Enhanced electrochemical insulin determination with ligand-free nickel nanoparticles synthesized via laser ablation in liquids

The performance of non-enzymatic electrochemical sensors for diabetes diagnostics has been significantly improved due to the high sensitivity and rapid response of nickel nanoparticles (Ni NPs). However, conventional synthesis routes often yield Ni NPs with ligand-passivated surfaces, limiting the accessibility of catalytically active sites. To overcome this limitation, we employed laser ablation in liquids (LAL) to produce ligand-free Ni NPs without the use of stabilizing agents, in a green and effective way. The resulting quasi-spherical Ni NPs (predominantly sub-10 nm in size) consisted of metallic Ni/NiO nanostructures that provided accessible redox-active surface and electrochemical stability. These Ni NPs were integrated into screen-printed carbon electrodes (SPCEs), forming rapid and catalytically active interfaces for insulin oxidation via thiol-to-disulfide conversion. After optimization of the NPs loading, the developed SPCE-based sensor exhibited a low detection limit of 28 nM, a linear response range of 0.25–5 μM, successful detection in blood serum sample, and retained ∼88% of its initial electrochemical response after four weeks. Overall, this work shows that LAL-derived Ni-based nanostructures provide a simple, scalable, and environmentally benign platform for non-enzymatic insulin detection, with broader relevance for electrochemical sensing and analytical applications.