Ferrocenyl Compounds as Alternative Redox Labels for Robust and Versatile Electrochemical Aptamer-Based Sensors

Area of Science:

• Electrochemistry
• Biosensors
• Nanomaterials

Background:

• Electrochemical aptamer-based (E-AB) sensors are crucial for sensitive analyte detection.
• Methylene blue (MB) is a common redox label, but its performance can be limited.
• Development of alternative, more robust redox labels is needed for improved E-AB sensor functionality.

Purpose of the Study:

• To evaluate ferrocenyl (Fc) compounds with cross-linking groups as potential redox labels for E-AB sensors.
• To compare the performance of Fc compounds against methylene blue (MB).
• To identify a superior Fc-based redox label for enhanced sensor sensitivity, stability, and versatility.

Main Methods:

• Synthesis and characterization of seven ferrocenyl compounds with cross-linking functionalities.
• Evaluation of cross-linking efficiency, formal potential (E0'), and electrochemical durability.
• Attachment of the lead Fc compound (Fc1a-X) to an amine-terminated monolayer on a gold electrode.
• Electrochemical analysis using square wave voltammetry in various conditions, including serum.
• Detection of doxorubicin using the developed E-AB sensor.

Main Results:

• Compound Fc1a-X demonstrated superior performance, including efficient cross-linking and a moderate, pH-insensitive formal potential (0.14 V vs Ag/AgCl).
• Fc1a-X exhibited enhanced electrochemical durability during repeated potential scans and maintained stable peak currents in serum over 12 hours compared to MB.
• An E-AB sensor utilizing Fc1a-X successfully detected doxorubicin in serum across the clinical range.

Conclusions:

• Fc1a-X is a promising alternative redox label for E-AB sensors due to its efficient cross-linking, optimal and stable electrochemical properties, and superior durability.
• The developed Fc1a-X-based E-AB sensor offers robustness, versatility, and high sensitivity for detecting analytes in complex biological matrices.
• This work paves the way for the development of next-generation E-AB sensors with improved performance characteristics.