Design considerations of aptasensors for continuous monitoring of biomarkers in digestive tract fluids

We present a porous Si (PSi)-based label-free optical biosensor for sensitive and continuous detection of a model target protein biomarker in gastrointestinal (GI) tract fluids. The biosensing platform is designed to continuously monitor its target protein within the complex GI fluids without sample preparation and washing steps. An oxidized PSi Fabry-Pérot thin films are functionalized with aptamers, which are used as the capture probes. The optical response of the aptamer-conjugated PSi is studied upon exposure to unprocessed GI fluids, originated from domestic pigs, spiked with the target protein. We investigate biological and chemical surface passivation methods to stabilize the surface and reduce non-specific adsorption of interfering proteins and molecules within the GI fluids. For the passivated PSi aptasensor we simulate continuous in vivo biosensing conditions, demonstrating that the aptasensor could successfully detect the target in a continuous manner without any need for surface washing after the target protein binding events, at a clinically relevant range. Furthermore, we simulate biosensing conditions within a smart capsule, in which the aptasensor is occasionally exposed to GI fluids in flow or via repeated cycles of injection and static incubation events. Such biosensor can be implemented within ingestible capsule devices and used for in situ biomarker detection in the GI tract.