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Emerging optofluidic technologies for point-of-care genetic analysis systems: a review

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Abstract

This review describes recently emerging optical and microfluidic technologies suitable for point-of-care genetic analysis systems. Such systems must rapidly detect hundreds of mutations from biological samples with low DNA concentration. We review optical technologies delivering multiplex sensitivity and compatible with lab-on-chip integration for both tagged and non-tagged optical detection, identifying significant source and detector technology emerging from telecommunications technology. We highlight the potential for improved hybridization efficiency through careful microfluidic design and outline some novel enhancement approaches using target molecule confinement. Optimization of fluidic parameters such as flow rate, channel height and time facilitates enhanced hybridization efficiency and consequently detection performance as compared with conventional assay formats (e.g. microwell plates). We highlight lab-on-chip implementations with integrated microfluidic control for “sample-to-answer” systems where molecular biology protocols to realize detection of target DNA sequences from whole blood are required. We also review relevant technology approaches to optofluidic integration, and highlight the issue of biomolecule compatibility. Key areas in the development of an integrated optofluidic system for DNA hybridization are optical/fluidic integration and the impact on biomolecules immobilized within the system. A wide range of technology platforms have been advanced for detection, quantification and other forms of characterization of a range of biomolecules (e.g. RNA, DNA, protein and whole cell). Owing to the very different requirements for sample preparation, manipulation and detection of the different types of biomolecules, this review is focused primarily on DNA–DNA interactions in the context of point-of-care analysis systems.

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References

  1. Dobson MG, Galvin P, Barton DE (2007) Expert Rev Mol Diagn 7(4):359–370

    Article  CAS  PubMed  Google Scholar 

  2. Nanosphere Inc. (2009) Gold Particle Technology Overview. http://www.nanosphere-inc.com. Accessed 12 March 2009

  3. Hahn S, Mergenthaler S, Zimmermann B, Holzgreve W (2005) Bioelectrochemistry 67(2):151–154

    Article  CAS  PubMed  Google Scholar 

  4. Von Lode P (2005) Clin Biochem 38(7):591–606

    Article  CAS  Google Scholar 

  5. Park T, Lee S, Seong GH, Choo J, Lee EK, Kim YS, Ji WJ, Hwang SY, Gweon D, Lee S (2005) Lab Chip 5:437–442

    Article  CAS  PubMed  Google Scholar 

  6. Ronaghi M, Karamohamed S, Pettersson B, Uhlen M, Nyren P (1996) Anal Biochem 242:84–89

    Article  CAS  PubMed  Google Scholar 

  7. Russom A, Tooke N, Andersson H, Stemme G (2003) J Chromatogr A 1014:37–45

    Article  CAS  PubMed  Google Scholar 

  8. Marasso SL, Carnavese G, Cocuzza M, Ferranini M, Guiri E, Bartolo SL, Mantero G, Perrone D, Quaglio M, Vallini I (2008) Microelectron Eng 85:1326–1329

    Article  CAS  Google Scholar 

  9. Spurgeon SL, Jones RC, Ramakrishnan R (2008) PLoS ONE 3(2):1662

    Article  CAS  Google Scholar 

  10. Wang Y, Vaidya B, Farquar HD (2003) Anal Chem 75(5):1130–1140

    Article  CAS  PubMed  Google Scholar 

  11. Wang J, Chen Z, Corstjens P, Mauk MG, Bau HH (2006) Lab Chip 6:46–53

    Article  CAS  PubMed  Google Scholar 

  12. Berney H, Oliver K (2005) Biosens Bioelectron 21(4):618–626

    Article  CAS  PubMed  Google Scholar 

  13. Lillis B, Manning M, Berney H, Hurley E, Mathewson A, Sheehan MM (2006) Biosens Bioelectron 21(8):1459–1467

    Article  CAS  PubMed  Google Scholar 

  14. Zhao Z, Peytavi R,Diaz-Quijada GA, Picard FJ, Huletsky A, Leblanc E, Frenette J, Boivin G, Veres T, Dumoulin MM, Bergeron MG (2008) J Clin Microbiol 46(11):3752–3758

    Article  CAS  Google Scholar 

  15. Zhang C, Xing D (2007) Nucleic Acids Res 35(13):4223–4237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Waters LC, Jacobson SC, Kroutchinina N, Khandurina J, Foote FR, Ramsey JM (1998) Anal Chem 70:158–162

    Article  CAS  PubMed  Google Scholar 

  17. Li P, Harrison J (1997) Anal Chem 69:1564–1568

    Article  CAS  PubMed  Google Scholar 

  18. Belgrader P, Hansford D, Kovacs G, Venkateswaran K, Mariella R, Milanovich F, Nasarabadi S, Okuzumi M, Porahmadi F, Northrup A (1999) Anal Chem 71:4232–4236

    Article  CAS  PubMed  Google Scholar 

  19. Taylor M, Belgrader P, Furman B, Pourahmadi F, Kovacs G, Northrup A (2001) Anal Chem 73:492–496

    Article  CAS  PubMed  Google Scholar 

  20. Lee S, Tai Y (1999) Sens Actuators 73:74–79

    Article  CAS  Google Scholar 

  21. Schilling E, Kamholz A, Yager P (2002) Anal Chem 74:1798–1804

    Article  CAS  PubMed  Google Scholar 

  22. Nevill JT, Cooper R, Dueck M, Breslauer DN, Lee LP (2007) Lab Chip 7:1689–1695

    Article  CAS  PubMed  Google Scholar 

  23. Cady NC, Stelick S, Batt CA (2003) Biosens Bioelectron 19(59):59–66

    Article  CAS  Google Scholar 

  24. Breadmore MC, Wolfe K, Arcibal IG, Leung WK, Dickson D, Giordano BC, Power ME, Ferrance JP, Feldman S, Norris PM, Landers JP (2003) Anal Chem 75:1880–1886

    Article  CAS  PubMed  Google Scholar 

  25. Torielloa NM, Douglas ES, Thaitrong N, Hsiao SC, Francis MB, Bertozzi CR, Mathiesa RA (2008) Proc Natl Aacad Sci USA 105:20173–20178

    Article  Google Scholar 

  26. Easley CJ, Karlinsey JM, Bienvenue JM, Legendre LA, Roper MG, Feldman SH, Hughes MA, Hewett EL, Merkel TJ, Ferrance JP, Landers JP (2006) Proc Natl Acad Sci USA 103:19272–1927

    Article  Google Scholar 

  27. Huang FC, Liao CS, Lee GB (2006) Electrophoresis 27:3297–3305

    Article  CAS  PubMed  Google Scholar 

  28. Prakash AR, Adamia S, Sieben V, Pilarski P, Pilarski LM, Backhouse CJ (2006) Sens Actuators B Chem 113:398–409

    Article  CAS  Google Scholar 

  29. Cheng JY, Hsieh CJ, Chuang YC, Hsieh JR (2005) Analyst 130:931–940

    Article  CAS  PubMed  Google Scholar 

  30. Liao CS, Lee GB, Wu JJ, Chang CC, Hsieh TM, Huang FC, Luo CH (2005) Biosens Bioelectron 20:1341–1348

    Article  CAS  PubMed  Google Scholar 

  31. Zhang CS, Xu JL, Ma WL, Zheng WL (2006) Biotechnol Adv 24:243–284

    Article  CAS  PubMed  Google Scholar 

  32. Hui WC, Yobas L, Samper VD, Heng CK, Liwa S, Ji H, Chena Y, Cong L, Li J, Limb TM (2007) Sens Actuators A 133:335–339

