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Analytical and Bioanalytical Chemistry

, Volume 378, Issue 7, pp 1678–1692 | Cite as

Micro- and nanofluidics for DNA analysis

  • Jonas O. TegenfeldtEmail author
  • Christelle Prinz
  • Han Cao
  • Richard L. Huang
  • Robert H. Austin
  • Stephen Y. Chou
  • Edward C. Cox
  • James C. Sturm
Paper in Forefront

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.

Keywords

PDMS Microfluidic Channel Electron Beam Lithography Relevant Length Scale Entropic Barrier 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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).

References

  1. 1.
    Campbell NA (1996) Biology, 4th ed. Benjamin/Cummings, Menlo ParkGoogle Scholar
  2. 2.
    Stryer L (1995) Biochemistry, 4th ed. Freeman, New YorkGoogle Scholar
  3. 3.
    Ptashne M (1992) A genetic switch: phage lambda and higher organisms, 2nd ed. Blackwell, Cambridge, MAGoogle Scholar
  4. 4.
    Ptashne M, Gann A (2002) Genes and signals. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NYGoogle Scholar
  5. 5.
    Hoch HC, Jelinski LW, Craighead HC (eds) (1996) Nanofabrication and biosystems: integrating materials science, engineering, and biology. Cambridge University Press, Cambridge, UKGoogle Scholar
  6. 6.
    Craighead HG (2000) Nanoelectromechanical systems. Science 290:1532–1535CrossRefPubMedGoogle Scholar
  7. 7.
    Manz A, Graber N, Widmer HM (1990) Miniaturized total chemical-analysis systems—a novel concept for chemical sensing. Sens Actuators B 1:244–248CrossRefGoogle Scholar
  8. 8.
    Lockhart DJ, Winzeler EA (2000) Genomics, gene expression and DNA arrays. Nature 405:827–836CrossRefPubMedGoogle Scholar
  9. 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 324–346Google Scholar
  10. 10.
    Wolffe A (1998) Chromatin, structure and function, 3rd ed. Academic Press, LondonGoogle Scholar
  11. 11.
    Li E, Beard C, Jaenisch R (1993) The role of DNA methylation in genomic imprinting. Nature 366:362–365PubMedGoogle Scholar
  12. 12.
    Dennis C (2003) Altered states. Nature 421:686–688PubMedGoogle Scholar
  13. 13.
    Tilghman SM (1991–2) Parental imprinting in the mouse. The Harvey Lectures 87:69–84Google Scholar
  14. 14.
    Chicurel M (2001) Faster, better, cheaper genotyping. Nature 412:580–582CrossRefPubMedGoogle Scholar
  15. 15.
    Wall JD, Pritchard JK (2003) Haplotype blocks and linkage disequilibrium in the human genome. Nature Rev Genet 4(8):587–597CrossRefGoogle Scholar
  16. 16.
    Goldstein DB (2001) Islands of linkage disequilibrium. Nature Genet 29:109–111CrossRefPubMedGoogle Scholar
  17. 17.
    Kwok PY (2001) Methods for genotyping single nucleotide polymorphisms. Annu Rev Genomics Human Genet 2:235–258CrossRefGoogle Scholar
  18. 18.
    Schwartz DC, Li XJ, Hernandez LI et al (1993) Ordered restriction maps of saccharomyces-cerevisiae chromosomes constructed by optical mapping. Science 262:110–114PubMedGoogle Scholar
  19. 19.
    Cox EC, Vocke CD, Walter S et al (1990) Electrophoretic karyotype for Dictyostelium discoideum. Proc Natl Acad Sci USA 87:8247–8251Google Scholar
  20. 20.
    Bakajin O, Duke TAJ, Tegenfeldt J et al (2001) Separation of 100-kilobase DNA molecules in 10 seconds. Anal Chem 73(24):6053–6056CrossRefPubMedGoogle Scholar
  21. 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):1048–1051CrossRefGoogle Scholar
  22. 22.
