Inductively Detectable Nanorobots for Detecting Protease Activity

Proteases, a class of enzymes that cleave peptide bonds, are centrally involved in healthy processes throughout the human body. Many chronic ailments, including cancer, arthritis, and nonhealing wounds exhibit altered patterns of extracellular protease activity, making proteases a powerful diagnostic target for stratifying patients, monitoring treatment, or informing therapeutic decision making. For measurement of proteolytic activity to become commonplace in the clinic, new technologies are needed to lower the barrier to detection at the point-of-care.<br/><br/>Here, we explore a concept for the inductive detection of protease activity based on magnetic nanorobots. These nanorobots consist of a self-assembled monolayer of iron oxide magnetic nanoparticles (25 nm) on a larger silica core (600 nm), covalently bound via selectively cleavable peptide linkers. Cleavage of these linkers then triggers the magnetic nanoparticles to dissociate from the core particle, altering their magnetization response to applied magnetic fields. To detect their disassembly, a prototype pulsed field magnetometer has been designed, which makes use of capacitive discharge to produce a driving field with a variable timescale of 100s of µs and adjustable magnitude of 10s of mT. Compared to inductive detection based on alternating magnetic fields, the pulsed field approach offers the possibility for a smaller form factor and full integration into mass producible printed circuit boards, considerations that suggest greater suitability for point-of-care detection devices.