Review article: Current status and future directions of ingestible electronic devices in gastroenterology.

BACKGROUND: Advances in microelectronics have greatly expanded the capabilities and clinical potential of ingestible electronic devices. AIM: To provide an overview of the structure and potential impact of ingestible devices in development that are relevant to the gastrointestinal tract. METHODS: We performed a detailed literature search to inform this narrative review. RESULTS: Technical success of ingestible electronic devices relies on the ability to miniaturise the microelectronic circuits, sensors and components for interventional functions while being sufficiently powered to fulfil the intended function. These devices offer the advantages of being convenient and minimally invasive, with real-time assessment often possible and with minimal interference to normal physiology. Safety has not been a limitation, but defining and controlling device location in the gastrointestinal tract remains challenging. The success of capsule endoscopy has buoyed enthusiasm for the concepts, but few ingestible devices have reached clinical practice to date, partly due to the novelty of the information they provide and also due to the challenges of adding this novel technology to established clinical paradigms. Nonetheless, with ongoing technological advancement and as understanding of their potential impact emerges, acceptance of such technology will grow. These devices have the capacity to provide unique insight into gastrointestinal physiology and pathophysiology. Interventional functions, such as sampling of tissue or luminal contents and delivery of therapies, may further enhance their ability to sharpen gastroenterological diagnoses, monitoring and treatment. CONCLUSIONS: The development of miniaturised ingestible microelectronic-based devices offers exciting prospects for enhancing gastroenterological research and the delivery of personalised, point-of-care medicine.

Detection of changes in regional colonic fermentation in response to supplementing a low FODMAP diet with dietary fibres by hydrogen concentrations, but not by luminal pH.

BACKGROUND: Carbohydrate fermentation plays a pivotal role in maintaining colonic health with excessive proximal and deficient distal fermentation being detrimental. AIMS: To utilise telemetric gas- and pH-sensing capsule technologies for defining patterns of regional fermentation following dietary manipulations, alongside conventional techniques of measuring fermentation. METHODS: In a double-blind crossover trial, 20 patients with irritable bowel syndrome were fed low FODMAP diets that included no extra fibre (total fibre content 24 g/day), or additional poorly fermented fibre, alone (33 g/day) or with fermentable fibre (45 g/day) for 2 weeks. Plasma and faecal biochemistry, luminal profiles defined by tandem gas- and pH-sensing capsules, and faecal microbiota were assessed. RESULTS: Plasma short-chain fatty acid (SCFA) concentrations (µmol/L) were median (IQR) 121 (100-222) with fibre combination compared with 66 (44-120) with poorly fermented fibre alone (p = 0.028) and 74 (55-125) control (p = 0.069), but no differences in faecal content were observed. Luminal hydrogen concentrations (%), but not pH, were higher in distal colon (mean 4.9 [95% CI: 2.2-7.5]) with fibre combination compared with 1.8 (0.8-2.8) with poorly fermented fibre alone (p = 0.003) and 1.9 (0.7-3.1) control (p = 0.003). Relative abundances of saccharolytic fermentative bacteria were generally higher in association with supplementation with the fibre combination. CONCLUSIONS: A modest increase in fermentable plus poorly fermented fibres had minor effects on faecal measures of fermentation, despite increases in plasma SCFA and abundance of fermentative bacteria, but the gas-sensing capsule, not pH-sensing capsule, detected the anticipated propagation of fermentation distally in the colon. The gas-sensing capsule technology provides unique insights into localisation of colonic fermentation. TRIAL REGISTRATION: ACTRN12619000691145.

Comparison of gastrointestinal landmarks using the gas-sensing capsule and wireless motility capsule.