    Madou MJ (2002) Fundamentals of microfabrication: the science of miniaturization, 2nd ed. CRC Press, Boca Raton, FLGoogle Scholar
  23. 23.
    Campbell SA (1996) The science and engineering of microelectronic fabrication. Oxford University Press, New YorkGoogle Scholar
  24. 24.
    Moore GE (1965) Cramming more components onto integrated circuits. Electronics 38(8):114–117Google Scholar
  25. 25.
    Intel Corporation (2003) http://www.intel.com/research/silicon/lithography.htm. Cited 4 Nov 2003Google Scholar
  26. 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):2389–9235CrossRefGoogle Scholar
  27. 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):2829–2833CrossRefGoogle Scholar
  28. 28.
    Junno T, Deppert K, Montelius L et al (1995) Controlled manipulation of nanoparticles with an atomic force microscope. Appl Phys Lett 66(26):3627CrossRefGoogle Scholar
  29. 29.
    Eigler DM, Schweizer EK (1990) Positioning single atoms with a scanning tunneling microscope. Nature 344:524–526CrossRefGoogle Scholar
  30. 30.
    Chou SY, Krauss PR, Renstrom PJ (1996) Imprint lithography with 25-nanometer resolution. Science 272:85–87Google Scholar
  31. 31.
    Chou SY, Krauss PR, Zhang W et al (1997) Sub-10 nm imprint lithography and applications. J Vac Sci Technol B 15(6):2897–2904CrossRefGoogle Scholar
  32. 32.
    Heidari B, Maximov I, Montelius L (2000) Nanoimprint lithography at the 6 in wafer scale. J Vac Sci Technol B 18(6):3557–3560CrossRefGoogle Scholar
  33. 33.
    Smith HI (2001) Low cost nanolithography with nanoaccuracy. Phys E Low-Dimension Syst Nanostructures 11(2–3):104–109Google Scholar
  34. 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):2844–2848CrossRefGoogle Scholar
  35. 35.
    Solak HH, David C, Gobrecht J et al (2003) Sub-50 nm period patterns with EUV interference lithography. Microelectron Eng 67–68:56–62Google Scholar
  36. 36.
    Mansky P, Harrison CK, Chaikin PM et al (1996) Nanolithographic templates from diblock copolymer thin films. Appl Phys Lett 68(18):2586–2588CrossRefGoogle Scholar
  37. 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-PMSEGoogle Scholar
  38. 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 276:1401–1404CrossRefGoogle Scholar
  39. 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-MACRGoogle Scholar
  40. 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):544–552CrossRefGoogle Scholar
  41. 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-PMSEGoogle Scholar
  42. 42.
    van Blaaderen A, Ruel R, Wiltzius P (1997) Template-directed colloidal crystallization. Nature 385:321–324CrossRefGoogle Scholar
  43. 43.
    Vlasov YA, Bo XZ, Sturm JC et al (2001) On-chip natural assembly of silicon photonic bandgap crystals. Nature 414:289–293CrossRefGoogle Scholar
  44. 44.
    Tong Q-Y, Gösele U (1998) Semiconductor wafer bonding: science and technology. WileyGoogle Scholar
  45. 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):946–955CrossRefGoogle Scholar
  46. 46.
    Cao H, Yu Z, Wang J et al (2002) Fabrication of enclosed nanofluidic channels. Appl Phys Lett 81(1):174–176CrossRefGoogle Scholar
  47. 47.
    Turner SW, Perez AM, Lopez A et al (1998) Monolithic nanofluid sieving structures for DNA manipulation. J Vac Sci Technol B 16(6):3835–3840CrossRefGoogle Scholar
  48. 48.
    Reed HA, White CE, Rao V et al (2001) Fabrication of microchannels using polycarbonates as sacrificial materials. J Micromech Microeng 11(6):733–737CrossRefGoogle Scholar
  49. 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):2842–2845CrossRefGoogle Scholar
  50. 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):400–408CrossRefGoogle Scholar
  51. 51.
    Li W, Tegenfeldt JO, Chen L et al (2003) Sacrificial polymers for nanofluidic channels in biological applications. Nanotechnology 14(6):578–583CrossRefGoogle Scholar
  52. 52.
    Quake SR, Scherer A (2000) From micro- to nanofabrication with soft materials. Science 290:1536–1540CrossRefPubMedGoogle Scholar
  53. 53.
    Love JC, Anderson JR, Whitesides GM (2001) Fabrication of three-dimensional microfluidic systems by soft lithography. MRS Bull 26(7):523–528Google Scholar
  54. 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):3158–3164PubMedGoogle Scholar
  55. 55.
    McDonald JC, Duffy DC, Anderson JR et al (2000) Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21(1):27–40CrossRefPubMedGoogle Scholar
  56. 56.
    Unger MA, Chou HP, Thorsen T et al (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288:113–116CrossRefPubMedGoogle Scholar
  57. 57.
    Thorsen T, Maerkl SJ, Quake SR (2002) Microfluidic large-scale integration. Science 298:580–584CrossRefPubMedGoogle Scholar
  58. 58.
    Delamarche E, Bernard A, Schmid H et al (1997) Patterned delivery of immunoglobulins to surfaces using microfluidic networks. Science 276:779–781PubMedGoogle Scholar
  59. 59.
    Kenis PJA, Ismagilov RF, Whitesides GM (1999) Microfabrication inside capillaries using multiphase laminar flow patterning. Science 285:83–85CrossRefPubMedGoogle Scholar
  60. 60.
    Brody JP, Yager P, Goldstein RE et al (1996) Biotechnology at low Reynolds numbers. Biophys J 71(6):3430–3441PubMedGoogle Scholar
  61. 61.
    Beebe DJ, Mensing GA, Walker GM (2002) Physics and applications of microfluidics in biology. Annu Rev Biomed Eng 4:261–286CrossRefPubMedGoogle Scholar
  62. 62.
    Duffy DC, Gillis HL, Lin J et al (1999) Microfabricated centrifugal microfluidic systems: characterization and multiple enzymatic assays. Anal Chem 71(20):4669–4678CrossRefGoogle Scholar
  63. 63.
    Taylor G (1953) Dispersaion of soluble matter in solvent flowing slowly through a tube. Proc Royal Soc London Ser A Math Phys Sci 219:186–203Google Scholar
  64. 64.
    Landau LD, Lifshitz EM (1987) Fluid mechanics, 2nd ed. Pergamon, OxfordGoogle Scholar
  65. 65.
    Hjertén S (1967) Free zone electrophoresis. Chromatogr Rev 9:122–219PubMedGoogle Scholar
  66. 66.
    Liao JL, Abramson J, Hjerten S (1995) A highly stable methyl cellulose coating for capillary electrophoresis. J Capillary Electrophor 2(4):191–196PubMedGoogle Scholar
  67. 67.
    Hjerten S (1985) High-performance electrophoresis—elimination of electroendosmosis and solute adsorption. J Chromatogr 347(2):191–198Google Scholar
  68. 68.
    Gaudioso J, Craighead HG (2002) Characterizing electroosmotic flow in microfluidic devices. J Chromatogr A 971(1–2):249–253Google Scholar
  69. 69.
    Rodriguez I, Li SFY (1999) Surface deactivation in protein and peptide analysis by capillary electrophoresis. Anal Chim Acta 383(1–2):1–26Google Scholar
  70. 70.
    Milton HJ (ed) (1992) Poly(ethylene glycol) chemistry: biotechnical and biomedical applications. Plenum, New YorkGoogle Scholar
  71. 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, 680:400–419Google Scholar
  72. 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 248:61–78Google Scholar
  73. 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):509–5018CrossRefPubMedGoogle Scholar
  74. 74.
