Zwitterion-Functionalized Cuprous Oxide Nanoparticles for Highly Specific and Enzymeless Electrochemical Creatinine Biosensing in Human Serum

Herein, we report the development of a novel enzymeless electrochemical biosensor for highly specific detection of creatinine utilizing zwitterion-functionalized cuprous oxide nanoparticles (Cu 2 O NPs). We utilized a simple yet effective alternative to traditionally used cover layers based on the surface engineering of Cu 2 O NPs with N -hexadecyl- N, N dimethyl-3-ammonio-1-propanesulfonate zwitterion. This surface modification generates a pseudo-proton-exchange membrane which electrostatically hinders interfering agents from reaching the electrode surface, thus resulting in highly specific creatinine detection without loss in sensitivity. To fabricate the enzymeless biosensor, single-crystalline Cu 2 O NPs were synthesized via a sulfonate ion-directed seed aging protocol and were simply drop-cast onto screen-printed carbon electrodes. The shape directional effect of sulfonate ions to induce truncation in the final morphologies of the synthesized Cu 2 O NPs is also reported for the first time. The creatinine biosensor demonstrated fast response time (<50 s), good reproducibility (RSD = 2.8%, n = 10), and high specificity against interferents like ascorbic acid, acetic acid, glucose, urea, and uric acid. A linear response to creatinine concentration from 10 to 200 μM ( R 2 = 0.9876 and LOD = 5.0 μM) was observed, which covers the entire range of physiological creatinine in human serum. Moreover, robust storage stability with a negligible decrease in signal strength over an extended storage period of 6 months was achieved, thus highlighting the practical feasibility for point-of-care testing of creatinine.