BACKGROUND: Accurate definition of the gastroduodenal and ileocaecal junctions (GDJ, ICJ) is essential for the measurement of regional transit times. AIMS: To compare the assessment of these landmarks using the novel gas-sensing capsule and validated wireless motility capsule (WMC), and to evaluate intra-subject variance in transit times METHODS: Healthy subjects ingested the gas-sensing capsule and WMC tandemly in random order. Inter-observer agreement was evaluated by intra-class correlation coefficient (ICC). Agreement between the paired devices' transit times was assessed using Bland-Altman analysis; coefficient of variation was performed to express intra-individual variance in transit times. Similar analyses were completed with tandemly ingested gas-sensing capsules. RESULTS: The inter-observer agreement for landmarks for both capsules was excellent (mean ICC ≥0.97) in 50 studies. The GDJ was identifiable in 92% of the gas-sensing capsule studies versus 82% of the WMC studies (p = 0.27); the ICJ in 96% versus 84%, respectively (p = 0.11). In the primary cohort (n = 26), median regional transit times differed by less than 6 min between paired capsules. Bland-Altman revealed a bias of -0.12 (95% limits of agreement, -0.94 to 0.70) hours for GDJ and - 0.446 (-2.86 to 2.0) hours for ICJ. Similar results were found in a demographically distinct validation cohort (n = 24). For tandemly ingested gas-sensing capsules, coefficients of variation of transit times were 11%-35%, which were similar to variance between the paired gas-sensing capsule and WMC, as were the biases. The capsules were well tolerated. CONCLUSIONS: Key anatomical landmarks are accurately identified with the gas-sensing capsule in healthy individuals. Intra-individual differences in transit times between capsules are probably due to physiological factors. Studies in populations with gastrointestinal diseases are now required.

Intestinal gases: influence on gut disorders and the role of dietary manipulations.

The inner workings of the intestines, in which the body and microbiome intersect to influence gut function and systemic health, remain elusive. Carbon dioxide, hydrogen, methane and hydrogen sulfide, as well as a variety of trace gases, are generated by the chemical interactions and microbiota within the gut. Profiling of these intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. Indeed, different tools for measuring these intestinal gases have been developed, including newly developed gas-sensing capsule technology. Gases can, according to their type, concentration and volume, induce or relieve abdominal symptoms, and might also have physiological, pathogenic and therapeutic effects. Thus, profiling and modulating intestinal gases could be powerful tools for disease prevention and/or therapy. As the interactions between the microbiota, chemical constituents and fermentative substrates of the gut are principally influenced by dietary intake, altering the diet, which, in turn, changes gas profiles, is the main therapeutic approach for gastrointestinal disorders. An improved understanding of the complex interactions within the intestines that generate gases will enhance our ability to prevent, diagnose, treat and monitor many gastrointestinal disorders.

The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis.

BACKGROUND: Intestinal gases are currently used for the diagnosis of disorders including small intestinal bacterial overgrowth and carbohydrate malabsorption. AIM: To compare the performance of measuring hydrogen production within the gut directly with the telemetric gas-sensing capsule with that of indirect measurement through breath testing. METHODS: Using standard breath testing protocols, the capsules and breath tests were simultaneously evaluated in a single-blinded trial in 12 healthy subjects. Eight received a single dose of 1.25-40 g inulin and four 20 or 40 g glucose. Safety and reliability of the capsules were also assessed. RESULTS: There were no reported adverse events. All capsules were retrieved and operated without failure. Capsule measurements were in agreement with breath test measurements in magnitude but not in timing; minimal hydrogen production was observed after glucose ingestion and capsule measurements correlated with breath hydrogen after ingestion of 40 g inulin. A dose-dependent increase in concentration of hydrogen was observed from the capsule following ingestion of inulin as low as 1.25 g compared with >10 g for breath measurements. Specifically, the capsule measured >3000 times higher concentrations of hydrogen compared to breath tests, resulting in a signal-to-noise ratio of 23.4 for the capsule compared to 4.2 for the breath test. CONCLUSIONS: The capsule showed high sensitivity and signal-to-noise ratio in measuring luminal hydrogen concentrations, provided information on the site of intestinal gas production, and demonstrated safety and reliability. The capsule has potential for improving diagnostic precision for disorders such as small intestinal bacterial overgrowth.

Ultrafast Acoustofluidic Exfoliation of Stratified Crystals.

While the remarkable properties of 2D crystalline materials offer tremendous opportunities for their use in optics, electronics, energy systems, biotechnology, and catalysis, their practical implementation largely depends critically on the ability to exfoliate them from a 3D stratified bulk state. This goal nevertheless remains elusive, particularly in terms of a rapid processing method that facilitates high yield and dimension control. An ultrafast multiscale exfoliation method is reported which exploits the piezoelectricity of stratified materials that are noncentrosymmetric in nature to trigger electrically-induced mechanical failure across weak grain boundaries associated with their crystal domain planes. In particular, it is demonstrated that microfluidic nebulization using high frequency acoustic waves exposes bulk 3D piezoelectric crystals such as molybdenum disulphide (MoS2 ) and tungsten disulphide (WS2 ) to a combination of extraordinarily large mechanical acceleration (≈108 m s-2 ) and electric field (≈107 V m-1 ). This results in the layered bulk material being rapidly cleaved into pristine quasi-2D-nanosheets that predominantly comprise single layers, thus constituting a rapid and high throughput chip-scale method that opens new possibilities for scalable production and spray coating deposition.

A Gallium-Based Magnetocaloric Liquid Metal Ferrofluid.

We demonstrate a magnetocaloric ferrofluid based on a gadolinium saturated liquid metal matrix, using a gallium-based liquid metal alloy as the solvent and suspension medium. The material is liquid at room temperature, while exhibiting spontaneous magnetization and a large magnetocaloric effect. The magnetic properties were attributed to the formation of gadolinium nanoparticles suspended within the liquid gallium alloy, which acts as a reaction solvent during the nanoparticle synthesis. High nanoparticle weight fractions exceeding 2% could be suspended within the liquid metal matrix. The liquid metal ferrofluid shows promise for magnetocaloric cooling due to its high thermal conductivity and its liquid nature. Magnetic and thermoanalytic characterizations reveal that the developed material remains liquid within the temperature window required for domestic refrigeration purposes, which enables future fluidic magnetocaloric devices. Additionally, the observed formation of nanometer-sized metallic particles within the supersaturated liquid metal solution has general implications for chemical synthesis and provides a new synthetic pathway toward metallic nanoparticles based on highly reactive rare earth metals.

Ingestible Sensors.

Ingestible sensing capsules are fast emerging as a critical technology that has the ability to greatly impact health, nutrition, and clinical areas. These ingestible devices are noninvasive and hence are very attractive for customers. With widespread access to smart phones connected to the Internet, the data produced by this technology can be readily seen and reviewed online, and accessed by both users and physicians. The outputs provide invaluable information to reveal the state of gut health and disorders as well as the impact of food, medical supplements, and environmental changes on the gastrointestinal tract. One unique feature of such ingestible sensors is that their passage through the gut lumen gives them access to each individual organ of the gastrointestinal tract. Therefore, ingestible sensors offer the ability to gather images and monitor luminal fluid and the contents of each gut segment including electrolytes, enzymes, metabolites, hormones, and the microbial communities. As such, an incredible wealth of knowledge regarding the functionality and state of health of individuals through key gut biomarkers can be obtained. This Review presents an overview of the gut structure and discusses current and emerging digestible technologies. The text is an effort to provide a comprehensive overview of ingestible sensing capsules, from both a body physiology point of view as well as a technological view, and to detail the potential information that they can generate.

Surface Water Dependent Properties of Sulfur-Rich Molybdenum Sulfides: Electrolyteless Gas Phase Water Splitting.

Sulfur-rich molybdenum sulfides are an emerging class of inorganic coordination polymers that are predominantly utilized for their superior catalytic properties. Here we investigate surface water dependent properties of sulfur-rich MoSx (x = 32/3) and its interaction with water vapor. We report that MoSx is a highly hygroscopic semiconductor, which can reversibly bind up to 0.9 H2O molecule per Mo. The presence of surface water is found to have a profound influence on the semiconductor's properties, modulating the material's photoluminescence by over 1 order of magnitude, in transition from dry to moist ambient. Furthermore, the conductivity of a MoSx-based moisture sensor is modulated in excess of 2 orders of magnitude for 30% increase in humidity. As the core application, we utilize the discovered properties of MoSx to develop an electrolyteless water splitting photocatalyst that relies entirely on the hygroscopic nature of MoSx as the water source. The catalyst is formulated as an ink that can be coated onto insulating substrates, such as glass, leading to efficient hydrogen and oxygen evolution from water vapor. The concept has the potential to be widely adopted for future solar fuel production.

Wafer-scale two-dimensional semiconductors from printed oxide skin of liquid metals.

A variety of deposition methods for two-dimensional crystals have been demonstrated; however, their wafer-scale deposition remains a challenge. Here we introduce a technique for depositing and patterning of wafer-scale two-dimensional metal chalcogenide compounds by transforming the native interfacial metal oxide layer of low melting point metal precursors (group III and IV) in liquid form. In an oxygen-containing atmosphere, these metals establish an atomically thin oxide layer in a self-limiting reaction. The layer increases the wettability of the liquid metal placed on oxygen-terminated substrates, leaving the thin oxide layer behind. In the case of liquid gallium, the oxide skin attaches exclusively to a substrate and is then sulfurized via a relatively low temperature process. By controlling the surface chemistry of the substrate, we produce large area two-dimensional semiconducting GaS of unit cell thickness (∼1.5 nm). The presented deposition and patterning method offers great commercial potential for wafer-scale processes.

Excitation dependent bidirectional electron transfer in phthalocyanine-functionalised MoS2 nanosheets.

Two-dimensional (2D) transition metal chalcogenides such as 2D MoS2 are considered prime candidate materials for the design of next generation optoelectronics. Functionalisation of these materials is considered to be a key step in tailoring their properties towards specific applications and unlocking their full potential. Here we present a van der Waals functionalisation strategy for creating MoS2 nanosheets decorated with free base phthalocyanine chromophores. The semiconducting sheets are found to intimately interact with these optoelectronically active chromophores, resulting in an electronic heterostructure that exhibits enhanced optoelectronic properties and exploitable charge transfer. We show that by utilising laterally confined MoS2 nanosheets, the conduction band of the semiconductor could be positioned between the chromophore's S1 and S2 states. Consequently, bidirectional photoinduced electron transfer processes are observed, with excitation of the functionalised nanosheet's semiconductor transition resulting in electron transfer to the phthalocyanine's LUMO, and excitation of the chromophore's S2 state leading to electron injection into the MoS2 conduction band. However, charge transfer from the dye's S1 transition to the MoS2 nanosheet is found to be thermodynamically unfavourable, resulting in intense radiative recombination. These findings may enable controlling and tuning the charge carrier density of semiconducting nanosheets via optical means through the exploitation of photoinduced electron transfer. Furthermore this work provides access to 2D semiconductor-hybrids with tailored absorption profiles and photoluminescence.

Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model.

Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO2 concentration and with the cinnamon treatment, CO2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.

Enhanced quantum efficiency from a mosaic of two dimensional MoS2 formed onto aminosilane functionalised substrates.

Developing scalable methods of growing two dimensional molybdenum disulphide (2D MoS2) with strong optical properties, on any desired substrates, is a necessary step towards industrial uptake of this material for optical applications. In this study, Si/SiO2 substrates were functionalised using self-assembled monolayers of three different aminosilanes with various numbers of amine groups and molecular lengths as underlayers for enhancing the adherence of the molybdenum precursor. The tetrahedral [MoS4](2-) anion groups from the molybdenum precursor were bonded on these silanised Si/SiO2 substrates afterwards. The substrates were then treated with a combined thermolysis and sulphurisation step. The results showed that silanisation of the substrates using the longest chains and the largest number of amine groups provided a good foundation to grow quasi 2D MoS2 made from adjacent flakes in a mosaic formation. Microscopy and spectroscopy investigations revealed that these quasi 2D MoS2 formed using this long chain aminosilane resulted in flakes with lateral dimensions in micron and submicron ranges composed of adjoining MoS2 pieces of 20 to 60 nm in lateral dimensions, dominantly made of 3 to 5 MoS2 fundamental layers. The obtained quasi 2D MoS2 shows a high internal quantum efficiency of 2.6% associated with the quantum confinement effect and high stoichiometry of the adjoining nanoflakes that form the structure of the sheets. The synthesis technique in this study is reliable and facile and offers a procedure to form large, scalable and patternable quasi 2D MoS2 sheets on various substrates with enhanced optical properties for practical applications.

Controlled Electrochemical Deformation of Liquid-Phase Gallium.

Pure gallium is a soft metal with a low temperature melting point of 29.8 °C. This low melting temperature can potentially be employed for creating optical components with changeable configurations on demand by manipulating gallium in its liquid state. Gallium is a smooth and highly reflective metal that can be readily maneuvered using electric fields. These features allow gallium to be used as a reconfigurable optical reflector. This work demonstrates the use of gallium for creating reconfigurable optical reflectors manipulated through the use of electric fields when gallium is in a liquid state. The use of gallium allows the formed structures to be frozen and preserved as long as the temperature of the metal remains below its melting temperature. The lens can be readily reshaped by raising the temperature above the melting point and reapplying an electric field to produce a different curvature of the gallium reflector.

Exfoliation Solvent Dependent Plasmon Resonances in Two-Dimensional Sub-Stoichiometric Molybdenum Oxide Nanoflakes.

Few-layer two-dimensional (2D) molybdenum oxide nanoflakes are exfoliated using a grinding assisted liquid phase sonication exfoliation method. The sonication process is carried out in five different mixtures of water with both aprotic and protic solvents. We found that surface energy and solubility of mixtures play important roles in changing the thickness, lateral dimension, and synthetic yield of the nanoflakes. We demonstrate an increase in proton intercalation in 2D nanoflakes upon simulated solar light exposure. This results in substoichiometric flakes and a subsequent enhancement in free electron concentrations, producing plasmon resonances. Two plasmon resonance peaks associated with the thickness and the lateral dimension axes are observable in the samples, in which the plasmonic peak positions could be tuned by the choice of the solvent in exfoliating 2D molybdenum oxide. The extinction coefficients of the plasmonic absorption bands of 2D molybdenum oxide nanoflakes in all samples are found to be high (ε > 10(9) L mol(-1) cm(-1)). It is expected that the tunable plasmon resonances of 2D molybdenum oxide nanoflakes presented in this work can be used in future electronic, optical, and sensing devices.

2D MoS2 PDMS Nanocomposites for NO2 Separation.

At a relatively low loading concentration (≈0.02 wt%) of 2D MoS 2 flakes in PDMS, the composite membrane is able to almost completely block the permeation of NO2 gas molecules at ppm levels. This major reduction is ascribed to the strong physisorption of NO2 gas molecules onto the 2D MoS2 flake basal planes.

A unique in vivo approach for investigating antimicrobial materials utilizing fistulated animals.

Unique in vivo tests were conducted through the use of a fistulated ruminant, providing an ideal environment with a diverse and vibrant microbial community. Utilizing such a procedure can be especially invaluable for investigating the performance of antimicrobial materials related to human and animal related infections. In this pilot study, it is shown that the rumen of a fistulated animal provides an excellent live laboratory for assessing the properties of antimicrobial materials. We investigate microbial colonization onto model nanocomposites based on silver (Ag) nanoparticles at different concentrations into polydimethylsiloxane (PDMS). With implantable devices posing a major risk for hospital-acquired infections, the present study provides a viable solution to understand microbial colonization with the potential to reduce the incidence of infection through the introduction of Ag nanoparticles at the optimum concentrations. In vitro measurements were also conducted to show the validity of the approach. An optimal loading of 0.25 wt% Ag is found to show the greatest antimicrobial activity and observed through the in vivo tests to reduce the microbial diversity colonizing the surface.