Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models

Three-dimensional (3D) culture models have gained relevant interest in tissue engineering and drug discovery owing to their suitability to reproduce in vitro some key aspects of human tissues and to provide predictive information for in vivo tests. In this context, the use of hydrogels as artificial extracellular matrices is of paramount relevance, since they allow closer recapitulation of (patho)physiological features of human tissues. However, most of the analyses aimed at characterizing these models are based on time-consuming and endpoint assays, which can provide only static and limited data on cellular behavior. On the other hand, biosensing systems could be adopted to measure on-line cellular activity, as currently performed in bi-dimensional, i.e., monolayer, cell culture systems; however, their translation and integration within 3D hydrogel-based systems is not straight forward, due to the geometry and materials properties of these advanced cell culturing approaches. Therefore, researchers have adopted different strategies, through the development of biochemical, electrochemical and optical sensors, but challenges still remain in employing these devices. In this review, after examining recent advances in adapting existing biosensors from traditional cell monolayers to polymeric 3D cells cultures, we will focus on novel designs and outcomes of a range of biosensors specifically developed to provide real-time analysis of hydrogel-based cultures

Recent progress in piezotronic sensors based on one-dimensional zinc oxide nanostructures and its regularly ordered arrays: from design to application

Piezotronic sensors and self-powered gadgets are highly sought-after for flexible, wearable, and intelligent electronics for their applications in cutting-edge healthcare and human-machine interfaces. With the advantages of a well-known piezoelectric effect, excellent mechanical properties, and emerging nanotechnology applications, one-dimensional (1D) ZnO nanostructures organized in the form of a regular array have been regarded as one of the most promising inorganic active materials for piezotronics. This report intends to review the recent developments of 1D ZnO nanostructure arrays for multifunctional piezotronic sensors. Prior to discussing rational design and fabrication approaches for piezotronic devices in precisely controlled dimensions, well-established synthesis methods for high-quality and well-controlled 1D ZnO nanostructures are addressed. The challenges associated with the well-aligned, site-specific synthesis of 1D ZnO nanostructures, development trends of piezotronic devices, advantages of an ordered array of 1D ZnO in device performances, exploring new sensing mechanisms, incorporating new functionalities by constructing heterostructures, the development of novel flexible device integration technology, the deployment of novel synergistic strategies in piezotronic device performances, and potential multifunctional applications are covered. A brief evaluation of the end products, such as small-scale miniaturized unconventional power sources in sensors, high-resolution image sensors, and personalized healthcare medical devices, is also included. The paper is summarized towards the conclusion by outlining the present difficulties and promising future directions. This study will provide guidance for future research directions in 1D ZnO nanostructure-based piezotronics, which will hasten the development of multifunctional devices, sensors, chips for human-machine interfaces, displays, and self-powered systems

Electromechanical Performance of HASEL Actuators: Fundamentals and Applications

Soft robotic systems are well-suited to unstructured, dynamic tasks and environments, but are currently limited by the soft actuators that power them. Most current soft actuators are based on pneumatics or shape-memory alloys, which have issues with efficiency, response speed, and portability. More recently, dielectric elastomer actuators (DEAs) have shown promise, but they have limited material selection, fabrication methods, and modes of actuation. As such, there remains a need for new types of high performance and well-rounded soft actuators. This dissertation focuses on the development and exploration of a new class of soft electrohydraulic actuators called hydraulically amplified self-healing electrostatic (HASEL) actuators. The first part of this dissertation (Chapter 2) presents of a subclass of HASEL actuators called Peano-HASELs that simultaneously introduce a breakthrough materials system based on thermoplastic films as well as a novel contractile mode of actuation. This approach enables industrially-amenable fabrication techniques, vastly expands the usable materials for actuator construction, and results in high performance actuators with fast linear contraction on activation. The second part of this dissertation (Chapter 3) elucidates the fundamentals of the electromechanical coupling that drives HASEL actuators. An analytical model is developed that accurately describes the quasi-static actuation behavior of Peano-HASEL actuators without relying on fitting parameters. Using this model, we identify a theory-driven approach to actuator design, including a roadmap for actuators with drastically improved specific energies. The final section of this dissertation (Chapter 4 and 5) looks towards more integrated and applied designs of HASEL actuators. First, a new type of articulating actuator is presented that integrates both compliant and rigid components. These spider-inspired electrohydraulic soft-actuated (SES) joints demonstrate high torque and high-speed actuation in an independently-addressable multi-joint limb, a bidirectional actuator, and a versatile gripper. Second, a biodegradable materials system is presented for high performance Peano-HASEL actuators that reduce environmental impact. Finally, a new method of capacitive self-sensing is presented that enables inexpensive and compact circuits that use only off-the-shelf and low voltage components. The results presented in this dissertation provide a framework for the development of high-performance actuators that may one day power the next generation of capable soft robots.</p

