Simultaneous Dopamine and Serotonin Monitoring in Freely Moving Crayfish Using a Wireless Electrochemical Sensing System.

Dopamine (DA) and serotonin (5-HT) are neurotransmitters that regulate a wide range of physiological and behavioral processes. Monitoring of both neurotransmitters with real-time analysis offers important insight into the mechanisms that shape animal behavior. However, bioelectronic tools to simultaneously monitor DA and 5-HT interactive dynamics in freely moving animals are underdeveloped. This is mainly due to the limited sensor sensitivity with miniaturized electronics. Here, we present a semi-implantable electrochemical device achieved by integrating a multi-surface-modified carbon fiber microelectrode with a miniaturized potentiostat module to detect DA and 5-HT in vivo with high sensitivity and selectivity. Specifically, carbon fiber microelectrodes were modified through electrochemical treatment and surface coatings to improve sensitivity, selectivity, and antifouling properties. A customized, lightweight potentiostat module was developed for untethered electrochemical measurements. Integrated with the microelectrode, the microsystem is compact (2.8 × 2.3 × 2.1 cm) to minimize its impacts on animal behavior and achieved simultaneous detection of DA and 5-HT with sensitivities of 48.4 and 133.0 nA/µM, respectively, within submicromolar ranges. The system was attached to the crayfish dorsal carapace, allowing electrode implantation into the heart of a crayfish to monitor DA and 5-HT dynamics, followed by drug injections. The semi-implantable biosensor system displayed a significant increase in oxidation peak currents after DA and 5-HT injections. The device successfully demonstrated the application for in vivo simultaneous monitoring of DA and 5-HT in the hemolymph (i.e., blood) of freely behaving crayfish underwater, yielding a valuable experimental tool to expand our understanding of the comodulation of DA and 5-HT.

Miniaturized Capsule System Toward Real-Time Electrochemical Detection of H2 S in the Gastrointestinal Tract.

Hydrogen sulfide (H2 S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H2 S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H2 S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H2 S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H2 S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H2 S concentration ranging from 0.21 to 4.5 ppm (R2 = 0.954) with a normalized sensitivity of 12.4% ppm-1 when evaluated in a benchtop setting. The sensor proves highly selective toward H2 S in the presence of known interferent gases, such as hydrogen (H2 ), with a selectivity ratio of H2 S:H2 = 1340, as well as toward methane (CH4 ) and carbon dioxide (CO2 ). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H2 S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H2 S.

Freestanding region-responsive bilayer for functional packaging of ingestible devices.

Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit® FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.

A portable electrochemical sensing platform for serotonin detection based on surface-modified carbon fiber microelectrodes.

Serotonin (5-HT) is one of the key neurotransmitters in the human body, regulating numerous physiological functions. A disruption in 5-HT homeostasis could result in serious health problems, including neurodegenerative disorders, depression, and 5-HT syndrome. Detection of 5-HT concentrations in biological fluids, such as urine, is a potential solution for early diagnosis of these diseases. In this study, we developed a novel, simple, and low-cost electrochemical sensing platform consisting of a portable workstation with customized electrodes for 5-HT detection in artificial biological fluids. Nafion/carbon nanotubes (CNTs) and electrochemically modified carbon fiber microelectrodes (Nafion-CNT/EC CFMEs) displayed improved 5-HT sensitivity and selectivity. Together with a customized Ag/AgCl reference electrode and Pt counter electrode, the portable 5-HT sensing platform had a sensitivity of 0.074 µA µM-1 and a limit of detection (LOD) of 140 nM. This system was also assessed to measure 5-HT spiked in artificial urine samples, showing nearly full recovery rates. These satisfactory results demonstrated that the portable system exhibits outstanding performance and confirmed the feasibility of 5-HT detection, which can be used to provide point-of-care analysis in actual biological samples.

Integrated System for Bacterial Detection and Biofilm Treatment on Indwelling Urinary Catheters.

