What is a MIP-based biosensor? A guide to "plastic antibodies"

Antibodies are nature's specialists in molecular recognition: they bind their targets by shape and chemistry. Molecularly imprinted polymers (MIPs) borrow the same idea, but build the receptor from synthetic polymer instead of protein. That is why they are often called "plastic antibodies". Placed on an electrode, a MIP becomes the recognition layer of a sensor that can measure a single compound in a complex sample.

Why look beyond antibodies?

Biological receptors such as antibodies and enzymes are highly selective, but they can be costly to produce and sensitive to heat, pH and storage conditions. MIPs are synthetic receptors made for a chosen target molecule. Because they are cross-linked polymers, they are generally robust, inexpensive and stable, which makes them attractive for sensors that need to work outside a specialised laboratory.

How a MIP is made, in three steps

1. Pre-complex: functional monomers arrange around a template molecule (the target, or a close analogue) through interactions such as hydrogen bonds, electrostatic or hydrophobic contacts.

2. Polymerisation: a cross-linker is added and the mixture is polymerised (thermally, by light or electrochemically), freezing the monomers in place around the template.

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

A useful analogy is a key pressed into soft clay that is then allowed to harden: only that key, or one very much like it, fits the print.

Schematic, not to scale: a screen-printed electrode (bottom) and a magnified view of its imprinted polymer layer. Target molecules (gold) sit in shape-matched cavities; a look-alike molecule (blue) does not fit.

From recognition to a measurable signal

In a MIP-based sensor, the imprinted layer sits on a transducer. Electrochemical transducers, such as small disposable electrodes, are a popular choice because they are sensitive, inexpensive and portable. When target molecules occupy the cavities, the electrode's response changes. A common readout is the current of a redox probe, which falls as more cavities are filled and the probe's access to the electrode surface is reduced. Measuring standards of known concentration turns this change into a calibration curve.

Selectivity is checked rather than assumed. A non-imprinted polymer (NIP), made in the same way but without the template, serves as a control, and structurally similar molecules are tested as potential interferents. A look-alike molecule with a different shape fits poorly and gives a smaller response.

Key takeaways

• MIPs are synthetic receptors shaped by the target molecule itself.

• Cross-linked polymers are robust, low-cost and stable compared with many biological receptors.

• Coupled with an electrode, a MIP turns molecular recognition into a measurable electrical signal.

MIP sensors at SAOnS Lab

At SAOnS Lab, we design MIP-based electrochemical sensors for drugs and biomarkers in pharmaceutical and biological samples. One example from our group is a sensor in which a ZnO nanoparticle-supported MIP was used for the selective detection of the anticancer drug sorafenib (Çetinkaya et al., 2023).

Which molecule would you like to see a "plastic antibody" made for? Tell us on LinkedIn or via our website.

References

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

Saylan, Y., Akgönüllü, S., Yavuz, H., et al. (2019). Molecularly imprinted polymer based sensors for medical applications. Sensors, 19(6), 1279. https://doi.org/10.3390/s19061279

Çetinkaya, A., Kaya, S. I., Alahmad, W., et al. (2023). Designing an electrochemical sensor based on ZnO nanoparticle-supported molecularly imprinted polymer for ultra-sensitive and selective detection of sorafenib. Analytica Chimica Acta, 1280, 341866. https://doi.org/10.1016/j.aca.2023.341866