Advertisement

Biomedical Microdevices

, 20:91 | Cite as

An automated microfluidic chemiluminescence immunoassay platform for quantitative detection of biomarkers

  • Xiaoping Min
  • Da Fu
  • Jianzhong Zhang
  • Juntian Zeng
  • Zhenyu Weng
  • Wendi Chen
  • Shiyin Zhang
  • Dongxu ZhangEmail author
  • Shengxiang GeEmail author
  • Jun Zhang
  • Ningshao Xia
Article

Abstract

A rapid, sensitive and quantitative biomarker detection platform is of great importance to the small clinic or point-of-care (POC) diagnosis. In this work, we realize that an automated diagnostic platform mainly includes two components: (1) an instrument that can complete all steps of the chemiluminescence immunoassay automatically and (2) an integrated microfluidic chip which is disposable and harmless. In the instrument, we adopt vacuum suction cups which are driven by linear motor to realize a simple, effective and convenient control. The method of acridine esterification chemiluminescence is adopted to achieve a quantitative detection, and a photomultiplier tube is used to detect photons from acridine ester producing in alkaline conditions. We use the laser cutting machine and hot press machine to accomplish the product of microfluidic chips. The automated microfluidics-based system is demonstrated by implementation of a chemiluminescence immunoassay for quantitative detection of ferritin. We observe alinear relationship between CL intensity and the concentration of ferritin from 5.1 to 1300 ng mL −1and the limit of detection (LoD) is 2.55 ng mL −1. At the same time, we also used the automated microfluidics-based system to test clinical serum samples. The whole process of chemiluminescence experiment can complete within 45 min. We realize that this lab-on-a-chip chemiluminescence immunoassay platform with features of automation and quantitation provides a promising strategy for POC diagnosis.

Keywords

Chemiluminescence Microfluidicchip Acridine ester Ferritin 

References

  1. D. Cai, M. Xiao, P. Xu, et al., An integrated microfluidic device utilizing dielectrophoresis and multiplex array PCR for point-of-care detection of pathogens. Lab Chip 14(20), 3917–3924 (2014)CrossRefGoogle Scholar
  2. Z. Chen, Y. Fu, F. Zhang, et al., Spinning micropipette liquid emulsion generator for single cell whole genome amplification. Lab Chip 16(23), 4512–4516 (2016)CrossRefGoogle Scholar
  3. Z. Chen, P. Liao, F. Zhang, et al., Centrifugal micro-channel array droplet generation for highly parallel digital PCR. Lab Chip 17(2), 235–240 (2017)CrossRefGoogle Scholar
  4. G. Czilwik, S.K. Vashist, V. Klein, et al., Magnetic chemiluminescent immunoassay for human C-reactive protein on the centrifugal microfluidics platform. RSC Adv. 5(76), 61906–61912 (2015)CrossRefGoogle Scholar
  5. R. Fan, O. Vermesh, A. Srivastava, et al., Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood. Nat. Biotechnol. 26(12), 1373–1378 (2008)CrossRefGoogle Scholar
  6. X. Fang, H. Chen, S. Yu, et al., Predicting viruses accurately by a multiplex microfluidic loop-mediated isothermal amplification chip. Anal. Chem. 83(3), 690–695 (2011)CrossRefGoogle Scholar
  7. W. Gan, B. Zhuang, P. Zhang, et al., A filter paper-based microdevice for low-cost, rapid, and automated DNA extraction and amplification from diverse sample types. Lab Chip 14(19), 3719–3728 (2014)CrossRefGoogle Scholar
  8. L. Gervais, N. de Rooij, E. Delamarche, et al., Microfluidic chips for point-of-care immunodiagnostics. Adv. Mater. 23(24), H151–H176 (2011)CrossRefGoogle Scholar
  9. R. Gorkin, J. Park, J. Siegrist, et al., Centrifugal microfluidics for biomedical applications. Lab Chip 10(14), 1758–1773 (2010)CrossRefGoogle Scholar
  10. K.A. Hyun, T.Y. Lee, S.H. Lee, et al., Two-stage microfluidic chip for selective isolation of circulating tumor cells (CTCs). Biosens. Bioelectron. 67, 86–92 (2015)CrossRefGoogle Scholar
  11. W. Lee, J. Jung, Y.K. Hahn, et al., A centrifugally actuated point-of-care testing system for the surface acoustic wave immunosensing of cardiac troponin I. Analyst 138(9), 2558–2566 (2013)CrossRefGoogle Scholar
  12. X. Li, P. Zwanenburg, X. Liu, Magnetic timing valves for fluid control in paper-based microfluidics. Lab Chip 13(13), 2609–2614 (2013)CrossRefGoogle Scholar
  13. Z. Li, S.Y. Mak, A. Sauret, et al., Syringe-pump-induced fluctuation in all-aqueous microfluidic system implications for flow rate accuracy. Lab Chip 14(4), 744–749 (2014)CrossRefGoogle Scholar
  14. C. Liu, X. Qiu, S. Ongagna, et al., A timer-actuated immunoassay cassette for detecting molecular markers in oral fluids. Lab Chip 9(6), 768–776 (2009)CrossRefGoogle Scholar
  15. X. Liu, M. Mwangi, X. Li, et al., Paper-based piezoresistive MEMS sensors. Lab Chip 11(13), 2189–2196 (2011)CrossRefGoogle Scholar
  16. W.W. Liu, Y. Zhu, Y.M. Feng, et al., Droplet-based multivolume digital polymerase chain reaction by a surface-assisted multifactor fluid segmentation approach. Anal. Chem. 89(1), 822–829 (2017)CrossRefGoogle Scholar
  17. E. Marzocchi, S. Grilli, L. Della Ciana, et al., Chemiluminescent detection systems of horseradish peroxidase employing nucleophilic acylation catalysts. Anal. Biochem. 377(2), 189–194 (2008)CrossRefGoogle Scholar
  18. M.P. McRae, G. Simmons, J. Wong, et al., Programmable bio-nanochip platform: A point-of-care biosensor system with the capacity to learn. Acc. Chem. Res. 49(7), 1359–1368 (2016)CrossRefGoogle Scholar
  19. S. Nahavandi, S. Baratchi, R. Soffe, et al., Microfluidic platforms for biomarker analysis. Lab Chip 14(9), 1496–1514 (2014)CrossRefGoogle Scholar
  20. A.H. Ng, U. Uddayasankar, A.R. Wheeler, Immunoassays in microfluidic systems. Anal. Bioanal. Chem. 397(3), 991–1007 (2010)CrossRefGoogle Scholar
  21. S. Nie, W.H. Henley, S.E. Miller, et al., An automated integrated platform for rapid and sensitive multiplexed protein profiling using human saliva samples. Lab Chip 14(6), 1087–1098 (2014)CrossRefGoogle Scholar
  22. C. Shen, P. Xu, Z. Huang, et al., Bacterial chemotaxis on SlipChip. Lab Chip 14(16), 3074–3080 (2014)CrossRefGoogle Scholar
  23. Y. Song, H.C. Shum, Monodisperse w/w/w double emulsion induced by phase separation. Langmuir 28(33), 12054–12059 (2012)CrossRefGoogle Scholar
  24. S. Zehnle, F. Schwemmer, G. Roth, et al., Centrifugo-dynamic inward pumping of liquids on a centrifugal microfluidic platform. Lab Chip 12(24), 5142–5145 (2012)CrossRefGoogle Scholar
  25. Y. Zhang, Y. Zhu, B. Yao, et al., Nanolitre droplet array for real time reverse transcription polymerase chain reaction. Lab Chip 11(8), 1545–1549 (2011)CrossRefGoogle Scholar
  26. S. Zhao, J. Liu, Y. Huang, et al., Introducing chemiluminescence resonance energy transfer into immunoassay in a microfluidic format for an improved assay sensitivity. Chem. Commun. 48(5), 699–701 (2012)CrossRefGoogle Scholar
  27. B. Zhuang, J. Han, G. Xiang, et al., A fully integrated and automated microsystem for rapid pharmacogenetic typing of multiple warfarin-related single-nucleotide polymorphisms. Lab Chip 16(1), 86–95 (2016)CrossRefGoogle Scholar
  28. H. Zirath, J.R. Peham, G. Schnetz, et al., A compact and integrated immunoassay with on-chip dispensing and magnetic particle handling. Biomed. Microdevices 18(1), 16 (2016)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xiaoping Min
    • 1
    • 2
    • 3
  • Da Fu
    • 2
    • 4
  • Jianzhong Zhang
    • 2
    • 4
  • Juntian Zeng
    • 2
  • Zhenyu Weng
    • 2
    • 4
  • Wendi Chen
    • 2
  • Shiyin Zhang
    • 2
    • 3
    • 4
  • Dongxu Zhang
    • 2
    • 3
    • 4
    Email author
  • Shengxiang Ge
    • 2
    • 3
    • 4
    Email author
  • Jun Zhang
    • 2
    • 3
    • 4
  • Ningshao Xia
    • 2
    • 3
    • 4
  1. 1.School of Information Science and TechnologyXiamen UniversityXiamenChina
  2. 2.National Institute of Diagnostics and Vaccine Development in Infectious DiseaseXiamenChina
  3. 3.State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsXiamen UniversityXiamenChina
  4. 4.School of Public HealthXiamen UniversityXiamenChina

Personalised recommendations