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 (Cu2O NPs). We utilized a simple yet effective alternative to traditionally used cover layers based on the surface engineering of Cu2O 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 Cu2O 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 Cu2O 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 (R2 = 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.