Abstract
A three-dimensional microfluidic chip that combines sample manipulation and SERS detection on-chip was developed. This was successfully achieved by chip integration of a nanoporous polycarbonate track-etched (PCTE) membrane which connects microfluidic channels on two different levels with each other. The membrane fulfills two functions at the same time. On the one hand, it enables sample enrichment by selective electrokinetic transport processes through the membrane. On the other hand, the silver nanoparticle–coated backside of the same membrane enables SERS detection of the enriched analytes. The SERS substrate performance and the electrokinetic transport phenomena were studied using Rhodamine B (RhB) by Raman microscopy and fluorescence video microscopy. After system validation, the approach was attested by on-chip processing of a complex food sample. In a proof-of-concept study, the microfluidic device with the SERS substrate membrane was used to detect a concentration of 1 ppm melamine (705 cm−1) in whole milk. Electrokinetic transport across the nanoporous SERS substrate facilitates the extraction of analyte molecules from a sample channel into a detection channel via a potential gradient, thus easily removing obscuring compounds present in the sample matrix. The SERS signal of the analyte could be significantly increased by on-target sample drying. This was achieved by guiding an additional gas flow over the membrane which further extends the microfluidic functionality of the chip device. The proposed method possesses the advantages of combining a rapid (within 15 min) sample clean-up using electrokinetic transport in a three-dimensional microfluidic device which is highly suitable for sensitive and selective SERS detection of chemical and biological analytes.
Similar content being viewed by others
References
Moskovits M. Surface-enhanced Raman spectroscopy: a brief retrospective. J Raman Spectrosc. 2005;36:485–96. https://doi.org/10.1002/jrs.1362.
Fleischmann M, Hendra PJ, McQuillan AJ. Raman spectra of pyridine adsorbed at a silver electrode. Chem Phys Lett. 1974;26:163–6. https://doi.org/10.1016/0009-2614(74)85388-1.
Kneipp K, Wang Y, Kneipp H, Perelman LT, Itzkan I, Dasari RR, et al. Single molecule detection using surface-enhanced Raman scattering (SERS). Phys Rev Lett. 1997;78:1667–70. https://doi.org/10.1103/PhysRevLett.78.1667.
Giovannozzi AM, Rolle F, Sega M, Abete MC, Marchis D, Rossi AM. Rapid and sensitive detection of melamine in milk with gold nanoparticles by surface enhanced Raman scattering. Food Chem. 2014;159:250–6. https://doi.org/10.1016/j.foodchem.2014.03.013.
Premasiri WR, Clarke RH, Londhe S, Womble ME. Determination of cyanide in waste water by low-resolution surface enhanced Raman spectroscopy on sol-gel substrates. J Raman Spectrosc. 2001;32:919–22. https://doi.org/10.1002/jrs.762.
Cheng IF, Chang HC, Chen TY, Hu C, Yang FL. Rapid (<5 min) identification of pathogen in human blood by electrokinetic concentration and surface-enhanced raman spectroscopy. Sci Rep. 2013;3:2365. https://doi.org/10.1038/srep02365.
Li X, Feng S, Hu Y, Sheng W, Zhang Y, Yuan S, et al. Rapid detection of melamine in milk using immunological separation and surface Enhanced raman spectroscopy. J Food Sci. 2015;80:C1196–201. https://doi.org/10.1111/1750-3841.12876.
Li R, Yang J, Han J, Liu J, Huang M. Quantitative determination of melamine in milk using Ag nanoparticle monolayer film as SERS substrate. Phys E Low-Dimens Syst Nanostruct. 2017;88:164–8. https://doi.org/10.1016/j.physe.2016.12.013.
Shanmukh S, Jones L, Driskell J, Zhao Y, Dluhy R, Tripp RA. Rapid and sensitive detection of respiratory virus molecular signatures using a silver nanorod array SERS substrate. Nano Lett. 2006;6:2630–6. https://doi.org/10.1021/nl061666f.
Chen L, Choo J. Recent advances in surface-enhanced Raman scattering detection technology for microfluidic chips. Electrophoresis. 2008;29:1815–28. https://doi.org/10.1002/elps.200700554.
White IM, Yazdi SH, Yu WW. Optofluidic SERS: synergizing photonics and microfluidics for chemical and biological analysis. Microfluid Nanofluid. 2012;13:205–16. https://doi.org/10.1007/s10404-012-0962-2.
Jahn IJ, Žukovskaja O, Zheng X-S, Weber K, Bocklitz TW, Cialla-May D, et al. Surface-enhanced Raman spectroscopy and microfluidic platforms: challenges, solutions and potential applications. Analyst. 2017;142:1022–47. https://doi.org/10.1039/C7AN00118E.
Tycova A, Gerhardt RF, Belder D. Surface enhanced Raman spectroscopy in microchip electrophoresis. J Chromatogr A. 2018;1541:39–46. https://doi.org/10.1016/j.chroma.2018.02.014.
