Thin Film Biosensors

  • Hatice Ceylan Koydemir
  • Haluk Külah
  • Canan Özgen
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


New generation biosensors are analytical compact devices made of thin films. Sensitivity, specificity, rapid response time, ease-of-use, and low cost are the major advantages of these biosensors. All of these properties are closely related with thicknesses of the films used in fabrication of the sensor. The detection principle of a biosensor is mainly based on the interaction of the biological analyte with the surface-modified thin film. The thin film acts as a physicochemical—optical, mechanical, magnetic, and electrical—transducer and converts the signal resulting from the recognition of the biological analyte into another measurable signal. In this chapter, first, the roles of thin films in biosensor applications will be discussed. Then, different types of thin films used in the fabrication of biosensors will be explained. The methods to form organic thin films on sensitive layers for adsorption of biological analytes will be given together with four main methods of detection as: optical, mechanical, magnetic, and electrical. Finally, recent developments will be outlined.


Microfluidic Device Localize Surface Plasmon Resonance Microfluidic Chip Roll Circle Amplification Organic Thin Film 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Newman, J., Setford, S.: Enzymatic biosensors. Mol. Biotechnol. 32(3), 249–268 (2006). doi: 10.1385/mb:32:3:249 CrossRefGoogle Scholar
  2. 2.
    Kong, T., Su, R., Zhang, B., Zhang, Q., Cheng, G.: CMOS-compatible, label-free silicon-nanowire biosensors to detect cardiac troponin I for acute myocardial infarction diagnosis. Biosens. Bioelectron. 34(1), 267–272 (2012). doi: 10.1016/j.bios.2012.02.019 CrossRefGoogle Scholar
  3. 3.
    Tan, C.P., Craighead, H.G.: Surface engineering and patterning using parylene for biological applications. Materials 3(3), 1803–1832 (2010). doi: 10.3390/ma3031803 ADSCrossRefGoogle Scholar
  4. 4.
    Li, W., Kabius, B., Auciello, O.: Science and technology of biocompatible thin films for implantable biomedical devices. In: 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society Conference Proceedings, pp. 6237–6242. (2010). doi: 10.1109/IEMBS.2010.5628056
  5. 5.
    Farra, R., Sheppard, N.F., McCabe, L., Neer, R.M., Anderson, J.M., Santini, J.T., Cima, M.J., Langer, R.: First-in-human testing of a wirelessly controlled drug delivery microchip. Sci. Transl. Med. 4(122), 121–122 (2012)CrossRefGoogle Scholar
  6. 6.
    Ainslie, K.M., Desai, T.A.: Microfabricated implants for applications in therapeutic delivery, tissue engineering, and biosensing. Lab Chip 8(11), 1864–1878 (2008). doi: 10.1039/b806446f CrossRefGoogle Scholar
  7. 7.
    Sokolov, A.N., Tee, B.C.K., Bettinger, C.J., Tok, J.B.H., Bao, Z.: Chemical and engineering approaches to enable organic field-effect transistors for electronic skin applications. Acc. Chem. Res. 45(3), 361–371 (2011). doi: 10.1021/ar2001233 CrossRefGoogle Scholar
  8. 8.
    Chiang, T.-C.: Superconductivity in thin films. Science 306(5703), 1900–1901 (2004). doi: 10.1126/science.1106675 CrossRefGoogle Scholar
  9. 9.
    Dew-Hughes, D.: The critical current of superconductors: An historical review. Low Temp. Phys. 27(9–10), 713–722 (2001). doi: 10.1063/1.1401180 ADSCrossRefGoogle Scholar
  10. 10.
    Ceylan Koydemir, H., Kulah, H., Ozgen, C., Alp, A., Hascelik, G.: MEMS biosensors for detection of methicillin resistant Staphylococcus aureus. Biosens. Bioelectron. 29(1), 1–12 (2011). doi: 10.1016/j.bios.2011.07.071 CrossRefGoogle Scholar
  11. 11.
    Maloney, J.M., Uhland, S.A., Polito, B.F., Sheppard Jr, N.F., Pelta, C.M., Santini Jr, J.T.: Electrothermally activated microchips for implantable drug delivery and biosensing. J. Controlled Release 109(1–3), 244–255 (2005). doi: 10.1016/j.jconrel.2005.09.035 CrossRefGoogle Scholar
  12. 12.
    Carlisle, J.A.: Diamond films: Precious biosensors. Nat. Mater. 3(10), 668–669 (2004). doi: 10.1038/nmat1225 ADSCrossRefGoogle Scholar
  13. 13.
    Marcon, L., Spriet, C., Coffinier, Y., Galopin, E., Rosnoblet, C., Szunerits, S., Héliot, L., Angrand, P.-O., Boukherroub, R.: Cell adhesion properties on chemically micropatterned boron-doped diamond surfaces. Langmuir 26(19), 15065–15069 (2010). doi: 10.1021/la101757f CrossRefGoogle Scholar
  14. 14.
    Wang, H., Griffiths, J.-P., Egdell, R.G., Moloney, M.G., Foord, J.S.: Chemical functionalization of diamond surfaces by reaction with diaryl carbenes. Langmuir 24(3), 862–868 (2008). doi: 10.1021/la702701p CrossRefGoogle Scholar
  15. 15.
    Shao, Y.Y., Wang, J., Wu, H., Liu, J., Aksay, I.A., Lin, Y.H.: Graphene based electrochemical sensors and biosensors: A review. Electroanalysis 22(10), 1027–1036 (2010). doi: 10.1002/elan.200900571 CrossRefGoogle Scholar
  16. 16.
    Becker, H., Gartner, C.: Polymer microfabrication technologies for microfluidic systems. Anal. Bioanal. Chem. 390(1), 89–111 (2008). doi: 10.1007/s00216-007-1692-2 CrossRefGoogle Scholar
  17. 17.
    Lin, L., Mason, A.J., Post-CMOS parylene packaging for on-chip biosensor arrays. In: Sensors, 2010 IEEE, pp. 1613–1616, 1–4 Nov 2010. doi: 10.1109/ICSENS.2010.5690397
  18. 18.
    Yildirim, E., Kulah, H.: Analysis and characterization of an electrostatically actuated in-plane parylene microvalve. J. Micromech. Microeng. 21(10), 105009 (2011). doi: 10500910.1088/0960-1317/21/10/105009 ADSCrossRefGoogle Scholar
  19. 19.
    Choi, C.K., English, A.E., Jun, S.-I., Kihm, K.D., Rack, P.D.: An endothelial cell compatible biosensor fabricated using optically thin indium tin oxide silicon nitride electrodes. Biosens. Bioelectron. 22(11), 2585–2590 (2007). doi: 10.1016/j.bios.2006.10.006 CrossRefGoogle Scholar
  20. 20.
    Ouyang, B.Y., Chi, C.W., Chen, F.C., Xi, Q.F., Yang, Y.: High-conductivity poly (3,4-ethylenedioxythiophene): poly(styrene sulfonate) film and its application in polymer optoelectronic devices. Adv. Funct. Mater. 15(2), 203–208 (2005). doi: 10.1002/adfm.200400016 CrossRefGoogle Scholar
  21. 21.
    Schreiber, F.: Structure and growth of self-assembling monolayers. Prog. Surf. Sci. 65(5–8), 151–257 (2000). doi: 10.1016/S0079-6816(00)00024-1 ADSCrossRefGoogle Scholar
  22. 22.
    Greg, T.H.: Homobifunctional crosslinkers. In: Bioconjugate Techniques, 2nd edn. Academic Press, New York, pp. 234–275 (2008) doi: 10.1016/B978-0-12-370501-3.00004-7 (Chap. 4)
  23. 23.
    Greg, T.H.: Heterobifunctional crosslinkers. In: Bioconjugate Techniques, 2nd edn. Academic Press, New York, pp. 276–335 (2008) doi: 10.1016/B978-0-12-370501-3.00005-9 (Chap. 5)
  24. 24.
    Besselink, G.A.J., Schasfoort, R.B.M., Bergveld, P.: Modification of ISFETs with a monolayer of latex beads for specific detection of proteins. Biosens. Bioelectron. 18(9), 1109–1114 (2003). doi: 10.1016/S0956-5663(02)00243-9 CrossRefGoogle Scholar
  25. 25.
    Wang, C., Trau, D.: A portable generic DNA bioassay system based on in situ oligonucleotide synthesis and hybridization detection. Biosens. Bioelectron. 26(5), 2436–2441 (2011). doi: 10.1016/j.bios.2010.10.028 CrossRefGoogle Scholar
  26. 26.
    Arya, S.K., Chornokur, G., Venugopal, M., Bhansali, S.: Dithiobis (succinimidyl propionate) modified gold microarray electrode based electrochemical immunosensor for ultrasensitive detection of cortisol. Biosens. Bioelectron. 25(10), 2296–2301 (2010). doi: 10.1016/j.bios.2010.03.016 CrossRefGoogle Scholar
  27. 27.
    Chang, S.-C., Pereira-Rodrigues, N., Henderson, J.R., Cole, A., Bedioui, F., McNeil, C.J.: An electrochemical sensor array system for the direct, simultaneous in vitro monitoring of nitric oxide and superoxide production by cultured cells. Biosens. Bioelectron. 21(6), 917–922 (2005). doi: 10.1016/j.bios.2005.02.015 CrossRefGoogle Scholar
  28. 28.
    Kim, N., Park, I.-S.: Application of a flow-type antibody sensor to the detection of Escherichia coli in various foods. Biosens. Bioelectron. 18(9), 1101–1107 (2003). doi: 10.1016/S0956-5663(02)00240-3 CrossRefGoogle Scholar
  29. 29.
    Capobianco, J.A., Shih, W.-H., Leu, J.-H., Lo, G.C.-F., Shih, W.Y.: Label free detection of white spot syndrome virus using lead magnesium niobate–lead titanate piezoelectric microcantilever sensors. Biosens. Bioelectron. 26(3), 964–969 (2010). doi: 10.1016/j.bios.2010.08.004 CrossRefGoogle Scholar
  30. 30.
    Viswanathan, S., Rani, C., Vijay Anand, A., Ho, J-aA: Disposable electrochemical immunosensor for carcinoembryonic antigen using ferrocene liposomes and MWCNT screen-printed electrode. Biosens. Bioelectron. 24(7), 1984–1989 (2009). doi: 10.1016/j.bios.2008.10.006 CrossRefGoogle Scholar
  31. 31.
    Cha, J., Han, J.I., Choi, Y., Yoon, D.S., Oh, K.W., Lim, G.: DNA hybridization electrochemical sensor using conducting polymer. Biosens. Bioelectron. 18(10), 1241–1247 (2003). doi: 10.1016/S0956-5663(03)00088-5 CrossRefGoogle Scholar
  32. 32.
    Lee, K.-H., Su, Y.-D., Chen, S.-J., Tseng, F.-G., Lee, G.-B.: Microfluidic systems integrated with two-dimensional surface plasmon resonance phase imaging systems for microarray immunoassay. Biosens. Bioelectron. 23(4), 466–472 (2007). doi: 10.1016/j.bios.2007.05.007 CrossRefGoogle Scholar
  33. 33.
