A highly sensitive ion-selective chemiresistive sensor for online monitoring of lead ions in water.

Dissolved lead is a serious but common health hazard in drinking water, yet there is still no practical way to monitor its levels continuously in the distribution system or at the point of use. Here we propose using a lead-selective membrane on top of a chemiresistive device to continuously measure Pb2+ ion concentrations in real time. The detection limit was lowered by stabilizing the surface of the resistive film with sodium hydroxide and 15-crown-5 ether and optimizing the sensor geometry to maximize the effective surface area. The detection mechanism is based on the complexation of the Pb2+ ions by the lead ionophores within the membrane, thus modulating the interactions between the ionophores and the chemiresistive film. The limit of detection of the fabricated devices was reliably below 2 µg L-1, with concentrations up to 3 mg L-1 routinely quantifiable over several measurement cycles. The chemiresistive sensors can thus achieve lower detection limits than potentiometric devices while being more robust and simpler to fabricate by omitting the reference electrode. Ion-selective membrane-covered chemiresistors can therefore be deployed to continuously monitor drinking water sources and detect harmful levels of lead in real time.

A self-assembly and cellular migration based fabrication of high-density 3D tubular constructs of barrier forming membranes.

Three-dimensional (3D) in vitro models, superior in simulating physiological conditions compared to 2D models, offer intricate cell-cell and cell-ECM interactions with diverse signaling cues like fluid shear stress and growth factor gradients. Yet, developing 3D tissue barrier models, specifically perfusable luminal structures with dense, multicellular constructs maintained for extended durations with oxygen and nutrients, remains a technical challenge. Here, we describe a molding-based approach for the fabrication of free-standing, perfusable, high cellular density tissue constructs using a self-assembly and migration process to form functional barriers. This technique utilizes a polytetrafluoroethylene (PTFE)-coated stainless-steel wire, held by stainless steel needles, as a template for a perfusable channel within an elongated PDMS well. Upon adding a bio-ink mix of cells and collagen, it self-assembles into a high cell density layer conformally around the wire. Removing the wire reveals a hollow construct, connectable to an inlet and outlet for perfusion. This scalable method allows creating varied dimensions and multicellular configurations. Notably, post-assembly, cells such as human umbilical vein endothelial cells (HUVECs) migrate to the surface and form functional barriers with adherens junctions. Permeability tests and fluorescence imaging confirm that these constructs closely mimic in vivo endothelial barrier permeability, exhibiting the lowest permeability among all in vitro models in the literature. Unlike traditional methods involving uneven post-seeding of endothelial cells leading to subpar barriers, our approach is a straightforward alternative for fabricating complex perfusable 3D tissue constructs and effective tissue barriers for use in various applications, including tissue engineering, drug screening, and disease modeling.

The Effects of Exercise on Synaptic Plasticity in Individuals With Mild Cognitive Impairment: Protocol for a Pilot Intervention Study.

BACKGROUND: Mild cognitive impairment (MCI) is a syndrome preceding more severe impairment characterized by dementia. MCI affects an estimated 15% to 20% of people older than 65 years. Nonpharmacological interventions including exercise are recommended as part of overall MCI management based on the positive effects of exercise on cognitive performance. Interval training involves brief intermittent bouts of exercise interspersed with short recovery periods. This type of exercise promotes cognitive improvement and can be performed in individuals with MCI. Synaptic plasticity can be assessed in vivo by the neurophysiological response to repetitive transcranial magnetic stimulation (rTMS). A method to assess synaptic plasticity uses an intermittent theta burst stimulation (iTBS), which is a patterned form of rTMS. Individuals with MCI have decreased responses to iTBS, reflecting reduced synaptic plasticity. It is unknown whether interval training causes changes in synaptic plasticity in individuals living with MCI. OBJECTIVE: This research will determine whether interval training performed using a cycle ergometer enhances synaptic plasticity in individuals with MCI. The three aims are to (1) quantify synaptic plasticity after interval training performed at a self-determined intensity in individuals with MCI; (2) determine whether changes in synaptic plasticity correlate with changes in serum brain-derived neurotrophic factor, osteocalcin, and cognition; and (3) assess participant compliance to the exercise schedule. METHODS: 24 individuals diagnosed with MCI will be recruited for assignment to 1 of the 2 equally sized groups: exercise and no exercise. The exercise group will perform exercise 3 times per week for 4 weeks. Synaptic plasticity will be measured before and following the 4-week intervention. At these time points, synaptic plasticity will be measured as the response to single-pulse TMS, reflected as the percent change in the average amplitude of 20 motor-evoked potentials before and after an iTBS rTMS protocol, which is used to induce synaptic plasticity. In addition, individuals will complete a battery of cognitive assessments and provide a blood sample from the antecubital vein to determine serum brain-derived neurotrophic factor and osteocalcin. RESULTS: The study began in September 2023. CONCLUSIONS: The proposed research is the first to assess whether synaptic plasticity is enhanced after exercise training in individuals with MCI. If exercise does indeed modify synaptic plasticity, this will create a new avenue by which we can study and manipulate neural plasticity in these individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05663918; https://clinicaltrials.gov/study/NCT05663918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50030.

