Packaging for Bio-micro-electro-mechanical Systems (BioMEMS) and Microfluidic Chips

  • Edward S. Park
  • Jan Krajniak
  • Hang Lu


In the last two decades, fundamental and application-driven research on microfluidics and bio-micro-electro-mechanical systems (BioMEMS) has flourished in academia and industries and has begun to make impact on medicine and biosciences. Packaging of these systems is an integral if not critical part of the device/system design and function. Because the applications and the designs of the chips are wide ranging, it is difficult to achieve a universal packaging scheme that meets the requirements of all applications. Instead, research and manufacturing practices of each type of biochip have come up with specialty techniques. This chapter will review these techniques in the specific contexts of the chip applications, as well as materials requirements. In addition, we will highlight common and advanced practices and point out research needs in these areas.


Packaging Lab-on-a-chip BioMEMS Microfluidics Medical diagnostics Chip-to-world connection Biocompatibility Surface modification Interface Integration Fluidic interconnect Electrical interconnect Optical transparency Disposable Point-of-care diagnostic Sample preparation Fluid handling Soft lithography Large-scale integration Microfabrication 


  1. 1.
    Chin C.D., V. Linder, S.K. Sia. Lab-on-a-chip devices for global health: Past studies and future opportunities. Lab on a Chip 2007;7(1):41–57.CrossRefGoogle Scholar
  2. 2.
    Yager P., T. Edwards, E. Fu, K. Helton, K. Nelson, M.R. Tam, B.H. Weigl. Microfluidic diagnostic technologies for global public health. Nature 2006;442(7101):412–418.CrossRefGoogle Scholar
  3. 3.
    Engler K.H., A. Efstratiou, D. Norn, R.S. Kozlov, I. Selga, T.G. Glushkevich, M. Tam, V.G. Melnikov, I.K. Mazurova, V.E. Kim, G.Y. Tseneva, L.P. Titov, R.C. George. Immunochromatographic strip test for rapid detection of diphtheria toxin: Description and multicenter evaluation in areas of low and high prevalence of diphtheria. Journal of Clinical Microbiology 2002;40(1):80–83.CrossRefGoogle Scholar
  4. 4.
    Arai H., B. Petchclai, K. Khupulsup, T. Kurimura, K. Takeda. Evaluation of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus. Journal of Clinical Microbiology 1999;37(2):367–370.Google Scholar
  5. 5.
    Patterson K., B. Olsen, C. Thomas, D. Norn, M. Tam, C. Elkins. Development of a rapid immunodiagnostic test for Haemophilus ducreyi. Journal of Clinical Microbiology 2002;40(10):3694–3702.CrossRefGoogle Scholar
  6. 6.
    Zarakolu P., I. Buchanan, M. Tam, K. Smith, E.W. Hook. Preliminary evaluation of an immunochromatographic strip test for specific Treponema pallidum antibodies. Journal of Clinical Microbiology 2002;40(8):3064–3065.CrossRefGoogle Scholar
  7. 7.
    Martinez A.W., S.T. Phillips, M.J. Butte, G.M. Whitesides. Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angewandte Chemie-International Edition 2007;46(8):1318–1320.CrossRefGoogle Scholar
  8. 8.
    Martinez A.W., S.T. Phillips, E. Carrilho, S.W. Thomas, H. Sindi, G.M. Whitesides. Simple telemedicine for developing regions: Camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Analytical Chemistry 2008;80(10):3699–3707.CrossRefGoogle Scholar
  9. 9.
    Martinez A.W., S.T. Phillips, G.M. Whitesides. Three-dimensional microfluidic devices fabricated in layered paper and tape. Proceedings of the National Academy of Sciences 2008;105(50):19606–19611.CrossRefGoogle Scholar
  10. 10.
    Hintsche R., B. Moller, I. Dransfeld, U. Wollenberger, F. Scheller, B. Hoffmann. Chip Biosensors on Thin-Film Metal-Electrodes. Sensors and Actuators B-Chemical 1991;4(3–4):287–291.CrossRefGoogle Scholar
  11. 11.
    Shulga A.A., A.P. Soldatkin, A.V. Elskaya, S.V. Dzyadevich, S.V. Patskovsky, V.I. Strikha. Thin-Film Conductometric Biosensors for Glucose and Urea Determination. Biosensors & Bioelectronics 1994;9(3):217–223.CrossRefGoogle Scholar
  12. 12.
    Hunt H.C., J.S. Wilkinson. Optofluidic integration for microanalysis. Microfluidics and Nanofluidics 2008;4(1–2):53–79.CrossRefGoogle Scholar
  13. 13.
    Cui Y., Q.Q. Wei, H.K. Park, C.M. Lieber. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 2001;293(5533):1289–1292.CrossRefGoogle Scholar
  14. 14.
    Zheng G.F., F. Patolsky, Y. Cui, W.U. Wang, C.M. Lieber. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nature Biotechnology 2005;23(10):1294–1301.CrossRefGoogle Scholar
  15. 15.
    Bashir R. BioMEMS: state-of-the-art in detection, opportunities and prospects. Advanced Drug Delivery Reviews 2004;56(11):1565–1586.CrossRefGoogle Scholar
  16. 16.
    Waggoner P.S., H.G. Craighead. Micro- and nanomechanical sensors for environmental, chemical, and biological detection. Lab on a Chip 2007;7(10):1238–1255.CrossRefGoogle Scholar
  17. 17.
    Fritz J., M.K. Baller, H.P. Lang, H. Rothuizen, P. Vettiger, E. Meyer, H.J. Guntherodt, C. Gerber, J.K. Gimzewski. Translating biomolecular recognition into nanomechanics. Science 2000;288(5464):316–318.CrossRefGoogle Scholar
  18. 18.
    Hansen K.M., H.F. Ji, G.H. Wu, R. Datar, R. Cote, A. Majumdar, T. Thundat. Cantilever-based optical deflection assay for discrimination of DNA single-nucleotide mismatches. Analytical Chemistry 2001;73(7):1567–1571.CrossRefGoogle Scholar
  19. 19.
    Gupta A., D. Akin, R. Bashir. Single virus particle mass detection using microresonators with nanoscale thickness. Applied Physics Letters 2004;84(11):1976–1978.CrossRefGoogle Scholar
  20. 20.
    Ilic B., D. Czaplewski, H.G. Craighead, P. Neuzil, C. Campagnolo, C. Batt. Mechanical resonant immunospecific biological detector. Applied Physics Letters 2000;77(3):450–452.CrossRefGoogle Scholar
  21. 21.
    McKendry R., J.Y. Zhang, Y. Arntz, T. Strunz, M. Hegner, H.P. Lang, M.K. Baller, U. Certa, E. Meyer, H.J. Guntherodt, C. Gerber. Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array. Proceedings of the National Academy of Sciences of the United States of America 2002;99(15):9783–9788.CrossRefGoogle Scholar
  22. 22.
    Wu G.H., R.H. Datar, K.M. Hansen, T. Thundat, R.J. Cote, A. Majumdar. Bioassay of prostate-specific antigen (PSA) using microcantilevers. Nature Biotechnology 2001;19(9):856–860.CrossRefGoogle Scholar
  23. 23.
    Burg T.P., M. Godin, S.M. Knudsen, W. Shen, G. Carlson, J.S. Foster, K. Babcock, S.R. Manalis. Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature 2007;446:1066–1069.CrossRefGoogle Scholar
  24. 24.
    Burg T.P., A.R. Mirza, N. Milovic, C.H. Tsau, G.A. Popescu, J.S. Foster, S.R. Manalis. Vacuum-packaged suspended microchannel resonant mass sensor for biomolecular detection. Journal of Microelectromechanical Systems 2006;15(6):1466–1476.CrossRefGoogle Scholar
  25. 25.
    Fruetel J.A., R.F. Renzi, V.A. VanderNoot, J. Stamps, B.A. Horn, J.A.A. West, S. Ferko, R. Crocker, C.G. Bailey, D. Arnold, B. Wiedenman, W.Y. Choi, D. Yee, I. Shokair, E. Hasselbrink, P. Paul, D. Rakestraw, D. Padgen. Microchip separations of protein biotoxins using an integrated hand-held device. Electrophoresis 2005;26(6):1144–1154.CrossRefGoogle Scholar
  26. 26.
    Stratis-Cullum D.N., G.D. Griffin, J. Mobley, A.A. Vass, T. Vo-Dinh. A miniature biochip system for detection of aerosolized Bacillus globigii spores. Analytical Chemistry 2003;75(2):275–280.CrossRefGoogle Scholar
  27. 27.
    Psaltis D., S.R. Quake, C.H. Yang. Developing optofluidic technology through the fusion of microfluidics and optics. Nature 2006;442(7101):381–386.CrossRefGoogle Scholar
  28. 28.
