LogicOperations. Journal of the American Chemical Society,2013.135(28): p.10512-10518.
12. Rothemund, P.W.K., Folding DNA to create nanoscale shapes and patterns. Nature,2006.440(7082): p.297-302.
13. Fu, Y., et al., Single-Step Rapid Assembly of DNA Origami Nanostructures forAddressable Nanoscale Bioreactors. Journal of the American Chemical Society,2013.135(2): p.696-702.
14. Douglas, S.M., I. Bachelet, and G.M. Church, A Logic-Gated Nanorobot for TargetedTransport of Molecular Payloads. Science,2012.335(6070): p.831-834.
15. Ke, Y., et al., Self-assembled water-soluble nucleic acid probe tiles for label-free RNAhybridization assays. Science,2008.319(5860): p.180-183.
16. Pinheiro, A.V., et al., Challenges and opportunities for structural DNA nanotechnology.Nature Nanotechnology,2011.6(12): p.763-772.
17. Kuzyk, A., et al., DNA-based self-assembly of chiral plasmonic nanostructures withtailored optical response. Nature,2012.483(7389): p.311-314.
18. Shen, J., S.A. Stass, and F. Jiang, MicroRNAs as potential biomarkers in human solidtumors. Cancer Letters,2013.329(2): p.125-136.
19. Bartel, D.P., MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell,2004.116(2): p.281-297.
20. Bentwich, I., et al., Identification of hundreds of conserved and nonconserved humanmicroRNAs. Nature Genetics,2005.37(7): p.766-770.
21. Berezikov, E., et al., Phylogenetic shadowing and computational identification ofhuman microRNA genes. Cell,2005.120(1): p.21-24.
22. Thum, T., et al., MicroRNAs in the human heart-A clue to fetal gene reprogramming inheart failure. Circulation,2007.116(3): p.258-267.
23. van Rooij, E., et al., A signature pattern of stress-responsive microRNAs that can evokecardiac hypertrophy and heart failure. Proceedings of the National Academy ofSciences of the United States of America,2006.103(48): p.18255-18260.
24. Sharma, J., et al., DNA-tile-directed self-assembly of quantum dots intotwo-dimensional nanopatterns. Angewandte Chemie-International Edition,2008.47(28): p.5157-5159.
25. Zhang, Z., et al., Asymmetric DNA Origami for Spatially Addressable and Index-FreeSolution-Phase DNA Chips. Advanced Materials,2010.22(24): p.2672-+.
26. Wong, N.Y., et al., Nano-Encrypted Morse Code: A Versatile Approach to Programmableand Reversible Nanoscale Assembly and Disassembly. Journal of the AmericanChemical Society,2013.135(8): p.2931-2934.
27. Wickham, S.F.J., et al., Direct observation of stepwise movement of a syntheticmolecular transporter. Nature Nanotechnology,2011.6(3): p.166-169.
28. Wickham, S.F.J., et al., A DNA-based molecular motor that can navigate a network oftracks. Nature Nanotechnology,2012.7(3): p.169-173.
29. Gu, H., et al., A proximity-based programmable DNA nanoscale assembly line. Nature,2010.465(7295): p.202-U86.
1. A map of human genome sequence variation containing1.42million single nucleotidepolymorphisms. Nature,2001.409(6822): p.928-933.
2. Li, H., et al., Ultrasensitive Coincidence Fluorescence Detection of Single DNAMolecules. Analytical Chemistry,2003.75(7): p.1664-1670.
3. Wittwer, C.T., et al., Real-time multiplex PCR assays. Methods,2001.25(4): p.430-442.
4. Menzies, A.C., The Raman effect. Nature,1930.125: p.205-207.
5. Fabian, H. and P. Anzenbacher, New Developments In Raman-Spectroscopy OfBiological-Systems. Vibrational Spectroscopy,1993.4(2): p.125-148.
6. Song, S.P., et al., Functional nanoprobes for ultrasensitive detection of biomolecules.Chemical Society Reviews,2010.39(11): p.4234-4243.
7. Schatz, G.C., Theoretical-Studies Of Surface Enhanced Raman-Scattering. Accounts ofChemical Research,1984.17(10): p.370-376.
8. Otto, A., et al., Surface-Enhanced Raman-Scattering. Journal of Physics-CondensedMatter,1992.4(5): p.1143-1212.
9. Fleischmann, M., P.J. Hendra, and McQuilla.Aj, Raman-Spectra Of Pyridine Adsorbed AtA Silver Electrode. Chemical Physics Letters,1974.26(2): p.163-166.
10. Kneipp, K., et al., Single Molecule Detection Using Surface-Enhanced Raman Scattering(SERS). Physical Review Letters,1997.78(9): p.1667-1670.
11. Nie, S. and S.R. Emory, Probing Single Molecules and Single Nanoparticles bySurface-Enhanced Raman Scattering. Science,1997.275(5303): p.1102-1106.
12. Etchegoin, P.G. and E.C. Le Ru, A perspective on single molecule SERS: current statusand future challenges. Physical Chemistry Chemical Physics,2008.10(40): p.6079-6089.
13. Blackie, E.J., E.C.L. Ru, and P.G. Etchegoin, Single-Molecule Surface-Enhanced RamanSpectroscopy of Nonresonant Molecules. Journal of the American Chemical Society,2009.131(40): p.14466-14472.
14. Lim, D.-K., et al., Nanogap-engineerable Raman-active nanodumbbells forsingle-molecule detection. Nat Mater,2010.9(1): p.60-67.
15. Wang, Y., B. Yan, and L. Chen, SERS Tags: Novel Optical Nanoprobes for Bioanalysis.Chemical Reviews,2012.113(3): p.1391-1428.
16. Jiang, et al., Single Molecule Raman Spectroscopy at the Junctions of Large AgNanocrystals. The Journal of Physical Chemistry B,2003.107(37): p.9964-9972.
17. Lee, S.J., A.R. Morrill, and M. Moskovits, Hot Spots in Silver Nanowire Bundles forSurface-Enhanced Raman Spectroscopy. Journal of the American Chemical Society,2006.128(7): p.2200-2201.
18. Li, W., et al., Dimers of Silver Nanospheres: Facile Synthesis and Their Use as Hot Spotsfor Surface-Enhanced Raman Scattering. Nano Letters,2008.9(1): p.485-490.
19. Qian, X.M. and S.M. Nie, Single-molecule and single-nanoparticle SERS: fromfundamental mechanisms to biomedical applications. Chemical Society Reviews,2008.37(5): p.912-920.
20. Ou, F.S., et al., Hot-Spot Engineering in Polygonal Nanofinger Assemblies for SurfaceEnhanced Raman Spectroscopy. Nano Letters,2011.11(6): p.2538-2542.
21. Talley, C.E., et al., Surface-Enhanced Raman Scattering from Individual AuNanoparticles and Nanoparticle Dimer Substrates. Nano Letters,2005.5(8): p.1569-1574.
22. Camden, J.P., et al., Probing the Structure of Single-Molecule Surface-Enhanced RamanScattering Hot Spots. Journal of the American Chemical Society,2008.130(38): p.12616-12617.
23. McMahon, J.M., et al., Modeling the Effect of Small Gaps in Surface-Enhanced RamanSpectroscopy. The Journal of Physical Chemistry C,2011.116(2): p.1627-1637.
