Target-Triggered Polymerization for Biosensing

Because of the potential applications of biosensors in clinical diagnosis, biomedical research, environmental analysis, and food quality control, researchers are very interested in developing sensitive, selective, rapid, reliable, and low-cost versions of these devices. A classic biosensor directly transduces ligand-target binding events into a measurable physical readout. Because of the limited detection sensitivity and selectivity in earlier biosensors, researchers have developed a number of sensing/signal amplification strategies. Through the use of nanostructured or long chain polymeric materials to increase the upload of signal tags for amplification of the signal readout associated with the ligand-target binding events, researchers have achieved high sensitivity and exceptional selectivity. Very recently, target-triggered polymerization-assisted signal amplification strategies have been exploited as a new biosensing mechanism with many attractive features. This strategy couples a small initiator molecule to the DNA/protein detection probe prior to DNA hybridization or DNA/protein and protein/protein binding events. After ligand-target binding, the in-situ polymerization reaction is triggered. As a result, tens to hundreds of small monomer signal reporter molecules assemble into long chain polymers at the location where the initiator molecule was attached. The resulting polymer materials changed the optical and electrochemical properties at this location, which make the signal easily distinguishable from the background. The assay time ranged from minutes to hours and was determined by the degree of amplification needed. In this Account, we summarize a series of electrochemical and optical biosensors that employ target-triggered polymerization. We focus on the use of atom transfer radical polymerization (ATRP), as well as activator generated electron transfer for atom transfer radical polymerization (AGET ATRP) for in-situ formation of polymer materials for optically or electrochemically transducing DNA hybridization and protein-target binding. ATRP and AGET ATRP can tolerate a wide range of functional monomers. They also allow for the preparation of well-controlled polymers with narrow molecular weight distribution, which was predetermined by the concentration ratio of the consumed monomer to the introduced initiator. Because the reaction initiator can be attached to a variety of detection probes through well-established cross-linking reactions, this technique could be expanded as a universal strategy for the sensitive detection of DNA and proteins. We see enormous potential for this' new sensing technology in the development of portable DNA/protein sensors for point-of-need applications.