3D-printed electrochemical cells for multi-point aptamer-based drug measurements

Electrochemical aptamer-based (E-AB) sensors achieve detection and quantitation of biomedically relevant targets such as small molecule drugs and protein biomarkers in biological samples. E-ABs are usually fabricated on commercially available macroelectrodes which, although functional for rapid sensor prototyping, can be costly and are not compatible with the microliter sample volumes typically available in biorepositories for clinical validation studies. Seeking to develop a multi-point sensing platform for sensor validation in sample volumes characteristic of clinical studies, we report a protocol for in-house assembly of 3D-printed E-ABs. We employed a commercially available 3D stereolithographic printer (FormLabs, $5k USD) for electrochemical cell fabrication and directly embedded electrodes within the 3D-printed cell structure. This approach offers a reproducible and reusable electrode fabrication process resulting in four independent and simultaneous measurements for statistically weighted results. We demonstrate compatibility with aptamer sequences binding antibiotics and antineoplastic agents. We also demonstrate a proof-of-concept validation of serum vancomycin measurements using clinical samples. Our results demonstrate that 3D-printing can be used in conjunction with E-ABs for accessible, rapid, and statistically meaningful validation of E-AB sensors in biological matrices.