24. Liusman, C., et al., Surface-Enhanced Raman Scattering of Ag–Au NanodiskHeterodimers. The Journal of Physical Chemistry C,2012.116(18): p.10390-10395.
25. Lee, S., et al., Fabrication of SERS-fluorescence dual modal nanoprobes and applicationto multiplex cancer cell imaging. Nanoscale,2012.4(1): p.124-129.
26. Fang, Y., N.-H. Seong, and D.D. Dlott, Measurement of the Distribution of SiteEnhancements in Surface-Enhanced Raman Scattering. Science,2008.321(5887): p.388-392.
27. Song, S., et al., Gold-Nanoparticle-Based Multicolor Nanobeacons for Sequence-SpecificDNA Analysis. Angewandte Chemie,2009.121(46): p.8826-8830.
28. Im, H., et al., Vertically Oriented Sub-10-nm Plasmonic Nanogap Arrays. Nano Letters,2010.10(6): p.2231-2236.
29. Lim, D.-K., et al., Highly uniform and reproducible surface-enhanced Raman scatteringfrom DNA-tailorable nanoparticles with1-nm interior gap. Nat Nano,2011.6(7): p.452-460.
30. Xie, W., et al., Synthesis of Bifunctional Au/Pt/Au Core/Shell Nanoraspberries for in SituSERS Monitoring of Platinum-Catalyzed Reactions. Journal of the American ChemicalSociety,2011.133(48): p.19302-19305.
31. Pei, H., et al., Designed Diblock Oligonucleotide for the Synthesis of Spatially Isolatedand Highly Hybridizable Functionalization of DNA–Gold Nanoparticle Nanoconjugates.Journal of the American Chemical Society,2012.134(29): p.11876-11879.
32. Rivas, L., et al., Mixed Silver/Gold Colloids: A Study of Their Formation, Morphology,and Surface-Enhanced Raman Activity. Langmuir,2000.16(25): p.9722-9728.
33. Rycenga, M., et al., Controlling the Synthesis and Assembly of Silver Nanostructures forPlasmonic Applications. Chemical Reviews,2011.111(6): p.3669-3712.
34. Shen, A., et al., Triplex Au–Ag–C Core–Shell Nanoparticles as a Novel Raman Label.Advanced Functional Materials,2010.20(6): p.969-975.
35. Li, J.-M., et al., Poly(styrene-co-acrylic acid) core and silver nanoparticle/silica shellcomposite microspheres as high performance surface-enhanced Raman spectroscopy(SERS) substrate and molecular barcode label. Journal of Materials Chemistry,2011.21(16): p.5992-5998.
36. Kong, X., et al., Synthesis and application of surface enhanced Raman scattering (SERS)tags of Ag@SiO2core/shell nanoparticles in protein detection. Journal of MaterialsChemistry,2012.22(16): p.7767-7774.
37. Li, J.-M., et al., Multiplexed SERS detection of DNA targets in a sandwich-hybridizationassay using SERS-encoded core-shell nanospheres. Journal of Materials Chemistry,2012.22(24): p.12100-12106.
38. Wang, Z., et al., SERS-Fluorescence Joint Spectral Encoding Using Organic–Metal–QDHybrid Nanoparticles with a Huge Encoding Capacity for High-Throughput Biodetection:Putting Theory into Practice. Journal of the American Chemical Society,2012.134(6): p.2993-3000.
1. Novoselov, K.S., et al., Electric field effect in atomically thin carbon films. Science,2004.306(5696): p.666-669.
2. Zhang, Y.B., et al., Experimental observation of the quantum Hall effect and Berry'sphase in graphene. Nature,2005.438(7065): p.201-204.
3. Avouris, P., Z. Chen, and V. Perebeinos, Carbon-based electronics. NatureNanotechnology,2007.2(10): p.605-615.
4. Balandin, A.A., et al., Superior thermal conductivity of single-layer graphene. NanoLetters,2008.8(3): p.902-907.
5. Lee, C., et al., Measurement of the elastic properties and intrinsic strength of monolayergraphene. Science,2008.321(5887): p.385-388.
6. Castro Neto, A.H., et al., The electronic properties of graphene. Reviews of ModernPhysics,2009.81(1): p.109-162.
7. Bonaccorso, F., et al., Graphene photonics and optoelectronics. Nature Photonics,2010.4(9): p.611-622.
8. Schwierz, F., Graphene transistors. Nature Nanotechnology,2010.5(7): p.487-496.
9. Yun, W., et al., Selective immobilization of tris(2,2'-bipyridyl)ruthenium (II) onto arrayelectrode for solid-state electrochemiluminescene sensor fabrication. Sensors andActuators B-Chemical,2009.141(1): p.244-248.
10. Yun, W., et al., Solid-state electrochemiluminescence sensor through the electrodepositionof Ru(bpy)(3)(2+)/AuNPs/chitosan composite film onto electrode. Analytica ChimicaActa,2009.635(1): p.58-62.
11. Geim, A.K., Graphene: Status and Prospects. Science,2009.324(5934): p.1530-1534.
12. Wang, Y., et al., Graphene and graphene oxide: biofunctionalization and applications inbiotechnology. Trends in Biotechnology,2011.29(5): p.205-212.
13. Sun, X., et al., Nano-Graphene Oxide for Cellular Imaging and Drug Delivery. NanoResearch,2008.1(3): p.203-212.
14. He, S., et al., A Graphene Nanoprobe for Rapid, Sensitive, and Multicolor FluorescentDNA Analysis. Advanced Functional Materials,2010.20(3): p.453-459.
15. Wang, Y., et al., Aptamer/Graphene Oxide Nanocomplex for in Situ Molecular Probing inLiving Cells. Journal of the American Chemical Society,2010.132(27): p.9274-9276.
16. Niemeyer, C.M., Nanoparticles, proteins, and nucleic acids: Biotechnology meetsmaterials science. Angewandte Chemie-International Edition,2001.40(22): p.4128-4158.
17. Kitano, H., Systems biology: A brief overview. Science,2002.295(5560): p.1662-1664.
18. Welsh, J.B., et al., Analysis of gene expression profiles in normal and neoplastic ovariantissue samples identifies candidate molecular markers of epithelial ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America,2001.98(3): p.1176-1181.
19. Wilson, D.S. and S. Nock, Recent developments in protein microarray technology.Angewandte Chemie-International Edition,2003.42(5): p.494-500.
20. Ludwig, J.A. and J.N. Weinstein, Biomarkers in cancer staging, prognosis and treatmentselection. Nature Reviews Cancer,2005.5(11): p.845-856.
21. Yu, X., et al., Carbon nanotube amplification strategies for highly sensitiveimmunodetection of cancer biomarkers. Journal of the American Chemical Society,2006.128(34): p.11199-11205.
22. Zhang, H., et al., Ultrasensitive assays for proteins. Analyst,2007.132(8): p.724-737.
23. Giljohann, D.A. and C.A. Mirkin, Drivers of biodiagnostic development. Nature,2009.462(7272): p.461-464.
24. Song, S., et al., Functional nanoprobes for ultrasensitive detection of biomolecules.Chemical Society Reviews,2010.39(11): p.4234-4243.
25. Zhang, Q., et al., Nanotube-Based Colorimetric Probe for Ultrasensitive Detection ofAtaxia Telangiectasia Mutated Protein. Analytical Chemistry,2011.83(23): p.9191-9196.