    Article  CAS  Google Scholar 

  33. Hoffman D, O’Brien J, Brennan D (2008) Sens Actuators B 12(2):653–658

    Article  CAS  Google Scholar 

  34. Gao X, Nie S (2004) Anal Chem 76(8):2406–2410

    Article  CAS  PubMed  Google Scholar 

  35. Cao YC, Huang ZL, Liu TC, Wang HQ, Zhu XX, Wang Z, Zhao YD, Liu MX, Luo QM (2006) Anal Biochem 351:193–200

    Article  CAS  PubMed  Google Scholar 

  36. Ymeti A, Greve J, Lambeck PV, Wink T, van Hövell S, Beumer TA, Wijn RR, Heideman RG, Subramaniam V, Kanger JS (2007) Nano Lett 7(2):394–397

    Article  CAS  PubMed  Google Scholar 

  37. Pappaert K, Van Mummelen P, Vanderhoeven J, Dutta B, Clicq D, Baron GV, Desmet G (2003) J Chromatogr A 1014:1–9

    Article  CAS  PubMed  Google Scholar 

  38. Pappaert K, Van Mummelen P, Vanderhoeven J, Baron GV, Desmet G (2003) Chem Eng Sci 58:4921–4930

    Article  CAS  Google Scholar 

  39. Persa H, Chin CD, Mongkolwisetwara P, Lee BW, Wang J, Sia SK (2008) Lab Chip 8:2062–2070

    Article  CAS  Google Scholar 

  40. Hu G, Gao Y, Li D (2007) Biosens Bioelectron 22:1403–1409

    Article  CAS  PubMed  Google Scholar 

  41. Hoffman O, Voirin G, Niedermann P, Manz A (2002) Anal Chem 20:5243–5250

    Article  CAS  Google Scholar 

  42. Sigurdson M, Wang D, Meinhart CD (2005) Lab Chip 5:1366–1373

    Article  CAS  PubMed  Google Scholar 

  43. Golden JP, Floyd-Smith TM, Mott DR, Ligler FS (2007) Biosens Bioelectron 22:2763–2767

    Article  CAS  PubMed  Google Scholar 

  44. Peterson AW, Heaton RJ, Georgiadis RM (2001) Nucleic Acids Res 29(24):5163–5168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Brennan D, Lambkin P, Moore EJ, Galvin P (2008) IEEE Sens J 8(5):536–542

    Article  CAS  Google Scholar 

  46. ATIK Instruments (2009) ATIK Instruments products. http://www.atik-instruments.com/html/products.html. Accessed 12 March 2009

  47. Starlight Express Ltd. (2009) Starlight express products. http://www.starlight-xpress.co.uk. Accessed 12 March 2009

  48. SensL the low light company (2009) SensL products. http://www.sensl.com/Technology/. Accessed 12 March 2009

  49. Tung YC, Zhang M, Lin CT, Kurabayashi K, Skerlos SJ (2004) Sens Actuators B Chem 98:356–367

    Article  CAS  Google Scholar 

  50. Chabinyc ML, Chiu DT, McDonald JC, Stroock AD, Christian JF, Karger AM, Whitesides GM (2001) Anal Chem 73:4491–4498

    Article  CAS  PubMed  Google Scholar 

  51. Hofmann O, Miller P, Sullivan P, Jones TS, deMello JC, Bradley DC, deMello AJ (2005) Sens Actuators B 106:878–884

    Article  CAS  Google Scholar 

  52. Mavrogiannopoulou E, Petrou PS, Kakabakos SE, Misiakos K (2009) Biosens Bioelectron 24:1341–1347

    Article  CAS  PubMed  Google Scholar 

  53. Roulet JC, Volkel R, Herzig, HP, Verpoorte E, de Rooij NF, Dandliker R (2001) J Microelectromech Syst 10(4):482–490

    Article  CAS  Google Scholar 

  54. Llobera A, Demming S, Wilke R, Büttgenbach S (2007) Lab Chip 7:1560–1565

    Article  CAS  PubMed  Google Scholar 

  55. Luminex Corporation (2009) Xmap technology. http://www.luminexcorp.com/technology/index.html. Accessed 12 March 2009

  56. Affymetrix Inc. (2009) Genome Wide Association. http://www.affymetrix.com/products_services/research_solutions/methods/genome-wide-association.affx. Accessed 12 March 2009