    Wang, Y., He, X., Wang, K., Ni, X., Su, J., Chen, Z.: Electrochemical detection of thrombin based on aptamer and ferrocenylhexanethiol loaded silica nanocapsules. Biosens. Bioelectron. 26(8), 3536–3541 (2011). doi: 10.1016/j.bios.2011.01.041 CrossRefGoogle Scholar
  34. 34.
    Yin, H., Zhou, Y., Zhang, H., Meng, X., Ai, S.: Electrochemical determination of microRNA-21 based on graphene, LNA integrated molecular beacon, AuNPs and biotin multifunctional bio bar codes and enzymatic assay system. Biosens. Bioelectron. 33(1), 247–253 (2012). doi: 10.1016/j.bios.2012.01.014 CrossRefGoogle Scholar
  35. 35.
    Ishikawa, F.N., Chang, H.K., Curreli, M., Liao, H.I., Olson, C.A., Chen, P.C., Zhang, R., Roberts, R.W., Sun, R., Cote, R.J., Thompson, M.E., Zhou, C.W.: Label-free, electrical detection of the SARS virus N-protein with nanowire biosensors utilizing antibody mimics as capture probes. ACS Nano 3(5), 1219–1224 (2009). doi: 10.1021/nn900086c CrossRefGoogle Scholar
  36. 36.
    Sellers, H., Ulman, A., Shnidman, Y., Eilers, J.E.: Structure and binding of alkanethiolates on gold and silver surfaces: implications for self-assembled monolayers. J. Am. Chem. Soc. 115(21), 9389–9401 (1993). doi: 10.1021/ja00074a004 CrossRefGoogle Scholar
  37. 37.
    Frank, S.: Structure and growth of self-assembling monolayers. Prog. Surf. Sci. 65(5–8), 151–257 (2000)Google Scholar
  38. 38.
    Love, J.C., Estroff, L.A., Kriebel, J.K., Nuzzo, R.G., Whitesides, G.M.: Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem. Rev. 105(4), 1103–1169 (2005). doi: 10.1021/cr0300789 CrossRefGoogle Scholar
  39. 39.
    Greg, T.H.: The chemistry of reactive groups. In: Bioconjugate Techniques. Academic Press, San Diego, pp. 137–166 (1996). doi: 10.1016/B978-012342335-1/50003-8
  40. 40.
    Hermanson, G.T.: Silane coupling agents. In: Bioconjugate Techniques, 2nd edn. Academic Press, New York, pp. 562–581 (2008). doi: 10.1016/B978-0-12-370501-3.00013-8 (Chap. 13)
  41. 41.
    Gotz, S., Karst, U.: Recent developments in optical detection methods for microchip separations. Anal. Bioanal. Chem. 387(1), 183–192 (2007). doi: 10.1007/s00216-006-0820-8 CrossRefGoogle Scholar
  42. 42.
    Stedtfeld, R.D., Tourlousse, D.M., Seyrig, G., Stedtfeld, T.M., Kronlein, M., Price, S., Ahmad, F., Gulari, E., Tiedje, J.M., Hashsham, S.A.: Gene-Z: A device for point of care genetic testing using a smartphone. Lab Chip 12, 1454–1462 (2012). doi: 10.1039/C2LC21226A CrossRefGoogle Scholar
  43. 43.
    Yao, B., Luo, G., Wang, L., Gao, Y., Lei, G., Ren, K., Chen, L., Wang, Y., Hu, Y., Qiu, Y.: A microfluidic device using a green organic light emitting diode as an integrated excitation source. Lab Chip 5(10), 1041–1047 (2005). doi: 10.1039/B504959H CrossRefGoogle Scholar
  44. 44.
    Bashir, R.: BioMEMS: State-of-the-art in detection, opportunities and prospects. Adv. Drug Deliv. Rev. 56(11), 1565–1586 (2004). doi: 10.1016/j.addr.2004.03.002 CrossRefGoogle Scholar
  45. 45.
    Johnson, B.N., Mutharasan, R.: Biosensing using dynamic-mode cantilever sensors: A review. Biosens. Bioelectron. 32(1), 1–18 (2012). doi: 10.1016/j.bios.2011.10.054 CrossRefGoogle Scholar
  46. 46.
    Eroglu, D., Kulah, H.: Quality factor enhancement of lateral microresonators in liquid media by hydrophobic coating. J. Microelectromech. Syst. 20(5), 1068–1070 (2011). doi: 10.1109/jmems.2011.2160936 CrossRefGoogle Scholar
  47. 47.
    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(7139), 1066–1069 (2007). doi: 10.1038/nature05741 ADSCrossRefGoogle Scholar
  48. 48.
    Ceylan Koydemir, H., Kulah, H., Ozgen, C.: A micro electrochemical sensor for the detection of methicillin resistance in Staphylococcus aureus. Paper presented at the Biosensors 2012: 22nd Anniversary World Congress on Biosensors, Cancun, Mexico (2012)Google Scholar
  49. 49.
    Gervais, L., de Rooij, N., Delamarche, E.: Microfluidic chips for point-of-care immunodiagnostics. Adv. Mater. 23(24), H151–H176 (2011). doi: 10.1002/adma.201100464 CrossRefGoogle Scholar
  50. 50.
