Integrated motor protein based nanodevices for biomolecular transport

A living cell can be considered as a miniaturized device, which carries out complicated tasks such as reproduction, energy conversion and molecule transport. Many cellular functions are highly efficient and mostly performed at nanoscale, which is pursued in fields of Micro total analysis system (&mgr;-TAS) or lab-on-a-chip. Due to unique mechanical functions performing micro/nano transport with high efficiency of the chemo-mechanical energy conversion in cells, motor proteins have been emphasized to perform laboratory functions such as delivery, assembly, detection, and micro/nano-engines. However, several issues ranging from in vitro stability of motor proteins to understanding their functionalities with inorganic materials remain unsolved and continue to hinder the applications of motor proteins. One such issue includes directional control in the motion of motor proteins. Associated filaments are precisely controlled by cellular signals and provide tracks for motor proteins to play critical roles in biological movement and transportation in cells, which is difficult to mimic in vitro..;This study investigates the development of a new methodology for the directional transport of particles using actomyosin. This methodology is applicable to new devices for security, health or environmental applications. The general approach to be developed is based on creating unipolar F-actin arrays on an inorganic substrate. The barbed end of actin filament is anchored on streptavidin-coated surfaces through biotinylated gelsolin. A flow field driven by a mechanical pump is utilized to lay down actin filaments aligned along the direction of the flow. Meanwhile, fascin crosslinks actin filaments to prevent their resuspension. These precisely oriented F-actin arrays provide unidirectional transport of heavy meromyosin-coated particles over distances of several hundred micrometers. In processes of creating unipolar F-actin arrays, blocking solutions are investigated to prevent non-specific binding of F-actin on streptavidin-coated surfaces. Additionally, Ca2+ regulated gelsolin activity with actin filament is investigated in a function of free Ca2+ concentrations.;The advantages of this study are 1) no external regulation and influence is required to guide HMM-coated particles or maintain F-actin arrays, 2) a linear transport of micro/nano particles to desired locations can be accomplished, and 3) patterned tracks of F-actin arrays constructed using micropatterning techniques are available for various applications. This study may provide fundamental understanding of potential roles of myosin II as a nonprocessive motor protein in further applications and may significantly improve the applicability of hybrid devices using biomolecular motor proteins

Biomolecular Shuttles under Dielectrophoretic Forces

Motor proteins and filaments are essential elements in living cells. They are employed in skeletal muscles to generate forces, they transport cargos such as organelles to specific locations in the cells or they reorganize themselves to change a cell\u27s structure. Moreover, motor proteins and filaments use hydrolysis of adenosine triphosphate (ATP) as chemical fuel to generate mechanical movement in their interaction. Understanding the behavior of these enticed nano-sized machines and their properties, yet to be mimicked and synthesized by humans is very important to the future development of transport in nanoscale. Thus far, researchers succeeded in demonstrating the interaction of motor proteins and filaments in in vitro environment and controlling their random movement by various methods such as with the influence of DC electric field, driven flow field and engineered tracks by photolithographic method. In this thesis, dielectrophoretic forces, which are generated under nonuniform electric field by AC, are explored as a candidate to control the direction of biomolecular shuttles, actin filaments which glide on heavy meromyosin coated surface. Under dielectrophoretic forces, actin filaments showed bidirectional movement between embedded electrodes. The orientation and velocity of actin filaments were measured under various AC voltages, frequencies and distances between electrodes. Additionally, the effect of temperature on myosin-actin motility was further investigated and loading cargo on actin filaments was demonstrated by using a streptavidin-biotin binding system

Skin-Like Electronics for a Persistent Brain-Computer Interface

There exists a high demand for a continuous, persistent recording of non-invasive electroencephalograms in both clinical and research fields. Head-cap electrodes with metal conductors and conductive gels are widely used and considered as the gold standard for such measurement. This physical interface, however, is poorly suited to uninterrupted, long-term use due to the uncomfortable rigid electrodes, skin irritation due to the gel, and electrical degradation as the gel dries. These issues can be addressed by using a newly developed, dry form of electronics. Here, we briefly review a class of soft electronic technology in the aspects of mechanics, materials, and its capabilities for a long-term recording of electroencephalograms and a brain-computer interface (BCI). We summarize the progress in the development of a skin-like electronic system with a focus on key mechanical factors to achieve conformal skin contact. The design of hard electronics, integrated with soft membranes, uses deterministic fractal motifs to offer bending and stretching mechanics. We also introduce a most recent example of such electronics, an ‘auricle-integrated system’, which includes a strategy of conformal integration on the complex surface topology, a quantitative study of biocompatibility, and an application as a persistent BCI

Microstructured Thin Film Nitinol for a Neurovascular Flow-Diverter

A cerebral aneurysm occurs as a result of a weakened blood vessel, which allows blood to flow into a sac or a ballooned section. Recent advancement shows that a new device, ‘flow-diverter’, can divert blood flow away from the aneurysm sac. People found that a flow-diverter based on thin film nitinol (TFN), works very effectively, however there are no studies proving the mechanical safety in irregular, curved blood vessels. Here, we study the mechanical behaviors and structural safety of a novel microstructured TFN membrane through the computational and experimental studies, which establish the fundamental aspects of stretching and bending mechanics of the structure. The result shows a hyper-elastic behavior of the TFN with a negligible strain change up to 180° in bending and over 500% in radial stretching, which is ideal in the use in neurovascular curved arteries. The simulation determines the optimal joint locations between the TFN and stent frame. In vitro experimental test qualitatively demonstrates the mechanical flexibility of the flow-diverter with multi-modal bending. In vivo micro X-ray and histopathology study demonstrate that the TFN can be conformally deployed in the curved blood vessel of a swine model without any significant complications or abnormalities

SKINTRONICS: Wireless, Skin-Wearable Electronics for Monitoring of Electrocardiogram

The ECGs I micro-fabricate are designed to be flexible, stretchable and wireless circuits that can be applied to the skin directly. The device is encased in a conformal, silicon-like substrate, that allows the ECG to be attached with the electrodes. Each electrode has been previously measured and verified that it will be correctly placed for an accurate reading. Prototyping this ECG/electrode device allows the user to mount the prototype directly to the patient without having to attach and wire ten other electrodes. This prototype solves the issue that comes about when a doctor, nurse or emergency medical technician must attach a traditional 12-lead ECG that requires sufficient knowledge and experience to place each electrode accurately and precisely in order to achieve an accurate reading. In my fabricated device, the ECG is wired directly to the three most crucial electrodes placed at V2, V3 and V4 based on the traditional precordial electrode placement for a 12-lead ECG. By covering these three positions, my research team and I can ensure we achieve an accurate reading, and will find the correct placement due to the compact design with pre-placed electrodes. Another benefit of this prototype is its flexibility. This allows the circuit to be more durable when being picked-up, transferred to the patient, and then removed; this may also allow for multiple applications whereas conventional electrodes can only be used once. This prototype is currently in the preliminary stages of testing and will hopefully be implemented into medical practice in the future.https://scholarscompass.vcu.edu/uresposters/1245/thumbnail.jp

Trabecular bone organoid model for studying the regulation of localized bone remodeling

Trabecular bone maintains physiological homeostasis and consistent structure and mass through repeated cycles of bone remodeling by means of tightly localized regulation. The molecular and cellular processes that regulate localized bone remodeling are poorly understood because of a lack of relevant experimental models. A tissue-engineered model is described here that reproduces bone tissue complexity and bone remodeling processes with high fidelity and control. An osteoid-inspired biomaterial-demineralized bone paper-directs osteoblasts to deposit structural mineralized bone tissue and subsequently acquire the resting-state bone lining cell phenotype. These cells activate and shift their secretory profile to induce osteoclastogenesis in response to chemical stimulation. Quantitative spatial mapping of cellular activities in resting and activated bone surface coculture showed that the resting-state bone lining cell network actively directs localized bone remodeling by means of paracrine signaling and cell-to-cell contact. This model may facilitate further investigation of trabecular bone niche biology