  57. Nam JM, Steova S, Mirkin CA (2004) J Am Chem Soc 126:5932–5933

    Article  CAS  PubMed  Google Scholar 

  58. Ramsay G (1998) Nat Biotechnol 16:40–44

    Article  CAS  PubMed  Google Scholar 

  59. Heller MJ (2002) Annu Rev Biomed Eng 4:129–153

    Article  CAS  Google Scholar 

  60. Stoughton RB (2005) Annu Rev Biochem 74:53–82

    Article  CAS  PubMed  Google Scholar 

  61. Wei Y, Cao C, Jin R, Mirkin CA (2002) Science 297:1536–1540

    Article  Google Scholar 

  62. Sowell J, Strekowski L, Patonay G (2002) J Biomed Opt 7:571–578

    Article  CAS  PubMed  Google Scholar 

  63. Schmidt H, Hawkins AR (2008) J Microfluidics Nanofluidics 4:1–2

    Article  Google Scholar 

  64. Wang J, Engelund M, Gotsæd T, Perch-Nielsen IR, Mogensen KB, Snakenborg D, Kutter JP, Wolff A (2004) Lab Chip 4:372–377

    Article  CAS  PubMed  Google Scholar 

  65. Seo J, Lee LP (2004) Sens Actuators B Chem 99:615–622

    Article  CAS  Google Scholar 

  66. Chediak JA, Luo Z, Seo J, Cheung N, Lee LP, Sands TD (2004) Sens Actuators A 111:1–7

    Article  CAS  Google Scholar 

  67. Thrush E, Levi O, Ha W, Wang K, Smith SJ, Harris JS (2003) J Chromatogr A 1013:103–110

    Article  CAS  PubMed  Google Scholar 

  68. Yeh HC, Puleo CM, Lim TC, Ho YP, Giza PE, Huang RCC, Wang TH (2006) Nucleic Acids Res 34:144–152

    Article  Google Scholar 

  69. Kim S, Chen L, Lee S, Seong GH, Choo J, Lee EK, Oh C, Lee S (2007) Anal Sci 23:401–405

  70. Liu AQ, Huang HJ, Chin LK ,Yu YF, Li XC (2008) Anal Bioanal Chem 391:2443–2452

    Article  CAS  Google Scholar 

  71. Fan X, White IM, Shopova SI, Zhu H, Suter JD, Sun Y (2008) Anal Chim Acta 620:8–26

    Article  CAS  PubMed  Google Scholar 

  72. Heideman RG, Lambeck PV (1999) Sens Actuators B Chem 61:100–127

    Article  CAS  Google Scholar 

  73. Sánchez del Rio J, Carrascosa LG, Blanco FG, Moreno M (2007) Proc SPIE 6477:64771B

    Article  CAS  Google Scholar 

  74. Sepúlvedal B, Sánchez del Río J, Moreno M, Blanco FJ, Mayora K, Domínguez C, Lechuga LM (2006) J Opt A Pure Appl Opt 8:561–566

    Article  CAS  Google Scholar 

  75. Hsu SH, Huang YT (2005) J Lightwave Technol 23(12):4200–4207

    Article  Google Scholar 

  76. Bernini R, Testa G, Zeni L, Sarro PM (2008) Appl Phys Lett 93:011106. doi:10.1063/1.2957031

    Article  CAS  Google Scholar 

  77. GE Healthcare (2009) Label free interaction analysis in real time. http://www.biacore.com/lifesciences/introduction/index.html. Accessed 12 March 2009

