Publications

Biofilm colonies are typically resistant to general antibiotic treatment and require targeted methods for their removal. One of these methods includes the use of nanoparticles as carriers for antibiotic delivery, where they randomly circulate in fluid until they make contact with the infected areas. However, the required proximity of the particles to the biofilm results in only moderate efficacy. We demonstrate here that the nonpathogenic magnetotactic bacteria Magnetosopirrillum gryphiswalense (MSR-1) can be integrated with drug-loaded mesoporous silica microtubes to build controllable microswimmers (biohybrids) capable of antibiotic delivery to target an infectious biofilm. Applying external magnetic guidance capability and swimming power of the MSR-1 cells, the biohybrids are directed to and forcefully pushed into matured Escherichia coli (E. coli) biofilms. Release of the antibiotic, ciprofloxacin, is triggered by the acidic microenvironment of the biofilm, ensuring an efficient drug delivery system. The results reveal the capabilities of a nonpathogenic bacteria species to target and dismantle harmful biofilms, indicating biohybrid systems have great potential for antibiofilm applications.

High-performance, multifunctional bacteria-driven microswimmers are introduced using an optimized design and fabrication method for targeted drug delivery applications. These microswimmers are made of mostly single Escherichia coli bacterium attached to the surface of drug-loaded polyelectrolyte multilayer (PEM) microparticles with embedded magnetic nanoparticles. The PEM drug carriers are 1 μm in diameter and are intentionally fabricated with a more viscoelastic material than the particles previously studied in the literature. The resulting stochastic microswimmers are able to swim at mean speeds of up to 22.5 μm/s. They can be guided and targeted to specific cells, because they exhibit biased and directional motion under a chemoattractant gradient and a magnetic field, respectively. Moreover, we demonstrate the microswimmers delivering doxorubicin anticancer drug molecules, encapsulated in the polyelectrolyte multilayers, to 4T1 breast cancer cells under magnetic guidance in vitro. The results reveal the feasibility of using these active multifunctional bacteria-driven microswimmers to perform targeted drug delivery with significantly enhanced drug transfer, when compared with the passive PEM microparticles.

In travelling towards the oviducts, sperm cells undergo transitions between planar to helical flagellar propulsion by a beating tail based on the viscosity of the environment. In this work, we aim to model and mimic this behaviour in low Reynolds number fluids using externally actuated soft robotic sperms. We numerically investigate the effects of transition between planar to helical flagellar propulsion on the swimming characteristics of the robotic sperm using a model based on resistive-force theory to study the role of viscous forces on its flexible tail. Experimental results are obtained using robots that contain magnetic particles within the polymer matrix of its head and an ultra-thin flexible tail. The planar and helical flagellar propulsion are achieved using in-plane and out-of-plane uniform fields with sinusoidally varying components, respectively. We experimentally show that the swimming speed of the robotic sperm increases by a factor of 1.4 (fluid viscosity 5 Pa.s) when it undergoes a controlled transition between planar to helical flagellar propulsion, at relatively low actuation frequencies.

Dipole words are sequences of magnetic dipoles, in which alike elements repel and opposite elements attract. Magnetic dipoles contrast with more general sets of bonding types, called glues, in which pairwise bonding strength is specified by a glue function. We prove that every glue function g has a set of dipole words, called a dipole code, that attractively encodes g: the pairwise attractions (positive or non-positive bond strength) between the words are identical to those of g. Moreover, we give such word sets of asymptotically optimal length. Similar results are obtained for a commonly used subclass of glue functions.

Steady progress in understanding and implementation are establishing self-assembly as a versatile, parallel and scalable approach to the fabrication of transducers. In this contribution, I illustrate the principles and reach of self-assembly with three applications at different scales - namely, the capillary self-alignment of millimetric components, the sealing of liquid-filled polymeric microcapsules, and the accurate capillary assembly of single nanoparticles - and propose foreseeable directions for further developments.

The development of optimal XY θz flexure mechanisms, which can deliver high precision motion about the z-axis, and along the x- and y-axes is highly desirable for a wide range of micro/nano-positioning tasks pertaining to biomedical research, microscopy technologies and various industrial applications. Although maximizing the stiffness ratios is a very critical design requirement, the achievable translational and rotational stiffness ratios of existing XY θz flexure mechanisms are still restricted between 0.5 and 130. As a result, these XY θz flexure mechanisms are unable to fully optimize their workspace and capabilities to reject disturbances. Here, we present an optimal XY θz flexure mechanism, which is designed to have maximum stiffness ratios. Based on finite element analysis (FEA), it has translational stiffness ratio of 248, rotational stiffness ratio of 238 and a large workspace of 2.50 mm × 2.50 mm × 10°. Despite having such a large workspace, FEA also predicts that the proposed mechanism can still achieve a high bandwidth of 70 Hz. In comparison, the bandwidth of similar existing flexure mechanisms that can deflect more than 0.5 mm or 0.5° is typically less than 45 Hz. Hence, the high stiffness ratios of the proposed mechanism are achieved without compromising its dynamic performance. Preliminary experimental results pertaining to the mechanism's translational actuating stiffness and bandwidth were in agreement with the FEA predictions as the deviation was within 10%. In conclusion, the proposed flexure mechanism exhibits superior performance and can be used across a wide range of applications.