    Irawan R., S.C. Tjin, X.Q. Fang, C.Y. Fu. Integration of optical fiber light guide, fluorescence detection system, and multichannel disposable microfluidic chip. Biomedical Microdevices 2007;9(3):413–419.CrossRefGoogle Scholar
  29. 29.
    Lin C.H., G.B. Lee, S.H. Chen, G.L. Chang. Micro capillary electrophoresis chips integrated with buried SU-8/SOG optical waveguides for bio-analytical applications. Sensors and Actuators a-Physical 2003;107(2):125–131.CrossRefGoogle Scholar
  30. 30.
    Kou Q., I. Yesilyurt, V. Studer, M. Belotti, E. Cambril, Y. Chen. On-chip optical components and microfluidic systems. Microelectronic Engineering 2004;73–74:876–880.CrossRefGoogle Scholar
  31. 31.
    Misiakos K., S.E. Kakabakos, P.S. Petrou, H.H. Ruf. A monolithic silicon optoelectronic transducer as a real-time affinity biosensor. Analytical Chemistry 2004;76(5):1366–1373.CrossRefGoogle Scholar
  32. 32.
    Balslev S., A.M. Jorgensen, B. Bilenberg, K.B. Mogensen, D. Snakenborg, O. Geschke, J.P. Kutter, A. Kristensen. Lab-on-a-chip with integrated optical transducers. Lab on a Chip 2006;6(2):213–217.CrossRefGoogle Scholar
  33. 33.
    Dandin M., P. Abshire, E. Smela. Optical filtering technologies for integrated fluorescence sensors. Lab on a Chip 2007;7(8):955–977.CrossRefGoogle Scholar
  34. 34.
    Prakash A.R., S. Adamia, V. Sieben, P. Pilarski, L.M. Pilarski, C.J. Backhouse. Small volume PCR in PDMS biochips with integrated fluid control and vapour barrier. Sensors and Actuators B-Chemical 2006;113(1):398–409.CrossRefGoogle Scholar
  35. 35.
    Kaigala G.V., V.N. Hoang, A. Stickel, J. Lauzon, D. Manage, L.M. Pilarski, C.J. Backhouse. An inexpensive and portable microchip-based platform for integrated RT-PCR and capillary electrophoresis. Analyst 2008;133(3):331–338.CrossRefGoogle Scholar
  36. 36.
    Weibel D.B., M. Kruithof, S. Potenta, S.K. Sia, A. Lee, G.M. Whitesides. Torque-actuated valves for microfluidics. Analytical Chemistry 2005;77(15):4726–4733.CrossRefGoogle Scholar
  37. 37.
    Burns M.A., B.N. Johnson, S.N. Brahmasandra, K. Handique, J.R. Webster, M. Krishnan, T.S. Sammarco, P.M. Man, D. Jones, D. Heldsinger, C.H. Mastrangelo, D.T. Burke. An integrated nanoliter DNA analysis device. Science 1998;282(5388):484–487.CrossRefGoogle Scholar
  38. 38.
    Liu R.H., J.N. Yang, R. Lenigk, J. Bonanno, P. Grodzinski. Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection. Analytical Chemistry 2004;76(7):1824–1831.CrossRefGoogle Scholar
  39. 39.
    Pal R., M. Yang, R. Lin, B.N. Johnson, N. Srivastava, S.Z. Razzacki, K.J. Chomistek, D.C. Heldsinger, R.M. Haque, V.M. Ugaz, P.K. Thwar, Z. Chen, K. Alfano, M.B. Yim, M. Krishnan, A.O. Fuller, R.G. Larson, D.T. Burke, M.A. Burns. An integrated microfluidic device for influenza and other genetic analyses. Lab on a Chip 2005;5(10):1024–1032.CrossRefGoogle Scholar
  40. 40.
    Fu E., T. Chinowsky, K. Nelson, K. Johnston, T. Edwards, K. Helton, M. Grow, J.W. Miller, P. Yager. SPR imaging-based salivary diagnostics system for the detection of small molecule analytes. Oral-Based Diagnostics. Blackwell Publishing: Oxford, UK, 2007. 335–344.Google Scholar
  41. 41.
    Velten T., H.H. Ruf, D. Barrow, N. Aspragathos, P. Lazarou, E. Jung, C.K. Malek, M. Richter, J. Kruckow. Packaging of bio-MEMS: Strategies, technologies, and applications. IEEE Transactions on Advanced Packaging 2005;28(4):533–546.CrossRefGoogle Scholar
  42. 42.
    Herr A.E., A.V. Hatch, D.J. Throckmorton, H.M. Tran, J.S. Brennan, W.V. Giannobile, A.K. Singh. Microfluidic immunoassays as rapid saliva-based clinical diagnostics. Proceedings of the National Academy of Sciences of the United States of America 2007;104(13):5268–5273.CrossRefGoogle Scholar
  43. 43.
    Lagally E.T., J.R. Scherer, R.G. Blazej, N.M. Toriello, B.A. Diep, M. Ramchandani, G.F. Sensabaugh, L.W. Riley, R.A. Mathies. Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. Analytical Chemistry 2004;76(11):3162–3170.CrossRefGoogle Scholar
  44. 44.
    Wang J., M.P. Chatrathi, A. Mulchandani, W. Chen. Capillary electrophoresis microchips for separation and detection of organophosphate nerve agents. Analytical Chemistry 2001;73(8):1804–1808.CrossRefGoogle Scholar
  45. 45.
    Chinowsky T.M., S.D. Soelberg, P. Baker, N.R. Swanson, P. Kauffman, A. Mactutis, M.S. Grow, R. Atmar, S.S. Yee, C.E. Furlong. Portable 24-analyte surface plasmon resonance instruments for rapid, versatile biodetection. Biosensors & Bioelectronics 2007;22(9–10):2268–2275.CrossRefGoogle Scholar
  46. 46.
    DeBusschere B.D., G.T.A. Kovacs. Portable cell-based biosensor system using integrated CMOS cell-cartridges. Biosensors & Bioelectronics 2001;16(7–8):543–556.CrossRefGoogle Scholar
  47. 47.
    Hood L., J.R. Heath, M.E. Phelps, B.Y. Lin. Systems biology and new technologies enable predictive and preventative medicine. Science 2004;306(5696):640–643.CrossRefGoogle Scholar
  48. 48.
    Weston A.D., L. Hood. Systems biology, proteomics, and the future of health care: Toward predictive, preventative, and personalized medicine. Journal of Proteome Research 2004;3(2):179–196.CrossRefGoogle Scholar
  49. 49.
    Bhattacharyya A., C.M. Klapperich. Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples. Biomedical Microdevices 2007;9(2):245–251.CrossRefGoogle Scholar
  50. 50.
    Linder V., S.K. Sia, G.M. Whitesides. Reagent-loaded cartridges for valveless and automated fluid delivery in microfluidic devices. Analytical Chemistry 2005;77(1):64–71.CrossRefGoogle Scholar
  51. 51.
    Grayson A.C.R., R.S. Shawgo, A.M. Johnson, N.T. Flynn, Y.W. Li, M.J. Cima, R. Langer. A BioMEMS review: MEMS technology for physiologically integrated devices. Proceedings of the IEEE 2004;92(1):6–21.CrossRefGoogle Scholar
  52. 52.
    Fonseca M A.M.D.S.J.W.J.K.; Cardiomems, Innc., assignee. Implantable Wireless Sensor for Pressure Measurement within the Heart. US patent 6855115. 2005 Feb 15Google Scholar
  53. 53.
    Santini J.T.M.J.C.R.S.L.; MIT, assignee. Microchip Drug Delivery Devices. US. 1998 Aug 25Google Scholar
  54. 54.
    Kudo H., T. Sawada, E. Kazawa, H. Yoshida, Y. Iwasaki, K. Mitsubayashi. A flexible and wearable glucose sensor based on functional polymers with Soft-MEMS techniques. Biosensors & Bioelectronics 2006;22(4):558–562.CrossRefGoogle Scholar
  55. 55.
    Zhao Y.J., S.Q. Li, A. Davidson, B.Z. Yang, Q. Wang, Q. Lin. A MEMS viscometric sensor for continuous glucose monitoring. Journal of Micromechanics and Microengineering 2007;17(12):2528–2537.CrossRefGoogle Scholar
  56. 56.
    Jauniaux E., A. Watson, O. Ozturk, D. Quick, G. Burton. In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy. Human Reproduction 1999;14(11):2901–2904.CrossRefGoogle Scholar
  57. 57.
    Prausnitz M.R. Microneedles for transdermal drug delivery. Advanced Drug Delivery Reviews 2004;56(5):581–587.CrossRefGoogle Scholar
  58. 58.
