Capsule endoscopy of the future: What's on the horizon?

Capsule endoscopes have evolved from passively moving diagnostic devices to actively moving systems with potential therapeutic capability. In this review, we will discuss the state of the art, define the current shortcomings of capsule endoscopy, and address research areas that aim to overcome said shortcomings. Developments in capsule mobility schemes are emphasized in this text, with magnetic actuation being the most promising endeavor. Research groups are working to integrate sensor data and fuse it with robotic control to outperform today's standard invasive procedures, but in a less intrusive manner. With recent advances in areas such as mobility, drug delivery, and therapeutics, we foresee a translation of interventional capsule technology from the bench-top to the clinical setting within the next 10 years

Dynamic simulation of a peristaltic micropump considering coupled fluid flow and structural motion

This paper presents lumped-parameter simulation of dynamic characteristics of peristaltic micropumps. The pump consists of three pumping cells connected in series, each of which is equipped with a compliant diaphragm that is electrostatically actuated in a peristaltic sequence to mobilize the fluid. Diaphragm motion in each pumping cell is first represented by an effective spring subjected to hydrodynamic and electrostatic forces. These cell representations are then used to construct a system-level model for the entire pump, which accounts for both cell- and pump-level interactions of fluid flow and diaphragm vibration. As the model is based on first principles, it can be evaluated directly from the device's geometry, material properties and operating parameters without using any experimentally identified parameters. Applied to an existing pump, the model correctly predicts trends observed in experiments. The model is then used to perform a systematic analysis of the impact of geometry, materials and pump loading on device performance, demonstrating its utility as an efficient tool for peristaltic micropump design

Microdosing for drug delivery application—A review

There is an increasing amount of research on microfluidic actuators with the aim to improve drug dosing applications. Micropumps are promising as they reduce the size and energy consumption of dosing concepts and enable new therapies. Even though there are evident advantages, there are only few examples of industrial microdosing units and micropump technology has not yet found widespread application. To answer the evoked question of what limits the application of microdosing technology for drug delivery, this work provides a comprehensive insight into the subject of drug dosing. We highlight and analyse specific microfluidic challenges and requirements in medical dosing: safety relevant aspects, such as prevention of freeflow and backflow; dosing-specific requirements, such as dosing precision and stability; and system-specific aspects, such as size, weight, and power restrictions or economic aspects. Based on these requirements, we evaluate the suitability of different mechanical micropumps and actuation mechanisms for drug administration. In addition to research work, we present industrial microdosing systems that are commercially available or close to market release. We then summarize outstanding technical solutions that ensure sufficient fluidic performance, guarantee a safe use, and fulfil the specific requirements of medical microdosing

REMOTE CONTROLLED HYDROGEL NANOCOMPOSITES: SYNTHESIS, CHARACTERIZATION, AND APPLICATIONS

There is significant interest in the development of hydrogels and hydrogel nanocomposites for a variety of biomedical applications including drug delivery, sensors and actuators, and hyperthermia cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled (RC) actuation. In this dissertation, the development of hydrogel nanocomposites containing magnetic nanoparticles/carbon nanotubes, actuation with remote stimulus, and some of their applications are highlighted. The primary hydrogel nanocomposite systems were synthesized by incorporation of magnetic nanoparticles into temperature responsive N-isopropylacrylamide (NIPAAm) matrices. Various nanocomposite properties were characterized such as temperature responsive swelling, RC heating with a 300 kHz alternating magnetic field (AMF), and resultant collapse. The nanoparticle loadings and hydrogel composition were tailored to obtain a nanocomposite system that exhibited significant change in its volume when exposed to AMF. The nanocomposites were loaded with model drugs of varying molecular weights, and RC pulsatile release was demonstrated. A microfluidic device was fabricated using the low temperature co-fired ceramic (LTCC) processing technique. A magnetic nanocomposite of PNIPAAm was placed as a valve in one of the channels. The remote controlled liquid flow with AMF was observed for multiple on-off cycles, and the kinetics of the RC valve were quantified by pressure measurements. The addition of multi-walled carbon nanotubes (MWCNTs) in NIPAAm matrices was also explored for the possibility of enhancement in mechanical properties and achieving remote heating capabilities. The application of a radiofrequency (RF) field of 13.56 MHz resulted in the remote heating of the nanocomposites. The intensity of the resultant heating was dependent on the MWCNT loadings. In order to further understand the RC actuation phenomenon, a semi-empirical heat transfer model was developed for heating of a nanocomposite disc in air. The model successfully predicted the temperature rise as well as equilibrium temperatures for different hydrogel dimensions, swelling properties, nanoparticles loadings, and AMF amplitude. COMSOL was used to simulate temperature rise of the hydrogel nanocomposite and the surrounding tissue for hyperthermia cancer treatment application

