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

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Nano-Bio- Electronic, Photonic and MEMS Packaging

Abstract

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 bio-sciences. 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.

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References

  1. Chin, C.D., Linder, V., Sia, S.K.: Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip. 7(1), 41–57 (2007)

    Article  CAS  Google Scholar 

  2. Yager, P., Edwards, T., Fu, E., Helton, K., Nelson, K., Tam, M.R., Weigl, B.H.: Microfluidic diagnostic technologies for global public health. Nature. 442(7101), 412–418 (2006)

    Article  CAS  Google Scholar 

  3. Engler, K.H., Efstratiou, A., Norn, D., Kozlov, R.S., Selga, I., Glushkevich, T.G., Tam, M., Melnikov, V.G., Mazurova, I.K., Kim, V.E., Tseneva, G.Y., Titov, L.P., George, R.C.: Immunochromatographic strip test for rapid detection of diphtheria toxin: description and multicenter evaluation in areas of low and high prevalence of diphtheria. J. Clin. Microbiol. 40(1), 80–83 (2002)

    Article  CAS  Google Scholar 

  4. Arai, H., Petchclai, B., Khupulsup, K., Kurimura, T., Takeda, K.: Evaluation of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus. J. Clin. Microbiol. 37(2), 367–370 (1999)

    Article  CAS  Google Scholar 

  5. Patterson, K., Olsen, B., Thomas, C., Norn, D., Tam, M., Elkins, C.: Development of a rapid immunodiagnostic test for Haemophilus ducreyi. J. Clin. Microbiol. 40(10), 3694–3702 (2002)

    Article  CAS  Google Scholar 

  6. Zarakolu, P., Buchanan, I., Tam, M., Smith, K., Hook, E.W.: Preliminary evaluation of an immunochromatographic strip test for specific Treponema pallidum antibodies. J. Clin. Microbiol. 40(8), 3064–3065 (2002)

    Article  CAS  Google Scholar 

  7. Martinez, A.W., Phillips, S.T., Butte, M.J., Whitesides, G.M.: Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew. Chem. Int. Ed. 46(8), 1318–1320 (2007)

    Article  CAS  Google Scholar 

  8. Martinez, A.W., Phillips, S.T., Carrilho, E., Thomas, S.W., Sindi, H., Whitesides, G.M.: Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal. Chem. 80(10), 3699–3707 (2008)

    Article  CAS  Google Scholar 

  9. Martinez, A.W., Phillips, S.T., Whitesides, G.M.: Three-dimensional microfluidic devices fabricated in layered paper and tape. Proc. Natl. Acad. Sci. 105(50), 19606–19611 (2008)

    Article  CAS  Google Scholar 

  10. Hintsche, R., Moller, B., Dransfeld, I., Wollenberger, U., Scheller, F., Hoffmann, B.: Chip biosensors on thin-film metal-electrodes. Sensors Actuators B Chem. 4(3–4), 287–291 (1991)

    Article  CAS  Google Scholar 

  11. Shulga, A.A., Soldatkin, A.P., Elskaya, A.V., Dzyadevich, S.V., Patskovsky, S.V., Strikha, V.I.: Thin-film conductometric biosensors for glucose and urea determination. Biosens. Bioelectron. 9(3), 217–223 (1994)

    Article  CAS  Google Scholar 

  12. Hunt, H.C., Wilkinson, J.S.: Optofluidic integration for microanalysis. Microfluid. Nanofluid. 4(1–2), 53–79 (2008)

    Article  CAS  Google Scholar 

  13. Cui, Y., Wei, Q.Q., Park, H.K., Lieber, C.M.: Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science. 293(5533), 1289–1292 (2001)

    Article  CAS  Google Scholar 

  14. Zheng, G.F., Patolsky, F., Cui, Y., Wang, W.U., Lieber, C.M.: Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat. Biotechnol. 23(10), 1294–1301 (2005)

    Article  CAS  Google Scholar 

  15. Bashir, R.: BioMEMS: state-of-the-art in detection, opportunities and prospects. Adv. Drug Deliv. Rev. 56(11), 1565–1586 (2004)

    Article  CAS  Google Scholar 

  16. Waggoner, P.S., Craighead, H.G.: Micro- and nanomechanical sensors for environmental, chemical, and biological detection. Lab Chip. 7(10), 1238–1255 (2007)

    Article  CAS  Google Scholar 

  17. Fritz, J., Baller, M.K., Lang, H.P., Rothuizen, H., Vettiger, P., Meyer, E., Guntherodt, H.J., Gerber, C., Gimzewski, J.K.: Translating biomolecular recognition into nanomechanics. Science. 288(5464), 316–318 (2000)

    Article  CAS  Google Scholar 

  18. Hansen, K.M., Ji, H.F., Wu, G.H., Datar, R., Cote, R., Majumdar, A., Thundat, T.: Cantilever- based optical deflection assay for discrimination of DNA single-nucleotide mismatches. Anal. Chem. 73(7), 1567–1571 (2001)

    Article  CAS  Google Scholar 

  19. Gupta, A., Akin, D., Bashir, R.: Single virus particle mass detection using microresonators with nanoscale thickness. Appl. Phys. Lett. 84(11), 1976–1978 (2004)

    Article  CAS  Google Scholar 

  20. Ilic, B., Czaplewski, D., Craighead, H.G., Neuzil, P., Campagnolo, C., Batt, C.: Mechanical resonant immunospecific biological detector. Appl. Phys. Lett. 77(3), 450–452 (2000)

    Article  CAS  Google Scholar 

  21. McKendry, R., Zhang, J.Y., Arntz, Y., Strunz, T., Hegner, M., Lang, H.P., Baller, M.K., Certa, U., Meyer, E., Guntherodt, H.J., Gerber, C.: Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array. Proc. Natl. Acad. Sci. U. S. A. 99(15), 9783–9788 (2002)

    Article  CAS  Google Scholar 

  22. Wu, G.H., Datar, R.H., Hansen, K.M., Thundat, T., Cote, R.J., Majumdar, A.: Bioassay of prostate-specific antigen (PSA) using microcantilevers. Nat. Biotechnol. 19(9), 856–860 (2001)

    Article  CAS  Google Scholar 

  23. Burg, T.P., Godin, M., Knudsen, S.M., Shen, W., Carlson, G., Foster, J.S., Babcock, K., Manalis, S.R.: Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature. 446, 1066–1069 (2007)

    Article  CAS  Google Scholar 

  24. Burg, T.P., Mirza, A.R., Milovic, N., Tsau, C.H., Popescu, G.A., Foster, J.S., Manalis, S.R.: Vacuum-packaged suspended microchannel resonant mass sensor for biomolecular detection. J. Microelectromech. Syst. 15(6), 1466–1476 (2006)

    Article  Google Scholar 

  25. Fruetel, J.A., Renzi, R.F., VanderNoot, V.A., Stamps, J., Horn, B.A., West, J.A.A., Ferko, S., Crocker, R., Bailey, C.G., Arnold, D., Wiedenman, B., Choi, W.Y., Yee, D., Shokair, I., Hasselbrink, E., Paul, P., Rakestraw, D., Padgen, D.: Microchip separations of protein biotoxins using an integrated hand-held device. Electrophoresis. 26(6), 1144–1154 (2005)

    Article  CAS  Google Scholar 

  26. Stratis-Cullum, D.N., Griffin, G.D., Mobley, J., Vass, A.A., Vo-Dinh, T.: A miniature biochip system for detection of aerosolized Bacillus globigii spores. Anal. Chem. 75(2), 275–280 (2003)

    Article  CAS  Google Scholar 

  27. Psaltis, D., Quake, S.R., Yang, C.H.: Developing optofluidic technology through the fusion of microfluidics and optics. Nature. 442(7101), 381–386 (2006)

    Article  CAS  Google Scholar 

  28. Irawan, R., Tjin, S.C., Fang, X.Q., Fu, C.Y.: Integration of optical fiber light guide, fluorescence detection system, and multichannel disposable microfluidic chip. Biomed. Microdevices. 9(3), 413–419 (2007)

    Article  CAS  Google Scholar 

  29. Lin, C.H., Lee, G.B., Chen, S.H., Chang, G.L.: Micro capillary electrophoresis chips integrated with buried SU-8/SOG optical waveguides for bio-analytical applications. Sensors Actuators A Phys. 107(2), 125–131 (2003)

    Article  CAS  Google Scholar 

  30. Kou, Q., Yesilyurt, I., Studer, V., Belotti, M., Cambril, E., Chen, Y.: On-chip optical components and microfluidic systems. Microelectron. Eng. 73–74, 876–880 (2004)

