Nano Research

, Volume 10, Issue 7, pp 2296–2310 | Cite as

Toward integrated detection and graphene-based removal of contaminants in a lab-on-a-chip platform

  • Andrzej Chałupniak
  • Arben MerkoçiEmail author
Research Article


A novel, miniaturized microfluidic platform was developed for the simultaneous detection and removal of polybrominated diphenyl ethers (PBDEs). The platform consists of a polydimethylsiloxane (PDMS) microfluidic chip for an immunoreaction step, a PDMS chip with an integrated screen-printed electrode (SPCE) for detection, and a PDMS-reduced graphene oxide (rGO) chip for physical adsorption and subsequent removal of PBDE residues. The detection was based on competitive immunoassay-linked binding between PBDE and PBDE modified with horseradish peroxidase (HRP-PBDE) followed by the monitoring of enzymatic oxidation of o-aminophenol (o-AP) using square wave anodic stripping voltammetry (SW-ASV). PBDE was detected with good sensitivity and a limit of detection similar to that obtained with a commercial colorimetric test (0.018 ppb), but with the advantage of using lower reagent volumes and a reduced analysis time. The use of microfluidic chips also provides improved linearity and a better reproducibility in comparison to those obtained with batch-based measurements using screen-printed electrodes. In order to design a detection system suitable for toxic compounds such as PBDEs, a reduced graphene oxide–PDMS composite was developed and optimized to obtain increased adsorption (based on both the hydrophobicity and π–π stacking between rGO and PBDE molecules) compared to those of non-modified PDMS. To the best of our knowledge, this is the first demonstration of electrochemical detection of flame retardants and a novel application of the rGO-PDMS composite in a biosensing system. This system can be easily applied to detect any analyte using the appropriate immunoassay and it supports operation in complex matrices such as seawater.


electrochemistry microfluidics graphene oxide flame retardants lab on a chip polydimethylsiloxane 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



We acknowledge FP7 EU Project “SMS” (No. 613844). ICN2 acknowledges support from the Severo Ochoa Program (MINECO, No. SEV-2013-0295) and Secretaria d’Universitats i Recerca del Departament d′Economia i Coneixement de la Generalitat de Catalunya (2014 SGR 260). The authors would also like to thank Dr. Mariana Medina Sánchez for microfluidic mold fabrication that was employed in GO-CHIP development.

Supplementary material

12274_2016_1420_MOESM1_ESM.pdf (931 kb)
Toward integrated detection and graphene-based removal of contaminants in a lab-on-a-chip platform