  78. Sensata Technologies (2009) Spreeta SPR sensors. http://www.sensata.com/sensors/spreeta-analytical-sensor-highlights.htm. Accessed 12 March 2009

  79. Chinowsky TM, Grow MS, Johnston KS, Nelson K, Edwards T, Fu E, Yager P (2007) Biosens Bioelectron 22:2208–2215

    Article  CAS  PubMed  Google Scholar 

  80. Lee HJ, Goodrich TJ, Corn RM (2001) Anal Chem 73(22):5525–5531

    Article  CAS  Google Scholar 

  81. Nelson BP, Grimsrud TE, Liles MR, Goodman RM, Corn RM (2001) Anal Chem 73(1):1–7

    Article  CAS  PubMed  Google Scholar 

  82. He L, Musick MD, Nicewarner SR, Salinas FG, Benkovic SJ, Natan MJ, Keating CD (2000) J Am Chem Soc 122(38):9071–9077

    Article  CAS  Google Scholar 

  83. Hayashida M, Yamaguchi A, Misawa H (2005) Jpn J Appl Phys 44:1544–1546

    Article  CAS  Google Scholar 

  84. Lindquist NC, Lesuffleur A, Im H, Oh SH (2009) Lab Chip 9:382–387

    Article  CAS  PubMed  Google Scholar 

  85. Measor P, Seballos L, Yin D, Zhang JZ, Lunt EJ, Hawkins AR, Schmidt H (2007) Appl Phys Lett 90(21):1–3

    Article  Google Scholar 

  86. Taton TA, Mirkin CA, Letsinger RL (2000) Science 289:1757–1760

    Article  CAS  PubMed  Google Scholar 

  87. Vollmer F, Arnold S (2008) Nat Methods 5(7):591–596

    Article  CAS  PubMed  Google Scholar 

  88. Armani AM, Kulkarni RP, Fraser SE, Flagan RC, Vahala KJ (2007) Science 317:783–786

    Article  CAS  PubMed  Google Scholar 

  89. Vollmer F, Arnold S, Braun D, Teraoko I, Libchaber A (2003) Biophys J 85:1974–1979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yang G, White IM, Fan X (2008) Sens Actuators B 133:105–112

    Article  CAS  Google Scholar 

  91. Chao CY,.Fung W,Goa LJ (2006) IEEE J Sel Top Quantum Electron 12(1):1438–1449

    Google Scholar 

  92. Mandal S, Erickson D (2008) Opt Express 16(3):1623–1631

    Article  PubMed  PubMed Central  Google Scholar 

  93. Li M, He F, Liao Q, Liu J, Xu L, Jiang L, Song Y, Wang S, Zhu D (2008) Angew Chem Int Ed 47:7258–7262

    Article  CAS  Google Scholar 

  94. Dodson JM, Feldstein MJ, Leatzow DM, Flack LK, Golden JP, Ligler FS (2001) Anal Chem 73:3776–3780

    Article  CAS  PubMed  Google Scholar 

  95. Tsai JH, Lin LW (2002) J Microelectromech Syst 11:665–671

    Article  CAS  Google Scholar 

  96. Bohm S, Olthuis W, Bergveld P (1999) Sens Actuators A 77:223–228

    Article  CAS  Google Scholar 

  97. Beebe DJ, Moore JS, Bauer JM, Yu Q, Liu RH, Devadoss C, Jo BH (2000) Nature 404:588–590

    Article  CAS  PubMed  Google Scholar 

  98. Liu RH, Yu Q, Beebe DJ (2002) J Microelectromech Syst 11:45–53

    Article  CAS  Google Scholar 

  99. Burns MA, Johnson BN, Brahmasandra SN, Handique K, Webster JR, Krishnan M, Sammarco TS, Man PM, Jones D, Heldsinger D, Mastrangelo CH, Burke DT (1998) Science 282:484–487