    Article  Google Scholar 

  31. Misiakos, K., Kakabakos, S.E., Petrou, P.S., Ruf, H.H.: A monolithic silicon optoelectronic transducer as a real-time affinity biosensor. Anal. Chem. 76(5), 1366–1373 (2004)

    Article  CAS  Google Scholar 

  32. Balslev, S., Jorgensen, A.M., Bilenberg, B., Mogensen, K.B., Snakenborg, D., Geschke, O., Kutter, J.P., Kristensen, A.: Lab-on-a-chip with integrated optical transducers. Lab Chip. 6(2), 213–217 (2006)

    Article  CAS  Google Scholar 

  33. Dandin, M., Abshire, P., Smela, E.: Optical filtering technologies for integrated fluorescence sensors. Lab Chip. 7(8), 955–977 (2007)

    Article  CAS  Google Scholar 

  34. Prakash, A.R., Adamia, S., Sieben, V., Pilarski, P., Pilarski, L.M., Backhouse, C.J.: Small volume PCR in PDMS biochips with integrated fluid control and vapour barrier. Sensors Actuators B Chem. 113(1), 398–409 (2006)

    Article  CAS  Google Scholar 

  35. Kaigala, G.V., Hoang, V.N., Stickel, A., Lauzon, J., Manage, D., Pilarski, L.M., Backhouse, C.J.: An inexpensive and portable microchip-based platform for integrated RT-PCR and capillary electrophoresis. Analyst. 133(3), 331–338 (2008)

    Article  CAS  Google Scholar 

  36. Weibel, D.B., Kruithof, M., Potenta, S., Sia, S.K., Lee, A., Whitesides, G.M.: Torque-actuated valves for microfluidics. Anal. Chem. 77(15), 4726–4733 (2005)

    Article  CAS  Google Scholar 

  37. Burns, M.A., Johnson, B.N., Brahmasandra, S.N., Handique, K., Webster, J.R., Krishnan, M., Sammarco, T.S., Man, P.M., Jones, D., Heldsinger, D., Mastrangelo, C.H., Burke, D.T.: An integrated nanoliter DNA analysis device. Science. 282(5388), 484–487 (1998)

    Article  CAS  Google Scholar 

  38. Liu, R.H., Yang, J.N., Lenigk, R., Bonanno, J., Grodzinski, P.: Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection. Anal. Chem. 76(7), 1824–1831 (2004)

    Article  CAS  Google Scholar 

  39. Pal, R., Yang, M., Lin, R., Johnson, B.N., Srivastava, N., Razzacki, S.Z., Chomistek, K.J., Heldsinger, D.C., Haque, R.M., Ugaz, V.M., Thwar, P.K., Chen, Z., Alfano, K., Yim, M.B., Krishnan, M., Fuller, A.O., Larson, R.G., Burke, D.T., Burns, M.A.: An integrated microfluidic device for influenza and other genetic analyses. Lab Chip. 5(10), 1024–1032 (2005)

    Article  CAS  Google Scholar 

  40. Fu, E., Chinowsky, T., Nelson, K., Johnston, K., Edwards, T., Helton, K., Grow, M., Miller, J.W., Yager, P.: SPR Imaging-Based Salivary Diagnostics System for the Detection of Small Molecule Analytes. Oral-Based Diagnostics, pp. 335–344. Blackwell Publishing, Oxford (2007)

    Google Scholar 

  41. Velten, T., Ruf, H.H., Barrow, D., Aspragathos, N., Lazarou, P., Jung, E., Malek, C.K., Richter, M., Kruckow, J.: Packaging of bio-MEMS: strategies, technologies, and applications. IEEE Trans. Adv. Packag. 28(4), 533–546 (2005)

    Article  Google Scholar 

  42. Herr, A.E., Hatch, A.V., Throckmorton, D.J., Tran, H.M., Brennan, J.S., Giannobile, W.V., Singh, A.K.: Microfluidic immunoassays as rapid saliva-based clinical diagnostics. Proc. Natl. Acad. Sci. U. S. A. 104(13), 5268–5273 (2007)

    Article  CAS  Google Scholar 

  43. Lagally, E.T., Scherer, J.R., Blazej, R.G., Toriello, N.M., Diep, B.A., Ramchandani, M., Sensabaugh, G.F., Riley, L.W., Mathies, R.A.: Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. Anal. Chem. 76(11), 3162–3170 (2004)

    Article  CAS  Google Scholar 

  44. Wang, J., Chatrathi, M.P., Mulchandani, A., Chen, W.: Capillary electrophoresis microchips for separation and detection of organophosphate nerve agents. Anal. Chem. 73(8), 1804–1808 (2001)

    Article  CAS  Google Scholar 

  45. Chinowsky, T.M., Soelberg, S.D., Baker, P., Swanson, N.R., Kauffman, P., Mactutis, A., Grow, M.S., Atmar, R., Yee, S.S., Furlong, C.E.: Portable 24-analyte surface plasmon resonance instruments for rapid, versatile biodetection. Biosens. Bioelectron. 22(9–10), 2268–2275 (2007)

    Article  CAS  Google Scholar 

  46. DeBusschere, B.D., Kovacs, G.T.A.: Portable cell-based biosensor system using integrated CMOS cell-cartridges. Biosens. Bioelectron. 16(7–8), 543–556 (2001)

    Article  CAS  Google Scholar 

  47. Hood, L., Heath, J.R., Phelps, M.E., Lin, B.Y.: Systems biology and new technologies enable predictive and preventative medicine. Science. 306(5696), 640–643 (2004)

    Article  CAS  Google Scholar 

  48. Weston, A.D., Hood, L.: Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. J. Proteome Res. 3(2), 179–196 (2004)

    Article  CAS  Google Scholar 

  49. Bhattacharyya, A., Klapperich, C.M.: Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples. Biomed. Microdevices. 9(2), 245–251 (2007)

    Article  CAS  Google Scholar 

  50. Linder, V., Sia, S.K., Whitesides, G.M.: Reagent-loaded cartridges for valveless and automated fluid delivery in microfluidic devices. Anal. Chem. 77(1), 64–71 (2005)

    Article  CAS  Google Scholar 

  51. Grayson, A.C.R., Shawgo, R.S., Johnson, A.M., Flynn, N.T., Li, Y.W., Cima, M.J., Langer, R.: A BioMEMS review: MEMS technology for physiologically integrated devices. Proc. IEEE. 92(1), 6–21 (2004)

    Article  CAS  Google Scholar 

  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 February 15)

    Google Scholar 

  53. Santini, J.T.M.J.C.R.S.L.; MIT, assignee. Microchip Drug Delivery Devices. US. (1998 August 25)

    Google Scholar 

  54. Kudo, H., Sawada, T., Kazawa, E., Yoshida, H., Iwasaki, Y., Mitsubayashi, K.: A flexible and wearable glucose sensor based on functional polymers with Soft-MEMS techniques. Biosens. Bioelectron. 22(4), 558–562 (2006)

    Article  CAS  Google Scholar 

  55. Zhao, Y.J., Li, S.Q., Davidson, A., Yang, B.Z., Wang, Q., Lin, Q.: A MEMS viscometric sensor for continuous glucose monitoring. J. Micromech. Microeng. 17(12), 2528–2537 (2007)

    Article  CAS  Google Scholar 

  56. Jauniaux, E., Watson, A., Ozturk, O., Quick, D., Burton, G.: In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy. Hum. Reprod. 14(11), 2901–2904 (1999)

    Article  CAS  Google Scholar 

  57. Prausnitz, M.R.: Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev. 56(5), 581–587 (2004)

    Article  CAS  Google Scholar 

  58. Prausnitz, M.R., Allen, M.G., Gujral, I.J. Microneedle Drug Delivery Device. US Patent 7, 226, 439; (2007)

    Google Scholar 

  59. Gujral I.J., Allen, M.G., Prausnitz M.R. Microneedle Device for Extraction and Sensing of Bodily Fluids. US Patent 7,344,499; (2008)

    Google Scholar 

  60. McAllister, D.V., Wang, P.M., Davis, S.P., Park, J.H., Canatella, P.J., Allen, M.G., Prausnitz, M.R.: Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc. Natl. Acad. Sci. 100(24), 13755–13760 (2003)

    Article  CAS  Google Scholar 

  61. Li, P.Y., Shih, J., Lo, R., Saati, S., Agrawal, R., Humayun, M.S., Tai, Y.C., Meng, E.: An electrochemical intraocular drug delivery device. Sensors Actuators A Phys. 143(1), 41–48 (2008)