    Prausnitz M.R., M.G. Allen, I.J. Gujral. Microneedle drug delivery device. US Patent 7, 226, 439; 2007.Google Scholar
  59. 59.
    Gujral I.J., M.G. Allen, M.R. Prausnitz. Microneedle device for extraction and sensing of bodily fluids. US Patent 7,344,499; 2008.Google Scholar
  60. 60.
    McAllister D.V., P.M. Wang, S.P. Davis, J.H. Park, P.J. Canatella, M.G. Allen, M.R. Prausnitz. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proceedings of the National Academy of Sciences 2003;100(24):13755–13760.CrossRefGoogle Scholar
  61. 61.
    Li P.Y., J. Shih, R. Lo, S. Saati, R. Agrawal, M.S. Humayun, Y.C. Tai, E. Meng. An electrochemical intraocular drug delivery device. Sensors and Actuators a-Physical 2008;143(1):41–48.CrossRefGoogle Scholar
  62. 62.
    Santini J.T., M.J. Cima, R. Langer. A controlled-release microchip. Nature 1999;397(6717):335–338.CrossRefGoogle Scholar
  63. 63.
    Voskerician G., R.S. Shawgo, P.A. Hiltner, J.M. Anderson, M.J. Cima, R. Langer. In vivo inflammatory and wound healing effects of gold electrode voltammetry for MEMS micro-reservoir drug delivery device. Ieee Transactions on Biomedical Engineering 2004;51(4):627–635.CrossRefGoogle Scholar
  64. 64.
    Razzacki S.Z., P.K. Thwar, M. Yang, V.M. Ugaz, M.A. Burns. Integrated microsystems for controlled drug delivery. Advanced Drug Delivery Reviews 2004;56(2):185–198.CrossRefGoogle Scholar
  65. 65.
    Wu C.C., T. Yasukawa, H. Shiku, T. Matsue. Fabrication of miniature Clark oxygen sensor integrated with microstructure. Sensors and Actuators B-Chemical 2005;110(2):342–349.CrossRefGoogle Scholar
  66. 66.
    Wu H.K., B. Huang, R.N. Zare. Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding. Lab on a Chip 2005;5(12):1393–1398.CrossRefGoogle Scholar
  67. 67.
    Hungar K., M. Gortz, E. Slavcheva, G. Spanier, C. Weidig, W. Mokwa. Production processes for a flexible retina implant (Eurosensors XVIII, Session C6.6). Sensors and Actuators a-Physical 2005;123–24:172–178.Google Scholar
  68. 68.
    Schanze T., L. Hesse, C. Lau, N. Greve, W. Haberer, S. Kammer, T. Doerge, A. Rentzos, T. Stieglitz. An optically powered single-channel stimulation implant as test-system for chronic biocompatibility and biostability of miniaturized retinal vision prostheses. Ieee Transactions on Biomedical Engineering 2007;54(6):983–992.CrossRefGoogle Scholar
  69. 69.
    Schwarz M., L. Ewe, R. Hauschild, B.J. Hosticka, J. Huppertz, S. Kolnsberg, W. Mokwa, H.K. Trieu. Single chip CMOS imagers and flexible microelectronic stimulators for a retina implant system. Sensors and Actuators a-Physical 2000;83(1–3):40–46.CrossRefGoogle Scholar
  70. 70.
    Loeb G.E., R.A. Peck, W.H. Moore, K. Hood. BION (TM) system for distributed neural prosthetic interfaces. Medical Engineering & Physics 2001;23(1):9–18.CrossRefGoogle Scholar
  71. 71.
    Weiland J.D., W.T. Liu, M.S. Humayun. Retinal prosthesis. Annual Review of Biomedical Engineering 2005;7:361-401.CrossRefGoogle Scholar
  72. 72.
    Schwartz A.B. Cortical Neural Prosthetics. Annual Review of Neuroscience 2004;27(1):487–507.CrossRefGoogle Scholar
  73. 73.
    Cheung K.C. Implantable microscale neural interfaces. Biomedical Microdevices 2007;9(6):923–938.CrossRefGoogle Scholar
  74. 74.
    Kipke D.R., R.J. Vetter, J.C. Williams, J.F. Hetke. Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex. IEEE Trans on Rehabilitation Engineering 2003;11(2):151–155.CrossRefGoogle Scholar
  75. 75.
    Rutten W.L.C. Selective electrical interfaces with the nervous system. Annual Review of Biomedical Engineering 2002;4(1):407–452.CrossRefGoogle Scholar
  76. 76.
    Cogan S.F. Neural Stimulation and Recording Electrodes. Annual Review of Biomedical Engineering 2008;10(1):275–309.CrossRefGoogle Scholar
  77. 77.
    Tokuda T., Y.L. Pan, A. Uehara, K. Kagawa, M. Nunoshita, J. Ohta. Flexible and extendible neural interface device based on cooperative multi-chip CMOS LSI architecture. Sensors and Actuators a-Physical 2005;122(1):88–98.CrossRefGoogle Scholar
  78. 78.
    Smith B., Z.N. Tang, M.W. Johnson, S. Pourmehdi, M.M. Gazdik, J.R. Buckett, P.H. Peckham. An externally powered, multichannel, implantable stimulator-telemeter for control of paralyzed muscle. Ieee Transactions on Biomedical Engineering 1998;45(4):463–475.CrossRefGoogle Scholar
  79. 79.
    Windecker S., I. Mayer, G. De Pasquale, W. Maier, O. Dirsch, P. De Groot, Y.P. Wu, G. Noll, B. Leskosek, B. Meier, O.M. Hess, C. Working Grp Novel Surface. Stent coating with titanium-nitride-oxide for reduction of neointimal hyperplasia. Circulation 2001;104(8):928–933.Google Scholar
  80. 80.
    Grube E., U. Gerckens, S. Rowold, R. Muller, G. Selbach, J. Stamm, M. Staberock. Inhibition of in-stent restenosis by the Quanam drug eluting polymer stent; Two year follow-up. Journal of the American College of Cardiology 2001;37(2):74A–74A.CrossRefGoogle Scholar
  81. 81.
    Hiatt B.L., F. Ikeno, A.C. Yeung, A.J. Carter. Drug-eluting stents for the prevention of restenosis: In quest for the holy grail. Catheterization and Cardiovascular Interventions 2002;55(3):409–417.CrossRefGoogle Scholar
  82. 82.
    Allen M. G M.E.J.K.D.J.M.; CardioMEMS, Inc., assignee. Communication wit an Implanted Wireless Sensor. US. 2007Google Scholar
  83. 83.
    Klose J., E. Rehtanz, C. Rothe, I. Eulitz, V. Guther, W. Beck. Manufacture of titanium implants. Materialwissenschaft Und Werkstofftechnik 2008;39(4–5):304–308.CrossRefGoogle Scholar
  84. 84.
    Wiegand U.K.H., J. Potratz, F. Luninghake, G. Taubert, A. Brandes, K.W. Diederich. Electrophysiological characteristics of bipolar membrane carbon leads with and without steroid elution compared with a conventional carbon and a steroid-eluting platinum lead. Pace-Pacing and Clinical Electrophysiology 1996;19(8):1155–1161.CrossRefGoogle Scholar
  85. 85.
    Wiegand U.K.H., A. Zhdanov, E. Stammwitz, I. Crozier, R.J.J. Claessens, J. Meier, R.J. Bos, F. Bode, J. Potratz. Electrophysiological performance of a bipolar membrane-coated titanium nitride electrode: A randomized comparison of steroid and nonsteroid lead designs. Pace-Pacing and Clinical Electrophysiology 1999;22(6):935–941.CrossRefGoogle Scholar
  86. 86.
    Wiggins M.J., B. Wilkoff, J.M. Anderson, A. Hiltner. Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads. Journal of Biomedical Materials Research 2001;58(3):302–307.CrossRefGoogle Scholar
  87. 87.
    Russell R.J., M.V. Pishko, C.C. Gefrides, M.J. McShane, G.L. Cote. A Fluorescence-Based Glucose Biosensor Using Concanavalin A and Dextran Encapsulated in a Poly(ethylene glycol) Hydrogel. Analytical Chemistry 1999;71(15):3126–3132.CrossRefGoogle Scholar
  88. 88.
    Receveur R.A.M., F.W. Lindemans, N.F. de Rooij. Microsystem technologies for implantable applications. Journal of Micromechanics and Microengineering 2007;17(5):R50–R80.CrossRefGoogle Scholar
  89. 89.
    Mokwa W., U. Schnakenberg. Micro-transponder systems for medical applications. Ieee Transactions on Instrumentation and Measurement 2001;50(6):1551–1555.CrossRefGoogle Scholar
  90. 90.