Magnetic control of drug carriers using systems with open-configurations is essential to enable scaling to the size of in vivo applications. In this study, we demonstrate motion control of paramagnetic microparticles in a low Reynolds number fluid, using a permanent magnet-based robotic system with an open-configuration. The microparticles are controlled in three-dimensional (3D) space using a cylindrical NdFeB magnet that is fixed to the end-effector of a robotic arm. We develop a kinematic map between the position of the microparticles and the configuration of the robotic arm, and use this map as a basis of a closed-loop control system based on the position of the microparticles. Our experimental results show the ability of the robot configuration to control the exerted field gradient on the dipole of the microparticles, and achieve positioning in 3D space with maximum error of 300 µm and 600 µm in the steady-state during setpoint and trajectory tracking, respectively.

Abstract Objectives The advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro‐gas exchanger integrated with microfluidics to study RBC adhesion under hypoxic flow conditions mimicking postcapillary venules. Methods We simulated a range of physiological conditions and explored RBC adhesion to endothelial or subendothelial components (FN or LN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation of RBC adhesion was performed on 35 subjects with homozygous SCD. Results Significant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a HEA population showed a significantly greater increase in adhesion compared to RBCs from a HNA population, for both FN and LN. Conclusions The approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification of RBC adhesion in a cost‐efficient and patient‐specific manner. We identified a unique patient population in which RBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.

The dynamic analysis has been considered as one of the important design methods to design robots. In this research, we derive dynamic equation of hexapedal water-running robot to design compliant joints. The compliant joints that connect three bodies will be used to improve mobility and stability of water-running motion's pitch behavior. We considered all of parts as rigid body including links of six Klann mechanisms and three main frames. And then, we derived dynamic equation by using the Lagrangian method with external force of the water. We are expecting that the dynamic analysis is going to be used to design parts of the water running robot.

Animals using adhesive pads to climb smooth surfaces face the problem of keeping their pads clean and functional. Here, a self-cleaning mechanism is proposed whereby soiled feet would slip on the surface due to a lack of adhesion but shed particles in return. Our study offers an in situ quantification of self-cleaning performance in fibrillar adhesives, using the dock beetle as a model organism. After beetles soiled their pads by stepping into patches of spherical beads, we found that their gait was significantly affected. Specifically, soiled pads slipped 10 times further than clean pads, with more particles deposited for longer slips. Like previous studies, we found that particle size affected cleaning performance. Large (45 μm) beads were removed most effectively, followed by medium (10 μm) and small (1 μm). Consistent with our results from climbing beetles, force measurements on freshly severed legs revealed larger detachment forces of medium particles from adhesive pads compared to a flat surface, possibly due to interlocking between fibres. By contrast, dock leaves showed an overall larger affinity to the beads and thus reduced the need for cleaning. Self-cleaning through slippage provides a mechanism robust to particle size and may inspire solutions for artificial adhesives.

Water-running robots have been developed inspired by a basilisk lizard, which demonstrates highly agile, stable, and energy-efficient locomotion on water surfaces. Current water-running robots are not as stable and agile as their biological counterparts. This study shows how the stability of a water-running robot in the pitch direction can be improved by using an active tail to enable increased propulsion. The mobility of the robot is also increased. To generate force in the pitch and yaw directions, a two-degrees-of-freedom tail is implemented with two circular plates to provide drag. We developed two types of dynamic models for pitch and yaw behavior, and the results are recursively calculated by considering the correlation between the models. The relationship between pitch motion and propulsion was analyzed by simulations. The steering behavior of the robot is also validated while considering the pitch behavior. Experiments were conducted to verify the simulation results.

Abstract Nature manufactures biological systems in three dimensions with precisely controlled spatiotemporal profiles on hierarchical length and time scales. In this article, we review 3D patterning of biological systems on synthetic platforms for neuropharmacological applications. We briefly describe 3D versus 2D chemical and topographical patterning methods and their limitations. Subsequently, an overview of introducing a third dimension in neuropharmacological research with delineation of chemical and topographical roles is presented. Finally, toward the end of this article, an explanation of how 3D patterning has played a pivotal role in relevant fields of neuropharmacology to understand neurophysiology during development, normal health, and disease conditions is described. The future prospects of organs‐on‐a‐‐like devices to mimic patterned blood–brain barrier in the context of neurotherapeutic discovery and development for the prioritization of lead candidates, membrane potential, and toxicity testing are also described. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1369–1382, 2018.