Trabecular Bone Organoid Model for Studying the Regulation of Localized Bone Remodeling

Trabecular bone maintains physiological homeostasis and consistent structure and mass through repeated cycles of bone remodeling by means of tightly localized regulation. The molecular and cellular processes that regulate localized bone remodeling are poorly understood because of a lack of relevant experimental models. A tissue-engineered model is described here that reproduces bone tissue complexity and bone remodeling processes with high fidelity and control. An osteoid-inspired biomaterial-demineralized bone paper-directs osteoblasts to deposit structural mineralized bone tissue and subsequently acquire the resting-state bone lining cell phenotype. These cells activate and shift their secretory profile to induce osteoclastogenesis in response to chemical stimulation. Quantitative spatial mapping of cellular activities in resting and activated bone surface coculture showed that the resting-state bone lining cell network actively directs localized bone remodeling by means of paracrine signaling and cell-to-cell contact. This model may facilitate further investigation of trabecular bone niche biology

Soft Electronics Enabled Ergonomic Human-Computer Interaction for Swallowing Training

We introduce a skin-friendly electronic system that enables human-computer interaction (HCI) for swallowing training in dysphagia rehabilitation. For an ergonomic HCI, we utilize a soft, highly compliant (“skin-like”) electrode, which addresses critical issues of an existing rigid and planar electrode combined with a problematic conductive electrolyte and adhesive pad. The skin-like electrode offers a highly conformal, user-comfortable interaction with the skin for long-term wearable, high-fidelity recording of swallowing electromyograms on the chin. Mechanics modeling and experimental quantification captures the ultra-elastic mechanical characteristics of an open mesh microstructured sensor, conjugated with an elastomeric membrane. Systematic in vivo studies investigate the functionality of the soft electronics for HCI-enabled swallowing training, which includes the application of a biofeedback system to detect swallowing behavior. The collection of results demonstrates clinical feasibility of the ergonomic electronics in HCI-driven rehabilitation for patients with swallowing disorders

Fully portable and wireless universal brain-machine interfaces enabled by flexible scalp electronics and deep-learning algorithm

Variation in human brains creates difficulty in implementing electroencephalography (EEG) into universal brain-machine interfaces (BMI). Conventional EEG systems typically suffer from motion artifacts, extensive preparation time, and bulky equipment, while existing EEG classification methods require training on a per-subject or per-session basis. Here, we introduce a fully portable, wireless, flexible scalp electronic system, incorporating a set of dry electrodes and flexible membrane circuit. Time domain analysis using convolutional neural networks allows for an accurate, real-time classification of steady-state visually evoked potentials on the occipital lobe. Simultaneous comparison of EEG signals with two commercial systems captures the improved performance of the flexible electronics with significant reduction of noise and electromagnetic interference. The two-channel scalp electronic system achieves a high information transfer rate (122.1 ± 3.53 bits per minute) with six human subjects, allowing for a wireless, real-time, universal EEG classification for an electronic wheelchair, motorized vehicle, and keyboard-less presentation

Swallowing detection for game control: using skin-like electronics to support people with dysphagia

In this paper, we explore the feasibility of developing a sensor-driven rehabilitation game for people suffering from dysphagia. This study utilizes the skin-like electronics for unobtrusive, comfortable, continuous recording of surface electromyograms (EMG) during swallowing and use them for driving game-based, user-controlled feedback. The experimental study includes the development and evaluation of a real-time swallow detection algorithm using skin-like sensors and a game-based human-computer interaction. The user evaluations support the ease of use of the skin-like electronics as a motivational tool for people with dysphagia