    Flick B.B., R. Orglmeister. A portable microsystem-based telemetric pressure and temperature measurement unit. Ieee Transactions on Biomedical Engineering 2000;47(1):12–16.CrossRefGoogle Scholar
  91. 91.
    Esashi M., S. Sugiyama, K. Ikeda, Y.L. Wang, H. Miyashita. Vacuum-sealed silicon micromachined pressure sensors. Proceedings of the Ieee 1998;86(8):1627–1639.CrossRefGoogle Scholar
  92. 92.
    Chen P.J., D.C. Rodger, R. Agrawal, S. Saati, E. Meng, R. Varma, M.S. Humayun, Y.C. Tai. Implantable micromechanical parylene-based pressure sensors for unpowered intraocular pressure sensing. Journal of Micromechanics and Microengineering 2007;17(10):1931–1938.CrossRefGoogle Scholar
  93. 93.
    Chen L., A. Manz, P.J.R. Day. Total nucleic acid analysis integrated on microfluidic devices. Lab on a Chip 2007;7(11):1413–1423.CrossRefGoogle Scholar
  94. 94.
    Heyries K.A., M.G. Loughran, D. Hoffmann, A. Homsy, L.J. Blum, C.A. Marquette. Microfluidic biochip for chemiluminescent detection of allergen-specific antibodies. Biosensors & Bioelectronics 2008;23(12):1812–1818.CrossRefGoogle Scholar
  95. 95.
    Isoda T., I. Urushibara, M. Sato, H. Uemura, H. Sato, N. Yamauchi. Development of a sensor-array chip with immobilized antibodies and the application of a wireless antigen-screening system. Sensors and Actuators B-Chemical 2008;129(2):958–970.CrossRefGoogle Scholar
  96. 96.
    Prakash R., K. Kaler. An integrated genetic analysis microfluidic platform with valves and a PCR chip reusability method to avoid contamination. Microfluidics and Nanofluidics 2007;3(2):177–187.CrossRefGoogle Scholar
  97. 97.
    Zhang C.S., J.L. Xu, W.L. Ma, W.L. Zheng. PCR microfluidic devices for DNA amplification. Biotechnology Advances 2006;24(3):243–284.CrossRefGoogle Scholar
  98. 98.
    Sethu P., A. Sin, M. Toner. Microfluidic diffusive filter for apheresis (leukapheresis). Lab on a Chip 2006;6(1):83–89.CrossRefGoogle Scholar
  99. 99.
    Battrell C. F M.S.B.H.W.J.M.H.C.A.L.W.B.; Micronics, Inc., assignee. Method and System for Microfluidic Manipulation, Amplification and Analysis of Fluirds, for Example, Bacteria Assays and Antiglobulin Testing. US. 2004Google Scholar
  100. 100.
    Chamot S.R., C. Depeursinge. MEMS for enhanced optical diagnostics in endoscopy. Minimally Invasive Therapy & Allied Technologies 2007;16(2):101–108.CrossRefGoogle Scholar
  101. 101.
    Hupert M.L., M.A. Witek, Y. Wang, M.W. Mitchell, Y. Liu, Y. Bejat, D.E. Nikitopoulos, J. Goettert, M.C. Murphy, S.A. Soper. Polymer-based microfluidic devices for biomedical applications. Proceedings of SPIE 2003;4982:52–64.CrossRefGoogle Scholar
  102. 102.
    Mitchell M.W., X. Liu, Y. Bejat, D.E. Nikitopoulos, S.A. Soper, M.C. Murphy. Modeling and validation of a molded polycarbonate continuous flow polymerase chain reaction device. Proceedings of SPIE 2003;4982:83–98.CrossRefGoogle Scholar
  103. 103.
    Lee D.S., S.H. Park, H.S. Yang, K.H. Chung, T.H. Yoon, S.J. Kim, K. Kim, Y.T. Kim. Bulk-micromachined submicroliter-volume PCR chip with very rapid thermal response and low power consumption. Lab on a Chip 2004;4(4):401–407.CrossRefGoogle Scholar
  104. 104.
    Koh C.G., W. Tan, M.Q. Zhao, A.J. Ricco, Z.H. Fan. Integrating polymerase chain reaction, valving, and electrophoresis in a plastic device for bacterial detection. Analytical Chemistry 2003;75(17):4591–4598.CrossRefGoogle Scholar
  105. 105.
    Krishnan M., D.T. Burke, M.A. Burns. Polymerase chain reaction in high surface-to-volume ratio SiO2 microstructures. Analytical Chemistry 2004;76(22):6588–6593.CrossRefGoogle Scholar
  106. 106.
    Woolley A.T., D. Hadley, P. Landre, A.J. deMello, R.A. Mathies, M.A. Northrup. Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. Analytical Chemistry 1996;68(23):4081–4086.CrossRefGoogle Scholar
  107. 107.
    West J., B. Karamata, B. Lillis, J.P. Gleeson, J. Alderman, J.K. Collins, W. Lane, A. Mathewson, H. Berney. Application of magnetohydrodynamic actuation to continuous flow chemistry. Lab on a Chip 2002;2(4):224–230.CrossRefGoogle Scholar
  108. 108.
    Hong J.W., T. Fujii, M. Seki, T. Yamamoto, I. Endo. Integration of gene amplification and capillary gel electrophoresis on a polydimethylsiloxane-glass hybrid microchip. Electrophoresis 2001;22(2):328–333.CrossRefGoogle Scholar
  109. 109.
    Shen K.Y., X.F. Chen, M. Guo, J. Cheng. A microchip-based PCR device using flexible printed circuit technology. Sensors and Actuators B-Chemical 2005;105(2):251–258.CrossRefGoogle Scholar
  110. 110.
    Daniel J.H., S. Iqbal, R.B. Millington, D.F. Moore, C.R. Lowe, D.L. Leslie, M.A. Lee, M.J. Pearce. Silicon microchambers for DNA amplification. Sensors and Actuators a-Physical 1998;71(1–2):81–88.CrossRefGoogle Scholar
  111. 111.
    Northrup M.A., B. Benett, D. Hadley, P. Landre, S. Lehew, J. Richards, P. Stratton. A miniature analytical instrument for nucleic acids based on micromachined silicon reaction chambers. Analytical Chemistry 1998;70(5):918–922.CrossRefGoogle Scholar
  112. 112.
    Sun K., A. Yamaguchi, Y. Ishida, S. Matsuo, H. Misawa. A heater-integrated transparent microchannel chip for continuous-flow PCR. Sensors and Actuators B-Chemical 2002;84(2–3):283–289.CrossRefGoogle Scholar
  113. 113.
    Khandurina J., T.E. McKnight, S.C. Jacobson, L.C. Waters, R.S. Foote, J.M. Ramsey. Integrated system for rapid PCR-based DNA analysis in microfluidic devices. Analytical Chemistry 2000;72(13):2995–3000.CrossRefGoogle Scholar
  114. 114.
    Lin Y.C., M.Y. Huang, K.C. Young, T.T. Chang, C.Y. Wu. A rapid micro-polymerase chain reaction system for hepatitis C virus amplification. Sensors and Actuators B-Chemical 2000;71(1–2):2–8.CrossRefGoogle Scholar
  115. 115.
    Lin Y.C., C.C. Yang, M.Y. Huang. Simulation and experimental validation of micro polymerase chain reaction chips. Sensors and Actuators B-Chemical 2000;71(1–2):127–133.CrossRefGoogle Scholar
  116. 116.
    Zhou Z.M., D.Y. Liu, R.T. Zhong, Z.P. Dai, D.P. Wu, H. Wang, Y.G. Du, Z.N. Xia, L.P. Zhang, X.D. Mei, B.C. Lin. Determination of SARS-coronavirus by a microfluidic chip system. Electrophoresis 2004;25(17):3032–3039.CrossRefGoogle Scholar
  117. 117.
    Gulliksen A., L. Solli, F. Karlsen, H. Rogne, E. Hovig, T. Nordstrom, R. Sirevag. Real-time nucleic acid sequence-based amplification in nanoliter volumes. Analytical Chemistry 2004;76(1):9–14.CrossRefGoogle Scholar
  118. 118.
    Matsubara Y., K. Kerman, M. Kobayashi, S. Yamamura, Y. Morita, E. Tamiya. Microchamber array based DNA quantification and specific sequence detection from a single copy via PCR in nanoliter volumes. Biosensors & Bioelectronics 2005;20(8):1482–1490.CrossRefGoogle Scholar
  119. 119.
    Curcio M., J. Roeraade. Continuous segmented-flow polymerase chain reaction for high-throughput miniaturized DNA amplification. Analytical Chemistry 2003;75(1):1–7.CrossRefGoogle Scholar
  120. 120.