    Carlson RH, Gabel CV, Chan SS et al (1997) Self-sorting of white blood cells in a lattice. Phys Rev Lett 79(11):2149–2152CrossRefGoogle Scholar
  75. 75.
    Gifford SC, Frank MG, Derganc J et al (2003) Parallel microchannel-based measurements of individual erythrocyte areas and volumes. Biophys J 84(1):623–6233PubMedGoogle Scholar
  76. 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):2224–2232PubMedGoogle Scholar
  77. 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):829–834CrossRefGoogle Scholar
  78. 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):860–864PubMedGoogle Scholar
  79. 79.
    Berger M, Castelino J, Huang R et al (2001) Design of a microfabricated magnetic cell separator. Electrophoresis 22(18):3883–3892CrossRefPubMedGoogle Scholar
  80. 80.
    Fu AY, Chou HP, Spence C et al (2002) An integrated microfabricated cell sorter. Anal Chem 74(11):2451–2457CrossRefPubMedGoogle Scholar
  81. 81.
    Prinz C, Tegenfeldt JO, Austin RH et al (2002) Bacterial chromosome extraction and isolation. Lab Chip 2:207–212CrossRefGoogle Scholar
  82. 82.
    Pohl HA (1978) Dielectrophoresis. Cambridge University Press, CambridgeGoogle Scholar
  83. 83.
    Washizu M, Suzuki S, Kurosawa O et al (1994) Molecular dielectrophoresis of biopolymers. IEEE Trans Ind Appl 30(4):835–843Google Scholar
  84. 84.
    Morgan H, Hughes MP, Green NG (1999) Separation of submicron bioparticles by dielectrophoresis. Biophys J 77(1):516–525PubMedGoogle Scholar
  85. 85.
    Asbury CL, van den Engh G (1998) Trapping of DNA in nonuniform oscillating electric fields. Biophys J 74(2):1024–1030PubMedGoogle Scholar
  86. 86.
    Asbury CL, Diercks AH, van den Engh G (2002) Trapping of DNA by dielectrophoresis. Electrophoresis 23(16):2658–2666CrossRefPubMedGoogle Scholar
  87. 87.
    Chou CF, Tegenfeldt JO, Bakajin O et al (2000) DNA trapping by electrodeless dielectrophoresis. APS March Meeting, Minneapolis, MN, USAGoogle Scholar
  88. 88.
    Chou C-F, Tegenfeldt JO, Bakajin O et al (2002) Electrodeless dielectrophoresis of single- and double-stranded DNA. Biophys J 83(4):2170–2179PubMedGoogle Scholar
  89. 89.
    Cummings EB, Singh AK (2000) Dielectrophoretic trapping without embedded electrodes. In: Mastrangelo CH, Becker H (eds) Microfluidic devices and systems III 4177:164–73Google Scholar
  90. 90.
    Ajdari A, Prost J (1991) Free-flow electrophoresis with trapping by a transverse inhomogenous field. Proc Natl Acad Sci USA 88:4468–4471PubMedGoogle Scholar
  91. 91.
    Washizu M, Kurosawa O (1990) Electrostatic manipulation of DNA in microfabricated structures. IEEE Trans Ind Appl 26(6):1165–1172Google Scholar
  92. 92.
    Washizu M, Kurosawa O, Arai I et al (1995) Applications of electrostatic stretch-and-positioning of DNA. IEEE Trans Ind Appl 31(3):447–455CrossRefGoogle Scholar
  93. 93.
    Green NG, Morgan H, Milner JJ (1997) Dielectrophoresis of tobacco mosaic virus. Biophys J 72(2):MP448-MPGoogle Scholar
  94. 94.
    Morgan H, Green NG (1997) Dielectrophoretic manipulation of rod-shaped viral particles. J Electrostat 42(3):279–293CrossRefGoogle Scholar
  95. 95.
