eesti teaduste
akadeemia kirjastus
Estonian Journal of Engineering
Microfabrication of biomedical lab-on-chip devices. A review; pp. 109–139
PDF | doi: 10.3176/eng.2011.2.03

Athanasios T. Giannitsis
Lab-on-chip systems are a class of miniaturized analytical devices that integrate fluidics, electronics and various sensorics. They are capable of analysing biochemical liquid samples, like solutions of metabolites, macromolecules, proteins, nucleic acids, or cells and viruses. Supple­mentary to their measuring capabilities, the lab-on-chip devices facilitate fluidic trans­portation, sorting, mixing, or separation of liquid samples. A type of lab-on-chip devices, named biochip, is devoted specifically to genomic, proteomic and pharmaceutical tests. The significance of such miniaturized devices lies in their potentiality of automating laboratory procedures, which highly reduces the time of biomedical tests and laboratory work. This review summarizes numerous fabrication methods and procedures for producing lab-on-chip devices and also envisages future evolution.

1. Li, P. C. H. Microfluidic Lab-on-a-chip for Chemical and Biological Analysis and Discovery. CRC Press, 2006.

2. Zhang, T., Chakrabarty, K. and Fair, R. B. Microelectrofluidic Systems. CRC Press, 2002.

3. Reyes, D. R., Iossifidis, D., Auroux, P. A. and Manz, P. A. Micro total analysis systems: 1. Introduction, theory, and technology. Anal. Chem., 2002, 74, 2623–2636.

4. Auroux, A., Reyes, D. R., Iossifidis, D. and Manz, P. A. Micro total analysis systems: 2. Analytical standard operations and applications. Anal. Chem., 2002, 74, 2637–2652.

5. West, J., Becker, M., Tombrink, S. and Manz, A. Micro total analysis systems: latest achieve­ments. Anal. Chem., 2008, 80, 4403–4419.

6. Kost, G. J. Principles and Practice of Point-of-care Testing. Lippincott Williams and Wilkins, 2002.

7. Rossier, J. S., Roberts, M. A., Ferrigno, R. and Girault, H. H. Electrochemical detection in polymer microchannels. Anal. Chem., 1999, 71, 4294–4299.

 8. Wang, J. and Pumera, M. Dual conductivity/amperometric detection system for microchip capillary electrophoresis. Anal. Chem., 2002, 74, 5919–5923.

 9. Chan, J., Timperman, A. T., Qin, T. and Aebersold, R. Microfabricated polymer devices for automated sample delivery of peptides for analysis by electrospray ionization tandem mass spectrometry. Anal. Chem., 1999, 71, 4437–4444.

10. Kameoka, J., Craighead, H. G., Zhang, H. and Henion, J. A polymeric microfluidic chip for CE/MS determination of small molecules. Anal. Chem., 2001, 73, 1935–1941.

11. Hawkes, J. J. and Coakley, W. T. Force field particle filter, combining ultrasound standing waves and laminar flow. Sens. Actuators B: Chemical, 2001, 75, 213–222.

12. Becker, H., Lowack, K. and Manz, A. Planar quartz chips with submicron channels for two-dimensional capillary electrophoresis applications. J. Micromech. Microeng., 1998, 8, 24–28.

13. Harrison, D. J., Manz, A., Fan, Z., Luedi, H. and Widmer, H. M. Capillary electrophoresis and sample injection systems integrated on a planar glass chip. Anal. Chem., 1992, 64, 1926–1932.

14. Wang, J., Chen, G. and Muck, A. Movable contactless-conductivity detector for microchip capillary electrophoresis. Anal. Chem., 2003, 75, 4475–4479.

15. Wang, J., Pumera, M., Collins, G. E. and Mulchandani, A. Measurements of chemical warfare agent degradation products using an electrophoresis microchip with contactless con­ductivity detector. Anal. Chem., 2002, 74, 6121–6125.

16. Zalewski, D. R., Schlautmann, S., Schasfoort, R. B. M. and Gardeniers, H. J. G. E. Electro­kinetic sorting and collection of fractions for preparative capillary electrophoresis on a chip. Lab Chip, 2008, 8, 801–809.

17. Laugere, F., Guijt, R. M., Bastemeijer, J., van der Steen, G., Berthold, A., Baltussen, E., Sarro, P., van Dedem, G. W. K., Vellekoop, M. and Bossche, A. On-chip contactless four-electrode conductivity detection for capillary electrophoresis devices. Anal. Chem., 2003, 75, 306–312.

18. Kutter, J. P. Current developments in electrophoretic and chromatographic separation methods on microfabricated devices. Trends Analyt. Chem., 2000, 19, 352–363.