    Article  CAS  Google Scholar 

  62. Santini, J.T., Cima, M.J., Langer, R.: A controlled-release microchip. Nature. 397(6717), 335–338 (1999)

    Article  CAS  Google Scholar 

  63. Voskerician, G., Shawgo, R.S., Hiltner, P.A., Anderson, J.M., Cima, M.J., Langer, R.: In vivo inflammatory and wound healing effects of gold electrode voltammetry for MEMS micro-reservoir drug delivery device. IEEE Trans. Biomed. Eng. 51(4), 627–635 (2004)

    Article  Google Scholar 

  64. Razzacki, S.Z., Thwar, P.K., Yang, M., Ugaz, V.M., Burns, M.A.: Integrated microsystems for controlled drug delivery. Adv. Drug Deliv. Rev. 56(2), 185–198 (2004)

    Article  CAS  Google Scholar 

  65. Wu, C.C., Yasukawa, T., Shiku, H., Matsue, T.: Fabrication of miniature Clark oxygen sensor integrated with microstructure. Sensors Actuators B Chem. 110(2), 342–349 (2005)

    Article  CAS  Google Scholar 

  66. Wu, H.K., Huang, B., Zare, R.N.: Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding. Lab Chip. 5(12), 1393–1398 (2005)

    Article  CAS  Google Scholar 

  67. Hungar, K., Gortz, M., Slavcheva, E., Spanier, G., Weidig, C., Mokwa, W.: Production processes for a flexible retina implant (Eurosensors XVIII, Session C6.6). Sensors Actuators A Phys. 123–24, 172–178 (2005)

    Article  CAS  Google Scholar 

  68. Schanze, T., Hesse, L., Lau, C., Greve, N., Haberer, W., Kammer, S., Doerge, T., Rentzos, A., Stieglitz, T.: An optically powered single-channel stimulation implant as test-system for chronic biocompatibility and biostability of miniaturized retinal vision prostheses. IEEE Trans. Biomed. Eng. 54(6), 983–992 (2007)

    Article  Google Scholar 

  69. Schwarz, M., Ewe, L., Hauschild, R., Hosticka, B.J., Huppertz, J., Kolnsberg, S., Mokwa, W., Trieu, H.K.: Single chip CMOS imagers and flexible microelectronic stimulators for a retina implant system. Sensors Actuators A Phys. 83(1–3), 40–46 (2000)

    Article  CAS  Google Scholar 

  70. Loeb, G.E., Peck, R.A., Moore, W.H., Hood, K.: BION (TM) system for distributed neural prosthetic interfaces. Med. Eng. Phys. 23(1), 9–18 (2001)

    Article  CAS  Google Scholar 

  71. Weiland, J.D., Liu, W.T., Humayun, M.S.: Retinal prosthesis. Annu. Rev. Biomed. Eng. 7, 361–401 (2005)

    Article  CAS  Google Scholar 

  72. Schwartz, A.B.: Cortical neural prosthetics. Annu. Rev. Neurosci. 27(1), 487–507 (2004)

    Article  CAS  Google Scholar 

  73. Cheung, K.C.: Implantable microscale neural interfaces. Biomed. Microdevices. 9(6), 923–938 (2007)

    Article  Google Scholar 

  74. Kipke, D.R., Vetter, R.J., Williams, J.C., Hetke, J.F.: Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex. IEEE Trans. Rehabil. Eng. 11(2), 151–155 (2003)

    Google Scholar 

  75. Rutten, W.L.C.: Selective electrical interfaces with the nervous system. Annu. Rev. Biomed. Eng. 4(1), 407–452 (2002)

    Article  CAS  Google Scholar 

  76. Cogan, S.F.: Neural stimulation and recording electrodes. Annu. Rev. Biomed. Eng. 10(1), 275–309 (2008)

    Article  CAS  Google Scholar 

  77. Tokuda, T., Pan, Y.L., Uehara, A., Kagawa, K., Nunoshita, M., Ohta, J.: Flexible and extendible neural interface device based on cooperative multi-chip CMOS LSI architecture. Sensors Actuators A Phys. 122(1), 88–98 (2005)

    Article  CAS  Google Scholar 

  78. Smith, B., Tang, Z.N., Johnson, M.W., Pourmehdi, S., Gazdik, M.M., Buckett, J.R., Peckham, P.H.: An externally powered, multichannel, implantable stimulator-telemeter for control of paralyzed muscle. IEEE Trans. Biomed. Eng. 45(4), 463–475 (1998)

    Article  CAS  Google Scholar 

  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. 104(8), 928–933 (2001)

    Article  CAS  Google Scholar 

  80. Grube, E., Gerckens, U., Rowold, S., Muller, R., Selbach, G., Stamm, J., Staberock, M.: Inhibition of in-stent restenosis by the Quanam drug eluting polymer stent; Two year follow-up. J. Am. Coll. Cardiol. 37(2), 74A–74A (2001)

    Google Scholar 

  81. Hiatt, B.L., Ikeno, F., Yeung, A.C., Carter, A.J.: Drug-eluting stents for the prevention of restenosis: in quest for the holy grail. Catheter. Cardiovasc. Interv. 55(3), 409–417 (2002)

    Article  Google Scholar 

  82. Allen, M. G M.E.J.K.D.J.M.; CardioMEMS, Inc., assignee. Communication with an Implanted Wireless Sensor. US. (2007)

    Google Scholar 

  83. Klose, J., Rehtanz, E., Rothe, C., Eulitz, I., Guther, V., Beck, W.: Manufacture of titanium implants. Mater. Werkst. 39(4–5), 304–308 (2008)

    Article  CAS  Google Scholar 

  84. Wiegand, U.K.H., Potratz, J., Luninghake, F., Taubert, G., Brandes, A., Diederich, K.W.: Electrophysiological characteristics of bipolar membrane carbon leads with and without steroid elution compared with a conventional carbon and a steroid-eluting platinum lead. Pacing Clin. Electrophysiol. 19(8), 1155–1161 (1996)

    Article  CAS  Google Scholar 

  85. Wiegand, U.K.H., Zhdanov, A., Stammwitz, E., Crozier, I., Claessens, R.J.J., Meier, J., Bos, R.J., Bode, F., Potratz, J.: Electrophysiological performance of a bipolar membrane-coated titanium nitride electrode: a randomized comparison of steroid and nonsteroid lead designs. Pacing Clin. Electrophysiol. 22(6), 935–941 (1999)

    Article  CAS  Google Scholar 

  86. Wiggins, M.J., Wilkoff, B., Anderson, J.M., Hiltner, A.: Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads. J. Biomed. Mater. Res. 58(3), 302–307 (2001)

    Article  CAS  Google Scholar 

  87. Russell, R.J., Pishko, M.V., Gefrides, C.C., McShane, M.J., Cote, G.L.: A fluorescence-based glucose biosensor using Concanavalin a and dextran encapsulated in a poly(ethylene glycol) hydrogel. Anal. Chem. 71(15), 3126–3132 (1999)

    Article  CAS  Google Scholar 

  88. Receveur, R.A.M., Lindemans, F.W., de Rooij, N.F.: Microsystem technologies for implantable applications. J. Micromech. Microeng. 17(5), R50–R80 (2007)

    Article  Google Scholar 

  89. Mokwa, W., Schnakenberg, U.: Micro-transponder systems for medical applications. IEEE Trans. Instrum. Meas. 50(6), 1551–1555 (2001)

    Article  Google Scholar 

  90. Flick, B.B., Orglmeister, R.: A portable microsystem-based telemetric pressure and temperature measurement unit. IEEE Trans. Biomed. Eng. 47(1), 12–16 (2000)

    Article  CAS  Google Scholar 

  91. Esashi, M., Sugiyama, S., Ikeda, K., Wang, Y.L., Miyashita, H.: Vacuum-sealed silicon micromachined pressure sensors. Proc. IEEE. 86(8), 1627–1639 (1998)

    Article  Google Scholar 

  92. Chen, P.J., Rodger, D.C., Agrawal, R., Saati, S., Meng, E., Varma, R., Humayun, M.S., Tai, Y.C.: Implantable micromechanical parylene-based pressure sensors for unpowered intraocular pressure sensing. J. Micromech. Microeng. 17(10), 1931–1938 (2007)

    Article  Google Scholar 

  93. Chen, L., Manz, A., Day, P.J.R.: Total nucleic acid analysis integrated on microfluidic devices. Lab Chip. 7(11), 1413–1423 (2007)

    Article  CAS  Google Scholar 

  94. Heyries, K.A., Loughran, M.G., Hoffmann, D., Homsy, A., Blum, L.J., Marquette, C.A.: Microfluidic biochip for chemiluminescent detection of allergen-specific antibodies. Biosens. Bioelectron. 23(12), 1812–1818 (2008)

