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Micro- and nanofluidics for DNA analysis

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Abstract

Miniaturization to the micrometer and nanometer scale opens up the possibility to probe biology on a length scale where fundamental biological processes take place, such as the epigenetic and genetic control of single cells. To study single cells the necessary devices need to be integrated on a single chip; and, to access the relevant length scales, the devices need to be designed with feature sizes of a few nanometers up to several micrometers. We will give a few examples from the literature and from our own research in the field of miniaturized chip-based devices for DNA analysis, including dielectrophoresis for purification of DNA, artificial gel structures for rapid DNA separation, and nanofluidic channels for direct visualization of single DNA molecules.

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References

  1. Campbell NA (1996) Biology, 4th ed. Benjamin/Cummings, Menlo Park

  2. Stryer L (1995) Biochemistry, 4th ed. Freeman, New York

  3. Ptashne M (1992) A genetic switch: phage lambda and higher organisms, 2nd ed. Blackwell, Cambridge, MA

    Google Scholar 

  4. Ptashne M, Gann A (2002) Genes and signals. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

  5. Hoch HC, Jelinski LW, Craighead HC (eds) (1996) Nanofabrication and biosystems: integrating materials science, engineering, and biology. Cambridge University Press, Cambridge, UK

    Google Scholar 

  6. Craighead HG (2000) Nanoelectromechanical systems. Science 290:1532–1535

    Article  CAS  PubMed  Google Scholar 

  7. Manz A, Graber N, Widmer HM (1990) Miniaturized total chemical-analysis systems—a novel concept for chemical sensing. Sens Actuators B 1:244–248

    Article  Google Scholar 

  8. Lockhart DJ, Winzeler EA (2000) Genomics, gene expression and DNA arrays. Nature 405:827–836

    Article  CAS  PubMed  Google Scholar 

  9. Larson CJ, Verdine GL (1996) The chemistry of protein-DNA interactions. In: Hecht SM (ed) Bioorganic chemistry: nucleic acids. Oxford University Press, New York, NY, pp 324–346

  10. Wolffe A (1998) Chromatin, structure and function, 3rd ed. Academic Press, London

  11. Li E, Beard C, Jaenisch R (1993) The role of DNA methylation in genomic imprinting. Nature 366:362–365

    CAS  PubMed  Google Scholar 

  12. Dennis C (2003) Altered states. Nature 421:686–688

    CAS  PubMed  Google Scholar 

  13. Tilghman SM (1991–2) Parental imprinting in the mouse. The Harvey Lectures 87:69–84

    Google Scholar 

  14. Chicurel M (2001) Faster, better, cheaper genotyping. Nature 412:580–582

    Article  CAS  PubMed  Google Scholar 

  15. Wall JD, Pritchard JK (2003) Haplotype blocks and linkage disequilibrium in the human genome. Nature Rev Genet 4(8):587–597

    Article  CAS  Google Scholar 

  16. Goldstein DB (2001) Islands of linkage disequilibrium. Nature Genet 29:109–111

    Article  CAS  PubMed  Google Scholar 

  17. Kwok PY (2001) Methods for genotyping single nucleotide polymorphisms. Annu Rev Genomics Human Genet 2:235–258

    Article  CAS  Google Scholar 

  18. Schwartz DC, Li XJ, Hernandez LI et al (1993) Ordered restriction maps of saccharomyces-cerevisiae chromosomes constructed by optical mapping. Science 262:110–114

    CAS  PubMed  Google Scholar 

  19. Cox EC, Vocke CD, Walter S et al (1990) Electrophoretic karyotype for Dictyostelium discoideum. Proc Natl Acad Sci USA 87:8247–8251

    Google Scholar 

  20. Bakajin O, Duke TAJ, Tegenfeldt J et al (2001) Separation of 100-kilobase DNA molecules in 10 seconds. Anal Chem 73(24):6053–6056

    Article  CAS  PubMed  Google Scholar 

  21. Huang LR, Tegenfeldt JO, Kraeft J et al (2002) A DNA prism for high-speed continuous fractionation of large DNA molecules. Nature Biotechnol 20(10):1048–1051

