Bio-applied molecularly imprinted polymers (MIPs) are biomimetic materials with tailor-made synthetic recognition sites, mimicking biological counterparts known for their sensitive and selective analyte detection. MIPs, specifically designed for biomarker analysis...

Today, we heavily rely on technology and increasingly utilize it to monitor our own health. The identification of sensitive, accurate biosensors that are capable of real-time cortisol analysis is one important potential feature for these technologies to aid us in the maintenance of our physical and mental wellbeing. Detection and quantification of cortisol, a well-known stress biomarker present in sweat, offers a noninvasive and potentially real-time method for monitoring anxiety. Molecularly imprinted polymers are attractive candidates for cortisol recognition elements in such devices as they can selectively rebind a targeted template molecule. However, mechanisms of imprinting and subsequent rebinding depend on the choice and composition of the prepolymerization mixture where the molecular interactions between the template, functional monomer, cross-linker, and solvent molecules are not fully understood. Here, we report the synthesis and evaluation of a molecularly imprinted polymer selective for cortisol detection. Molecular dynamics simulations were used to investigate the interactions between all components in the prepolymerization mixture of the as-synthesized molecularly imprinted polymer. Varying the component ratio of the prepolymerization mixture indicates that the number of cross-linker molecules relative to the template impacts the quality of imprinting. It was determined that a component ratio of 1:6:30 of cortisol, methacrylic acid, and ethylene glycol dimethacrylate, respectively, yields the optimal theoretical complexation of cortisol for the polymeric systems investigated. Experimental synthesis and rebinding results demonstrate an imprinting factor of up to 6.45. The trends in cortisol affinity predicted by molecular dynamics simulations of the prepolymerization mixture were also corroborated through experimental analysis of those modeled molecularly imprinted compositions, demonstrating the predictive capabilities of these simulations.

Conductive polymeric microneedle (MN) arrays as biointerface materials show promise for the minimally invasive monitoring of analytes in biodevices and wearables. There is increasing interest in microneedles 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, which create translational barriers. In this work, additive manufacturing, which provides the user with design flexibility and upscale manufacturing, is employed to fabricate acrylic‐based microneedle devices. These microneedle devices are used as platforms to produce intrinsically‐conductive, polymer‐based surfaces based on polypyrrole (PPy) and poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS). These entirely polymer‐based solid microneedle arrays act as dry conductive electrodes while omitting the requirement of a metallic seed layer. Two distinct coating methods of 3D‐printed solid microneedles, in situ polymerization and drop casting, enable conductive functionality. The microneedle arrays penetrate ex vivo porcine skin grafts without compromising conductivity or microneedle morphology and demonstrate coating durability over multiple penetration cycles. The non‐cytotoxic nature of the conductive microneedles is evaluated using human fibroblast cells. The proposed fabrication strategy offers a compelling approach to manufacturing polymer‐based conductive microneedle surfaces that can be further exploited as platforms for biosensing.

The development of sensitive and selective robust sensor materials for targeted biomarker detection aims to contribute to self-health monitoring and management. Molecularly imprinted polymeric (MIP) materials can perform as biomimetic recognition elements via tailored routes of synthesis for specific target analyte extraction and/or detection. In this work, a sensitiveand selective-lactate MIP has been developed utilizing methacrylic acid and ethylene glycol dimethacrylate as the functional monomer and cross-linker, respectively. The sensitivity of the assynthesized imprinted species was evaluated by determining the target analyte retention, imprinting factor, and selectivity adsorption of up to 63.5%, 6.86, and 0.82, respectively. MIP selectivity elucidated the imprinting mechanism between the functional monomers and target analyte lactate, further experimentally evidenced by using structurally competitive analytes malic acid and sodium 2-hydroxybutyrate, where retentions of 22.6 and 25.2%, respectively, were observed. Understanding the specific intermolecular mechanisms of both the template analyte and structural interferents with the MIP enables experimentalists to make informed decisions regarding monomer-target and porogen selections and possible sites of interaction for improved molecular imprinting. This imprinting system highlights the potential to be further developed into artificial receptor sensor materials for the detection of disease.