Pneumatic unidirectional cell stretching device for mechanobiological studies of cardiomyocytes

In this paper, we present a transparent mechanical stimulation device capable of uniaxial stimulation, which is compatible with standard bioanalytical methods used in cellular mechanobiology. We validate the functionality of the uniaxial stimulation system using human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs). The pneumatically controlled device is fabricated from polydimethylsiloxane (PDMS) and provides uniaxial strain and superior optical performance compatible with standard inverted microscopy techniques used for bioanalytics (e.g., fluorescence microscopy and calcium imaging). Therefore, it allows for a continuous investigation of the cell state during stretching experiments. The paper introduces design and fabrication of the device, characterizes the mechanical performance of the device and demonstrates the compatibility with standard bioanalytical analysis tools. Imaging modalities, such as high-resolution live cell phase contrast imaging and video recordings, fluorescent imaging and calcium imaging are possible to perform in the device. Utilizing the different imaging modalities and proposed stretching device, we demonstrate the capability of the device for extensive further studies of hiPSC-CMs. We also demonstrate that sarcomere structures of hiPSC-CMs organize and orient perpendicular to uniaxial strain axis and thus express more maturated nature of cardiomyocytes

Three Dimensional Numerical Simulation, Design and Structural Optimization of Pneumatically Actuated Cell Stretching Device

Utilizing biomimetic mechanical forces for differentiation of stem cells toward osteogenic, cardiomyocytes and other cell types is a technique that has been applied increasingly in recent years. Different types of apparatuses and devices are being designed and fabricated in order to accurately direct these mechanical forces onto stem cells in both 2D and 3D configurations. In this thesis, a novel and easy-to-fabricate structure is designed to provide mechanical stimulation of cells in a cell culture environment. This is facilitated by means of pneumatic actuation. The pneumatic actuation of the hyperelastic PolyDiMethylSiloxane (PDMS) material directs a tensile strain on cell population in the environment. The structure has been previously designed at Micro- and Nanosystems research group to provide equiaxial strain. In this study, steps are taken to modify the structure to provide not only the equiaxial strain, but also uniaxial strain for stimulation of stem cells in vitro. As the primary objective of this study, the modified structure makes two aforementioned types of mechanical strain achievable. In this study, computational model of the device is developed based on Neo-Hookean hyperelastic material model using COMSOL Multiphysics 5.1 software. Finite element based model of the structure is implemented and numerical simulations are performed to analyze stress and strain under applied vacuum. The structure is then optimized based on various geometric parameters to improve the performance of the device according to defined requirements and objective functions. The optimized structure is then further analyzed to completely identify the performance characteristics of the device. Two different geometries are proposed for the device structure. The designed structures are demonstrated to provide relatively good performance based on requirements. The structures provide rather high strain magnitude in case of equiaxial strain. In case of uniaxial strain, they provide a relatively high average value for the first principal strain and a low average value for the second principal strain. The structures also exhibit an almost uniform uniaxial strain field. The results indicate an acceptable performance of the devices in both cases

Relationship Between Velocity of Contraction and Force Applied On Air Muscles

Air muscles are simple pneumatic devices that have high potential to be used as robotic manipulators, as they have a behavior similar to biological motors or muscles. Hence, they have a wide range of potential applications in areas such as robotics, bio-robotics, biomechanics, and artificial limb replacements. In addition to the similarity to biological muscle, air muscles have the advantages of good power-to-weight ratio, being compliant, and low cost. This thesis primarily quantifies the relationship between velocity of contraction of air muscles and the force applied on it, which is a key characteristic of biological skeletal muscle. First, an experimental test rig was used to measure the velocity of contraction of air muscles as a function of applied force, supply pressure, and supply volumetric flow rate. Second, a theoretical model is proposed to quantify the relationship between the velocity of contraction and force applied on it and to explain the experimental results. Three air muscles having different lengths and diameters were tested for loads ranging from 0 to 6 kg at 20 psi, 40 psi and 60 psi at two different flow rates. All three air muscles were made up of latex tubing sheathed with the Techflex, FlexoPet braided sleeve. The primary air muscle was 5 inches long, with the diameter of the inner tube measuring 3/4 of an inch. The second muscle had half the length (2.5 inches) and was the same diameter as the primary air muscle. The third air muscle was the same length as the first (5 inches long), but half of the diameter (3/8 of an inch). The velocity of the contraction was measured with the help of the linear potentiometer. Both the theoretical model and the experimental results found that as the force applied on the air muscles is increased, maximum length of contraction and velocity of contraction decrease. Both model and experiment showed that the velocity of contraction increases as a function of both pressure and volume flow rate

