Leveraging the detection of proteins to new limits

Researchers from Drexel University in Pennsylvania, US, have published details of the new sensor, that utilises piezoelectric lead zirconate titanate (PZT) films bonded to a base glass cantilever that give very sensitive piezoelectric responses to small stresses - allowing greater response sensitivity and stability than previous approaches. The new research, led by Professor Raj Mutharasan, was published in the latest edition of Analytical Chemistry​ and enhances the successful employment of cantilever biosensors in DNA hybridisation studies and the detection of known cancer proteins, pathogens, biomarkers and explosives. Most current pathogen detection methods require an enrichment step before measurement because the pathogens are often present in concentrations below detection limits. Enrichment by polymerisation chain reaction (PCR) incurs higher costs and requires trained personnel. Cantilever biosensors have attracted considerable interest over the past decade because of their ability to detect proteins and pathogens with high sensitivity and no need to label the molecules of interest. When an antigen binds to the cantilever, the lever bends much like a diving board bends when someone stands on it allowing detection of the antigen's presence. However, many traditional designs have suffered from tedious two-step measurement methods that first bind the antigen to the cantilever before resonance measurement in a vacuum. In dynamic modes, this binding of antigen causes a resonant frequency decrease because of the increase in mass. However, this response is significantly damped under liquid immersion, leading to static deflection methods being preferred for liquid conditions. In flowing samples, perturbations in the liquid flow can cause the cantilever to fluctuate giving noisy background readings and reducing sensitivity. Under these conditions a trade off between the width and the sensitivity is usually observed, with wider cantilevers (mm scale) undergoing less liquid damping but suffering from weaker bending responses that limit detection sensitivity. The new sensor overcomes both these problems with its unique design that allows the detection of a mass change of as little as one femtogram (10^-15​g). The group has shown that these sensors can detect DNA hybridisation at concentrations as low as 1femto Mol (fM) as well as detecting prostate cancer biomarkers even under liquid flow conditions of 0.1 cm/s. The researchers believe that the sensor's sensitivity is comparable to the best performance reported for microcantilevers. This technique also boasts the simplicity of electronic read-out compared with more traditional immunoassay methods. The group is currently seeking interested investors and organisations to commercialise the sensor technology.