The Journal of the Friends' Historical Society vol. 23 No. 3-4

In motion simulation, motion input scaling is often applied to deal with the limited motion envelopes of motion simulators. In this research, the time-varying effects of scaling the lateral specific force up or down during passive curve driving in a car driving simulation are investigated through a simulator experiment. It is concluded that lateral specific force scaling has a time-varying effect on the perceived fidelity of a curve-driving simulation. In particular, motion scaling during a curve entry is found to be less detrimental than motion scaling during a curve's sustained part and during the curve exit.Control & SimulationControl & Operation

Studying the Drug Delivery Kinetics of Nanosponges Using a MIP-Based Thermal Sensing Platform

The implementation of Molecularly Imprinted Polymers (MIPs) into sensing systems has been demonstrated abundantly over the past few decades. In this article, a novel application for an MIP-based thermal sensing platform is introduced by using the sensor to characterize the drug release kinetics of a nanoporous silver-organic framework. This Ag nanoporous matrix was loaded with acetylsalicylic acid (aspirin) which was used as a model drug compound in this study. The drug elution properties were studied by placing the nanoporous matrix in phosphate buffered saline solution for two days and measuring the drug concentration at regular time intervals. To this extent, an acrylamide-based MIP was synthesized that was able to detect aspirin in a specific and selective manner. Rebinding of the template to the MIP was analyzed using a thermal sensor platform. The results illustrate that the addition of aspirin into the sensing chamber leads to a concentration-dependent increase in the phase shift of a thermal wave that propagates through the MIP-coated sensor chip. After constructing a dose-response curve, this system was used to study the drug release kinetics of the nanoporous matrix, clearly demonstrating that the metalorganic framework releases the drug steadily over the course of the first hour, after which the concentration reaches a plateau. These findings were further confirmed by UV–Visible spectroscopy, illustrating a similar time-dependent release in the same concentration range, which demonstrates that the MIP-based platform can indeed be used as a low-cost straightforward tool to assess the efficacy of drug delivery systems in a lab environmen

Introducing Thermal Wave Transport Analysis (TWTA): A Thermal Technique for Dopamine Detection by Screen-Printed Electrodes Functionalized with Molecularly Imprinted Polymer (MIP) Particles.

A novel procedure is developed for producing bulk modified Molecularly Imprinted Polymer (MIP) screen-printed electrodes (SPEs), which involves the direct mixing of the polymer particles within the screen-printed ink. This allowed reduction of the sample preparation time from 45 min to 1 min, and resulted in higher reproducibility of the electrodes. The samples are measured with a novel detection method, namely, thermal wave transport analysis (TWTA), relying on the analysis of thermal waves through a functional interface. As a first proof-of-principle, MIPs for dopamine are developed and successfully incorporated within a bulk modified MIP SPE. The detection limits of dopamine within buffer solutions for the MIP SPEs are determined via three independent techniques. With cyclic voltammetry this was determined to be 4.7 × 10−6 M, whereas by using the heat-transfer method (HTM) 0.35 × 10−6 M was obtained, and with the novel TWTA concept 0.26 × 10−6 M is possible. This TWTA technique is measured simultaneously with HTM and has the benefits of reducing measurement time to less than 5 min and increasing effect size by nearly a factor of two. The two thermal methods are able to enhance dopamine detection by one order of magnitude compared to the electrochemical method. In previous research, it was not possible to measure neurotransmitters in complex samples with HTM, but with the improved signal-to-noise of TWTA for the first time, spiked dopamine concentrations were determined in a relevant food sample. In summary, novel concepts are presented for both the sensor functionalization side by employing screen-printing technology, and on the sensing side, the novel TWTA thermal technique is reported. The developed bio-sensing platform is cost-effective and suitable for mass-production due to the nature of screen-printing technology, which makes it very interesting for neurotransmitter detection in clinical diagnostic applications

A novel thermal detection method based on molecularly imprinted nanoparticles as recognition elements.

Molecularly Imprinted Polymers (MIPs) are synthetic receptors that are able to selectively bind their target molecule and, for this reason, they are currently employed as recognition elements in sensors. In this work, MIP nanoparticles (nanoMIPs) are produced by solid-phase synthesis for a range of templates with different sizes, including a small molecule (biotin), two peptides (one derived from the epithelial growth factor receptor and vancomycin) and a protein (trypsin). NanoMIPs are then dipcoated on the surface of thermocouples that measure the temperature inside a liquid flow cell. Binding of the template to the MIP layer on the sensitive area of the thermocouple tip blocks the heat-flow from the sensor to the liquid, thereby lowering the overall temperature measured by the thermocouple. This is subsequently correlated to the concentration of the template, enabling measurement of target molecules in the low nanomolar regime. The significant improvement in the limit of detection (a magnitude of three orders compared to previously used MIP microparticles) can be attributed to their high affinity, enhanced conductivity and increased surface-to-volume ratio. It is the first time that these nanosized recognition elements are used in combination with thermal detection, and it is the first report on MIP-based thermal sensors for determining protein levels. The developed thermal sensors have a high selectivity, fast measurement time (<5 min), and data analysis is straightforward, which makes it possible to monitor biomolecules in real-time. The set of biomolecules discussed in this manuscript show that it is possible to cover a range of template molecules regardless of their size, demonstrating the general applicability of the biosensor platform. In addition, with its high commercial potential and biocompatibility of the MIP receptor layer, this is an important step towards sensing assays for diagnostic applications that can be used in vivo