We investigate the parallel assembly of two-dimensional{,} geometrically-closed modular target structures out of homogeneous sets of macroscopic components of varying anisotropy. The yield predicted by a chemical reaction network (CRN)-based model is quantitatively shown to reproduce experimental results over a large set of conditions. Scaling laws for parallel assembling systems are then derived from the model. By extending the validity of the CRN-based modelling{,} this work prompts analysis and solutions to the incompatible substructure problem.

Magnetic untethered millirobots, which are actuated and controlled by remote magnetic fields, have been proposed for medical applications due to their ability to safely pass through tissues at long ranges. For example, magnetic resonance imaging (MRI) systems with a 3-7 T constant unidirectional magnetic field and 3D gradient coils have been used to actuate magnetic robots. Such magnetically constrained systems place limits on the degrees of freedom that can be actuated for untethered devices. This paper presents a design and actuation methodology for a magnetic millirobot that exhibits both position and orientation control in 2D under a magnetic field, dominated by a constant unidirectional magnetic field as found in MRI systems. Placing a spherical permanent magnet, which is free to rotate inside the millirobot and located away from the center of mass, allows the generation of net forces and torques with applied 3D magnetic field gradients. We model this system in a 3D planar case and experimentally demonstrate open-loop control of both position and orientation by the applied 2D field gradients. The actuation performance is characterized across the most important design variables, and we experimentally demonstrate that the proposed approach is feasible.

This paper presents a magnetically actuated soft capsule endoscope for fine-needle aspiration biopsy (B-MASCE) in the upper gastrointestinal tract. A thin and hollow needle is attached to the capsule, which can penetrate deeply into tissues to obtain subsurface biopsy sample. The design utilizes a soft elastomer body as a compliant mechanism to guide the needle. An internal permanent magnet provides a means for both actuation and tracking. The capsule is designed to roll towards its target and then deploy the biopsy needle in a precise location selected as the target area. B-MASCE is controlled by multiple custom-designed electromagnets while its position and orientation are tracked by a magnetic sensor array. In in vitro trials, B-MASCE demonstrated rolling locomotion and biopsy of a swine tissue model positioned inside an anatomical human stomach model. It was confirmed after the experiment that a tissue sample was retained inside the needle.

Bacteria-driven biohybrid microswimmers (bacteriabots), which integrate motile bacterial cells and functional synthetic cargo parts (e.g., microparticles encapsulating drug), are recently studied for targeted drug delivery. However, adhesion of such bacteriabots to the tissues on the site of a disease (which can increase the drug delivery efficiency) is not studied yet. Here, this paper proposes an approach to attach bacteriabots to certain types of epithelial cells (expressing mannose on the membrane), based on the affinity between lectin molecules on the tip of bacterial type I pili and mannose molecules on the epithelial cells. It is shown that the bacteria can anchor their cargo particles to mannose-functionalized surfaces and mannose-expressing cells (ATCC HTB-9) using the lectin–mannose bond. The attachment mechanism is confirmed by comparing the adhesion of bacteriabots fabricated from bacterial strains with or without type I pili to mannose-covered surfaces and cells. The proposed bioadhesive motile system can be further improved by expressing more specific adhesion moieties on the membrane of the bacteria.

A facile approach is proposed for superior conformation and adhesion of wearable sensors to dry and wet skin. Bioinspired skin-adhesive films are composed of elastomeric microfibers decorated with conformal and mushroom-shaped vinylsiloxane tips. Strong skin adhesion is achieved by crosslinking the viscous vinylsiloxane tips directly on the skin surface. Furthermore, composite microfibrillar adhesive films possess a high adhesion strength of 18 kPa due to the excellent shape adaptation of the vinylsiloxane tips to the multiscale roughness of the skin. As a utility of the skin-adhesive films in wearable-device applications, they are integrated with wearable strain sensors for respiratory and heart-rate monitoring. The signal-to-noise ratio of the strain sensor is significantly improved to 59.7 because of the considerable signal amplification of microfibrillar skin-adhesive films.

For adhering to three-dimensional (3D) surfaces or objects, current adhesion systems are limited by a fundamental trade-off between 3D surface conformability and high adhesion strength. This limitation arises from the need for a soft, mechanically compliant interface, which enables conformability to nonflat and irregularly shaped surfaces but significantly reduces the interfacial fracture strength. In this work, we overcome this trade-off with an adhesion-based soft-gripping system that exhibits enhanced fracture strength without sacrificing conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric microfibrillar adhesive membrane supported by a pressure-controlled deformable gripper body, the proposed soft-gripping system controls the bonding strength by changing its internal pressure and exploiting the mechanics of interfacial equal load sharing. The soft adhesion system can use up to ∼26% of the maximum adhesion of the fibrillar membrane, which is 14× higher than the adhering membrane without load sharing. Our proposed load-sharing method suggests a paradigm for soft adhesion-based gripping and transfer-printing systems that achieves area scaling similar to that of a natural gecko footpad.