    Sethu P., C.H. Mastrangelo. Cast epoxy-based microfluidic systems and their application in biotechnology. Sensors and Actuators B-Chemical 2004;98(2–3):337–346.CrossRefGoogle Scholar
  121. 121.
    Swerdlow H., B.J. Jones, C.T. Wittwer. Fully automated DNA reaction and analysis in a fluidic capillary instrument. Analytical Chemistry 1997;69(5):848–855.CrossRefGoogle Scholar
  122. 122.
    Zhang N.Y., E.S. Yeung. On-line coupling of polymerase chain reaction and capillary electrophoresis for automatic DNA typing and HIV-1 diagnosis. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 1998;714(1):3–11.CrossRefGoogle Scholar
  123. 123.
    Ferrance J.P., Q.R. Wu, B. Giordano, C. Hernandez, Y. Kwok, K. Snow, S. Thibodeau, J.P. Landers. Developments toward a complete micro-total analysis system for Duchenne muscular dystrophy diagnosis. Analytica Chimica Acta 2003;500(1–2):223–236.CrossRefGoogle Scholar
  124. 124.
    Huhmer A.F.R., J.P. Landers. Noncontact infrared-mediated thermocycling for effective polymerase chain reaction amplification of DNA in nanoliter volumes. Analytical Chemistry 2000;72(21):5507–5512.CrossRefGoogle Scholar
  125. 125.
    Oda R.P., M.A. Strausbauch, A.F.R. Huhmer, N. Borson, S.R. Jurrens, J. Craighead, P.J. Wettstein, B. Eckloff, B. Kline, J.P. Landers. Infrared-mediated thermocycling for ultrafast polymerase chain reaction amplification of DNA. Analytical Chemistry 1998;70(20):4361–4368.CrossRefGoogle Scholar
  126. 126.
    Tanaka Y., M.N. Slyadnev, A. Hibara, M. Tokeshi, T. Kitamori. Non-contact photothermal control of enzyme reactions on a microchip by using a compact diode laser. Journal of Chromatography A 2000;894(1–2):45–51.CrossRefGoogle Scholar
  127. 127.
    Schneegass I., R. Brautigam, J.M. Kohler. Miniaturized flow-through PCR with different template types in a silicon chip thermocycler. Lab on a Chip 2001;1(1):42–49.CrossRefGoogle Scholar
  128. 128.
    Chou C.F., R. Changrani, P. Roberts, D. Sadler, J. Burdon, F. Zenhausern, S. Lin, A. Mulholland, N. Swami, R. Terbrueggen. A miniaturized cyclic PCR device - modeling and experiments. Microelectronic Engineering 2002;61–62:921–925.CrossRefGoogle Scholar
  129. 129.
    Liu J., M. Enzelberger, S. Quake. A nanoliter rotary device for polymerase chain reaction. Electrophoresis 2002;23(10):1531–1536.CrossRefGoogle Scholar
  130. 130.
    Shi Y.N., P.C. Simpson, J.R. Scherer, D. Wexler, C. Skibola, M.T. Smith, R.A. Mathies. Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis. Analytical Chemistry 1999;71(23):5354–5361.CrossRefGoogle Scholar
  131. 131.
    Waters L.C., S.C. Jacobson, N. Kroutchinina, J. Khandurina, R.S. Foote, J.M. Ramsey. Multiple sample PCR amplification and electrophoretic analysis on a microchip. Analytical Chemistry 1998;70(24):5172–5176.CrossRefGoogle Scholar
  132. 132.
    Waters L.C., S.C. Jacobson, N. Kroutchinina, J. Khandurina, R.S. Foote, J.M. Ramsey. Microchip device for cell lysis, multiplex PCR amplification, and electrophoretic sizing. Analytical Chemistry 1998;70(1):158–162.CrossRefGoogle Scholar
  133. 133.
    Perch-Nielsen I.R., D.D. Bang, C.R. Poulsen, J. El-Ali, A. Wolff. Removal of PCR inhibitors using dielectrophoresis as a selective filter in a microsystem. Lab on a Chip 2003;3(3):212–216.CrossRefGoogle Scholar
  134. 134.
    Gascoyne P., C. Mahidol, M. Ruchirawat, J. Satayavivad, P. Watcharasit, F.F. Becker. Microsample preparation by dielectrophoresis: isolation of malaria. Lab on a Chip 2002;2(2):70–75.CrossRefGoogle Scholar
  135. 135.
    Namasivayam V., R.S. Lin, B. Johnson, S. Brahmasandra, Z. Razzacki, D.T. Burke, M.A. Burns. Advances in on-chip photodetection for applications in miniaturized genetic analysis systems. Journal of Micromechanics and Microengineering 2004;14(1):81–90.CrossRefGoogle Scholar
  136. 136.
    Kumar A., G. Goel, E. Fehrenbach, A.K. Puniya, K. Singh. Microarrays: The technology, analysis and application. Engineering in Life Sciences 2005;5(3):215–222.CrossRefGoogle Scholar
  137. 137.
    Bulyk M.L. DNA microarray technologies for measuring protein-DNA interactions. Current Opinion in Biotechnology 2006;17(4):422–430.CrossRefGoogle Scholar
  138. 138.
    Cretich M., F. Damin, G. Pirri, M. Chiari. Protein and peptide arrays: Recent trends and new directions. Biomolecular Engineering 2006;23(2–3):77–88.CrossRefGoogle Scholar
  139. 139.
    Hoheisel J.D. Microarray technology: beyond transcript profiling and genotype analysis. Nature Reviews Genetics 2006;7(3):200–210.CrossRefGoogle Scholar
  140. 140.
    Hultschig C., J. Kreutzberger, H. Seitz, Z. Konthur, K. Bussow, H. Lehrach. Recent advances of protein microarrays. Current Opinion in Chemical Biology 2006;10(1):4–10.CrossRefGoogle Scholar
  141. 141.
    Stoughton R.B. Applications of DNA microarrays in biology. Annual Review of Biochemistry 2005;74:53–82.CrossRefGoogle Scholar
  142. 142.
    Barbulovic-Nad I., M. Lucente, Y. Sun, M.J. Zhang, A.R. Wheeler, M. Bussmann. Bio-microarray fabrication techniques - A review. Critical Reviews in Biotechnology 2006;26(4):237–259.CrossRefGoogle Scholar
  143. 143.
  144. 144.
    Anderson R.C., X. Su, G.J. Bogdan, J. Fenton. A miniature integrated device for automated multistep genetic assays. Nucleic Acids Research 2000;28(12):e60i–vi.Google Scholar
  145. 145.
    Lenigk R., R.H. Liu, M. Athavale, Z.J. Chen, D. Ganser, J.N. Yang, C. Rauch, Y.J. Liu, B. Chan, H.N. Yu, M. Ray, R. Marrero, P. Grodzinski. Plastic biochannel hybridization devices: a new concept for microfluidic DNA arrays. Analytical Biochemistry 2002;311(1):40–49.CrossRefGoogle Scholar
  146. 146.
    Liu J., C. Hansen, S.R. Quake. Solving the "world-to-chip" interface problem with a microfluidic matrix. Analytical Chemistry 2003;75(18):4718–4723.CrossRefGoogle Scholar
  147. 147.
    Martynova L., L.E. Locascio, M. Gaitan, G.W. Kramer, R.G. Christensen, W.A. MacCrehan. Fabrication of plastic microfluid channels by imprinting methods. Analytical Chemistry 1997;69(23):4783–4789.CrossRefGoogle Scholar
  148. 148.
    Qi S.Z., X.Z. Liu, S. Ford, J. Barrows, G. Thomas, K. Kelly, A. McCandless, K. Lian, J. Goettert, S.A. Soper. Microfluidic devices fabricated in poly(methyl methacrylate) using hot-embossing with integrated sampling capillary and fiber optics for fluorescence detection. Lab on a Chip 2002;2(2):88–95.CrossRefGoogle Scholar
  149. 149.
    Soper S.A., S.M. Ford, S. Qi, R.L. McCarley, K. Kelly, M.C. Murphy. Polymeric microelectromechanical systems. Analytical Chemistry 2000;72(19):642A–651A.CrossRefGoogle Scholar
  150. 150.
    Situma C., M. Hashimoto, S.A. Soper. Merging microfluidics with microarray-based bioassays. Biomolecular Engineering 2006;23(5):213–231.CrossRefGoogle Scholar
  151. 151.
    Thorsen T., S.J. Maerkl, S.R. Quake. Microfluidic large-scale integration. Science 2002;298(5593):580–584.CrossRefGoogle Scholar
  152. 152.
    Duffy D.C., J.C. McDonald, O.J.A. Schueller, G.M. Whitesides. Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Analytical Chemistry 1998;70(23):4974–4984.CrossRefGoogle Scholar
  153. 153.
