Devin Neal

Ensemble analysis of angiogenic growth in three-dimensional microfluidic cell cultures.

We demonstrate ensemble three-dimensional cell cultures and quantitative analysis of angiogenic growth from uniform endothelial monolayers. Our approach combines two key elements: a micro-fluidic assay that enables parallelized angiogenic growth instances subject to common extracellular conditions, and an automated image acquisition and processing scheme enabling high-throughput, unbiased quantification of angiogenic growth. Because of the increased throughput of the assay in comparison to existing three-dimensional morphogenic assays, statistical properties of angiogenic growth can be reliably estimated. We used the assay to evaluate the combined effects of vascular endothelial growth factor (VEGF) and the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the importance of S1P in amplifying the angiogenic response in the presence of VEGF gradients. Furthermore, the application of S1P with VEGF gradients resulted in angiogenic sprouts with higher aspect ratio than S1P with background levels of VEGF, despite reduced total migratory activity. This implies a synergistic effect between the growth factors in promoting angiogenic activity. Finally, the variance in the computed angiogenic metrics (as measured by ensemble standard deviation) was found to increase linearly with the ensemble mean. This finding is consistent with stochastic agent-based mathematical models of angiogenesis that represent angiogenic growth as a series of independent stochastic cell-level decisions.

Bipolar Piezoelectric Buckling Actuators

A nonlinear piezoelectric amplification mechanism utilizing structural buckling is presented, and its static and dynamic properties are measured and analyzed. Buckling is a pronounced nonlinear effect that occurs at a structurally singular point. A small piezoelectric displacement on the order of 10 μm results in a large buckling displacement on the order of millimeter. Furthermore, the usable stroke is doubled if both sides of the singular point can be reached resulting in bipolar motion. Despite the large gain, buckling is an erratic, singular phenomenon; the side on which deflection will occur is unpredictable. In this paper, multiple design concepts are presented for regulating the buckling direction as well as for extending its usable stroke to bipolar motion. Nonlinear force-displacement relationships are modeled and measured. Nonlinear dynamic analysis using phase planes reveals that the buckling actuator can generate bipolar motion above a specific amplitude. Below this amplitude, it generates only monopolar oscillation. The proposed design concepts are implemented on monolithic flexure mechanisms, and prototype buckling actuators are tested to verify the concepts. Experiments show promising results: 20 N of peak-to-peak output force, and 6.2 mm of bipolar displacement generated by piezoelectric actuators with free displacement of 42 μm.

Co-fabrication of live skeletal muscles as actuators in A millimeter scale mechanical system

Functional muscle tissue holds promise as a practical actuator for use in engineering applications. Previously, functional live-cell muscle actuators used for robotics have not scaled greater than about 10 µm, the size of a single monolayer of cells. We present a method to produce larger scale muscle actuators fully integrated into a mechanical structure. We use manufacturing techniques including printing a mold, pouring a molded part, and deposition of cell suspension. Our method allows for co-fabrication of actuator and mechanism through muscle self-assembly. We incorporate muscle construct technologies such that the muscle is fully 3D, anchored, and aligned, yielding a 10 mm long and 0.5 mm thick aligned muscle actuator. By co-fabricating the mechanism and actuators, the muscles are produced and used in the same environmental conditions, the process is more robust and repeatable, and evaluation of performance is under identical conditions to those in which the actuator is used. By using the presented method, variable geometry and multiple degrees of freedom can all be incorporated in a single mechanical structure.

Dynamic Performance of Nonlinear 100X Displacement Amplification Piezoelectric Actuator

The dynamic frequency response of a nonlinear piezoelectric amplification mechanism capable of over 150 fold displacement amplification is presented. Research to amplify the displacement of piezoelectric actuators has included flexure based approaches that utilize geometric configuration, and has included frequency based approaches that utilize resonance and small steps to contribute to a full motion. The dynamic operation of the actuator presented here utilizes the benefits from both of these methods. The geometry allows for great displacement amplification, and operation within a specific frequency band allows for the exploitation of a nonlinear singularity. The actuator has three distinct modes of dynamic operation, one of which achieves significant displacement by utilizing momentum to pass through a singular configuration. A nonlinear model, linear models for each frequency response mode, and multiple prototypes are presented. This actuator operating in the high displacement frequency band is promising as an input actuator for stepping mechanisms.Copyright

Engineered muscle systems having individually addressable distributed muscle actuators controlled by optical stimuli

A multi degree-of-freedom system using live skeletal muscles as actuators is presented. Millimeter-scale, optically excitable 3D skeletal muscle strips are created by culturing genetically coded precursory muscle cells that are activated with light: optogenetics. These muscle bio-actuators are networked together to create a distributed actuator system. Unlike traditional mechanical systems where fixed axis joints are rotated with electric motors, the new networked muscle bio-actuators can activate loads having no fixed joint. These types of loads include shoulders, the mouth, and the jaw. The optogenetic approach offers high spatiotemporal resolution for precise control of muscle activation, and opens up the possibility to activate hundreds of interconnected muscles in a spatiotemporally coordinated manner. In this work, we explore the design of robotic systems composed of multiple light-activated live muscular actuator units. We describe and compare massively parallel and highly serial/networked distributions of these building-block actuator units. We have built functional fundamental prototypes and present experimental results to demonstrate the feasibility of the construction of larger scale muscle systems.

