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

Author
Athanasios T. Giannitsis
Abstract
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.
References

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.
doi:10.1021/ac0202435

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.
doi:10.1021/ac020239t

5. West, J., Becker, M., Tombrink, S. and Manz, A. Micro total analysis systems: latest achieve­ments. Anal. Chem., 2008, 80, 4403–4419.
doi:10.1021/ac800680j

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.
doi:10.1021/ac981382i

 8. Wang, J. and Pumera, M. Dual conductivity/amperometric detection system for microchip capillary electrophoresis. Anal. Chem., 2002, 74, 5919–5923.
doi:10.1021/ac020416q

 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.
doi:10.1021/ac9906678

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.
doi:10.1021/ac001533t

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.
doi:10.1016/S0925-4005(01)00553-6

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.
doi:10.1088/0960-1317/8/1/004

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.
doi:10.1021/ac00041a030

14. Wang, J., Chen, G. and Muck, A. Movable contactless-conductivity detector for microchip capillary electrophoresis. Anal. Chem., 2003, 75, 4475–4479.
doi:10.1021/ac030122k

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.
doi:10.1021/ac025746p

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.
doi:10.1039/b717785b

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.
doi:10.1021/ac0157371

18. Kutter, J. P. Current developments in electrophoretic and chromatographic separation methods on microfabricated devices. Trends Analyt. Chem., 2000, 19, 352–363.
doi:10.1016/S0165-9936(00)00014-5

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.
doi:10.1016/j.chroma.2004.05.065

20. Pumera, M. Microchip-based electrochromatography: Designs and applications. Talanta, 2005, 66, 1048–1062.
doi:10.1016/j.talanta.2005.01.006

21. Végvári, Á. and Hjertén, S. A hybrid microdevice for electrophoresis and electro­chromato­graphy using UV detection. Electrophoresis, 2002, 23, 3479–3486.
doi:10.1002/1522-2683(200210)23:20<3479::AID-ELPS3479>3.0.CO;2-W

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.
doi:10.1021/ac0109467

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.
doi:10.1021/ac011077o

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.
doi:10.1002/elps.200305568

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.
doi:10.1021/ac950768f

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.
doi:10.1039/b511766f

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.
doi:10.1039/b602702d

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.
doi:10.1109/LPT.2007.892906

29. MacDonald, M. P., Spalding, G. C. and Dholakia, K. Microfluidic sorting in an optical lattice. Nature, 2003, 426, 421–424.
doi:10.1038/nature02144

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.
doi:10.1021/ac802668z

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.
doi:10.1021/ac990644t

32. Squires, T. M. and Quake, S. R. Microfluidics: Fluid physics at the nanoliter scale. Rev. Mod. Phys., 2005, 77, 977–1026.
doi:10.1103/RevModPhys.77.977

33. Pamme, N. Continuous flow separations in microfluidic devices. Lab Chip, 2007, 7, 1644–1659.
doi:10.1039/b712784g

34. Teh, S. Y., Lin, R., Hung, L. H. and Lee, A. P. Droplet microfluidics. Lab Chip, 2008, 8, 198–220.
doi:10.1039/b715524g

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.
doi:10.1039/b301258c

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.
doi:10.1002/elsc.200720229

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.
doi:10.1109/84.623109

39. Hayes, R. A. and Feenstra, B. J. Video-speed electric paper based on electrowetting. Nature, 2003, 425, 383–385.
doi:10.1038/nature01988

40. Kuiper, S. and Hendriks, B. H. W. Variable-focus liquid lens for miniature cameras. Appl. Phys. Lett., 2004, 85, 1128–1130.
doi:10.1063/1.1779954

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.
doi:10.1039/b501885d

42. Yamada, M. and Seki, M. Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. Lab Chip, 2005, 5, 1233–1239.
doi:10.1039/b509386d

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.
doi:10.1039/b701227f

45. Zhang, C. X. and Manz, A. High-speed free-flow electrophoresis on chip. Anal. Chem., 2003, 75, 5759–5766.
doi:10.1021/ac0345190

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.
doi:10.1021/la0347511

47. Jones, T. B. On the relationship of dielectrophoresis and electrowetting. Langmuir, 2002, 18, 4437–4443.
doi:10.1021/la025616b

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.
doi:10.1063/1.1308534

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.
doi:10.1039/b110474h

50. Washizu, M. Electrostatic actuation of liquid droplets for micro-reactor applications. IEEE Trans. Ind. Appl., 1998, 34, 732–737.
doi:10.1109/28.703965

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.
doi:10.1063/1.1504171

52. Pamme, N. and Wilhelm, C. Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis. Lab Chip, 2006, 6, 974–980.
doi:10.1039/b604542a

53. Laser, D. J. and Santiago, J. G. A review of micropumps. J. Micromech. Microeng., 2004, 14, R35–R64.
doi:10.1088/0960-1317/14/6/R01

