Microdialysis SPR: diffusion-gated sensing in blood† †Electronic supplementary information (ESI) available: Materials and supplementary figures. See DOI: 10.1039/c5sc00716j

Chemical measurements are rarely performed in crude blood due to the poor performance of sensors and devices exposed to biofluids. In particular, biosensors have been severely limited for detection in whole blood due to surface fouling from proteins, the interaction of cells with the sensor surface and potential optical interference when considering optical methods of analysis. To solve this problem, a dialysis chamber was introduced to a surface plasmon resonance (SPR) biosensor to create a diffusion gate for large molecules. This dialysis chamber relies on the faster migration of small molecules through a microporous membrane towards a sensor, located at a specified distance from the membrane. Size filtering and diffusion through a microporous membrane restricted the access of blood cells and larger biomolecules to a sensing chamber, while smaller, faster diffusing biomolecules migrated preferentially to the sensor with limited interference from blood and serum. The affinity of a small peptide (DBG178) with anti-atherosclerotic activity and targeting type B scavenger receptor CD36 was successfully monitored at micromolar concentrations in human serum and blood without any pre-treatment of the sample. This concept could be generally applied to a variety of targets for biomolecular interaction monitoring and quantification directly in whole blood, and could find potential applications in biochemical assays, pharmacokinetic drug studies, disease treatment monitoring, implantable plasmonic sensors, and point-of-care diagnostics.