19. Jindal, R. and Cramer, S. M. On-chip electrochromatography using sol-gel immobilized stationary phase with UV absorbance detection. J. Chromatogr. A, 2004, 1044, 277–285.

20. Pumera, M. Microchip-based electrochromatography: Designs and applications. Talanta, 2005, 66, 1048–1062.

21. Végvári, Á. and Hjertén, S. A hybrid microdevice for electrophoresis and electro­chromato­graphy using UV detection. Electrophoresis, 2002, 23, 3479–3486.

22. Ceriotti, L., de Rooij, N. F. and Verpoorte, E. An integrated fritless column for on-chip capillary electrochromatography with conventional stationary phases. Anal. Chem., 2002, 74, 639–647.

23. Throckmorton, D. J., Shepodd, T. J. and Singh, A. K. Electrochromatography in microchips: Reversed-phase separation of peptides and amino acids using photopatterned rigid polymer monoliths. Anal. Chem., 2002, 74, 784–789.

24. Ro, K. W., Chang, W.-J., Kim, Ho, Koo, Y.-M. and Hahn, J. H. Capillary electrochromato­graphy and preconcentration of neutral compounds on poly(dimethylsiloxane) microchips. Electrophoresis, 2003, 24, 3253–3259.

25. Liang, Z., Chiem, N., Ocvirk, G., Tang, T., Fluri, K. and Harrison, D. J. Microfabrication of a planar absorbance and fluorescence cell for integrated capillary electrophoresis devices. Anal. Chem., 1996, 68, 1040–1046.

26. Zhu, L., Lee, C. S. and DeVoe, D. L. Integrated microfluidic UV absorbance detector with attomol-level sensitivity for BSA. Lab Chip, 2006, 6, 115–120.

27. Cristobal, G., Arbouet, L., Sarrazin, F., Talaga, D., Bruneel, J. L., Joanicot, M. and Servant, L. On-line laser Raman spectroscopic probing of droplets engineered in microfluidic devices. Lab Chip, 2006, 6, 1140–1146.

28. Chen, C. H., Tsai, F., Lien, V., Justis, N. and Lo, Y. H. Scattering-based cytometric detection using integrated arrayed waveguides with microfluidics. IEEE Photonics Technol. Lett., 2007, 19, 441–443.

29. MacDonald, M. P., Spalding, G. C. and Dholakia, K. Microfluidic sorting in an optical lattice. Nature, 2003, 426, 421–424.

30. Krishnamoorthy, G., Carlen, E. T., Kohlheyer, D., Schasfoort, R. B. M. and van den Berg, A. Integrated electrokinetic sample focusing and surface plasmon resonance imaging system for measuring biomolecular interactions. Anal. Chem., 2009, 81, 1957–1963.

31. Haab, B. B. and Mathies, R. A. Single-molecule detection of DNA separations in micro­fabricated capillary electrophoresis chips employing focused molecular streams. Anal. Chem., 1999, 71, 5137–5145.

32. Squires, T. M. and Quake, S. R. Microfluidics: Fluid physics at the nanoliter scale. Rev. Mod. Phys., 2005, 77, 977–1026.

33. Pamme, N. Continuous flow separations in microfluidic devices. Lab Chip, 2007, 7, 1644–1659.

34. Teh, S. Y., Lin, R., Hung, L. H. and Lee, A. P. Droplet microfluidics. Lab Chip, 2008, 8, 198–220.

35. Martin, K., Henkel, T., Baier, V., Grodrian, A., Schon, T., Roth, M., Kohler, J. M. and Metze, J. Generation of large numbers of separated microbial populations by cultivation in segmented-flow microdevices. Lab Chip, 2003, 3, 202–207.

36. Gastrock, G., Lemke, K., Römer, R., Howitz, S., Bertram, J., Hottenrott, M. and Metze, J. Protein-processing platform (3P) – A new concept for the characterization of cell cultures in the mL-scale using microfluidic components. Eng. Life Sci., 2008, 8, 73–80.

37. Tchavtchavadze, M. B., Perrier, M. and Jolicoeur, M. Small scale bioreactor platform for bioprocess optimisation. Pharmaceut. Eng., 2007, 27, 1–10.

38. Simon, J., Saffer, S. and Kim, C.-J. A liquid-filled microrelay with a moving mercury microdrop. J. Microelectromech. Syst. 1997, 6, 208–216.

