Real-Time Monitoring of Biomolecules: Dynamic Response Limits of Affinity-Based Sensors

[Image: see text] Sensors for monitoring biomolecular dynamics in biological systems and biotechnological processes in real time, need to accurately and precisely reconstruct concentration–time profiles. This requirement becomes challenging when transport processes and biochemical kinetics are important, as is typically the case for biomarkers at low concentrations. Here, we present a comprehensive methodology to study the concentration–time profiles generated by affinity-based sensors that continuously interact with a biological system of interest. Simulations are performed for sensors with diffusion-based sampling (e.g., a sensor patch on the skin) and advection-based sampling (e.g., a sensor connected to a catheter). The simulations clarify how transport processes and molecular binding kinetics result in concentration gradients and time delays in the sensor system. Using these simulations, measured and true concentration–time profiles of insulin were compared as a function of sensor design parameters. The results lead to guidelines on how biomolecular monitoring sensors can be designed for optimal bioanalytical performance in terms of concentration and time properties.