On the Interaction between 1D Materials and Living Cells

One-dimensional (1D) materials allow for cutting-edge applications in biology, such as single-cell bioelectronics investigations, stimulation of the cellular membrane or the cytosol, cellular capture, tissue regeneration, antibacterial action, traction force investigation, and cellular lysis among others. The extraordinary development of this research field in the last ten years has been promoted by the possibility to engineer new classes of biointerfaces that integrate 1D materials as tools to trigger reconfigurable stimuli/probes at the sub-cellular resolution, mimicking the in vivo protein fibres organization of the extracellular matrix. After a brief overview of the theoretical models relevant for a quantitative description of the 1D material/cell interface, this work offers an unprecedented review of 1D nano- and microscale materials (inorganic, organic, biomolecular) explored so far in this vibrant research field, highlighting their emerging biological applications. The correlation between each 1D material chemistry and the resulting biological response is investigated, allowing to emphasize the advantages and the issues that each class presents. Finally, current challenges and future perspectives are discussed

Field-Effect Sensors

This Special Issue focuses on fundamental and applied research on different types of field-effect chemical sensors and biosensors. The topics include device concepts for field-effect sensors, their modeling, and theory as well as fabrication strategies. Field-effect sensors for biomedical analysis, food control, environmental monitoring, and the recording of neuronal and cell-based signals are discussed, among other factors

Nanocarbon/elastomer composites : characterization and applications in photo-mechanical actuation.

