Analytical and Bioanalytical Chemistry

, Volume 408, Issue 26, pp 7255–7264 | Cite as

Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer

Review
Part of the following topical collections:
  1. Chemical Sensing Systems

Abstract

The detection of cancer biomarkers freely circulating in blood offers new opportunities for cancer early diagnosis, patient follow-up, and therapy efficacy assessment based on liquid biopsy. In particular, circulating cell-free nucleic acids released from tumor cells have recently attracted great attention also because they become detectable in blood before the appearance of other circulating biomarkers, such as circulating tumor cells. The detection of circulating nucleic acids poses several technical challenges that arise from their low concentration and relatively small size. Here, possibilities offered by innovative biosensing approaches for the detection of circulating DNA in peripheral blood and blood-derived products such as plasma and serum blood are discussed. Different transduction principles are used to detect circulating DNAs and great advantages are derived from the combined use of nanostructured materials.

Keywords

Biosensor DNA Electrochemistry Surface plasmon resonance Liquid biopsy 

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods, and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):359–86.CrossRefGoogle Scholar
  2. 2.
    Ortmann CA, Kent DG, Nangalia J. Effect of mutation order on myeloproliferative neoplasms. N Engl J Med. 2015;372:1865–6.CrossRefGoogle Scholar
  3. 3.
    Diamantis A, Magiorkinis E, Koutselini H. Fine-needle aspiration (FNA) biopsy: historical aspects. Folia Histochem Cytobiol. 2009;47(2):191–7.CrossRefGoogle Scholar
  4. 4.
    Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10:472–84.CrossRefGoogle Scholar
  5. 5.
    Gerlinger M. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.CrossRefGoogle Scholar
  6. 6.
    Alix-Panabières C, Pantel K. Challenges in circulating tumor cell research. Nat Rev Cancer. 2014;14:623–31.CrossRefGoogle Scholar
  7. 7.
    Taylor DD, Gercel-Taylor C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol. 2011;33(5):441–54.CrossRefGoogle Scholar
  8. 8.
    Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;2087–2092.Google Scholar
  9. 9.
    Deprimo SE, Bello CL, Smeraglia J, Baum CM, Spinella D, Rini BI, Michaelson MD, Motzer RJ. Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med. 2007;5:32.CrossRefGoogle Scholar
  10. 10.
    Luna Coronell JA, Syed P, Sergelen K, Gyurján I, Weinhäusel A. The current status of cancer biomarker research using tumor-associated antigens for minimal invasive and early cancer diagnostics. J Proteom. 2012;76:102–15.CrossRefGoogle Scholar
  11. 11.
    Tsui DWY, Berger MF. Profiling non-small cell lung cancer: from tumor to blood. Clin Cancer Res. 2016;22(4):790–2.CrossRefGoogle Scholar
  12. 12.
    Chi KR. The tumor trail left in blood. Nature. 2016;532:269–71.CrossRefGoogle Scholar
  13. 13.
    Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370:1287–97.CrossRefGoogle Scholar
  14. 14.
    Market analysis report. Global liquid biopsy market outlook to 2020. RNCOS. 2016.Google Scholar
  15. 15.
    Thierry AR, Mouliere F, El Messaoudi S, Mollevi C, Lopez-Crapez E, Rolet F. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med. 2014;20(4):430–6.CrossRefGoogle Scholar
  16. 16.
    Bettegowda C, Sausen M, Leary RJ. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.CrossRefGoogle Scholar
  17. 17.
    Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209.CrossRefGoogle Scholar
  18. 18.
    Mandel P, Metais P. Les acides nucleiques du plasma sanguin chez l’homme. C R Seances Soc Biol Fil. 1948;142:241–3.Google Scholar
  19. 19.
    Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37(3):646–50.Google Scholar
  20. 20.
    Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology. 1989;46(5):318–22.CrossRefGoogle Scholar
  21. 21.
    Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994;86(4):774–9.CrossRefGoogle Scholar
  22. 22.
