Biosensors with label-free detection designed for diagnostic applications

Analytical and Bioanalytical Chemistry volume 398, pages2403–2412(2010)Cite this article

Abstract

Since the first biosensor was introduced in 1962 by Clark and Lyons, there has been increasing demand for such analytical devices in diagnostic applications. Research initially focussed mainly on detector principles and recognition elements, whereas the packaging of the biosensors and the microfluidic integration has been discussed only more recently. However, to obtain a user-friendly and well-performing analytical device, those components have to be considered all together. This review outlines the requirements and the solutions suggested for the integration of suitable biosensors in packaging and the integration of those encapsulated biosensors into a microfluidic surrounding resulting in a complete and efficient analytical device for diagnostic applications. The components required for a complete biosensor instrument are described and the latest developments which meet the requirements for diagnostic applications, such as single-use components and arrays for multiparameter detection, are discussed. The current state and the future of biosensors in the field of clinical diagnostics are outlined, particularly on the basis of label-free assay formats and the detection of prominent biomarkers for cancer and autoimmune disorders.

Components to be considered in an efficient biosensor system

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

Fig. 1

References

  1. 1.

    Thévenot DR, Toth K, Durst RA, Wilson GS (1999) Pure Appl Chem 71:2333–2348

    Article  Google Scholar 

  2. 2.

    Clark LC, Lyons C (1977) Ann N Y Acad Sci 102:29–45

    Article  Google Scholar 

  3. 3.

    Mascini M, Tombelli S (2008) Biomarkers 13:637–657

    CAS  Article  Google Scholar 

  4. 4.

    Yu D, Blankert B, Viré JC, Kauffmann JM (2005) Anal Lett 38:1687–1701

    CAS  Article  Google Scholar 

  5. 5.

    Jiménez C, León DE (2009) Vitae Rev Fac Quim Farm 16:144–154

    Google Scholar 

  6. 6.

    Farré M, Kantiani L, Pérez S, Barceló D (2009) Trends Anal Chem 28:170–185

    Article  Google Scholar 

  7. 7.

    Bilitewski U (2005) In: Gorton L (ed) Biosensors and modern biospecific analytical techniques. Comprehensive analytical chemistry, vol. 44, 1st edn. Elsevier, Amsterdam

  8. 8.

    Guilbault GG (2004) Anal Lett 37:1481–1496

    CAS  Article  Google Scholar 

  9. 9.

    Luong JHT, Male KB, Glennon JD (2008) Biotechnol Adv 26:492–500

    CAS  Article  Google Scholar 

  10. 10.

    Conroy PJ, Hearty S, Leonard P, O’Kennedy RJ (2009) Semin Cell Dev Biol 20:10–26

    CAS  Article  Google Scholar 

  11. 11.

    Qavi AJ, Washburn AL, Byeon JY, Bailey RC (2009) Anal Bioanal Chem 394:121–135

    CAS  Article  Google Scholar 

  12. 12.

    Leca-Bouvier B, Blum LJ (2005) Anal Lett 38:1491–1517

    CAS  Article  Google Scholar 

  13. 13.

    Lec RM (2001) IEEE Int Freq Control Symp PDA Exhib 419–429

  14. 14.

    Cass T, Toumazou C (2006) In: Foresight infectious diseases: preparing for the future. Department of Trade and Industry, London. http://www.foresight.gov.uk/Infectious Diseases/s7.pdf. Accessed 30 Jan 2008

  15. 15.

    Jiang X, Li D, Xu X, Ying Y, Li Y, Ye Z, Wang J (2008) Biosens Bioelectron 23:1577–1587

    CAS  Article  Google Scholar 

  16. 16.

    Bilitewski U (2006) Anal Chim Acta 568:232–247

    CAS  Article  Google Scholar 

  17. 17.

    Gauglitz G (2005) Anal Bioanal Chem 381:141–155

    CAS  Article  Google Scholar 

  18. 18.

    Grieshaber D, MacKenzie R, Vörös J, Reimhult E (2008) Sensors 8:1400–1458

    CAS  Article  Google Scholar 

  19. 19.

    Gauglitz G, Proll G (2008) Biosens 21st Century 109:395–435

    Google Scholar 

  20. 20.

    Lucklum R, Hauptmann P (2006) Anal Bioanal Chem 384:667–682

    CAS  Article  Google Scholar 

  21. 21.

    Ramanathan K, Danielsson B (2001) Biosens Bioelectron 16:417–423

    CAS  Article  Google Scholar 

  22. 22.

    Tothill IE (2009) Semin Cell Dev Biol 20:55–62

    CAS  Article  Google Scholar 

  23. 23.