26. Lin, Y.H., et al., Glucose biosensors based on carbon nanotube nanoelectrode ensembles.Nano Letters,2004.4(2): p.191-195.
27. Lee, Y.M., et al., Immobilization of horseradish peroxidase on multi-wall carbonnanotubes and its electrochemical properties. Biotechnology Letters,2006.28(1): p.39-43.
28. Li, D., et al., Processable aqueous dispersions of graphene nanosheets. NatureNanotechnology,2008.3(2): p.101-105.
29. Li, J., et al., Enzyme-based multi-component optical nanoprobes for sequence-specificdetection of DNA hybridization. Advanced Materials,2008.20(3): p.497-+.
30. Sperling, R.A., et al., Biological applications of gold nanoparticles. Chemical SocietyReviews,2008.37(9): p.1896-1908.
31. Giljohann, D.A., et al., Gold Nanoparticles for Biology and Medicine. AngewandteChemie-International Edition,2010.49(19): p.3280-3294.
32. Wang, J., G.D. Liu, and M.R. Jan, Ultrasensitive electrical biosensing of proteins andDNA: Carbon-nanotube derived amplification of the recognition and transduction events.Journal of the American Chemical Society,2004.126(10): p.3010-3011.
33. Wan, Y., et al., Carbon nanotube-based ultrasensitive multiplexing electrochemicalimmunosensor for cancer biomarkers. Biosensors&Bioelectronics,2011.30(1): p.93-99.
34. Hummers, W.S. and R.E. Offeman, Preparation Of Graphitic Oxide. Journal of theAmerican Chemical Society,1958.80(6): p.1339-1339.
35. Zhang, J., et al., Graphene Oxide as a Matrix for Enzyme Immobilization. Langmuir,2010.26(9): p.6083-6085.
36. Asuri, P., et al., Structure, function, and stability of enzymes covalently attached tosingle-walled carbon nanotubes. Langmuir,2007.23(24): p.12318-12321.
37. Park, S. and R.S. Ruoff, Chemical methods for the production of graphenes. NatureNanotechnology,2009.4(4): p.217-224.
38. Tung, V.C., et al., High-throughput solution processing of large-scale graphene. NatureNanotechnology,2009.4(1): p.25-29.
39. Zhang, Y., et al., Assembly of Graphene Oxide-Enzyme Conjugates through HydrophobicInteraction. Small,2012.8(1): p.154-159.
40. Silverton, E.W., M.A. Navia, and D.R. Davies,3-Dimensional Structure Of An IntactHuman Immunoglobulin. Proceedings of the National Academy of Sciences of the UnitedStates of America,1977.74(11): p.5140-5144.
41. Droz, E., et al., Influence Of Surface And Protein Modification On Immunoglobulin-GAdsorption Observed By Scanning Force Microscopy. Biophysical Journal,1994.67(3): p.1316-1323.
2. Wang, J. and X. Qu, Recent progress in nanosensors for sensitive detection ofbiomolecules. Nanoscale,2013.5(9): p.3589-3600.
3. Kumar, P.S., et al., High-yield synthesis and optical response of goldnanostars. Nanotechnology,2008.19(1): p.015606.
4. Aili, D., et al., Hybrid Nanoparticle Liposome Detection of PhospholipaseActivity. Nano Letters,2010.11(4): p.1401-1405.
5. Gupta, S., et al., Kinase-Actuated Immunoaggregation of Peptide-ConjugatedGold Nanoparticles. Small,2010.6(14): p.1509-1513.
6. Giljohann, D.A., et al., Gold Nanoparticles for Biology and Medicine.Angewandte Chemie International Edition,2010.49(19): p.3280-3294.
7. Medley, C.D., et al., Gold Nanoparticle-Based Colorimetric Assay for theDirect Detection of Cancerous Cells. Analytical Chemistry,2008.80(4): p.1067-1072.
8. Wang, X., et al., The gold-nanoparticle-based surface plasmon resonancelight scattering and visual DNA aptasensor for lysozyme. Analytical andBioanalytical Chemistry,2011.400(7): p.2085-2091.
9. Rodríguez-Lorenzo, L., et al., Plasmonic nanosensors with inverse sensitivityby means of enzyme-guided crystal growth. Nat Mater,2012.11(7): p.604-607.
10. de la Rica, R. and M.M. Stevens, Plasmonic ELISA for the ultrasensitivedetection of disease biomarkers with the naked eye. Nat Nano,2012.7(12):p.821-824.
11. Yamamichi, J., et al., Single-step, label-free quantification of antibody inhuman serum for clinical applications based on localized surface plasmonresonance. Nanomedicine: Nanotechnology, Biology and Medicine,2011.7(6): p.889-895.
12. Guo, L. and D.-H. Kim, LSPR biomolecular assay with high sensitivityinduced by aptamer–antigen–antibody sandwich complex. Biosensors andBioelectronics,2012.31(1): p.567-570.
13. Inci, F., et al., Nanoplasmonic Quantitative Detection of Intact Viruses fromUnprocessed Whole Blood. ACS Nano,2013.7(6): p.4733-4745.
14. Otte, M.A., et al., Improved Biosensing Capability with Novel SuspendedNanodisks. The Journal of Physical Chemistry C,2011.115(13): p.5344-5351.
15. Polavarapu, L. and L.M. Liz-Marzan, Towards low-cost flexible substrates fornanoplasmonic sensing. Physical Chemistry Chemical Physics,2013.15(15): p.5288-5300.
16. DuVal, D. and L.M. Lechuga, Breakthroughs in Photonics2012:2012Breakthroughs in Lab-on-a-Chip and Optical Biosensors. Photonics Journal,IEEE,2013.5(2): p.0700906-0700906.
17. Tang, L., J. Casas, and M. Venkataramasubramani, Magnetic NanoparticleMediated Enhancement of Localized Surface Plasmon Resonance forUltrasensitive Bioanalytical Assay in Human Blood Plasma. AnalyticalChemistry,2012.85(3): p.1431-1439.
18. Chen, J.-Y. and Y.-C. Chen, A label-free sensing method for phosphopeptidesusing two-layer gold nanoparticle-based localized surface plasma resonancespectroscopy. Analytical and Bioanalytical Chemistry,2011.399(3): p.1173-1180.
19. Jeanmaire, D.L. and R.P. Van Duyne, Surface raman spectroelectrochemistry:Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on theanodized silver electrode. Journal of Electroanalytical Chemistry andInterfacial Electrochemistry,1977.84(1): p.1-20.
20. Rodríguez-Lorenzo, L., et al., Zeptomol Detection Through ControlledUltrasensitive Surface-Enhanced Raman Scattering. Journal of theAmerican Chemical Society,2009.131(13): p.4616-4618.
21. Shafer-Peltier, K.E., et al., Toward a Glucose Biosensor Based onSurface-Enhanced Raman Scattering. Journal of the American ChemicalSociety,2002.125(2): p.588-593.
22. Stuart, D.A., et al., In Vivo Glucose Measurement by Surface-EnhancedRaman Spectroscopy. Analytical Chemistry,2006.78(20): p.7211-7215.
23. Ma, K., et al., In Vivo, Transcutaneous Glucose Sensing UsingSurface-Enhanced Spatially Offset Raman Spectroscopy: Multiple Rats,Improved Hypoglycemic Accuracy, Low Incident Power, and ContinuousMonitoring for Greater than17Days. Analytical Chemistry,2011.83(23): p.9146-9152.