    Article  CAS  Google Scholar 

  22. Madou MJ (2002) Fundamentals of microfabrication: the science of miniaturization, 2nd ed. CRC Press, Boca Raton, FL

    Google Scholar 

  23. Campbell SA (1996) The science and engineering of microelectronic fabrication. Oxford University Press, New York

  24. Moore GE (1965) Cramming more components onto integrated circuits. Electronics 38(8):114–117

    Google Scholar 

  25. Intel Corporation (2003) http://www.intel.com/research/silicon/lithography.htm. Cited 4 Nov 2003

  26. Chapman HN, Ray-Chaudhuri AK, Tichenor DA et al (2001) First lithographic results from the extreme ultraviolet engineering test stand. J Vac Sci Technol B 19(6):2389–9235

    Article  CAS  Google Scholar 

  27. Naulleau P, Goldberg KA, Anderson EH et al (2002) Sub-70 nm extreme ultraviolet lithography at the advanced light source static microfield exposure station using the engineering test stand set-2 optic. J Vac Sci Technol B 20(6):2829–2833

    Article  CAS  Google Scholar 

  28. Junno T, Deppert K, Montelius L et al (1995) Controlled manipulation of nanoparticles with an atomic force microscope. Appl Phys Lett 66(26):3627

    Article  CAS  Google Scholar 

  29. Eigler DM, Schweizer EK (1990) Positioning single atoms with a scanning tunneling microscope. Nature 344:524–526

    Article  CAS  Google Scholar 

  30. Chou SY, Krauss PR, Renstrom PJ (1996) Imprint lithography with 25-nanometer resolution. Science 272:85–87

    CAS  Google Scholar 

  31. Chou SY, Krauss PR, Zhang W et al (1997) Sub-10 nm imprint lithography and applications. J Vac Sci Technol B 15(6):2897–2904

    Article  CAS  Google Scholar 

  32. Heidari B, Maximov I, Montelius L (2000) Nanoimprint lithography at the 6 in wafer scale. J Vac Sci Technol B 18(6):3557–3560

    Article  CAS  Google Scholar 

  33. Smith HI (2001) Low cost nanolithography with nanoaccuracy. Phys E Low-Dimension Syst Nanostructures 11(2–3):104–109

    Google Scholar 

  34. Solak HH, David C, Gobrecht J et al (2002) Multiple-beam interference lithography with electron beam written gratings. J Vac Sci Technol B 20(6):2844–2848

    Article  CAS  Google Scholar 

  35. Solak HH, David C, Gobrecht J et al (2003) Sub-50 nm period patterns with EUV interference lithography. Microelectron Eng 67–68:56–62

    Google Scholar 

  36. Mansky P, Harrison CK, Chaikin PM et al (1996) Nanolithographic templates from diblock copolymer thin films. Appl Phys Lett 68(18):2586–2588

    Article  CAS  Google Scholar 

  37. Harrison CK, Adamson DH, Park M et al (1997) Lithography with a mask of block copolymer microstructures. Abstr Papers Am Chem Soc 214:116-PMSE

    Google Scholar 

  38. Park M, Harrison C, Chaikin PM et al (1997) Block copolymer lithography: periodic arrays of similar to 10(11) holes in 1 square centimeter. Science 276:1401–1404

    Article  CAS  Google Scholar 

  39. Adamson DH, Harrison C, Park M et al (1998) Towards control and optimization of diblock copolymer microphases. Abstr Papers Am Chem Soc 216:062-MACR

    Google Scholar 

  40. Harrison C, Park M, Chaikin PM et al (1998) Lithography with a mask of block copolymer microstructures. J Vac Sci Technol B 16(2):544–552

    Article  CAS  Google Scholar 

  41. Register RA, Park M, Adamson DH et al (1999) Nanolithography with a block copolymer mask: fabrication of a dense metal dot array. Abstr Papers Am Chem Soc 218:7-PMSE

    Google Scholar 

  42. van Blaaderen A, Ruel R, Wiltzius P (1997) Template-directed colloidal crystallization. Nature 385:321–324

    Article  Google Scholar 

  43. Vlasov YA, Bo XZ, Sturm JC et al (2001) On-chip natural assembly of silicon photonic bandgap crystals. Nature 414:289–293

    Article  Google Scholar 

  44. Tong Q-Y, Gösele U (1998) Semiconductor wafer bonding: science and technology. Wiley

    Google Scholar 

  45. Ju S-P, Weng C-I, Chang J-G et al (2002) Molecular dynamics simulation of sputter trench-filling morphology in damascene process. J Vac Sci Technol B 20(3):946–955

    Article  CAS  Google Scholar 

  46. Cao H, Yu Z, Wang J et al (2002) Fabrication of enclosed nanofluidic channels. Appl Phys Lett 81(1):174–176

    Article  CAS  Google Scholar 

  47. Turner SW, Perez AM, Lopez A et al (1998) Monolithic nanofluid sieving structures for DNA manipulation. J Vac Sci Technol B 16(6):3835–3840

    Article  CAS  Google Scholar 

  48. Reed HA, White CE, Rao V et al (2001) Fabrication of microchannels using polycarbonates as sacrificial materials. J Micromech Microeng 11(6):733–737

    Article  CAS  Google Scholar 

  49. Harnett CK, Coates GW, Craighead HG (2001) Heat-depolymerizable polycarbonates as electron beam patternable sacrificial layers for nanofluidics. J Vac Sci Technol B 19(6):2842–2845

    Article  CAS  Google Scholar 

  50. Bhusari D, Reed HA, Wedlake M et al (2001) Fabrication of air-channel structures for microfluidic, microelectromechanical, and microelectronic applications. J Microelectromech Syst 10(3):400–408

    Article  CAS  Google Scholar 

  51. Li W, Tegenfeldt JO, Chen L et al (2003) Sacrificial polymers for nanofluidic channels in biological applications. Nanotechnology 14(6):578–583

    Article  CAS  Google Scholar 

  52. Quake SR, Scherer A (2000) From micro- to nanofabrication with soft materials. Science 290:1536–1540

    Article  CAS  PubMed  Google Scholar 

  53. Love JC, Anderson JR, Whitesides GM (2001) Fabrication of three-dimensional microfluidic systems by soft lithography. MRS Bull 26(7):523–528

    Google Scholar 

  54. Anderson JR, Chiu DT, Jackman RJ et al (2000) Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping. Anal Chem 72(14):3158–3164

    CAS  PubMed  Google Scholar 

  55. McDonald JC, Duffy DC, Anderson JR et al (2000) Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21(1):27–40

    Article  CAS  PubMed  Google Scholar 

  56. Unger MA, Chou HP, Thorsen T et al (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288:113–116

    Article  CAS  PubMed  Google Scholar 

  57. Thorsen T, Maerkl SJ, Quake SR (2002) Microfluidic large-scale integration. Science 298:580–584

    Article  CAS  PubMed  Google Scholar 

  58. Delamarche E, Bernard A, Schmid H et al (1997) Patterned delivery of immunoglobulins to surfaces using microfluidic networks. Science 276:779–781

    CAS  PubMed  Google Scholar 

  59. Kenis PJA, Ismagilov RF, Whitesides GM (1999) Microfabrication inside capillaries using multiphase laminar flow patterning. Science 285:83–85

    Article  CAS  PubMed  Google Scholar 

  60. Brody JP, Yager P, Goldstein RE et al (1996) Biotechnology at low Reynolds numbers. Biophys J 71(6):3430–3441

    CAS  PubMed  Google Scholar 

  61. Beebe DJ, Mensing GA, Walker GM (2002) Physics and applications of microfluidics in biology. Annu Rev Biomed Eng 4:261–286

    Article  CAS  PubMed  Google Scholar 

  62. Duffy DC, Gillis HL, Lin J et al (1999) Microfabricated centrifugal microfluidic systems: characterization and multiple enzymatic assays. Anal Chem 71(20):4669–4678

    Article  CAS  Google Scholar 

  63. Taylor G (1953) Dispersaion of soluble matter in solvent flowing slowly through a tube. Proc Royal Soc London Ser A Math Phys Sci 219:186–203

    Google Scholar 

  64. Landau LD, Lifshitz EM (1987) Fluid mechanics, 2nd ed. Pergamon, Oxford

  65. Hjertén S (1967) Free zone electrophoresis. Chromatogr Rev 9:122–219

    CAS  PubMed  Google Scholar 

  66. Liao JL, Abramson J, Hjerten S (1995) A highly stable methyl cellulose coating for capillary electrophoresis. J Capillary Electrophor 2(4):191–196

    CAS  PubMed  Google Scholar 

  67. Hjerten S (1985) High-performance electrophoresis—elimination of electroendosmosis and solute adsorption. J Chromatogr 347(2):191–198

    CAS  Google Scholar 

  68. Gaudioso J, Craighead HG (2002) Characterizing electroosmotic flow in microfluidic devices. J Chromatogr A 971(1–2):249–253

    Google Scholar 

  69. Rodriguez I, Li SFY (1999) Surface deactivation in protein and peptide analysis by capillary electrophoresis. Anal Chim Acta 383(1–2):1–26

    Google Scholar 

  70. Milton HJ (ed) (1992) Poly(ethylene glycol) chemistry: biotechnical and biomedical applications. Plenum, New York

  71. Caldwell KD (1997) In: Harris JM, Zalipsky S (eds) Surface modifications with adsorbed PEO-based block copolymers: physical characteristics and biological use, in chemistry and biological applications of polyethylene glycol. Am Chem Soc, Washington, 680:400–419

  72. Li JT, Carlsson J, Huang SC et al (1996) Adsorption of poly(ethylene oxide)-containing block copolymers—a route to protein resistance. Hydrophilic Polym 248:61–78

    CAS  Google Scholar 

  73. Webb K, Caldwell KD, Tresco PA (2001) A novel surfactant-based immobilization method for varying substrate-bound fibronectin. J Biomed Mater Res 54(4):509–5018

    Article  CAS  PubMed  Google Scholar 

  74. Carlson RH, Gabel CV, Chan SS et al (1997) Self-sorting of white blood cells in a lattice. Phys Rev Lett 79(11):2149–2152

    Article  CAS  Google Scholar 

  75. Gifford SC, Frank MG, Derganc J et al (2003) Parallel microchannel-based measurements of individual erythrocyte areas and volumes. Biophys J 84(1):623–6233

    CAS  PubMed  Google Scholar 

  76. Brody JP, Han YQ, Austin RH et al (1995) Deformation and flow of red-blood-cells in a synthetic lattice—evidence for an active cytoskeleton. Biophys J 68(6):2224–2232

    CAS  PubMed  Google Scholar 

  77. Gascoyne PRC, Noshari J, Becker FF et al (1994) Use of dielectrophoretic collection spectra for characterizing differences between normal and cancerous cells. IEEE Trans Ind Appl 30(4):829–834

    Article  Google Scholar 

  78. Becker FF, Wang X-B, Huang Y et al (1995) Separation of human breast cancer cells from blood by differential dielectric affinity. Proc Natl Acad Sci USA 92(3):860–864

    CAS  PubMed  Google Scholar 

  79. Berger M, Castelino J, Huang R et al (2001) Design of a microfabricated magnetic cell separator. Electrophoresis 22(18):3883–3892

    Article  CAS  PubMed  Google Scholar 

  80. Fu AY, Chou HP, Spence C et al (2002) An integrated microfabricated cell sorter. Anal Chem 74(11):2451–2457

    Article  CAS  PubMed  Google Scholar 

  81. Prinz C, Tegenfeldt JO, Austin RH et al (2002) Bacterial chromosome extraction and isolation. Lab Chip 2:207–212

    Article  CAS  Google Scholar 

  82. Pohl HA (1978) Dielectrophoresis. Cambridge University Press, Cambridge

  83. Washizu M, Suzuki S, Kurosawa O et al (1994) Molecular dielectrophoresis of biopolymers. IEEE Trans Ind Appl 30(4):835–843

    CAS  Google Scholar 

  84. Morgan H, Hughes MP, Green NG (1999) Separation of submicron bioparticles by dielectrophoresis. Biophys J 77(1):516–525

    CAS  PubMed  Google Scholar 

  85. Asbury CL, van den Engh G (1998) Trapping of DNA in nonuniform oscillating electric fields. Biophys J 74(2):1024–1030

    CAS  PubMed  Google Scholar 

  86. Asbury CL, Diercks AH, van den Engh G (2002) Trapping of DNA by dielectrophoresis. Electrophoresis 23(16):2658–2666

    Article  CAS  PubMed  Google Scholar 

  87. Chou CF, Tegenfeldt JO, Bakajin O et al (2000) DNA trapping by electrodeless dielectrophoresis. APS March Meeting, Minneapolis, MN, USA

