Tiny plastic particles engineered to grab specific molecules are being put through a new separation technique that could reveal their structure and behaviour for the first time. These particles—molecularly imprinted polymer nanoparticles, or nanoMIPs—are synthetic mimics of natural antibodies. They can bind to targets like proteins or toxins with high selectivity, making them promising for diagnostics, drug delivery, and environmental monitoring. But current analytical tools, such as dynamic light scattering or electron microscopy, cannot resolve their complex, heterogeneous structures or track how they interact with biological targets. This limits their development and commercial use. The project will adapt asymmetric flow field-flow fractionation (AF4)—a high-resolution separation method—to sort nanoMIPs by size and shape. Researchers at the University of Manchester and the University of Sheffield will combine expertise in AF4 and MIP design, working with industry partner PostNova to ensure the protocols are commercially viable. If successful, AF4 could become a routine tool for characterising nanoMIPs. That would accelerate their use as stable, durable alternatives to antibodies in biosensors, enable more selective drug carriers, and improve detection of pollutants in water. The work is applied, not fundamental science—it directly targets a bottleneck in bringing nanoMIPs from lab to market.
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Molecularly imprinted polymers (MIPs) are synthetic materials engineered to mimic natural recognition processes, offering high selectivity and affinity for target molecules. NanoMIPs, the nanoscale version of MIPs, have shown great promise in fields such as diagnostics, drug delivery, and environmental monitoring. However, a major challenge remains in the detailed characterisation of nanoMIPs, particularly in understanding their structure, heterogeneity, and interactions with biological targets like proteins or extracellular vesicles (EVs). Current techniques, such as dynamic light scattering (DLS) or transmission electron microscopy (TEM), provide limited insight, often lacking the resolution and detail needed for complex, polydisperse systems. This project aims to address this gap by developing asymmetric flow field-flow fractionation (AF4) as a powerful platform for studying nanoMIPs. AF4 is a versatile separation technique that provides high-resolution fractionation of particles based on size and shape making it well-suited for the analysis of sensitive materials like nanoMIPs. Our project seeks to unlock the potential of AF4 for high-resolution characterisation of nanoMIPs, providing new tools to study their structure and molecular recognition properties in unprecedented detail. This project will bring together experts from the University of Manchester and the University of Sheffield, combining complementary strengths. McDonald’s group at Manchester specialises in AF4 and nanoparticle characterisation, while Turner’s team at Sheffield is a leader in MIP design and synthesis. Together, they will leverage cutting-edge AF4 instrumentation at the Henry Royce Institute and collaborate with PostNova, an industry leader in AF4 technology, to ensure the development of protocols that are both scientifically rigorous and commercially viable. The characterisation and understanding of nanoMIPs remain limited by current analytical techniques, which struggle to resolve the complex structures and heterogeneous nature of these materials. This project seeks to overcome these limitations by developing AF4 into a robust platform capable of separating and analysing nanoMIPs at high resolution. Moreover, the project will explore the interactions between nanoMIPs and biological targets, which is crucial for applications in fields like biosensing and targeted drug delivery. Aims and Objectives: This project will develop AF4 as a routine analytical tool for nanoMIP characterisation. The specific objectives are: Design and optimise methods for the AF4 platform to provide high-resolution separation and analysis of MIP nanoparticles. Validate the AF4 platform by comparing it with existing analytical techniques demonstrating its capabilities, and limitations. Characterise the size, shape, and molecular recognition properties of nanoMIPs using AF4 when interacting with either a free protein, or surface-bound protein (EV model). Explore the relationship between nanoMIP synthesis parameters and their ability to be studied via the AF4 technique. The successful development of AF4 as a platform for nanoMIP characterization will have wide-reaching impacts across several fields. In diagnostics, nanoMIPs could be used as robust alternatives to antibodies, leading to more stable and durable biosensors. In drug delivery, understanding nanoMIP-target interactions will enable the design of more selective drug carriers, improving therapeutic outcomes. The ability to precisely characterise nanoMIPs will also be critical in environmental monitoring, where these materials could be used for detecting pollutants or toxins with high specificity. Overall, this project will establish AF4 as an essential tool for nanomaterials research, supporting the commercialisation of nanoMIPs.
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