24. Barhoumi, A., et al., Surface-Enhanced Raman Spectroscopy of DNA. Journalof the American Chemical Society,2008.130(16): p.5523-5529.
25. Cho, H., et al., Label-free and highly sensitive biomolecular detection usingSERS and electrokinetic preconcentration. Lab on a Chip,2009.9(23): p.3360-3363.
26. Papadopoulou, E. and S.E.J. Bell, Label-Free Detection of Single-BaseMismatches in DNA by Surface-Enhanced Raman Spectroscopy. AngewandteChemie International Edition,2011.50(39): p.9058-9061.
27. Ock, K., et al., Real-Time Monitoring of Glutathione-Triggered ThiopurineAnticancer Drug Release in Live Cells Investigated by Surface-EnhancedRaman Scattering. Analytical Chemistry,2012.84(5): p.2172-2178.
28. Kang, B., et al., Exploiting the Nanoparticle Plasmon Effect: Observing DrugDelivery Dynamics in Single Cells via Raman/Fluorescence ImagingSpectroscopy. ACS Nano,2013.7(8): p.7420-7427.
29. Jin, R., et al., Glass-Bead-Based Parallel Detection of DNA Using CompositeRaman Labels. Small,2006.2(3): p.375-380.
30. Faulds, K., et al., Quantitative Simultaneous Multianalyte Detection of DNAby Dual-Wavelength Surface-Enhanced Resonance Raman Scattering.Angewandte Chemie International Edition,2007.46(11): p.1829-1831.
31. Kang, T., et al., Patterned Multiplex Pathogen DNA Detection by AuParticle-on-Wire SERS Sensor. Nano Letters,2010.10(4): p.1189-1193.
32. Xu, S., et al., Immunoassay using probe-labelling immunogold nanoparticleswith silver staining enhancement via surface-enhanced Raman scattering.Analyst,2004.129(1): p.63-68.
33. Wang, G., et al., Detection of the Potential Pancreatic Cancer Marker MUC4in Serum Using Surface-Enhanced Raman Scattering. Analytical Chemistry,2011.83(7): p.2554-2561.
34. Chen, Z., et al., Protein microarrays with carbon nanotubes as multicolorRaman labels. Nat Biotech,2008.26(11): p.1285-1292.
35. Hwang, H., et al., Optoelectrofluidic Sandwich Immunoassays for Detectionof Human Tumor Marker Using Surface-Enhanced Raman Scattering.Analytical Chemistry,2010.82(18): p.7603-7610.
36. Sha, M.Y., et al., Surface-Enhanced Raman Scattering Tags for Rapid andHomogeneous Detection of Circulating Tumor Cells in the Presence ofHuman Whole Blood. Journal of the American Chemical Society,2008.130(51): p.17214-17215.
37. Zavaleta, C.L., et al., Multiplexed imaging of surface enhanced Ramanscattering nanotags in living mice using noninvasive Raman spectroscopy.Proceedings of the National Academy of Sciences,2009.106(32): p.13511-13516.
38. Qian, X., et al., In vivo tumor targeting and spectroscopic detection withsurface-enhanced Raman nanoparticle tags. Nat Biotech,2008.26(1): p.83-90.
39. Stone, N., et al., Surface enhanced spatially offset Raman spectroscopic(SESORS) imaging-the next dimension. Chemical Science,2011.2(4): p.776-780.
40. Kircher, M.F., et al., A brain tumor molecular imaging strategy using a newtriple-modality MRI-photoacoustic-Raman nanoparticle. Nat Med,2012.18(5): p.829-834.
41. Samanta, A., et al., Ultrasensitive Near-Infrared Raman Reporters forSERS-Based In Vivo Cancer Detection. Angewandte Chemie InternationalEdition,2011.50(27): p.6089-6092.
42. Mirkin, C.A., et al., A DNA-based method for rationally assemblingnanoparticles into macroscopic materials. Nature,1996.382(6592): p.607-609.
43. Taton, T.A., C.A. Mirkin, and R.L. Letsinger, Scanometric DNA ArrayDetection with Nanoparticle Probes. Science,2000.289(5485): p.1757-1760.
44. Kim, D., W.L. Daniel, and C.A. Mirkin, Microarray-Based MultiplexedScanometric Immunoassay for Protein Cancer Markers Using GoldNanoparticle Probes. Analytical Chemistry,2009.81(21): p.9183-9187.
45. Alhasan, A.H., et al., Scanometric MicroRNA Array Profiling of ProstateCancer Markers Using Spherical Nucleic Acid–Gold Nanoparticle Conjugates.Analytical Chemistry,2012.84(9): p.4153-4160.
46. Seeman, N.C., DNA in a material world. Nature,2003.421(6921): p.427-431.
47. Seeman, N.C., Nucleic acid junctions and lattices. Journal of TheoreticalBiology,1982.99(2): p.237-247.
48. Mao, C., W. Sun, and N.C. Seeman, Designed Two-Dimensional DNA HollidayJunction Arrays Visualized by Atomic Force Microscopy. Journal of theAmerican Chemical Society,1999.121(23): p.5437-5443.
49. Yan, H., et al., A robust DNA mechanical device controlled by hybridizationtopology. Nature,2002.415(6867): p.62-65.
50. Dietz, H., S.M. Douglas, and W.M. Shih, Folding DNA into Twisted andCurved Nanoscale Shapes. Science,2009.325(5941): p.725-730.
51. Voigt, N.V., et al., Single-molecule chemical reactions on DNA origami. NatNano,2010.5(3): p.200-203.
52. Song, S., et al., Gold-Nanoparticle-Based Multicolor Nanobeacons forSequence-Specific DNA Analysis. Angewandte Chemie International Edition,2009.48(46): p.8670-8674.
53. Pei, H., et al., Designed Diblock Oligonucleotide for the Synthesis of SpatiallyIsolated and Highly Hybridizable Functionalization of DNA–GoldNanoparticle Nanoconjugates. Journal of the American Chemical Society,2012.134(29): p.11876-11879.
54. Suzuki, K., K. Hosokawa, and M. Maeda, Controlling the Number andPositions of Oligonucleotides on Gold Nanoparticle Surfaces. Journal of theAmerican Chemical Society,2009.131(22): p.7518-7519.
55. Josephs, E.A. and T. Ye, A Single-Molecule View of Conformational Switchingof DNA Tethered to a Gold Electrode. Journal of the American ChemicalSociety,2012.134(24): p.10021-10030.
56. Kimura-Suda, H., et al., Base-Dependent Competitive Adsorption ofSingle-Stranded DNA on Gold. Journal of the American Chemical Society,2003.125(30): p.9014-9015.
57. Herne, T.M. and M.J. Tarlov, Characterization of DNA Probes Immobilized onGold Surfaces. Journal of the American Chemical Society,1997.119(38): p.8916-8920.
58. Fan, C., K.W. Plaxco, and A.J. Heeger, Electrochemical interrogation ofconformational changes as a reagentless method for the sequence-specificdetection of DNA. Proceedings of the National Academy of Sciences,2003.100(16): p.9134-9137.
59. Liu, G., et al., An Enzyme-Based E-DNA Sensor for Sequence-SpecificDetection of Femtomolar DNA Targets. Journal of the American ChemicalSociety,2008.130(21): p.6820-6825.
