Authors’ contributions AS (first author) carried

out the experimental studies and drafted the manuscript. SM enabled to carry out the in vitro testing of T47Dluc cells and helped to perform one part of the statistical analysis. HH conceived of the study and participated in its design. AS conceived of the study and participated in the sequence alignment. HM participated in the design of the study and helped to perform the statistical analysis and to draft the manuscript. All authors read and approved the final manuscript.”
“Background Metal island films (MIFs) have attracted significant attention due to the strong surface plasmon resonance (SPR) MI-503 chemical structure effect in these nanoislands. The spectral position of the SPR is influenced and can be tuned by the MIF density as well as the substrate and cover materials used [1–3]. Surface-enhanced Raman spectroscopy (SERS) in biological and MAPK inhibitor chemical sensing [4] can be regarded as one of the most intriguing applications of MIFs. It can provide at least 1010- to 1012-fold intensity enhancement compared to the normal Raman scattering [3]. The main reason for this intensity enhancement is the electromagnetic learn more (EM) enhancement mechanism prevailing over the chemical

enhancement (CHEM) by several orders of magnitude [3]. This is because the EM enhancement is proportional to about the forth power of the SPR-increased local electric field input in Raman scattering, i.e., in the analyzed media adsorbed on the MIF (an adsorbate), while the reported CHEM enhancement factors, due to metal island-adsorbate interaction, are approximately 102. It is essential to decrease the distance between separate metal islands in a MIF, which results in the increase of the local electric

field intensity and, consequently, in a larger SERS signal [5]. Other prospective applications of MIFs include catalysis [6, 7], photovoltaics [8], and fluorescence ifenprodil enhancement [9]. For many practical uses, MIFs should be protected with a dielectric cover, which influences not only the CHEM but also the EM enhancement of SERS through the change of local electric field in adsorbates. At the same time, cover-induced shifts of the SPR spectral position can be used to tune SERS measurements for a specific wavelength, which is of high importance for surface-enhanced resonance Raman scattering [10]. The influence of MIF dielectric covers (spacers between the MIF and an analyte) on SERS intensity has been studied for more than two decades [11]. However, only the recent use of a very precise atomic layer deposition (ALD) technique has allowed obtaining quantitative results related to the SERS influence by alumina spacers deposited on metal microspheres [3], MIFs [12], and metal nanowires [13]. However, due to the difference in metal nanoislands and nanoparticles used in the experiment, these results can hardly be compared, and they contradict the data obtained in SERS experiments using MIFs covered with non-ALD spacers [14].