    Hughes MP, Morgan H, Rixon FJ et al (1998) Manipulation of herpes simplex virus type 1 by dielectrophoresis. Biochim Biophys Acta 1425(1):119–126PubMedGoogle Scholar
  96. 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):268–272CrossRefGoogle Scholar
  97. 97.
    Green NG, Morgan H, Milner JJ (1997) Manipulation and trapping of sub-micron bioparticles using dielectrophoresis. J Biochem Biophys Methods 35(2):89–102CrossRefPubMedGoogle Scholar
  98. 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):2833–2842PubMedGoogle Scholar
  99. 99.
    Krupke R, Hennrich F, von Löhneysen H et al (2003) Separation of metallic from semiconducting single-walled carbon nanotubes. Science 301:344–347CrossRefGoogle Scholar
  100. 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 281:26–35CrossRefPubMedGoogle Scholar
  101. 101.
    Schwartz DC, Cantor CR (1984) Separation of yeast chromosome-sized DNAs by pulsed field gradient gel-electrophoresis. Cell 37(1):67–75PubMedGoogle Scholar
  102. 102.
    Kim Y, Morris MD (1995) Rapid pulsed field capillary electrophoretic separation of megabase nucleic acids. Anal Chem 67(5):784–786PubMedGoogle Scholar
  103. 103.
    Mitnik L, Heller C, Prost J et al (1995) Segregation of DNA solutions induced by electric fields. Science 267:219–222PubMedGoogle Scholar
  104. 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):1415–1422CrossRefPubMedGoogle Scholar
  105. 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):11–13PubMedGoogle Scholar
  106. 106.
    Chu G, Vollrath D, Davis RW (1986) Separation of large DNA-molecules by contour-clamped homogeneous electric-fields. Science 234:1582–1585PubMedGoogle Scholar
  107. 107.
    Carle GF, Frank , Olson MV (1986) Electrophoretic separations of large DNA molecules by periodic inversion. Science 232:65–68PubMedGoogle Scholar
  108. 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):1688–1691CrossRefGoogle Scholar
  109. 109.
    Han J, Craighead HG (2000) Separation of long DNA molecules in a microfabricated entropic trap array. Science 288:1026–1029PubMedGoogle Scholar
  110. 110.
    Han JY, Craighead HG (2002) Characterization and optimization of an entropic trap for DNA separation. Anal Chem 74(2):394–401CrossRefPubMedGoogle Scholar
  111. 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 128103CrossRefGoogle Scholar
  112. 112.
    Duke TAJ, Austin RH, Cox EC et al (1996) Pulsed-field electrophoresis in microlithographic arrays. Electrophoresis 17(6):1075–1079PubMedGoogle Scholar
  113. 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 363–366Google Scholar
  114. 114.
    Astumian RD (1997) Thermodynamics and kinetics of a Brownian motor. Science 276:917–922CrossRefPubMedGoogle Scholar
  115. 115.
    Astumian RD, Hanggi P (2002) Brownian motors. Phys Today 55(11):33–39Google Scholar
  116. 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):13762–13765CrossRefPubMedGoogle Scholar
  117. 117.
    van Oudenaarden A, Boxer SG (1999) Brownian ratchets: molecular separations in lipid bilayers supported on patterned arrays. Science 285:1046–1048CrossRefPubMedGoogle Scholar
  118. 118.
    Duke TAJ, Austin RH (1998) Microfabricated sieve for the continuous sorting of macromolecules. Phys Rev Lett 80(7):1552–1555Google Scholar
  119. 119.
    Ertas D (1998) Lateral separation of macromolecules and polyelectrolytes in microlithographic arrays. Phys Rev Lett 80(7):8–1551Google Scholar
  120. 120.
    Huang LR, Silberzan P, Tegenfeldt JO et al (2002) Role of molecular size in ratchet fractionation. Phys Rev Lett 89(17): art no 178301Google Scholar
  121. 121.