60. Wei, F., et al., Electrochemical detection of low-copy number salivary RNAbased on specific signal amplification with a hairpin probe. Nucleic AcidsResearch,2008.36(11): p. e65.
61. Wen, Y., et al., DNA Nanostructure-based Interfacial engineering forPCR-free ultrasensitive electrochemical analysis of microRNA. Sci. Rep.,2012.2.
62. Wen, Y., et al., DNA Nanostructure-Decorated Surfaces for EnhancedAptamer-Target Binding and Electrochemical Cocaine Sensors. AnalyticalChemistry,2011.83(19): p.7418-7423.
63. Pei, H., et al., Regenerable electrochemical immunological sensing at DNAnanostructure-decorated gold surfaces. Chemical Communications,2011.47(22): p.6254-6256.
64. Ge, Z., et al., Electrochemical single nucleotide polymorphisms genotypingon surface immobilized three-dimensional branched DNA nanostructure.Science China Chemistry,2011.54(8): p.1273-1276.
65. Bu, N.-N., et al., Tetrahedron-structured DNA and functional oligonucleotidefor construction of an electrochemical DNA-based biosensor. ChemicalCommunications,2011.47(27): p.7689-7691.
66. Bu, N.-N., et al., Electrochemiluminescent biosensor of ATP usingtetrahedron structured DNA and a functional oligonucleotide forRu(phen)3 2+intercalation and target identification. Biosensors andBioelectronics,2013.43(0): p.200-204.
67. Zhao, Z., et al., Encapsulation of Gold Nanoparticles in a DNA Origami Cage.Angewandte Chemie International Edition,2011.50(9): p.2041-2044.
68. Ke, Y., et al., Self-Assembled Water-Soluble Nucleic Acid Probe Tiles forLabel-Free RNA Hybridization Assays. Science,2008.319(5860): p.180-183.
69. Qian, L., et al., Analogic China map constructed by DNA. Chinese ScienceBulletin,2006.51(24): p.2973-2976.
70. Zhang, Z., et al., Asymmetric DNA Origami for Spatially Addressable andIndex-Free Solution-Phase DNA Chips. Advanced Materials,2010.22(24): p.2672-2675.
71. Zhang, Z., et al., A DNA-Origami Chip Platform for Label-Free SNPGenotyping Using Toehold-Mediated Strand Displacement. Small,2010.6(17): p.1854-1858.
72. Subramanian, H.K.K., et al., The Label-Free Unambiguous Detection andSymbolic Display of Single Nucleotide Polymorphisms on DNA Origami.Nano Letters,2011.11(2): p.910-913.
73. Goodman, R.P., et al., Reconfigurable, braced, three-dimensional DNAnanostructures. Nat Nano,2008.3(2): p.93-96.
74. Pei, H., et al., Reconfigurable Three-Dimensional DNA Nanostructures forthe Construction of Intracellular Logic Sensors. Angewandte ChemieInternational Edition,2012.51(36): p.9020-9024.
75. Kuzuya, A., et al., Nanomechanical DNA origami 'single-molecule beacons'directly imaged by atomic force microscopy. Nat Commun,2011.2: p.449.
76. Mei, Q., et al., Stability of DNA Origami Nanoarrays in Cell Lysate. NanoLetters,2011.11(4): p.1477-1482.
77. Li, J., et al., Self-Assembled Multivalent DNA Nanostructures for NoninvasiveIntracellular Delivery of Immunostimulatory CpG Oligonucleotides. ACSNano,2011.5(11): p.8783-8789.
78. Walsh, A.S., et al., DNA Cage Delivery to Mammalian Cells. ACS Nano,2011.5(7): p.5427-5432.
79. Modi, S., et al., A DNA nanomachine that maps spatial and temporal pHchanges inside living cells. Nat Nano,2009.4(5): p.325-330.
80. Surana, S., et al., An autonomous DNA nanomachine maps spatiotemporalpH changes in a multicellular living organism. Nat Commun,2011.2: p.340.
81. Moshe, M., J. Elbaz, and I. Willner, Sensing of UO22+and Design of LogicGates by the Application of Supramolecular Constructs of Ion-DependentDNAzymes. Nano Letters,2009.9(3): p.1196-1200.
82. Elbaz, J., et al., pH-Programmable DNA Logic Arrays Powered by ModularDNAzyme Libraries. Nano Letters,2012.12(12): p.6049-6054.
83. Weizmann, Y., et al., Autonomous Fueled Mechanical Replication of NucleicAcid Templates for the Amplified Optical Detection of DNA. AngewandteChemie International Edition,2006.45(14): p.2238-2242.
84. Hemphill, J. and A. Deiters, DNA Computation in Mammalian Cells:MicroRNA Logic Operations. Journal of the American Chemical Society,2013.135(28): p.10512-10518.
85. Bennett, C., The thermodynamics of computation—a review. InternationalJournal of Theoretical Physics,1982.21(12): p.905-940.
86. Adleman, L.M., Molecular Computation Of Solutions To CombinatorialProblems. Science,1994.266(5187): p.1021-1024.
87. Lipton, R.J., DNA Solution Of Hard Computational Problems. Science,1995.268(5210): p.542-545.
88. Benenson, Y., et al., Programmable and autonomous computing machinemade of biomolecules. Nature,2001.414(6862): p.430-434.
89. Braich, R.S., et al., Solution of a20-variable3-SAT problem on a DNAcomputer. Science,2002.296(5567): p.499-502.
90. Benenson, Y., et al., DNA molecule provides a computing machine with bothdata and fuel. Proceedings of the National Academy of Sciences of theUnited States of America,2003.100(5): p.2191-2196.
91. Adar, R., et al., Stochastic computing with biomolecular automata.Proceedings of the National Academy of Sciences of the United States ofAmerica,2004.101(27): p.9960-9965.
92. Macdonald, J., et al., Medium scale integration of molecular logic gates in anautomaton. Nano Letters,2006.6(11): p.2598-2603.
93. Benenson, Y., et al., An autonomous molecular computer for logical controlof gene expression. Nature,2004.429(6990): p.423-429.
94. Seelig, G., et al., Enzyme-free nucleic acid logic circuits. Science,2006.314(5805): p.1585-1588.
95. Wang, J., Electrochemical biosensors: Towards point-of-care cancerdiagnostics. Biosensors&Bioelectronics,2006.21(10): p.1887-1892.
96. Rinaudo, K., et al., A universal RNAi-based logic evaluator that operates inmammalian cells. Nature Biotechnology,2007.25(7): p.795-801.
97. Win, M.N. and C.D. Smolke, Higher-Order Cellular Information Processingwith Synthetic RNA Devices. Science,2008.322(5900): p.456-460.
98. Benenson, Y., Biocomputers: from test tubes to live cells. MolecularBiosystems,2009.5(7): p.675-685.
99. Xie, Z., et al., Logic integration of mRNA signals by an RNAi-based molecularcomputer. Nucleic Acids Research,2010.38(8): p.2692-2701.
100. de Silva, A.P. and N.D. McClenaghan, Molecular-scale logic gates.Chemistry-a European Journal,2004.10(3): p.574-586.
101. Penchovsky, R. and R.R. Breaker, Computational design and experimentalvalidation of oligonucleotide-sensing allosteric ribozymes. NatureBiotechnology,2005.23(11): p.1424-1433.