54. Gascoyne, P. R. and Vykoukal, J. Particle separation by dielectrophoresis. Electrophoresis, 2002, 23, 1973–1983.
doi:10.1002/1522-2683(200207)23:13<1973::AID-ELPS1973>3.0.CO;2-1

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.
doi:10.1016/0250-6874(88)87005-7

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.
doi:10.1016/j.snb.2007.10.064

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.
doi:10.1016/S0924-4247(01)00764-6

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.
doi:10.1016/S0924-4247(01)00628-8

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.
doi:10.1016/j.sna.2003.10.012

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.
doi:10.1021/ja971735f

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.
doi:10.1021/ac9606564

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.
doi:10.1016/0165-9936(91)85116-9

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.
doi:10.1109/T-ED.1979.19791

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.
doi:10.1088/0960-1317/16/2/013

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.
doi:10.1007/s10544-007-9098-7

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.
doi:10.1021/ja056641h

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.
doi:10.1021/ac049863r

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.
doi:10.1021/ac049037i

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.
doi:10.1021/ac071311w

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.
doi:10.1039/b711874k

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.
doi:10.1146/annurev.biophys.36.040306.132646

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.
doi:10.1017/S0031182099004126

73. Kopp, M. U., De Mello, A. and Manz, J. A. Chemical amplification: Continuous-flow PCR on a chip. Science, 1998, 280, 1046–1048.
doi:10.1126/science.280.5366.1046

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.
doi:10.1006/abio.1997.2530

  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.
doi:10.1093/nar/24.2.375

  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.
doi:10.1093/nar/24.2.380

  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.
doi:10.1039/b408850f

  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.
doi:10.1088/0960-1317/15/8/001

  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.
doi:10.1021/ac701809w

  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.
doi:10.1021/ac0353029

  81. Urban, G. A. Micro- and nanobiosensors – State of the art and trends. Meas. Sci. Technol., 2009, 20, 012001.
doi:10.1088/0957-0233/20/1/012001

  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.
doi:10.1021/ac0256078

  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.
doi:10.1016/S0925-4005(01)00989-3

  84. Niemeyer, C. M. and Blohm, D. DNA microarray. Angew. Chemie Int. Ed., 1999, 38, 2865–2869.
doi:10.1002/(SICI)1521-3773(19991004)38:19<2865::AID-ANIE2865>3.0.CO;2-F

  85. Blohm, D. H. and Guiseppi-Elie, A. New developments in microarray technology. Curr. Opin. Biotechnol., 2001, 12, 41–47.
doi:10.1016/S0958-1669(00)00175-0

  86. Pirrung, M. C. How to make a DNA chip. Angew. Chemie Int. Ed., 2002, 41, 1276–1289.
doi:10.1002/1521-3773(20020415)41:8<1276::AID-ANIE1276>3.0.CO;2-2

  87. Jung, A. DNA chip technology. Anal. Bioanal. Chem., 2002, 372, 41–42.
doi:10.1007/s00216-001-1161-2

  88. Saliterman, S. S. Education, bioMEMS and the medical microdevice revolution. Expert. Rev. Med. Devices, 2005, 2, 515–519.
doi:10.1586/17434440.2.5.515

  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.
doi:10.1038/nbt873

  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.
doi:10.1039/b802941e

  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.
doi:10.1039/b703546b

  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.
doi:10.1063/1.2737751

  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.
doi:10.1088/0022-3727/40/1/S10

  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.
doi:10.1038/15095

  98. Zemann, A. J., Schnell, E., Volgger, D. and Bonn, G. K. Contactless conductivity detection for capillary electrophoresis. Analyt. Chem., 1998, 70, 563–567.
doi:10.1021/ac9707592

  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.
doi:10.1021/ac011219e

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.
doi:10.1002/1522-2683(200211)23:21<3769::AID-ELPS3769>3.0.CO;2-E

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.
doi:10.1002/elps.200600113

102. Gorbatsova, J., Jaanus, M. and Kaljurand, M. Digital microfluidic sampler for a portable capillary electropherograph. Analyt. Chem., 2009, 81, 8590–8595.
doi:10.1021/ac9015825

103. da Silva, J. A. F. and do Lago, C. L. An oscillometric detector for capillary electrophoresis. Analyt. Chem., 1998, 70, 4339–4343.
doi:10.1021/ac980185g

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.
doi:10.1002/elps.200500149

105. Cabrera, C. R. and Yager, P. Continuous concentration of bacteria in a microfluidic flow cell using electrokinetic techniques. Electrophoresis, 2001, 22, 355–362.
doi:10.1002/1522-2683(200101)22:2<355::AID-ELPS355>3.0.CO;2-C

106. Lu, H., Schmidt, M. A. and Jensen, K. F. A microfluidic electroporation device for cell lysis. Lab Chip, 2005, 5, 23–29.
doi:10.1039/b406205a