Dynamic self-assembled material systems constantly consume energy to maintain their spatiotemporal structures and functions. Programmable self-assembly translates information from individual parts to the collective whole. Combining dynamic and programmable self-assembly in a single platform opens up the possibilities to investigate both types of self-assembly simultaneously and to explore their synergy. This task is challenging because of the difficulty in finding suitable interactions that are both dissipative and programmable. We present a dynamic and programmable self-assembling material system consisting of spinning at the air-water interface circular magnetic micro-rafts of radius 50 μm and with cosinusoidal edge-height profiles. The cosinusoidal edge-height profiles not only create a net dissipative capillary repulsion that is sustained by continuous torque input but also enable directional assembly of micro-rafts. We uncover the layered arrangement of micro-rafts in the patterns formed by dynamic self-assembly and offer mechanistic insights through a physical model and geometric analysis. Furthermore, we demonstrate programmable self-assembly and show that a 4-fold rotational symmetry encoded in individual micro-rafts translates into 90° bending angles and square-based tiling in the assembled structures of micro-rafts. We anticipate that our dynamic and programmable material system will serve as a model system for studying nonequilibrium dynamics and statistical mechanics in the future

Organizational complexity and functional diversity of the extracellular matrix regulate cellular behaviors. The extracellular matrix is composed of various proteins in the form of proteoglycans{,} glycoproteins{,} and nanofibers whose types and combinations change depending on the tissue type. Proteoglycans{,} which are proteins that are covalently attached to glycosaminoglycans{,} contribute to the complexity of the microenvironment of the cells. The sulfation degree of the glycosaminoglycans is an important and distinct feature at specific developmental stages and tissue types. Peptide amphiphile nanofibers can mimic natural glycosaminoglycans and/or proteoglycans{,} and they form a synthetic nanofibrous microenvironment where cells can proliferate and differentiate towards different lineages. In this study{,} peptide nanofibers were used to provide varying degrees of sulfonation mimicking the natural glycosaminoglycans by forming a microenvironment for the survival and differentiation of stem cells. The effects of glucose{,} carboxylate{,} and sulfonate groups on the peptide nanofibers were investigated by considering the changes in the differentiation profiles of rat mesenchymal stem cells in the absence of any specific differentiation inducers in the culture medium. The results showed that a higher sulfonate-to-glucose ratio is associated with adipogenic differentiation and a higher carboxylate-to-glucose ratio is associated with osteochondrogenic differentiation of the rat mesenchymal stem cells. Overall{,} these results demonstrate that supramolecular peptide nanosystems can be used to understand the fine-tunings of the extracellular matrix such as sulfation profile on specific cell types.

Despite the large body of experimental work recently on biohybrid microsystems, few studies have focused on theoretical modeling of such systems, which is essential to understand their underlying functioning mechanisms and hence design them optimally for a given application task. Therefore, this study focuses on developing a mathematical model to describe the 3D motion and chemotaxis of a type of widely studied biohybrid microswimmer, where spherical microbeads are driven by multiple attached bacteria. The model is developed based on the biophysical observations of the experimental system and is validated by comparing the model simulation with experimental 3D swimming trajectories and other motility characteristics, including mean squared displacement, speed, diffusivity, and turn angle. The chemotaxis modeling results of the microswimmers also agree well with the experiments, where a collective chemotactic behavior among multiple bacteria is observed. The simulation result implies that such collective chemotaxis behavior is due to a synchronized signaling pathway across the bacteria attached to the same microswimmer. Furthermore, the dependencies of the motility and chemotaxis of the microswimmers on certain system parameters, such as the chemoattractant concentration gradient, swimmer body size, and number of attached bacteria, toward an optimized design of such biohybrid system are studied. The optimized microswimmers would be used in targeted cargo, e.g., drug, imaging agent, gene, and RNA, transport and delivery inside the stagnant or low-velocity fluids of the human body as one of their potential biomedical applications.

The considerable morbidity associated with hospitalized patients and clinics in developed countries due to biofilm formation on biomedical implants and surgical instruments is a heavy economic burden. An alternative to chemically treated surfaces for bactericidal activity started emerging from micro/nanoscale topographical cues in the last decade. Here, we demonstrate a putative antibacterial surface using copper nanowhiskers deposited by molecular beam epitaxy. Furthermore, the control of biological response is based on hydrophobic pinning of water droplets in the Wenzel regime, causing mechanical injury and cell death. Scanning electron microscopy images revealed the details of the surface morphology and non-contact mode laser scanning of the surface revealed the microtopography-associated quantitative parameters. Introducing the bacterial culture over nanowhiskers produces mechanical injury to cells, leading to a reduction in cell density over time due to local pinning of culture medium to whisker surfaces. Extended culture to 72 hours to observe biofilm formation revealed biofilm inhibition with scattered microcolonies and significantly reduced biovolume on nanowhiskers. Therefore, surfaces patterned with copper nanowhiskers can serve as potential antibiofilm surfaces. The topography-based antibacterial surfaces introduce a novel prospect in developing mechanoresponsive nanobiomaterials to reduce the risk of medical device biofilm-associated infections, contrary to chemical leaching of copper as a traditional bactericidal agent.

