Industrial food processes
are monitored to ensure that
food is
being produced with good quality, yield, and productivity. For developing
innovative real-time monitoring and control strategies, real-time
sensors are needed that can continuously report chemical and biochemical
data of the manufacturing process. Here, we describe a generalizable
methodology to develop affinity-based biosensors for the continuous
monitoring of small molecules in industrial food processes. Phage-display
antibody fragments were developed for the measurement of small molecules,
as exemplified with the measurement of glycoalkaloids (GAs) in potato
fruit juice. The recombinant antibodies were selected for use in a
competition-based biosensor with single-molecule resolution, called
biosensing by particle motion, using assay architectures with free
particles as well as tethered particles. The resulting sensor measures
GAs in the micromolar range, is reversible, has a measurement response
time below 5 min, and enables continuous monitoring of GAs in protein-rich
solutions for more than 20 h with concentration measurement errors
below 15%. The demonstrated biosensor gives the perspective to enable
a variety of monitoring and control strategies based on continuous
measurement of small molecules in industrial food processes.