39. Hayes, R. A. and Feenstra, B. J. Video-speed electric paper based on electrowetting. Nature, 2003, 425, 383–385.

40. Kuiper, S. and Hendriks, B. H. W. Variable-focus liquid lens for miniature cameras. Appl. Phys. Lett., 2004, 85, 1128–1130.

41. Takagi, J., Yamada, M., Yasuda, M. and Seki, M. Continuous particle separation in a micro­channel having asymmetrically arranged multiple branches. Lab Chip, 2005, 5, 778–784.

42. Yamada, M. and Seki, M. Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. Lab Chip, 2005, 5, 1233–1239.

43. Jäggi, R. D., Sandoz, R. and Effenhauser, C. S. Microfluidic depletion of red blood cells from whole blood in high-aspect-ratio microchannels. Microfluid. Nanofluid., 2007, 3, 47–53.

44. Choi, S. and Park, J. K. Continuous hydrophoretic separation and sizing of microparticles using slanted obstacles in a microchannel. Lab Chip, 2007, 7, 890–897.

45. Zhang, C. X. and Manz, A. High-speed free-flow electrophoresis on chip. Anal. Chem., 2003, 75, 5759–5766.

46. Jones, T. B., Fowler, J. D., Chang, Y. S and Kim, C. J. Frequency-based relationship of electro­wetting and dielectrophoretic liquid microactuation. Langmuir, 2003, 19, 7646–7651.

47. Jones, T. B. On the relationship of dielectrophoresis and electrowetting. Langmuir, 2002, 18, 4437–4443.

48. Pollack, M. G., Fair, R. B. and Shenderov, A. D. Electrowetting-based actuation of liquid droplets for microfluidic applications. Appl. Phys. Lett., 2000, 77, 1725–1726.

49. Pollack, M. G., Shenderov, A. D. and Fair, R. B. Electrowetting-based actuation of droplets for integrated microfluidics. Lab Chip, 2002, 2, 96–101.

50. Washizu, M. Electrostatic actuation of liquid droplets for micro-reactor applications. IEEE Trans. Ind. Appl., 1998, 34, 732–737.

51. Moon, H., Cho, S. K., Garell, R. L. and Kim, C. J. Low voltage electrowetting-on-dielectric. J. Appl. Phys., 2002, 92, 4080–4087.

52. Pamme, N. and Wilhelm, C. Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis. Lab Chip, 2006, 6, 974–980.

53. Laser, D. J. and Santiago, J. G. A review of micropumps. J. Micromech. Microeng., 2004, 14, R35–R64.

54. Gascoyne, P. R. and Vykoukal, J. Particle separation by dielectrophoresis. Electrophoresis, 2002, 23, 1973–1983.

55. van Lintel, H. T. G., van de Pol, F. C. M. and Bouwstra, S. A piezoelectric micropump based on micromachining of silicon. Sensors Actuators, 1988, 15, 153–167.

56. Nisar, A., Afzulpurkar, N., Mahaisavariya, B. and Tuantranont, A. MEMS-based micropumps in drug delivery and biomedical applications. Sensors Actuators B, 2008, 130, 917–942.

57. Zhong, J., Yi, M. and Bau, H. H. Magneto hydrodynamic (MHD) pump fabricated with ceramic tapes. Sensors Actuators A: Physical, 2002, 96, 59–66.

58. Xu, D., Wang, L., Ding, G., Zhou, Y., Yu, A. and Cai, B. Characteristics and fabrication of NiTi/Si diaphragm micropump. Sensors Actuators A: Physical, 2001, 93, 87–92.

59. Yokoyama, Y., Takeda, M., Umemoto, T. and Ogushi, T. Thermal micro pumps for a loop-type micro channel. Sensors Actuators A: Physical. 2004, 111, 123–128.

60. Salimi-Moosavi, H., Tang, T. and Harrison, D. Electroosmotic pumping of organic solvents and reagents in microfabricated reactor chips. J. Am. Chem. Soc., 1997, 119, 8716–8717.

61. Li, P. C. and Harrison, D. J. Transport, manipulation and reaction of biological cells on-chip using electrokinetic effects. Anal. Chem., 1997, 69, 1564–1568.

62. Manz, A., Fettinger, J. C., Verpoorte, E., Lude, H., Widmer, H. M. and Harrison, D. J. Micro­machining of monocrystalline silicon and glass for chemical analysis systems. A look into next century’s technology or just a fashionable craze? Trends Anal. Chem., 1991, 10, 144–149.

63. Terry, S. C., Jerman, J. H. and Angell, J. B. A gas chromatographic air analyzer fabricated on a silicon wafer. IEEE Trans. Electron. Devices, 1979, ED-26, 1880–1886.

