Electrochemical sensor for rapid detection of fentanyl using laser-induced porous carbon-electrodes.

The growing pervasiveness of opioid-based drugs such as fentanyl and its analogs represent a foremost hazard to the civilian population and burden on the first responders and clinicians. Thus, to enable a rapid and low-cost surveillance system to detect fentanyl in a non-ideal environment, we demonstrate the use of laser-induced nano-porous carbon structures directly onto commercially available polyimide sheets for rapid and cost-effective manufacturing of electrochemical sensors for fentanyl detection. The porous carbon surface instigated by various laser energy densities was analyzed towards morphological, vibrational, and fentanyl sensing properties. The results showed that laser carbonized electrode (LCE) prepared with 31 J/cm2 laser energy densities showed the highest level of porosity, surface roughness, and thereby enhanced sensitivity towards fentanyl detection by square-wave voltammetry (SWV) with a 1 µM limit of detection. This new disposable sensor strip offers an information-rich electrochemical fingerprint of fentanyl oxidation at + 0.526 V (vs Ag/AgCl) on the surface of laser carbonized electrodes with high linear (R2 = 0.99) sensitivity (0.025 µA⋅µM-1⋅cm-2) and reproducibility (RSD = 5%), within the clinically relevant working range of 20-200 µM with similar performance in both PBS and serum samples. The laser carbonized electrode surface was further found to be selective towards fentanyl concentrations in the presence of various cutting agents. This technology could provide a new route towards scalable manufacturing of cost-effective sensors for rapid detection of opioid misuse and potentially save the lives from systemic side effects.

Organ-on-a-Chip Platform with an Integrated Screen-Printed Electrode Array for Real-Time Monitoring Trans-Epithelial Barrier and Bubble Formation.

Cellular tight junctions play a key role in establishing a barrier between different compartments of the body by regulating the selective passage of different solutes across epithelial and endothelial tissues. Over the past decade, significant efforts have been conducted to develop more clinically relevant "organ-on-a-chip" models with integrated trans-epithelial electrical resistance (TEER) monitoring systems to help better understand the fundamental underpinnings of epithelial tissue physiology upon exposure to different substances. However, most of these platforms require the use of high-cost and time-consuming photolithography processes, which limits their scalability and practical implementation in clinical research. To address this need, we have developed a low-cost microfluidic platform with an integrated electrode array that allows continuous real-time monitoring of TEER and the risk of bubble formation in the microfluidic system by using scalable manufacturing technologies such as screen printing and laser processing. The integrated printed electrode array exhibited excellent stability (with less than ∼0.02 Ω change in resistance) even after long-term exposure to a complex culture medium. As a proof of concept, the fully integrated platform was tested with HMT3522 S1 epithelial cells to evaluate the tight barrier junction formation through TEER measurement and validated with standard immunostaining procedures for Zonula occludens-1 protein. This platform could be regarded as a stepping stone for the fabrication of disposable and low-cost organ and tissue-on-a-chip models with integrated sensors to facilitate studying the dynamic response of epithelial tissues to different substances in more physiologically relevant conditions.

Cold Atmospheric Plasma-Assisted Direct Deposition of Polypyrrole-Ag Nanocomposites for Flexible Electronic Sensors.

Conductive polymers and their composite materials have attracted considerable interest due to their potential applications in sensors, actuators, drug delivery systems, and energy storage devices. Despite their wide range of applications, many challenges remain primarily with respect to the complex synthesis and time-consuming manufacturing steps that are often required in the fabrication process of various devices with conductive polymers. Here, we demonstrate the novel use of cold atmospheric plasma (CAP)-assisted deposition technologies as a solvent-free and scalable approach for in situ polymerization and direct deposition of conductive polypyrrole-silver (PPy-Ag) nanocomposites onto the desired substrates under atmospheric conditions. In this study, a systematic approach with different precursor composition mixtures containing pyrrole as the monomer and AgNO3 as the photoinitiator was investigated to assess the effect of precursor composition on the final chemical, electrical, and mechanical properties of the PPy-Ag nanocomposite thin-film coatings which were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and cyclic bending tests. The characterizations indicated the possibility of fabricating PPy-Ag nanocomposite films with tunable degrees of polymerization and Ag nanoparticle loading by simply varying the percentage of AgNO3 in precursor composition mixtures. Finally, as a proof of concept, the potential use of the PPy-Ag nanocomposite films with different Ag nanoparticle loading percentages was assessed for humidity sensing by measuring their level of change in electrical resistance in the relative humidity range of 12-60%. It is envisioned that the developed CAP-assisted deposition technology can provide a new stepping stone toward scalable additive manufacturing of various functional nanocomposite films for different low-cost and flexible electronic applications.