    Article  CAS  Google Scholar 

  95. Isoda, T., Urushibara, I., Sato, M., Uemura, H., Sato, H., Yamauchi, N.: Development of a sensor-array chip with immobilized antibodies and the application of a wireless antigen- screening system. Sensors Actuators B Chem. 129(2), 958–970 (2008)

    Article  CAS  Google Scholar 

  96. Prakash, R., Kaler, K.: An integrated genetic analysis microfluidic platform with valves and a PCR chip reusability method to avoid contamination. Microfluid. Nanofluid. 3(2), 177–187 (2007)

    Article  CAS  Google Scholar 

  97. Zhang, C.S., Xu, J.L., Ma, W.L., Zheng, W.L.: PCR microfluidic devices for DNA amplification. Biotechnol. Adv. 24(3), 243–284 (2006)

    Article  CAS  Google Scholar 

  98. Sethu, P., Sin, A., Toner, M.: Microfluidic diffusive filter for apheresis (leukapheresis). Lab Chip. 6(1), 83–89 (2006)

    Article  CAS  Google Scholar 

  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. (2004)

    Google Scholar 

  100. Chamot, S.R., Depeursinge, C.: MEMS for enhanced optical diagnostics in endoscopy. Minim. Invasive Ther. Allied Technol. 16(2), 101–108 (2007)

    Article  Google Scholar 

  101. Hupert, M.L., Witek, M.A., Wang, Y., Mitchell, M.W., Liu, Y., Bejat, Y., Nikitopoulos, D.E., Goettert, J., Murphy, M.C., Soper, S.A.: Polymer-based microfluidic devices for biomedical applications. Proc. SPIE. 4982, 52–64 (2003)

    Article  Google Scholar 

  102. Mitchell, M.W., Liu, X., Bejat, Y., Nikitopoulos, D.E., Soper, S.A., Murphy, M.C.: Modeling and validation of a molded polycarbonate continuous flow polymerase chain reaction device. Proc. SPIE. 4982, 83–98 (2003)

    Article  Google Scholar 

  103. Lee, D.S., Park, S.H., Yang, H.S., Chung, K.H., Yoon, T.H., Kim, S.J., Kim, K., Kim, Y.T.: Bulk- micromachined submicroliter-volume PCR chip with very rapid thermal response and low power consumption. Lab Chip. 4(4), 401–407 (2004)

    Article  CAS  Google Scholar 

  104. Koh, C.G., Tan, W., Zhao, M.Q., Ricco, A.J., Fan, Z.H.: Integrating polymerase chain reaction, valving, and electrophoresis in a plastic device for bacterial detection. Anal. Chem. 75(17), 4591–4598 (2003)

    Article  CAS  Google Scholar 

  105. Krishnan, M., Burke, D.T., Burns, M.A.: Polymerase chain reaction in high surface-to-volume ratio SiO2 microstructures. Anal. Chem. 76(22), 6588–6593 (2004)

    Article  CAS  Google Scholar 

  106. Woolley, A.T., Hadley, D., Landre, P., de Mello, A.J., Mathies, R.A., Northrup, M.A.: Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. Anal. Chem. 68(23), 4081–4086 (1996)

    Article  CAS  Google Scholar 

  107. West, J., Karamata, B., Lillis, B., Gleeson, J.P., Alderman, J., Collins, J.K., Lane, W., Mathewson, H.B.: Application of magnetohydrodynamic actuation to continuous flow chemistry. Lab Chip. 2(4), 224–230 (2002)

    Article  CAS  Google Scholar 

  108. Hong, J.W., Fujii, T., Seki, M., Yamamoto, T., Endo, I.: Integration of gene amplification and capillary gel electrophoresis on a polydimethylsiloxane-glass hybrid microchip. Electrophoresis. 22(2), 328–333 (2001)

    Article  CAS  Google Scholar 

  109. Shen, K.Y., Chen, X.F., Guo, M., Cheng, J.: A microchip-based PCR device using flexible printed circuit technology. Sensors Actuators B Chem. 105(2), 251–258 (2005)

    Article  CAS  Google Scholar 

  110. Daniel, J.H., Iqbal, S., Millington, R.B., Moore, D.F., Lowe, C.R., Leslie, D.L., Lee, M.A., Pearce, M.J.: Silicon microchambers for DNA amplification. Sensors Actuators A Phys. 71(1–2), 81–88 (1998)

    Article  CAS  Google Scholar 

  111. Northrup, M.A., Benett, B., Hadley, D., Landre, P., Lehew, S., Richards, J., Stratton, P.: A miniature analytical instrument for nucleic acids based on micromachined silicon reaction chambers. Anal. Chem. 70(5), 918–922 (1998)

    Article  CAS  Google Scholar 

  112. Sun, K., Yamaguchi, A., Ishida, Y., Matsuo, S., Misawa, H.: A heater-integrated transparent microchannel chip for continuous-flow PCR. Sensors Actuators B Chem. 84(2–3), 283–289 (2002)

    Article  CAS  Google Scholar 

  113. Khandurina, J., McKnight, T.E., Jacobson, S.C., Waters, L.C., Foote, R.S., Ramsey, J.M.: Integrated system for rapid PCR-based DNA analysis in microfluidic devices. Anal. Chem. 72(13), 2995–3000 (2000)

    Article  CAS  Google Scholar 

  114. Lin, Y.C., Huang, M.Y., Young, K.C., Chang, T.T., Wu, C.Y.: A rapid micro-polymerase chain reaction system for hepatitis C virus amplification. Sensors Actuators B Chem. 71(1–2), 2–8 (2000)

    Article  CAS  Google Scholar 

  115. Lin, Y.C., Yang, C.C., Huang, M.Y.: Simulation and experimental validation of micro polymerase chain reaction chips. Sensors Actuators B Chem. 71(1–2), 127–133 (2000)

    Article  CAS  Google Scholar 

  116. Zhou, Z.M., Liu, D.Y., Zhong, R.T., Dai, Z.P., Wu, D.P., Wang, H., Du, Y.G., Xia, Z.N., Zhang, L.P., Mei, X.D., Lin, B.C.: Determination of SARS-coronavirus by a microfluidic chip system. Electrophoresis. 25(17), 3032–3039 (2004)

    Article  CAS  Google Scholar 

  117. Gulliksen, A., Solli, L., Karlsen, F., Rogne, H., Hovig, E., Nordstrom, T., Sirevag, R.: Real- time nucleic acid sequence-based amplification in nanoliter volumes. Anal. Chem. 76(1), 9–14 (2004)

    Article  CAS  Google Scholar 

  118. Matsubara, Y., Kerman, K., Kobayashi, M., Yamamura, S., Morita, Y., Tamiya, E.: Microchamber array based DNA quantification and specific sequence detection from a single copy via PCR in nanoliter volumes. Biosens. Bioelectron. 20(8), 1482–1490 (2005)

    Article  CAS  Google Scholar 

  119. Curcio, M., Roeraade, J.: Continuous segmented-flow polymerase chain reaction for high- throughput miniaturized DNA amplification. Anal. Chem. 75(1), 1–7 (2003)

    Article  CAS  Google Scholar 

  120. Sethu, P., Mastrangelo, C.H.: Cast epoxy-based microfluidic systems and their application in biotechnology. Sensors Actuators B Chem. 98(2–3), 337–346 (2004)

    Article  CAS  Google Scholar 

  121. Swerdlow, H., Jones, B.J., Wittwer, C.T.: Fully automated DNA reaction and analysis in a fluidic capillary instrument. Anal. Chem. 69(5), 848–855 (1997)

    Article  CAS  Google Scholar 

  122. Zhang, N.Y., Yeung, E.S.: On-line coupling of polymerase chain reaction and capillary electrophoresis for automatic DNA typing and HIV-1 diagnosis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 714(1), 3–11 (1998)

    Article  CAS  Google Scholar 

  123. Ferrance, J.P., Wu, Q.R., Giordano, B., Hernandez, C., Kwok, Y., Snow, K., Thibodeau, S., Landers, J.P.: Developments toward a complete micro-total analysis system for Duchenne muscular dystrophy diagnosis. Anal. Chim. Acta. 500(1–2), 223–236 (2003)

    Article  CAS  Google Scholar 

  124. Huhmer, A.F.R., Landers, J.P.: Noncontact infrared-mediated thermocycling for effective polymerase chain reaction amplification of DNA in nanoliter volumes. Anal. Chem. 72(21), 5507–5512 (2000)

