journal article·2024-04-26Open access

Label-Free Analysis of Protein Biomarkers Using Pattern-Optimized Graphene-Nanopyramid SERS for the Rapid Diagnosis of Alzheimer’s Disease

Heping Wu, Yan Duan, Luyue Jiang, Xinhao Cao, Zhen Xie, Yi Quan, Matthew Xinhu Ren, Shengli Wu, Nan Zhang, Zhugen Yang, Libo Zhao, Zhuangde Jiang, Gang Zhao, Wei Ren, Gang Niu

ACS Applied Nano Materials· Volume 7· Issue 8

Abstract

The quantitative and highly sensitive detection of biomarkers such as Tau proteins and Aβ polypeptides is considered one of the most effective methods for the early diagnosis of Alzheimer’s disease (AD). Surface-enhanced Raman spectroscopy (SERS) detection is a promising method that faces, however, challenges like insufficient sensitivity due to the non-optimized nanostructures for specialized analyte sizes and insufficient control of the location of SERS hot spots. Thus, the SERS detection of AD biomarkers is restricted. We reported here an in-depth study of the analytical Raman enhancement factor (EF) of the wafer-scale graphene-Au nanopyramid hybrid SERS substrates using a combination of both theoretical calculation and experimental measurements. Experimental results show that larger nanopyramids and smaller gap spacing lead to a larger SERS EF, with an optimized analytical EF up to 1.1 × 10 10 . The hybrid SERS substrate exhibited detection limits of 10 –15 M for Tau and phospho-Tau (P-Tau) proteins and 10 –14 M for Aβ polypeptides, respectively. Principal component analysis correctly categorized the SERS spectra of different biomarkers at ultralow concentrations (10 –13 M) using the optimized substrate. Amide III bands at 1200–1300 cm –1 reflect different structural conformations of proteins or polypeptides. Tau and P-Tau proteins are inherently disordered with a few α-helix residuals. The structure of Aβ42 polypeptides transitioned from the α-helix to the β-sheet as the concentration increased. These results demonstrate that the hybrid SERS method could be a simple and effective way for the label-free detection of protein biomarkers to enable the rapid early diagnosis of AD and other diseases.
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Research context

OpenAlex topics: Spectroscopy Techniques in Biomedical and Chemical Research · Gold and Silver Nanoparticles Synthesis and Applications · Protein Interaction Studies and Fluorescence Analysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory for Manufacturing Systems Engineering; Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education, School of Electronic Science and Engineering, Xi’an Jiaotong University, 710049 Xi’an, China

The College of Life Sciences and Medicine, Northwest University, No. 229 Taibai North Road, Xi’an, Shaanxi 710069, P. R. China

Department of Clinical Laboratory, Xi’an Daxing Hospital, Xi’an 710016, China

School of Microelectronics, Xidian University, Xi’an 710071, China

Biology Program, Faculty of Science, The University of British Columbia, Vancouver BC V6T 1Z4, Canada

Key Laboratory of Physical Electronics and Devices, Ministry of Education, School of Electronic Science and Engineering, Xi’an Jiaotong University, Xi’an 710049, China

Cranfield Water Science Institute, School of Water, Energy and Environment, Cranfield University, Cranfield MK43 0AL, U.K.

School of Instrument Science and Technology, State Key Laboratory for Manufacturing Systems Engineering & The International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi’an Jiaotong University, Xi’an 710049, China

The State Key Laboratory for Manufacturing Systems Engineering & The International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi’an Jiaotong University, Xi’an 710049, China

Funding

China Postdoctoral Science Foundation · Fundamental Research Funds for the Central Universities · Higher Education Discipline Innovation Project · Key Research and development Program of Shaanxi Province · Postdoctoral Research Project of Shaanxi Province

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