    Unger M.A., H.P. Chou, T. Thorsen, A. Scherer, S.R. Quake. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 2000;288(5463):113–116.CrossRefGoogle Scholar
  154. 154.
    Marcus J.S., W.F. Anderson, S.R. Quake. Microfluidic single-cell mRNA isolation and analysis. Analytical Chemistry 2006;78(9):3084–3089.CrossRefGoogle Scholar
  155. 155.
    Lee C.C., G.D. Sui, A. Elizarov, C.Y.J. Shu, Y.S. Shin, A.N. Dooley, J. Huang, A. Daridon, P. Wyatt, D. Stout, H.C. Kolb, O.N. Witte, N. Satyamurthy, J.R. Heath, M.E. Phelps, S.R. Quake, H.R. Tseng. Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science 2005;310(5755):1793–1796.CrossRefGoogle Scholar
  156. 156.
    Balagadde F.K., L.C. You, C.L. Hansen, F.H. Arnold, S.R. Quake. Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 2005;309(5731):137–140.CrossRefGoogle Scholar
  157. 157.
    Anderson M.J., C.L. Hansen, S.R. Quake. Phase knowledge enables rational screens for protein crystallization. Proceedings of the National Academy of Sciences of the United States of America 2006;103(45):16746–16751.CrossRefGoogle Scholar
  158. 158.
    Hansen C.L., S. Classen, J.M. Berger, S.R. Quake. A microfluidic device for kinetic optimization of protein crystallization and in situ structure determination. Journal of the American Chemical Society 2006;128(10):3142–3143.CrossRefGoogle Scholar
  159. 159.
    Hansen C.L., M.O.A. Sommer, S.R. Quake. Systematic investigation of protein phase behavior with a microfluidic formulator. Proceedings of the National Academy of Sciences of the United States of America 2004;101(40):14431–14436.CrossRefGoogle Scholar
  160. 160.
  161. 161.
    Schorzman D.A., J.M. Desimone, J.P. Rolland, S.R. Quake, R.M. Van Dam. Solvent-Resistant Photocurable “Liquid Teflon” for Microfluidic Device Fabrication. Journal of the American Chemical Society 2004;126(8):2322–2323.CrossRefGoogle Scholar
  162. 162.
    Melin J., S.R. Quake. Microfluidic large-scale integration: The evolution of design rules for biological automation. Annual Review of Biophysics and Biomolecular Structure 2007;36:213–231.CrossRefGoogle Scholar
  163. 163.
    Kamotani Y., T. Bersano-Begey, N. Kato, Y.C. Tung, D. Huh, J.W. Song, S. Takayama. Individually programmable cell stretching microwell arrays actuated by a Braille display. Biomaterials 2008;29(17):2646–2655.CrossRefGoogle Scholar
  164. 164.
    Song J.W., W. Gu, N. Futai, K.A. Warner, J.E. Nor, S. Takayama. Computer-controlled microcirculatory support system for endothelial cell culture and shearing. Analytical Chemistry 2005;77(13):3993–3999.CrossRefGoogle Scholar
  165. 165.
    Gu W., X.Y. Zhu, N. Futai, B.S. Cho, S. Takayama. Computerized microfluidic cell culture using elastomeric channels and Braille displays. Proceedings of the National Academy of Sciences of the United States of America 2004;101(45):15861–15866.CrossRefGoogle Scholar
  166. 166.
    Enzelberger M.M., C.L. Hansen, J. Liu, S.R. Quake, C. Ma. Nucleic acid amplification using microfluidic devices, WO/2002/081729. World Intellectual Property Organization; 2002.Google Scholar
  167. 167.
    Lee C., G. Sui, A. Elizarov, H.C. Kolb, J. Huang, J.R. Heath, M.E. Phelps, S.R. Quake, H. Tseng, P. Wyatt. Microfluidic Devices with Chemical Reaction Circuits. EP Patent 1,838,431; 2007.Google Scholar
  168. 168.
    El-Ali J., P.K. Sorger, K.F. Jensen. Cells on chips. Nature 2006;442(7101):403–411.CrossRefGoogle Scholar
  169. 169.
    Park T.H., M.L. Shuler. Integration of cell culture and microfabrication technology. Biotechnology Progress 2003;19(2):243–253.CrossRefGoogle Scholar
  170. 170.
    Sims C.E., N.L. Allbritton. Analysis of single mammalian cells on-chip. Lab on a Chip 2007;7(4):423–440.CrossRefGoogle Scholar
  171. 171.
    Cheng J.Y., M.H. Yen, C.T. Kuo, T.H. Young. A transparent cell-culture microchamber with a variably controlled concentration gradient generator and flow field rectifier. Biomicrofluidics 2008;2(2):12.CrossRefGoogle Scholar
  172. 172.
    Petronis S., M. Stangegaard, C.B.V. Christensen, M. Dufva. Transparent polymeric cell culture chip with integrated temperature control and uniform media perfusion. Biotechniques 2006;40(3):368–376.CrossRefGoogle Scholar
  173. 173.
    Park J., T. Bansal, M. Pinelis, M.M. Maharbiz. A microsystem for sensing and patterning oxidative microgradients during cell culture. Lab on a Chip 2006;6(5):611–622.CrossRefGoogle Scholar
  174. 174.
    Maharbiz M.M., W.J. Holtz, S. Sharifzadeh, J.D. Keasling, R.T. Howe. A microfabricated electrochemical oxygen generator for high-density cell culture arrays. Journal of Microelectromechanical Systems 2003;12(5):590–599.CrossRefGoogle Scholar
  175. 175.
    Vollmer A.P., R.F. Probstein, R. Gilbert, T. Thorsen. Development of an integrated microfluidic platform for dynamic oxygen sensing and delivery in a flowing medium. Lab on a Chip 2005;5(10):1059–1066.CrossRefGoogle Scholar
  176. 176.
    Ges I.A., B.L. Ivanov, D.K. Schaffer, E.A. Lima, A.A. Werdich, F.J. Baudenbacher. Thin-film IrOx pH microelectrode for microfluidic-based microsystems. Biosensors & Bioelectronics 2005;21(2):248–256.CrossRefGoogle Scholar
  177. 177.
    Taff B.M., J. Voldman. A scalable addressable positive-dielectrophoretic cell-sorting array. Analytical Chemistry 2005;77(24):7976–7983.CrossRefGoogle Scholar
  178. 178.
    Voldman J., M.L. Gray, M. Toner, M.A. Schmidt. A microfabrication-based dynamic array cytometer. Analytical Chemistry 2002;74(16):3984–3990.CrossRefGoogle Scholar
  179. 179.
    Wang X.B., J. Yang, Y. Huang, J. Vykoukal, F.F. Becker, P.R.C. Gascoyne. Cell separation by dielectrophoretic field-flow-fractionation. Analytical Chemistry 2000;72(4):832–839.CrossRefGoogle Scholar
  180. 180.
    Gomez-Sjoberg R., A.A. Leyrat, D.M. Pirone, C.S. Chen, S.R. Quake. Versatile, fully automated, microfluidic cell culture system. Analytical Chemistry 2007;79(22):8557–8563.CrossRefGoogle Scholar
  181. 181.
    Hung P.J., P.J. Lee, P. Sabounchi, R. Lin, L.P. Lee. Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnology and Bioengineering 2005;89(1):1–8.CrossRefGoogle Scholar
  182. 182.
    Lii J., W.J. Hsu, H. Parsa, A. Das, R. Rouse, S.K. Sia. Real-time microfluidic system for studying mammalian cells in 3D microenvironments. Analytical Chemistry 2008;80(10):3640–3647.CrossRefGoogle Scholar
  183. 183.
    Madou M., J. Zoval, G.Y. Jia, H. Kido, J. Kim, N. Kim. Lab on a CD. Annual Review of Biomedical Engineering 2006;8:601–628.CrossRefGoogle Scholar
  184. 184.
    Balaban N.Q., U.S. Schwarz, D. Riveline, P. Goichberg, G. Tzur, I. Sabanay, D. Mahalu, S. Safran, A. Bershadsky, L. Addadi, B. Geiger. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nature Cell Biology 2001;3(5):466–472.CrossRefGoogle Scholar
  185. 185.
    Tan J.L., J. Tien, D.M. Pirone, D.S. Gray, K. Bhadriraju, C.S. Chen. Cells lying on a bed of microneedles: An approach to isolate mechanical force. Proceedings of the National Academy of Sciences of the United States of America 2003;100(4):1484–1489.CrossRefGoogle Scholar
  186. 186.
    Hellmich W., C. Pelargus, K. Leffhalm, A. Ros, D. Anselmetti. Single cell manipulation, analytics, and label-free protein detection in microfluidic devices for systems nanobiology. Electrophoresis 2005;26(19):3689–3696.CrossRefGoogle Scholar
  187. 187.