64. Oh, H. J., Kim, S. H., Baek, J. Y., Seong, G. H. and Lee, S. H. Hydrodynamic micro­encapsulation of aqueous fluids and cells via ‘on the fly’ photopolymerization. J. Micro­mech. Microeng., 2006, 16, 285–291.

65. Choi, C. H., Jung, J. H., Rhee, Y., Kim, D. P., Shim, S. E. and Lee, C. S. Generation of monodisperse alginate microbeads and in situ encapsulation of cell in microfluidic device. Biomed. Microdevices, 2007, 9, 855–862.

66. Tan, Y. C., Hettiarachchi, K., Siu, M., Pan, Y. P. and Lee, A. P. Controlled microfluidic encapsulation of cells, proteins, and microbeads in lipid vesicles. J. Am. Chem. Soc., 2006, 128, 5656–5658.

67. Yamada, M., Nakashima, M. and Seki, M. Pinched flow fractionation: Continuous size separa­tion of particles utilizing a laminar flow profile in a pinched microchannel. Anal. Chem., 2004, 76, 5465–5471.

68. Shevkoplyas, S. S., Yoshida, T., Munn, L. L. and Bitensky, M. W. Biomimetic design of a microfluidic device for auto-separation of leukocytes from whole blood. Anal. Chem., 2005, 77, 933.

69. Gomez-Sjoberg, R., Leyrat, A. A., Pirone, D. M., Chen, C. S. and Quake, S. R. Versatile, fully automated, microfluidic cell culture system. Anal. Chem., 2007, 79, 8557–8563.

70. Nevill, J. T., Cooper, R., Dueck, M., Breslauer, D. N. and Lee, L. P. Integrated microfluidic cell culture and lysis on a chip. Lab Chip, 2007, 7, 1689–1695.

71. Melin, J. and Quake, S. R. Microfluidic large-scale integration: The evolution of design rules for biological automation. Ann. Rev. Biophys. Biomolecular Structure, 2007, 36, 213–231.

72. Talary, M. S., Burt, J. P. H. and Pethig, R. Future trends in diagnosis using laboratory-on-a-chip technologies. Parasitology, 1998, 117, S191–S203.

73. Kopp, M. U., De Mello, A. and Manz, J. A. Chemical amplification: Continuous-flow PCR on a chip. Science, 1998, 280, 1046–1048.

74. Wildinga, P., Kricka, L. J., Cheng, J., Hvichia, G., Shoffner, M. A. and Fortina, P. Integrated cell isolation and polymerase chain reaction analysis using silicon microfilter chambers. Analyt. Biochem., 1998, 257, 95–100.

  75. Shoffner, M. A., Cheng, J., Hvichia, G. E., Kricka, L. J. and Wilding, P. Chip PCR. I: Surface passivation of microfabricated silicon-glass chips for PCR. Nucleic Acids Res., 1996, 24, 375–379.

  76. Cheng, J., Shoffner, M. A., Hvichia, G. E., Kricka, L. J. and Wilding, P. Chip PCR. II: Investigation of different PCR amplification systems in microbabricated silicon-glass chips. Nucleic Acids Res., 1996, 24, 380–385.

  77. Auroux, P. A., Koc, Y., DeMello, A., Manz, A. and Day, P. J. R. Miniaturised nucleic acid analysis. Lab Chip, 2004, 4, 534–546.

  78. Wang, W., Li, Z. X., Luo, R., Lu, S. H., Xu, A. D. and Yang, Y. J. Droplet-based micro oscillating-flow PCR chip. J. Micromech. Microeng., 2005, 15, 1369–1377.

  79. Beer, N. R., Hindson, B. J., Wheeler, E. K., Hall, S. B., Rose, K. A., Kennedy, I. M. and Colston, B. W. On-chip, real-time, single-copy polymerase chain reaction in picoliter droplets. Anal. Chem., 2007, 79, 8471–8475.

  80. Liu, R. H., Yang, J. N., Lenigk, R., Bonanno, J. and Grodzinski, P. Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection. Analyt. Chem., 2004, 76, 1824–1831.

  81. Urban, G. A. Micro- and nanobiosensors – State of the art and trends. Meas. Sci. Technol., 2009, 20, 012001.

  82. Chmela, E. and Tijssen, R. A chip system for size separation of macromolecules and particles by hydrodynamic chromatography. Analyt. Chem., 2002, 74, 3470–3475.

  83. Blom, M. T., Chmela, E., Gardeniers, J. G. E., Tijssen, R., Elwenspoek, M. and van den Berg, A. Design and fabrication of a hydrodynamic chromatography chip. Sensors Actuators B: Chemical, 2002, 82, 111–116.