Bacteria biohybrids employ the motility and power of swimming bacteria to carry and maneuver microscale particles. They have the potential to perform microdrug and cargo delivery in vivo, but have been limited by poor design, reduced swimming capabilities, and impeded functionality. To address these challenge, motile Escherichia coli are captured inside electropolymerized microtubes, exhibiting the first report of a bacteria microswimmer that does not utilize a spherical particle chassis. Single bacterium becomes partially trapped within the tube and becomes a bioengine to push the microtube though biological media. Microtubes are modified with “smart” material properties for motion control, including a bacteria-attractant polydopamine inner layer, addition of magnetic components for external guidance, and a biochemical kill trigger to cease bacterium swimming on demand. Swimming dynamics of the bacteria biohybrid are quantified by comparing “length of protrusion” of bacteria from the microtubes with respect to changes in angular autocorrelation and swimmer mean squared displacement. The multifunctional microtubular swimmers present a new generation of biocompatible micromotors toward future microbiorobots and minimally invasive medical applications.

Bees, move over. A lily has been pollinated by a remote-controlled flying robot. The robot is hairy, just like a real bee, and sticks to pollen by virtue of an ionic liquid gel, whose fabrication is discussed by Svetlana Chechetka et al. in this issue of Chem.

Most studies on the adhesive mechanisms of climbing animals have addressed attachment against flat surfaces, yet many animals can climb highly curved surfaces, like twigs and small branches. Here we investigated whether tree frogs use a clamping grip by recording the ground reaction forces on a cylindrical object with either a smooth or anti-adhesive, rough surface. Furthermore, we measured the contact area of fore and hindlimbs against differently sized transparent cylinders and the forces of individual pads and subarticular tubercles in restrained animals. Our study revealed that frogs use friction and normal forces of roughly a similar magnitude for holding on to cylindrical objects. When challenged with climbing a non-adhesive surface, the compressive forces between opposite legs nearly doubled, indicating a stronger clamping grip. In contrast to climbing flat surfaces, frogs increased the contact area on all limbs by engaging not just adhesive pads but also subarticular tubercles on curved surfaces. Our force measurements showed that tubercles can withstand larger shear stresses than pads. SEM images of tubercles revealed a similar structure to that of toe pads including the presence of nanopillars, though channels surrounding epithelial cells were less pronounced. The tubercles' smaller size, proximal location on the toes and shallow cells make them probably less prone to buckling and thus ideal for gripping curved surfaces.

Predetermined and selective placement of nanoparticles onto large-area substrates with nanometre-scale precision is essential to harness the unique properties of nanoparticle assemblies, in particular for functional optical and electro-optical nanodevices. Unfortunately, such high spatial organization is currently beyond the reach of top-down nanofabrication techniques alone. Here, we demonstrate that topographic features comprising lithographed funnelled traps and auxiliary sidewalls on a solid substrate can deterministically direct the capillary assembly of Au nanorods to attain simultaneous control of position, orientation and interparticle distance at the nanometre level. We report up to 100% assembly yield over centimetre-scale substrates. We achieve this by optimizing the three sequential stages of capillary nanoparticle assembly: insertion of nanorods into the traps, resilience against the receding suspension front and drying of the residual solvent. Finally, using electron energy-loss spectroscopy we characterize the spectral response and near-field properties of spatially programmable Au nanorod dimers, highlighting the opportunities for precise tunability of the plasmonic modes in larger assemblies.

The risk of side effects from thrombolytic agents can be minimized by using smaller doses, assisted by mechanical rubbing against blood clots using helical robots. Quantifying this observation, we study the influence of rubbing against clots on their removal rate in vitro. First, we present a hydrodynamic model of the helical robot based on the resistive-force theory to investigate the rubbing behavior of the clots using robot driven by two rotating dipole fields. Second, we experimentally evaluate the influence of the rubbing on the removal rate of the blood clots. Not only do we find that the removal rate of mechanical rubbing (-0.56 ± 0.27 mm3 /min) is approximately three times greater than the dissolution rate of chemical lysis using streptokinase (-0.17 ± 0.032 mm3/min), but we also show that this removal rate can be controlled via the rubbing speed of the robot.

Background: Successful gene delivery requires overcoming both systemic and intracellular obstacles before the nucleic acid cargo can successfully reach its tissue and subcellular target location. Materials & Methods: Non-viral mechanisms to enable targeting while avoiding off-target delivery have arisen via biological, chemical, and physical engineering strategies. Discussion: Herein we will discuss the physical parameters in particle design that promote tissue- and cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such as circulation, tissue localization, and clearance, as well as cell-scale obstacles, such as cellular uptake and nucleic acid packaging. Conclusion: In particular, we will focus on engineering particle shape and size in order to enhance delivery and promote precise targeting. We will also address methods to program or change particle shape in situ using environmentally triggered cues.

