Template, monomer, cross-linker: how a molecularly imprinted polymer is made

Molecularly imprinted polymers (MIPs) are often called "plastic antibodies" because they recognise a target by shape and chemistry. But how do you actually make a polymer that remembers a molecule? The recipe has a handful of ingredients and three key steps.

The ingredients

• Template: the target molecule itself, or a close structural analogue, around which the polymer is built.

• Functional monomer: small molecules with groups that interact with the template, for example by hydrogen bonding, electrostatic or hydrophobic interactions.

• Cross-linker: a molecule with two or more polymerisable groups that ties the chains into a rigid three-dimensional network.

• Solvent (porogen) and initiator: the solvent dissolves everything and shapes the pore structure; the initiator starts the polymerisation.

Three steps from mixture to recognition site

1. Pre-complex formation: the functional monomers arrange themselves around the template. The strength and number of these template–monomer interactions largely decide how selective the final MIP will be.

2. Polymerisation: the network is formed around the complex. This can be started by heat (thermal polymerisation), by UV or visible light (photopolymerisation), or, for sensors, directly on the electrode surface by applying a potential to electroactive monomers (electropolymerisation).

3. Template removal: the template is washed or extracted out of the polymer. What remains are cavities that match the template in size, shape and the position of chemical groups.

Schematic, not to scale: pre-complex formation (left), polymerisation with a cross-linker (centre) and template removal leaving a shape-matched cavity (right).

Think of making a plaster cast of a hand: you position the hand, let the plaster set around it, and then gently pull the hand out. The cast keeps the exact imprint. In a MIP, the "hand" is a molecule and the plaster is a cross-linked polymer.

Details that make or break a MIP

Small choices have big effects. The ratio of template to monomer to cross-linker, the polarity of the solvent and the polymerisation conditions all influence how many good binding sites form and how accessible they are. Before synthesis, template–monomer interactions can be screened with computer simulations and spectroscopic methods such as UV-Vis, FTIR and NMR. After synthesis, the template must be removed as completely as possible, because leftover template can slowly leak out and be mistaken for a real signal. A non-imprinted polymer, made the same way but without the template, is prepared in parallel as a control.

Key takeaways

• A MIP is built from a template, functional monomers, a cross-linker, a solvent and an initiator.

• Pre-complex formation, polymerisation and template removal create shape-matched cavities.

• Thermal, photo- and electropolymerisation suit different formats; electropolymerisation builds the MIP directly on the sensor.

MIPs at SAOnS Lab

At SAOnS Lab, we design MIP-based electrochemical sensors for drugs and biomarkers, choosing monomers and polymerisation methods for each target. One example from our group is a molecularly imprinted polymer-based electrochemical sensor for the determination of the drug tofacitinib (Budak et al., 2023).

Which step of MIP synthesis do you find most challenging? Contact us and let us know.

References

Hasanah, A. N., Safitri, N., Zulfa, A., et al. (2021). Factors affecting preparation of molecularly imprinted polymer and methods on finding template-monomer interaction as the key of selective properties of the materials. Molecules, 26(18), 5612. https://doi.org/10.3390/molecules26185612

BelBruno, J. J. (2019). Molecularly imprinted polymers. Chemical Reviews, 119(1), 94–119. https://doi.org/10.1021/acs.chemrev.8b00171

Budak, F., Çetinkaya, A., Kaya, S. I., et al. (2023). A molecularly imprinted polymer-based electrochemical sensor for the determination of tofacitinib. Microchimica Acta, 190(6). https://doi.org/10.1007/s00604-023-05790-3