    Soper SA, Brown K, Ellington A, Frazier B, Garcia-Manero G, Gau V, Gutman SI, Hayes DF, Korte B, Landers JL, Larson D, Ligler F, Majumdar A, Mascini M, Nolte D, Rosenzweig Z, Wang J, Wilson D (2006) Biosens Bioelectron 21:1932–1942

    CAS  Article  Google Scholar 

  24. 24.

    Thaler M, Buhl A, Welter H, Schreiegg A, Kehrel M, Alber B, Metzger J, Luppa P (2009) Anal Bioanal Chem 393:1417–1429

    CAS  Article  Google Scholar 

  25. 25.

    Gedig ET (2008) In: Schasfoort RBM, Tudos AJ (eds) Handbook of surface plasmon resonance, 1st edn. RSC, Cambridge

    Google Scholar 

  26. 26.

    Collings AF, Caruso F (1997) Rep Prog Phys 60:1397–1445

    CAS  Article  Google Scholar 

  27. 27.

    Länge K, Grimm S, Rapp M (2007) Sens Actuators B 125:441–446

    Article  Google Scholar 

  28. 28.

    Masson JF, Battaglia TM, Khairallah P, Beaudoin S, Booksh KS (2007) Anal Chem 79:612–619

    CAS  Article  Google Scholar 

  29. 29.

    Cooper MA (2003) Anal Bioanal Chem 377:834–842

    CAS  Article  Google Scholar 

  30. 30.

    Löfas S, Johnsson J (1990) J Chem Soc Chem Commun 1526–1528

  31. 31.

    Piehler J, Brecht A, Valiokas R, Liedberg B, Gauglitz G (2000) Biosens Bioelectron 15:473–481

    CAS  Article  Google Scholar 

  32. 32.

    Länge K, Gruhl FJ, Rapp M (2009) IEEE Sens J 9:2033–2034

    Article  Google Scholar 

  33. 33.

    Länge K, Rapp M (2008) Anal Biochem 377:170–175

    Article  Google Scholar 

  34. 34.

    Blaess G (2006) Häusung von Surface Acoustic Wave Sensoren für die Bioanalytik (Packaging of surface acoustic wave sensors for usage in bioanalytics). Doctoral thesis, Technical University of Karlsruhe

  35. 35.

    Rapp BE (2009) Entwicklung eines Biosensorarray-Systems auf der Basis von akustischen Oberflächenwellensensoren mit integrierter einwegtauglicher Mikrofluidik (Development of a surface acoustic wave based biosensor array with integrated disposable microfluidics). Doctoral thesis, KIT Scientific Publishing, Karlsruhe

  36. 36.

    Länge K, Rapp BE, Rapp M (2008) Anal Bioanal Chem 391:509–519

    Article  Google Scholar 

  37. 37.

    Hsu TR (2006) IEEE Int Reliab Phys Symp Proc 44th Annu 398–402

  38. 38.

    Hsu TR (2000) IEEE Trans Adv Pack 23:596–601

    Article  Google Scholar 

  39. 39.

    Shaw M, Ziglioli F, Combi C, Baldo L (2008) IEEE Electron Compon Technol Conf Proc 834–840

  40. 40.

    Miki N (2005) Sens Lett 3:263–273

    CAS  Article  Google Scholar 

  41. 41.

    Esashi M (2008) J Micromech Microeng 18:073001

    Article  Google Scholar 

  42. 42.

    Zhu XW, Aslarn DM (2006) Diamond Relat Mater 15:254–258

    CAS  Article  Google Scholar 

  43. 43.

    Faheem FF, Lee YC (2009) Int J Mater Prod Technol 34:66–76

    CAS  Article  Google Scholar 

  44. 44.

    Velten T, Ruf HH, Barrow D, Aspragathos N, Lazarou P, Jung E, Khan Malek C, Richter M, Kruckow J, Wackerle M (2005) IEEE Trans Adv Pack 28:533–546

    Article  Google Scholar 

  45. 45.

    Heckele M, Schomburg WK (2004) J Micromech Microeng 14:R1–R14

    CAS  Article  Google Scholar 

  46. 46.

    Giboz J, Copponnex T, Mele P (2007) J Micromech Microeng 17:R96–R109

    CAS  Article  Google Scholar 

  47. 47.

    Worgull M, Heckele M, Schomburg WK (2005) Microsyst Technol 12:110–115

    CAS  Article  Google Scholar 

  48. 48.

    Yu LY, Xu GJ, Lee LJ, Koelling KW (2004) AIP Conf Proc 712:186–191

    CAS  Article  Google Scholar 

  49. 49.

    Mehne C, Steger R, Koltay P, Warkentin D, Heckele MP (2008) Proc Inst Mech Eng Part B J Eng Manufact 222:93–99

    Article  Google Scholar 

  50. 50.