Recent Advances in Electrosynthesized Molecularly Imprinted Polymer Sensing Platforms for Bioanalyte Detection

The accurate detection of biological materials has remained at the forefront of scientific research for decades. This includes the detection of molecules, proteins, and bacteria. Biomimetic sensors look to replicate the sensitive and selective mechanisms that are found in biological systems and incorporate these properties into functional sensing platforms. Molecularly imprinted polymers (MIPs) are synthetic receptors that can form high affinity binding sites complementary to the specific analyte of interest. They utilise the shape, size, and functionality to produce sensitive and selective recognition of target analytes. One route of synthesizing MIPs is through electropolymerization, utilising predominantly constant potential methods or cyclic voltammetry. This methodology allows for the formation of a polymer directly onto the surface of a transducer. The thickness, morphology, and topography of the films can be manipulated specifically for each template. Recently, numerous reviews have been published in the production and sensing applications of MIPs; however, there are few reports on the use of electrosynthesized MIPs (eMIPs). The number of publications and citations utilising eMIPs is increasing each year, with a review produced on the topic in 2012. This review will primarily focus on advancements from 2012 in the use of eMIPs in sensing platforms for the detection of biologically relevant materials, including the development of increased polymer layer dimensions for whole bacteria detection and the use of mixed monomer compositions to increase selectivity toward analytes

Development of a Flexible MIP-Based Biosensor Platform for the Thermal Detection of Neurotransmitters

We have developed high affinity Molecularly Imprinted Polymers (MIPs) for neurotransmitters such as dopamine, noradrenaline and caffeine. These polymer particles are mixed within the bulk of screen-printed ink allowing masss-producible bulk modified MIP Screen-Printed Electrodes (MIP-SPEs) to be realised. We have explored different SPE supporting surfaces, such as polyester, tracing paper and household-printing paper. The performance of those MIP-SPEs is studied using the Heat-Transfer Method (HTM), a patented thermal method. With the combination of screen-printing techniques and thermal detection, it is possible to develop a portable sensor platform that is capable of low-cost and straightforward detection of biomolecules on-site. In the future, this unique sensor architecture holds great promise for the use in biomedical devices

Substrate displacement colorimetry for the detection of diarylethylamines

In this work, a novel detection assay for the new psychoactive substance (NPS) 2-methoxiphenidine (2-MXP) and other diarylethylamines is introduced. The assay is based on the competitive displacement of dye molecules from molecularly imprinted polymers (MIPs) by the target molecule. The assay was fully characterized by studying the affinity of the MIP for six common dyes, expressed as the binding factor (BF). The results of this study indicate that the mathematical relationship between the BF of a dye and the imprinting factor (IF) for the target could be used for the prediction of the efficacy of the displacement assay. Dye-loaded MIP particles where incubated with the target, two adulterants and two legal pharmacological compounds. The target has a higher affinity for the MIP than the dye and displaces it out of the nanocavities of the receptor leading to a colour change in the filtrate that can be observed with the naked eye. Incubation of the MIP particles with the adulterants and legal medicines did not result in any observable change in absorbance. The robust, fast and low-cost nature of the assay, combined with its tailorable selectivity and generic nature, illustrate its potential as a pre-screening tool for the identification of narcotic substances in unidentified powders. Keywords: Molecularly imprinted polymer, displacement assay, colorimetry, new psychoactive substance identificatio

Thermistors coated with molecularly imprinted nanoparticles for the electrical detection of peptides and proteins

In this communication, molecularly imprinted nanoparticles (nanoMIPs) that are produced by solid-phase synthesis are functionalised onto thermistors via dip-coating. These thermistors are soldered onto a printed-circuit board to facilitate electrical detection. Subsequently, these are inserted into a home-made thermal device that can measure the selective binding of biomolecules to the nanoMIP layer via monitoring the thermal resistance (Rth) at the solid-liquid interface. This thermal analysis technique, referred to as the Heat-Transfer Method, has previously been used for detection of proteins with MIP-based binders. While offering the advantages of low-cost and label free analysis, this method is limited by the high noise on the feedback loop and not being commercially available. These disadvantages can be overcome by the use of thermistors, which offer superior temperature sensitivity compared to thermocouples, and its electrical read-out can be easily integrated into portable devices. To our knowledge, this is the first report where MIPs are directly integrated onto thermistors for detection purposes. Measurements were conducted with an epitope of epidermal growth factor receptor (EGFR) and trypsin, where the electrical resistance was correlated to the biomolecule concentration. For both EGFR and trypsin, an enhanced signal to noise ratio for the electrical measurements was observed compared to previous analysis that was based on thermal resistance. The sensitivity of the sensors in buffered solution was in the nanomolar range, which is compatible with physiologically relevant concentrations. Upon exposure of the nanoMIP for EGFR towards pepsin no significant change in the resistance was yielded, establishing the selectivity of the developed sensor platform. Besides the enhanced sensitivity, the use of thermistors will enable miniaturisation of the device and has potential for in vivo measurements since specified electrochemical measurements are compatible with human use. To highlight the versatility of the nanoMIPs, this work should be extended to a set of biomolecules with various structures, with the possibility of extending this to an array format

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