Abstract
The progressive development of biosensors aims to simultaneously provide a high degree of sensitivity in addition to instantaneous detection of specific biomarkers for accurate health surveillance purposes. These self-monitoring health technologies aid in the maintenance of both the physical and mental wellbeing of humankind. The detection and quantification of cortisol and lactate, biomarkers associated with stress, hypoxemia, and bacterial infections (e.g., sepsis) can be achieved via molecularly imprinted polymers (MIPs) performing as synthetic recognition elements in biodevices.Bio-applied MIPs are biomimetic materials with tailor-made synthetic recognition sites, mimicking biological counterparts known for their sensitive and selective analyte detection. Mechanisms of imprinting and subsequent rebinding depend on the choice and composition of the pre- polymerisation mixture, where molecular interactions between the template, functional monomer, crosslinker, and solvent molecules are not fully understood. Here, the synthesis and evaluation of two chemically polymerised molecularly imprinted cortisol- and lactate-selective polymers are reported. These target analytes were selected due to ability to perform as biomarkers for early identification and monitoring of sepsis. Initially, molecular dynamics simulations were utilised to investigate the interactions between all components in the pre-polymerisation mixture of the cortisol- sensitive biomimetic material. Varying the component ratio of the pre-polymerisation mixture indicates that the number of crosslinker molecules relative to the template impacts the quality of imprinting. Understanding the specific intermolecular mechanisms occurring between the template and polymeric network enables experimentalists to make informed decisions regarding monomer- target-porogen selections for improved molecular imprinting and better binding affinities.
To support the development of a rapid, affordable, and portable disease detection system at the point- of-care (POC), an array of conductive polymeric microneedles (MNs), performing as a biointerface material was fabricated. MNs have the potential to provide a miniaturised platform for developed imprinting technologies, owed to their minimally invasive monitoring of analytes in biodevices and wearables. In addition, their miniature structures support their application at POC. There is increasing interest in MNs as electrodes for biosensing, but efforts have been limited to metallic substrates, which lack biological stability and are associated with high manufacturing costs and laborious fabrication methods, creating translational barriers. In this work, additive manufacturing, providing the user with design flexibility and upscale manufacturing was employed to fabricate acrylic-based MN devices. These MN devices were used as platforms to produce two intrinsically conductive, polymer-based surfaces centred on polypyrrole and poly(3,4-ethylenedioxythiophene)- poly(styrenesulfonate) (PEDOT:PSS). These entirely polymer-based solid MN arrays act as dry conductive electrodes while omitting the requirement of a metallic seed layer. Two distinct coating methods of 3D-printed solid MNs, in-situ polymerisation and drop casting, enabled conductive functionality. The MN arrays penetrated ex vivo porcine skin grafts without compromising conductivity or MN morphology and demonstrated coating durability over multiple penetration cycles. The non-cytotoxic nature of the conductive MNs was demonstrated using human adult dermal fibroblast cells.
These fabricated conductive MNs enabled the integration of molecular imprinting via electropolymerisation, facilitating in-situ deposition of the bioanalyte cortisol in the presence of pyrrole. The outlined process supports the development of a molecularly imprinted substrate for targeted biomarker detection, contributing towards self-health monitoring and management through dual conductive layering. Cortisol detection capabilities of the designed molecularly imprinted MNs has been assessed via sensitivity and selectivity experiments in the presence of the structural analogue prednisolone. The proposed fabrication strategy offers a compelling approach to manufacturing polymer-based conductive MN surfaces that have the potential to assist developments toward smart medical devices. Designing conductive MN systems via additive manufacturing, incorporating biocompatible conductive polymer coatings, and integrating a physicochemical stable biomimetic sensing element, serves as a potential pedestal to drive disease diagnostics to an efficiency that could one day outperform current practices.
| Date of Award | 11 Oct 2023 |
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| Original language | English |
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| Supervisor | Hannah Leese (Supervisor), Pedro Estrela (Supervisor) & Despina Moschou (Supervisor) |