Analytical and Bioanalytical Chemistry

, Volume 410, Issue 23, pp 5993–6000 | Cite as

Rapid and sensitive SERS detection of the cytokine tumor necrosis factor alpha (tnf-α) in a magnetic bead pull-down assay with purified and highly Raman-active gold nanoparticle clusters

  • Yuming Lai
  • Sebastian Schlücker
  • Yuling WangEmail author
Research Paper


Tumor necrosis factor alpha (TNF-α) is a cytokine with significance in early diagnosis of cardiovascular diseases, obesity and insulin resistance. We demonstrate the proof of concept for a rapid and sensitive detection of TNF-α using a magnetic bead pull-down assay in combination with surface-enhanced Raman scattering (SERS). The use of purified and highly SERS-active small clusters of gold nanoparticles (AuNP) provides the high sensitivity of the assay with a limit of detection of ca. 1 pg/mL. Continuous density gradient centrifugation was employed for separating the very bright silica-encapsulated AuNP dimers and trimers from the significantly weaker AuNP monomers. Negative control experiments with other cytokines (IL-6, IL-8) and bovine serum albumin (BSA) confirm the high specificity of the assay, but indicate also space for future improvements by further reducing non-specific binding between proteins and the SERS nanotags. The multiplexing potential of this SERS-based detection scheme is exemplarily demonstrated by using a set of three spectrally distinct and highly SERS-active AuNP clusters with unique spectral barcodes.

Graphical abstract


Silica encapsulation Gold nanoparticles Surface-enhanced Raman scattering TNF-α Multiplexing 



Y.M.L. thanks the China Scholarship Council (CSC) for the financial support of her research visit at the University of Duisburg-Essen. YML also thanks the Fundamental Research Funds from the Central Universities (FRF-TP-15-012A2) for the financial support. SS and YW acknowledge financial support from the German Research Foundation (DFG, WA 3369/1-1).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1218_MOESM1_ESM.pdf (1.3 mb)
ESM 1 (PDF 1374 kb)


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Copyright information

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

Authors and Affiliations

  1. 1.National Center for Materials Service SafetyUniversity of Science and Technology BeijingBeijingChina
  2. 2.Department of Chemistry, Center for Nanointegration Duisburg-Essen (CENIDE) and Center of Medical Biotechnology (ZMB)University of Duisburg-EssenEssenGermany
  3. 3.Department of Molecular Sciences and ARC Centre of Excellence for Nanoscale BioPhotonics, Faculty of Science and EngineeringMacquarie UniversitySydneyAustralia

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