    Article  CAS  Google Scholar 

  125. Oda, R.P., Strausbauch, M.A., Huhmer, A.F.R., Borson, N., Jurrens, S.R., Craighead, J., Wettstein, P.J., Eckloff, B., Kline, B., Landers, J.P.: Infrared-mediated thermocycling for ultrafast polymerase chain reaction amplification of DNA. Anal. Chem. 70(20), 4361–4368 (1998)

    Article  CAS  Google Scholar 

  126. Tanaka, Y., Slyadnev, M.N., Hibara, A., Tokeshi, M., Kitamori, T.: Non-contact photothermal control of enzyme reactions on a microchip by using a compact diode laser. J. Chromatogr. A. 894(1–2), 45–51 (2000)

    Article  CAS  Google Scholar 

  127. Schneegass, I., Brautigam, R., Kohler, J.M.: Miniaturized flow-through PCR with different template types in a silicon chip thermocycler. Lab Chip. 1(1), 42–49 (2001)

    Article  CAS  Google Scholar 

  128. Chou, C.F., Changrani, R., Roberts, P., Sadler, D., Burdon, J., Zenhausern, F., Lin, S., Mulholland, N.S., Terbrueggen, R.: A miniaturized cyclic PCR device - modeling and experiments. Microelectron. Eng. 61–62, 921–925 (2002)

    Article  Google Scholar 

  129. Liu, J., Enzelberger, M., Quake, S.: A nanoliter rotary device for polymerase chain reaction. Electrophoresis. 23(10), 1531–1536 (2002)

    Article  CAS  Google Scholar 

  130. Shi, Y.N., Simpson, P.C., Scherer, J.R., Wexler, D., Skibola, C., Smith, M.T., Mathies, R.A.: Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis. Anal. Chem. 71(23), 5354–5361 (1999)

    Article  CAS  Google Scholar 

  131. Waters, L.C., Jacobson, S.C., Kroutchinina, N., Khandurina, J., Foote, R.S., Ramsey, J.M.: Multiple sample PCR amplification and electrophoretic analysis on a microchip. Anal. Chem. 70(24), 5172–5176 (1998)

    Article  CAS  Google Scholar 

  132. Waters, L.C., Jacobson, S.C., Kroutchinina, N., Khandurina, J., Foote, R.S., Ramsey, J.M.: Microchip device for cell lysis, multiplex PCR amplification, and electrophoretic sizing. Anal. Chem. 70(1), 158–162 (1998)

    Article  CAS  Google Scholar 

  133. Perch-Nielsen, I.R., Bang, D.D., Poulsen, C.R., El-Ali, J., Wolff, A.: Removal of PCR inhibitors using dielectrophoresis as a selective filter in a microsystem. Lab Chip. 3(3), 212–216 (2003)

    Article  CAS  Google Scholar 

  134. Gascoyne, P., Mahidol, C., Ruchirawat, M., Satayavivad, J., Watcharasit, P., Becker, F.F.: Microsample preparation by dielectrophoresis: isolation of malaria. Lab Chip. 2(2), 70–75 (2002)

    Article  CAS  Google Scholar 

  135. Namasivayam, V., Lin, R.S., Johnson, B., Brahmasandra, S., Razzacki, Z., Burke, D.T., Burns, M.A.: Advances in on-chip photodetection for applications in miniaturized genetic analysis systems. J. Micromech. Microeng. 14(1), 81–90 (2004)

    Article  CAS  Google Scholar 

  136. Kumar, A., Goel, G., Fehrenbach, E., Puniya, A.K., Singh, K.: Microarrays: the technology, analysis and application. Eng. Life Sci. 5(3), 215–222 (2005)

    Article  CAS  Google Scholar 

  137. Bulyk, M.L.: DNA microarray technologies for measuring protein-DNA interactions. Curr. Opin. Biotechnol. 17(4), 422–430 (2006)

    Article  CAS  Google Scholar 

  138. Cretich, M., Damin, F., Pirri, G., Chiari, M.: Protein and peptide arrays: recent trends and new directions. Biomol. Eng. 23(2–3), 77–88 (2006)

    Article  CAS  Google Scholar 

  139. Hoheisel, J.D.: Microarray technology: beyond transcript profiling and genotype analysis. Nat. Rev. Genet. 7(3), 200–210 (2006)

    Article  CAS  Google Scholar 

  140. Hultschig, C., Kreutzberger, J., Seitz, H., Konthur, Z., Bussow, K., Lehrach, H.: Recent advances of protein microarrays. Curr. Opin. Chem. Biol. 10(1), 4–10 (2006)

    Article  CAS  Google Scholar 

  141. Stoughton, R.B.: Applications of DNA microarrays in biology. Annu. Rev. Biochem. 74, 53–82 (2005)

    Article  CAS  Google Scholar 

  142. Barbulovic-Nad, I., Lucente, M., Sun, Y., Zhang, M.J., Wheeler, A.R., Bussmann, M.: Bio-microarray fabrication techniques - a review. Crit. Rev. Biotechnol. 26(4), 237–259 (2006)

    Article  CAS  Google Scholar 

  143. http://www.affymetrix.com

  144. Anderson, R.C., Su, X., Bogdan, G.J., Fenton, J.: A miniature integrated device for automated multistep genetic assays. Nucleic Acids Res. 28(12), e60i–e60vi (2000)

    Article  Google Scholar 

  145. Lenigk, R., Liu, R.H., Athavale, M., Chen, Z.J., Ganser, D., Yang, J.N., Rauch, C., Liu, Y.J., Chan, B., Yu, H.N., Ray, M., Marrero, R., Grodzinski, P.: Plastic biochannel hybridization devices: a new concept for microfluidic DNA arrays. Anal. Biochem. 311(1), 40–49 (2002)

    Article  CAS  Google Scholar 

  146. Liu, J., Hansen, C., Quake, S.R.: Solving the "world-to-chip" interface problem with a microfluidic matrix. Anal. Chem. 75(18), 4718–4723 (2003)

    Article  CAS  Google Scholar 

  147. Martynova, L., Locascio, L.E., Gaitan, M., Kramer, G.W., Christensen, R.G., MacCrehan, W.A.: Fabrication of plastic microfluid channels by imprinting methods. Anal. Chem. 69(23), 4783–4789 (1997)

    Article  CAS  Google Scholar 

  148. Qi, S.Z., Liu, X.Z., Ford, S., Barrows, J., Thomas, G., Kelly, K., McCandless, A., Lian, K., Goettert, J., Soper, S.A.: Microfluidic devices fabricated in poly(methyl methacrylate) using hot-embossing with integrated sampling capillary and fiber optics for fluorescence detection. Lab Chip. 2(2), 88–95 (2002)

    Article  CAS  Google Scholar 

  149. Soper, S.A., Ford, S.M., Qi, S., McCarley, R.L., Kelly, K., Murphy, M.C.: Polymeric microelectromechanical systems. Anal. Chem. 72(19), 642A–651A (2000)

    Article  CAS  Google Scholar 

  150. Situma, C., Hashimoto, M., Soper, S.A.: Merging microfluidics with microarray-based bioassays. Biomol. Eng. 23(5), 213–231 (2006)

    Article  CAS  Google Scholar 

  151. Thorsen, T., Maerkl, S.J., Quake, S.R.: Microfluidic large-scale integration. Science. 298(5593), 580–584 (2002)

    Article  CAS  Google Scholar 

  152. Duffy, D.C., McDonald, J.C., Schueller, O.J.A., Whitesides, G.M.: Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal. Chem. 70(23), 4974–4984 (1998)

    Article  CAS  Google Scholar 

  153. Unger, M.A., Chou, H.P., Thorsen, T., Scherer, A., Quake, S.R.: Monolithic microfabricated valves and pumps by multilayer soft lithography. Science. 288(5463), 113–116 (2000)

    Article  CAS  Google Scholar 

  154. Marcus, J.S., Anderson, W.F., Quake, S.R.: Microfluidic single-cell mRNA isolation and analysis. Anal. Chem. 78(9), 3084–3089 (2006)

    Article  CAS  Google Scholar 

  155. Lee, C.C., Sui, G.D., Elizarov, A., Shu, C.Y.J., Shin, Y.S., Dooley, A.N., Huang, J., Daridon, A., Wyatt, P., Stout, D., Kolb, H.C., Witte, O.N., Satyamurthy, N., Heath, J.R., Phelps, M.E., Quake, S.R., Tseng, H.R.: Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science. 310(5755), 1793–1796 (2005)