    Rapp BE, Schneider M, Worgull M (2010) Microsyst Technol 16:1201–1206

    Google Scholar 

  51. 51.

    Liang JX, Ueda T (2009) J Micro/Nanolith MEMS MOEMS 8:021118

    Article  Google Scholar 

  52. 52.

    Sarvar F, Hutt DA, Whalley DC (2002) IEEE Int Conf Polym Adhes Microelectron Photonics Proc 22–28

  53. 53.

    Terry SC, Jerman JH, Angell JB (1979) IEEE Trans Electron Devices 26:1880–1886

    Article  Google Scholar 

  54. 54.

    Manz A, Graber N, Widmer HM (1990) Sens Actuators B 1:244–248

    Article  Google Scholar 

  55. 55.

    Laser DJ, Santiago JG (2004) J Micromech Microeng 14:R35–R64

    Article  Google Scholar 

  56. 56.

    Oh KW, Ahn CH (2006) J Micromech Microeng 16:R13–R39

    Article  Google Scholar 

  57. 57.

    Gwo-Bin L, Huang CJ, Yi-Hsin C, Chih-Hao W, Tse-Chuan C (2007) Sens Actuators B 122:461–468

    Article  Google Scholar 

  58. 58.

    Wang CH, Lee GB (2005) Biosens Bioelectron 21:419–425

    CAS  Article  Google Scholar 

  59. 59.

    Becker H (2009) Lab Chip 9:1659–1660

    CAS  Article  Google Scholar 

  60. 60.

    Becker H (2009) Lab Chip 9:2119–2122

    CAS  Article  Google Scholar 

  61. 61.

    Becker H (2009) Lab Chip 9:2759–2762

    CAS  Article  Google Scholar 

  62. 62.

    Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR (2000) Science 288:113–116

    CAS  Article  Google Scholar 

  63. 63.

    Melin J, Quake SR (2007) Annu Rev Biophys Biomol Struct 36:213–231

    CAS  Article  Google Scholar 

  64. 64.

    Thorsen T, Maerkl SJ, Quake SR (2002) Science 298:580–584

    CAS  Article  Google Scholar 

  65. 65.

    Lee JN, Park C, Whitesides GM (2003) Anal Chem 75:6544–6554

    CAS  Article  Google Scholar 

  66. 66.

    Rapp BE, Carneiro L, Länge K, Rapp M (2009) Lab Chip 9:354–356

    CAS  Article  Google Scholar 

  67. 67.

    Chung KH, Hong JW, Lee DS, Yoon HC (2007) Anal Chim Acta 585:1–10

    CAS  Article  Google Scholar 

  68. 68.

    Ko JS, Yoon HC, Yang H, Pyo HB, Chung KH, Kim SJ, Kim YT (2003) Lab Chip 3:106–113

    CAS  Article  Google Scholar 

  69. 69.

    Bange A, Halsall HB, Heineman WR (2005) Biosens Bioelectron 20:2488–2503

    CAS  Article  Google Scholar 

  70. 70.

    Hartmann M, Roeraade J, Stoll D, Templin MF, Joos TO (2009) Anal Bioanal Chem 393:1407–1416

    CAS  Article  Google Scholar 

  71. 71.

    Newman JD, Turner APF (2005) Biosens Bioelectron 20:2435–2453

    CAS  Article  Google Scholar 

  72. 72.

    Gauglitz G, Luppa PB (2009) Chem Unserer Zeit 43:308–318

    CAS  Article  Google Scholar 

  73. 73.

    Braun S, Spannagl M, Völler H (2009) Anal Bioanal Chem 393:1463–1471

    CAS  Article  Google Scholar 

  74. 74.

    Warsinke A (2009) Anal Bioanal Chem 393:1393–1405

    CAS  Article  Google Scholar 

  75. 75.

    Rasooly A, Jacobson J (2006) Biosens Bioelectron 21:1851–1858

    CAS  Article  Google Scholar 

  76. 76.

    Rich RL, Myszka DG (2008) J Mol Recognit 21:355–400

    CAS  Article  Google Scholar 

  77. 77.

    World Health Organization (2010). http://www.who.int. Accessed 10 Mar 2010

  78. 78.

    Wang J (2006) Biosens Bioelectron 21:1887–1892

    CAS  Article  Google Scholar 

  79. 79.

    Lamerz R, Stieber P (2004) Dtsch Med Wochenschr 129:2722–2728

    CAS  Article  Google Scholar 

  80. 80.

    Healy DA, Hayes CJ, Leonard P, McKenna L, O’Kennedy R (2007) Trends Biotechnol 25:125–131

    CAS  Article  Google Scholar 

  81. 81.