Characterization of Electromagnetic Valveless Micropump

This paper presents an electromagnetically-actuated micropump for microfluidic application. The system comprises two modules; an electromagnetic actuator module and a diffuser module. Fabrication of the diffuser module can be achieved using photolithography process with a master template and a PDMS prepolymer as the structural material. The actuator module consists of two power inductors and two NdFeB permanent magnets placed between the diffuser elements. The choice of this actuation principle merits from low operating voltage (1.5 Vdc) and the flow direction can be controlled by changing the orientation of the magnet vibration. Maximum volumetric flow rate of the fabricated device at zero backpressure is 0.9756 µLs-1 and 0.4659 µLs-1 at the hydrostatic backpressure of 10 mmH2O at 9 Hz of switching speed

Bio-inspired Magnetic Systems: Controlled Swimming, Fluid Pumps, and Collective Behaviour

This thesis details the original experimental investigations of magnetically actuated and controlled microscopic systems enabling a range of actions at low Reynolds number. From millimetre-robots and self-propelled swimmers to microfluidic and lab-on-a-chip technology applications. The main theme throughout the thesis is that the systems reply on the interactions between magnetic and elastic components. Scientists often take inspiration from nature for many aspects of science. Millimetre to micrometre machines are no exception to this. Nature demonstrates how soft materials can be used to deform in a manner to create actuation at the microscale in biological environments. Nature also shows the effectiveness of using beating tails known as flagella and the apparent enhancements in flow speeds of collective motion. To begin with, a swimmer comprised of two ferromagnetic particles coupled together with an elastic link (the two-ferromagnetic particle swimmer), was fabricated. The system was created to mimic the swimming mechanism seen by eukaryotic cells, in which these cells rely on morphological changes which allows them to propel resulting in approximate speeds of up to 2 body lengths per second. The aim of this system was to create a net motion and control the direction of propagation by manipulating the external magnetic field parameters. It was shown that the direction of swimming has a dependence on both the frequency and amplitude of the applied external magnetic field. A key factor discovered was that the influence of a small bias field, in this case, the Earth’s magnetic field (100 orders of magnitude smaller than the external magnetic field) resulted in robust control over the speed (resulting in typical swimming speeds of 4 body lengths per second) and direction of propulsion. Following this work, swimmers with a hard ferromagnetic head attached to an elastic tail (the torque driven ferromagnetic swimmer) were investigated. These systems were created to be analogous to the beating flagella of many natural microscopic swimmers, two examples would be sperm cells and chlamydomonas cells. These biological cells have typical speeds of 10s of body lengths per second. The main focus of this investigation was to understand how the tail length affects the swimming performance. An important observation was that there is an obvious length tail (5.7 times the head length) at which the swimming speed is maximised (approximately 13 body lengths per second). The experimental results were compared to a theoretical model based on three beads, one of which having a fixed magnetic moment and the other two non-magnetic, connected via elastic filaments. The model shows sufficient complexity to break time symmetry and create a net motion, giving good agreement with experiment. Portable point-of-care systems have the potential to revolutionise medical diagnostics. Such systems require active pumps with low power (USB powered devices) external triggers. Due to the wireless and localisation of magnetic fields could possibly allow these portable point-of-care devices to come to life. The main focus of this investigation was to create fluid pump systems comprising from the previously investigated two-ferromagnetic particle swimmer and the torque driven ferromagnetic swimmer. Building on the fact that if a system can generate a net motion it would also be able to create a net flow. Utilising the geometry of the systems, it has been demonstrated that a swimmer-based system can become a fluid pump by restricting the translational motion. The flow structure generated by a pinned swimmer in different scenarios, such as unrestricted flow around it as well as flow generated in straight, cross-shaped, Y-shaped and circular channels were investigated. This investigation