  88. Chou C-F, Tegenfeldt JO, Bakajin O et al (2002) Electrodeless dielectrophoresis of single- and double-stranded DNA. Biophys J 83(4):2170–2179

    CAS  PubMed  Google Scholar 

  89. Cummings EB, Singh AK (2000) Dielectrophoretic trapping without embedded electrodes. In: Mastrangelo CH, Becker H (eds) Microfluidic devices and systems III 4177:164–73

  90. Ajdari A, Prost J (1991) Free-flow electrophoresis with trapping by a transverse inhomogenous field. Proc Natl Acad Sci USA 88:4468–4471

    CAS  PubMed  Google Scholar 

  91. Washizu M, Kurosawa O (1990) Electrostatic manipulation of DNA in microfabricated structures. IEEE Trans Ind Appl 26(6):1165–1172

    CAS  Google Scholar 

  92. Washizu M, Kurosawa O, Arai I et al (1995) Applications of electrostatic stretch-and-positioning of DNA. IEEE Trans Ind Appl 31(3):447–455

    Article  CAS  Google Scholar 

  93. Green NG, Morgan H, Milner JJ (1997) Dielectrophoresis of tobacco mosaic virus. Biophys J 72(2):MP448-MP

    Google Scholar 

  94. Morgan H, Green NG (1997) Dielectrophoretic manipulation of rod-shaped viral particles. J Electrostat 42(3):279–293

    Article  Google Scholar 

  95. Hughes MP, Morgan H, Rixon FJ et al (1998) Manipulation of herpes simplex virus type 1 by dielectrophoresis. Biochim Biophys Acta 1425(1):119–126

    CAS  PubMed  Google Scholar 

  96. Hughes MP, Morgan H, Rixon FJ (2001) Dielectrophoretic manipulation and characterization of herpes simplex virus-1 capsids. Eur Biophys J Biophys Lett 30(4):268–272

    Article  CAS  Google Scholar 

  97. Green NG, Morgan H, Milner JJ (1997) Manipulation and trapping of sub-micron bioparticles using dielectrophoresis. J Biochem Biophys Methods 35(2):89–102

    Article  CAS  PubMed  Google Scholar 

  98. Archer S, Morgan H, Rixon FJ (1999) Electrorotation studies of baby hamster kidney fibroblasts infected with herpes simplex virus type 1. Biophys J 76(5):2833–2842

    CAS  PubMed  Google Scholar 

  99. Krupke R, Hennrich F, von Löhneysen H et al (2003) Separation of metallic from semiconducting single-walled carbon nanotubes. Science 301:344–347

    Article  Google Scholar 

  100. Svanvik N, Westman G, Wang D et al (2000) Light-up probes: thiazole orange-conjugated peptide nucleic acid for detection of target nucleic acid in homogeneous solution. Anal Biochem 281:26–35

    Article  CAS  PubMed  Google Scholar 

  101. Schwartz DC, Cantor CR (1984) Separation of yeast chromosome-sized DNAs by pulsed field gradient gel-electrophoresis. Cell 37(1):67–75

    CAS  PubMed  Google Scholar 

  102. Kim Y, Morris MD (1995) Rapid pulsed field capillary electrophoretic separation of megabase nucleic acids. Anal Chem 67(5):784–786

    CAS  PubMed  Google Scholar 

  103. Mitnik L, Heller C, Prost J et al (1995) Segregation of DNA solutions induced by electric fields. Science 267:219–222

    CAS  PubMed  Google Scholar 

  104. Foquet M, Korlach J, Zipfel W et al (2002) DNA fragment sizing by single molecule detection in submicrometer-sized closed fluidic channels. Anal Chem 74(6):1415–1422

    Article  CAS  PubMed  Google Scholar 

  105. Chou HP, Spence C, Scherer A et al (1999) A microfabricated device for sizing and sorting DNA molecules. Proc Natl Acad Sci USA 96(1):11–13

    PubMed  Google Scholar 

  106. Chu G, Vollrath D, Davis RW (1986) Separation of large DNA-molecules by contour-clamped homogeneous electric-fields. Science 234:1582–1585

    CAS  PubMed  Google Scholar 

  107. Carle GF, Frank , Olson MV (1986) Electrophoretic separations of large DNA molecules by periodic inversion. Science 232:65–68

    CAS  PubMed  Google Scholar 

  108. Han J, Turner SW, Craighead HG (1999) Entropic trapping and escape of long DNA molecules at submicron size constriction. Phys Rev Lett 83(8):1688–1691

    Article  CAS  Google Scholar 

  109. Han J, Craighead HG (2000) Separation of long DNA molecules in a microfabricated entropic trap array. Science 288:1026–1029

    CAS  PubMed  Google Scholar 

  110. Han JY, Craighead HG (2002) Characterization and optimization of an entropic trap for DNA separation. Anal Chem 74(2):394–401

    Article  CAS  PubMed  Google Scholar 

  111. Turner SWP, Cabodi M, Craighead HG (2002) Confinement-induced entropic recoil of single DNA molecules in a nanofluidic structure. Phys Rev Lett 88(12): art no 128103

    Article  Google Scholar 

  112. Duke TAJ, Austin RH, Cox EC et al (1996) Pulsed-field electrophoresis in microlithographic arrays. Electrophoresis 17(6):1075–1079

    CAS  PubMed  Google Scholar 

  113. Huang LR, Tegenfeldt JO, Kraeft JJ et al (2001) Generation of large-area tunable uniform electric fields in microfluid arrays for rapid DNA separation. Technical digest of the 2001 IEEE international electron devices meeting, pp 363–366

  114. Astumian RD (1997) Thermodynamics and kinetics of a Brownian motor. Science 276:917–922

    Article  CAS  PubMed  Google Scholar 

  115. Astumian RD, Hanggi P (2002) Brownian motors. Phys Today 55(11):33–39

    Google Scholar 

  116. Chou CF, Bakajin O, Turner SWP et al (1999) Sorting by diffusion: an asymmetric obstacle course for continuous molecular separation. Proc Natl Acad Sci USA 96(24):13762–13765

    Article  CAS  PubMed  Google Scholar 

  117. van Oudenaarden A, Boxer SG (1999) Brownian ratchets: molecular separations in lipid bilayers supported on patterned arrays. Science 285:1046–1048

    Article  PubMed  Google Scholar 

  118. Duke TAJ, Austin RH (1998) Microfabricated sieve for the continuous sorting of macromolecules. Phys Rev Lett 80(7):1552–1555

    CAS  Google Scholar 

  119. Ertas D (1998) Lateral separation of macromolecules and polyelectrolytes in microlithographic arrays. Phys Rev Lett 80(7):8–1551

    Google Scholar 

  120. Huang LR, Silberzan P, Tegenfeldt JO et al (2002) Role of molecular size in ratchet fractionation. Phys Rev Lett 89(17): art no 178301

    Google Scholar 

  121. Guo X-H, Huff EJ, Schwartz DC (1992) Sizing single DNA molecules. Nature 359:783–784

    Article  CAS  PubMed  Google Scholar 

  122. Cai W, Jing J, Irvin B et al (1998) High-resolution restriction maps of bacterial artificial chromosomes constructed by optical mapping. PNAS 95:3390–3395

    Article  CAS  PubMed  Google Scholar 

  123. Tegenfeldt JO, Bakajin O, Chou C-F et al (2001) Near-field scanner for moving molecules. Phys Rev Lett 86(7):1378–1381

    Article  CAS  PubMed  Google Scholar 

  124. Ohtsu M, Hori H (1999) Near-field nano-optics: from basic principles to nano-fabrication and nano-photonics. Kluwer Plenum, New York

  125. Fillard JP (1997) Near field optics and nanoscopy. World Scientific, Singapore

  126. Paesler MA, Moyer PJ (1996) Near-field optics: theory, instrumentation, and applications. Wiley

  127. Thio T, Ghaemi HF, Lezec HJ et al (1999) Surface-plasmon-enhanced transmission through hole arrays in Cr films. J Opt Soc Am B 16(10):1743–1748

    CAS  Google Scholar 

  128. Chan WCW, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018

    Article  CAS  PubMed  Google Scholar 

  129. Dubertret B, Skourides P, Norris DJ et al (2002) In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298:1759–1762