    Baier, T., Hansen-Hagge, T.E., Gransee, R., Crombe, A., Schmahl, S., Paulus, C., Drese, K.S., Keegan, H., Martin, C., O’Leary, J.J., Furuberg, L., Solli, L., Gronn, P., Falang, I.M., Karlgard, A., Gulliksen, A., Karlsen, F.: Hands-free sample preparation platform for nucleic acid analysis. Lab Chip 9(23), 3399–3405 (2009). doi: 10.1039/B910421F CrossRefGoogle Scholar
  51. 51.
    Tarhan, M.C., Yokokawa, R., Bottier, C., Collard, D., Fujita, H.: A nano-needle/microtubule composite gliding on a kinesin-coated surface for target molecule transport. Lab Chip 10(1), 86–91 (2010). doi: 10.1039/B913312G CrossRefGoogle Scholar
  52. 52.
    Bottier, C., Fattaccioli, J., Tarhan, M.C., Yokokawa, R., Morin, F.O., Kim, B., Collard, D., Fujita, H.: Active transport of oil droplets along oriented microtubules by kinesin molecular motors. Lab Chip 9(12), 1694–1700 (2009). doi: 10.1039/B822519B CrossRefGoogle Scholar
  53. 53.
    Beech, J.P., Holm, S.H., Adolfsson, K., Tegenfeldt, J.O.: Sorting cells by size, shape and deformability. Lab Chip 12(6), 1048–1051 (2012). doi: 10.1039/C2LC21083E CrossRefGoogle Scholar
  54. 54.
    Nam, J., Lim, H., Kim, D., Jung, H., Shin, S.: Continuous separation of microparticles in a microfluidic channel via the elasto-inertial effect of non-Newtonian fluid. Lab Chip 12(7), 1347–1354 (2012). doi: 10.1039/C2LC21304D CrossRefGoogle Scholar
  55. 55.
    Zhang, C., Khoshmanesh, K., Mitchell, A., Kalantar-zadeh, K.: Dielectrophoresis for manipulation of micro/nano particles in microfluidic systems. Anal. Bioanal. Chem. 396(1), 401–420 (2010). doi: 10.1007/s00216-009-2922-6 CrossRefGoogle Scholar
  56. 56.
    Hong, J.W., Studer, V., Hang, G., Anderson, W.F., Quake, S.R.: A nanoliter-scale nucleic acid processor with parallel architecture. Nat. Biotechnol. 22(4), 435–439 (2004). doi: 10.1038/nbt951 CrossRefGoogle Scholar
  57. 57.
    Easley, C.J., Karlinsey, J.M., Bienvenue, J.M., Legendre, L.A., Roper, M.G., Feldman, S.H., Hughes, M.A., Hewlett, E.L., Merkel, T.J., Ferrance, J.P., Landers, J.P.: A fully integrated microfluidic genetic analysis system with sample-in–answer-out capability. Proc. Nat. Acad. Sci. 103(51), 19272–19277 (2006). doi: 10.1073/pnas.0604663103 ADSCrossRefGoogle Scholar
  58. 58.
    Bienvenue, J.M., Duncalf, N., Marchiarullo, D., Ferrance, J.P., Landers, J.P.: Microchip-based cell lysis and DNA extraction from sperm cells for application to forensic analysis. J. Forensic Sci. 51(2), 266–273 (2006). doi: 10.1111/j.1556-4029.2006.00054.x CrossRefGoogle Scholar
  59. 59.
    Lee, J.-G., Cheong, K.H., Huh, N., Kim, S., Choi, J.-W., Ko, C.: Microchip-based one step DNA extraction and real-time PCR in one chamber for rapid pathogen identification. Lab Chip 6(7), 886–895 (2006). doi: 10.1039/B515876A CrossRefGoogle Scholar
  60. 60.
    Cho, Y.-K., Lee, J.-G., Park, J.-M., Lee, B.-S., Lee, Y., Ko, C.: One-step pathogen specific DNA extraction from whole blood on a centrifugal microfluidic device. Lab Chip 7(5), 565–573 (2007). doi: 10.1039/B616115D CrossRefGoogle Scholar
  61. 61.
    Focke, M., Kosse, D., Muller, C., Reinecke, H., Zengerle, R., von Stetten, F.: Lab-on-a-foil: microfluidics on thin and flexible films. Lab Chip 10(11), 1365–1386 (2010). doi: 10.1039/C001195A CrossRefGoogle Scholar
  62. 62.
    Hoffmann, J., Mark, D., Lutz, S., Zengerle, R., von Stetten, F.: Pre-storage of liquid reagents in glass ampoules for DNA extraction on a fully integrated lab-on-a-chip cartridge. Lab Chip 10(11), 1480–1484 (2010). doi: 10.1039/B926139G CrossRefGoogle Scholar
  63. 63.
    Hitzbleck, M., Gervais, L., Delamarche, E.: Controlled release of reagents in capillary-driven microfluidics using reagent integrators. Lab Chip 11(16), 2680–2685 (2011). doi: 10.1039/C1LC20282K CrossRefGoogle Scholar
  64. 64.
    Asiello, P.J., Baeumner, A.J.: Miniaturized isothermal nucleic acid amplification, a review. Lab Chip 11(8), 1420–1430 (2011). doi: 10.1039/C0LC00666A CrossRefGoogle Scholar
  65. 65.
    Schoder, D., Schwalwiess, A., Schauberger, G., Kuhn, M., Hoorfar, J., Wagner, M.: Physical characteristics of six new thermocyclers. Clin. Chem. 49(6), 960–963 (2003). doi: 10.1373/49.6.960 CrossRefGoogle Scholar
  66. 66.
