Small cast, big hopes

March 9, 2001

A technique that lets you make a plastic mould of molecules could help clean blood of toxins and perform many industrial applications. Geoff Watts reports.

Press a coin firmly into a piece of Plasticine, then remove it. What remains is a cavity into which only another coin of the same denomination can fit perfectly. Now imagine that instead of using a coin, you use a molecule. That, in essence, is the principle of molecularly imprinted polymers, or “mips”.

This most unlikely technique was dreamed up 20 years ago by a Swede working in Lund, Klaus Mosback, and a German from Düsseldorf, Gunter Wulff. Coins pressed into Plasticine - or the old prisoners’ trick of making an impression of the jailer’s key in a bar of soap - are helpful analogies. But mips need neither Plasticine nor soap. The technique, as its name suggests, relies on polymerisation, the process by which small molecules, or monomers, can be induced to link together to form long-chain molecules, or polymers. It is the chemical basis of plastics manufacture and of acrylic glues. To make an impression of a molecule, you mix a solution of it with a liquid monomer that you then polymerise. You end up with a solid lump of plastic in which are entombed countless numbers of the molecules for which you want a mould.

The next step is to smash the lump of plastic. Some of the breakage planes will happen to go straight through trapped molecules, any two such bits of the plastic then separating like the halves of a conventional mould. But there is another way in which the desired molecular impressions can be recovered. The polymerised plastic may look solid, but it has a sponge-like structure that encloses vast numbers of tiny bubbles. Many of these bubbles will have the molecules of interest lying at their surface. When they are washed out of the exposed plastic fragments, they leave behind tiny but faithful impressions. “Getting the technique to work is quite easy,” says Keith Brain of Cardiff University’s School of Pharmacy. But he adds an important rider. “Getting it to work well is much harder.”

When Mosback and Wulff first described what they had done, critics were disinclined to believe them. Once it became clear that molecular imprinting does occur, the critics’ view changed from disbelief to dismissal. They saw no use for the technique. Only in the past two to three years has it stopped being seen as an academic curiosity and have scientists begun  to discover its industrial potential.

The list of potential applications of mips is growing rapidly. Mips act, for example, like biological catalysts: enzymes. The imprint of a large molecule you want to make will provide a site in which its smaller components can come together in the correct configuration and then unite to form it. “The difference is that they will do this under conditions in which real enzymes would never survive,” Brain says. “You can boil mips in acid and they remain just as active. Biosensors for detecting the presence of specific chemicals often rely on enzymes. Mips may not be as sensitive, but there are applications in which what counts is to be robust. Mips are ideal.”

Another mips researcher is Cameron Alexander of the School of Pharmacy and Biomedical Sciences at Portsmouth University. Among his interests is the removal of toxins from biological fluids. A smart filter, in other words, perhaps to clean the blood of someone who has swallowed a poison. “Mips may also have a role in environmental problems,” he says. “You can imagine suspending printed polymers in the water flowing out of a chemical plant to recover unpleasant materials that might otherwise find their way into a river.”

Other ideas for using mips are as “plastibodies” (artificial equivalents of the immune defence system’s antibody molecules) in extracting organophosphorous compounds from spent sheep-dip and for screening molecules of possible value to the drug industry.

Research is also going ahead to improve the process of making the impressions. Kal Karim works at Cranfield University’s Institute of Biosciences and Technology. “So far, people have been fascinated by the fact that you can do this at all and have not been thinking too much about doing it more effectively. We are trying to do things more rationally using molecular modelling and a computational approach.”

He and his colleagues have collected data on all the commercially available monomers that polymerise easily and can be used for molecular imprinting. They use computer software to predict which monomers will yield the best imprint of any given molecule.

“Most molecularly imprinted polymers have been made by a trial-and-error process,” Alexander notes. “I’m interested in trying to construct them stepwise, rather as one might build using Lego blocks.

“Normally when you make a polymer, its growth is not very well controlled. The resulting chains are all tangled up. It’s like a pit of snakes of vastly different sizes all writhing around. What we would like to do is have all the snakes of the same size, and all grabbing one another at the same point.” More consistent polymers should yield, among other things, better impressions.

At least one mip is already being used commercially to perform a chemical separation. More industrial applications seem likely to follow soon. You might say that they have begun to make an impression.         

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