Dipstick sensor based on molecularly imprinted polymer-coated screen-printed electrodes for the single-shot detection of glucose in urine samples—from fundamental study toward point-of-care application

Glucose biosensors play an extremely important role in health care systems worldwide. Therefore, the field continues to attract significant attention leading to the development of innovative technologies. Due to their characteristics, Molecularly Imprinted Polymers (MIPs) represent a promising alternative to commercial enzymatic sensors. In this work, a low-cost, flexible MIP-based platform for glucose sensing by integrating MIP particles directly into screen-printed electrodes (SPEs) is realized. The sensor design allows the detection of glucose via two different transducer principles, the so-called “heat-transfer method” (HTM) and electrochemical impedance spectroscopy (EIS). The sensitivity and selectivity of the sensor are demonstrated by comparing the responses obtained toward three different saccharides. Furthermore, the application potential of the MIP-SPE sensor is demonstrated by analyzing the response in urine samples, showing a linear range of 14.38–330 µm with HTM and 1.37–330 µm with EIS. To bring the sensor closer to a real life application, a handheld dipstick sensor is developed, allowing the single-shot detection of glucose in urine using EIS. This study illustrates that the simplicity of the dipstick readout coupled with the straightforward manufacturing process opens up the possibility for mass production, making this platform a very attractive alternative to commercial glucose sensors

Deposition Methods for the Integration of Molecularly Imprinted Polymers (MIPs) in Sensor Applications

Abstract Offering high specificity and selectivity, molecularly imprinted polymers (MIPs) are synthetic polymeric affinity reagents that have become increasingly popular over the last couple of decades. Due to their long‐term chemical and physical stability and low production cost, they have become an increasingly popular choice of receptor in the realm of sense. MIPs have therefore been associated with the detection of small molecules, proteins, cells, and pathogens, proving a highly robust and useful tool in the production of next‐gen sensing platforms. This said, the development of these sensors pivots on one simple fact; these receptors have to be deposited onto a substrate for their desired application. The deposition of MIPs during sensor fabrication is therefore of great importance, with the field utilizing an array of mechanical and chemical deposition methods to achieve this. To this end, this review, therefore, sets aim at coalescing these different deposition approaches, classifying them, and outlining their utility when it comes to receptor design and integration. Thus, offering a knowledge base on current deposition methods, potential future approaches and analyzing where the MIP deposition field is tending toward

Recent Advances in Molecularly Imprinted Polymers for Glucose Monitoring: From Fundamental Research to Commercial Application

Molecularly imprinted polymers (MIPs) have gained growing interest among researchers worldwide, due to their key features that make these materials interesting candidates for implementation as receptors into sensor applications. In fact, MIP-based glucose sensors could overcome the stability issues associated with the enzymes present in commercial glucose devices. Various reports describe the successful development of glucose MIPs and their coupling to a wide variety of transducers for creating sensors that are able to detect glucose in various matrices. In this review, we have summarized and critically evaluated the different production methods of glucose MIPs and the different transducer technologies used in MIP-based glucose sensors, and analyzed these from a commercial point of view. In this way, this review sets out to highlight the most promising approaches in MIP-based sensing in terms of both manufacturing methods and readout technologies employed. In doing so, we aim at delineating potential future approaches and identifying potential obstacles that the MIP-sensing field may encounter in an attempt to penetrate the commercial, analytical market

A Molecularly Imprinted Polymer-Based Thermal Sensor for the Selective Detection of Melamine in Milk Samples

In recent years, melamine-sensing technologies have increasingly gained attention, mainly due to the misuse of the molecule as an adulterant in milk and other foods. Molecularly imprinted polymers (MIPs) are ideal candidates for the recognition of melamine in real-life samples. The prepared MIP particles were incorporated into a thermally conductive layer via micro-contact deposition and its response towards melamine was analyzed using the heat-transfer method (HTM). The sensor displayed an excellent selectivity when analyzing the thermal response to other chemicals commonly found in foods, and its applicability in food safety was demonstrated after evaluation in untreated milk samples, demonstrating a limit of detection of 6.02 μM. As the EU/US melamine legal limit in milk of 2.5 mg/kg falls within the linear range of the sensor, it can offer an innovative solution for routine screening of milk samples in order to detect adulteration with melamine. The results shown in this work thus demonstrate the great potential of a low-cost thermal platform for the detection of food adulteration in complex matrices

A Molecularly Imprinted Polymer-based Dye Displacement Assay for the Rapid Visual Detection of Amphetamine in Urine