Towards rapid 3D direct manufacture of biomechanical microstructures

The field of stereolithography has developed rapidly over the last 20 years, and commercially available systems currently have sufficient resolution for use in microengineering applications. However, they have not as yet been fully exploited in this field. This thesis investigates the possible microengineering applications of microstereolithography systems, specifically in the areas of active microfluidic devices and microneedles. The fields of micropumps and microvalves, stereolithography and microneedles are reviewed, and a variety of test builds were fabricated using the EnvisionTEC Perfactory Mini Multi-Lens stereolithography system in order to define its capabilities. A number of microneedle geometries were considered. This number was narrowed down using finite element modelling, before another simulation was used to optimise these structures. 9 × 9 arrays of 400 μm tall, 300 μm base diameter microneedles were subjected to mechanical testing. Per needle failure forces of 0.263 and 0.243 N were recorded for the selected geometries, stepped cone and inverted trumpet. The 90 μm needle tips were subjected to between 30 and 32 MPa of pressure at their failure point - more than 10 times the required pressure to puncture average human skin. A range of monolithic micropumps were produced with integrated 4 mm diameter single-layer 70 μm-thick membranes used as the basis for a reciprocating displacement operating principle. The membranes were tested using an oscillating pneumatic actuation, and were found reliable (>1,000,000 cycles) up to 2.0 PSIG. Pneumatic single-membrane nozzle/diffuser rectified devices produced flow rates of up to 1,000 μl/min with backpressures of up to 375 Pa. Another device rectified using active membrane valves was found to self-prime, and produced backpressures of up to 4.9 kPa. These devices and structures show great promise for inclusion in complex, fully integrated and active microfluidic systems fabricated using microstereolithography alone, with implications for both cost of manufacture and lead time

Droplet Microfluidics

Droplet microfluidics has dramatically developed in the past decade and has been established as a microfluidic technology that can translate into commercial products. Its rapid development and adoption have relied not only on an efficient stabilizing system (oil and surfactant), but also on a library of modules that can manipulate droplets at a high-throughput. Droplet microfluidics is a vibrant field that keeps evolving, with advances that span technology development and applications. Recent examples include innovative methods to generate droplets, to perform single-cell encapsulation, magnetic extraction, or sorting at an even higher throughput. The trend consists of improving parameters such as robustness, throughput, or ease of use. These developments rely on a firm understanding of the physics and chemistry involved in hydrodynamic flow at a small scale. Finally, droplet microfluidics has played a pivotal role in biological applications, such as single-cell genomics or high-throughput microbial screening, and chemical applications. This Special Issue will showcase all aspects of the exciting field of droplet microfluidics, including, but not limited to, technology development, applications, and open-source systems

Liquid crystal elastomer actuators and sensors: Glimpses of the past, the present and perhaps the future

Liquid crystal elastomers (LCEs) are programmable materials par excellence. I review the history and state of the art of LCE materials and processing development from the perspective of the important remaining step of moving out of the academic research lab and applying LCEs as soft actuators or strain sensors. After a brief introduction for the non-expert of what LCEs are and which their main advantages and limitations are, I discuss the key breakthroughs that LCE research has undergone over its 50-year history. Building on this and drawing from fresh results from on-going research, I consider possible future development trajectories that would help address the outstanding key obstacles to reach mass production at competitive cost. I end with discussing a selected set of application scenarios with good opportunities for LCEs to perform functions that no other material could deliver. Specifically, I focus on responsive buildings incorporating LCE actuator fibres and sheets/ribbons, structural health monitoring with LCE strain sensors monitoring crack growth and propagation or alerting residents of buildings exposed to dangerous levels of deformation, and kinetic and responsive garments incorporating LCE fibre actuators and/or strain sensors