An ion-selective chemiresistive platform as demonstrated for the detection of nitrogen species in water.

The use of ion-selective electrodes (ISE) is a well-established technique for the detection of ions in aqueous solutions but requires the use of a reference electrode. Here, we introduce a platform of ion-selective chemiresistors for the detection of nitrogen species in water as an alternative method without the need for reference electrodes. Chemiresistors have a sensitive surface that is prone to damage during operation in aqueous solutions. By applying a layer of ion-selective membrane to the surface of the chemiresistive device, the surface becomes protected and highly selective. We demonstrate both anion-selective (NO3-, NO2-) and cation-selective (NH4+) membranes. The nitrate sensors are able to measure nitrate ions in a range of 2.2-220 ppm with a detection limit of 0.3 ppm. The nitrite sensors respond between 67 ppb and 67 ppm of nitrite ions (64 ppb detection limit). The ammonium sensors can measure ammonium concentrations in a wide range from 10 ppb to 100 ppm (0.5 ppb detection limit). The fast responses to nitrate and nitrite are due to a mechanism involving electrostatic gating repulsion between negative charge carriers of the film and anions while ammonium detection arises from two mechanisms based on electrostatic gating repulsion and adsorption of ammonium ions at the surface of the p-doped chemiresistive film. The adsorption phenomenon slows down the recovery time of the ammonium sensor. This sensor design is a new platform to continuously monitor ions in industrial, domestic, and environmental water resources by robust chemiresistive devices.

Bending Drosophila larva using a microfluidic device enables imaging of its brain and nervous system at single neuronal resolution.

Single neuronal imaging of a fully intact Drosophila larva is a difficult challenge for neurosciences due to the robust digging/burrowing behaviour of the Drosophila larva and the lack of intact immobilization methods at single-neuron resolution. In this paper, for the first time, a simple microfluidic device to completely immobilize the brain and the CNS of a live, fully-functioning Drosophila larva for single neuronal imaging has been demonstrated. The design of the microfluidic device contains a unique clamping feature which pins and bends the body of the larva at 1/3rd of its length from the head. This simple twist combined with the pinning mechanism not only could stop the locomotion of the larva but also could immobilize the major movement of internal organs including the CNS. The results showed that the bent trap could keep the single neuron completely inside the field of view (FOV) (50 µm × 50 µm) over 10 min of confocal imaging. The range of motion in the x- and y-axis was approximately 8 µm and 2.5 µm, respectively. This corresponds to a range of 16% and 6% along the axis of the channel and across it compared to the size of the FOV (50 µm × 50 µm). The calcium activity of the single neurons in a 3rd instar GCaMP5 larva (Cha-Gal4/CyO; UAS-GCaMP5G/TM3) was measured while its mouth region was exposed to 20 mM sodium azide (NaN3) for 5 s. The results showed that the activity of the neurons has been statistically (p < 0.0005) increased (∼60%).

Detection of free chlorine in water using graphene-like carbon based chemiresistive sensors.