102. Baron, R., et al., Elementary arithmetic operations by enzymes: A model formetabolic pathway based computing. Angewandte Chemie-InternationalEdition,2006.45(10): p.1572-1576.
103. Baron, R., et al., Logic gates and elementary computing by enzymes. Journalof Physical Chemistry A,2006.110(27): p.8548-8553.
104. Macdonald, J., D. Stefanovic, and M.N. Stojanovic, Solution-phasemolecular-scale computation with deoxyribozyme-based logic gates andfluorescent readouts, in Methods in Molecular Biology, V.V. Didenko, Editor.2006. p.343-363.
105. Strack, G., et al., Boolean logic gates that use enzymes as input signals.Chembiochem,2008.9(8): p.1260-1266.
106. Zhou, J., et al., Enzyme-Based NAND and NOR Logic Gates with ModularDesign. Journal of Physical Chemistry B,2009.113(49): p.16065-16070.
107. Parker, J., Computing with DNA-Although DNA clearly outclasses anysilicon-based computer when it comes to information storage andprocessing speed, a DNA-based PC is still a long way off. Embo Reports,2003.4(1): p.7-10.
108. Mao, C.D., et al., Logical computation using algorithmic self-assembly ofDNA triple-crossover molecules. Nature,2000.407(6803): p.493-496.
109. Rothemund, P.W.K., N. Papadakis, and E. Winfree, Algorithmic self-assemblyof DNA Sierpinski triangles. Plos Biology,2004.2(12): p.2041-2053.
110. An, C.I., V.B. Trinh, and Y. Yokobayashi, Artificial control of gene expressionin mammalian cells by modulating RNA interference through aptamer-smallmolecule interaction. Rna-a Publication of the Rna Society,2006.12(5): p.710-716.
111. Simmel, F.C., Towards biomedical applications for nucleic acid nanodevices.Nanomedicine,2007.2(6): p.817-830.
112. Teller, C., S. Shimron, and I. Willner, Aptamer-DNAzyme Hairpins forAmplified Biosensing. Analytical Chemistry,2009.81(21): p.9114-9119.
113. Culler, S.J., K.G. Hoff, and C.D. Smolke, Reprogramming Cellular Behaviorwith RNA Controllers Responsive to Endogenous Proteins. Science,2010.330(6008): p.1251-1255.
114. Shi, J., et al., Nanotechnology in Drug Delivery and Tissue Engineering: FromDiscovery to Applications. Nano Letters,2010.10(9): p.3223-3230.
115. Zhou, M., et al., Aptamer-Controlled Biofuel Cells in Logic Systems and Usedas Self-Powered and Intelligent Logic Aptasensors. Journal of the AmericanChemical Society,2010.132(7): p.2172-+.
116. Gil, B., et al., Detection of Multiple Disease Indicators by an AutonomousBiomolecular Computer. Nano Letters,2011.11(7): p.2989-2996.
1. Adleman, L.M., Molecular computation of solutions to combinatorial problems. Science,1994.266(5187): p.1021-4.
2. Lipton, R.J., DNA Solution Of Hard Computational Problems. Science,1995.268(5210):p.542-545.
3. Ouyang, Q., et al., DNA solution of the maximal clique problem. Science,1997.278(5337): p.446-449.
4. Gil, B., et al., Detection of Multiple Disease Indicators by an Autonomous BiomolecularComputer. Nano Letters,2011.11(7): p.2989-2996.
5. Chen, J.H. and D.H. Wood, Computation with biomolecules. Proceedings of theNational Academy of Sciences of the United States of America,2000.97(4): p.1328-1330.
6. Benenson, Y., et al., Programmable and autonomous computing machine made ofbiomolecules. Nature,2001.414(6862): p.430-434.
7. Adar, R., et al., Stochastic computing with biomolecular automata. Proceedings of theNational Academy of Sciences of the United States of America,2004.101(27): p.9960-9965.
8. Benenson, Y., et al., An autonomous molecular computer for logical control of geneexpression. Nature,2004.429(6990): p.423-429.
9. Rinaudo, K., et al., A universal RNAi-based logic evaluator that operates in mammaliancells. Nature Biotechnology,2007.25(7): p.795-801.
10. Konry, T. and D.R. Walt, Intelligent Medical Diagnostics via Molecular Logic. Journal ofthe American Chemical Society,2009.131(37): p.13232-+.
11. Hemphill, J. and A. Deiters, DNA Computation in Mammalian Cells: MicroRNA LogicOperations. Journal of the American Chemical Society,2013.135(28): p.10512-10518.
12. Rothemund, P.W.K., Folding DNA to create nanoscale shapes and patterns. Nature,2006.440(7082): p.297-302.
13. Fu, Y., et al., Single-Step Rapid Assembly of DNA Origami Nanostructures forAddressable Nanoscale Bioreactors. Journal of the American Chemical Society,2013.135(2): p.696-702.
14. Douglas, S.M., I. Bachelet, and G.M. Church, A Logic-Gated Nanorobot for TargetedTransport of Molecular Payloads. Science,2012.335(6070): p.831-834.
15. Ke, Y., et al., Self-assembled water-soluble nucleic acid probe tiles for label-free RNAhybridization assays. Science,2008.319(5860): p.180-183.
16. Pinheiro, A.V., et al., Challenges and opportunities for structural DNA nanotechnology.Nature Nanotechnology,2011.6(12): p.763-772.
17. Kuzyk, A., et al., DNA-based self-assembly of chiral plasmonic nanostructures withtailored optical response. Nature,2012.483(7389): p.311-314.
18. Shen, J., S.A. Stass, and F. Jiang, MicroRNAs as potential biomarkers in human solidtumors. Cancer Letters,2013.329(2): p.125-136.
19. Bartel, D.P., MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell,2004.116(2): p.281-297.
20. Bentwich, I., et al., Identification of hundreds of conserved and nonconserved humanmicroRNAs. Nature Genetics,2005.37(7): p.766-770.
21. Berezikov, E., et al., Phylogenetic shadowing and computational identification ofhuman microRNA genes. Cell,2005.120(1): p.21-24.
22. Thum, T., et al., MicroRNAs in the human heart-A clue to fetal gene reprogramming inheart failure. Circulation,2007.116(3): p.258-267.
23. van Rooij, E., et al., A signature pattern of stress-responsive microRNAs that can evokecardiac hypertrophy and heart failure. Proceedings of the National Academy ofSciences of the United States of America,2006.103(48): p.18255-18260.
24. Sharma, J., et al., DNA-tile-directed self-assembly of quantum dots intotwo-dimensional nanopatterns. Angewandte Chemie-International Edition,2008.47(28): p.5157-5159.
25. Zhang, Z., et al., Asymmetric DNA Origami for Spatially Addressable and Index-FreeSolution-Phase DNA Chips. Advanced Materials,2010.22(24): p.2672-+.
26. Wong, N.Y., et al., Nano-Encrypted Morse Code: A Versatile Approach to Programmableand Reversible Nanoscale Assembly and Disassembly. Journal of the AmericanChemical Society,2013.135(8): p.2931-2934.
27. Wickham, S.F.J., et al., Direct observation of stepwise movement of a syntheticmolecular transporter. Nature Nanotechnology,2011.6(3): p.166-169.