    Lebofsky R, Decraene C, Bernard V, Kamal M, Blin A, Leroy Q, Frio TR, Pierron G, Callens C, Bieche I, Saliou A, Madic J, Rouleau E, Bidard FC, Lantz O, Stern MH, Tourneau CL, Pierga JY. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types. Mol Oncol. 2015;9:783–90.CrossRefGoogle Scholar
  23. 23.
    Benesova L, Belsanova B, Suchanek S, Kopeckova M, Minarikova P, Lipska L, Levy M, Visokai V, Zavoral M, Minarik M. Mutation-based detection and monitoring of cell-free tumor DNA in peripheral blood of cancer patients. Anal Biochem. 2013;433(2):227–34.CrossRefGoogle Scholar
  24. 24.
    Mauger F, Dulary C, Daviaud C, Deleuze J-F, Tost J. Comprehensive evaluation of methods to isolate, quantify, and characterize circulating cell-free DNA from small volumes of plasma. Anal Bioanal Chem. 2015;407(22):6873–8.CrossRefGoogle Scholar
  25. 25.
    Szpechcinski A, Chorostowska-Wynimko J, Struniawski R, Kupis W, Rudzinski P, Langfort R, Puscinska E, Bielen P, Sliwinski P, Orlowski T. Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease. Br J Cancer. 2015;113(3):476–83.CrossRefGoogle Scholar
  26. 26.
    Perkins G, Yap TA, Pope L, Cassidy AM, Dukes JP, Riisnaes R. Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers. PLoS ONE. 2012;7(11), e47020.CrossRefGoogle Scholar
  27. 27.
    Garm Spindler KL, Pallisgaard N, Andersen RF, Brandslund I, Jakobsen A. Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer. PLoS ONE. 2015;10(4), e0108247.CrossRefGoogle Scholar
  28. 28.
    Cristofanilli M, Fortina P. Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;369:93–4.CrossRefGoogle Scholar
  29. 29.
    Panabières CA, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6(5):479–91.CrossRefGoogle Scholar
  30. 30.
    Siravegna G, Bardelli A. Blood circulating tumor DNA for noninvasive genotyping of colon cancer patients. Mol Oncol. 2015;10(3):475–80.CrossRefGoogle Scholar
  31. 31.
    Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90.CrossRefGoogle Scholar
  32. 32.
    Diaz Jr LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–86.CrossRefGoogle Scholar
  33. 33.
    Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11(1):31–46.CrossRefGoogle Scholar
  34. 34.
    Banerji S. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012;486(7403):405–9.CrossRefGoogle Scholar
  35. 35.
    Bratman SV, Newman AM, Alizadeh AA, Diehn M. Potential clinical utility of ultrasensitive circulating tumor DNA detection with CAPP-Seq. Expert Rev Mol Diagn. 2015;15(6):715–9.Google Scholar
  36. 36.
    Ogasawara N, Bando H, Kawamoto Y, Yoshino T, Tsuchihara K, Ohtsu A, Esumiet H. Feasibility and robustness of amplification refractory mutation system (ARMS)-based KRAS testing using clinically available formalin-fixed, paraffin-embedded samples of colorectal cancers. J Clin Oncol. 2011;41(1):52–6.Google Scholar
  37. 37.
    Chen Z, Feng J, Buzin CH, Liu Q, Weiss L, Kernstine K, Somlo G, Sommeret SS. Analysis of cancer mutation signatures in blood by a novel ultra-sensitive assay: monitoring of therapy or recurrence in non-metastatic breast cancer. PLoS ONE. 2009;4(9), e7220.CrossRefGoogle Scholar
  38. 38.
    Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D, Hadfield J, May AP, Caldas C, Brenton JD, Rosenfeld N. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med. 2012;4(136):136ra68.Google Scholar
  39. 39.
    Mancini I, Santucci C, Sestini R, Simi L, Pratesi N, Cianchi F, Valanzano R, Pinzani P, Orlando C. The Use of COLD-PCR and high-resolution melting analysis improves the limit of detection of KRAS and BRAF mutations in colorectal cancer. J Mol Diagn. 2010;12(5):705–11.CrossRefGoogle Scholar
  40. 40.