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.
doi:10.1039/b613344d

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.
doi:10.1016/j.sna.2005.01.030

109. Huang, Y. and Pethig, R. Electrode design for negative dielectrophoresis. Meas. Sci. Technol., 1991, 2, 1142–1146.
doi:10.1088/0957-0233/2/12/005

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.
doi:10.1109/28.585856

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.
doi:10.1016/S0006-3495(97)78834-9

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.
doi:10.1016/j.oraloncology.2006.02.012

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.
doi:10.1016/j.mimet.2004.05.002

114. Jones, T. B. Electromechanics of Particles. Cambridge University Press, 1995.
doi:10.1017/CBO9780511574498

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.
doi:10.1039/b210621n

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.
doi:10.1039/b514327f

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.
doi:10.1109/TNB.2003.820276

122. Valberg, P. A. and Butler, J. P. Magnetic particle motions within living cells – Physical theory and techniques. Biophys. J., 1987, 52, 537–550.
doi:10.1016/S0006-3495(87)83243-5

123. Wang, N., Butler, J. P. and Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science, 1993, 260, 1124–1127.
doi:10.1126/science.7684161

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.
doi:10.1063/1.2227517

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.
doi:10.1016/j.snb.2005.12.053

126. Xia, Y. and Whitesides, G. M. Soft lithography. Ann. Rev. Mater. Sci., 1998, 28, 153–184.
doi:10.1146/annurev.matsci.28.1.153

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.
doi:10.1063/1.110628

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.
doi:10.1016/0925-4005(93)80033-8

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.
doi:10.1021/ac950766v

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.
doi:10.1021/ac00073a029

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.
doi:10.1021/ac00079a028

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.
doi:10.1021/ac961038q

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.
doi:10.1021/ac0029511

135. Friend, J. and Yeo, L. Fabrication of microfluidic devices using polydimethylsiloxane. Bio­microfluidics, 2010, 4, 026502.
doi:10.1063/1.3259624

136. Toepke, M. W. and Beebe, D. J. PDMs absorption of small molecules and consequences in microfluidic applications. Lab Chip, 2006, 6, 1484–1486.
doi:10.1039/b612140c

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.
doi:10.1088/0960-1317/9/2/003

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.
doi:10.1063/1.370817

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.
doi:10.1016/j.snb.2008.12.041

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.
doi:10.1016/j.apsusc.2005.03.224

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.
doi:10.1021/jp066101m

143. Hoque, E., DeRose, J. A., Hoffmann, P. and Mathieu, H. J. Robust perfluorosilanized copper surfaces. Surf. Interface Anal., 2006, 38, 62–68.
doi:10.1002/sia.2179

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.
doi:10.1063/1.2735682

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.
doi:10.1016/j.mee.2007.01.263

146. Seyrat, E. and Hayes, R. A. Amorphous fluoropolymers as insulators for reversible low-voltage electrowetting. J. Appl. Phys., 2001, 90, 1383–1386.
doi:10.1063/1.1383583

147. Kedzierski, J. and Berry, S. Engineering the electrocapillary behavior of electrolyte droplets on thin fluoropolymer films. Langmuir, 2006, 22, 5690–5696.
doi:10.1021/la060204e

148. Schreiber, F. Structure and growth of self-assembling monolayers. Progress in Surface Science, 2000, 65, 151–256.
doi:10.1016/S0079-6816(00)00024-1

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.
doi:10.1109/JMEMS.2005.851837

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.
doi:10.1088/0960-1317/17/8/015

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.
doi:10.1088/0960-1317/18/5/055019

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.
doi:10.1016/S0142-9612(02)00007-8

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.
doi:10.1016/S0142-9612(02)00565-3

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.
doi:10.1016/S0925-4005(98)00099-9

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.
doi:10.4028/www.scientific.net/KEM.342-343.89

156. Klapperich, C. M. Microfluidic diagnostics: Time for industry standards. Expert Rev. Medical Devices, 2009, 6, 211–213.
doi:10.1586/erd.09.11

157. Pfohl, T., Mugele, F., Seemann, R. and Herminghaus, S. Trends in microfluidics with complex fluids. Chemphyschem, 2003, 4, 1291–1298.
doi:10.1002/cphc.200390120

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.
doi:10.1016/S0960-9822(01)00187-7

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.
doi:10.1016/S0303-2647(99)00043-X

161. Hug, H. and Schuler, R. Strategies for the development of a peptide computer. Bioinformatics, 2001, 17, 364–368.
doi:10.1093/bioinformatics/17.4.364

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.
doi:10.1126/science.288.5469.1223

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.
doi:10.1364/OE.16.012607

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.
doi:10.1016/j.snb.2006.08.033

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.
doi:10.1049/iet-nbt:20070020

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.
doi:10.1016/j.trac.2007.12.006

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.
doi:10.1126/science.282.5388.484
Back to Issue

Back issues