Biomimetic self-oxygen-carrying electrochemical biosensor for highly sensitive detection of sarcosine in a single drop of whole blood

Riboflavin (Rf)-based sarcosine-oxidase mimicry is promising for point-of-care testing (POCT) for sarcosine (Sar) in ultra-micro whole blood. However, its sensitivity is limited by oxygen deficiency and blood interferents. Herein, we engineered a polydopamine (PDA)-coated red blood cell (RBC)-based Rf biosensor (PDA@Rf@RBC) with self-carrying oxygen via haemoglobin, boosting Rf catalysis of Sar while the RBC membrane excludes interferents and the PDA shell relays the electrical signal transmission. These integrated functionalities enable the biomimetic PDA@Rf@RBC biosensor to exhibit high sensitivity and robust anti-interference ability, allowing differential pulse voltammetry analysis with a low detection limit of 200 fM and a wide detection range of 10 pM to 100 μM for Sar. Under normal air conditions, the PDA@Rf@RBC biosensor demonstrates good reproducibility and stability for more than 30 days. Its precision is validated across serum, plasma, and whole blood, allowing POCT of trace abnormal Sar levels from a single drop (25 μL) of whole blood. This capability supports the auxiliary diagnosis of PCa and aids in assessing the risk of cardiovascular diseases. The proposed biomimetic electrochemical biosensor offers an efficient, rapid, and convenient approach for detecting blood Sar levels and establishes a novel design paradigm for oxygen-dependent sensors.