  84. Niemeyer, C. M. and Blohm, D. DNA microarray. Angew. Chemie Int. Ed., 1999, 38, 2865–2869.

  85. Blohm, D. H. and Guiseppi-Elie, A. New developments in microarray technology. Curr. Opin. Biotechnol., 2001, 12, 41–47.

  86. Pirrung, M. C. How to make a DNA chip. Angew. Chemie Int. Ed., 2002, 41, 1276–1289.

  87. Jung, A. DNA chip technology. Anal. Bioanal. Chem., 2002, 372, 41–42.

  88. Saliterman, S. S. Education, bioMEMS and the medical microdevice revolution. Expert. Rev. Med. Devices, 2005, 2, 515–519.

  89. Fan, Z. H. and Ricco, A. J. Plastic microfluidic devices for DNA and protein analyses. In BioMEMS and Biomedical Nanotechnology: Micro/Nano Technology for Genomics and Proteomics (Ozkan, M., Heller, M. J. and Ferrari, M., eds). Vol. II, Springer, 2006, 311–328.

  90. Wagenknecht, H. A. Photoinduced electron transport in DNA. In Nanobiotechnology: Bio­inspired Devices and Materials of the Future (Shoseyov, O. and Levy, I., eds). Hamana Press, Totowa, New Jersey, 2008, 89–106.

  91. Drummond, T. G., Hill, M. G. and Barton, J. K. Electrochemical DNA sensors. Nat. Bio­technol., 2003, 21, 1192–1199.

  92. Porath, D., Cuniberti, G. and Di Felice, R. Charge transport in DNA-based devices. Top Curr. Chem., 2004, 237, 183–227.

  93. Köster, S., Angile, F. E., Duan, H., Agresti, J. J., Wintner, A., Schmitz, C., Rowat, A. C., Merten, C. A., Pisignano, D., Griffiths, A. D. and Weitz, D. A. Drop-based microfluidic devices for encapsulation of single cells. Lab Chip, 2008, 8, 1110–1115.

  94. Sun, T., Holmes, D., Gawad, S., Green, N. G. and Morgan, H. High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences. Lab Chip, 2007, 7, 1034–1040.

  95. Gawad, S., Sun, T., Green, N. G. and Morgan, H. Impedance spectroscopy using maximum length sequences: Application to single cell analysis. Rev. Sci. Instruments, 2007, 78, 054301-1.

  96. Morgan, H., Sun, T., Holmes, D., Gawad, S. and Green, N. G. Single cell dielectric spectro­scopy. J. Phys. D: Appl. Phys., 2007, 40, 61–70.

  97. Fu, A. Y., Spence, C., Scherer, A., Arnold, F. H. and Quake, S. R. A microfabricated fluorescence-activated cell sorter. Nature Biotechnol., 1999, 17, 1109–1111.

  98. Zemann, A. J., Schnell, E., Volgger, D. and Bonn, G. K. Contactless conductivity detection for capillary electrophoresis. Analyt. Chem., 1998, 70, 563–567.

  99. Pumera, M., Wang, J., Opekar, F., Jelínek, I., Feldman, J., Löwe, H. and Hardt, S. Contactless conductivity detector for microchip capillary electrophoresis. Analyt. Chem., 2002, 74, 1968–1971.

100. Lichtenberg, J., de Rooij, N. F. and Verpoorte, E. A microchip electrophoresis system with integrated in-plane electrodes for contactless conductivity detection. Electrophoresis, 2002, 23, 3769–3780.

101. Lee, C.-Y., Chen, C. M., Chang, G.-L., Lin, C.-H. and Fu, L.-M. Fabrication and charac­terization of semicircular detection electrodes for contactless conductivity detector – CE microchips. Electrophoresis, 2006, 27, 5043–5050.

102. Gorbatsova, J., Jaanus, M. and Kaljurand, M. Digital microfluidic sampler for a portable capillary electropherograph. Analyt. Chem., 2009, 81, 8590–8595.

103. da Silva, J. A. F. and do Lago, C. L. An oscillometric detector for capillary electrophoresis. Analyt. Chem., 1998, 70, 4339–4343.

104. Abad-Villar, E. M., Kubáň, P. and Hauser, P. C. Determination of biochemical species on electrophoresis chips with an external contactless conductivity detector. Electrophoresis, 2005, 26, 3609–3614.

105. Cabrera, C. R. and Yager, P. Continuous concentration of bacteria in a microfluidic flow cell using electrokinetic techniques. Electrophoresis, 2001, 22, 355–362.

106. Lu, H., Schmidt, M. A. and Jensen, K. F. A microfluidic electroporation device for cell lysis. Lab Chip, 2005, 5, 23–29.

107. Li, Y. L., Dalton, C., Crabtree, H. J., Nilsson, G. and Kaler, K. Continuous dielectrophoretic cell separation microfluidic device. Lab Chip, 2007, 7, 239–248.

108. Doh, I. and Cho, Y. H. A continuous cell separation chip using hydrodynamic dielectro­phoresis (DEP) process. Sens. Actuators A: Physical, 2005, 121, 59–65.

109. Huang, Y. and Pethig, R. Electrode design for negative dielectrophoresis. Meas. Sci. Technol., 1991, 2, 1142–1146.

110. Gascoyne, P. R. C., Wang, X.-B., Huang, Y. and Becker, F. F. Dielectrophoretic separation of cancer cells from blood. IEEE Trans. Industry Applications, 1997, 33, 670–678.

111. Wang, X.-B., Huang, Y., Wang, X., Becker, F. F. and Gascoyne, P. R. C. Dielectrophoretic manipulation of cells with spiral electrodes. Biophys. J., 1997, 72, 1887–1899.

112. Broche, L. M., Bhadal, N., Lewis, M. P., Porter, S., Hughes, M. P. and Labeed, F. H. Early detection of oral cancer – Is dielectrophoresis the answer? Oral Oncology, 2007, 43, 199– 203.

113. Cen, E. G., Dalton, C., Li, Y., Adamia, S., Pilarski, L. M. and Kaler, K. V. I. S. A combined dielectrophoresis, traveling wave dielectrophoresis and electrorotation microchip for the manipulation and characterization of human malignant cells. J. Microbiol. Methods, 2004, 58, 387–401.

114. Jones, T. B. Electromechanics of Particles. Cambridge University Press, 1995.

115. Kirby, B. J. Micro- and Nanoscale Fluid Mechanics: Transport in Microfluidic Devices. Cambridge University Press, 2010.

116. Cahill, B. P., Heyderman, L. J., Gobrecht, J. and Stemmer, A. Electro-osmotic streaming on application of traveling-wave electric fields. Phys. Rev., 2004, 70, 036305.

117. Kirby, B. J., Wheeler, A. R., Zare, R. N., Fruetela, J. A. and Shepodd, T. J. Programmable modification of cell adhesion and zeta potential in silica microchips. Lab Chip, 2003, 3, 5–10.

118. Chun, M.-S., Shim, M. S. and Choi, N. W. Fabrication and validation of a multi-channel type microfluidic chip for electrokinetic streaming potential devices. Lab Chip, 2006, 6, 302–309.

119. Estes, M. D., Do, J. and Ahn, C. H. On chip cell separator using magnetic bead-based enrichment and depletion of various surface markers. Biomed. Devices, 2009, 11, 509–515.

120. Gijs, M. Magnetic bead handling on-chip: New opportunities for analytical applications. Microfluid. Nanofluid., 2004, 1, 22–40.

121. Ogiue-Ikeda, M., Sato, Y. and Ueno, S. A new method to destruct targeted cells using magnetizable beads and pulsed magnetic force. IEEE Trans. Nanobiosci., 2003, 2, 262–265.

122. Valberg, P. A. and Butler, J. P. Magnetic particle motions within living cells – Physical theory and techniques. Biophys. J., 1987, 52, 537–550.

123. Wang, N., Butler, J. P. and Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science, 1993, 260, 1124–1127.

124. Egatz-Gómez, A., Melle, S., García, A. A., Lindsay, S. A., Márquez, M., Picraux, S. T., Taraci, J. L., Clement, T., Yang, D., Hayes, M. A. and Gust, D. Discrete magnetic micro­fluidics, Appl. Phys. Lett., 2006, 89, 034106.

125. Lehmann, U., Hadjidj, S., Parashar, V. K., Vandevyver, C., Rida, A. and Gijs, M. A. M. Two-dimensional magnetic manipulation of microdroplets on a chip as a platform for bioanalytical applications. Sensors Actuators B: Chemical, 2006, 117, 457–463.

126. Xia, Y. and Whitesides, G. M. Soft lithography. Ann. Rev. Mater. Sci., 1998, 28, 153–184.

127. Kumar, A. and Whitesides, G. M. Features of gold having micrometer to centimeter dimensions can be formed through a combination of stamping with an elastomeric stamp and an alkanethiol ‘ink’ followed by chemical etching. Appl. Phys. Lett., 1993, 63, 2002–2004.