    Munce N.R., J.Z. Li, P.R. Herman, L. Lilge. Microfabricated system for parallel single-cell capillary electrophoresis. Analytical Chemistry 2004;76(17):4983–4989.CrossRefGoogle Scholar
  188. 188.
    Klaus J.W., S.M. George. SiO2 chemical vapor deposition at room temperature using SiCl4 and H2O with an NH3 catalyst. Journal of the Electrochemical Society 2000;147(7):2658–2664.CrossRefGoogle Scholar
  189. 189.
    Senturia S.D. Microsystem Design. Springer Science+Business Media, LLC: New York, 2005.Google Scholar
  190. 190.
    Lim K.S., W.J. Chang, Y.M. Koo, R. Bashir. Reliable fabrication method of transferable micron scale metal pattern for poly(dimethylsiloxane) metallization. Lab on a Chip 2006;6(4):578–580.CrossRefGoogle Scholar
  191. 191.
    Niu X.Z., S.L. Peng, L.Y. Liu, W.J. Wen, P. Sheng. Characterizing and patterning of PDMS-based conducting composites. Advanced Materials 2007;19(18):2682–2686.CrossRefGoogle Scholar
  192. 192.
    Bowden N., S. Brittain, A.G. Evans, J.W. Hutchinson, G.M. Whitesides. Spontaneous formation of ordered structures in thin films of metals supported on an elastomeric polymer. Nature 1998;393(6681):146–149.CrossRefGoogle Scholar
  193. 193.
    Trau D., J. Jiang, N.J. Sucher. Preservation of the biofunctionality of DNA and protein during microfabrication. Langmuir 2006;22(3):877–881.CrossRefGoogle Scholar
  194. 194.
    Kentsch J., S. Breisch, M. Stezle. Low temperature adhesion bonding for BioMEMS. Journal of Micromechanics and Microengineering 2006;16(4):802–807.CrossRefGoogle Scholar
  195. 195.
    Ghafar-Zadeh E., M. Sawan, D. Therriault. Novel direct-write CMOS-based laboratory-on-chip: Design, assembly and experimental results. Sensors and Actuators a-Physical 2007;134(1):27–36.CrossRefGoogle Scholar
  196. 196.
    Zimmermann S., D. Fienbork, A.W. Flounders, D. Liepmann. In-device enzyme immobilization: wafer-level fabrication of an integrated glucose sensor. Sensors and Actuators B-Chemical 2004;99(1):163–173.CrossRefGoogle Scholar
  197. 197.
    Linder V., S. Koster, W. Franks, T. Kraus, E. Verpoorte, F. Heer, A. Hierlemann, N.F. de Rooij. Microfluidics/CMOS orthogonal capabilities for cell biology. Biomedical Microdevices 2006;8(2):159–166.CrossRefGoogle Scholar
  198. 198.
    Pan J.Y. Reliability considerations for the BioMEMS designer. Proceedings of the Ieee 2004;92(1):174–184.CrossRefGoogle Scholar
  199. 199.
    Bhagat A.A.S., P. Jothimuthu, A. Pais, I. Papautsky. Re-usable quick-release interconnect for characterization of microfluidic systems. Journal of Micromechanics and Microengineering 2007;17(1):42–49.CrossRefGoogle Scholar
  200. 200.
    Christensen A.M., D.A. Chang-Yen, B.K. Gale. Characterization of interconnects used in PDMS microfluidic systems. Journal of Micromechanics and Microengineering 2005;15(5):928–934.CrossRefGoogle Scholar
  201. 201.
    Han K.H., R.D. McConnell, C.J. Easley, J.M. Bienvenue, J.P. Ferrance, J.P. Landers, A.B. Frazier. An active microfluidic system packaging technology. Sensors and Actuators B-Chemical 2007;122(1):337–346.CrossRefGoogle Scholar
  202. 202.
    Puntambekar A., C.H. Ahn. Self-aligning microfluidic interconnects for glass- and plastic-based microfluidic systems. Journal of Micromechanics and Microengineering 2002;12(1):35–40.CrossRefGoogle Scholar
  203. 203.
    Fujii T., Y. Sando, K. Higashino, Y. Fujii. A plug and play microfluidic device. Lab on a Chip 2003;3(3):193–197.CrossRefGoogle Scholar
  204. 204.
    Igata E., M. Arundell, H. Morgan, J.M. Cooper. Interconnected reversible lab-on-a-chip technology. Lab on a Chip 2002;2(2):65–69.CrossRefGoogle Scholar
  205. 205.
    Yuen P.K. SmartBuild–A truly plug-n-play modular microfluidic system. Lab on a Chip 2008;8:1374–1378.CrossRefGoogle Scholar
  206. 206.
    Shaikh K.A., K.S. Ryu, E.D. Goluch, J.M. Nam, J.W. Liu, S. Thaxton, T.N. Chiesl, A.E. Barron, Y. Lu, C.A. Mirkin, C. Liu. A modular microfluidic architecture for integrated biochemical analysis. Proceedings of the National Academy of Sciences of the United States of America 2005;102(28):9745–9750.CrossRefGoogle Scholar
  207. 207.
    Ko W.H. Packaging of Microfabricated Devices and Systems. Materials Chemistry and Physics 1995;42(3):169–175.CrossRefGoogle Scholar
  208. 208.
    Murarka S.P. Multilevel interconnections for ULSI and GSI era. Materials Science & Engineering R-Reports 1997;19(3–4):87–151.CrossRefGoogle Scholar
  209. 209.
    Tong H.M. Microelectronics Packaging - Present and Future. Materials Chemistry and Physics 1995;40(3):147–161.CrossRefGoogle Scholar
  210. 210.
    James C.D., A.J.H. Spence, N.M. Dowell-Mesfin, R.J. Hussain, K.L. Smith, H.G. Craighead, M.S. Isaacson, W. Shain, J.N. Turner. Extracellular recordings from patterned neuronal networks using planar microelectrode arrays. Ieee Transactions on Biomedical Engineering 2004;51(9):1640–1648.CrossRefGoogle Scholar
  211. 211.
    Fair R.B. Digital microfluidics: is a true lab-on-a-chip possible? Microfluidics and Nanofluidics 2007;3(3):245–281.CrossRefGoogle Scholar
  212. 212.
    Hartley L., K. Kaler, O. Yadid-Pecht. Hybrid integration of an active pixel sensor and microfluidics for cytometry on a chip. Ieee Transactions on Circuits and Systems I-Regular Papers 2007;54(1):99–110.CrossRefGoogle Scholar
  213. 213.
    Huang Y., J.M. Yang, P.J. Hopkins, S. Kassegne, M. Tirado, A.H. Forster, H. Reese. Separation of simulants of biological warfare agents from blood by a miniaturized dielectrophoresis device. Biomedical Microdevices 2003;5(3):217–225.CrossRefGoogle Scholar
  214. 214.
    Petrou P.S., I. Moser, G. Jobst. BioMEMS device with integrated microdialysis probe and biosensor array. Biosensors & Bioelectronics 2002;17(10):859–865.CrossRefGoogle Scholar
  215. 215.
    Piruska A., I. Nikcevic, S.H. Lee, C. Ahn, W.R. Heineman, P.A. Limbach, C.J. Seliskar. The autofluorescence of plastic materials and chips measured under laser irradiation. Lab on a Chip 2005;5(12):1348–1354.CrossRefGoogle Scholar
  216. 216.
    Bliss C.L., J.N. McMullin, C.J. Backhouse. Rapid fabrication of a microfluidic device with integrated optical waveguides for DNA fragment analysis. Lab on a Chip 2007;7(10):1280–1287.CrossRefGoogle Scholar
  217. 217.
    Lee K.S., H.L.T. Lee, R.J. Ram. Polymer waveguide backplanes for optical sensor interfaces in microfluidics. Lab on a Chip 2007;7(11):1539–1545.CrossRefGoogle Scholar
  218. 218.
    Chung K., M.M. Crane, H. Lu. Automated on-chip rapid microscopy, phenotyping and sorting of C.elegans. Nat Meth 2008;5(7):637–643.CrossRefGoogle Scholar
  219. 219.
    El-Ali J., S. Gaudet, A. Gunther, P.K. Sorger, K.F. Jensen. Cell stimulus and lysis in a microfluidic device with segmented gas-liquid flow. Analytical Chemistry 2005;77(11):3629–3636.CrossRefGoogle Scholar
  220. 220.
    Voskerician G., M.S. Shive, R.S. Shawgo, H. von Recum, J.M. Anderson, M.J. Cima, R. Langer. Biocompatibility and biofouling of MEMS drug delivery devices. Biomaterials 2003;24(11):1959–1967.CrossRefGoogle Scholar
  221. 221.
