Citation: Wu, H.-Y.; Lin, H.-C.; Hung, G.-Y.; Tu, C.-S.; Liu, T.-Y.; Hong, C.-H.; Yu, G.; Hsu, J.-C. High Sensitivity SERS Substrate of a Few Nanometers Single-Layer Silver Thickness Fabricated by DC Magnetron Sputtering Technology. Nanomaterials 2022, 12, 2742. https:// doi.org/10.3390/nano12162742 Academic Editor: Maria Losurdo Received: 18 July 2022 Accepted: 9 August 2022 Published: 10 August 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nanomaterials Article High Sensitivity SERS Substrate of a Few Nanometers Single-Layer Silver Thickness Fabricated by DC Magnetron Sputtering Technology Hsing-Yu Wu 1,2 , Hung-Chun Lin 3 , Guan-Yi Hung 4 , Chi-Shun Tu 3 , Ting-Yu Liu 5 , Chung-Hung Hong 6 , Guoyu Yu 7 and Jin-Cherng Hsu 3,8, * 1 System Manufacturing Center, National Chung-Shan Institute of Science and Technology, New Taipei City 237209, Taiwan 2 Center for Astronomical Physics and Engineering, Department of Optics and Photonics, National Central University, Taoyuan City 320317, Taiwan 3 Department of Physics, Fu Jen Catholic University, New Taipei City 242062, Taiwan 4 Department of International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices, Ming Chi University of Technology, New Taipei City 243303, Taiwan 5 Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 243303, Taiwan 6 Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan 7 Department of Engineering and Technology, School of Computing and Engineering, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK 8 Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City 242062, Taiwan * Correspondence: 054326@mail.fju.edu.tw; Tel.: +886-2-29053765 Abstract: Surface-enhanced Raman spectroscopy (SERS) is commonly used for super-selective analy- sis through nanostructured silver layers in the environment, food quality, biomedicine, and materials science. To fabricate a high-sensitivity but a more accessible device of SERS, DC magnetron sputtering technology was used to realize high sensitivity, low cost, a stable deposition rate, and rapid mass production. This study investigated various thicknesses of a silver film ranging from 3.0 to 12.1 nm by field emission scanning electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy. In the rhodamine 6G (R6G) testing irradiated by a He-Ne laser beam, the analytical enhancement factor (AEF) of 9.35 × 10 8 , the limit of detection (LOD) of 10 −8 M, and the relative standard deviation (RSD) of 1.61% were better than the other SERS substrates fabricated by the same DC sputtering process because the results showed that the 6 nm thickness silver layer had the highest sensitivity, stability, and lifetime. The paraquat and acetylcholine analytes were further investigated and high sensitivity was also achievable. The proposed SERS samples were evaluated and stored in a low humidity environment for up to forty weeks, and no spectrum attenuation could be detected. Soon, the proposed technology to fabricate high sensitivity, repeatability, and robust SERS substrate will be an optimized process technology in multiple applications. Keywords: surface-enhanced Raman scattering (SERS); silver nanoparticle (AgNP); rhodamine 6G (R6G); DC magnetron sputtering; SERS substrate; hotspot; analytical enhancement factor (AEF); limit of detection (LOD); relative standard deviation (RSD) 1. Introduction Since the development of Raman spectroscopy in 1928, its measurement spectrum has been applied to many research areas such as molecular vibrations [1], crystal structures [2,3], and its fingerprint-like specificity [4] to identify the specific chemical structure [5,6]. In 1974, British scientist Fleischmann discovered the surface-enhanced Raman spectroscopy (SERS) effect to improve the limitation of detecting the dilute molecule concentration Raman- active vibration signal amplified on a rough silver electrode bottom plate by a factor of Nanomaterials 2022, 12, 2742. https://doi.org/10.3390/nano12162742 https://www.mdpi.com/journal/nanomaterials