Deng Y-L, Juang Y-J. Electrokinetic trapping and surface enhanced Raman scattering detection of biomolecules using optofluidic device integrated with a microneedles array. Biomicrofluidics. 2013;7:014111. https://doi.org/10.1063/1.4793224.
Kohlheyer D, Eijkel JCT, Schlautmann S, van den Berg A, Schasfoort RBM. Microfluidic high-resolution free-flow isoelectric focusing. Anal Chem. 2007;79:8190–8. https://doi.org/10.1021/ac071419b.
Bottenus D, Jubery TZ, Ouyang Y, Dong W-J, Dutta P, Ivory CF. 10 000-fold concentration increase of the biomarker cardiac troponin I in a reducing union microfluidic chip using cationic isotachophoresis. Lab Chip. 2011;11:890. https://doi.org/10.1039/c04lc00490a.
Huh YS, Chung AJ, Cordovez B, Erickson D. Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells. Lab Chip. 2009;9:433–9. https://doi.org/10.1039/B809702J.
Li D, Duan H, Wang Y, Zhang Q, Cao H, Deng W, et al. On-site preconcentration of pesticide residues in a drop of seawater by using electrokinetic trapping, and their determination by surface-enhanced Raman scattering. Microchim Acta. 2018;185:10. https://doi.org/10.1007/s00604-017-2580-x.
Li D, Li DW, Fossey JS, Long YT. Portable surface-enhanced raman scattering sensor for rapid detection of aniline and phenol derivatives by on-site electrostatic preconcentration. Anal Chem. 2010;82:9299–305. https://doi.org/10.1021/ac101812x.
Park M, Oh Y-J, Park S-G, Yang S-B, Jeong K-H. Electrokinetic preconcentration of small molecules within volumetric electromagnetic hotspots in surface enhanced Raman scattering. Small. 2015;11:2487–92. https://doi.org/10.1002/smll.201402942.
Kuo TC, Cannon DM, Shannon MA, Bohn PW, Sweedler JV. Hybrid three-dimensional nanofluidic/microfluidic devices using molecular gates. Sensors Actuators A Phys. 2003;102:223–33. https://doi.org/10.1016/S0924-4247(02)00394-1.
Flachsbart BR, Wong K, Iannacone JM, Abante EN, Vlach RL, Rauchfuss PA, et al. Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing. Lab Chip. 2006;6:667. https://doi.org/10.1039/b514300d.
Aran K, Fok A, Sasso LA, Kamdar N, Guan Y, Sun Q, et al. Microfiltration platform for continuous blood plasma protein extraction from whole blood during cardiac surgery. Lab Chip. 2011;11:2858. https://doi.org/10.1039/c1lc20080a.
Du W-B, Fang Q, He Q-H, Fang Z-L. High-throughput nanoliter sample introduction microfluidic chip-based flow injection analysis system with gravity-driven flows. Anal Chem. 2005;77:1330–7. https://doi.org/10.1021/ac048675y.
Nge PN, Yang W, Pagaduan JV, Woolley AT. Ion-permeable membrane for on-chip preconcentration and separation of cancer marker proteins. Electrophoresis. 2011;32:1133–40. https://doi.org/10.1002/elps.201000698.
Kuo T-C, Cannon DM, Chen Y, Tulock JJ, Shannon MA, Sweedler JV, et al. Gateable nanofluidic interconnects for multilayered microfluidic separation systems. Anal Chem. 2003;75:1861–7.
Li F, Guijt RM, Breadmore MC. Nanoporous membranes for microfluidic concentration prior to electrophoretic separation of proteins in urine. Anal Chem. 2016;88:8257–63. https://doi.org/10.1021/acs.analchem.6b02096.
Rajapandiyan P, Yang J. Sensitive cylindrical SERS substrate array for rapid microanalysis of nucleobases. Anal Chem. 2012;84:10277–82. https://doi.org/10.1021/ac302175q.
Yu WW, White IM. A simple filter-based approach to surface enhanced Raman spectroscopy for trace chemical detection. Analyst. 2012;137:1168. https://doi.org/10.1039/c2an15947c.
Gao S, Pearson B, He L. Mapping bacteria on filter membranes, an innovative SERS approach. J Microbiol Methods. 2018;147:69–75. https://doi.org/10.1016/j.mimet.2018.03.005.
Lin M, He L, Awika J, Yang L, Ledoux DR, Li H, et al. Detection of melamine in gluten, chicken feed, and processed foods using surface enhanced Raman spectroscopy and HPLC. J Food Sci. 2008;73:T129–34. https://doi.org/10.1111/j.1750-3841.2008.00901.x.
Tyan Y-C, Yang M-H, Jong S-B, Wang C-K, Shiea J. Melamine contamination. Anal Bioanal Chem. 2009;395:729–35. https://doi.org/10.1007/s00216-009-3009-0.