    Brischwein M., E.R. Motrescu, E. Cabala, A.M. Otto, H. Grothe, B. Wolf. Functional cellular assays with multiparametric silicon sensor chips. Lab on a Chip 2003;3(4):234–240.CrossRefGoogle Scholar
  222. 222.
    Szarowski D.H., M.D. Andersen, S. Retterer, A.J. Spence, M. Isaacson, H.G. Craighead, J.N. Turner, W. Shain. Brain responses to micro-machined silicon devices. Brain Research 2003;983(1–2):23–35.CrossRefGoogle Scholar
  223. 223.
  224. 224.
    Shawgo R.S., A.C.R. Grayson, Y.W. Li, M.J. Cima. BioMEMS for drug delivery. Current Opinion in Solid State & Materials Science 2002;6(4):329–334.CrossRefGoogle Scholar
  225. 225.
    Fallahi D., H. Mirzadeh, M.T. Khorasani. Physical, mechanical, and biocompatibility evaluation of three different types of silicone rubber. Journal of Applied Polymer Science 2003;88(10):2522–2529.CrossRefGoogle Scholar
  226. 226.
    Mata A., A.J. Fleischman, S. Roy. Characterization of polydimethylsiloxane (PDMS) properties for biomedical micro/nanosystems. Biomedical Microdevices 2005;7(4):281–293.CrossRefGoogle Scholar
  227. 227.
    Lee J.N., X. Jiang, D. Ryan, G.M. Whitesides. Compatibility of mammalian cells on surfaces of poly(dimethylsiloxane). Langmuir 2004;20(26):11684–11691.CrossRefGoogle Scholar
  228. 228.
    Millet L.J., M.E. Stewart, J.V. Sweedler, R.G. Nuzzo, M.U. Gillette. Microfluidic devices for culturing primary mammalian neurons at low densities. Lab on a Chip 2007;7(8):987–994.CrossRefGoogle Scholar
  229. 229.
    Kim L., Y.C. Toh, J. Voldman, H. Yu. A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab on a Chip 2007;7(6):681–694.CrossRefGoogle Scholar
  230. 230.
    Kasemo B. Biological surface science. Surface Science 2002;500(1–3):656–677.CrossRefGoogle Scholar
  231. 231.
    Makamba H., J.H. Kim, K. Lim, N. Park, J.H. Hahn. Surface modification of poly(dimethylsiloxane) microchannels. Electrophoresis 2003;24(21):3607–3619.CrossRefGoogle Scholar
  232. 232.
    Fritz J.L., M.J. Owen. Hydrophobic Recovery of Plasma-Treated Polydimethylsiloxane. The Journal of Adhesion 1995;54(1):33–45.CrossRefGoogle Scholar
  233. 233.
    Hu S., X. Ren, M. Bachman, C.E. Sims, G.P. Li, N. Allbritton. Surface Modification of Poly(dimethylsiloxane) Microfluidic Devices by Ultraviolet Polymer Grafting. Analytical Chemistry 2002;74(16):4117–4123.CrossRefGoogle Scholar
  234. 234.
    Slentz B.E., N.A. Penner, F.E. Regnier. Capillary electrochromatography of peptides on microfabricated poly(dimethylsiloxane) chips modified by cerium(IV)-catalyzed polymerization. Journal of Chromatography A 2002;948(1–2):225–233.CrossRefGoogle Scholar
  235. 235.
    Ocvirk G., M. Munroe, T. Tang, R. Oleschuk, K. Westra, D.J. Harrison. Electrokinetic control of fluid flow in native poly(dimethylsiloxane) capillary electrophoresis devices. Electrophoresis 2000;21(1):107–115.CrossRefGoogle Scholar
  236. 236.
    Dou Y.H., N. Bao, J.J. Xu, H.Y. Chen. A dynamically modified microfluidic poly(dimethylsiloxane) chip with electrochemical detection for biological analysis. Electrophoresis 2002;23(20):3558–3566.CrossRefGoogle Scholar
  237. 237.
    Decher G. Fuzzy nanoassemblies: Toward layered polymeric multicomposites. Science 1997;277(5330):1232–1237.CrossRefGoogle Scholar
  238. 238.
    Sung W.C., C.C. Chang, H. Makamba, S.H. Chen. Long-term affinity modification on poly(dimethylsiloxane) substrate and its application for ELISA analysis. Analytical Chemistry 2008;80(5):1529–1535.CrossRefGoogle Scholar
  239. 239.
    Hanein Y., Y.V. Pan, B.D. Ratner, D.D. Denton, K.F. Bohringer. Micromachining of non-fouling coatings for bio-MEMS applications. Sensors and Actuators B-Chemical 2001;81(1):49–54.CrossRefGoogle Scholar
  240. 240.
    Lopez G.P., B.D. Ratner, C.D. Tidwell, C.L. Haycox, R.J. Rapoza, T.A. Horbett. Glow-Discharge Plasma Deposition of Tetraethylene Glycol Dimethyl Ether for Fouling-resistant Biomaterial Surfaces. Journal of Biomedical Materials Research 1992;26(4):415–439.CrossRefGoogle Scholar
  241. 241.
    Dhayal M., J.S. Choi, C.H. So. Biological fluid interaction with controlled surface properties of organic micro-fluidic devices. Vacuum 2006;80(8):876–879.CrossRefGoogle Scholar
  242. 242.
    Bajaj P., D. Akin, A. Gupta, D. Sherman, B. Shi, O. Auciello, R. Bashir. Ultrananocrystalline diamond film as an optimal cell interface for biomedical applications. Biomedical Microdevices 2007;9(6):787–794.CrossRefGoogle Scholar
  243. 243.
    Hoivik N.D., J.W. Elam, R.J. Linderman, V.M. Bright, S.M. George, Y.C. Lee. Atomic layer deposited protective coatings for micro-electromechanical systems. Sensors and Actuators a-Physical 2003;103(1–2):100–108.CrossRefGoogle Scholar
  244. 244.
    Wang Y.L., J.H. Pai, H.H. Lai, C.E. Sims, M. Bachman, G.P. Li, N.L. Allbritton. Surface graft polymerization of SU-8 for bio-MEMS applications. Journal of Micromechanics and Microengineering 2007;17(7):1371–1380.CrossRefGoogle Scholar
  245. 245.
    Wang Y.L., M. Bachman, C.E. Sims, G.P. Li, N.L. Allbritton. Simple photografting method to chemically modify and micropattern the surface of SU-8 photoresist. Langmuir 2006;22(6):2719–2725.CrossRefGoogle Scholar
  246. 246.
    Nordstrom M., R. Marie, M. Calleja, A. Boisen. Rendering SU-8 hydrophilic to facilitate use in micro channel fabrication. Journal of Micromechanics and Microengineering 2004;14(12):1614–1617.CrossRefGoogle Scholar
  247. 247.
    Joshi M., N. Kale, R. Lal, V.R. Rao, S. Mukherji. A novel dry method for surface modification of SU-8 for immobilization of biomolecules in Bio-MEMS. Biosensors & Bioelectronics 2007;22(11):2429–2435.CrossRefGoogle Scholar
  248. 248.
    Chen C.S., M. Mrksich, S. Huang, G.M. Whitesides, D.E. Ingber. Micropatterned surfaces for control of cell shape, position, and function. Biotechnology Progress 1998;14(3):356–363.CrossRefGoogle Scholar
  249. 249.
    Duncan A.C., F. Weisbuch, F. Rouais, S. Lazare, C. Baquey. Laser microfabricated model surfaces for controlled cell growth. Biosensors & Bioelectronics 2002;17(5):413–426.CrossRefGoogle Scholar
  250. 250.
    Duncan A.C., F. Rouais, S. Lazare, L. Bordenave, C. Baquey. Effect of laser modified surface microtopochemistry on endothelial cell growth. Colloids and Surfaces B-Biointerfaces 2007;54(2):150–159.CrossRefGoogle Scholar
  251. 251.
    Edell D.J., V.V. Toi, V.M. McNeil, L.D. Clark. Factors influencing the biocompatibility of insertable silicon microshafts in cerebral-cortex. Ieee Transactions on Biomedical Engineering 1992;39(6):635–643.CrossRefGoogle Scholar
  252. 252.
    Hoogerwerf A.C., K.D. Wise. A 3-dimensional microelectrode array for chronic neural recording. Ieee Transactions on Biomedical Engineering 1994;41(12):1136–1146.CrossRefGoogle Scholar
  253. 253.
    Schmidt S., K. Horch, R. Normann. Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue. Journal of Biomedical Materials Research 1993;27(11):1393–1399.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.School of Chemical Biomolecular EngineeringGeorgia Institute of TechnologyAtlantaUSA

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