    Article  CAS  Google Scholar 

  156. Balagadde, F.K., You, L.C., Hansen, C.L., Arnold, F.H., Quake, S.R.: Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science. 309(5731), 137–140 (2005)

    Article  CAS  Google Scholar 

  157. Anderson, M.J., Hansen, C.L., Quake, S.R.: Phase knowledge enables rational screens for protein crystallization. Proc. Natl. Acad. Sci. U. S. A. 103(45), 16746–16751 (2006)

    Article  CAS  Google Scholar 

  158. Hansen, C.L., Classen, S., Berger, J.M., Quake, S.R.: A microfluidic device for kinetic optimization of protein crystallization and in situ structure determination. J. Am. Chem. Soc. 128(10), 3142–3143 (2006)

    Article  CAS  Google Scholar 

  159. Hansen, C.L., Sommer, M.O.A., Quake, S.R.: Systematic investigation of protein phase behavior with a microfluidic formulator. Proc. Natl. Acad. Sci. U. S. A. 101(40), 14431–14436 (2004)

    Article  CAS  Google Scholar 

  160. http://www.fluidigm.com

  161. Schorzman, D.A., Desimone, J.M., Rolland, J.P., Quake, S.R., Van Dam, R.M.: Solvent- resistant Photocurable “liquid Teflon” for microfluidic device fabrication. J. Am. Chem. Soc. 126(8), 2322–2323 (2004)

    Article  CAS  Google Scholar 

  162. Melin, J., Quake, S.R.: Microfluidic large-scale integration: the evolution of design rules for biological automation. Annu. Rev. Biophys. Biomol. Struct. 36, 213–231 (2007)

    Article  CAS  Google Scholar 

  163. Kamotani, Y., Bersano-Begey, T., Kato, N., Tung, Y.C., Huh, D., Song, J.W., Takayama, S.: Individually programmable cell stretching microwell arrays actuated by a Braille display. Biomaterials. 29(17), 2646–2655 (2008)

    Article  CAS  Google Scholar 

  164. Song, J.W., Gu, W., Futai, N., Warner, K.A., Nor, J.E., Takayama, S.: Computer-controlled microcirculatory support system for endothelial cell culture and shearing. Anal. Chem. 77(13), 3993–3999 (2005)

    Article  CAS  Google Scholar 

  165. Gu, W., Zhu, X.Y., Futai, N., Cho, B.S., Takayama, S.: Computerized microfluidic cell culture using elastomeric channels and Braille displays. Proc. Natl. Acad. Sci. U. S. A. 101(45), 15861–15866 (2004)

    Article  CAS  Google Scholar 

  166. Enzelberger, M.M., Hansen, C.L., Liu, J., Quake, S.R., Ma, C. Nucleic acid amplification using microfluidic devices, WO/2002/081729. World Intellectual Property Organization; (2002)

    Google Scholar 

  167. Lee, C., Sui, G., Elizarov, A., Kolb, H.C., Huang, J., Heath, J.R., Phelps, M.E., Quake, S.R., Tseng, H., Wyatt, P. Microfluidic Devices with Chemical Reaction Circuits. EP Patent 1,838,431; (2007)

    Google Scholar 

  168. El-Ali, J., Sorger, P.K., Jensen, K.F.: Cells on chips. Nature. 442(7101), 403–411 (2006)

    Article  CAS  Google Scholar 

  169. Park, T.H., Shuler, M.L.: Integration of cell culture and microfabrication technology. Biotechnol. Prog. 19(2), 243–253 (2003)

    Article  CAS  Google Scholar 

  170. Sims, C.E., Allbritton, N.L.: Analysis of single mammalian cells on-chip. Lab Chip. 7(4), 423–440 (2007)

    Article  CAS  Google Scholar 

  171. Cheng, J.Y., Yen, M.H., Kuo, C.T., Young, T.H.: A transparent cell-culture micro chamber with a variably controlled concentration gradient generator and flow field rectifier. Biomicrofluidics. 2(2), 12 (2008)

    Article  CAS  Google Scholar 

  172. Petronis, S., Stangegaard, M., Christensen, C.B.V., Dufva, M.: Transparent polymeric cell culture chip with integrated temperature control and uniform media perfusion. BioTechniques. 40(3), 368–376 (2006)

    Article  CAS  Google Scholar 

  173. Park, J., Bansal, T., Pinelis, M., Maharbiz, M.M.: A microsystem for sensing and patterning oxidative microgradients during cell culture. Lab Chip. 6(5), 611–622 (2006)

    Article  CAS  Google Scholar 

  174. Maharbiz, M.M., Holtz, W.J., Sharifzadeh, S., Keasling, J.D., Howe, R.T.: A microfabricated electrochemical oxygen generator for high-density cell culture arrays. J. Microelectromech. Syst. 12(5), 590–599 (2003)

    Article  CAS  Google Scholar 

  175. Vollmer, A.P., Probstein, R.F., Gilbert, R., Thorsen, T.: Development of an integrated microfluidic platform for dynamic oxygen sensing and delivery in a flowing medium. Lab Chip. 5(10), 1059–1066 (2005)

    Article  CAS  Google Scholar 

  176. Ges, I.A., Ivanov, B.L., Schaffer, D.K., Lima, E.A., Werdich, A.A., Baudenbacher, F.J.: Thin-film IrOx pH microelectrode for microfluidic-based microsystems. Biosens. Bioelectron. 21(2), 248–256 (2005)

    Article  CAS  Google Scholar 

  177. Taff, B.M., Voldman, J.: A scalable addressable positive-dielectrophoretic cell-sorting array. Anal. Chem. 77(24), 7976–7983 (2005)

    Article  CAS  Google Scholar 

  178. Voldman, J., Gray, M.L., Toner, M., Schmidt, M.A.: A microfabrication-based dynamic array cytometer. Anal. Chem. 74(16), 3984–3990 (2002)

    Article  CAS  Google Scholar 

  179. Wang, X.B., Yang, J., Huang, Y., Vykoukal, J., Becker, F.F., Gascoyne, P.R.C.: Cell separation by dielectrophoretic field-flow-fractionation. Anal. Chem. 72(4), 832–839 (2000)

    Article  CAS  Google Scholar 

  180. Gomez-Sjoberg, R., Leyrat, A.A., Pirone, D.M., Chen, C.S., Quake, S.R.: Versatile, fully automated, microfluidic cell culture system. Anal. Chem. 79(22), 8557–8563 (2007)

    Article  CAS  Google Scholar 

  181. Hung, P.J., Lee, P.J., Sabounchi, P., Lin, R., Lee, L.P.: Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnol. Bioeng. 89(1), 1–8 (2005)

    Article  CAS  Google Scholar 

  182. Lii, J., Hsu, W.J., Parsa, H., Das, A., Rouse, R., Sia, S.K.: Real-time microfluidic system for studying mammalian cells in 3D microenvironments. Anal. Chem. 80(10), 3640–3647 (2008)

    Article  CAS  Google Scholar 

  183. Madou, M., Zoval, J., Jia, G.Y., Kido, H., Kim, J., Kim, N.: Lab on a CD. Annu. Rev. Biomed. Eng. 8, 601–628 (2006)

    Article  CAS  Google Scholar 

  184. Balaban, N.Q., Schwarz, U.S., Riveline, D., Goichberg, P., Tzur, G., Sabanay, I., Mahalu, D., Safran, S., Bershadsky, A., Addadi, L., Geiger, B.: Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3(5), 466–472 (2001)

    Article  CAS  Google Scholar 

  185. Tan, J.L., Tien, J., Pirone, D.M., Gray, D.S., Bhadriraju, K., Chen, C.S.: Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl. Acad. Sci. U. S. A. 100(4), 1484–1489 (2003)

    Article  CAS  Google Scholar 

  186. Hellmich, W., Pelargus, C., Leffhalm, K., Ros, A., Anselmetti, D.: Single cell manipulation, analytics, and label-free protein detection in microfluidic devices for systems nanobiology. Electrophoresis. 26(19), 3689–3696 (2005)

    Article  CAS  Google Scholar 

  187. Munce, N.R., Li, J.Z., Herman, P.R., Lilge, L.: Microfabricated system for parallel single-cell capillary electrophoresis. Anal. Chem. 76(17), 4983–4989 (2004)

    Article  CAS  Google Scholar 

  188. Klaus, J.W., George, S.M.: SiO2 chemical vapor deposition at room temperature using SiCl4 and H2O with an NH3 catalyst. J. Electrochem. Soc. 147(7), 2658–2664 (2000)