Free chlorine is the most commonly used water disinfectant. Measuring its concentration during and after water treatment is crucial to ensure its effectiveness. However, many of the existing methods do not allow for continuous on-line monitoring. Here we demonstrate a solid state chemiresistive sensor using graphene-like carbon (GLC) that overcomes that issue. GLC films that were either bare or non-covalently functionalized with the redox-active phenyl-capped aniline tetramer (PCAT) were successfully employed to quantify aqueous free chlorine, although functionalized devices showed better performance. The response of the sensors to increasing concentrations of free chlorine followed a Langmuir adsorption isotherm in the two tested ranges: 0.01-0.2 ppm and 0.2-1.4 ppm. The limit of detection was estimated to be 1 ppb, permitting the detection of breaches in chlorine filters. The devices respond to decreasing levels of free chlorine without the need for a reset, allowing for the continuous monitoring of fluctuations in the concentration. The maximum sensor response and saturation concentration were found to depend on the thickness of the GLC film. Hence, the sensitivity and dynamic range of the sensors can be tailored to different applications by adjusting the thickness of the films. Tap water samples from a residential area were tested using these sensors, which showed good agreement with standard colorimetric measurement methods. The devices did not suffer from interferences in the presence of ions commonly found in drinking water. Overall, these sensors are a cost-effective option for the continuous automated monitoring of free chlorine in drinking water.

Tuning the Chemical and Mechanical Properties of Conductive MoS2 Thin Films by Surface Modification with Aryl Diazonium Salts.

Molybdenum disulfide (MoS2) is a promising material for applications in sensors, energy storage, energy conversion devices, solar cells, and fuel cells. Because many of those applications require conductive materials, we recently developed a method for preparing a conductive form of MoS2 (c-MoS2) using dilute aqueous hydrogen peroxide in a simple and safe way. Here, we investigate modulating the chemical and mechanical surface properties of c-MoS2 thin films using diazonium chemistry. In addition to a direct passivation strategy of c-MoS2 with diazonium salts for electron-withdrawing groups, we also propose a novel in situ synthetic pathway for modification with electron-donating groups. The obtained results are examined by Raman spectroscopy and X-ray photoelectron spectroscopy. The degree of surface passivation of pristine and functionalized c-MoS2 films was tested by exposing them to aqueous solutions of different metal cations (Fe2+, Zn2+, Cu2+, and Co2+) and detecting the chemiresistive response. While pristine films were found to interact with several of the cations, modified films did not. We propose that a surface charge transfer mechanism is responsible for the chemiresistive response of the pristine films, while both modification routes succeeded at complete surface passivation. Functionalization was also found to lower the coefficient of friction for semiconducting 2H-MoS2, while all conductive materials (modified or not) also had lower coefficients of friction. This opens up a pathway to a palette of dry lubricant materials with improved chemical stability and tunable conductivity. Thus, both in situ and direct diazonium chemistries are powerful tools for tuning chemical and mechanical properties of conductive MoS2 for new devices and lubricants based on conductive MoS2.

Surface Modification of PDMS-Based Microfluidic Devices with Collagen Using Polydopamine as a Spacer to Enhance Primary Human Bronchial Epithelial Cell Adhesion.

Polydimethylsiloxane (PDMS) is a silicone-based synthetic material used in various biomedical applications due to its properties, including transparency, flexibility, permeability to gases, and ease of use. Though PDMS facilitates and assists the fabrication of complicated geometries at micro- and nano-scales, it does not optimally interact with cells for adherence and proliferation. Various strategies have been proposed to render PDMS to enhance cell attachment. The majority of these surface modification techniques have been offered for a static cell culture system. However, dynamic cell culture systems such as organ-on-a-chip devices are demanding platforms that recapitulate a living tissue microenvironment's complexity. In organ-on-a-chip platforms, PDMS surfaces are usually coated by extracellular matrix (ECM) proteins, which occur as a result of a physical and weak bonding between PDMS and ECM proteins, and this binding can be degraded when it is exposed to shear stresses. This work reports static and dynamic coating methods to covalently bind collagen within a PDMS-based microfluidic device using polydopamine (PDA). These coating methods were evaluated using water contact angle measurement and atomic force microscopy (AFM) to optimize coating conditions. The biocompatibility of collagen-coated PDMS devices was assessed by culturing primary human bronchial epithelial cells (HBECs) in microfluidic devices. It was shown that both PDA coating methods could be used to bind collagen, thereby improving cell adhesion (approximately three times higher) without showing any discernible difference in cell attachment between these two methods. These results suggested that such a surface modification can help coat extracellular matrix protein onto PDMS-based microfluidic devices.