The present invention are methods for fabrication of micro- and/or nano-scale adhesive fibers and their use for movement and manipulation of objects. Further disclosed is a method of manipulating a part by providing a manipulation device with a plurality of fibers, where each fiber has a tip with a flat surface that is parallel to a backing layer, contacting the flat surfaces on an object, moving the object to a new location, then disengaging the tips from the object.

Biohybrid cell-driven microsystems offer unparalleled possibilities for realization of soft microrobots at the micron scale. Here, we introduce a bacteria-driven microswimmer that combines the active locomotion and sensing capabilities of bacteria with the desirable encapsulation and viscoelastic properties of a soft double-micelle microemulsion for active transport and delivery of cargo (e.g., imaging agents, genes, and drugs) to living cells. Quasi-monodisperse double emulsions were synthesized with an aqueous core that encapsulated the fluorescence imaging agents, as a proof-of-concept cargo in this study, and an outer oil shell that was functionalized with streptavidin for specific and stable attachment of biotin-conjugated Escherichia coli. Motile bacteria effectively propelled the soft microswimmers across a Transwell membrane, actively delivering imaging agents (i.e., dyes) encapsulated inside of the micelles to a monolayer of cultured MCF7 breast cancer and J744A.1 macrophage cells, which enabled real-time, live-cell imaging of cell organelles, namely mitochondria, endoplasmic reticulum, and Golgi body. This in vitro model demonstrates the proof-of-concept feasibility of the proposed soft microswimmers and offers promise for potential biomedical applications in active and/or targeted transport and delivery of imaging agents, drugs, stem cells, siRNA, and therapeutic genes to live tissue in in vitro disease models (e.g., organ-on-a-chip devices) and stagnant or low-flow-velocity fluidic regions of the human body.

Progress in micro- and nano-scale science and technology has created a demand for new microsystems for high-impact applications in healthcare, biotechnology, manufacturing, and mobile sensor networks. The new robotics field of microrobotics has emerged to extend our interactions and explorations to sub-millimeter scales. This is the first textbook on micron-scale mobile robotics, introducing the fundamentals of design, analysis, fabrication, and control, and drawing on case studies of existing approaches. The book covers the scaling laws that can be used to determine the dominant forces and effects at the micron scale; models forces acting on microrobots, including surface forces, friction, and viscous drag; and describes such possible microfabrication techniques as photo-lithography, bulk micromachining, and deep reactive ion etching. It presents on-board and remote sensing methods, noting that remote sensors are currently more feasible; studies possible on-board microactuators; discusses self-propulsion methods that use self-generated local gradients and fields or biological cells in liquid environments; and describes remote microrobot actuation methods for use in limited spaces such as inside the human body. It covers possible on-board powering methods, indispensable in future medical and other applications; locomotion methods for robots on surfaces, in liquids, in air, and on fluid-air interfaces; and the challenges of microrobot localization and control, in particular multi-robot control methods for magnetic microrobots. Finally, the book addresses current and future applications, including noninvasive medical diagnosis and treatment, environmental remediation, and scientific tools.

Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments.

Plasmonic antennas have enabled a wealth of applications that exploit tailored near-fields and radiative properties, further endowed by the bespoke interactions of multiple resonant building blocks. Specifically, when the interparticle distances are reduced to a few nanometers, coupling may be greatly enhanced leading to ultimate near-field intensities and confinement along with a large energy splitting of resonant modes. While this concept is well-known, the fabrication and characterization of suitable multimers with controlled geometries and few-nanometer gaps remains highly challenging. In this article, we present the topographically templated assembly of single-crystal colloidal gold nanorods into trimers, with a dolmen geometry. This fabrication method enables the precise positioning of high-quality nanorods, with gaps as small as 1.5 nm, which permits a gradual and controlled symmetry breaking by tuning the arrangement of these strongly coupled nanostructures. To characterize the fabricated structures, we perform electron energy loss spectroscopy (EELS) near-field hyperspectral imaging and geometrically accurate EELS, plane wave, and eigenmode full-wave computations to reveal the principles governing the electromagnetic response of such nanostructures that have been extensively studied under plane wave excitation for their Fano resonant properties. These experiments track the evolution of the multipolar interactions with high accuracy as the antenna geometry varies. Our results provide new insights in strongly coupled single-crystal building blocks and open news opportunities for the design and fabrication of plasmonic systems.

To add to the current state of knowledge about bacterial swimming dynamics, in this paper, we study the fractal swimming dynamics of populations of Serratia marcescens bacteria both in vitro and in silico, while accounting for realistic conditions like volume exclusion, chemical interactions, obstacles and distribution of chemoattractant in the environment. While previous research has shown that bacterial motion is non-ergodic, we demonstrate that, besides the non-ergodicity, the bacterial swimming dynamics is multi-fractal in nature. Finally, we demonstrate that the multi-fractal characteristic of bacterial dynamics is strongly affected by bacterial density and chemoattractant concentration.