    Article  CAS  Google Scholar 

  189. Senturia, S.D.: Microsystem Design. Springer Science+Business Media, LLC, New York (2005)

    Google Scholar 

  190. Lim, K.S., Chang, W.J., Koo, Y.M., Bashir, R.: Reliable fabrication method of transferable micron scale metal pattern for poly(dimethylsiloxane) metallization. Lab Chip. 6(4), 578–580 (2006)

    Article  CAS  Google Scholar 

  191. Niu, X.Z., Peng, S.L., Liu, L.Y., Wen, W.J., Sheng, P.: Characterizing and patterning of PDMS- based conducting composites. Adv. Mater. 19(18), 2682–2686 (2007)

    Article  CAS  Google Scholar 

  192. Bowden, N., Brittain, S., Evans, A.G., Hutchinson, J.W., Whitesides, G.M.: Spontaneous formation of ordered structures in thin films of metals supported on an elastomeric polymer. Nature. 393(6681), 146–149 (1998)

    Article  CAS  Google Scholar 

  193. Trau, D., Jiang, J., Sucher, N.J.: Preservation of the biofunctionality of DNA and protein during microfabrication. Langmuir. 22(3), 877–881 (2006)

    Article  CAS  Google Scholar 

  194. Kentsch, J., Breisch, S., Stezle, M.: Low temperature adhesion bonding for BioMEMS. J. Micromech. Microeng. 16(4), 802–807 (2006)

    Article  CAS  Google Scholar 

  195. Ghafar-Zadeh, E., Sawan, M., Therriault, D.: Novel direct-write CMOS-based laboratory- on-chip: design, assembly and experimental results. Sensors Actuators A Phys. 134(1), 27–36 (2007)

    Article  CAS  Google Scholar 

  196. Zimmermann, S., Fienbork, D., Flounders, A.W., Liepmann, D.: In-device enzyme immobilization: wafer-level fabrication of an integrated glucose sensor. Sensors Actuators B Chem. 99(1), 163–173 (2004)

    Article  CAS  Google Scholar 

  197. Linder, V., Koster, S., Franks, W., Kraus, T., Verpoorte, E., Heer, F., Hierlemann, A., de Rooij, N.F.: Microfluidics/CMOS orthogonal capabilities for cell biology. Biomed. Microdevices. 8(2), 159–166 (2006)

    Article  Google Scholar 

  198. Pan, J.Y.: Reliability considerations for the BioMEMS designer. Proc. IEEE. 92(1), 174–184 (2004)

    Article  CAS  Google Scholar 

  199. Bhagat, A.A.S., Jothimuthu, P., Pais, A., Papautsky, I.: Re-usable quick-release interconnect for characterization of microfluidic systems. J. Micromech. Microeng. 17(1), 42–49 (2007)

    Article  Google Scholar 

  200. Christensen, A.M., Chang-Yen, D.A., Gale, B.K.: Characterization of interconnects used in PDMS microfluidic systems. J. Micromech. Microeng. 15(5), 928–934 (2005)

    Article  Google Scholar 

  201. Han, K.H., McConnell, R.D., Easley, C.J., Bienvenue, J.M., Ferrance, J.P., Landers, J.P., Frazier, A.B.: An active microfluidic system packaging technology. Sensors Actuators B Chem. 122(1), 337–346 (2007)

    Article  CAS  Google Scholar 

  202. Puntambekar, A., Ahn, C.H.: Self-aligning microfluidic interconnects for glass- and plastic-based microfluidic systems. J. Micromech. Microeng. 12(1), 35–40 (2002)

    Article  Google Scholar 

  203. Fujii, T., Sando, Y., Higashino, K., Fujii, Y.: A plug and play microfluidic device. Lab Chip. 3(3), 193–197 (2003)

    Article  CAS  Google Scholar 

  204. Igata, E., Arundell, M., Morgan, H., Cooper, J.M.: Interconnected reversible lab-on-a-chip technology. Lab Chip. 2(2), 65–69 (2002)

    Article  CAS  Google Scholar 

  205. Yuen, P.K.: SmartBuild–A truly plug-n-play modular microfluidic system. Lab Chip. 8, 1374–1378 (2008)

    Article  CAS  Google Scholar 

  206. Shaikh, K.A., Ryu, K.S., Goluch, E.D., Nam, J.M., Liu, J.W., Thaxton, S., Chiesl, T.N., Barron, A.E., Lu, Y., Mirkin, C.A., Liu, C.: A modular microfluidic architecture for integrated bio- chemical analysis. Proc. Natl. Acad. Sci. U. S. A. 102(28), 9745–9750 (2005)

    Article  CAS  Google Scholar 

  207. Ko, W.H.: Packaging of microfabricated devices and systems. Mater. Chem. Phys. 42(3), 169–175 (1995)

    Article  CAS  Google Scholar 

  208. Murarka, S.P.: Multilevel interconnections for ULSI and GSI era. Mater. Sci. Eng. R. Rep. 19(3–4), 87–151 (1997)

    Article  Google Scholar 

  209. Tong, H.M.: Microelectronics packaging – present and future. Mater. Chem. Phys. 40(3), 147–161 (1995)

    Article  CAS  Google Scholar 

  210. James, C.D., Spence, A.J.H., Dowell-Mesfin, N.M., Hussain, R.J., Smith, K.L., Craighead, H.G., Isaacson, M.S., Shain, W., Turner, J.N.: Extracellular recordings from patterned neuronal networks using planar microelectrode arrays. IEEE Trans. Biomed. Eng. 51(9), 1640–1648 (2004)

    Article  Google Scholar 

  211. Fair, R.B.: Digital microfluidics: is a true lab-on-a-chip possible? Microfluid. Nanofluid. 3(3), 245–281 (2007)

    Article  CAS  Google Scholar 

  212. Hartley, L., Kaler, K., Yadid-Pecht, O.: Hybrid integration of an active pixel sensor and microfluidics for cytometry on a chip. IEEE Trans. Circuits Syst. Regul. Pap. 54(1), 99–110 (2007)

    Article  Google Scholar 

  213. Huang, Y., Yang, J.M., Hopkins, P.J., Kassegne, S., Tirado, M., Forster, A.H., Reese, H.: Separation of simulants of biological warfare agents from blood by a miniaturized dielectrophoresis device. Biomed. Microdevices. 5(3), 217–225 (2003)

    Article  CAS  Google Scholar 

  214. Petrou, P.S., Moser, I., Jobst, G.: BioMEMS device with integrated microdialysis probe and biosensor array. Biosens. Bioelectron. 17(10), 859–865 (2002)

    Article  CAS  Google Scholar 

  215. Piruska, A., Nikcevic, I., Lee, S.H., Ahn, C., Heineman, W.R., Limbach, P.A., Seliskar, C.J.: The autofluorescence of plastic materials and chips measured under laser irradiation. Lab Chip. 5(12), 1348–1354 (2005)

    Article  CAS  Google Scholar 

  216. Bliss, C.L., McMullin, J.N., Backhouse, C.J.: Rapid fabrication of a microfluidic device with integrated optical waveguides for DNA fragment analysis. Lab Chip. 7(10), 1280–1287 (2007)

    Article  CAS  Google Scholar 

  217. Lee, K.S., Lee, H.L.T., Ram, R.J.: Polymer waveguide backplanes for optical sensor interfaces in microfluidics. Lab Chip. 7(11), 1539–1545 (2007)

    Article  CAS  Google Scholar 

  218. Chung, K., Crane, M.M., Lu, H.: Automated on-chip rapid microscopy, phenotyping and sorting of C.elegans. Nat. Methods. 5(7), 637–643 (2008)

    Article  CAS  Google Scholar 

  219. El-Ali, J., Gaudet, S., Gunther, A., Sorger, P.K., Jensen, K.F.: Cell stimulus and lysis in a microfluidic device with segmented gas-liquid flow. Anal. Chem. 77(11), 3629–3636 (2005)

    Article  CAS  Google Scholar 

  220. Voskerician, G., Shive, M.S., Shawgo, R.S., von Recum, H., Anderson, J.M., Cima, M.J., Langer, R.: Biocompatibility and biofouling of MEMS drug delivery devices. Biomaterials. 24(11), 1959–1967 (2003)

    Article  CAS  Google Scholar 

  221. Brischwein, M., Motrescu, E.R., Cabala, E., Otto, A.M., Grothe, H., Wolf, B.: Functional cellular assays with multiparametric silicon sensor chips. Lab Chip. 3(4), 234–240 (2003)

    Article  CAS  Google Scholar 

  222. Szarowski, D.H., Andersen, M.D., Retterer, S., Spence, A.J., Isaacson, M., Craighead, H.G., Turner, J.N., Shain, W.: Brain responses to micro-machined silicon devices. Brain Res. 983(1–2), 23–35 (2003)

