Elastohydrodynamic propulsion of a filament magnetically driven at both ends.

The elastohydrodynamic interaction between an elastic filament and its surrounding fluid was exploited to develop the first microswimmers. These flexible microswimmers are typically actuated magnetically at one end and their propulsion behavior is relatively well understood. In this work, we move beyond the traditional single-end actuation setup and explore the propulsion characteristics of an elastic filament driven by magnetic torques at both ends. We report the emergence of new modes of propulsion behaviors in different physical regimes, depending on the balance of elastic and viscous forces as well as the arrangement of the magnetic moments at the filament ends. In particular, under the same magnetic actuation, a filament driven at both ends can propel either forward or backward depending on its relative stiffness. Moreover, this new backward propulsion mode can generate a magnitude of propulsion that is unattainable by the traditional single-end actuation setup. We characterize these new propulsion behaviors and provide some physical insights into how they emerge from the complex interplay between viscous and elastic forces and magnetic actuation in various configurations. Taken together, these findings could guide the development of soft microrobots with enhanced propulsion performance and maneuverability for future biomedical applications.

Learning to cooperate for low-Reynolds-number swimming: a model problem for gait coordination.

Biological microswimmers can coordinate their motions to exploit their fluid environment-and each other-to achieve global advantages in their locomotory performance. These cooperative locomotion require delicate adjustments of both individual swimming gaits and spatial arrangements of the swimmers. Here we probe the emergence of such cooperative behaviors among artificial microswimmers endowed with artificial intelligence. We present the first use of a deep reinforcement learning approach to empower the cooperative locomotion of a pair of reconfigurable microswimmers. The AI-advised cooperative policy comprises two stages: an approach stage where the swimmers get in close proximity to fully exploit hydrodynamic interactions, followed a synchronization stage where the swimmers synchronize their locomotory gaits to maximize their overall net propulsion. The synchronized motions allow the swimmer pair to move together coherently with an enhanced locomotion performance unattainable by a single swimmer alone. Our work constitutes a first step toward uncovering intriguing cooperative behaviors of smart artificial microswimmers, demonstrating the vast potential of reinforcement learning towards intelligent autonomous manipulations of multiple microswimmers for their future biomedical and environmental applications.

Effects of membrane viscoelasticity on the red blood cell dynamics in a microcapillary.

The mechanical properties of red blood cells (RBCs) play key roles in their biological functions in microcirculation. In particular, RBCs must deform significantly to travel through microcapillaries with sizes comparable with or even smaller than their own. Although the dynamics of RBCs in microcapillaries have received considerable attention, the effect of membrane viscoelasticity has been largely overlooked. In this work, we present a computational study based on the boundary integral method and thin-shell mechanics to examine how membrane viscoelasticity influences the dynamics of RBCs flowing through straight and constricted microcapillaries. Our results reveal that the cell with a viscoelastic membrane undergoes substantially different motion and deformation compared with results based on a purely elastic membrane model. Comparisons with experimental data also suggest the importance of accounting for membrane viscoelasticity to properly capture the transient dynamics of an RBC flowing through a microcapillary. Taken together, these findings demonstrate the significant effects of membrane viscoelasticity on RBC dynamics in different microcapillary environments. The computational framework also lays the groundwork for more accurate quantitative modeling of the mechanical response of RBCs in their mechanotransduction process in subsequent investigations.

Data-Driven Intelligent Manipulation of Particles in Microfluidics.

Automated manipulation of small particles using external (e.g., magnetic, electric and acoustic) fields has been an emerging technique widely used in different areas. The manipulation typically necessitates a reduced-order physical model characterizing the field-driven motion of particles in a complex environment. Such models are available only for highly idealized settings but are absent for a general scenario of particle manipulation typically involving complex nonlinear processes, which has limited its application. In this work, the authors present a data-driven architecture for controlling particles in microfluidics based on hydrodynamic manipulation. The architecture replaces the difficult-to-derive model by a generally trainable artificial neural network to describe the kinematics of particles, and subsequently identifies the optimal operations to manipulate particles. The authors successfully demonstrate a diverse set of particle manipulations in a numerically emulated microfluidic chamber, including targeted assembly of particles and subsequent navigation of the assembled cluster, simultaneous path planning for multiple particles, and steering one particle through obstacles. The approach achieves both spatial and temporal controllability of high precision for these settings. This achievement revolutionizes automated particle manipulation, showing the potential of data-driven approaches and machine learning in improving microfluidic technologies for enhanced flexibility and intelligence.