Intrinsic cell chirality has been implicated in the left--right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels.

Most demonstrated mobile microrobot tasks so far have been achieved via pick-and-placing and dynamic trapping with teleoperation or simple path following algorithms. In our previous work, an untethered magnetic microgripper has been developed which has advanced functions, such as gripping objects. Both teleoperated manipulation in 2D and 3D have been demonstrated. However, it is challenging to control the magnetic microgripper to carry out manipulation tasks, because the grasping of objects so far in the literature relies heavily on teleoperation, which takes several minutes with even a skilled human expert. Here, we propose a new spin-walking locomotion and an automated 2D grasping motion planner for the microgripper, which enables time-efficient automatic grasping of microobjects that has not been achieved yet for untethered microrobots. In its locomotion, the microgripper repeatedly rotates about two principal axes to regulate its pose and move precisely on a surface. The motion planner could plan different motion primitives for grasping and compensate the uncertainties in the motion by learning the uncertainties and planning accordingly. We experimentally demonstrated that, using the proposed method, the microgripper could align to the target pose with error less than 0.1 body length and grip the objects within 40 seconds. Our method could significantly improve the time efficiency of micro-scale manipulation and have potential applications in microassembly and biomedical engineering.

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs.

Surface tension-driven self-alignment is a passive and highly-accurate positioning mechanism that can significantly simplify and enhance the construction of advanced microsystems. After years of research{,} demonstrations and developments{,} the surface engineering and manufacturing technology enabling capillary self-alignment has achieved a degree of maturity conducive to a successful transfer to industrial practice. In view of this transition{,} a broad and accessible review of the physics{,} material science and applications of capillary self-alignment is presented. Statics and dynamics of the self-aligning action of deformed liquid bridges are explained through simple models and experiments{,} and all fundamental aspects of surface patterning and conditioning{,} of choice{,} deposition and confinement of liquids{,} and of component feeding and interconnection to substrates are illustrated through relevant applications in micro- and nanotechnology. A final outline addresses remaining challenges and additional extensions envisioned to further spread the use and fully exploit the potential of the technique.

Many highly dynamic novel mobile robots have been developed being inspired by animals. In this study, we are inspired by a basilisk lizard's ability to run and steer on water surface for a hexapedal robot. The robot has an active tail with a circular plate, which the robot rotates to steer on water. We dynamically modeled the platform and conducted simulations and experiments on steering locomotion with a bang-bang controller. The robot can steer on water by rotating the tail, and the controlled steering locomotion is stable. The dynamic modelling approximates the robot's steering locomotion and the trends of the simulations and experiments are similar, although there are errors between the desired and actual angles. The robot's maneuverability on water can be improved through further research.

This paper introduces a new five-dimensional localization method for an untethered meso-scale magnetic robot, which is manipulated by a computer-controlled electromagnetic system. The developed magnetic localization setup is a two-dimensional array of mono-axial Hall-effect sensors, which measure the perpendicular magnetic fields at their given positions. We introduce two steps for localizing a magnetic robot more accurately. First, the dipole modeled magnetic field of the electromagnet is subtracted from the measured data in order to determine the robot's magnetic field. Secondly, the subtracted magnetic field is twice differentiated in the perpendicular direction of the array, so that the effect of the electromagnetic field in the localization process is minimized. Five variables regarding the position and orientation of the robot are determined by minimizing the error between the measured magnetic field and the modeled magnetic field in an optimization method. The resulting position error is 2.1±0.8 mm and angular error is 6.7±4.3° within the applicable range (5 cm) of magnetic field sensors at 200 Hz. The proposed localization method would be used for the position feedback control of untethered magnetic devices or robots for medical applications in the future.

There is an increasing demand for soft actuators because of their importance in soft robotics, artificial muscles, biomimetic devices, and beyond. However, the development of soft actuators capable of low-voltage operation, powerful actuation, and programmable shape-changing is still challenging. In this work, we propose programmable bilayer actuators that operate based on the large hygroscopic contraction of the copy paper and simultaneously large thermal expansion of the polypropylene film upon increasing the temperature. The electrothermally activated bending actuators can function with low voltages (≤ 8 V), low input electric power per area (P ≤ 0.14 W cm–2), and low temperature changes (≤ 35 °C). They exhibit reversible shape-changing behavior with curvature radii up to 1.07 cm–1 and bending angle of 360°, accompanied by powerful actuation. Besides the electrical activation, they can be powered by humidity or light irradiation. We finally demonstrate the use of our paper actuators as a soft gripper robot and a lightweight paper wing for aerial robotics.