PHAIR: a biosensor for pH measurement in air-liquid interface cell culture.

In many biological systems, pH can be used as a parameter to understand and study cell dynamics. However, measuring pH in live cell culture is limited by the sensor ion specificity, proximity to the cell surface, and scalability. Commercially available pH sensors are difficult to integrate into a small-scale cell culture system due to their size and are not cost-effective for disposable use. We made PHAIR-a new pH sensor that uses a micro-wire format to measure pH in vitro human airway cell culture. Tungsten micro-wires were used as the working electrodes, and silver micro-wires with a silver/silver chloride coating were used as a pseudo reference electrode. pH sensitivity, in a wide and narrow range, and stability of these sensors were tested in common standard buffer solutions as well as in culture media of human airway epithelial cells grown at the air-liquid interface in a 24 well cell culture plate. When measuring the pH of cells grown under basal and challenge conditions using PHAIR, cell viability and cytokine responses were not affected. Our results confirm that micro-wire-based sensors have the capacity for miniaturization and detection of diverse ions while maintaining sensitivity. This suggests the broad application of PHAIR in various biological experimental settings.

Facile fabrication of conductive MoS2 thin films by sonication in hot water and evaluation of their electrocatalytic performance in the hydrogen evolution reaction.

Molybdenum disulfide (MoS2) has long been used in catalysis and is a promising material for energy conversion devices. In order to utilize MoS2 in electrocatalytic applications, it needs to be sufficiently conductive. Even though a metallic 1T phase of MoS2 exists, its exfoliation process is expensive and difficult to scale because it involves hazardous materials and procedures, limiting its practical applications. We have previously reported an efficient and environmentally friendly procedure to exfoliate conductive MoS2 via sonication in very dilute aqueous hydrogen peroxide. Here, we report a new way of exfoliating heavily doped conductive MoS2 by sonication in pure water at 60 °C without additives. Conductivity measurements, Raman spectroscopy and X-ray photoelectron spectroscopy demonstrate that controlling the sonication time and temperature lead to the generation of small quantities of hydrogen peroxide in the water that interact with MoS2 to form a small amount of sub-stoichiometric MoO3-y . This impurity acts as a dopant and is responsible for the increase in conductivity of the MoS2 films without compromising their structural integrity. We also evaluate the performance of the doped MoS2 films as electrocatalysts in the hydrogen evolution reaction. We elucidate the mechanistic origin of the catalytic properties of these materials which may be of future use to develop a family of electrocatalysts based on doped MoS2.

Solid State Sensors for Hydrogen Peroxide Detection.

Hydrogen peroxide (H2O2) is a key molecule in numerous physiological, industrial, and environmental processes. H2O2 is monitored using various methods like colorimetry, luminescence, fluorescence, and electrochemical methods. Here, we aim to provide a comprehensive review of solid state sensors to monitor H2O2. The review covers three categories of sensors: chemiresistive, conductometric, and field effect transistors. A brief description of the sensing mechanisms of these sensors has been provided. All three sensor types are evaluated based on the sensing parameters like sensitivity, limit of detection, measuring range and response time. We highlight those sensors which have advanced the field by using innovative materials or sensor fabrication techniques. Finally, we discuss the limitations of current solid state sensors and the future directions for research and development in this exciting area.

A 3D Self-Assembled In Vitro Model to Simulate Direct and Indirect Interactions between Adipocytes and Skeletal Muscle Cells.

The molecular mechanisms of the development and progression of diabetes and obesity involve complex interactions between adipocytes and skeletal muscle cells. Although 2D in-vitro models are the gold standard for the mechanistic study of such behaviors, they do not recreate the complexity and dynamics of the interactions between the cell types involved. Alternatively, animal models are used but are expensive, difficult to visualize or analyze, are not completely representative of human physiology or genetic background, and have associated ethical considerations. 3D co-culture systems can be complementary to these approaches. Here, using a newly developed 3D biofabrication method, adipocytes and myoblasts are positioned precisely either in direct physical contact or in close proximity such that the paracrine effects could be systematically studied. Suitable protocols for growth and differentiation of both cells in the co-culture system is also developed. Cells show more restrained lipid and protein production in 3D systems compared to 2D ones and adipocytes show more lipolysis in indirect contact with myoblasts as response to drug treatment. These findings emphasize importance of physical contact between cells that have been overlooked in co-culture systems using transwell inserts and can be used in studies for the development of anti-obesity drugs.