    Shen, K., Chen, X., Guo, M., Cheng, J.: A microchip-based PCR device using flexible printed circuit technology. Sens. Actuators B Chemical 105(2), 251–258 (2005). doi: 10.1016/j.snb.2004.05.069 Google Scholar
  67. 67.
    Northrup, M.A., Ching, M.T., White, R.M., Watson, R.T., (1993) DNA amplification with a microfabricated reaction chamber. Paper presented at the 7th International Conference Solid-State Sensors and Actuators (Transducers ‘93), Yokohama, Japan, 7–10 June 1993Google Scholar
  68. 68.
    Jung, J.H., Choi, S.J., Park, B.H., Choi, Y.K., Seo, T.S.: Ultrafast rotary PCR system for multiple influenza viral RNA detection. Lab Chip 12(9), 1598–1600 (2012). doi: 10.1039/C2LC21269B CrossRefGoogle Scholar
  69. 69.
    Chung, K.H., Park, S.H., Choi, Y.H.: A palmtop PCR system with a disposable polymer chip operated by the thermosiphon effect. Lab Chip 10(2), 202–210 (2010). doi: 10.1039/B915022F CrossRefGoogle Scholar
  70. 70.
    Liu, Y., Rauch, C.B., Stevens, R.L., Lenigk, R., Yang, J., Rhine, D.B., Grodzinski, P.: DNA amplification and hybridization assays in integrated plastic monolithic devices. Anal. Chem. 74(13), 3063–3070 (2002). doi: 10.1021/ac020094q CrossRefGoogle Scholar
  71. 71.
    Gulliksen, A., Solli, L., Karlsen, F., Rogne, H., Hovig, E., Nordstrøm, T., Sirevåg, R.: Real-time nucleic acid sequence-based amplification in nanoliter volumes. Anal. Chem. 76(1), 9–14 (2003). doi: 10.1021/ac034779h CrossRefGoogle Scholar
  72. 72.
    Deiman, B., van Aarle, P., Sillekens, P.: Characteristics and applications of nucleic acid sequence-based amplification (NASBA). Mol. Biotechnol. 20(2), 163–179 (2002). doi: 10.1385/mb:20:2:163 CrossRefGoogle Scholar
  73. 73.
    Furuberg, L., Mielnik, M., Gulliksen, A., Solli, L., Johansen, I.R., Voitel, J., Baier, T., Riegger, L., Karlsen, F.: RNA amplification chip with parallel microchannels and droplet positioning using capillary valves. Microsys. Technol. Micro. Nanosystems Inf Storage Process. Sys. 14(4–5), 673–681 (2008). doi: 10.1007/s00542-007-0515-x Google Scholar
  74. 74.
    Dimov, I.K., Garcia-Cordero, J.L., O’Grady, J., Poulsen, C.R., Viguier, C., Kent, L., Daly, P., Lincoln, B., Maher, M., O’Kennedy, R., Smith, T.J., Ricco, A.J., Lee, L.P.: Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics. Lab Chip 8(12), 2071–2078 (2008). doi: 10.1039/B812515E CrossRefGoogle Scholar
  75. 75.
    Yang, J.M., Bell, J., Huang, Y., Tirado, M., Thomas, D., Forster, A.H., Haigis, R.W., Swanson, P.D., Wallace, R.B., Martinsons, B., Krihak, M.: An integrated, stacked microlaboratory for biological agent detection with DNA and immunoassays. Biosens. Bioelectron. 17(6–7), 605–618 (2002). doi: 10.1016/S0956-5663(02)00023-4 CrossRefGoogle Scholar
  76. 76.
    Notomi, T., Okayama, H., Masubuchi, H., Yonekawa, T., Watanabe, K., Amino, N., Hase, T.: Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 28(12), e63 (2000). doi: 10.1093/nar/28.12.e63 CrossRefGoogle Scholar
  77. 77.
    Mori, Y., Notomi, T.: Loop-mediated isothermal amplification (LAMP): A rapid, accurate, and cost-effective diagnostic method for infectious diseases. J. Infect. Chemotherapy 15(2), 62–69 (2009). doi: 10.1007/s10156-009-0669-9 CrossRefGoogle Scholar
  78. 78.
    Fang, X.E., Liu, Y.Y., Kong, J.L., Jiang, X.Y.: Loop-mediated isothermal amplification integrated on microfluidic chips for point-of-care quantitative detection of pathogens. Anal. Chem. 82(7), 3002–3006 (2010). doi: 10.1021/ac1000652 CrossRefGoogle Scholar
  79. 79.
    Liu, C.C., Mauk, M.G., Bau, H.H.: A disposable, integrated loop-mediated isothermal amplification cassette with thermally actuated valves. Microfluid. Nanofluid. 11(2), 209–220 (2011). doi: 10.1007/s10404-011-0788-3 CrossRefGoogle Scholar
  80. 80.
    Mahalanabis, M., Do, J., Almuayad, H., Zhang, J.Y., Klapperich, C.M.: An integrated disposable device for DNA extraction and helicase dependent amplification. Biomed. Microdevices 12(2), 353–359 (2010). doi: 10.1007/s10544-009-9391-8 CrossRefGoogle Scholar
  81. 81.
    Mahalanabis, M., Do, J., Almuayad, H., Zhang, J.Y., Klapperich, C.M.: An integrated disposable device for DNA extraction and helicase dependent amplification, vol 12, p. 353, 2010. Biomedical Microdevices 13(3), 599–602 (2011). doi: 10.1007/s10544-011-9518-6
  82. 82.