At the sub-millimeter scale, capillary forces enable robust and reversible adhesion between biological organisms and varied substrates. Current human-engineered mobile untethered micromanipulation systems rely on forces which scale poorly or utilize gripper-part designs that promote manipulation. Capillary forces, alternatively, are dependent upon the surface chemistry (which is scale independent) and contact perimeter, which conforms to the part surface. We report a mobile capillary microgripper that is able to pick and place parts of various materials and geometries, and is thus ideal for microassembly tasks that cannot be accomplished by large tethered manipulators. We achieve the programmable assembly of sub-millimeter parts in an enclosed three-dimensional aqueous environment by creating a capillary bridge between the targeted part and a synthetic, untethered, mobile body. The parts include both hydrophilic and hydrophobic components: hydrogel, kapton, human hair, and biological tissue. The 200 μm untethered system can be controlled with five-degrees-of-freedom and advances progress towards autonomous desktop manufacturing for tissue engineering, complex micromachines, microfluidic devices, and meta-materials.

On page 2325, Ajay Vikram Singh and Metin Sitti propose a facile surface patterning technique and a specific, strong biotin–streptavidin bonding of bacteria on patterned surfaces to fabricate Janus particles that are propelled by the attached bacteria. Such bacteria-driven Janus microswimmers could be used for future medicine in targeted drug delivery and environmental remediation.

Interfacial adhesion-mediated transfer printing processes can integrate functional electronic microstructures with polymeric substrates that are bendable and stretchable. Transfer printing has also been extended to catechol-bearing adhesive hydrogels. This study presents indentation adhesion tests between catechol-bearing hydrogel substrates with catechol concentrations varying from 0 to 10% (mol/mol) and thin-film materials commonly used in microelectronic fabrication including polymers, noble metals and oxides. The results indicate that the interfacial adhesion of catechol-bearing hydrogels is positively correlated with the concentration of catechol-bearing monomers as well as the retraction velocity during transfer printing. This study can inform transfer printing processes for microfabricated structures to compliant hydrated substrates such as hygroscopic monomers, mesoporous polymer networks and hydrogels. © 2016 Society of Chemical Industry

The adhesive system of geckos has inspired hundreds of synthetic adhesives. While this system has been used relentlessly as a source of inspiration, less work has been done in reverse, where synthetics are used to test questions and hypotheses about the natural system. Here we take such an approach. We tested shear adhesion of a mushroom-tipped synthetic gecko adhesive under conditions that produced perplexing results in the natural adhesive system. Synthetic samples were tested at two temperatures (12 °C and 32 °C) and four different humidity levels (30%, 55%, 70%, and 80% RH). Surprisingly, adhesive performance of the synthetic samples matched that of living geckos, suggesting that uncontrolled parameters in the natural system, such as surface chemistry and material changes, may not be as influential in whole-animal performance as previously thought. There was one difference, however, when comparing natural and synthetic adhesive performance. At 12 °C and 80% RH, adhesion of the synthetic structures was lower than expected based on the natural system’s performance. Our approach highlights a unique opportunity for both biologists and material scientists, where new questions and hypotheses can be fueled by joint comparisons of the natural and synthetic systems, ultimately improving knowledge of both.

Sperm-shaped microrobots are controlled under the influence of weak oscillating magnetic fields (milliTesla range) to selectively target cell mockups (i.e., gas bubbles with average diameter of 200 μm). The sperm-shaped microrobots are fabricated by electrospinning using a solution of polystyrene, dimethylformamide, and iron oxide nanoparticles. These nanoparticles are concentrated within the head of the microrobot, and hence enable directional control along external magnetic fields. The magnetic dipole moment of the microrobot is characterized (using the flip-time technique) to be 1.4×10-11 A.m2, at magnetic field of 28 mT. In addition, the morphology of the microrobot is characterized using Scanning Electron Microscopy images. The characterized parameters and morphology are used in the simulation of the locomotion mechanism of the microrobot to prove that its motion depends on breaking the time-reversal symmetry, rather than pulling with the magnetic field gradient. We experimentally demonstrate that the microrobot can controllably follow S-shaped, U-shaped, and square paths, and selectively target the cell mockups using image guidance and under the influence of the oscillating magnetic fields.

In this paper, we present the analysis of the torque transmitted to a tilted permanent magnet that is to be embedded in a capsule robot to achieve targeted drug delivery. This analysis is carried out by using an analytical model and experimental results for a small cubic permanent magnet that is driven by an external magnetic system made of an array of arc-shaped permanent magnets (ASMs). Our experimental results, which are in agreement with the analytical results, show that the cubic permanent magnet can safely be actuated for inclinations lower than 75° without having to make positional adjustments in the external magnetic system. We have found that with further inclinations, the cubic permanent magnet to be embedded in a drug delivery mechanism may stall. When it stalls, the external magnetic system's position and orientation would have to be adjusted to actuate the cubic permanent magnet and the drug release mechanism. This analysis of the transmitted torque is helpful for the development of real-time control strategies for magnetically articulated devices.