Phased-array piezoelectric actuators using a buckling mechanism having large displacement amplification and nonlinear stiffness

Novel designs of an array of piezoelectric stack actuators using a unique buckling mechanism are presented in this paper. Multiple PZT actuator units with high gain displacement amplification mechanisms are arranged in parallel with spatial phase differences. Having an inherent kinematic singularity, the buckling mechanism provides not only an extremely high gain of displacement amplification, but also varying stiffness and nonlinear force-displacement characteristics. The phased array PZT actuator exploits this nonlinearity for gaining a large output displacement as well as for combining multiple PZT stacks in parallel without conflicting with each other. Three specific designs of arrayed buckling actuators are presented. The aggregate output force-displacement relationship is analyzed and its profile is shaped with respect to spatial phase differences and nonlinear stiffness and force characteristics of individual PZT buckling actuator units.

Design of Cellular Piezoelectric Actuators With High Blocking Force and High Strain

Preliminary design and analysis of a new concept for efficiently amplifying piezoelectric actuators are presented in this paper. Piezoelectric actuators, such as Lead Zirconate Titanate (PZT), have produced substantial stress at high bandwidth, but at very small strains on the order of 0.1%. This paper presents a new strain amplification design to be utilized as the first layer in the previously designed “nested rhombus” multi-layer mechanism. This mechanism produces substantial strain through exponentially increasing strain with each subsequent layer. However, the blocking force produced in previous designs is insufficient for many practical applications. Through static and kinematic analysis, this paper addresses how this new concept sufficiently amplifies strain, and presents numerous issues to consider in designing for greater blocking force. A prototype of this new concept provides 126 N of blocking force and displacement of 0.3 mm.Copyright

Design Method for Buckling Amplified Piezoelectric Actuator Using Flexure Joint and its Application to an Energy Efficient Brake System

This paper shows a practical design method for a displacement amplification mechanism for a piezoelectric actuator which employs a buckling-like phenomenon. This mechanical singularity realizes a substantial displacement magnification, at least 50 times, within a simple structure. An SMA preload mechanism essentially provides potential for full range push-pull actuation to the piezoelectric actuator. This integrated actuator performs a high energy transfer ratio and is suitable for brake mechanisms due to their requirement of high force, specific displacement and energy efficiency. A practical design method is shown and is evaluated by comparing the analytical model with finite element analysis and experimental hardware performance. The actuator properties obtained by these methods fit well each other with errors less than 13%.The experimental actuators are applied to a brake for a commercial motor and its properties are evaluated. The brake can produce more than 2.5Nm in the displacement range of 0.5mm. These experimental results suggest that this novel piezoelectric actuator has potential for use in a wide range of applications.Copyright

Distributed Live Muscle Actuators Controlled by Optical Stimuli

A multi degree of freedom skeletal muscle system stimulated via optical control is presented. These millimeter-scale, optically excitable 3D skeletal muscle bio-actuators are created by culturing genetically modified precursory muscle cells that are activated with light: optogenetics. These muscle bio-actuators are networked together to create a distributed muscle system. Muscle systems can manipulate loads having no fixed joint. These types of loads include shoulders, the mouth, and the jaw.Copyright

Towards the development of optogenetically-controlled skeletal muscle actuators

Engineered skeletal muscle tissue has the potential to be used as dual use actuator and stress-bearing material providing numerous degrees of freedom and with significant active stress generation. To exploit the potential features, however, technologies must be established to generate mature muscle strips that can be controlled with high fidelity. Here, we present a method for creating mature 3-D skeletal muscle tissues that contract in response to optical activation stimuli. The muscle strips are fascicle-like, consisting of several mm-long multi-nucleate muscle cells bundled together. We have found that applying a tension to the fascicle-like muscle tissue promotes maturation of the muscle. The fascicle-like muscle tissue is controlled with high spatiotemporal resolution based on optogenetic coding. The mouse myoblasts C2C12 were transfected with Channelrhodopsin-2 to enable light (∼470 nm) to control muscle contraction. The 3D muscle tissue not only twitches in response to an impulse light beam, but also exhibits a type of tetanus, a prolonged contraction of continuous stimuli, for the first time. In the following, the materials and culturing method used for 3D muscle generation is presented, followed by experimental results of muscle constructs and optogenetic control of the 3D muscle tissue.Copyright