    Carotenuto P, Roma C, Cozzolino S, Fenizia F, Rachiglio AM, Tatangelo F, Iannaccone A, Baron L, Botti G, Normanno N. Detection of KRAS mutations in colorectal cancer with Fast COLD-PCR. Int J Oncol. 2012;40(2):378–84.Google Scholar
  41. 41.
    Pinzani P, Santucci C, Mancini I, Simi L, Salvianti F, Pratesi N. BRAFV600E detection in melanoma is highly improved by COLD-PCR. Clin Chim Acta. 2011;412(11/12):901–5.CrossRefGoogle Scholar
  42. 42.
    Ausch C, Buxhofer-Ausch V, Oberkanins C, Holzer B, Minai-Pour M, Jahn S, Dandachi N, Zeillinger R, Kriegshäuser G. Sensitive detection of KRAS mutations in archived formalin-fixed paraffin-embedded tissue using mutant-enriched PCR and reverse-hybridization. J Mol Diagn. 2009;11(6):508–13.CrossRefGoogle Scholar
  43. 43.
    Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, Diaz Jr. LA, Goodman SN, David KA, Juhl H, Kinzler KW, Vogelstein B. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A. 2005;102(45):16368–73.CrossRefGoogle Scholar
  44. 44.
    Higgins MJ, Jelovac D, Barnathan E, Blair B, Slater S, Powers P. Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood. Clin Cancer Res. 2012;18(12):3462–9.CrossRefGoogle Scholar
  45. 45.
    Taniguchi K, Uchida J, Nishino K, Kumagai T, Okuyama T, Okami J. Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas. Clin Cancer Res. 2011;17(24):7808–15.CrossRefGoogle Scholar
  46. 46.
    Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, O’Shaughnessy J, Kinzler KW, Parmigiani G, Vogelstein B, Diaz Jr. LA, Velculescu VE. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci Transl Med. 2012;4(162):162ra154.Google Scholar
  47. 47.
    Sanmamed MF, Fernandez-Landazuri S, Rodriguez C, Zarate R, Lozano MD, Zubiri L. Quantitative cell-free circulating BRAFV600E mutation analysis by use of droplet digital PCR in the follow-up of patients with melanoma being treated with BRAF inhibitors. Clin Chem. 2015;61(1):297–304.CrossRefGoogle Scholar
  48. 48.
    Abdel-Wahab O, Klimek VM, Gaskell AA, Viale A, Cheng D, Kim E. Efficacy of intermittent combined RAF and MEK inhibition in a patient with concurrent BRAF- and NRAS-mutant malignancies. Cancer Discov. 2014;4(5):538–45.CrossRefGoogle Scholar
  49. 49.
    Oxnard GR, Paweletz CP, Kuang Y, Mach SL, O'Connell A, Messineo MM. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res. 2014;20(6):1698–705.CrossRefGoogle Scholar
  50. 50.
    Beaver JA, Jelovac D, Balukrishna S, Cochran RL, Croessmann S, Zabransky DJ. Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clin Cancer Res. 2014;20(10):2643–50.CrossRefGoogle Scholar
  51. 51.
    Stadler J, Eder J, Pratscher B, Brandt S, Schneller D, Müllegger R. SNPase-ARMS qPCR: ultrasensitive mutation-based detection of cell-free tumor DNA in melanoma patients. PLoS ONE. 2015;10(11), e0142273.CrossRefGoogle Scholar
  52. 52.
    Florence M, Dulary C, Daviaud C, Deleuze J-F, Tost J. Comprehensive evaluation of methods to isolate, quantify and characterize circulating cell-free DNA from small volumes of plasma. Anal Bioanal Chem. 2015;407:6873–8.CrossRefGoogle Scholar
  53. 53.
    Schwarzenbach H, Hoon DSB, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–37.CrossRefGoogle Scholar
  54. 54.
    Spoto G, Corradini R. Detection of non-amplified genomic DNA. Dordrecht: Springer; 2012.Google Scholar
  55. 55.
    Kelley SO, Mirkin CA, Walt DR, Ismagilov RF, Toner M, Sargent EH. Advancing the speed, sensitivity, and accuracy of biomolecular detection with multi-length scale engineering. Nat Nanotechnol. 2014;9:969–80.CrossRefGoogle Scholar
  56. 56.