    Kuhn, H., Demidov, V.V., Frank-Kamenetskii, M.D.: Rolling-circle amplification under topological constraints. Nucleic Acids Res. 30(2), 574–580 (2002). doi: 10.1093/nar/30.2.574 CrossRefGoogle Scholar
  83. 83.
    Mahmoudian, L., Kaji, N., Tokeshi, M., Nilsson, M., Baba, Y.: Rolling circle amplification and circle-to-circle amplification of a specific gene integrated with electrophoretic analysis on a single chip. Anal. Chem. 80(7), 2483–2490 (2008). doi: 10.1021/ac702289j CrossRefGoogle Scholar
  84. 84.
    Sato, K., Tachihara, A., Renberg, B., Mawatari, K., Tanaka, Y., Jarvius, J., Nilsson, M., Kitamori, T.: Microbead-based rolling circle amplification in a microchip for sensitive DNA detection. Lab Chip 10(10), 1262–1266 (2010). doi: 10.1039/b927460j CrossRefGoogle Scholar
  85. 85.
    Lutz, S., Weber, P., Focke, M., Faltin, B., Hoffmann, J., Muller, C., Mark, D., Roth, G., Munday, P., Armes, N., Piepenburg, O., Zengerle, R., von Stetten, F.: Microfluidic lab-on-a-foil for nucleic acid analysis based on isothermal recombinase polymerase amplification (RPA). Lab Chip 10(7), 887–893 (2010). doi: 10.1039/b921140c CrossRefGoogle Scholar
  86. 86.
    Marcy, Y., Ishoey, T., Lasken, R.S., Stockwell, T.B., Walenz, B.P., Halpern, A.L., Beeson, K.Y., Goldberg, S.M.D., Quake, S.R.: Nanoliter reactors improve multiple displacement amplification of genomes from single cells. PLoS Genet. 3(9), 1702–1708 (2007). doi: 10.1371/journal.pgen.0030155 CrossRefGoogle Scholar
  87. 87.
    Tan, E., Erwin, B., Dames, S., Ferguson, T., Buechel, M., Irvine, B., Voelkerding, K., Niemz, A.: Specific versus nonspecific isothermal dna amplification through thermophilic polymerase and nicking enzyme activities†. Biochemistry 47(38), 9987–9999 (2008). doi: 10.1021/bi800746p CrossRefGoogle Scholar
  88. 88.
    Heidenreich, P.A., Trogdon, J.G., Khavjou, O.A., Butler, J., Dracup, K., Ezekowitz, M.D., Finkelstein, E.A., Hong, Y., Johnston, S.C., Khera, A., Lloyd-Jones, D.M., Nelson, S.A., Nichol, G., Orenstein, D., Wilson, P.W.F., Woo, Y.J.: Forecasting the future of cardiovascular disease in the United States. Circulation (2011). doi: 10.1161/CIR.0b013e31820a55f5 zbMATHGoogle Scholar
  89. 89.
    EUROPA: Cardiovascular diseases: European commission. (2012). Accessed 01 April 2012
  90. 90.
    Mohammed, M.-I., Desmulliez, M.P.Y.: Lab-on-a-chip based immunosensor principles and technologies for the detection of cardiac biomarkers: A review. Lab Chip 11(4), 569–595 (2011). doi: 10.1039/C0LC00204F CrossRefGoogle Scholar
  91. 91.
    Kim, W.-J., Kim, B.K., Kim, A., Huh, C., Ah, C.S., Kim, K.-H., Hong, J., Park, S.H., Song, S., Song, J., Sung, G.Y.: Response to cardiac markers in human serum analyzed by guided-mode resonance biosensor. Anal. Chem. 82(23), 9686–9693 (2010). doi: 10.1021/ac101716p CrossRefGoogle Scholar
  92. 92.
    Shen, W., Tian, D., Cui, H., Yang, D., Bian, Z.: Nanoparticle-based electrochemiluminescence immunosensor with enhanced sensitivity for cardiac troponin I using N-(aminobutyl)-N-(ethylisoluminol)-functionalized gold nanoparticles as labels. Biosens. Bioelectron. 27(1), 18–24 (2011). doi: 10.1016/j.bios.2011.05.022 CrossRefGoogle Scholar
  93. 93.
    NHLBI: NHLBI Fact book, fiscal year 2008. Bethesda (MD): National Heart, Lung, and Blood Institute (2009)Google Scholar
  94. 94.
    Group USCSW: United States cancer statistics: 1999–2007 incidence and mortality web-based report. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. (2010)
  95. 95.
    Waggoner, P.S., Varshney, M., Craighead, H.G.: Detection of prostate specific antigen with nanomechanical resonators. Lab Chip 9(21), 3095–3099 (2009). doi: 10.1039/B907309B CrossRefGoogle Scholar
  96. 96.
    Truong, P.L., Kim, B.W., Sim, S.J.: Rational aspect ratio and suitable antibody coverage of gold nanorod for ultra-sensitive detection of a cancer biomarker. Lab Chip 12(6), 1102–1109 (2012). doi: 10.1039/C2LC20588B CrossRefGoogle Scholar
  97. 97.
    Chuah, K., Lai, L.M.H., Goon, I.Y., Parker, S.G., Amal, R., Justin Gooding, J.: Ultrasensitive electrochemical detection of prostate-specific antigen (PSA) using gold-coated magnetic nanoparticles as ‘dispersible electrodes’. Chem. Commun. 48(29), 3503–3505 (2012). doi: 10.1039/C2CC30512G CrossRefGoogle Scholar
  98. 98.