    Soerjomataram I, Louwman MWJ, Ribot JG, Roukema JA, Coebergh JWW (2008) Breast Cancer Res Treat 107:309–330

    CAS  Article  Google Scholar 

  82. 82.

    Duffy MJ (2006) Clin Chem 52:345–351

    CAS  Article  Google Scholar 

  83. 83.

    Lipton A, Ali SM, Leitzel K, Demers L, Chinchilli V, Engle L, Harvey HA, Brady C, Nalin CM, Dugan M, Carney W, Allard J (2002) J Clin Oncol 20:1467–72

    CAS  Article  Google Scholar 

  84. 84.

    Payne RC, Allard JW, Anderson-Mauser L, Humphreys JD, Tenney DY, Morris DL (2000) Clin Chem 46:175–182

    CAS  Google Scholar 

  85. 85.

    Martin VS, Sullivan BA, Walzer K, Hawk H, Sullivan BP, Noe LJ (2006) Appl Spectrosc 60:994–1003

    CAS  Article  Google Scholar 

  86. 86.

    Gruhl FJ, Rapp M, Länge K (2010) Surface modification of acoustic biosensors for the detection of marker proteins for breast cancer. Paper presented at the 11th world congress on biosensors, Glasgow, 26–28 May 2010

  87. 87.

    Sadik OA, Aluoch AO, Zhou A (2009) Biosens Bioelectron 24:2749–2765

    CAS  Article  Google Scholar 

  88. 88.

    Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM (2005) Nat Biotechnol 23:1294–1301

    CAS  Article  Google Scholar 

  89. 89.

    Fournel S, Muller S (2003) Curr Protein Pept Sci 4:261–276

    CAS  Article  Google Scholar 

  90. 90.

    Carter PH, Zhao QH (2010) Expert Opin Investig Drugs 19:195–213

    CAS  Article  Google Scholar 

  91. 91.

    Carlsson J, Gullstrand C, Westermark GT, Ludvigsson J, Enander K, Liedberg B (2008) Biosens Bioelectron 24:876–881

    CAS  Article  Google Scholar 

  92. 92.

    Kim JY, Lee MH, Jung KI, Na HY, Cha HS, Koh EM, Kim TJ (2003) Exp Mol Med 35:310–316

    CAS  Google Scholar 

  93. 93.

    Bhavsar K, Fairchild A, Alonas E, Bishop DK, La Belle JT, Sweeney J, Alford TL Lokesh J (2009) Biosens Bioelectron 25:506–509

    CAS  Article  Google Scholar 

  94. 94.

    Mahler M, Fritzler MJ (2010) Ann N Y Acad Sci 1183:267–287

    CAS  Article  Google Scholar 

  95. 95.

    Ali M, Manolios M (2005) Semin Arthritis Rheum 35:67–76

    CAS  Article  Google Scholar 

  96. 96.

    Beusink LAMC, JB BGAJ, Pruijn GJM, Schasfoort RBM (2007) J Am Chem Soc 129:14013–14018

    Article  Google Scholar 

  97. 97.

    Roitt IM, Brostoff J, Male DK (1985) Immunology. Gower, London

    Google Scholar 

  98. 98.

    Lernmark Å (2001) J Clin Invest 108:1091–1096

    CAS  Google Scholar 

  99. 99.

    Schellekens GA, de Jong BA, Van den Hoogen FH, Van de Putte LB, Van Venrooij WJ (1998) J Clin Invest 101:273–281

    CAS  Article  Google Scholar 

  100. 100.

    Venrooij WJ, Zendman AJW, Pruijn GJM (2006) Autoimmun Rev 6:37–41

    Article  Google Scholar 

  101. 101.

    Drouvalakis KA, Bangsaruntip S, Hueber W, Kozar LG, Utz PJ, Dai H (2008) Biosens Bioelectron 23:1413–1421

    CAS  Article  Google Scholar 

  102. 102.

    Ayela C, Roquet F, Valera L, Granier C, Nicu L, Pugnière M (2007) Biosens Bioelectron 22:3113–3119

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Institute for Microstructure Technology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

    Bastian E. Rapp, Friederike J. Gruhl & Kerstin Länge

Authors
  1. Bastian E. Rapp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Friederike J. Gruhl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kerstin Länge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kerstin Länge.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rapp, B.E., Gruhl, F.J. & Länge, K. Biosensors with label-free detection designed for diagnostic applications. Anal Bioanal Chem 398, 2403–2412 (2010). https://doi.org/10.1007/s00216-010-3906-2

Download citation

Keywords

  • Biosensors
  • Label-free
  • Single-use
  • Packaging
  • Microfluidics/microfabrication
  • Diagnostics