128. Harrison, D. J., Glavina, P. G. and Manz, A. Towards miniaturized electrophoresis and chemical analysis systems on silicon: An alternative to chemical sensors. Sensors Actuators B: Chemical, 1993, 10, 107–116.

129. Wilding, P., Shoffner, M. A. and Kricka, L. PCR in a silicon microstructure. J. Clin. Chem., 1994, 40, 1815–1818.

130. Raymond, D. E., Manz, A. and Widmer, H. M. Continuous separation of high molecular weight compounds using a microliter volume free-flow electrophoresis microstructure. Anal. Chem., 1996, 68, 2515–2522.

131. Fan, Z. H. and Harrison, D. J. Micromachining of capillary electrophoresis injectors and separators of glass chips and evaluation of flow at capillary intersections. Analyt. Chem., 1994, 66, 177–184.

132. Jacobson, S. C., Hergenroder, R., Koutny, L. B., Warmack, R. J. and Ramsey, J. M. Effects of injection schemes and column geometry on the performance of microchip electrophoresis devices. Analyt. Chem., 1994, 66, 1107–1113.

133. Roberts, M. A., Rossier, J. S., Bercier, P. and Girault, H. H. UV laser machined polymer substrates for the development of microdiagnostic systems. Analyt. Chem., 1997, 69, 2035–2042.

134. Soper, S. A., Ford, S. M., Qi, S., McCarley, R. L., Kelly, K. and Murphy, M. C. Peer reviewed: Polymeric microelectromechanical systems. Analyt. Chem., 2000, 72, 643A–651A.

135. Friend, J. and Yeo, L. Fabrication of microfluidic devices using polydimethylsiloxane. Bio­microfluidics, 2010, 4, 026502.

136. Toepke, M. W. and Beebe, D. J. PDMs absorption of small molecules and consequences in microfluidic applications. Lab Chip, 2006, 6, 1484–1486.

137. Satas, D. Coatings Technology Handbook. Marcel Dekker Inc., 1991.

138. Christensen, C., de Reus, R. and Bouwstra, S. Tantalum oxide thin films as protective coatings for sensors. J. Micromech. Microeng., 1999, 9, 113–118.

139. Joshi, P. C. and Cole, M. W. Influence of postdeposition annealing on the enhanced structural and electrical properties of amorphous and crystalline Ta2O5 thin films for dynamic random access memory applications. J. Appl. Phys., 1999, 86, 15.

140. Cahill, B. P., Giannitsis, A. T., Land, R., Gastrock, G., Pliquett, U., Frense, D., Min, M. and Beckmann, D. Reversible electrowetting on silanized silicon nitride. Sensors Actuators B, 2010, 144, 380–386.

141. Li, J., Fu, J., Cong, Y., Wu, Y., Xue, L. and Han, Y. Macroporous fluoropolymeric films templated by silica colloidal assembly: A possible route to super-hydrophobic surfaces. Appl. Surface Sci., 2006, 252, 2229–2234.

142. Hoque, E., DeRose, J. A., Hoffmann, P., Bhushan, B. and Mathieu, H. J. Alkylperfluorosilane self-assembled monolayers on aluminum: A comparison with alkylphosphonate self-assembled monolayers. J. Phys. Chem. C, 2007, 111, 3956–3962.

143. Hoque, E., DeRose, J. A., Hoffmann, P. and Mathieu, H. J. Robust perfluorosilanized copper surfaces. Surf. Interface Anal., 2006, 38, 62–68.

144. Bayiati, P., Tserepi, A., Petrou, P. S., Kakabakos, S. E., Misiakos, K. and Gogolides, E. Electrowetting on plasma-deposited fluorocarbon hydrophobic films for biofluid transport in microfluidics. J. Appl. Phys., 2007, 101, 103306.

145. Bayiati, P., Tserepi, A., Petrou, P. S., Misiakos, K., Kakabakos, S. E., Gogolides, E. and Cardinaud, C. Biofluid transport on hydrophobic plasma-deposited fluorocarbon films. Microelectronic Eng., 2007, 84, 1677–1680.

146. Seyrat, E. and Hayes, R. A. Amorphous fluoropolymers as insulators for reversible low-voltage electrowetting. J. Appl. Phys., 2001, 90, 1383–1386.

147. Kedzierski, J. and Berry, S. Engineering the electrocapillary behavior of electrolyte droplets on thin fluoropolymer films. Langmuir, 2006, 22, 5690–5696.