Towards rapid 3D direct manufacture of biomechanical microstructures

The field of stereolithography has developed rapidly over the last 20 years, and commercially available systems currently have sufficient resolution for use in microengineering applications. However, they have not as yet been fully exploited in this field. This thesis investigates the possible microengineering applications of microstereolithography systems, specifically in the areas of active microfluidic devices and microneedles. The fields of micropumps and microvalves, stereolithography and microneedles are reviewed, and a variety of test builds were fabricated using the EnvisionTEC Perfactory Mini Multi-Lens stereolithography system in order to define its capabilities. A number of microneedle geometries were considered. This number was narrowed down using finite element modelling, before another simulation was used to optimise these structures. 9 × 9 arrays of 400 μm tall, 300 μm base diameter microneedles were subjected to mechanical testing. Per needle failure forces of 0.263 and 0.243 N were recorded for the selected geometries, stepped cone and inverted trumpet. The 90 μm needle tips were subjected to between 30 and 32 MPa of pressure at their failure point - more than 10 times the required pressure to puncture average human skin. A range of monolithic micropumps were produced with integrated 4 mm diameter single-layer 70 μm-thick membranes used as the basis for a reciprocating displacement operating principle. The membranes were tested using an oscillating pneumatic actuation, and were found reliable (>1,000,000 cycles) up to 2.0 PSIG. Pneumatic single-membrane nozzle/diffuser rectified devices produced flow rates of up to 1,000 μl/min with backpressures of up to 375 Pa. Another device rectified using active membrane valves was found to self-prime, and produced backpressures of up to 4.9 kPa. These devices and structures show great promise for inclusion in complex, fully integrated and active microfluidic systems fabricated using microstereolithography alone, with implications for both cost of manufacture and lead time.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (EPSRC)GBUnited Kingdo

Experimental and Numerical Study of Composite Lightweight Structural Insulated Panel with Expanded Polystyrene Core against Windborne Debris Impacts

Natural disasters such as cyclone, hurricane, tornado and typhoon cause tremendous loss around the world. The windborne debris usually imposes high speed localized impact on the building envelope, which may harm people inside the building and create dominant openings. A dominant opening in the building envelope might cause internal pressure increasing and result in substantial damage to the building structures, such as roof lifting up or even collapse. To withstand the impact of such extreme event, the penetration resistant capacity of wall or roof panels to windborne debris impact should meet the requirements specified in the wind loading codes, e.g., the Australian Wind Loading Code (AS/NZS 1170.2:2011). In this study, a composite Structural Insulated Panel (SIP) with Extended Polystyrene (EPS) core sandwiched by flat metal skins that is commonly used in building industry was investigated. To study the structural response and penetration resistant capacity of the composite panel against windborne debris impacts, a series of laboratory tests were carried out by using a pneumatic cannon testing system.The effects of various specimen configurations, impact locations and debris impact velocities on their performance were investigated. The failure modes under various projectile impact scenarios were observed and compared by using two high-speed cameras. The dynamic responses were examined quantitatively in terms of the opening size, residual velocity of projectile, deformation and strain time histories on the back skin measured in the tests. The penetration resistance capacity of the panels subjected to windborne debris impact were examined and analyzed. In addition, numerical models were developed in LS-DYNA to simulate the response and damage of the composite SIP under windborne debris impact. Laboratory tested panels were first modeled. The test data was used to calibrate the accuracy of the numerical model. The validated numerical model was then used to conduct more numerical simulations to obtain more results such as energy absorption, impact force and vulnerability curve of the SIP against windborne debris impact