    Krabbenborg SO, Nicosia C, Chen P, Huskens J. Reactivity mapping with electrochemical gradients for monitoring reactivity at surfaces in space and time. Nat Commun. 2013;4:1667.CrossRefGoogle Scholar
  57. 57.
    Corradini R, Sforza S, Tedeschi T, Totsingan F, Manicardi A, Marchelli R. Peptide nucleic acids with a structurally biased backbone. updated review and emerging challenges. Curr Top Med Chem. 2011;11(12):1535–54.CrossRefGoogle Scholar
  58. 58.
    D’Agata R, Spoto G. Artificial DNA and surface plasmon resonance. Artificial DNA: PNA and XNA. 2012;3(2):45–52.CrossRefGoogle Scholar
  59. 59.
    Li M, Cushing SK, Wu N. Plasmon-enhanced optical sensors: a review. Analyst. 2015;140(2):386–406.CrossRefGoogle Scholar
  60. 60.
    Zanoli LM, D’Agata R, Spoto G. Functionalized gold nanoparticles for ultrasensitive DNA detection. Anal Bioanal Chem. 2012;402(5):1759–71.CrossRefGoogle Scholar
  61. 61.
    Hyun KA, Kim J, Gwak H, Jung HI. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics. Analyst. 2016;141:382–92.CrossRefGoogle Scholar
  62. 62.
    Lubin AA, Plaxco KW. Folding-based electrochemical biosensors: the case for responsive nucleic acid architectures. Acc Chem Res. 2010;43(4):496–505.CrossRefGoogle Scholar
  63. 63.
    Ronkainen NJ, Halsall HB, Heineman WR. Electrochemical biosensors. Chem Soc Rev. 2010;39(5):1747–63.CrossRefGoogle Scholar
  64. 64.
    Das J, Kelley SO. Protein detection using arrayed microsensor chips: tuning sensor footprint to achieve ultrasensitive readout of CA-125 in SERUM AND WHOLE BLOOD. Anal Chem. 2011;83:1167–72.CrossRefGoogle Scholar
  65. 65.
    Yu X, Munge B, Patel V, Jensen G, Bhirde A, Gong JD, Kim SN, Gillespie J, Gutkind JS, Papadimitrakopoulos F, Rusling JF. Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers. J Am Chem Soc. 2006;128(34):11199–205.CrossRefGoogle Scholar
  66. 66.
    Hong CY, Chen X, Liu T, Li J, Yang HH, Chen JH, Chen GN. Ultrasensitive electrochemical detection of cancer-associated circulating microRNA in serum samples based on DNA concatamers. Biosens Bioelectron. 2013;50:132–6.CrossRefGoogle Scholar
  67. 67.
    Das J, Ivanov I, Montermini L, Rak J, Sargent EH, Kelley SO. An electrochemical clamp assay for direct, rapid analysis of circulating nucleic acids in serum. Nat Chem. 2015;7:569–75.CrossRefGoogle Scholar
  68. 68.
    Bin X, Sargent EH, Kelley SO. Nanostructuring of sensors determines the efficiency of biomolecular capture. Anal Chem. 2010;14:5928–31.CrossRefGoogle Scholar
  69. 69.
    Zhu C, Yang G, Li H, Du D, Lin Y. Electrochemical sensors and biosensors based on nanomaterials and nanostructures. Anal Chem. 2015;87:230–49.CrossRefGoogle Scholar
  70. 70.
    Wu ZS, Yang SB, Sun Y, Parvez K, Feng XL, Mullen K. 3D nitrogen-doped graphene aerogel-supported Fe3O4 nanoparticles as efficient eletrocatalysts for the oxygen reduction reaction. J Am Chem Soc. 2012;134(22):9082–5.CrossRefGoogle Scholar
  71. 71.
    Liu R, Wan L, Liu S, Pan L, Wu D, Zhao D. An interface-induced co-assembly approach towards ordered mesoporous carbon/graphene aerogel for high-performance supercapacitors. Adv Funct Mater. 2015;25:526–33.CrossRefGoogle Scholar
  72. 72.
