Tiny tracers

UK universities are developing a low-cost, ultra sensitive universal biosensor to measure minute concentrations of biological molecules

A consortium of UK universities is developing a low-cost, ultra sensitive universal biosensor that could be used for everything from home diagnosis of disease to chemical plant monitoring and anti-bioterrorism and pandemic detection.

Researchers from Cambridge, Manchester and Bolton universities, as well as China’s Zhejiang University, are taking part in the three-year, EPSRC-sponsored project, led by Prof Jack Luo of Bolton’s Centre for Materials Research and Innovation.

Biosensors are a type of microdevice that are able to measure very small concentrations of biological molecules or chemical substances through specific bio-binding or chemical absorption.

Their current uses include medical diagnosis, measuring such chemicals as anthrax in the fight against terrorism and the prevention of the spread of pandemics by detecting pathogens. They are showing great promise in the early diagnosis of cancers and genetic disorders.

Biosensors work by recording reactions between chemicals or agents on their surface and others to which they are exposed. For example, if an antibody is placed on their surface and then they are exposed to a sample from a patient such as blood, antigens within the blood may react with the antibodies and bind to the surface, showing that the antigen is present.

‘Our aim is to develop a universal detection system that can have various surface properties depending on what the sensor is to be used for,’ explained Luo.

Deployment of biosensors at key public locations could enable detection of communicable diseases or dangerous biological substances before an incident or mass infection occurred, preventing the spread of diseases or biochemical attack.

However, such high quality biosensors must be very sensitive, as well as being easy to use, low cost and able to work at speed with integrated electronics.

Although many technologies have been developed, such as microarrays and label-free electrochemical and optical biosensors, they all have various limitations including a lack of sensitivity and resolution, and precise control of the sample position. large device size and lack of scaleability is also a problem.

The consortium is therefore working to develop a technology for biochemical detection using the most advanced film bulk acoustic wave resonator (FBAR) techniques. The device has a structure similar to extremely sensitive mass sensing quartz crystal microbalance devices, but is several hundred times smaller, consisting of a submicrometer thick piezoelectric active layer with electrodes on both sides.

As a number of biosensors can be placed on a small area, this makes for much better accuracy of detection. ‘The biosensor can detect only a few molecules on its surface,’ said Luo. ‘It determines what the molecules are by measuring their weight. As this increases we can tell how many molecules there are. The advantages of an FBAR sensor is that each measurement device is so small we may be able to put several antigens or antibodies on each sensor, meaning it could detect a number of diseases from the same sample. As the system involves electronics, we can read results almost instantly, unlike fluorescent tagging based systems. This would be ideal for a self-diagnostic device using saliva, for example.’

Applying alternating current to the sensor generates a standing wave between the two electrodes and creates a resonant frequency that is extremely sensitive to mass attached on the electrode surface owing to the small dimensions of the device and high operating frequency.

The consortium will initially focus on the development of high performance FBARs using piezoelectric zinc oxide thin films, as the technology is relatively mature.

At the same time the group will develop biosensors using prostate-specific antigens and the peptide aptamers that specifically bind to them, creating a system that could detect prostate cancers.

They will then turn to development of novel FBARs on glass and plastic substrates using low-cost piezoelectric-polymers such as polyvinylidene fluoride that has similar properties to piezoelectric ceramics, but is both biocompatible and chemically inert. Owing to their flexibility, this will allow fabrication of biosensors on low-cost glass and plastic substrates.

The aim of the final device is to be universal, have ultra-high sensitivity, as well as the benefit of being small and suitable for multi-detection. It should also be low cost.

Bolton will work on modelling and design, as well as material and device characterisation. It will also be responsible for modelling and design. Meanwhile, Cambridge will add device fabrication expertise and experience. Manchester will concentrate on protein adsorption, interfacial conformation, structural unfolding, and synthesis and cloning of peptide aptamers.

Julia Pierce