    Guo X-H, Huff EJ, Schwartz DC (1992) Sizing single DNA molecules. Nature 359:783–784CrossRefPubMedGoogle Scholar
  122. 122.
    Cai W, Jing J, Irvin B et al (1998) High-resolution restriction maps of bacterial artificial chromosomes constructed by optical mapping. PNAS 95:3390–3395CrossRefPubMedGoogle Scholar
  123. 123.
    Tegenfeldt JO, Bakajin O, Chou C-F et al (2001) Near-field scanner for moving molecules. Phys Rev Lett 86(7):1378–1381CrossRefPubMedGoogle Scholar
  124. 124.
    Ohtsu M, Hori H (1999) Near-field nano-optics: from basic principles to nano-fabrication and nano-photonics. Kluwer Plenum, New YorkGoogle Scholar
  125. 125.
    Fillard JP (1997) Near field optics and nanoscopy. World Scientific, SingaporeGoogle Scholar
  126. 126.
    Paesler MA, Moyer PJ (1996) Near-field optics: theory, instrumentation, and applications. WileyGoogle Scholar
  127. 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):1743–1748Google Scholar
  128. 128.
    Chan WCW, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018CrossRefPubMedGoogle Scholar
  129. 129.
    Dubertret B, Skourides P, Norris DJ et al (2002) In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298:1759–1762CrossRefPubMedGoogle Scholar
  130. 130.
    Emory SR, Nie SM (1997) Near-field surface enhanced raman-spectroscopy on single silver nanoparticles. Anal Chem 69:2631CrossRefGoogle Scholar
  131. 131.
    Nie SM, Emory SR (1997) Probing single molecules and single nanoparticles by surface-enhanced Raman-scattering. Science 275:1102CrossRefPubMedGoogle Scholar
  132. 132.
    Emory SR, Haskins WE, Nie SM (1998) Direct observation of size-dependent optical enhancement in single metal nanoparticles. J Am Chem Soc 120:8009CrossRefGoogle Scholar
  133. 133.
    Brochard-Wyart F (1995) Polymer-chains under strong flows—stems and flowers. Europhys Lett 30(7):387–392Google Scholar
  134. 134.
    Hagerman PJ (1988) Flexibility of DNA. Annu Rev Biophys Biophys Chem 17:265–286CrossRefPubMedGoogle Scholar
  135. 135.
    Manning GS (1981) A procedure for extracting persistence lengths from light-scattering data on intermediate molecular-weight DNA. Biopolymers 20(8):1751–1755Google Scholar
  136. 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/)Google Scholar
  137. 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 300:2061–2065CrossRefPubMedGoogle Scholar
  138. 138.
    Thompson RE, Larson DR, Webb WW (2002) Precise nanometer localization analysis for individual fluorescent probes. Biophys J 82(5):2775–2783PubMedGoogle Scholar
  139. 139.
    Krylov SN, Arriaga E, Zhang ZR et al (2000) Single-cell analysis avoids sample processing bias. J Chromatogr B 741(1):31–35CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jonas O. Tegenfeldt
    • 1
    • 4
    Email author
  • Christelle Prinz
    • 2
    • 5
  • Han Cao
    • 3
    • 6
  • Richard L. Huang
    • 3
  • Robert H. Austin
    • 2
  • Stephen Y. Chou
    • 3
  • Edward C. Cox
    • 1
  • James C. Sturm
    • 3
  1. 1.Department of Molecular BiologyPrinceton UniversityPrincetonUSA
  2. 2.Department of PhysicsPrinceton UniversityPrincetonUSA
  3. 3.Department of Electrical EngineeringPrinceton UniversityPrincetonUSA
  4. 4.The Division of Solid State PhysicsLund UniversityLundSweden
  5. 5.The Division of Solid State PhysicsLund UniversityLundSweden
  6. 6.BioNanomatrixBlawenburgUSA

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