    Article  CAS  PubMed  Google Scholar 

  100. Zeng SL, Chen CH, Santiago JG, Chen JR, Zare RN, Tripp JA, Svec F, Frechet JM (2002) Sens Actuators B 82:209–212

    Article  CAS  Google Scholar 

  101. Woollery AT, Hadley D, Landre P, deMello AJ, Mathies RA, Northrup MA (1996) Anal Chem 68:4081–4086

    Article  Google Scholar 

  102. Anderson RC (2000) Nucleic Acids Res 28:e60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kartalov EP, Quake SR (2004) Nucleic Acids Res 32:2873–2879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Liu RH, Yang J, Lenigk R, Bonanno J, Grodzinski P (2004) Anal Chem 76(7):1824–1831

    Article  CAS  PubMed  Google Scholar 

  105. Huang SC, Lee GB, Chien FC, Chen SJ, Chen WJ, Yang MC (2006) J Micromech Microeng 16:1251–1257

    Article  CAS  Google Scholar 

  106. Lei KF, Law WC, Suen YK, Li WC,Yam Y, Ho H, Kong SK (2007) Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine. pp. 129–141

  107. Liu YJ, Yao DJ, Lin HD ,Chang WY, Chang HY (2008) J Micromech Microeng 18:1–7

    CAS  Google Scholar 

  108. Chang YH, Lee GB, Huang FC, Chen YY, Lin JL (2006) Biomed Microdevices 8:215–25

    Article  CAS  PubMed  Google Scholar 

  109. Wheeler AR, Moon H, Bird CA, Loo RR, Kim CJ, Loo JA, Garrell RL (2005) Anal Chem 77:534–540

    Article  CAS  PubMed  Google Scholar 

  110. Linder V, Sia SK, Whitesides GM (2005) Anal Chem 77:64–71

    Article  CAS  PubMed  Google Scholar 

  111. Woolley AT, Lao K (1998) Anal Chem 70:684–688

    Article  CAS  PubMed  Google Scholar 

  112. Colyer CL, Harrison D (1997) Electrophoresis 18:1733–1741

    Article  CAS  PubMed  Google Scholar 

  113. Martin P, Matson D (1998) Proc SPIE 3515:172–176

    Article  Google Scholar 

  114. Glasgow IK, Beebe DJ, White VE (1999) Sens Mater 11(5):269–273

    CAS  Google Scholar 

  115. Soper SA, Henry AC, Vaidya B, Galloway M, Wabuyele M, McCarley RL (2002) Anal Chim Acta 55:87–99

    Article  Google Scholar 

  116. Eddings MA, Johnson MA, Gale BK (2008) J Micromech Microeng 18:1–4

    Article  Google Scholar 

  117. Lee S, Jiang Y (2001) Anal Chem 73:2048–2053

    Article  CAS  PubMed  Google Scholar 

  118. Locascio L, Perso (1999) J Chromathogr A 857:275–284

    Article  CAS  Google Scholar 

  119. Zhang ZB, Luo Y, Wang XD, Zhang ZQ, Wang LD (2008) Ultrasonic bonding of polymer microfluidic chips. Paper presented at the international conference on electronic packaging technology & high density packaging (ICEPT-HDP 2008)

  120. Chantal G, Khan M (2006) Anal Bioanal Chem 385:1351–1361

    Article  CAS  Google Scholar 

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  1. Tyndall National Institute, Lee Maltings, Prospect Row, Cork City, Co. Cork, Ireland

    Desmond Brennan, John Justice, Brian Corbett & Paul Galvin

  2. Department of Biochemistry, University College, Cork, Lee Maltings, Prospect Row, Cork City, Co. Cork, Ireland

    Tommie McCarthy

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  1. Desmond Brennan
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Brennan, D., Justice, J., Corbett, B. et al. Emerging optofluidic technologies for point-of-care genetic analysis systems: a review. Anal Bioanal Chem 395, 621–636 (2009). https://doi.org/10.1007/s00216-009-2826-5

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