Kim A, Barcelo SJ, Williams RS, Li Z. Melamine sensing in milk products by using surface enhanced Raman scattering. Anal Chem. 2012;84:9303–9. https://doi.org/10.1021/ac302025q.
US Food and Drug Administration (FDA) (2008) Interim safety and risk assessment of melamine and its analogues in food for humans. In: Fed. Regist. https://www.federalregister.gov/documents/2008/11/13/E8-26869/interim-safety-and-risk-assessment-of-melamine-and-its-analogues-in-food-for-humans-availability. Accessed 23 Sep 2019
World Health Organization (2008) Melamine and cyanuric acid: toxicity, preliminary risk assessment and guidance on levels in food. 7
Cheng J, Wang S, Su X-O. Detection of melamine in feed using liquid-liquid extraction treatment combined with surface-enhanced Raman scattering spectroscopy. PLoS One. 2014;9:e107770. https://doi.org/10.1371/journal.pone.0107770.
Mircescu NE, Oltean M, Chiş V, Leopold N. FTIR, FT-Raman, SERS and DFT study on melamine. Vib Spectrosc. 2012;62:165–71. https://doi.org/10.1016/j.vibspec.2012.04.008.
Jang YH, Hwang S, Chang SB, Ku J, Chung DS. Acid dissociation constants of melamine derivatives from density functional theory calculations. J Phys Chem A. 2009;113:13036–40. https://doi.org/10.1021/jp9053583.
Leopold N, Stefancu A, Herman K, Tódor IS, Iancu SD, Moisoiu V, et al. The role of adatoms in chloride-activated colloidal silver nanoparticles for surface-enhanced Raman scattering enhancement. Beilstein J Nanotechnol. 2018;9:2236–47. https://doi.org/10.3762/bjnano.9.208.
Chong NS, Smith KA, Setti S, Ooi BG. Application of gold and silver colloidal nanoparticles for the surface-enhanced Raman spectrometric analysis of melamine and 4-aminobiphenyl. Int J Environ Technol Manag. 2013;16:3. https://doi.org/10.1504/IJETM.2013.050681.
Kong Y, Wei C, Wang Z, Hou Z, Li H, Yu J, et al. Determination of melamine in quail egg and milk with capillary zone electrophoresis. Am J Anal Chem. 2014;05:258–65. https://doi.org/10.4236/ajac.2014.54032.
Yazgan NN, Boyacı İH, Topcu A, Tamer U. Detection of melamine in milk by surface-enhanced Raman spectroscopy coupled with magnetic and Raman-labeled nanoparticles. Anal Bioanal Chem. 2012;403:2009–17. https://doi.org/10.1007/s00216-012-5971-1.
Wang R, Xu Y, Wang R, Wang C, Zhao H, Zheng X, et al. A microfluidic chip based on an ITO support modified with Ag-Au nanocomposites for SERS based determination of melamine. Microchim Acta. 2017;184:279–87. https://doi.org/10.1007/s00604-016-1990-5.
Han C, Li Y, Jia Q, Bradley LH, Gan Y, Yao Y, et al. On-demand fabrication of surface-enhanced Raman scattering arrays by pen writing, and their application to the determination of melamine in milk. Microchim Acta. 2017;184:2909–17. https://doi.org/10.1007/s00604-017-2307-z.
Nieuwoudt MK, Martin JW, Oosterbeek RN, Novikova NI, Wang X, Malmström J, et al. Gold-sputtered Blu-ray discs: simple and inexpensive SERS substrates for sensitive detection of melamine. Anal Bioanal Chem. 2016;408:4403–11. https://doi.org/10.1007/s00216-016-9545-5.
Lou T, Wang Y, Li J, Peng H, Xiong H, Chen L. Rapid detection of melamine with 4-mercaptopyridine-modified gold nanoparticles by surface-enhanced Raman scattering. Anal Bioanal Chem. 2011;401:333–8. https://doi.org/10.1007/s00216-011-5067-3.
Acknowledgments
The authors thank Dipl.-Phys. Jörg Lenzner (Felix-Bloch-Institut für Festkörperphysik, Universität Leipzig) for recording the SEM images and Monika Hahn (Felix-Bloch-Institut für Festkörperphysik, Universität Leipzig) for sputtering the silver thin film on the PCTE membranes. The authors also wish to thank Dr. Josef Heiland and Raphael Urban (Institut für analytische Chemie, Universität Leipzig) for support with the graphical design.
Funding
Financial support from the Deutsche Forschungsgemeinschaft (DFG) is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 854 kb)
Rights and permissions
About this article
Cite this article
Krafft, B., Panneerselvam, R., Geissler, D. et al. A microfluidic device enabling surface-enhanced Raman spectroscopy at chip-integrated multifunctional nanoporous membranes. Anal Bioanal Chem 412, 267–277 (2020). https://doi.org/10.1007/s00216-019-02228-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-019-02228-9