The rapid sensing of drug compounds has traditionally relied on antibodies, enzymes and electrochemical reactions. These technologies can frequently produce false positives/negatives and require specific conditions to operate. Akin to antibodies, molecularly imprinted polymers (MIPs) are a more robust synthetic alternative with the ability to bind a target molecule with an affinity comparable to that of its natural counterparts. With this in mind, the research presented in this article introduces a facile MIP-based dye displacement assay for the detection of (+/-) amphetamine in urine. The selective nature of MIPs coupled with a displaceable dye enables the resulting low-cost assay to rapidly produce a clear visual confirmation of a target's presence, offering huge commercial potential. The following manuscript characterizes the proposed assay, drawing attention to various facets of the sensor design and optimization. To this end, synthesis of a MIP tailored towards amphetamine is described, scrutinizing the composition and selectivity (ibuprofen, naproxen, 2-methoxphenidine, quetiapine) of the reported synthetic receptor. Dye selection for the development of the displacement assay follows, proceeded by optimization of the displacement process by investigating the time taken and the amount of MIP powder required for optimum displacement. An optimized dose-response curve is then presented, introducing (+/-) amphetamine hydrochloride (0.01-1 mg mL(-1)) to the engineered sensor and determining the limit of detection (LoD). The research culminates in the assay being used for the analysis of spiked urine samples (amphetamine, ibuprofen, naproxen, 2-methoxphenidine, quetiapine, bupropion, pheniramine, bromopheniramine) and evaluating its potential as a low-cost, rapid and selective method of analysis

Functionalized screen-printed electrodes for the thermal detection of Escherichia coli in dairy products

Accurate and fast on-site detection of harmful microorganisms in food products is a key preventive step to avoid food-borne illness and product recall. In this study, screen-printed electrodes (SPEs) were functionalized via a facile strategy with surface imprinted polymers (SIPs). The SIP-coated SPEs were used in combination with the heat transfer method (HTM) for the real-time detection of Escherichia coli. The sensor was tested in buffer, with a reproducible and sensitive response that attained a limit of detection of 180 CFU/mL. Furthermore, selectivity was assessed by analyzing the sensor's response to C. sakazakii, K. pneumoniae and S. aureus as analogue strains. Finally, the device was successfully used for the detection of E. coli in spiked milk as proof-of-application, requiring no additional sample preparation. These results suggest the proposed thermal biosensor possesses the potential of becoming a tool for routine, on-site monitoring of E. coli in food safety applications

Thermal Detection of Glucose in Urine Using a Molecularly Imprinted Polymer as a Recognition Element

[Image: see text] Glucose bio-sensing technologies have received increasing attention in the last few decades, primarily due to the fundamental role that glucose metabolism plays in diseases (e.g., diabetes). Molecularly imprinted polymers (MIPs) could offer an alternative means of analysis to a field that is traditionally dominated by enzyme-based devices, posing superior chemical stability, cost-effectiveness, and ease of fabrication. Their integration into sensing devices as recognition elements has been extensively studied with different readout methods such as quartz-crystal microbalance or impedance spectroscopy. In this work, a dummy imprinting approach is introduced, describing the synthesis and optimization of a MIP toward the sensing of glucose. Integration of this polymer into a thermally conductive receptor layer was achieved by micro-contact deposition. In essence, the MIP particles are pressed into a polyvinyl chloride adhesive layer using a polydimethylsiloxane stamp. The prepared layer is then evaluated with the so-called heat-transfer method, allowing the determination of the specificity and the sensitivity of the receptor layer. Furthermore, the selectivity was assessed by analyzing the thermal response after infusion with increasing concentrations of different saccharide analogues in phosphate-buffered saline (PBS). The obtained results show a linear range of the sensor of 0.0194–0.3300 mM for the detection of glucose in PBS. Finally, a potential application of the sensor was demonstrated by exposing the receptor layer to increasing concentrations of glucose in human urine samples, demonstrating a linear range of 0.0444–0.3300 mM. The results obtained in this paper highlight the applicability of the sensor both in terms of non-invasive glucose monitoring and for the analysis of food samples

Thermal Pyocyanin Sensor Based on Molecularly Imprinted Polymers for the Indirect Detection of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a ubiquitous multi-drug-resistant bacterium, capable of causing serious illnesses and infections. This research focuses on the development of a thermal sensor for the indirect detection of P. aeruginosa infection using molecularly imprinted polymers (MIPs). This was achieved by developing MIPs for the detection of pyocyanin, the main toxin secreted by P. aeruginosa. To this end, phenazine was used as a dummy template, evaluating several polymeric compositions to achieve a selective MIP for pyocyanin recognition. The sensitivity of the synthesized MIPs was investigated by UV–vis analysis, with the best composition having a maximum rebinding capacity of 30 μmol g–1 and an imprinting factor (IF) of 1.59. Subsequently, the MIP particles were immobilized onto planar aluminum chips using an adhesive layer, to perform thermal resistance measurements at clinically relevant concentrations of pyocyanin (1.4–9.8 μM), achieving a limit of detection (LoD) of 0.347 ± 0.027 μM. The selectivity of the sensor was also scrutinized by subjecting the receptor to potential interferents. Furthermore, the rebinding was demonstrated in King’s A medium, highlighting the potential of the sensor for the indirect detection of P. aeruginosa in complex fluids. The research culminates in the demonstration of the MIP-based sensor’s applicability for clinical diagnosis. To achieve this goal, an experiment was performed in which the sensor was exposed to pyocyanin-spiked saliva samples, achieving a limit of detection of 0.569 ± 0.063 μM and demonstrating that this technology is suitable to detect the presence of the toxin even at the very first stage of its production