Integration of 3D-Printed Micro/Nanostructures with Interdigitated Electrodes for Low-Matrix-Effect Sensing

Electrochemical sensors offer the advantages of low cost, high sensitivity, and miniaturization for a wide range of biological applications, including in situ detection of cell metabolites and monitoring cell behavior in real time. However, the complex matrix in biosystems often leads to electrode fouling and inferior sensing performance. In addition to chemical barriers featuring assorted antifouling molecules or coatings, creating micro/nano hierarchical structures on top of electrodes can provide physical barriers to mitigate matrix interference without affecting electron transfer. The emerging two-photon polymerization (TPP) 3D printing technique with the capability to produce precise submicron to several micrometer features on a variety of substrates has enabled the straightforward fabrication of complex hierarchical structures. In this paper, we integrate the value-added micro/nanostructures made by TPP printing with the interdigitated electrode-based sensors and demonstrate the platform's advantages in filtering out small interfering micro-objects and thus reducing matrix effects. Applying the novel approach to real-time cell monitoring, a 3D-printed microstructure-integrated platform shows higher sensitivity (i.e., the slope of the calibration curve) to model redox analytes in cell culture medium compared to bare electrodes, which display compromised sensitivity due to cell passivation. This research opens a new avenue for mitigating matrix interference and enhancing electrochemical sensing with significant implications across a broad range of applications.