28. Wickham, S.F.J., et al., A DNA-based molecular motor that can navigate a network oftracks. Nature Nanotechnology,2012.7(3): p.169-173.
29. Gu, H., et al., A proximity-based programmable DNA nanoscale assembly line. Nature,2010.465(7295): p.202-U86.
1. A map of human genome sequence variation containing1.42million single nucleotidepolymorphisms. Nature,2001.409(6822): p.928-933.
2. Li, H., et al., Ultrasensitive Coincidence Fluorescence Detection of Single DNAMolecules. Analytical Chemistry,2003.75(7): p.1664-1670.
3. Wittwer, C.T., et al., Real-time multiplex PCR assays. Methods,2001.25(4): p.430-442.
4. Menzies, A.C., The Raman effect. Nature,1930.125: p.205-207.
5. Fabian, H. and P. Anzenbacher, New Developments In Raman-Spectroscopy OfBiological-Systems. Vibrational Spectroscopy,1993.4(2): p.125-148.
6. Song, S.P., et al., Functional nanoprobes for ultrasensitive detection of biomolecules.Chemical Society Reviews,2010.39(11): p.4234-4243.
7. Schatz, G.C., Theoretical-Studies Of Surface Enhanced Raman-Scattering. Accounts ofChemical Research,1984.17(10): p.370-376.
8. Otto, A., et al., Surface-Enhanced Raman-Scattering. Journal of Physics-CondensedMatter,1992.4(5): p.1143-1212.
9. Fleischmann, M., P.J. Hendra, and McQuilla.Aj, Raman-Spectra Of Pyridine Adsorbed AtA Silver Electrode. Chemical Physics Letters,1974.26(2): p.163-166.
10. Kneipp, K., et al., Single Molecule Detection Using Surface-Enhanced Raman Scattering(SERS). Physical Review Letters,1997.78(9): p.1667-1670.
11. Nie, S. and S.R. Emory, Probing Single Molecules and Single Nanoparticles bySurface-Enhanced Raman Scattering. Science,1997.275(5303): p.1102-1106.
12. Etchegoin, P.G. and E.C. Le Ru, A perspective on single molecule SERS: current statusand future challenges. Physical Chemistry Chemical Physics,2008.10(40): p.6079-6089.
13. Blackie, E.J., E.C.L. Ru, and P.G. Etchegoin, Single-Molecule Surface-Enhanced RamanSpectroscopy of Nonresonant Molecules. Journal of the American Chemical Society,2009.131(40): p.14466-14472.
14. Lim, D.-K., et al., Nanogap-engineerable Raman-active nanodumbbells forsingle-molecule detection. Nat Mater,2010.9(1): p.60-67.
15. Wang, Y., B. Yan, and L. Chen, SERS Tags: Novel Optical Nanoprobes for Bioanalysis.Chemical Reviews,2012.113(3): p.1391-1428.
16. Jiang, et al., Single Molecule Raman Spectroscopy at the Junctions of Large AgNanocrystals. The Journal of Physical Chemistry B,2003.107(37): p.9964-9972.
17. Lee, S.J., A.R. Morrill, and M. Moskovits, Hot Spots in Silver Nanowire Bundles forSurface-Enhanced Raman Spectroscopy. Journal of the American Chemical Society,2006.128(7): p.2200-2201.
18. Li, W., et al., Dimers of Silver Nanospheres: Facile Synthesis and Their Use as Hot Spotsfor Surface-Enhanced Raman Scattering. Nano Letters,2008.9(1): p.485-490.
19. Qian, X.M. and S.M. Nie, Single-molecule and single-nanoparticle SERS: fromfundamental mechanisms to biomedical applications. Chemical Society Reviews,2008.37(5): p.912-920.
20. Ou, F.S., et al., Hot-Spot Engineering in Polygonal Nanofinger Assemblies for SurfaceEnhanced Raman Spectroscopy. Nano Letters,2011.11(6): p.2538-2542.
21. Talley, C.E., et al., Surface-Enhanced Raman Scattering from Individual AuNanoparticles and Nanoparticle Dimer Substrates. Nano Letters,2005.5(8): p.1569-1574.
22. Camden, J.P., et al., Probing the Structure of Single-Molecule Surface-Enhanced RamanScattering Hot Spots. Journal of the American Chemical Society,2008.130(38): p.12616-12617.
23. McMahon, J.M., et al., Modeling the Effect of Small Gaps in Surface-Enhanced RamanSpectroscopy. The Journal of Physical Chemistry C,2011.116(2): p.1627-1637.
24. Liusman, C., et al., Surface-Enhanced Raman Scattering of Ag–Au NanodiskHeterodimers. The Journal of Physical Chemistry C,2012.116(18): p.10390-10395.
25. Lee, S., et al., Fabrication of SERS-fluorescence dual modal nanoprobes and applicationto multiplex cancer cell imaging. Nanoscale,2012.4(1): p.124-129.
26. Fang, Y., N.-H. Seong, and D.D. Dlott, Measurement of the Distribution of SiteEnhancements in Surface-Enhanced Raman Scattering. Science,2008.321(5887): p.388-392.
27. Song, S., et al., Gold-Nanoparticle-Based Multicolor Nanobeacons for Sequence-SpecificDNA Analysis. Angewandte Chemie,2009.121(46): p.8826-8830.
28. Im, H., et al., Vertically Oriented Sub-10-nm Plasmonic Nanogap Arrays. Nano Letters,2010.10(6): p.2231-2236.
29. Lim, D.-K., et al., Highly uniform and reproducible surface-enhanced Raman scatteringfrom DNA-tailorable nanoparticles with1-nm interior gap. Nat Nano,2011.6(7): p.452-460.
30. Xie, W., et al., Synthesis of Bifunctional Au/Pt/Au Core/Shell Nanoraspberries for in SituSERS Monitoring of Platinum-Catalyzed Reactions. Journal of the American ChemicalSociety,2011.133(48): p.19302-19305.
31. Pei, H., et al., Designed Diblock Oligonucleotide for the Synthesis of Spatially Isolatedand Highly Hybridizable Functionalization of DNA–Gold Nanoparticle Nanoconjugates.Journal of the American Chemical Society,2012.134(29): p.11876-11879.
32. Rivas, L., et al., Mixed Silver/Gold Colloids: A Study of Their Formation, Morphology,and Surface-Enhanced Raman Activity. Langmuir,2000.16(25): p.9722-9728.
33. Rycenga, M., et al., Controlling the Synthesis and Assembly of Silver Nanostructures forPlasmonic Applications. Chemical Reviews,2011.111(6): p.3669-3712.
34. Shen, A., et al., Triplex Au–Ag–C Core–Shell Nanoparticles as a Novel Raman Label.Advanced Functional Materials,2010.20(6): p.969-975.
35. Li, J.-M., et al., Poly(styrene-co-acrylic acid) core and silver nanoparticle/silica shellcomposite microspheres as high performance surface-enhanced Raman spectroscopy(SERS) substrate and molecular barcode label. Journal of Materials Chemistry,2011.21(16): p.5992-5998.
36. Kong, X., et al., Synthesis and application of surface enhanced Raman scattering (SERS)tags of Ag@SiO2core/shell nanoparticles in protein detection. Journal of MaterialsChemistry,2012.22(16): p.7767-7774.
