[Paper Review] Highly fluorescent copper nanoclusters for sensing and bioimaging

Yu An, Ying Ren+3 more|arXiv (Cornell University)|Dec 29, 2019

Nanocluster Synthesis and Applications124 references4 citations

TL;DR

This review explores highly fluorescent copper nanoclusters (CuNCs) as low-cost, nontoxic alternatives to noble metal nanoclusters for sensing and bioimaging. It details how CuNCs achieve strong, tunable fluorescence through size-controlled synthesis and aggregation, enabling enhanced photostability and brightness for applications in live-cell imaging and biosensing.

ABSTRACT

Metal nanoclusters (NCs), typically consisting of a few to tens of metal atoms, bridge the gap between organometallic compounds and crystalline metal nanoparticles. As their size approaches the Fermi wavelength of electrons, metal NCs exhibit discrete energy levels, which in turn results in the emergence of intriguing physical and chemical (or physicochemical) properties, especially strong fluorescence. In the past few decades, dramatic growth has been witnessed in the development of different types of noble metal NCs (mainly AuNCs and AgNCs). However, compared with noble metals, copper is a relatively earth-abundant and cost-effective metal. Theoretical and experimental studies have shown that copper NCs (CuNCs) possess unique catalytic and photoluminescent properties. In this context, CuNCs are emerging as a new class of nontoxic, economic, and effective phosphors and catalysts, drawing significant interest across the life and medical sciences. To highlight these achievements, this review begins by providing an overview of a multitude of factors that play central roles in the fluorescence of CuNCs. Additionally, a critical perspective of how the aggregation of CuNCs can efficiently improve the florescent stability, tunability, and intensity is also discussed. Following, we present representative applications of CuNCs in detection and bioimaging. Finally, we outline current challenges and our perspective on the development of CuNCs.

Motivation & Objective

• To summarize the key factors governing fluorescence in copper nanoclusters (CuNCs), including size, ligand capping, and electronic structure.
• To examine how aggregation of CuNCs enhances their photoluminescent stability, intensity, and tunability.
• To highlight representative applications of CuNCs in biosensing and in vivo/in vitro bioimaging.
• To identify current challenges and future research directions for advancing CuNCs in biomedical applications.

Proposed method

• Systematic review of experimental and theoretical studies on CuNCs from 2000 to 2019.
• Analysis of synthesis strategies using stabilizing ligands (e.g., DNA, polymers, peptides) to control size and fluorescence.
• Investigation of aggregation-induced emission (AIE) effects in CuNCs to improve quantum yield and photostability.
• Evaluation of spectroscopic techniques (e.g., UV-Vis, fluorescence, EPR) used to characterize CuNCs' optical and electronic properties.
• Comparison of CuNCs with AuNCs and AgNCs in terms of cost, toxicity, and fluorescence performance.
• Use of computational modeling to explain discrete energy levels and fluorescence mechanisms in sub-10 nm CuNCs.

Experimental results

Research questions

• RQ1 What structural and chemical factors govern the strong fluorescence in copper nanoclusters?
• RQ2 How does aggregation of CuNCs enhance their photoluminescent properties such as quantum yield and stability?
• RQ3 What are the key advantages of CuNCs over noble metal nanoclusters (e.g., AuNCs, AgNCs) in bioimaging and sensing?
• RQ4 What are the current limitations and bottlenecks in the practical application of CuNCs in biomedical research?
• RQ5 How can the fluorescence of CuNCs be tuned for specific sensing and imaging applications?

Key findings

• Copper nanoclusters exhibit strong, tunable fluorescence due to discrete energy levels arising from quantum confinement at sub-10 nm sizes.
• Aggregation of CuNCs significantly enhances fluorescence intensity and photostability, enabling practical use in biological environments.
• CuNCs demonstrate high quantum yields comparable to noble metal nanoclusters, with some systems achieving quantum yields above 50%.
• Ligand engineering—particularly using DNA, polymers, or peptides—enables precise control over CuNC size, stability, and emission wavelength.
• CuNCs show low cytotoxicity and biocompatibility, making them suitable for live-cell and in vivo bioimaging applications.
• Despite progress, challenges remain in reproducible synthesis, long-term stability, and precise emission tuning for multiplexed detection.