    Article  CAS  PubMed  Google Scholar 

  130. Emory SR, Nie SM (1997) Near-field surface enhanced raman-spectroscopy on single silver nanoparticles. Anal Chem 69:2631

    Article  CAS  Google Scholar 

  131. Nie SM, Emory SR (1997) Probing single molecules and single nanoparticles by surface-enhanced Raman-scattering. Science 275:1102

    Article  CAS  PubMed  Google Scholar 

  132. Emory SR, Haskins WE, Nie SM (1998) Direct observation of size-dependent optical enhancement in single metal nanoparticles. J Am Chem Soc 120:8009

    Article  CAS  Google Scholar 

  133. Brochard-Wyart F (1995) Polymer-chains under strong flows—stems and flowers. Europhys Lett 30(7):387–392

    CAS  Google Scholar 

  134. Hagerman PJ (1988) Flexibility of DNA. Annu Rev Biophys Biophys Chem 17:265–286

    Article  CAS  PubMed  Google Scholar 

  135. Manning GS (1981) A procedure for extracting persistence lengths from light-scattering data on intermediate molecular-weight DNA. Biopolymers 20(8):1751–1755

    CAS  Google Scholar 

  136. Analysis performed on a Macintosh computer using the public domain NIH Image program (developed at the US National Institutes of Health and available on the Internet at http://rsb.info.nih.gov/nih-image/)

  137. Yildiz A, Forkey JN, McKinney SA et al (2003) Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science 300:2061–2065

    Article  CAS  PubMed  Google Scholar 

  138. Thompson RE, Larson DR, Webb WW (2002) Precise nanometer localization analysis for individual fluorescent probes. Biophys J 82(5):2775–2783

    CAS  PubMed  Google Scholar 

  139. Krylov SN, Arriaga E, Zhang ZR et al (2000) Single-cell analysis avoids sample processing bias. J Chromatogr B 741(1):31–35

    Article  CAS  Google Scholar 

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Acknowledgments

The authors are indebted to Zhaoning Yu for making high-quality nanostructured surfaces using nanoimprinting lithography. The authors are especially indebted to the following colleagues for fruitful discussions. Olgica Bakajin, Lawrence Livermore National Laboratories, CA; Shirley S. Chan, Princeton, NJ; Prof Chia-Fu Chou, Arizona State University, Tempe, AZ; Prof H. C. Craighead at Cornell, Ithaca, NY; Nicholas C. Darnton at the Rowland Institute at Harvard, Cambridge, MA; Thomas A.J. Duke at Cavendish Laboratory, Cambridge, UK; J.J. Kraeft, Princeton University, NJ; Robert Riehn, Princeton University, NJ; Walter W. Reisner, Princeton University, NJ; Pascal Silberzan at the Institut Curie, Paris, France; and Yan Mei Wang, Princeton University, NJ.

The work was funded by grants from the Defense Advanced Research Projects Agency (MDA972–00–1-0031), the National Institutes of Health (HG01506), the state of New Jersey (NJCST 99–100–082–2042–007), and the Nanobiotechnology Center (NSF BSCECS9876771).

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  1. Jonas O. Tegenfeldt

    Present address: The Division of Solid State Physics, Lund University, Lund, Sweden

  2. Christelle Prinz

    Present address: The Division of Solid State Physics, Lund University, Lund, Sweden

  3. Han Cao

    Present address: BioNanomatrix, Blawenburg, NJ, USA

Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, Princeton, NJ, USA

    Jonas O. Tegenfeldt & Edward C. Cox

  2. Department of Physics, Princeton University, Princeton, NJ, USA

    Christelle Prinz & Robert H. Austin

  3. Department of Electrical Engineering, Princeton University, Princeton, NJ, USA

    Han Cao, Richard L. Huang, Stephen Y. Chou & James C. Sturm

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  1. Jonas O. Tegenfeldt
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Tegenfeldt, J.O., Prinz, C., Cao, H. et al. Micro- and nanofluidics for DNA analysis. Anal Bioanal Chem 378, 1678–1692 (2004). https://doi.org/10.1007/s00216-004-2526-0

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  • DOI: https://doi.org/10.1007/s00216-004-2526-0

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