    Article  CAS  Google Scholar 

  223. http://www.mchips.com

  224. Shawgo, R.S., Grayson, A.C.R., Li, Y.W., Cima, M.J.: BioMEMS for drug delivery. Curr. Opin. Solid State Mater. Sci. 6(4), 329–334 (2002)

    Article  CAS  Google Scholar 

  225. Fallahi, D., Mirzadeh, H., Khorasani, M.T.: Physical, mechanical, and biocompatibility evaluation of three different types of silicone rubber. J. Appl. Polym. Sci. 88(10), 2522–2529 (2003)

    Article  CAS  Google Scholar 

  226. Mata, A., Fleischman, A.J., Roy, S.: Characterization of polydimethylsiloxane (PDMS) properties for biomedical micro/nanosystems. Biomed. Microdevices. 7(4), 281–293 (2005)

    Article  CAS  Google Scholar 

  227. Lee, J.N., Jiang, X., Ryan, D., Whitesides, G.M.: Compatibility of mammalian cells on surfaces of poly(dimethylsiloxane). Langmuir. 20(26), 11684–11691 (2004)

    Article  CAS  Google Scholar 

  228. Millet, L.J., Stewart, M.E., Sweedler, J.V., Nuzzo, R.G., Gillette, M.U.: Microfluidic devices for culturing primary mammalian neurons at low densities. Lab Chip. 7(8), 987–994 (2007)

    Article  CAS  Google Scholar 

  229. Kim, L., Toh, Y.C., Voldman, J., Yu, H.: A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab Chip. 7(6), 681–694 (2007)

    Article  CAS  Google Scholar 

  230. Kasemo, B.: Biological surface science. Surf. Sci. 500(1–3), 656–677 (2002)

    Article  CAS  Google Scholar 

  231. Makamba, H., Kim, J.H., Lim, K., Park, N., Hahn, J.H.: Surface modification of poly(dimethylsiloxane) microchannels. Electrophoresis. 24(21), 3607–3619 (2003)

    Article  CAS  Google Scholar 

  232. Fritz, J.L., Owen, M.J.: Hydrophobic recovery of plasma-treated polydimethylsiloxane. J. Adhes. 54(1), 33–45 (1995)

    Article  CAS  Google Scholar 

  233. Hu, S., Ren, X., Bachman, M., Sims, C.E., Li, G.P., Allbritton, N.: Surface modification of poly(dimethylsiloxane) microfluidic devices by ultraviolet polymer grafting. Anal. Chem. 74(16), 4117–4123 (2002)

    Article  CAS  Google Scholar 

  234. Slentz, B.E., Penner, N.A., Regnier, F.E.: Capillary electrochromatography of peptides on microfabricated poly(dimethylsiloxane) chips modified by cerium(IV)-catalyzed polymerization. J. Chromatogr. A. 948(1–2), 225–233 (2002)

    Article  CAS  Google Scholar 

  235. Ocvirk, G., Munroe, M., Tang, T., Oleschuk, R., Westra, K., Harrison, D.J.: Electrokinetic control of fluid flow in native poly(dimethylsiloxane) capillary electrophoresis devices. Electrophoresis. 21(1), 107–115 (2000)

    Article  CAS  Google Scholar 

  236. Dou, Y.H., Bao, N., Xu, J.J., Chen, H.Y.: A dynamically modified microfluidic poly(dimethylsiloxane) chip with electrochemical detection for biological analysis. Electrophoresis. 23(20), 3558–3566 (2002)

    Article  CAS  Google Scholar 

  237. Decher, G.: Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science. 277(5330), 1232–1237 (1997)

    Article  CAS  Google Scholar 

  238. Sung, W.C., Chang, C.C., Makamba, H., Chen, S.H.: Long-term affinity modification on poly(dimethylsiloxane) substrate and its application for ELISA analysis. Anal. Chem. 80(5), 1529–1535 (2008)

    Article  CAS  Google Scholar 

  239. Hanein, Y., Pan, Y.V., Ratner, B.D., Denton, D.D., Bohringer, K.F.: Micromachining of non-fouling coatings for bio-MEMS applications. Sensors Actuators B Chem. 81(1), 49–54 (2001)

    Article  CAS  Google Scholar 

  240. Lopez, G.P., Ratner, B.D., Tidwell, C.D., Haycox, C.L., Rapoza, R.J., Horbett, T.A.: Glow- discharge plasma deposition of Tetraethylene glycol dimethyl ether for fouling-resistant biomaterial surfaces. J. Biomed. Mater. Res. 26(4), 415–439 (1992)

    Article  CAS  Google Scholar 

  241. Dhayal, M., Choi, J.S., So, C.H.: Biological fluid interaction with controlled surface properties of organic micro-fluidic devices. Vacuum. 80(8), 876–879 (2006)

    Article  CAS  Google Scholar 

  242. Bajaj, P., Akin, D., Gupta, A., Sherman, D., Shi, B., Auciello, O., Bashir, R.: Ultrananocrystalline diamond film as an optimal cell interface for biomedical applications. Biomed. Microdevices. 9(6), 787–794 (2007)

    Article  CAS  Google Scholar 

  243. Hoivik, N.D., Elam, J.W., Linderman, R.J., Bright, V.M., George, S.M., Lee, Y.C.: Atomic layer deposited protective coatings for micro-electromechanical systems. Sensors Actuators A Phys. 103(1–2), 100–108 (2003)

    Article  CAS  Google Scholar 

  244. Wang, Y.L., Pai, J.H., Lai, H.H., Sims, C.E., Bachman, M., Li, G.P., Allbritton, N.L.: Surface graft polymerization of SU-8 for bio-MEMS applications. J. Micromech. Microeng. 17(7), 1371–1380 (2007)

    Article  CAS  Google Scholar 

  245. Wang, Y.L., Bachman, M., Sims, C.E., Li, G.P., Allbritton, N.L.: Simple photografting method to chemically modify and micropattern the surface of SU-8 photoresist. Langmuir. 22(6), 2719–2725 (2006)

    Article  CAS  Google Scholar 

  246. Nordstrom, M., Marie, R., Calleja, M., Boisen, A.: Rendering SU-8 hydrophilic to facilitate use in micro channel fabrication. J. Micromech. Microeng. 14(12), 1614–1617 (2004)

    Article  Google Scholar 

  247. Joshi, M., Kale, N., Lal, R., Rao, V.R., Mukherji, S.: A novel dry method for surface modification of SU-8 for immobilization of biomolecules in Bio-MEMS. Biosens. Bioelectron. 22(11), 2429–2435 (2007)

    Article  CAS  Google Scholar 

  248. Chen, C.S., Mrksich, M., Huang, S., Whitesides, G.M., Ingber, D.E.: Micropatterned surfaces for control of cell shape, position, and function. Biotechnol. Prog. 14(3), 356–363 (1998)

    Article  CAS  Google Scholar 

  249. Duncan, A.C., Weisbuch, F., Rouais, F., Lazare, S., Baquey, C.: Laser microfabricated model surfaces for controlled cell growth. Biosens. Bioelectron. 17(5), 413–426 (2002)

    Article  CAS  Google Scholar 

  250. Duncan, A.C., Rouais, F., Lazare, S., Bordenave, L., Baquey, C.: Effect of laser modified surface microtopochemistry on endothelial cell growth. Colloids Surf. B. Biointerfaces. 54(2), 150–159 (2007)

    Article  CAS  Google Scholar 

  251. Edell, D.J., Toi, V.V., McNeil, V.M., Clark, L.D.: Factors influencing the biocompatibility of insertable silicon microshafts in cerebral-cortex. IEEE Trans. Biomed. Eng. 39(6), 635–643 (1992)

    Article  CAS  Google Scholar 

  252. Hoogerwerf, A.C., Wise, K.D.: A 3-dimensional microelectrode array for chronic neural recording. IEEE Trans. Biomed. Eng. 41(12), 1136–1146 (1994)

    Article  CAS  Google Scholar 

  253. Schmidt, S., Horch, K., Normann, R.: Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue. J. Biomed. Mater. Res. 27(11), 1393–1399 (1993)

    Article  CAS  Google Scholar 

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Park, E.S., Krajniak, J., Lu, H. (2021). Packaging for Bio-micro-electro-mechanical Systems (BioMEMS) and Microfluidic Chips. In: Wong, C.PP., Moon, Ks.(., Li, Y. (eds) Nano-Bio- Electronic, Photonic and MEMS Packaging. Springer, Cham. https://doi.org/10.1007/978-3-030-49991-4_12

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