A Biomimetic Phosphatidylcholine‐Terminated Monolayer Greatly Improves the In Vivo Performance of Electrochemical Aptamer‐Based Sensors

Abstract The real‐time monitoring of specific analytes in situ in the living body would greatly advance our understanding of physiology and the development of personalized medicine. Because they are continuous (wash‐free and reagentless) and are able to work in complex media (e.g., undiluted serum), electrochemical aptamer‐based (E‐AB) sensors are promising candidates to fill this role. E‐AB sensors suffer, however, from often‐severe baseline drift when deployed in undiluted whole blood either in vitro or in vivo. We demonstrate that cell‐membrane‐mimicking phosphatidylcholine (PC)‐terminated monolayers improve the performance of E‐AB sensors, reducing the baseline drift from around 70 % to just a few percent after several hours in flowing whole blood in vitro. With this improvement comes the ability to deploy E‐AB sensors directly in situ in the veins of live animals, achieving micromolar precision over many hours without the use of physical barriers or active drift‐correction algorithms.