Materials that change shape or dimensions in response to external stimuli are widely used in actuation devices. While plenty of systems respond to heat, light, electricity, and magnetism, there is an emerging class of light-driven actuators based on carbon nanostructure/elastomer composites. The addition of nanomaterials to elastomeric polymers results not only in significant material property improvements such as mechanical strength, but also assists in creating entirely new composite functionalities as with photo-mechanical actuation. Efficient photon absorption by nanocarbons and subsequent energy transduction to the polymeric chains can be used to controllably produce significant amounts of pre-strain dependent motion. Photo-mechanical actuation offers a variety of advantages over traditional devices, including wireless actuation, electro-mechanical decoupling (and therefore low noise), electrical circuit elimination at point of use, massive parallel actuation of device arrays from single light source, and complementary metal–oxide–semiconductor / micro-electro-mechanical (CMOS/MEMS) compatible processing. Applications of photo-responsive materials encompass robotics, plastic motors, photonic switches, micro-grippers, and adaptive micro-mirrors. The magnitude and direction of photo-mechanical actuation responses generated in carbon nanostructure/elastomer composites depend on applied pre-strains. At low levels of pre-strains (3–9%), actuators show reversible photo-induced expansion while at high levels (15–40%), actuators exhibit reversible contraction. Large, light-induced reversible and elastic responses of graphene nanoplatelet (GNP) polymer composites were demonstrated for the first time, with an extraordinary optical-to-mechanical energy conversion factor (?M) of 7–9 MPa/W. Following this demonstration, similar elastomeric composite were fabricated with a variety of carbon nanostructures. Investigation into photo-actuation properties of these composites revealed both layer-dependent, as well as dimensionally-dependent responses. For a given carbon concentration, both steady-state photo-mechanical stress response and energy conversion efficiency were found to be directly related to dimensional state of carbon nanostructure additive, with one-dimensional (1D) carbon nanotubes demonstrating the highest responses (~60 kPa stress and ~5 × 10-3% efficiency at just 1 wt% loading) and three-dimensional (3D) highly ordered pyrolytic graphite demonstrating the lowest responses. Furthermore, development of an advanced dispersion technique (evaporative mixing) resulted in the ability to fabricate conductive composites. Actuation and relaxation kinetics responses were investigated and found to be related not to dimensionality, but rather the percolation threshold of carbon nanostructure additive in the polymer. Establishing a connective network of carbon nanostructure additive allowed for energy transduction responsible for photo-mechanical effect to activate carbon beyond the infrared (IR) illumination point, resulting in enhanced actuation. Additionally, in the conductive samples photoconductivity as a function of applied pre-strain was also measured. Photo-conductive response was found to be inversely proportional to applied pre-strain, demonstrating mechanical coupling. Following investigation into photo-mechanical actuation responses between the various carbon forms, use of these composite actuators to achieve both macroscopic as well as microscopic movement in practical applications was evaluated. Using dual GNP/elastomer actuators, a two-axis sub-micron translation stage was developed, and allowed for two-axis photo-thermal positioning (~100 µm per axis) with 120 nm resolution (limitation of the feedback sensor) and ~5 µm/s actuation speeds. A proportional-integral-derivative control loop automatically stabilizes the stage against thermal drift, as well as random thermal-induced position fluctuations (up to the bandwidth of the feedback and position sensor). Nanopositioner performance characteristics were found to be on par with other commercial systems, with resolution limited only by the feedback system used. A mathematical model was developed to describe the elastomeric composite actuators as a series of n springs, with each spring element having its own independent IR-tunable spring constant. Effects of illumination intensity, position, and amount of the composite actuator illuminated are discussed. This model provided several additional insights, such as demonstrating the ability to place not just one, but multiple stages on a single polymer composite strip and position them independently from one another, a benefit not seen in any other type of positioning system. Further investigation yielded interesting and novel photo-mechanical properties with actuation visible on macroscopic scales. Addition of a third component (thermally expanding microspheres), produced a new class of stimuli-responsive expanding polymer composites with ability to unidirectionally transform physical dimensions, elastic modulus, density, and electrical resistance. Carbon nanotubes and core-shell acrylic microspheres were dispersed in polydimethylsiloxane, resulting in composites that exhibit a binary set of material properties. Upon thermal or IR stimuli, liquid cores encapsulated within the microspheres vaporize, expanding the surrounding shells and stretching the matrix. Microsphere expansion results in visible dimensional changes, regions of reduced polymeric chain mobility, nanotube tensioning, and overall elastic to plastic-like transformation of the composite. Transformations include macroscopic volume expansion (\u3e500%), density reduction (\u3e80%), and elastic modulus increase (\u3e675%). Additionally, conductive nanotubes allow for remote expansion monitoring and exhibit distinct loading-dependent electrical responses. Compared to well-established actuation technologies, research into photo-mechanical properties of carbon-based polymer composites is still in its infancy. Results in this dissertation demonstrate some of the enormous potential of light-driven carbon-based composites for actuation and energy scavenging applications. Furthermore, mechanical response dependence to carbon nanostructure dimensional state could have significance in developing new types of carbon-based mixed-dimensional composites for sensor and actuator systems. As the fabrication processes used here are compatible with CMOS and MEMS processing, carbon-based polymer composites allow for not only scaling actuation systems, but also ability to pattern regions of tailorable expansion, strength, and electrical resistance into a single polymer skin, making these composites ideal for structural and electrical building blocks in smart systems. Continued development of carbon-based polymer composites will extend the promising potential of light-driven actuation technologies and will serve as a catalyst to inspire continued research into energy conversion devices and systems

Design and Implementation of a Passive Neurostimulator with Wireless Resonance-Coupled Power Delivery and Demonstration on Frog Sciatic Nerve and Gastrocnemius Muscle

The thesis presented has four goals: to perform a comprehensive literature review on current neurostimulator technology; to outline the current issues with the state-of-the-art; to provide a neurostimulator design that solves these issues, and to characterize the design and demonstrate its neurostimulation features. The literature review describes the physiology of a neuron, and then proceeds to outline neural interfaces and neurostimulators. The neurostimulator design process is then outlined and current requirements in the field are described. The novel neurostimulator circuit that implements a solution that has wireless capability, passive control, and small size is outlined and characterized. The circuit is demonstrated to operate wirelessly with a resonance-coupled multi-channel implementation, and is shown powering LEDs. The circuit was then fabricated in a miniature implementation which utilized a 10 x 20 x 3 mm&179 antenna, and occupied a volume approximating 1 cm&179. This miniature circuit is used to stimulate frog sciatic nerve and gastrocnemius muscle in vitro. These demonstrations and characterization show the device is capable of neurostimulation, can operate wirelessly, is controlled passively, and can be implemented in a small size, thus solving the aforementioned neurostimulator requirements. Further work in this area is focused on developing an extensive characterization of the device and the wireless power delivery system, optimizing the circuit design, and performing in vivo experiments with restoration of motor control in injured animals. This device shows promise to provide a comprehensive solution to many application-specific problems in neurostimulation, and be a modular addition to larger neural interface systems