Simultaneous pre-concentration and separation on simple paper-based analytical device for protein analysis

Research Paper

Abstract

In this work, fast isoelectric focusing (IEF) was successfully implemented on an open paper fluidic channel for simultaneous concentration and separation of proteins from complex matrix. With this simple device, IEF can be finished in 10 min with a resolution of 0.03 pH units and concentration factor of 10, as estimated by color model proteins by smartphone-based colorimetric detection. Fast detection of albumin from human serum and glycated hemoglobin (HBA1c) from blood cell was demonstrated. In addition, off-line identification of the model proteins from the IEF fractions with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was also shown. This PAD IEF is potentially useful either for point of care test (POCT) or biomarker analysis as a cost-effective sample pretreatment method.

Keywords

Isoelectric focusing (IEF) Paper-based analytical device (PAD) Point-of-care test (POCT) Protein sample pretreatment 

Notes

Acknowledgements

Following financial supports are acknowledged: National Natural Science Foundation of China (21575019), Education Department of the Liaoning Province of China (LZ2015036), National Basic Research Program of China (2014CBA02003), Novo Nordisk-Chinese Academy of Sciences Research Fund (NNCAS-2015-11), and the Strategic Priority Research Programs of the Chinese Academy of Sciences (XDA12030202).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2017_809_MOESM1_ESM.pdf (186 kb)
ESM 1 (PDF 186 kb)