    Worsley MA, Pauzauskie PJ, Olson TY, Biener J, Satcher JH, Baumann TF. Synthesis of graphene aerogel with high electrical conductivity. J Am Chem Soc. 2010;132:14067–9.CrossRefGoogle Scholar
  73. 73.
    Hu H, Zhao ZB, Wan WB, Gogotsi Y, Qiu JS. Polymer/graphene hybrid aerogel with high compressibility, conductivity, and “sticky” superhydrophobicity. ACS Appl Mater Interfaces. 2014;6:3242–9.CrossRefGoogle Scholar
  74. 74.
    Hongxia B, Ruiyi L, Zaijun L, Junkang L, Zhiguo G, Guangli W. Fabrication of a high density graphene aerogel–gold nanostar hybrid and its application for the electrochemical detection of hydroquinone and o-dihydroxybenzene. RSC Adv. 2015;5:54211–9.CrossRefGoogle Scholar
  75. 75.
    Ruiyi L, Ling L, Hongxia B, Zaijun L. Nitrogen-doped multiple graphene aerogel/gold nanostar as the electrochemical sensing platform for ultrasensitive detection of circulating free DNA in human serum. Biosens Bioelectron. 2016;79:457–66.CrossRefGoogle Scholar
  76. 76.
    Sassolas A, Leca-Bouvier BD, Blum LJ. DNA biosensors and microarrays. Chem Rev. 2008;108(1):109–39.CrossRefGoogle Scholar
  77. 77.
    Mouliere F, Rosenfeld N. Circulating tumor-derived DNA is shorter than somatic DNA in plasma. Proc Natl Acad Sci U S A. 2015;112(11):3178–9.CrossRefGoogle Scholar
  78. 78.
    Liu KJ, Brock MV, Shih IM, Wang TH. Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy. J Am Chem Soc. 2010;132:5793–8.CrossRefGoogle Scholar
  79. 79.
    Brolo AG. Plasmonics for future biosensors. Nat Photon. 2012;6:709–13.CrossRefGoogle Scholar
  80. 80.
    D’Agata R, Spoto G. Surface plasmon resonance imaging for nucleic acid detection. Anal Bioanal Chem. 2013;405(2/3):573–84.CrossRefGoogle Scholar
  81. 81.
    Spoto G, Minunni M. Surface plasmon resonance imaging: what next? J Phys Chem Lett. 2012;3(18):2682–91.CrossRefGoogle Scholar
  82. 82.
    Wilson R. The use of gold nanoparticles in diagnostics and detection. Chem Soc Rev. 2008;37:2028–45.CrossRefGoogle Scholar
  83. 83.
    Truong PL, Cao C, Park S, Kim M, Sim SJ. A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor. LabChip. 2011;11:2591–7.Google Scholar
  84. 84.
    Devi RV, Doble M, Verma RS. Nanomaterials for early detection of cancer biomarker with special emphasis on gold nanoparticles in immunoassays/sensors. Biosens Bioelectron. 2015;68:688–98.CrossRefGoogle Scholar
  85. 85.
    Ma W, Kuang H, Xu L, Ding L, Xu C, Wang L, Kotov NA. Attomolar DNA detection with chiral nanorod assemblies. Nat Commun. 2013;4:2689.Google Scholar
  86. 86.
    D’Agata R, Breveglieri G, Zanoli LM, Borgatti M, Spoto G, Gambari R. Direct detection of point mutations in nonamplified human genomic DNA. Anal Chem. 2011;83(22):8711–7.CrossRefGoogle Scholar
  87. 87.
    Ladd J, Taylor AD, Piliarik M, Homola J, Jiang S. Label-free detection of cancer biomarker candidates using surface plasmon resonance imaging. Anal Bioanal Chem. 2009;393(4):1157–63.CrossRefGoogle Scholar
  88. 88.
    Grasso G, D'Agata R, Zanoli L, Spoto G. Microfluidic networks for surface plasmon resonance imaging real-time kinetics experiments. Microchemistry J. 2009;93:82–6.CrossRefGoogle Scholar
  89. 89.