demonstrated the feasibility of incorporating the device into a channel and its capability of acting as a pump, valve and flow splitter. As well as a single pump system, networks of the previously mentioned pump systems were fabricated and experimentally investigated. The purpose of this investigation was to utilise the behaviour of the collective motion. Such networks could also be attached to the walls or top of the channel to create a less invasive system compared to pump based within the channel system. The final investigation involved creating collective motion systems which could mimic the beating of cilia - known as a metachronal wave. Two methods were used to create an analogous behaviour. The first was using arrays of identical magnetic rotors, which under the influence of an external magnetic field created two main rotational patterns. The rotational patterns were shown to be controllable producing useful flow fields at low Reynolds numbers. The second system relied on the magnetic components having different fixed magnetisation to create a phase lag between oscillations. The magnetic components were investigated within a channel and the separation between the components was shown to be a key parameter for controlling the induced flow. In both cases, a simple model was produced to help understand the behaviour. Finally, a selection of preliminary investigations into possible applications were conducted experimentally. These investigations included, measuring the effective surface viscosity of lipid monolayers, created cell growth microchannels, as well as systems which could be used for blood plasma separation. The properties of lipid monolayers vary with the surface density, resulting on distinct phase transitions. Slight differences in the molecular lattice are often accompanied by significant changes in the surface viscosity and elasticity. The idea was to use a swimmer as a reporter of the monolayer viscosity, resulting in a less invasive method compared to current techniques to monitor monolayer viscosity, for example torsion pendulums and channel viscometers. The reported effective surface viscosity closely matched the typical Langmuir trough measurements (with a systematic shift of approximately 17 Ų/molecule). The blood plasma separation preliminary work shows the previously investigated two-ferromagnetic particle swimmer mixing a typical volume (100 μm) blood sample with a buffer solution in 21 seconds. The system was also able to create locations with a high population of red blood cells. This resulted in a separation between the blood plasma and red blood cells. Two other preliminary results of future investigations were presented; the collective motion of free swimmers, and the fabrication of ribbon-like structures with fixed magnetic moment patterns.European CommissionEngineering and Physical Sciences Research Council (EPSRC

Recent advances in micro-electro-mechanical devices for controlled drug release applications

In recent years, controlled release of drugs has posed numerous challenges with the aim of optimizing parameters such as the release of the suitable quantity of drugs in the right site at the right time with the least invasiveness and the greatest possible automation. Some of the factors that challenge conventional drug release include long-term treatments, narrow therapeutic windows, complex dosing schedules, combined therapies, individual dosing regimens, and labile active substance administration. In this sense, the emergence of micro-devices that combine mechanical and electrical components, so called micro-electro-mechanical systems (MEMS) can offer solutions to these drawbacks. These devices can be fabricated using biocompatible materials, with great uniformity and reproducibility, similar to integrated circuits. They can be aseptically manufactured and hermetically sealed, while having mobile components that enable physical or analytical functions together with electrical components. In this review we present recent advances in the generation of MEMS drug delivery devices, in which various micro and nanometric structures such as contacts, connections, channels, reservoirs, pumps, valves, needles, and/or membranes can be included in their design and manufacture. Implantable single and multiple reservoir-based and transdermal-based MEMS devices are discussed in terms of fundamental mechanisms, fabrication, performance, and drug release applications.Fil: Villarruel Mendoza, Luis A.. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Scilletta, Natalia Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Bellino, Martin Gonzalo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Catalano, Paolo Nicolás. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin