Neuromorphic Liquid Marbles with Aqueous Carbon Nanotube Cores.

Neuromorphic computing devices attempt to emulate features of biological nervous systems through mimicking the properties of synapses toward implementing the emergent properties of their counterparts, such as learning. Inspired by recent advances in the utilization of liquid marbles (LMs, microliter quantities of fluid coated in hydrophobic powder) for the creation of unconventional computing devices, we describe the development of LMs with neuromorphic properties through the use of copper coatings and 1.0 mg mL-1 carbon nanotube (CNT)-containing fluid cores. Experimentation was performed through sandwiching the LMs between two cup-style electrodes and stimulating them with repeated dc pulses at 3.0 V. Our results demonstrate that "entrainment" of CNT-filled copper LMs via periodic pulses can cause their electrical resistance to rapidly switch between high to low resistance profiles upon inverting the polarity of stimulation: the reduction in resistance between high and low profiles was approximately 88% after two rounds of entrainment. This effect was found to be reversible through reversion to the original stimulus polarity and was strengthened by repeated experimentation, as evidenced by a mean reduction in time to switching onset of 43%. These effects were not replicated in nanotube solutions not bound inside LMs. Our electrical characterization also reveals that nanotube-filled LMs exhibit pinched loop hysteresis IV profiles consistent with the description of memristors. We conclude by discussing the applications of this technology to the development of unconventional computing devices and the study of emergent characteristics in biological neural tissue.

Waist belt and central obesity cause partial hiatus hernia and short-segment acid reflux in asymptomatic volunteers.

OBJECTIVE: There is a high incidence of inflammation and metaplasia at the gastro-oesophageal junction (GOJ) in asymptomatic volunteers. Additionally, the majority of patients with GOJ adenocarcinomas have no history of reflux symptoms. We report the effects of waist belt and increased waist circumference (WC) on the physiology of the GOJ in asymptomatic volunteers. DESIGN: 12 subjects with normal and 12 with increased WC, matched for age and gender were examined fasted and following a meal and with waist belts on and off. A magnet was clipped to the squamo-columnar junction (SCJ). Combined assembly of magnet-locator probe, 12-channel pH catheter and 36-channel manometer was passed. RESULTS: The waist belt and increased WC were each associated with proximal displacement of SCJ within the diaphragmatic hiatus (relative to upper border of lower oesophageal sphincter (LOS), peak LOS pressure point and pressure inversion point, and PIP (all p<0.05). The magnitude of proximal migration of SCJ during transient LOS relaxations was reduced by 1.6-2.6 cm with belt on versus off (p=0.01) and in obese versus non-obese (p=0.04), consistent with its resting position being already proximally displaced. The waist belt, but not increased WC, was associated with increased LOS pressure (vs intragastric pressure) and movement of pH transition point closer to SCJ. At 5 cm above upper border LOS, the mean % time pH <4 was <4% in all studied groups. Acid exposure 0.5-1.5 cm above SCJ was increased, with versus without, belt (p=0.02) and was most marked in obese subjects with belt. CONCLUSIONS: Our findings indicate that in asymptomatic volunteers, waist belt and central obesity cause partial hiatus herniation and short-segment acid reflux. This provides a plausible explanation for the high incidence of inflammation and metaplasia and occurrence of neoplasia at the GOJ in subjects without a history of reflux symptoms.

Measuring movement and location of the gastroesophageal junction: research and clinical implications.

Understanding the physiology of gastroesophageal junction (GEJ) is important as failure of its function is associated with reflux disease, hiatus hernia, and cancer. In recent years, there have been impressive developments in high resolution technologies allowing measurement of luminal pressure, pH, and impedance. One obvious deficiency is the lack of technique to monitor the movement and location of the GEJ over a prolonged period of time. Proximal movement of the GEJ during peristalsis and transient lower esophageal sphincter relaxations (TLESRs) is due to shortening of the longitudinal muscle of the esophagus. Techniques for measuring shortening include fluoroscopic imaging of mucosal clip, high-frequency intraluminal ultrasound, and high resolution manometry, but these techniques have limitations. Short segment reflux is recently found to be more common than traditional reflux and may account for the high prevalence of intestinal metaplasia and cancer seen at GEJ. While high resolution pHmetry is available, there is no technique that can reliably and continuously measure the position of the squamocolumnar junction. A new technique is recently reported allowing a precise and continuous measurement of the GEJ based on the principle of Hall effect. Reported studies have validated its accuracy both on the bench and against the gold standard, fluoroscopy. It has been used alongside high resolution manometry in studying the behavior of the GEJ during TLESRs and swallows. While there are challenges associated with this new technique, there are promising ongoing developments. There is exciting time ahead in research and clinical applications for this new technique.

Ring Attractors as the Basis of a Biomimetic Navigation System.

The ability to navigate effectively in a rich and complex world is crucial for the survival of all animals. Specialist neural structures have evolved that are implicated in facilitating this ability, one such structure being the ring attractor network. In this study, we model a trio of Spiking Neural Network (SNN) ring attractors as part of a bio-inspired navigation system to maintain an internal estimate of planar translation of an artificial agent. This estimate is dynamically calibrated using a memory recall system of landmark-free allotheic multisensory experiences. We demonstrate that the SNN-based ring attractor system can accurately model motion through 2D space by integrating ideothetic velocity information and use recalled allothetic experiences as a positive corrective mechanism. This SNN based navigation system has potential for use in mobile robotics applications where power supply is limited and external sensory information is intermittent or unreliable.

On measuring nanoparticle toxicity and clearance with Paramecium caudatum.

As the extent to which aquatic environments are polluted with nano-scale objects is becoming known, we are presented with an urgent need to study their effects on various forms of life and to clear and/or detoxify them. A range of methods exist to these ends, but a lack of inter-study comparability arising from an absence of experimental standardisation impedes progress. Here we present experiments that demonstrate measurement of orchestrated uptake and clearance of two environmentally-relevant nano- and micromaterials by a model aquatic microoraganism, Paramecium caudatum. Experiments were based on a simple, modular, multi-chamber platform that permits standardised control of organism behaviour and measurement of variables relevant to the study of nanotoxicology, including nanomaterial chemotaxis assays, bioaccumulation and deleterious effects on cell motility systems. Uptake of internalised materials may be estimated through the addition of a low-cost fluorescence spectrometer. P. caudatum cells can clear an estimated 0.7 fg of contaminant materials (or 161 of the particles used) per cell over a 5 mm distance per 6 hour experiment, whilst suffering few short-term adverse effects, suggesting that the organism and the platform used to investigate their properties are well-suited to a range of laboratory and field-based nanotoxicological studies.

A Parallel Modular Biomimetic Cilia Sorting Platform.

The aquatic unicellular organism Paramecium caudatum uses cilia to swim around its environment and to graze on food particles and bacteria. Paramecia use waves of ciliary beating for locomotion, intake of food particles and sensing. There is some evidence that Paramecia pre-sort food particles by discarding larger particles, but intake the particles matching their mouth cavity. Most prior attempts to mimic cilia-based manipulation merely mimicked the overall action rather than the beating of cilia. The majority of massive-parallel actuators are controlled by a central computer; however, a distributed control would be far more true-to-life. We propose and test a distributed parallel cilia platform where each actuating unit is autonomous, yet exchanging information with its closest neighboring units. The units are arranged in a hexagonal array. Each unit is a tileable circuit board, with a microprocessor, color-based object sensor and servo-actuated biomimetic cilia actuator. Localized synchronous communication between cilia allowed for the emergence of coordinated action, moving different colored objects together. The coordinated beating action was capable of moving objects up to 4 cm/s at its highest beating frequency; however, objects were moved at a speed proportional to the beat frequency. Using the local communication, we were able to detect the shape of objects and rotating an object using edge detection was performed; however, lateral manipulation using shape information was unsuccessful.

Particle sorting by Paramecium cilia arrays.

Motile cilia are cell-surface organelles whose purposes, in ciliated protists and certain ciliated metazoan epithelia, include generating fluid flow, sensing and substance uptake. Certain properties of cilia arrays, such as beating synchronisation and manipulation of external proximate particulate matter, are considered emergent, but remain incompletely characterised despite these phenomena having being the subject of extensive modelling. This study constitutes a laboratory experimental characterisation of one of the emergent properties of motile cilia: manipulation of adjacent particulates. The work demonstrates through automated videomicrographic particle tracking that interactions between microparticles and somatic cilia arrays of the ciliated model organism Paramecium caudatum constitute a form of rudimentary 'sorting'. Small particles are drawn into the organism's proximity by cilia-induced fluid currents at all times, whereas larger particles may be held immobile at a distance from the cell margin when the cell generates characteristic feeding currents in the surrounding media. These findings can contribute to the design and fabrication of biomimetic cilia, with potential applications to the study of ciliopathies.

Towards a Physarum learning chip.

