An inductive sensor for continuous in-line monitoring of proteolytic cleavage

Abstract

Proteases are an important type of enzyme that chemically cleave proteins and peptides, and can serve as useful biomarkers in both the context of healthcare and some industrial processes. Devices that enable routine and inexpensive measurement of proteolytic cleavage could facilitate ubiquitous protease activity monitoring and offer a wealth of actionable data. In this project, we developed a device intended for liquid samples in which magnetic nanoparticles are bound via cleavable peptides to a chemically modified mm-scale fluidic channel in a disposable glass and PDMS chip situated over an inductive sensor. When an active protease corresponding to the peptide substrate is present in the fluid passing through the device, the magnetic particles are released from the active region of the sensor and exit the device. The sensor, which includes a 7 turn excitation coil and a set of 14-turn gradiometer coils, is entirely formed by highly symmetric traces in an 8-layer printed circuit board. Using 100 µs pulsed fields generated through capacitive discharge and amplifying the output of the gradiometer, we are able to show a limit of detection below 1 µg of iron, and regulate the temperature of the fluidic device by varying the pulse rate to control Joule heating. While further optimization of the sensor is still required, our current prototype exhibits a detection sensitivity below 1 µM for the protease chymotrypsin.