Integrated Triboelectric Nanogenerators in the Era of the Internet of Things.

Since their debut in 2012, triboelectric nanogenerators (TENGs) have attained high performance in terms of both energy density and instantaneous conversion, reaching up to 500 W m-2 and 85%, respectively, synchronous with multiple energy sources and hybridized designs. Here, a comprehensive review of the design guidelines of TENGs, their performance, and their designs in the context of Internet of Things (IoT) applications is presented. The development stages of TENGs in large-scale self-powered systems and technological applications enabled by harvesting energy from water waves or wind energy sources are also reviewed. This self-powered capability is essential considering that IoT applications should be capable of operation anywhere and anytime, supported by a network of energy harvesting systems in arbitrary environments. In addition, this review paper investigates the development of self-charging power units (SCPUs), which can be realized by pairing TENGs with energy storage devices, such as batteries and capacitors. Consequently, different designs of power management circuits, supercapacitors, and batteries that can be integrated with TENG devices are also reviewed. Finally, the significant factors that need to be addressed when designing and optimizing TENG-based systems for energy harvesting and self-powered sensing applications are discussed.

Suppression of Biofouling on a Permeable Membrane for Dissolved Oxygen Sensing Using a Lubricant-Infused Coating.

Specific ranges of dissolved oxygen (DO) concentrations must be maintained in a waterbody for it to be hospitable for aquatic animals. DO sensor designs can employ selectively permeable membranes to isolate DO from untargeted compounds or organisms in waterbodies. Hence, the DO concentration can be monitored and the health of the water can be evaluated over time. However, the presence of bacteria in natural waterbodies can lead to the formation of biofilms that can block pores and prevent analyte from permeating the membrane, resulting in inaccurate readings. In this work, we demonstrate the implementation of a fluorosilane-based omniphobic lubricant-infused (OLI) coating on a selectively permeable membrane and investigate the rate of biofilm formation for a commercially available DO sensor. Coated and unmodified membranes were incubated in an environment undergoing accelerated bacterial growth, and the change in sensitivity was evaluated after 40, 100, 250, and 500 h. Our findings show that the OLI membranes attenuate biofouling by 70% and maintain sensitivity after 3 weeks of incubation, further demonstrating that oxygen transfer through the OLI coating is achievable. Meanwhile, unmodified membranes exhibit significant biofouling that results in a 3.35 higher rate of decay in oxygen measurement sensitivity and an over 70% decrease in static contact angle. These results show that the OLI coating can be applied on commercially available membranes to prevent biofouling. Therefore, OLI coatings are a suitable candidate to suppress biofilm formation in the widespread use of selectively permeable membranes for environmental, medical, and fluid separation applications.

All printable snow-based triboelectric nanogenerator.

The development of power generators that can function in harsh snowy environments and in contact with snow can be beneficial but challenging to accomplish. Herein, we introduce the first snow-based triboelectric nanogenerator (snow-TENG) that can be used as an energy harvester and a multifunctional sensor based on the principle of snow-triboelectrification. In this work, we used a 3D printing technique for the precise design and deposition of the electrode and triboelectric layer, leading to flexible, stretchable and metal-free triboelectric generators. Based on the single electrode mode, the device can generate an instantaneous output power density as high as 0.2 mW/m2, an open circuit voltage up to 8 V, and a current density of 40 µA/m2. In addition, the snow-TENG can function as a miniaturized weather station to monitor the weather in real time to provide accurate information about the snowfall rate, snow accumulation depth, wind direction, and speed in snowy and/or icy environments. In addition, the snow-TENG can be used as a wearable power source and biomechanical sensor to detect human body motions, which may prove useful for snow-related sports. Unlike conventional sensor platforms, our design works without the need for batteries or image processing systems. We envision these devices could potentially be integrated into solar panels to ensure continuous power supply during snowy weather conditions.