    Nagrath, S., Sequist, L.V., Maheswaran, S., Bell, D.W., Irimia, D., Ulkus, L., Smith, M.R., Kwak, E.L., Digumarthy, S., Muzikansky, A., Ryan, P., Balis, U.J., Tompkins, R.G., Haber, D.A., Toner, M.: Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173), 1235–1239 (2007). doi: 10.1038/nature06385 ADSCrossRefGoogle Scholar
  99. 99.
    Viswanathan, S., Rani, C., Ribeiro, S., Delerue-Matos, C.: Molecular imprinted nanoelectrodes for ultra sensitive detection of ovarian cancer marker. Biosens. Bioelectron. 33(1), 179–183 (2012). doi: 10.1016/j.bios.2011.12.049 CrossRefGoogle Scholar
  100. 100.
    Zhu, H., Yaglidere, O., Su, T.-W., Tseng, D., Ozcan, A.: Cost-effective and compact wide-field fluorescent imaging on a cell-phone. Lab Chip 11(2), 315–322 (2011). doi: 10.1039/C0LC00358A CrossRefGoogle Scholar
  101. 101.
    Wong, A.P., Gupta, M., Shevkoplyas, S.S., Whitesides, G.M.: Egg beater as centrifuge: isolating human blood plasma from whole blood in resource-poor settings. Lab Chip 8(12), 2032–2037 (2008). doi: 10.1039/B809830C CrossRefGoogle Scholar
  102. 102.
    Martinez, A.W., Phillips, S.T., Whitesides, G.M., Carrilho, E.: Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal. Chem. 82(1), 3–10 (2009). doi: 10.1021/ac9013989 CrossRefGoogle Scholar
  103. 103.
    Martinez, A.W., Phillips, S.T., Whitesides, G.M.: Three-dimensional microfluidic devices fabricated in layered paper and tape. Proc. Nat. Acad. Sci. 105(50), 19606–19611 (2008). doi: 10.1073/pnas.0810903105 ADSCrossRefGoogle Scholar
  104. 104.
    Nie, Z., Nijhuis, C.A., Gong, J., Chen, X., Kumachev, A., Martinez, A.W., Narovlyansky, M., Whitesides, G.M.: Electrochemical sensing in paper-based microfluidic devices. Lab Chip 10(4), 477–483 (2010). doi: 10.1039/B917150A CrossRefGoogle Scholar
  105. 105.
    Martinez, A.W., Phillips, S.T., Nie, Z., Cheng, C.-M., Carrilho, E., Wiley, B.J., Whitesides, G.M.: Programmable diagnostic devices made from paper and tape. Lab Chip 10(19), 2499–2504 (2010). doi: 10.1039/C0LC00021C CrossRefGoogle Scholar
  106. 106.
    Kim, D.-H., Lu, N., Ma, R., Kim, Y.-S., Kim, R.-H., Wang, S., Wu, J., Won, S.M., Tao, H., Islam, A., Yu, K.J., Kim, T-i, Chowdhury, R., Ying, M., Xu, L., Li, M., Chung, H.-J., Keum, H., McCormick, M., Liu, P., Zhang, Y.-W., Omenetto, F.G., Huang, Y., Coleman, T., Rogers, J.A.: Epidermal electronics. Science 333(6044), 838–843 (2011). doi: 10.1126/science.1206157 ADSCrossRefGoogle Scholar
  107. 107.
    Mahler, G.J., Esch, M.B., Glahn, R.P., Shuler, M.L.: Characterization of a gastrointestinal tract microscale cell culture analog used to predict drug toxicity. Biotechnol. Bioeng. 104(1), 193–205 (2009). doi: 10.1002/bit.22366 CrossRefGoogle Scholar
  108. 108.
    Kimura, H., Yamamoto, T., Sakai, H., Sakai, Y., Fujii, T.: An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models. Lab Chip 8(5), 741–746 (2008). doi: 10.1039/B717091B CrossRefGoogle Scholar
  109. 109.
    Sung, J.H., Yu, J., Luo, D., Shuler, M.L., March, J.C.: Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. Lab Chip 11(3), 389–392 (2011). doi: 10.1039/C0LC00273A CrossRefGoogle Scholar
  110. 110.
    Ghaemmaghami, A.M., Hancock, M.J., Harrington, H., Kaji, H., Khademhosseini, A.: Biomimetic tissues on a chip for drug discovery. Drug Discovery Today 17(3–4), 173–181 (2012). doi: 10.1016/j.drudis.2011.10.029 CrossRefGoogle Scholar
  111. 111.
    Domansky, K., Inman, W., Serdy, J., Dash, A., Lim, M.H.M., Griffith, L.G.: Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10(1), 51–58 (2010). doi: 10.1039/B913221J CrossRefGoogle Scholar
  112. 112.
    Khetani, S.R., Bhatia, S.N.: Microscale culture of human liver cells for drug development. Nat Biotech 26(1), 120–126 (2008). doi: 10.1038/nbt1361 CrossRefGoogle Scholar
  113. 113.
    Toh, Y.-C., Zhang, C., Zhang, J., Khong, Y.M., Chang, S., Samper, V.D., van Noort, D., Hutmacher, D.W., Yu, H.: A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip 7(3), 302–309 (2007). doi: 10.1039/B614872G CrossRefGoogle Scholar
  114. 114.
    van Midwoud, P.M., Merema, M.T., Verpoorte, E., Groothuis, G.M.M.: A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices. Lab Chip 10(20), 2778–2786 (2010). doi: 10.1039/C0LC00043D CrossRefGoogle Scholar
  115. 115.
