A dual-responsive electrochemical biosensor based on artificial protein imprinted polymers and natural hyaluronic acid for sensitive recognition towards biomarker CD44

Two main challenges for biosensors facing may be analytical sensitivity and selectivity. Ultra-highly specific protein molecularly imprinted polymers (MIPs) with characteristics of easy preparation, chemical stability, convenient assembly with transducer, offer unprecedented opportunities for high-performance recognition towards targets. A dual-responsive electrochemical biosensor was demonstrated, where integrated both artificial protein MIPs and natural hyaluronic acid (HA) probes into one flexible electrode to detect biomarker CD44. Their efficacy towards target of two types of probes were elucidated and contrasted. Dual-channel screen-printed electrodes (SPEs) were designed innovatively. As one responsive channel, protein MIPs were synthesized through a polymerization procedure between functional monomer of alginate gel, a biocompatible antifouling chemical, and template protein CD44. Natural HA probes were immobilized to produce the other responsive channel. Such binary channels realized highly sensitive and selective target quantifying with lower limit of detections (LODs) of 1.41 × 10−5 ng/mL for MIPs-based and 1.51 × 10−5 ng/mL for HA-based channels, attributing to superior specificity, antifouling property and biocompatibility of MIPs and HA, satisfying stability of SPEs, high sensitivity of electrochemical techniques. The dual-responsive strategy can be extended to other batched integration of functionalized materials and active biomolecules into electrochemical and electro-catalytic biosensors towards multiple components to monitor physical signs and diagnose human diseases.