A team of Imperial researchers has developed a tool which 'lights up' when it detects the chemical signature of harmful bacteria in the lung.

In a clinical first, the group from the Department of Medicine used the tools, called cell-free biosensors, to test samples of sputum from patients with cystic fibrosis (CF).

Biosensors are based on engineered DNA circuits, designed to detect changes in their environment, such as the presence of chemicals, or changes in pH or temperature.

These tools, which harness the biological machinery inside cells, can be used to quickly spot chemical traces of active microbial colonies in samples from the lung and could help to accurately diagnose bacterial infections in vulnerable patients.

In a small, proof-of-concept study, the team found that their biosensors could accurately detect markers of Pseudomonas bacteria – a leading cause of chest infections in people with weak immune systems or chronic conditions, such as CF – and were as sensitive as existing chemical diagnostic tests but could potentially be cheaper and easier to use.

The researchers are hopeful they could eventually develop their cell-free sensors into a range of rapid diagnostic tests which could be used either at home, GP surgeries or in hospital clinics or even in remote areas of the world with limited access to hospital diagnostics, at a fraction of the price of existing tests.

Professor Paul Freemont, co-founder and co-director of The Centre for Synthetic Biology and Innovation at Imperial, said: “The driving force behind this research is to show that these tools work and could be used to detect particular diagnostic markers associated with infection.”

He added: “By applying an engineering approach to biology, these systems could be altered to sense for any microbe we choose. The possibilities for public health and cost-savings for health systems could be considerable.”

Biosensors have emerged through the growing field of synthetic biology, with scientists tweaking living cells to respond to certain conditions, such as the presence of a chemical compound.

At the heart of the technique are lengths of engineered DNA which, when inserted into a living cell, act as a circuit. If the right signal – such as a specific chemical compound – is present, then the circuit is switched ‘on’ and the cell produces a signal in the form of a coloured output, in this case a green fluorescent protein. If the substrate is not present, then the circuit remains ‘off’ and there is no signal.

In the latest study researchers report on using a ‘cell-free’ form of sensor to test clinical samples for the first time. Instead of being contained within the membrane of a cell, the engineered DNA circuit and cellular machinery of their sensors are free-floating in a solution.

The team engineered their sensor’s circuit to respond to a molecule produced specifically by the bacterium Pseudomonas aeruginosa. These bacteria release a chemical signature in order to communicate with bacteria around them and to sense how many of them there are. As they replicate, more cells release the signature, and so the concentration of the signal increases, giving the bacteria an idea of the state of their population.

Previous studies have revealed levels of this same P. aeruginosa signature were higher in hospitalised patients than those with stable condition.

Samples taken from the lungs of patients, either with or without P. aeruginosa infection, were screened by adding them to tiny wells containing solutions of the biosensor. After four hours the samples were tested for green fluorescent protein – a sign that the bacterial signature was present.

Analysis revealed that the cell-free biosensor was able to detect the bacterial signature with the same accuracy as existing diagnostic tests, called liquid chromatography tandem mass spectrometry (LC-MS/MS).