Stephen, A.N. orcid.org/0009-0005-4471-080X, Holden, M.A. orcid.org/0000-0003-3060-7615, Sullivan, M.V. orcid.org/0000-0002-1771-8268 et al. (3 more authors) (2025) Optimised solution-phase synthesis of NanoMIPs for protein detection in electrochemical diagnostics. Biomedical Materials, 20 (2). 025043. ISSN 1748-6041
Abstract
NanoMIPs are nanoscale molecularly imprinted polymers (MIPs) ranging in size between 30 to 300 nm offering a high affinity binding reagent as an alternative to antibodies. They are being extensively research for applications in biological extraction, disease diagnostics and biosensors. Various methodologies for nanoMIP production have been reported demonstrating variable timescales required, sustainability, ease of synthesis and final yields. We report herein a fast (< 1hr) method for one pot aqueous phase synthesis of nanoMIPs using an acrylamide-based monomer and N,N'-methylenebisacrylamide crosslinker. NanoMIPs were produced for a model protein template namely haemoglobin from bovine species. We demonstrate that nanoMIPs can be produced within 15 minutes. We investigated reaction quenching times between 5 and 20 minutes. Dynamic light scattering results demonstrate a distribution of particle sizes (30 nm to 900 nm) depending on reaction termination time, with hydrodynamic particle diameter increasing with increasing reaction time. We attribute this to not only particle growth due to polymer chain growth but based on AFM analysis, also a tendency (after reaction termination) for particles to agglomerate at longer reaction times. Batches of nanoMIPs ranging 400 to 800 nm, 200 to 400 nm and 100 to 200 nm were isolated using membrane filtration. The batches were captured serially on decreasing pore size microporous polycarbonate membranes (800 to 100 nm) and then released with sonication to isolate nanoMIP batches in the aforementioned ranges. Rebinding affinities of each batch were determined using electrochemical impedance spectroscopy, by first trapping nanoMIP particles within an electropolymerized thin layer. Binding constants determined for NanoMIPs using the E-MIP sensor approach are in good agreement with surface plasmon resonance results. We offer a rapid (<2 hr) and scalable method for the mass production (40-80 mg per batch) of high affinity nanoMIPs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). Published by IOP Publishing Ltd. Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 license (https://creativecommons.org/licenses/by/4.0/). Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. |
Keywords: | affinity reagents; electrochemical; molecularly imprinted polymers; nanoMIPs; protein diagnostics |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematical and Physical Sciences |
Funding Information: | Funder Grant number Engineering and Physical Sciences Research Council EP/V046594/2 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Feb 2025 12:20 |
Last Modified: | 14 Mar 2025 10:55 |
Status: | Published |
Publisher: | IOP Publishing |
Refereed: | Yes |
Identification Number: | 10.1088/1748-605x/adb672 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223857 |