References

  1. 1.
    Martinez AW, Phillips ST, Butte MJ, Whitesides GM. Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew Chem Int Ed. 2007;46(8):1318–20.CrossRefGoogle Scholar
  2. 2.
    Boehle KE, Gilliand J, Wheeldon CR, Holder A, Adkins JA, Geiss BJ, et al. Utilizing paper-based devices for antimicrobial-resistant bacteria detection. Angew Chem Int Ed. 2017;24(129):6990–4.CrossRefGoogle Scholar
  3. 3.
    Li M, Tian J, Al-Tamimi M, Shen W. Paper-based blood typing device that reports patient’s blood type “in writing”. Angew Chem Int Ed. 2012;124(22):5593–7.CrossRefGoogle Scholar
  4. 4.
    Liu H, Xiang Y, Lu Y, Crooks RM. Aptamer-based origami paper analytical device for electrochemical detection of adenosine. Angew Chem Int Ed. 2012;28(124):7031–4.CrossRefGoogle Scholar
  5. 5.
    Yang Y, Noviana E, Nguyen MP, Geiss BJ, Dandy DS, Henry CS. Paper based microfluidic devices: emerging themes and applications. Anal Chem. 2016;89(1):71–91.CrossRefGoogle Scholar
  6. 6.
    Cheng CM, Martinez AW, Gong J, Mace CR, Phillips ST, Carrilho E, et al. Angew Chem Int Ed Engl. 2010;49(28):4771–4.CrossRefGoogle Scholar
  7. 7.
    Zang D, Ge L, Yan M, Song X, Yu J. Electrochemical immunoassay on a 3D microfluidic paper-based device. Chem Commun. 2012;48(39):4683–5.CrossRefGoogle Scholar
  8. 8.
    Zhang Y, Ge L, Li M, Yan M, Ge S, Yu J, et al. Flexible paper-based ZnO nanorod light-emitting diodes induced multiplexed photoelectrochemical immunoassay. Chem Commun. 2014;50(12):1417–9.CrossRefGoogle Scholar
  9. 9.
    Wu Y, Xue P, Kang Y, Hui KM. Paper-based microfluidic electrochemical immunodevice integrated with nanobioprobes onto graphene film for ultrasensitive multiplexed detection of cancer biomarkers. Anal Chem. 2013;85(18):8661–8.CrossRefGoogle Scholar
  10. 10.
    Wang S, Ge L, Song X, Yu J, Ge S, Huang J, et al. Paper based chemiluminescence ELISA: lab-on-paper based on chitosan modified paper device and wax-screen-printing. Biosens Bioelectron. 2012;31(1):212–8.CrossRefGoogle Scholar
  11. 11.
    Ge L, Yan J, Song X, Yan M, Ge S, Yu J. Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing. Biomaterials. 2012;33(4):1024–31.CrossRefGoogle Scholar
  12. 12.
    Moghadam BY, Connelly KT, Posner JD. Isotachophoretic preconcenetration on paper-based microfluidic devices. Anal Chem. 2014;86(12):5829–37.CrossRefGoogle Scholar
  13. 13.
    Moghadam BY, Connelly KT, Posner JD. Two orders of magnitude improvement in detection limit of lateral flow assays using isotachophoresis. Anal Chem. 2015;87(2):1009–17.CrossRefGoogle Scholar
  14. 14.
    Li X, Luo L, Crooks RM. Low-voltage paper isotachophoresis device for DNA focusing. Lab Chip. 2015;15(20):4090–8.CrossRefGoogle Scholar
  15. 15.
    Ma B, Song YZ, Niu JC, Wu ZY. Highly efficient sample stacking by enhanced field amplification on a simple paper device. Lab Chip. 2016;16(18):3460–5.CrossRefGoogle Scholar
  16. 16.
    Gong MM, Nosrati R, San Gabriel MC, Zini A, Sinton D. Direct DNA analysis with paper-based ion concentration polarization. J Am Chem Soc. 2015;137(43):13913–9.CrossRefGoogle Scholar
  17. 17.
    Ge L, Wang S, Ge S, Yu J, Yan M, Li N, et al. Electrophoretic separation in a microfluidic paper-based analytical device with an on-column wireless electrogenerated chemiluminescence detector. Chem Commun (Camb). 2014;50(43):5699–702.CrossRefGoogle Scholar
  18. 18.
    OuYang L, Wang C, Du F, Zheng T, Liang H. Electrochromatographic separations of multi-component metal complexes on a microfluidic paper-based device with a simplified photolithography. RSC Adv. 2014;4(3):1093–101.CrossRefGoogle Scholar
  19. 19.
    Xu C, Lin W, Cai L. Demonstrating electrophoretic separation in a straight paper channel delimited by a hydrophobic wax barrier. J Chem Educ. 2016;93(5):903–5.CrossRefGoogle Scholar
  20. 20.
    Nanthasurasak P, Cabot JM, See HH, Guijt RM, Breadmore MC. Electrophoretic separations on paper: past, present, and future—a review. Anal Chim Acta. 2017;985:7–23.CrossRefGoogle Scholar
  21. 21.
    Luo L, Li X, Crooks RM. Low-voltage origami-paper-based electrophoretic device for rapid protein separation. Anal Chem. 2014;86(24):12390–7.CrossRefGoogle Scholar
  22. 22.
    Z-Y W, Ma B, Xie S-F, Liu K, Fang F. Simultaneous electrokinetic concentration and separation of proteins on a paper-based analytical device. RSC Adv. 2017;7(7):4011–6.CrossRefGoogle Scholar
  23. 23.
    Gaspar C, Sikanen T, Franssila S, Jokinen V. Inkjet printed silver electrodes on macroporous paper for a paper-based isoelectric focusing device. Biomicrofluidics. 2016;10(6):064120.CrossRefGoogle Scholar
  24. 24.
    Gorg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technology for proteomics. Proteomics. 2004;4(12):3665–85.CrossRefGoogle Scholar
  25. 25.
    Bjellqvist B, Ek K, Righetti PG, Gianazza E, Görg A, Westermeier R, et al. Isoelectric focusing in immobilized pH gradients: principle, methodology and some applications. J Biochem Biophys Methods. 1982;6(4):317–39.CrossRefGoogle Scholar
  26. 26.
    Righetti PG, Sebastiano R, Citterio A. Capillary electrophoresis and isoelectric focusing in peptide and protein analysis. Proteomics. 2013;13(2):325–40.CrossRefGoogle Scholar
  27. 27.
    Ambler J. Isoelectric focussing of proteins on cellulose acetate gel membranes. Clin Chim Acta. 1978;85(2):183–91.CrossRefGoogle Scholar
  28. 28.
    Ambler J, Walker G. Isoelectric focusing of serum proteins on modified thin cellulose-acetate membranes. Clin Chem. 1979;25(7):1320–2.Google Scholar
  29. 29.
    Ambler J. Isoelectric focusing on cellulose acetate membranes: an up-date on materials and methods. Electrophoresis. 1989;10(7):520–3.CrossRefGoogle Scholar
  30. 30.
    Toda T, Sano-Shiba K, Cho H, Soon PL, Nakao M, Ohashi M. An improved method of high-voltage isoelectric focusing on cellulose acetate membranes. Electrophoresis. 1988;9(3):149–15019.CrossRefGoogle Scholar
  31. 31.
    Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin Epidemiol. 1997;50(6):693–703.CrossRefGoogle Scholar
  32. 32.
    Friedman AN, Fadem SZ. Reassessment of albumin as a nutritional marker in kidney disease. J Am Soc Nephrol. 2010;21(2):223–30.CrossRefGoogle Scholar
  33. 33.
    Nathan DM, Singer DE, Hurxthal K, Goodson JD. The clinical information value of the glycosylated hemoglobin assay. N Engl J Med. 1984;310(6):341–6.CrossRefGoogle Scholar
  34. 34.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA. 1988;260(19):2864–71.CrossRefGoogle Scholar
  35. 35.
    Li S, Dong JY, Guo CG, YX W, Zhang W, Fan LY, et al. A stable and high-resolution isoelectric focusing capillary array device for micropreparative separation of proteins. Talanta. 2013;116:259–65.CrossRefGoogle Scholar
  36. 36.
    Conti M, Gelfi C, Bosisio AB, Righetti PG. Quantitation of glycated hemoglobins in human adult blood by capillary isoelectric focusing. Electrophoresis. 1996;17(10):1590–6.CrossRefGoogle Scholar
  37. 37.
    Huang HL, Stasyk T, Morandell S, Dieplinger H, Falkensammer G, Griesmacher A, et al. Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/MALDI-TOF/TOF and data validation by routine clinical assays. Electrophoresis. 2006;27(8):1641–50.CrossRefGoogle Scholar
  38. 38.
    Li J, Xie Z, Shi L, Zhao Z, Hou J, Chen X, et al. Purification, identification and profiling of serum amyloid A proteins from sera of advanced-stage cancer patients. J Chromatogr B. 2012;889:3–9.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research Center for Analytical Sciences, Chemistry Department College of SciencesNortheastern UniversityShenyangChina
  2. 2.The Key Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of BiophysicsChinese Academy of SciencesBeijingChina

Personalised recommendations