  1. [1]
    Medina-Sánchez, M.; Miserere, S.; Morales-Narváez, E.; Merkoçi, A. On-chip magneto-immunoassay for Alzheimer’s biomarker electrochemical detection by using quantum dots as labels. Biosens. Bioelectron. 2014, 54, 279–284.CrossRefGoogle Scholar
  2. [2]
    Marasso, S. L.; Giuri, E.; Canavese, G.; Castagna, R.; Quaglio, M.; Ferrante, I.; Perrone, D.; Cocuzza, M. A multilevel lab on chip platform for DNA analysis. Biomed. Microdevices 2011, 13, 19–27.CrossRefGoogle Scholar
  3. [3]
    Lee, H. H.; Yager, P. Microfluidic lab-on-a-chip for microbial identification on a DNA microarray. Biotechnol. Bioprocess Eng. 2007, 12, 634–639.CrossRefGoogle Scholar
  4. [4]
    Kurbanoglu, S.; Mayorga-Martinez, C. C.; Medina-Sánchez, M.; Rivas, L.; Ozkan, S. A.; Merkoçi, A. Antithyroid drug detection using an enzyme cascade blocking in a nanoparticle-based lab-on-a-chip system. Biosens. Bioelectron. 2015, 67, 670–676.CrossRefGoogle Scholar
  5. [5]
    Kimura, H.; Ikeda, T.; Nakayama, H.; Sakai, Y.; Fujii, T. An on-chip small intestine-liver model for pharmacokinetic studies. J. Lab. Autom. 2015, 20, 265–273.CrossRefGoogle Scholar
  6. [6]
    Ozhikandathil, J.; Badilescu, S.; Packirisamy, M. Detection of bovine growth hormone using conventional and lab-ona-chip technologies: A review. Int. J. Adv. Eng. Sci. Appl. Math. 2015, 7, 177–190.CrossRefGoogle Scholar
  7. [7]
    Ozhikandathil, J.; Packirisamy, M. Nano-islands integrated evanescence-based lab-on-a-chip on silica-on-silicon and polydimethylsiloxane hybrid platform for detection of recombinant growth hormone. Biomicrofluidics 2012, 6, 46501.CrossRefGoogle Scholar
  8. [8]
    Medina-Sánchez, M.; Cadevall, M.; Ros, J.; Merkoçi, A. Eco-friendly electrochemical lab-on-paper for heavy metal detection. Anal. Bioanal. Chem. 2015, 407, 8445–8449.CrossRefGoogle Scholar
  9. [9]
    da Costa, E. T.; Santos, M. F. S.; Jiao, H.; do Lago, C. L.; Gutz, I. G. R.; Garcia, C. D. Fast production of microfluidic devices by CO2 laser engraving of wax-coated glass slides. Electrophoresis 2016, 37, 1691–1695.CrossRefGoogle Scholar
  10. [10]
    Ambrosi, A.; Guix, M.; Merkoçi, A. Magnetic and electrokinetic manipulations on a microchip device for bead-based immunosensing applications. Electrophoresis 2011, 32, 861–869.CrossRefGoogle Scholar
  11. [11]
    Medina-Sánchez, M.; Miserere, S.; Merkoçi, A. Nanomaterials and lab-on-a-chip technologies. Lab Chip 2012, 12, 1932–1943.CrossRefGoogle Scholar
  12. [12]
    Li, S. G.; Xu, Z. G.; Mazzeo, A.; Burns, D. J.; Fu, G.; Dirckx, M.; Shilpiekandula, V.; Chen, X.; Nayak, N. C.; Wong, E. et al. Review of production of microfluidic devices: Material, manufacturing and metrology. In Proceedings of the SPIE 6993, MEMS, MOEMS and Micromachining III, Strasbourg, France, 2008.Google Scholar
  13. [13]
    Bhise, N. S.; Manoharan, V.; Massa, S.; Tamayol, A.; Ghaderi, M.; Miscuglio, M.; Lang, Q.; Zhang, Y. S.; Shin, S. R.; Calzone, G. et al. A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication 2016, 8, 014101.CrossRefGoogle Scholar
  14. [14]
    He, J. K.; Chen, R. M.; Lu, Y. J.; Zhan, L.; Liu, Y. X.; Li, D. C.; Jin, Z. M. Fabrication of circular microfluidic network in enzymatically-crosslinked gelatin hydrogel. Mater. Sci. Eng. C-Mater. Biol. Appl. 2016, 59, 53–60.CrossRefGoogle Scholar
  15. [15]
    Xia, Y. N.; Whitesides, G. M. Soft lithography. Ann. Rev. Mater. Sci. 1998, 28, 153–184.CrossRefGoogle Scholar
  16. [16]
    Mayorga-Martinez, C. C.; Hlavata, L.; Miserere, S.; López-Marzo, A.; Labuda, J.; Pons, J.; Merkoçi, A. An integrated phenol “sensoremoval” microfluidic nanostructured platform. Biosens. Bioelectron. 2014, 55, 355–359.CrossRefGoogle Scholar
  17. [17]
    Mayorga-Martinez, C. C.; Hlavata, L.; Miserere, S.; López-Marzo, A.; Labuda, J.; Pons, J.; Merkoçi, A. Nanostructured CaCO3-poly(ethyleneimine) microparticles for phenol sensing in fluidic microsystem. Electrophoresis 2013, 34, 2011–2016.CrossRefGoogle Scholar
  18. [18]
