Through the process of living polymerisation, researchers at Cranfield University, UK, claim to have developed the first soluble monoclonal nanoscale molecular imprinted polymers (nanoMIPs) for potential application in analytical chemistry, pharmacology, crime prevention and the food industry.

Covalent and non-covalent molecular imprinted polymers (MIPs) have been in existence for decades, synthesised through template polymerisation, where a polymeric structure is formed in the presence of another polymer or organic template, which acts as a pattern for the new material. Anthony Turner, Professor of Biotechnology at Cranfield University, says, 'Subsequent removal of the template leaves binding sites within the polymer, processing both the shape and correction orientation to allow selective recognition of the imprint species.

It is this selectivity and stability, compared to natural receptors, that has enabled MIPs to be used in solid-phase extraction cartridges and chromatography in the pharmaceutical industry, as well as in affinity sensors.

Yet one of the main limitations of these MIPs is insolubility in water and organic solvents, restricting their use in pharmacology and medicine.

Pippetting particles of a molecular imprinted polymer into a quartz crystal microbalancing sensor chip (Image: Dr M Whitcombe)The team at Cranfield claims to have now successfully produced soluble nanoMIPs. Researchers have used a living polymerisation technique - template polymerisation occurs in the presence of an iniferter (a living initiator - diethyldithiocarbamic acid benzyl ester).

Professor Sergey Piletsky, co-worker on the research project, says, 'Living polymerisation has previously been used to produce bulk grafted MIPs, but no-one has developed soluble MIPs [using this process].' Living polymerisation enables polymer chains to grow at a more constant and controlled rate and length due to the absence of side reactions, such as the termination of a polymer chain or chain transfers.

Piletsky adds, 'In the Cranfield work, polymerisation is terminated at an early stage when the size of the molecules is small (30-100 kilodaltons). The product can exist in a soluble or colloidal form in either aqueous or organic liquids. Synthesised in this way, molecules have a higher affinity to the template and rebind it in vitro and/or in vivo.

The team believes nanoMIPs could eventually be used as 'biologically active molecules' - drugs, effectors, modulators or inhibitors - and as 'plastic antibodies' in analytical chemistry. In the latter application, Turner explains, 'This new class of highly stable nanoMIPs provides a direct substitute for a [less stable] biologically derived sensing element [such as antibodies] in affinity sensors, and can thus generate optical, electrochemical or piezoelectric sensors for a wide range of analytes.

Cranfield has already licensed the technology to two start-up companies to develop devices that, unlike biosensors, can withstand high temperatures for use in sectors such as process control in the pharmaceutical industry. New concepts that involve spraying these nanoparticles for detecting materials on surfaces and decontamination are also being put forward.

'This research opens up a wide range of avenues. It is not just restricted to new sensors, but could find application as novel imaging agents or for targetted drug release,' adds Turner.

To aid the selection of functional monomers from over 4,000 possibilities, the team has developed a more rational computational approach to nanoMIP design, which combines molecular modelling software with a virtual library of monomers. 

Further information:

Anthony Turner, email: a.p.turner@cranfield.ac.uk.