In recent years, various methods for the synthesis of fluorescent core-shell nanostructures were developed, optimized, and studied thoroughly in our research group. Metallic cores exhibiting plasmonic properties in the UV and visible regions of the electromagnetic spectrum were used to increase substantially the brightness and stability of organic fluorophores encapsulated in silica shells. Furthermore, the efficiency and range of F?rster resonant energy transfer (FRET) between donor and acceptor molecules located in the vicinity of the metallic core was shown to be enhanced. Such multilayer nanoparticle architectures offer, in addition to the aforementioned advantages, excellent chemical and physical stability, solubility in aqueous media, low toxicity, and high detectability. In view of these enviable characteristics, a plethora of applications have been envisioned in biology, analytical chemistry, and medical diagnostics. In this paper, advances in the development of multilayer core-shell luminescent nanoparticle structures and selected applications to bioanalytical chemistry will be described. 1. Introduction Fluorescence spectroscopy is a dominant research tool in many fields of science and technology, largely due to its high sensitivity, low cost, and ease of use, and has become massively popular in analytical and biological sciences, particularly in cellular and molecular imaging, flow cytometry, medical diagnostics, DNA sequencing, forensics, and genetic analysis [1–6]. To benefit from this high sensitivity, bright and stable luminescent labels are usually required. However, most commonly available organic dyes used for optical signaling suffer from some important limitations such as hydrophobicity, collisional quenching in aqueous media, low fluorescence quantum yield, and low resistance to photobleaching [7]. Therefore, the continued development of new fluorescence techniques relies on the investigation of novel strategies to overcome the limitations of current fluorescent probes. In this regard, the remarkable optical properties displayed by metal nanostructures, in particular the coupling between the free electrons responsible for surface plasmon resonance and nearby fluorophores, can increase the local electrical field and enhance the excitation and emission rates and decrease the lifetimes of excited states [8–11]. This phenomenon, termed metal-enhanced fluorescence (MEF), is being investigated intensively and represents a powerful technology to increase the detection sensitivity of various biological assays [12–19]. Most of the studies
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