Development of a new class of biosensors with unique capabilities

The sensor industry sees great promise in whole-cell-based biosensors, but because it relies on silicon-based microelectronics it requires biosensors with electrogenic outputs. We have recently developed technology that uses engineered cells that send the signal to the bacterial flagellar motor for electrical detection by producing a protein that interacts with the motor.

In such a way, we are changing any current existing whole-cell sensor for application with our bioelectrical interface. The bioelectrical interface is a biochip array of bacterial cells that produce an electrical biosensor output whose principle of action remains the same irrespective of the analyte.

In this project, we wish to develop several other sensors that are of interest for environmental water sensing and characterise the signal we are obtaining with our technology. Furthermore, we will attempt to engineer bacterial chemoreceptors themselves. Chemoreceptors are effectively antennas bacterial cells use to sense their environment and send the signal down to bacteria flagellar motor.

Because the motor controls the swimming, this effectively helps bacteria navigate the environment. By engineering chemoreceptors, (i) our current technology gains in response time (down to seconds), (ii) it will be easily reconfigurable (re-purposing current biosensors for novel analytes will take a few months instead of years), and (iii) we will learn about the fundamental principles of receptor signaling.

New candidate chemoreceptors that respond to analytes of interest will be obtained from different microbes and improved by directed evolution. These will be tested either by our bioelectrical interface of optically, with a high throughput microfluidic screening platform.

This project addresses a large challenge area because of the significant need for the development of new sensor technologies for a wide range of liquid-based applications, from monitoring of chemical markers of interest (e.g. toxins, pollutants) in environmental water to detecting biomarkers of disease or infection in diagnostic tests. The gold standard for many mentioned tests involves sample collection and processing in a laboratory facility, which is a time-consuming and expensive process.

Various sensor technologies exist to provide in situ detection or monitoring of markers of interest on a faster timescale, e.g. optical, electrochemical, cell-free, immunoassay, and microfluidic wet chemistry techniques. However, all come with capability gaps, such as bulky equipment, qualitative-only, single-use, and one-timepoint-only solutions. There are also fundamental limitations to what analytes can be detected with existing solutions, and, e.g. metals, nerve agents, and bespoke pharmaceuticals, are usually beyond reach.

Importantly, the lead time to develop new sensitivities to detect emerging threats for existing sensor technologies is long (years), because they require completely new protocols to be developed or new hardware to be engineered. Our technology can address these challenges and this project can develop a unique new class of biosensors.