Networks of protoplasmic tubes of organism Physarum polycehpalum are macro-scale structures which optimally span multiple food sources to avoid repellents yet maximize coverage of attractants. When data are presented by configurations of attractants and behaviour of the slime mould is tuned by a range of repellents, the organism preforms computation. It maps given data configuration into a protoplasmic network. To discover physical means of programming the slime mould computers we explore conductivity of the protoplasmic tubes; proposing that the network connectivity of protoplasmic tubes shows pathway-dependent plasticity. To demonstrate this we encourage the slime mould to span a grid of electrodes and apply AC stimuli to the network. Learning and weighted connections within a grid of electrodes is produced using negative and positive voltage stimulation of the network at desired nodes; low frequency (10 Hz) sinusoidal (0.5 V peak-to-peak) voltage increases connectivity between stimulated electrodes while decreasing connectivity elsewhere, high frequency (1000 Hz) sinusoidal (2.5 V peak-to-peak) voltage stimulation decreases network connectivity between stimulated electrodes. We corroborate in a particle model. This phenomenon may be used for computation in the same way that neural networks process information and has the potential to shed light on the dynamics of learning and information processing in non-neural metazoan somatic cell networks.

Quantitative transformation for implementation of adder circuits in physical systems.

Computing devices are composed of spatial arrangements of simple fundamental logic gates. These gates may be combined to form more complex adding circuits and, ultimately, complete computer systems. Implementing classical adding circuits using unconventional, or even living substrates such as slime mould Physarum polycephalum, is made difficult and often impractical by the challenges of branching fan-out of inputs and regions where circuit lines must cross without interference. In this report we explore whether it is possible to avoid spatial propagation, branching and crossing completely in the design of adding circuits. We analyse the input and output patterns of a single-bit full adder circuit. A simple quantitative transformation of the input patterns which considers the total number of bits in the input string allows us to map the respective input combinations to the correct outputs patterns of the full adder circuit, reducing the circuit combinations from a 2:1 mapping to a 1:1 mapping. The mapping of inputs to outputs also shows an incremental linear progression, suggesting its implementation in a range of physical systems. We demonstrate an example implementation, first in simulation, inspired by self-oscillatory dynamics of the acellular slime mould P. polycephalum. We then assess the potential implementation using plasmodium of slime mould itself. This simple transformation may enrich the potential for using unconventional computing substrates to implement digital circuits.

Transfer function of protoplasmic tubes of Physarum polycephalum.

The slime mould Physarum polycephalum is a large single celled myxomycete; its plasmodium consists of tubes which extend to find sources of food. It has been previously shown that the tubes are conductive with a resistance of approximately 3 MΩ, and have been used in basic DC circuits. Hybrid slime mould-electronic circuits have been proposed, using the protoplasmic tubes, grown between agar, as Physarum wires. This paper aims to evaluate the electrical properties of the protoplasmic tubes with respect to analogue and digital waveforms. The Physarum wires act as low pass filters with a mean cut off frequency of 19kHz (SD 9 KHz); they have a 12.1 dB/decade roll-off (SD 1.9 dB/decade). Mean attenuation across the band-pass range is -6 dB (S.D. 4.5 dB). The mechanism for the frequency dependant attenuation is unknown however a combination of protoplasmic electrolyte and the cytoskeletal structure is the most likely cause. The tubes last approximately 2 weeks before forming a dry sclerotia, when they cease being conductive and is the prevalent limiting factor of their practical use; this is caused by dehydration and lack of nutrition, a limitation which may be overcome. The potential for Physarum wires in hybrid circuits is strengthened; while previous circuits were simple DC circuits, this work demonstrates that they may be used as electronic components or wires in both digital and analogue circuits or even as a computing component in analogue computers.

Development and initial testing of a novel slime mould biosensor.

A plurality of whole cell biosensors have been developed using many different cell types. Biosensors incorporate biomolecular components or whole cells to facilitate specific analyte interaction; research documented here presents a novel whole cell biosensor based on the slime mould Physarum polycephalum (PP). The electrical response of PP when exposed to multiple chemicals are measured and quantified in terms of amplitude and frequency response. The PP biosensor is capable of detecting the tested chemicals and individually identifying a large number in terms of a specific shift in either oscillation frequency or amplitude. However, it does exhibit a sensitivity to environmental changes such as light level and temperature which may interfere with the detection of the target analyte but could also be used for wider sensing applications. It is proposed that this novel biosensor is capable of detecting many organic chemicals beyond those presented in this work and that the biosensor may be used for environmental monitoring and toxicity evaluation.

Sensory fusion in Physarum polycephalum and implementing multi-sensory functional computation.

Surface electrical potential and observational growth recordings were made of a protoplasmic tube of the slime mould Physarum polycephalum in response to a multitude of stimuli with regards to sensory fusion or multisensory integration. Each stimulus was tested alone and in combination in order to evaluate for the first time the effect that multiple stimuli have on the frequency of streaming oscillation. White light caused a decrease in frequency whilst increasing the temperature and applying a food source in the form of oat flakes both increased the frequency. Simultaneously stimulating P. polycephalum with light and oat flake produced no net change in frequency, while combined light and heat stimuli showed an increase in frequency smaller than that observed for heat alone. When the two positive stimuli, oat flakes and heat, were combined, there was a net increase in frequency similar to the cumulative increases caused by the individual stimuli. Boolean logic gates were derived from the measured frequency change.