Printed Low-Cost PEDOT:PSS/PVA Polymer Composite for Radiation Sterilization Monitoring.

During the γ-radiation sterilization process, the levels of radiation exposure to a medical device must be carefully monitored to achieve the required sterilization without causing deleterious effects on its intended physical and chemical properties. To address this issue, here we have demonstrated the development of an all-printed disposable low-cost sensor that exploits the change in electrical impedance of a semi-interpenetrating polymer network (SIPN) composed of poly(vinyl alcohol) (PVA) and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) as a functional polymer composite for radiation sterilization monitoring applications. Specifically, the PEDOT:PSS acts as the electrically conductive medium, while the PVA provides the ductility and stability of the printed sensors. During irradiation exposure, chain scission and cross-linking events occur concurrently in the PEDOT:PSS and PVA polymer chains, respectively. The concurrent scissoring of the PEDOT polymer and cross-linking of the PVA polymer network leads to the formation of a stable SIPN with reduced electrical conductivity, which was verified through FTIR, Raman, and TGA analysis. Systematic studies of different ratios of PEDOT:PSS and PVA mixtures were tested to identify the optimal ratio that provided the highest radiation sensitivity and stability performance. The results showed that PEDOT:PSS/PVA composites with 10 wt % PVA produced sensors with relative impedance changes of 30% after 25 kGy and up to 370% after 53 kGy (which are two of the most commonly used radiation exposure levels for sterilization applications). This composition showed high electrical impedance stability with less than ±5% change over 18 days after irradiation exposure. These findings demonstrate the feasibility of utilizing a printing technology for scalable manufacturing of low-cost, flexible radiation sensors for more effective monitoring of radiation sterilization processes.

Low-Cost Flexible Glass-Based pH Sensor via Cold Atmospheric Plasma Deposition.

Many commercially available pH sensors are fabricated with a glass membrane as the sensing component because of several advantages of glass-based electrodes such as versatility, high accuracy, and excellent stability in various conditions. However, because of their bulkiness and poor mechanical properties, conventional glass-based sensors are not ideal for wearable or flexible applications. Here, we report for the first time the fabrication of a flexible glass-based pH sensor suitable for biomedical and environmental applications where flexibility and stability of the sensor are critical for long-term and real-time monitoring. The sensor was fabricated via a simple and facile approach using the cold atmospheric plasma technique in which a pH sensitive silica coating was deposited from a siloxane precursor onto a carbon electrode. In order to increase the sensitivity and stability of the sensor, we employed a postprocessing step which involves annealing of the silica coated electrode at elevated temperatures. This process was optimized to ensure that the crucial properties such as porosity and hydration functionality were balanced to obtain the best and most reliable sensitivity of the sensor. Our sensitivity test results indicated that these sensors exhibit excellent and stable sensitivity with a slope of about 48 mV/pH (r2 = 0.998) and selectivity across a pH range of 4 to 10 in the presence of various cations. The optimized sensor has shown stable sensitivity for a long period of time (30 h of immersion) and in different bending conditions. We demonstrate in this investigation that this flexible cost-effective pH sensor can withstand the sterilization process resulting from ultraviolet radiation and shows repeatable sensitivity with less than ±5 mV potential drift from the sensitivity values of the standard optimized sensor.

Low-Cost Nonreversible Electronic-Free Wireless pH Sensor for Spoilage Detection in Packaged Meat Products.

