Key Takeaways & Executive Findings
- •• • NiHCF core retains 95% of its redox signal after 5000 electrochemical cycles, a degradation rate of ~0.001% per cycle, directly addressing the operational lifespan limitation of implantable sensors in complex biological fluids. • • Citrate-assisted synthesis yields uniform NiHCF nanocubes with low lattice strain, enabling consistent electrochemical signaling; DFT-verified monomer selection ensures precise molecular complementarity within the MIP cavity, improving selectivity for target biomarkers. • • Formulation of MIP/NiHCF nanoparticles into inkjet-printable ink enables scalable, additive manufacturing, reducing labor-intensive multi-step processes and enhancing reproducibility and production efficiency for mass production. • • The dual-functional architecture combines selective target capture (MIP shell) with stabilized electrochemical signaling (NiHCF core), achieving a balance between high selectivity and stability that conventional enzyme-based or unstable redox probes fail to maintain under physiological conditions.
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Abstract
Wearable and implantable biosensors enable real-time monitoring of physiological parameters and biomarkers such as glucose, lactate, and hormones, but face persistent limitations in selectivity, operational lifespan, and scalable manufacturing. Molecularly imprinted polymers (MIPs) and Prussian blue analogues (PBAs) offer customizable recognition and redox activity, yet PBAs degrade over electrochemical cycling and MIPs suffer from imprecise binding-site optimization. Wang et al. (Nat. Mater., 2025, 24, 589–598) address these bottlenecks with printable core-shell nanoparticles comprising a nickel hexacyanoferrate (NiHCF) core and an MIP shell. The NiHCF core, synthesized via a citrate-assisted method, yields uniform nanocubes with low lattice strain due to nickel's small atomic radius, retaining 95% of its redox signal after 5000 electrochemical cycles—significantly outperforming conventional PBAs. Density functional theory (DFT) calculations guided monomer selection to ensure precise molecular complementarity within the MIP cavity, resolving inefficient molecular recognition. Formulated into an inkjet-printable ink, the MIP/NiHCF nanoparticles enable scalable, additive manufacturing of biosensors. This platform establishes a new benchmark for wearable and implantable health monitoring, though challenges remain in extending dynamic range to picomolar cytokines, ensuring long-term stability in complex biofluids, and validating performance across diverse populations. The integration of molecular imprinting, redox-active nanomaterials, and additive manufacturing provides a foundation for next-generation diagnostics and therapeutic interventions.
1. Introduction
Wearable and implantable biosensors have emerged as transformative tools for real-time monitoring of physiological parameters and biomarkers, yet commercial adoption remains constrained by poor selectivity, short operational lifespans due to environmental degradation, and difficulties in interfacing with complex biological environments. Existing approaches using molecularly imprinted polymers (MIPs) and Prussian blue analogues (PBAs) offer customizable recognition and redox activity, but PBAs degrade over electrochemical cycling and MIPs suffer from imprecise binding-site optimization, compromising performance. Enzyme-based recognition elements and unstable redox probes further degrade under physiological conditions, causing signal drift and reduced operational lifespan.
Wang et al. (Nat. Mater., 2025, 24, 589–598) address these bottlenecks through printable core-shell nanoparticles with dual functionality: an MIP shell for selective target capture and a nickel hexacyanoferrate (NiHCF) core for stabilized electrochemical signaling. The NiHCF core, synthesized via a citrate-assisted method, yields uniform nanocubes with low lattice strain, retaining 95% of its redox signal after 5000 electrochemical cycles. DFT-guided monomer selection ensures precise molecular complementarity within the MIP cavity. By formulating these nanoparticles into inkjet-printable ink, the authors enable scalable, additive manufacturing, overcoming labor-intensive multi-step processes and improving reproducibility for mass production.
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WANG Xiaotian, LI Yang, ZHU Xianjun (2025). Printable Core-Shell Nanoparticles Empower Stable Biosensing. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-3314-0
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Frequently Asked Questions
What is the failure mechanism of conventional Prussian blue analogues (PBAs) under electrochemical cycling, and how does the NiHCF core mitigate it?
Conventional PBAs degrade over electrochemical cycling due to lattice strain and structural instability, leading to signal loss. The NiHCF core, with nickel's small atomic radius, imparts low lattice strain, enabling retention of 95% of its redox signal after 5000 cycles—a degradation rate of ~0.001% per cycle, significantly superior to conventional PBAs.
How does the citrate-assisted synthesis and DFT-guided monomer selection improve MIP cavity precision?
Citrate-assisted synthesis enables uniform production of NiHCF nanocubes, ensuring consistent electrochemical signaling. DFT calculations verify monomer selection, ensuring precise molecular complementarity within the MIP cavity, which resolves inefficient molecular recognition and enhances selectivity for target biomarkers.
What are the scalability bottlenecks of conventional biosensor manufacturing, and how does inkjet printing address them?
Conventional manufacturing is labor-intensive, involving complex, multi-step processes that limit scalability, reproducibility, and production efficiency. Formulating MIP/NiHCF nanoparticles into inkjet-printable ink enables additive manufacturing, reducing steps and enabling mass production with improved consistency.
What operational thresholds must be met for implantable biosensors in complex biological fluids, and how does this platform perform?
Implantable sensors must maintain long-term operational stability in complex biological fluids. The NiHCF core retains 95% of its redox signal after 5000 cycles, addressing degradation. However, extending dynamic range to picomolar cytokines and validating across diverse populations remain challenges requiring further engineering.
What are the remaining technical hurdles for clinical translation of this biosensor platform?
Key hurdles include extending dynamic range to detect ultralow biomarker concentrations (e.g., picomolar cytokines) via nanoscale MIP cavity engineering or signal amplification, and validating performance across diverse populations considering variations in sweat composition, skin physiology, and drug metabolism.
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