    Kang, J.H., Krause, S., Tobin, H., Mammoto, A., Kanapathipillai, M., Ingber, D.E.: A combined micromagnetic-microfluidic device for rapid capture and culture of rare circulating tumor cells. Lab Chip (2012). doi: 10.1039/C2LC40072C Google Scholar
  116. 116.
    Frimat, J.-P., Becker, M., Chiang, Y–.Y., Marggraf, U., Janasek, D., Hengstler, J.G., Franzke, J., West, J.: A microfluidic array with cellular valving for single cell co-culture. Lab Chip 11(2), 231–237 (2011). doi: 10.1039/C0LC00172D CrossRefGoogle Scholar
  117. 117.
    Hong, S., Pan, Q., Lee, L.P.: Single-cell level co-culture platform for intercellular communication. Integrative Biology 4(4), 374–380 (2012). doi: 10.1039/C2IB00166G CrossRefGoogle Scholar
  118. 118.
    Sung, J.H., Shuler, M.L.: A micro cell culture analog (μCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip 9(10), 1385–1394 (2009). doi: 10.1039/B901377F CrossRefGoogle Scholar
  119. 119.
    Raghavan, S., Nelson, C.M., Baranski, J.D., Lim, E., Chen, C.S.: geometrically controlled endothelial tubulogenesis in micropatterned gels. Tissue Eng. Part A 16(7), 2255–2263 (2010). doi: 10.1089/ten.tea.2009.0584 CrossRefGoogle Scholar
  120. 120.
    Chung, S., Sudo, R., Mack, P.J., Wan, C.-R., Vickerman, V., Kamm, R.D.: Cell migration into scaffolds under co-culture conditions in a microfluidic platform. Lab Chip 9(2), 269–275 (2009). doi: 10.1039/B807585A CrossRefGoogle Scholar
  121. 121.
    Gunther, A., Yasotharan, S., Vagaon, A., Lochovsky, C., Pinto, S., Yang, J., Lau, C., Voigtlaender-Bolz, J., Bolz, S–.S.: A microfluidic platform for probing small artery structure and function. Lab Chip 10(18), 2341–2349 (2010). doi: 10.1039/C004675B CrossRefGoogle Scholar
  122. 122.
    Shao, J., Wu, L., Wu, J., Zheng, Y., Zhao, H., Jin, Q., Zhao, J.: Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress. Lab Chip 9(21), 3118–3125 (2009). doi: 10.1039/B909312E CrossRefGoogle Scholar
  123. 123.
    Tourovskaia, A., Li, N.Z., Folch, A.: Localized acetylcholine receptor clustering dynamics in response to microfluidic focal stimulation with agrin. Biophys. J. 95(6), 3009–3016 (2008). doi: 10.1529/biophysj.107.128173 ADSCrossRefGoogle Scholar
  124. 124.
    Kelley, D.E., He, J., Menshikova, E.V., Ritov, V.B.: Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51(10), 2944–2950 (2002). doi: 10.2337/diabetes.51.10.2944 CrossRefGoogle Scholar
  125. 125.
    Nagamine, K., Kawashima, T., Sekine, S., Ido, Y., Kanzaki, M., Nishizawa, M.: Spatiotemporally controlled contraction of micropatterned skeletal muscle cells on a hydrogel sheet. Lab Chip 11(3), 513–517 (2011). doi: 10.1039/C0LC00364F CrossRefGoogle Scholar
  126. 126.
    Kaji, H., Ishibashi, T., Nagamine, K., Kanzaki, M., Nishizawa, M.: Electrically induced contraction of C2C12 myotubes cultured on a porous membrane-based substrate with muscle tissue-like stiffness. Biomaterials 31(27), 6981–6986 (2010). doi: 10.1016/j.biomaterials.2010.05.071 CrossRefGoogle Scholar
  127. 127.
    Bajaj, P., Reddy, B., Millet, L., Wei, C., Zorlutuna, P., Bao, G., Bashir, R.: Patterning the differentiation of C2C12 skeletal myoblasts. Integrative Biology 3(9), 897–909 (2011). doi: 10.1039/C1IB00058F CrossRefGoogle Scholar
  128. 128.
    Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y., Ingber, D.E.: Reconstituting organ-level lung functions on a chip. Science 328(5986), 1662–1668 (2010). doi: 10.1126/science.1188302 ADSCrossRefGoogle Scholar
  129. 129.
    Blake, A.J., Rodgers, F.C., Bassuener, A., Hippensteel, J.A., Pearce, T.M., Pearce, T.R., Zarnowska, E.D., Pearce, R.A., Williams, J.C.: A microfluidic brain slice perfusion chamber for multisite recording using penetrating electrodes. J. Neurosci. Methods 189(1), 5–13 (2010). doi: 10.1016/j.jneumeth.2010.02.017 CrossRefGoogle Scholar
  130. 130.
    Ingber, D.: Spleen-on-a-chip, sepsis therapeutic device. Hansjörg Wyss Institute for Biologically Inspired Engineering at Harvard University. (2012). Accessed 30 April 2012
  131. 131.
    Baker, M.: Tissue models: A living system on a chip. Nature 471(7340), 661–665 (2011). doi: 10.1038/471661a ADSCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Hatice Ceylan Koydemir
    • 1
    • 2
  • Haluk Külah
    • 1
    • 3
  • Canan Özgen
    • 2
  1. 1.METU-MEMS CenterMiddle East Technical UniversityÇankaya, AnkaraTurkey
  2. 2.Department of Chemical EngineeringMiddle East Technical UniversityÇankaya, AnkaraTurkey
  3. 3.Department of Electrical and Electronics EngineeringMiddle East Technical UniversityÇankaya, AnkaraTurkey

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