    Sato Y, Fujimoto K, Kawaguchi H. Detection of a K-ras point mutation employing peptide nucleic acid at the surface of a SPR biosensor. Colloid Surf B. 2003;27:23–31.CrossRefGoogle Scholar
  90. 90.
    Bertucci A, Manicardi A, Candiani A, Giannetti S, Cucinotta A, Spoto G, Konstantaki M, Pissadakis S, Selleri S, Corradini R. Detection of unamplified genomic DNA by a PNA-based microstructured optical fiber (MOF) Bragg-grating optofluidic system. Biosens Bioelectron. 2015;63:248–54.CrossRefGoogle Scholar
  91. 91.
    D’Agata R, Corradini R, Ferretti C, Zanoli L, Gatti M, Marchelli R, Spoto G. Ultrasensitive detection of non-amplified genomic DNA by nanoparticle-enhanced surface plasmon resonance imaging. Biosens Bioelectron. 2010;25(9):2095–100.CrossRefGoogle Scholar
  92. 92.
    Carrascosa LG, Sina AAI, Palanisamy R, Sepulveda B, Otte MA, Rauf S, Shiddikya MJA, Trau M. Molecular inversion probe-based SPR biosensing for specific, label-free and real-time detection of regional DNA methylation. Chem Commun. 2014. doi:10.1039/C3CC49607D.Google Scholar
  93. 93.
    Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene. 2002;21(35):5400–13.CrossRefGoogle Scholar
  94. 94.
    Shalabney A, Abdulhalim I. Sensitivity-enhancement methods for surface plasmon sensors. Laser Photon Rev. 2011;5(4):571–606.CrossRefGoogle Scholar
  95. 95.
    Willets KA, Van Duyne RP. Localized surface plasmon resonance spectroscopy and sensing. Annu Rev Phys Chem. 2007;58:267–97.CrossRefGoogle Scholar
  96. 96.
    Yonzon CR, Jeoung E, Zou S, Schatz GC, Mrksich M, Van Duyne RP. A comparative analysis of localized and propagating surface plasmon resonance sensors: the binding of concanavalin A to a monosaccharide functionalized self-assembled monolayer. J Am Chem Soc. 2004;126(39):12669–76.CrossRefGoogle Scholar
  97. 97.
    Fong KE, Yung LY. Localized surface plasmon resonance: a unique property of plasmonic nanoparticles for nucleic acid detection. Nanoscale. 2013;5(24):12043–71.CrossRefGoogle Scholar
  98. 98.
    Nguyen AH, Sim SJ. Nanoplasmonic biosensor: detection and amplification of dual bio-signatures of circulating tumor DNA. Biosens Bioelectron. 2015;67:443–9.CrossRefGoogle Scholar
  99. 99.
    Dias TM, Cardoso FA, Martins SAM, Martins VC, Cardoso S, Gaspar JF, Monteiro G, Freitas PP. Implementing a strategy for on-chip detection of cell-free DNA fragments using GMR sensors: a translational application in cancer diagnostics using ALU elements. Anal Methods. 2016;8:119–28.CrossRefGoogle Scholar
  100. 100.
    Wei F, Lin CC, Joon A, Feng Z, Troche G, Lira ME, Chia D, Mao M, Ho CL, Su WC, Wong DTW. Noninvasive saliva-based EGFR gene mutation detection in patients with lung cancer. Am J Respir Crit Care Med. 2014;190:1117–26.CrossRefGoogle Scholar
  101. 101.
    Wei F, Yang J, Wong DTW. Detection of exosomal biomarker by electric field-induced release and measurement (EFIRM). Biosens Bioelectron. 2013;44:115–21.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici, c/o Dipartimento di Scienze ChimicheUniversità di CataniaCataniaItaly
  2. 2.Dipartimento di Scienze ChimicheUniversità di CataniaCataniaItaly
  3. 3.Consorzio Interuniversitario Istituto Nazionale Biostrutture e Biosistemi, c/o Dipartimento di Scienze ChimicheUniversità di CataniaCataniaItaly

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