Slime mould logic gates based on frequency changes of electrical potential oscillation.

Physarum polycephalum is a large single amoeba cell, which in its plasmodial phase, forages and connects nearby food sources with protoplasmic tubes. The organism forages for food by growing these tubes towards detected foodstuff, this foraging behaviour is governed by simple rules of photoavoidance and chemotaxis. The electrical activity of the tubes oscillates, creating a peristaltic like action within the tubes, forcing cytoplasm along the lumen; the frequency of this oscillation controls the speed and direction of growth. External stimuli such as light and food cause changes in the oscillation frequency. We demonstrate that using these stimuli as logical inputs we can approximate logic gates using these tubes and derive combinational logic circuits by cascading the gates, with software analysis providing the output of each gate and determining the input of the following gate. Basic gates OR, AND and NOT were correct 90%, 77.8% and 91.7% of the time respectively. Derived logic circuits XOR, half adder and full adder were 70.8%, 65% and 58.8% accurate respectively. Accuracy of the combinational logic decreases as the number of gates is increased, however they are at least as accurate as previous logic approximations using spatial growth of P. polycephalum and up to 30 times as fast at computing the logical output. The results shown here demonstrate a significant advancement in organism-based computing, providing a solid basis for hybrid computers of the future.

Towards minimally invasive monitoring for gastroenterology - An external Squamocolumnar Junction Locator.

Transient lower oesophageal sphincter relaxations (TLOSRs) occur frequently and are the main mechanism of acid reflux. The only means of currently detecting TLOSRs is intra-luminal manometry and the probes themselves may stimulate TLOSRs. The squamo-columnar junction moves 4-5 centimeters proximally during TLOSRs and this provides a means of detecting such episodes. The objective of this work is to develop a sensor system capable of detecting the movement of a miniature magnet attached to the squamo-columnar junction from outside the body and thus allow detection of TLOSRs without the artifact associated with intraluminal detection probes. A GaAs Hall effect sensor was selected and an alternating current supply was developed with a combination of filters and a Phase Sensitive Detector, to detect the magnet. The oscillation frequency of the current was chosen in order to reduce electronic noise, and filtering outside this frequency means the signal to noise ratio was greatly improved. The phase sensitive detector was employed to accurately convert the amplitude of the sensor's output to a DC signal. With the addition of paired Flux Concentrators increases the range up to 10.2 centimetres, an improvement of 580% over commercial Hall effect sensors. The AC circuit and flux concentrator device far exceeds the sensitivity of the current Hall effect sensors supplied in the market, by rejecting noise and providing accurate measurement over significantly larger distances. The development of this sensor has applications beyond this specific medical device.

Development and validation of a probe allowing accurate and continuous monitoring of location of squamo-columnar junction.

INTRODUCTION: Most pathology of the upper gastrointestinal tract now occurs close to the gastro-oesophageal squamo-columnar junction (SCJ). Studying the pathophysiology of this region even using high resolution pH, impedance and manometry is unreliable due to constant movement with respiration, swallowing and transient lower oesophageal sphincter relaxations. AIMS AND METHODS: A technique is reported allowing continuous real-time monitoring of the position of the SCJ. It involves endoscopically clipping a magnet (2 mm × 1 mm) to the SCJ and monitoring its position relative to a probe in the oesophago-gastric lumen. The latter has 26 Hall-Effect sensors mounted at 5mm spacing on a circuit board within a silicone tube. RESULTS: Bench studies: The recorded position of the magnet along the length of the probe was compared with its actual position. Accuracy was related to the distance between magnet and probe, orientation of the magnet relative to the probe and whether the magnet was anterior, posterior or lateral to the probe. Including all possible orientations of the magnet at or nearer than 10mm from the probe, the median accuracy along the length of probe was 2.4 mm (IQR 2.1 mm). The proportion of all possible orientations within 10mm of the probe giving an accuracy of ±10 mm was 88.9%. In vivo studies: With simultaneous fluoroscopy, eight healthy subjects were asked to perform normal breathing, deep breathing, water swallows and finally advancement and retraction of probe over a 12 cm segment. The position recorded by fluoroscopy and probe at each second interval were compared. The correlation co-efficient for all 224 position readings was 0.96 (95% CI: 0.89-0.96). No significant interference was observed when the probe was tested alongside high resolution pH and manometry. CONCLUSION: Used in conjunction with high resolution pH, impedance and manometry, this technique will allow for the first time detailed studies at the squamo-columnar junction.