    Medina-Sánchez, M.; Mayorga-Martinez, C.; Watanabe, T.; Ivandini, T.; Honda, Y.; Pino, F.; Nakata, K.; Fujishima, A.; Einaga, Y.; Merkoçi, A. Microfluidic platform for environmental contaminants sensing and degradation based on boron-doped diamond electrodes. Biosens. Bioelectron. 2016, 75, 365–374.CrossRefGoogle Scholar
  19. [19]
    Tan, H. Y.; Loke, W. K.; Nguyen, N. T.; Tan, S. N.; Tay, N. B.; Wang, W.; Ng, S. H. Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin. Biomed. Microdevices 2014, 16, 269–275.CrossRefGoogle Scholar
  20. [20]
    Ibarlucea, B.; Díez-Gil, C.; Ratera, I.; Veciana, J.; Caballero, A.; Zapata, F.; Tárraga, A.; Molina, P.; Demming, S.; Büttgenbach, S. et al. PDMS based photonic lab-on-a-chip for the selective optical detection of heavy metal ions. Analyst 2013, 138, 839–844.CrossRefGoogle Scholar
  21. [21]
    Feng, C. Y.; Wei, J. F.; Li, Y. J.; Yang, Y. S.; Wang, Y. H.; Lu, L.; Zheng, G. X. An on-chip pollutant toxicity determination based on marine microalgal swimming inhibition. Analyst 2016, 141, 1761–1771.CrossRefGoogle Scholar
  22. [22]
    Zheng, G. X.; Li, Y. J.; Qi, L. L.; Liu, X. M.; Wang, H.; Yu, S. P.; Wang, Y. H. Marine phytoplankton motility sensor integrated into a microfluidic chip for high-throughput pollutant toxicity assessment. Mar. Pollut. Bull. 2014, 84, 147–154.CrossRefGoogle Scholar
  23. [23]
    Zheng, G. X.; Wang, Y. H.; Wang, Z. M.; Zhong, W. L.; Wang, H.; Li, Y. J. An integrated microfluidic device in marine microalgae culture for toxicity screening application. Mar. Pollut. Bull. 2013, 72, 231–243.CrossRefGoogle Scholar
  24. [24]
    Hooper, K.; McDonald, T. A. The PBDEs: An emerging environmental challenge and another reason for breast-milk monitoring programs. Environ. Health Perspect. 2000, 108, 387–392.CrossRefGoogle Scholar
  25. [25]
    Andrade, N. A.; McConnell, L. L.; Torrents, A.; Ramirez, M. Persistence of polybrominated diphenyl ethers in agricultural soils after biosolids applications. J. Agric. Food Chem. 2010, 58, 3077–3084.CrossRefGoogle Scholar
  26. [26]
    Guo, W. H.; Holden, A.; Smith, S. C.; Gephart, R.; Petreas, M.; Park, J. S. PBDE levels in breast milk are decreasing in California. Chemosphere 2016, 150, 505–513.CrossRefGoogle Scholar
  27. [27]
    Ward, J.; Mohapatra, S. P.; Mitchell, A. An overview of policies for managing polybrominated diphenyl ethers (PBDEs) in the Great Lakes Basin. Environ. Int. 2008, 34, 1148–1156.CrossRefGoogle Scholar
  28. [28]
    Darnerud, P. O.; Eriksen, G. S.; Jóhannesson, T.; Larsen, P. B.; Viluksela, M. Polybrominated diphenyl ethers: Occurrence, dietary exposure, and toxicology. Environ. Health Perspect. 2001, 109, 49–68.CrossRefGoogle Scholar
  29. [29]
    Porterfield, S. P. Vulnerability of the developing brain to thyroid abnormalities: Environmental insults to the thyroid system. Environ. Health Perspect. 1994, 102, 125–130.CrossRefGoogle Scholar
  30. [30]
    Ahn, K. C.; Gee, S. J.; Tsai, H. J.; Bennett, D.; Nishioka, M. G.; Blum, A.; Fishman, E.; Hammock, B. D. Immunoassay for monitoring environmental and human exposure to the polybrominated diphenyl ether BDE-47. Environ. Sci. Technol. 2009, 43, 7784–7790.CrossRefGoogle Scholar
  31. [31]
    Butryn, D. M.; Gross, M. S.; Chi, L. H.; Schecter, A.; Olson, J. R.; Aga, D. S. "One-shot" analysis of polybrominated diphenyl ethers and their hydroxylated and methoxylated analogs in human breast milk and serum using gas chromatography-tandem mass spectrometry. Anal. Chim. Acta 2015, 892, 140–147.CrossRefGoogle Scholar
  32. [32]
    Li, Z.; Li, C.; Lin, D.; Kang, W. J.; Pan, D. Y.; Wu, M. H. GC/MS analysis of polybrominated diphenyl ethers in vegetables collected from Shanghai, China. In Proceedings of the 2013 International Conference on Material Science and Environmental Engineering (MSEE 2013), 2013, pp 292–296.Google Scholar
  33. [33]
    Liu, Q.; Shi, J. B.; Sun, J. T.; Wang, T.; Zeng, L. X.; Zhu, N. L.; Jiang, G. B. Graphene-assisted matrix solid-phase dispersion for extraction of polybrominated diphenyl ethers and their methoxylated and hydroxylated analogs from environmental samples. Anal. Chim. Acta 2011, 708, 61–68.CrossRefGoogle Scholar