37. Li, J.-M., et al., Multiplexed SERS detection of DNA targets in a sandwich-hybridizationassay using SERS-encoded core-shell nanospheres. Journal of Materials Chemistry,2012.22(24): p.12100-12106.
38. Wang, Z., et al., SERS-Fluorescence Joint Spectral Encoding Using Organic–Metal–QDHybrid Nanoparticles with a Huge Encoding Capacity for High-Throughput Biodetection:Putting Theory into Practice. Journal of the American Chemical Society,2012.134(6): p.2993-3000.
1. Novoselov, K.S., et al., Electric field effect in atomically thin carbon films. Science,2004.306(5696): p.666-669.
2. Zhang, Y.B., et al., Experimental observation of the quantum Hall effect and Berry'sphase in graphene. Nature,2005.438(7065): p.201-204.
3. Avouris, P., Z. Chen, and V. Perebeinos, Carbon-based electronics. NatureNanotechnology,2007.2(10): p.605-615.
4. Balandin, A.A., et al., Superior thermal conductivity of single-layer graphene. NanoLetters,2008.8(3): p.902-907.
5. Lee, C., et al., Measurement of the elastic properties and intrinsic strength of monolayergraphene. Science,2008.321(5887): p.385-388.
6. Castro Neto, A.H., et al., The electronic properties of graphene. Reviews of ModernPhysics,2009.81(1): p.109-162.
7. Bonaccorso, F., et al., Graphene photonics and optoelectronics. Nature Photonics,2010.4(9): p.611-622.
8. Schwierz, F., Graphene transistors. Nature Nanotechnology,2010.5(7): p.487-496.
9. Yun, W., et al., Selective immobilization of tris(2,2'-bipyridyl)ruthenium (II) onto arrayelectrode for solid-state electrochemiluminescene sensor fabrication. Sensors andActuators B-Chemical,2009.141(1): p.244-248.
10. Yun, W., et al., Solid-state electrochemiluminescence sensor through the electrodepositionof Ru(bpy)(3)(2+)/AuNPs/chitosan composite film onto electrode. Analytica ChimicaActa,2009.635(1): p.58-62.
11. Geim, A.K., Graphene: Status and Prospects. Science,2009.324(5934): p.1530-1534.
12. Wang, Y., et al., Graphene and graphene oxide: biofunctionalization and applications inbiotechnology. Trends in Biotechnology,2011.29(5): p.205-212.
13. Sun, X., et al., Nano-Graphene Oxide for Cellular Imaging and Drug Delivery. NanoResearch,2008.1(3): p.203-212.
14. He, S., et al., A Graphene Nanoprobe for Rapid, Sensitive, and Multicolor FluorescentDNA Analysis. Advanced Functional Materials,2010.20(3): p.453-459.
15. Wang, Y., et al., Aptamer/Graphene Oxide Nanocomplex for in Situ Molecular Probing inLiving Cells. Journal of the American Chemical Society,2010.132(27): p.9274-9276.
16. Niemeyer, C.M., Nanoparticles, proteins, and nucleic acids: Biotechnology meetsmaterials science. Angewandte Chemie-International Edition,2001.40(22): p.4128-4158.
17. Kitano, H., Systems biology: A brief overview. Science,2002.295(5560): p.1662-1664.
18. Welsh, J.B., et al., Analysis of gene expression profiles in normal and neoplastic ovariantissue samples identifies candidate molecular markers of epithelial ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America,2001.98(3): p.1176-1181.
19. Wilson, D.S. and S. Nock, Recent developments in protein microarray technology.Angewandte Chemie-International Edition,2003.42(5): p.494-500.
20. Ludwig, J.A. and J.N. Weinstein, Biomarkers in cancer staging, prognosis and treatmentselection. Nature Reviews Cancer,2005.5(11): p.845-856.
21. Yu, X., et al., Carbon nanotube amplification strategies for highly sensitiveimmunodetection of cancer biomarkers. Journal of the American Chemical Society,2006.128(34): p.11199-11205.
22. Zhang, H., et al., Ultrasensitive assays for proteins. Analyst,2007.132(8): p.724-737.
23. Giljohann, D.A. and C.A. Mirkin, Drivers of biodiagnostic development. Nature,2009.462(7272): p.461-464.
24. Song, S., et al., Functional nanoprobes for ultrasensitive detection of biomolecules.Chemical Society Reviews,2010.39(11): p.4234-4243.
25. Zhang, Q., et al., Nanotube-Based Colorimetric Probe for Ultrasensitive Detection ofAtaxia Telangiectasia Mutated Protein. Analytical Chemistry,2011.83(23): p.9191-9196.
26. Lin, Y.H., et al., Glucose biosensors based on carbon nanotube nanoelectrode ensembles.Nano Letters,2004.4(2): p.191-195.
27. Lee, Y.M., et al., Immobilization of horseradish peroxidase on multi-wall carbonnanotubes and its electrochemical properties. Biotechnology Letters,2006.28(1): p.39-43.
28. Li, D., et al., Processable aqueous dispersions of graphene nanosheets. NatureNanotechnology,2008.3(2): p.101-105.
29. Li, J., et al., Enzyme-based multi-component optical nanoprobes for sequence-specificdetection of DNA hybridization. Advanced Materials,2008.20(3): p.497-+.
30. Sperling, R.A., et al., Biological applications of gold nanoparticles. Chemical SocietyReviews,2008.37(9): p.1896-1908.
31. Giljohann, D.A., et al., Gold Nanoparticles for Biology and Medicine. AngewandteChemie-International Edition,2010.49(19): p.3280-3294.
32. Wang, J., G.D. Liu, and M.R. Jan, Ultrasensitive electrical biosensing of proteins andDNA: Carbon-nanotube derived amplification of the recognition and transduction events.Journal of the American Chemical Society,2004.126(10): p.3010-3011.
33. Wan, Y., et al., Carbon nanotube-based ultrasensitive multiplexing electrochemicalimmunosensor for cancer biomarkers. Biosensors&Bioelectronics,2011.30(1): p.93-99.
34. Hummers, W.S. and R.E. Offeman, Preparation Of Graphitic Oxide. Journal of theAmerican Chemical Society,1958.80(6): p.1339-1339.
35. Zhang, J., et al., Graphene Oxide as a Matrix for Enzyme Immobilization. Langmuir,2010.26(9): p.6083-6085.
36. Asuri, P., et al., Structure, function, and stability of enzymes covalently attached tosingle-walled carbon nanotubes. Langmuir,2007.23(24): p.12318-12321.
37. Park, S. and R.S. Ruoff, Chemical methods for the production of graphenes. NatureNanotechnology,2009.4(4): p.217-224.
38. Tung, V.C., et al., High-throughput solution processing of large-scale graphene. NatureNanotechnology,2009.4(1): p.25-29.
39. Zhang, Y., et al., Assembly of Graphene Oxide-Enzyme Conjugates through HydrophobicInteraction. Small,2012.8(1): p.154-159.
40. Silverton, E.W., M.A. Navia, and D.R. Davies,3-Dimensional Structure Of An IntactHuman Immunoglobulin. Proceedings of the National Academy of Sciences of the UnitedStates of America,1977.74(11): p.5140-5144.
41. Droz, E., et al., Influence Of Surface And Protein Modification On Immunoglobulin-GAdsorption Observed By Scanning Force Microscopy. Biophysical Journal,1994.67(3): p.1316-1323.