Contamination of meat with pathogenic microorganisms can cause severe illnesses and food waste, which has significant negative impacts on both general health and the economy. In many cases, the expiration date is not a good indicator of meat freshness as there is a high risk of contamination during handling throughout the supply chain. Many biomarkers, including color, odor, pH, temperature, and volatile compounds, are used to determine spoilage. Among these, pH presents a simple and effective biomarker directly linked to the overgrowth of bacteria and degradation of the meat tissue. Low-cost methods for wireless pH monitoring are crucial in detecting spoilage on a large commercial scale. Existing technologies are often limited to short-range detection, with the use of batteries and different electronic components that increases both the manufacturing complexity and cost of the final device. To address these shortcomings, we have developed a cost-effective wireless pH sensor, which uses passive resonant frequency (RF) sensing, combined with a pH-responsive polymer that can be placed within packaged meat products and provide a remote assessment of the risk of microbial spoilage throughout the supply chain. The sensor tag consists of a sensing resonator coated with a pH-sensitive material and a passivated reference resonator operating in a differential frequency configuration. Upon exposure to elevated pH levels >6.8, the coating on the sensing resonator dissolves, which in turn results in a distinct change in the resonant frequency with respect to the reference resonator. Systematic theoretical and experimental results at different pH levels demonstrated that a 20% shift in resonant frequency demarcates the point for spoilage detection. As a proof of concept, the performance of the sensor in remotely detecting the risk of food spoilage was validated in packaged poultry over 10 days. The sensor fabrication process takes advantage of recent developments in the scalable manufacturing of flexible, low-cost devices, including selective laser etching of metalized plastic films and doctor-blade coating of stimuli-responsive polymer films. Furthermore, the biocompatibility of all the materials used in the sensor was confirmed with human intestinal cells (HCT-8 cells).

Small intestinal sampling capsule for inflammatory bowel disease type detection and management.

Although serum and fecal biomarkers (e.g., lactoferrin, and calprotectin) have been used in management and distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), none are proven to be a differential diagnostic tool between Crohn's disease (CD) and ulcerative colitis (UC). The main challenge with laboratory-based biomarkers in the stool test is the inability to indicate the location of the disease/inflammation in the gastrointestinal (GI) tract due to the homogenous nature of the collected fecal sample. For the first time, we have designed and developed a battery-free smart capsule that will allow targeted sampling of inflammatory biomarkers inside the gut lumen of the small intestine. The capsule is designed to provide a simple and non-invasive complementary tool to fecal biomarker analysis to differentiate the type of IBD by pinpointing the site of inflammatory biomarkers secretion (e.g., small or large bowel) throughout the GI tract. The capsule takes advantage of the rapid change from an acidic environment in the stomach to higher pH levels in the small intestine to dissolve a pH-sensitive polymeric coating as a means to activate the sampling process of the capsule within the small intestine. A swelling polyacrylamide hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid while also providing the required mechanical actuation to close the capsule once the sampling is completed. The hydrogel component along with the collected GI fluid can be easily obtained from the capsule through the screw-cap design for further extraction and analysis. As a proof of concept, the capsule's performance in sampling and extraction of bovine serum albumin (BSA) and calprotectin - a key biomarker of inflammation - was assessed within the physiologically relevant ranges. The ratio of extracted biomarkers relative to that in the initial sampling environment remained constant (∼3%) and independent of the sampling matrix in both in vitro and ex vivo studies. It is believed that the demonstrated technology will provide immediate impact in more effective IBD type differential diagnostic and treatment strategies by providing a non-invasive assessment of inflammation biomarkers profile throughout the digestive tract.

Ultrasonic Molding Technology: Recent Advances and Potential Applications in the Medical Industry.

Recently, ultrasonic molding (USM) has emerged as a promising replication technique for low and medium volume production of miniature and micro-scale parts. In a relatively short time cycle, ultrasonic molding can process a wide variety of polymeric materials without any noticeable thermal degradation into cost-effective molded parts. This research work reviews recent breakthroughs of the ultrasonic injection molding and ultrasonic compression molding process regarding the equipment and tooling development, materials processing and potential applications in the medical industry. The discussion is centered on the challenges of industrializing this technology, pointing out the need for improvement of the current process's robustness and repeatability. Among the most important research areas that were identified are the processing of novel engineered and nanomaterials, the understanding and control of the ultrasonic plasticization process and the tooling and equipment development.