高熵普魯士藍類似物在中性環境之電化學催化與葡萄糖感測研究

Abstract

高熵材料（High-Entropy Materials, HEMs）因多元素組成所產生的高混合熵效應（configurational entropy effect），能提升晶格穩定性與電化學耐久性，近年廣泛應用於電池與儲能領域，並被證實可有效提升比容量與循環壽命。普魯士藍類似物（Prussian Blue Analogues, PBAs）因具可逆氧化還原特性與良好導電性，廣泛應用於電催化與電化學感測領域。然而，傳統普魯士藍材料（Prussian Blue, PB）於中性或鹼性環境中易受氫氧根攻擊，導致金屬配位鍵結斷裂，造成結構不穩與感測能力衰退，限制其於生理樣本中之應用。近年來，高熵普魯士藍類似物（High-Entropy Prussian Blue Analogues, HEPBA）因其多金屬活性位點與高熵效應，在電池與儲能領域展現優異的電化學循環穩定性與比容量表現，成為新興研究焦點。然而，其在中性水相環境中的電化學行為與結構穩定性仍缺乏系統性探討。基於此，本研究將HEPBA引入電化學感測領域，系統性探討其在中性環境中的穩定性與電化學催化特性，並驗證其於生理模擬條件下作為感測平台之可行性。本研究透過共沉澱法合成多種金屬元素（Fe、Mn、Ni、Cu、Co）組成之HEPBA粉末，並以次微米粒子墨水結合滴塗法製備修飾電極，以建立穩定且具重現性的修飾電極製程。藉由TEM、EDX、XRD與FTIR等材料分析確認，所得HEPBA具單相高熵固溶體而非多金屬混摻結構。高熵組成有效穩定晶格，使其在中性環境下具更高結構穩定性。電化學分析顯示，HEPBA修飾電極於中性生理環境條件（pH 7.4）中展現良好氧化還原可逆性與高循環穩定性，多次循環後電流保留率超過80%，遠優於傳統普魯士藍僅約2%的表現，證明高熵效應可顯著提升材料於中性環境中的化學穩定性與電化學耐久度。此外，透過金屬元素比例調控，可進一步提升HEPBA對過氧化氫之電催化能力，顯示其作為電子媒介體（mediator）之潛力。感測應用方面，透過結合葡萄糖氧化酶（glucose oxidase, GOx）與幾丁聚醣（chitosan）形成GOx/chitosan/HEPBA修飾電極，並於模擬生理環境中進行葡萄糖感測實驗。結果顯示，該電極在0.5–3.0 mM葡萄糖濃度範圍內具良好線性響應，理論偵測極限為840 μM，靈敏度為6.43 μA/mM·cm²。與幾丁聚醣複合後，能有效抑制干擾物（如尿酸與抗壞血酸）對電流訊號的影響，同時提升GOx酵素之固定效率與親和性，使其更適用於生理樣本分析並顯著提升感測表現。值得強調的是，葡萄糖在本研究中僅作為示範案例，若更換其他氧化酶（如乳酸氧化酶等）即可延伸至不同生理分子檢測，展現該材料的高通用性與應用延展性。綜合而言，本研究為高熵普魯士藍類似物於電化學感測領域的首次系統性應用研究，證實其於中性環境中具優異穩定性與電化學活性。HEPBA不僅克服傳統PB於中性條件下易失活的限制，也展示其作為穩定、通用且可延伸之電化學平台的潛力，為高熵材料跨足電化學感測與生理催化領域開啟新的研究方向。

High-entropy materials (HEMs), characterized by their multi-element compositions and configurational entropy effects, exhibit enhanced lattice stability and electrochemical durability. In recent years, they have been widely applied in batteries and energy storage systems, demonstrating improvements in specific capacity and cycling performance. Prussian blue analogues (PBAs), known for their reversible redox behavior and good electrical conductivity, have been extensively studied for electrocatalysis and electrochemical sensing applications. However, conventional Prussian blue (PB) suffers from structural degradation in neutral or alkaline environments due to hydroxide attack that breaks metal–ligand coordination bonds, resulting in poor stability and limited applicability in physiological samples. Recently, high-entropy Prussian blue analogues (HEPBA) have emerged as promising materials in battery research, owing to their multiple active metal sites and entropy-stabilized structures that provide excellent cycling stability and capacity retention. Nevertheless, their electrochemical behavior and structural stability under neutral aqueous conditions remain largely unexplored. In this study, HEPBA was introduced into the electrochemical sensing field to systematically investigate its stability and electrocatalytic characteristics under neutral conditions, and to evaluate its feasibility as a sensing platform in simulated physiological environments. HEPBA powders composed of Fe, Mn, Ni, Cu, and Co were synthesized via a co-precipitation method, and submicron-particle inks combined with drop-casting techniques were employed to fabricate modified electrodes with high reproducibility. Structural analyses (TEM, EDX, XRD, and FTIR) confirmed the formation of a single-phase high-entropy solid solution rather than a mixed-metal composite. The high-entropy configuration effectively stabilized the lattice, leading to superior electrochemical stability in neutral media. Electrochemical measurements revealed that HEPBA-modified electrodes exhibited excellent redox reversibility and cycling stability under physiological conditions (pH 7.4), retaining over 80% of the initial current after multiple cycles, whereas traditional PB retained only about 2%. Furthermore, tuning the metal ratios enhanced the electrocatalytic activity toward hydrogen peroxide, indicating its potential as an effective redox mediator. For sensing applications, a GOx/chitosan/HEPBA modified electrode was constructed by incorporating glucose oxidase (GOx) and chitosan. The electrode showed a linear response to glucose concentrations ranging from 0.5 to 3.0 mM, with a theoretical detection limit of 840 μM and a sensitivity of 6.43 μA/mM·cm2. The chitosan layer effectively suppressed interference from uric acid and ascorbic acid while improving enzyme immobilization and biocompatibility, making the electrode suitable for physiological sample analysis. Importantly, glucose was used only as a demonstration; by substituting other oxidases (e.g., lactate oxidase), the system could be extended to detect various biomolecules. In summary, this work represents the first systematic application of HEPBA in electrochemical sensing, demonstrating its remarkable stability and electrocatalytic activity under neutral conditions. HEPBA not only overcomes the instability of conventional PB in neutral media but also establishes a stable, versatile, and extendable platform for electrochemical and biosensing applications.