A Bioprinted In Vitro Model for Osteoblast to Osteocyte Transformation by Changing Mechanical Properties of the ECM.

Osteocytes are key contributors to bone remodeling. During the remodeling process, trapped osteoblasts undergo a phenotypic change to become osteocytes. The specific mechanisms by which osteocytes work are still debatable and models that exist to study them are sparse. This work presents an in vitro, bioprinted model based on the previously developed technique, ExCeL, in which a cell-embedded hydrogel is printed and immediately crosslinked using paper as a crosslinker-storing substrate. This process mimics the phenotypical change of osteoblast to osteocyte by altering the mechanical properties of the hydrogel. By printing Saos-2, osteosarcoma cells, embedded in the alginate hydrogel with differing mechanical properties, their morphology, protein, and gene expression can be changed from osteoblast-like to osteocyte-like. The stiffer gel is 30 times stiffer and results in significantly smaller cells with reduced alkaline phosphatase activity and expression of osteoblast-marker genes such as MMP9 and TIMP2. There is no change in viability between cells despite encapsulation in gels with different mechanical properties. The results show that the phenomenon of osteoblasts becoming encapsulated during the bone remodeling process can be replicated using the ExCeL bioprinting technique. This model has potential for studying how osteocytes can interact with external mechanical stimuli or drugs.

Silicon Carbide Nanoparticles as an Effective Bioadhesive to Bond Collagen Containing Composite Gel Layers for Tissue Engineering Applications.

Additive manufacturing via layer-by-layer adhesive bonding holds much promise for scalable manufacturing of tissue-like constructs, specifically scaffolds with integrated vascular networks for tissue engineering applications. However, there remains a lack of effective adhesives capable of composite layer fusion without affecting the integrity of patterned features. Here, the use of silicon carbide is introduced as an effective adhesive to achieve strong bonding (0.39 ± 0.03 kPa) between hybrid hydrogel films composed of alginate and collagen. The techniques have allowed us to fabricate multilayered, heterogeneous constructs with embedded high-resolution microchannels (150 µm-1 mm) that are precisely interspaced (500-600 µm). Hydrogel layers are effectively bonded with silicon carbide nanoparticles without blocking the hollow microchannels and high cell viability (90.61 ± 3.28%) is maintained within the scaffold. Nanosilica is also tested and found to cause clogging of smaller microchannels when used for interlayer bonding, but is successfully used to attach synthetic polymers (e.g., Tygon) to the hydrogels (32.5 ± 2.12 mN bond strength). This allows us to form inlet and outlet interconnections to the gel constructs. This ability to integrate hollow channel networks into bulk soft material structures for perfusion can be useful in 3D tissue engineering applications.

Robust Chemiresistive Sensor for Continuous Monitoring of Free Chlorine Using Graphene-like Carbon.

Free chlorine is widely used in industry as a bleaching and oxidizing agent. Its concentration is tightly monitored to avoid environmental contamination and deleterious human health effects. Here, we demonstrate a solid state chemiresistive sensor using graphene like carbon (GLC) to detect free chlorine in water. A 15-20 nm thick GLC layer on a PET substrate was modified with a redox-active aniline oligomer (phenyl-capped aniline tetramer, PCAT) to increase sensitivity, improve selectivity, and impart fouling resistance. Both the bare GLC sensor and the PCAT-modified GLC sensor can detect free chlorine continuously and, unlike previous chemiresistive sensors, do not require a reset. The PCAT-modified sensor showed a linear response with a slope of 13.89 (mg/L)-1 to free chlorine concentrations between 0.2 and 0.8 mg/L which is relevant for free chlorine monitoring for drinking water and wastewater applications. The PCAT-modified GLC sensors were found to be selective and showed less than 0.5% change in current in response to species such as nitrates, phosphates and sulfates in water. They also were resistant to fouling from organic material and showed only a 2% loss in signal. Tap water samples from residential area were tested using this sensor which showed good agreement with standard colorimetric measurement methods. The GLC and PCAT-GLC sensors show high sensitivity and excellent selectivity to free chlorine and can be used for continuous automated monitoring of free chlorine.