148. Schreiber, F. Structure and growth of self-assembling monolayers. Progress in Surface Science, 2000, 65, 151–256.

149. Carlen, E. T., Heng, K. H., Bakshi, S., Pareek, A. and Mastrangelo, C. H. High-aspect ratio vertical comb-drive actuator with small self-aligned finger gaps. J. Microelectromech., 2005, 14, 1144–1154.

150. Christensen, T. B., Pedersen, C. M., Grondahl, K. G., Jensen, T. G., Sekulovic, A., Bang, D. D. and Wolff, A. J. PCR biocompatibility of lab-on-a-chip and MEMS materials. J. Micromech. Microeng., 2007, 17, 1527–1532.

151. Schumacher, J. T., Grodrian, A., Kremin, C., Hoffmann, M. and Metze, J. Hydrophobic coating of microfluidic chips structured by SU-8 polymer for segmented flow operation. J. Micromech. Microeng., 2008, 18, 055019.

152. Kotzar, G., Freas, M., Abel, P., Fleischman, A., Roy, S., Zorman, C., Moran, J. M. and Melzak, J. Evaluation of MEMS materials of construction for implantable medical devices. Biomaterials, 2002, 23, 2737–2750.

153. Voskerician, G., Shive, M. S., Shawgo, R. S., von Recum, H., Anderson, J. M., Cima, M. J. and Langer, R. Biocompatibility and biofouling of MEMS drug delivery device. Biomaterials, 2003, 24, 1959–1967.

154. Hernandez, P. R., Taboada, C., Leija, L., Tsutsumi, V., Vazquez, B., Valdes-Perezgasga, F. and Reyes, J. L. Evaluation of biocompatibility of pH-ISFET materials during long-term subcutaneous implantation. Sensors Actuators B, 1998, 46, 133–138.

155. Jeong, J. H., Moon, Y. M., Kim, S. O., Yun, S. S. and Shin, H. I. Human cartilage tissue engineering with pluronic and cultured chondocyte sheet. Key Eng. Mater., 2007, 342–343, 89–92.

156. Klapperich, C. M. Microfluidic diagnostics: Time for industry standards. Expert Rev. Medical Devices, 2009, 6, 211–213.

157. Pfohl, T., Mugele, F., Seemann, R. and Herminghaus, S. Trends in microfluidics with complex fluids. Chemphyschem, 2003, 4, 1291–1298.

158. Thies, W., Urbanski, J. P., Thorsen, T. and Amarasinghe, S. Abstraction layers for scalable microfluidic biocomputers. In Proc. International Meeting on DNA Computing (Mao, C. and Yokomori, T., eds). Seoul, Korea, 2006, 308–323.

159. Cox, J. C. and Ellington, A. D. DNA computation function. Curr. Biol., 2001, 11, R336.

160. Yurke, B., Mills, A. P. Jr and Cheng, S. L. DNA implementation of addition in which the input strands are separate from the operator strands. BioSystems, 1999, 52, 165–174.

161. Hug, H. and Schuler, R. Strategies for the development of a peptide computer. Bioinformatics, 2001, 17, 364–368.

162. Sakamoto, K., Gouzu, H., Komiya, K., Kiga, D., Yokoyama, S., Yokomori, T. and Hagiya, M. Molecular computation by DNA hairpin formation. Science, 2000, 288, 1223–1226.

163. Boulart, C., Mowlem, M. C., Connelly, D. P., Dutasta, J.-P. and German, C. R. A novel, low-cost, high performance dissolved methane sensor for aqueous environments. Optics Express, 2008, 16, 12607–12617.

164. Sosna, M., Denuault, G., Pascal, R. W., Prien, R. D. and Mowlem, M. Development of a reliable microelectrode dissolved oxygen sensor. Sensors Actuators B, 2007, 123, 344–351.

165. Benazzi, G., Holmes, D., Sun, T., Mowlem, M. C. and Morgan, H. Discrimination and analysis of phytoplankton using a microfluidic cytometer. IET Nanobiotechnology, 2007, 1, 94–101.

166. Patey, M. D., Rijkenberg, M. J. A., Statham, P. J., Mowlem, M., Stinchcombe, M. C. and Achterberg, E. P. Determination of nitrate and phosphate in seawater at nanomolar concentrations. Trends Analyt. Chem., 2008, 27, 169–182.

167. Burns, M. A., Johnson, B. N., Brahmasandra, S. N., Handique, K., Webster, J. R., Krishnan, M. T., Sammarco, S., Man, P. M., Jones, D., Heldsinger, D., Mastrangelo, C. H. and Burke, D. T. An integrated nanoliter DNA analysis device. Science, 1998, 282, 484–487.
Back to Issue

Back issues