GOAL: This work introduces an integrated system incorporated seamlessly with a commercial Foley urinary catheter for bacterial growth sensing and biofilm treatment. METHODS: The system is comprised of flexible, interdigitated electrodes incorporated with a urinary catheter via a 3D-printed insert for impedance sensing and bioelectric effect-based treatment. Each of the functions were wirelessly controlled using a custom application that provides a user-friendly interface for communicating with a custom PCB via Bluetooth to facilitate implementation in practice. RESULTS: The integrated catheter system maintains the primary functions of indwelling catheters - urine drainage, balloon inflation - while being capable of detecting the growth of Escherichia coli, with an average decrease in impedance of 13.0% after 24 hours, tested in a newly-developed simulated bladder environment. Furthermore, the system enables bioelectric effect-based biofilm reduction, which is performed by applying a low-intensity electric field that increases the susceptibility of biofilm bacteria to antimicrobials, ultimately reducing the required antibiotic dosage. CONCLUSION: Overall, this modified catheter system represents a significant step forward for catheter-associated urinary tract infection (CAUTI) management using device-based approaches, integrating flexible electrodes with an actual Foley catheter along with the control electronics and mobile application. SIGNIFICANCE: CAUTIs, exacerbated by the emergence of antibiotic-resistant pathogens, represent a significant challenge as one of the most prevalent healthcare-acquired infections. These infections are driven by the colonization of indwelling catheters by bacterial biofilms.

Capacitive sensing of triglyceride film reactions: a proof-of-concept demonstration for sensing in simulated duodenal contents with gastrointestinal targeting capsule system.

Ingestible capsule systems continue to evolve to overcome drawbacks associated with traditional gastrointestinal (GI) diagnostic and therapeutic processes, such as limitations on which sections of the GI tract can be accessed or the inability to measure local biomarker concentrations. We report an integrated capsule sensing system, utilizing a hybrid packaging scheme coupled with triglyceride film-coated capacitive sensors, for measuring biochemical species present in the duodenum, such as pancreatic lipase and bile acids. The system uses microfabricated capacitive sensors interfaced with a Bluetooth low-energy (BLE)-microcontroller, allowing wireless connectivity to a mobile app. The triglyceride films insulate the sensor surface and react either with 0.01-1 mM lipase via hydrolysis or 0.07-7% w/v bile acids via emulsification in simulated fluids, leading to measurable changes in capacitance. Cross reactivity of the triglyceride films is evaluated in both phosphate buffered saline (PBS) as well as pancreatic trypsin solutions. The film morphology is observed after exposure to each stimulus to better understand how these changes alter the sensor capacitance. The capsule utilizes a 3D-printed package coated with polymers that remain intact in acid solution (mimicking gastric conditions), then dissolve at a duodenum-mimicking neutral pH for triggered opening of the sensing chamber from which we can subsequently detect the presence of pancreatic lipase. This device strategy represents a significant step towards using embedded packaging and triglyceride-based materials to target specific regions of the GI tract and sensing biochemical contents for evaluating gastrointestinal health.

Ingestible Sensors and Sensing Systems for Minimally Invasive Diagnosis and Monitoring: The Next Frontier in Minimally Invasive Screening.

Ingestible electronic systems that are capable of embedded sensing, particularly within the gastrointestinal (GI) tract and its accessory organs, have the potential to screen for diseases that are difficult if not impossible to detect at an early stage using other means. Furthermore, these devices have the potential to (1) reduce labor and facility costs for a variety of procedures, (2) promote research for discovering new biomarker targets for associated pathologies, (3) promote the development of autonomous or semiautonomous diagnostic aids for consumers, and (4) provide a foundation for epithelially targeted therapeutic interventions. These technological advances have the potential to make disease surveillance and treatment far more effective for a variety of conditions, allowing patients to lead longer and more productive lives. This review will examine the conventional techniques, as well as ingestible sensors and sensing systems that are currently under development for use in disease screening and diagnosis for GI disorders. Design considerations, fabrication, and applications will be discussed.