  34. [34]
    Zhang, H.; Lee, H. K. Plunger-in-needle solid-phase microextraction with graphene-based sol–gel coating as sorbent for determination of polybrominated diphenyl ethers. J. Chromatogr. A 2011, 1218, 4509–4516.CrossRefGoogle Scholar
  35. [35]
    Orozco, J.; Mercante, L. A.; Pol, R.; Merkoçi, A. Graphenebased Janus micromotors for the dynamic removal of pollutants. J. Mater. Chem. A 2016, 4, 3371–3378.CrossRefGoogle Scholar
  36. [36]
    Chen, M. T.; Tao, T.; Zhang, L.; Gao, W.; Li, C. Z. Highly conductive and stretchable polymer composites based on graphene/MWCNT network. Chem. Commun. 2013, 49, 1612–1614.CrossRefGoogle Scholar
  37. [37]
    Shahzad, M. I.; Giorcelli, M.; Shahzad, N.; Guastella, S.; Castellino, M.; Jagdale, P.; Tagliaferro, A. Study of carbon nanotubes based polydimethylsiloxane composite films. In Proceedings of the 6th Vacuum and Surface Sciences Conference of Asia and Australia (VASSCAA-6), Islamabad, Pakistan, 2013.Google Scholar
  38. [38]
    Lee, A. C.; Liu, G. D.; Heng, C. K.; Tan, S. N.; Lim, T. M.; Lin, Y. H. Sensitive electrochemical detection of horseradish peroxidase at disposable screen-printed carbon electrode. Electroanalysis 2008, 20, 2040–2046.CrossRefGoogle Scholar
  39. [39]
    Medina-Sánchez, M.; Miserere, S.; Marín, S.; Aragay, G.; Merkoçi, A. On-chip electrochemical detection of CdS quantum dots using normal and multiple recycling flow through modes. Lab Chip 2012, 12, 2000–2005.CrossRefGoogle Scholar
  40. [40]
    Zhang, J. L.; Yang, H. J.; Shen, G. X.; Cheng, P.; Zhang, J. Y.; Guo, S. W. Reduction of graphene oxide via L-ascorbic acid. Chem. Commun. 2010, 46, 1112–1114.CrossRefGoogle Scholar
  41. [41]
    Nourani, S.; Ghourchian, H.; Boutorabi, S. M. Magnetic nanoparticle-based immunosensor for electrochemical detection of hepatitis B surface antigen. Anal. Biochem. 2013, 441, 1–7.CrossRefGoogle Scholar
  42. [42]
    Xu, R. Q.; Lu, Y. Q.; Jiang, C. H.; Chen, J.; Mao, P.; Gao, G. H.; Zhang, L. B.; Wu, S. Facile fabrication of threedimensional graphene foam/poly(dimethylsiloxane) composites and their potential application as strain sensor. ACS Appl. Mater. Interfaces 2014, 6, 13455–13460.CrossRefGoogle Scholar
  43. [43]
    Ju, T.; Ge, W.; Jiang, T.; Chai, C. Polybrominated diphenyl ethers in dissolved and suspended phases of seawater and in surface sediment from Jiaozhou Bay, North China. Sci. Total Environ. 2016, 557–558, 571–578.CrossRefGoogle Scholar
  44. [44]
    Lammel, G.; Audy, O.; Besis, A.; Efstathiou, C.; Eleftheriadis, K.; Kohoutek, J.; Kukucka, P.; Mulder, M. D.; Pribylová, P.; Prokeš, R. et al. Air and seawater pollution and air-sea gas exchange of persistent toxic substances in the Aegean Sea: Spatial trends of PAHs, PCBs, OCPs and PBDEs. Environ. Sci. Pollut. Res. 2015, 22, 11301–11313.CrossRefGoogle Scholar
  45. [45]
    Cristale, J.; Hurtado, A.; Gómez-Canela, C.; Lacorte, S. Occurrence and sources of brominated and organophosphorus flame retardants in dust from different indoor environments in Barcelona, Spain. Environ. Res. 2016, 149, 66–76.CrossRefGoogle Scholar
  46. [46]
    Xu, D.; Zhu, W.; Wang, C.; Tian, T.; Li, J.; Lan, Y.; Zhang, G. X.; Zhang, D. Q.; Li, G. T. Label-free detection and discrimination of poly-brominated diphenylethers using molecularly imprinted photonic cross-reactive sensor arrays. Chem. Commun. 2014, 50, 14133–14136.CrossRefGoogle Scholar
  47. [47]
    Radhakrishnan, R.; Suni, I. I.; Bever, C. S.; Hammock, B. D. Impedance biosensors: Applications to sustainability and remaining technical challenges. ACS Sustainable Chem. Eng. 2014, 2, 1649–1655.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Catalan Institute of Nanoscience and Nanotechnology (ICN2)CSIC and The Barcelona Institute of Science and Technology, Campus UAB, BellaterraBarcelonaSpain
  2. 2.ICREA, Pg. Lluís Companys 23BarcelonaSpain

Personalised recommendations