Ingestible Functional Magnetic Robot with Localized Flexibility (MR-LF).

The integration of an ingestible dosage form with sensing, actuation, and drug delivery capabilities can enable a broad range of surgical-free diagnostic and treatment strategies. However, the gastrointestinal (GI) tract is a highly constrained and complex luminal construct that fundamentally limits the size of an ingestible system. Recent advancements in mesoscale magnetic crawlers have demonstrated the ability to effectively traverse complex and confined systems by leveraging magnetic fields to induce contraction and bending-based locomotion. However, the integration of functional components (e.g., electronics) in the proposed ingestible system remains fundamentally challenging. Herein, the creation of a centralized compartment in a magnetic robot by imparting localized flexibility (MR-LF) is demonstrated. The centralized compartment enables MR-LF to be readily integrated with modular functional components and payloads, such as commercial off-the-shelf electronics and medication, while preserving its bidirectionality in an ingestible form factor. The ability of MR-LF to incorporate electronics, perform drug delivery, guide continuum devices such as catheters, and navigate air-water environments in confined lumens is demonstrated. The MR-LF enables functional integration to create a highly-integrated ingestible system that can ultimately address a broad range of unmet clinical needs.

Propulsion of an elastic filament in a shear-thinning fluid.

Some micro-organisms and artificial micro-swimmers propel at low Reynolds numbers (Re) via the interaction of their flexible appendages with the surrounding fluid. While their locomotion has been extensively studied with a Newtonian fluid assumption, in realistic biological environments these micro-swimmers invariably encounter rheologically complex fluids. In particular, many biological fluids such as blood and different types of mucus have shear-thinning viscosities. The influence of this ubiquitous non-Newtonian rheology on the performance of flexible swimmers remains largely unknown. Here, we present a first study to examine how shear-thinning rheology alters the fluid-structure interaction and hence the propulsion performance of elastic swimmers at low Re. Via a simple elastic swimmer actuated magnetically, we demonstrate that shear-thinning rheology can either enhance or hinder elastohydrodynamic propulsion, depending on the intricate interplay between elastic and viscous forces as well as the magnetic actuation. We also use a reduced-order model to elucidate the mechanisms underlying the enhanced and hindered propulsion observed in different physical regimes. These results and improved understanding could guide the design of flexible micro-swimmers in non-Newtonian fluids.

A 3D-Printed Self-Learning Three-Linked-Sphere Robot for Autonomous Confined-Space Navigation.

Reinforcement learning control methods can impart robots with the ability to discover effective behavior, reducing their modeling and sensing requirements, and enabling their ability to adapt to environmental changes. However, it remains challenging for a robot to achieve navigation in confined and dynamic environments, which are characteristic of a broad range of biomedical applications, such as endoscopy with ingestible electronics. Herein, a compact, 3D-printed three-linked-sphere robot synergistically integrated with a reinforcement learning algorithm that can perform adaptable, autonomous crawling in a confined channel is demonstrated. The scalable robot consists of three equally sized spheres that are linearly coupled, in which the extension and contraction in specific sequences dictate its navigation. The ability to achieve bidirectional locomotion across frictional surfaces in open and confined spaces without prior knowledge of the environment is also demonstrated. The synergistic integration of a highly scalable robotic apparatus and the model-free reinforcement learning control strategy can enable autonomous navigation in a broad range of dynamic and confined environments. This capability can enable sensing, imaging, and surgical processes in previously inaccessible confined environments in the human body.

Helical locomotion in a porous medium.

Microorganisms and artificial microswimmers often need to swim through environments that are more complex than purely viscous liquids in their natural habitats or operational environments, such as gel-like mucus, wet soil, and aquifers. The question of how the properties of these complex environments affect locomotion has attracted considerable recent attention. In this paper, we present a theoretical model to examine how the additional resistance due to the network of stationary obstacles in a porous medium affects helical locomotion. Here, we focus on helical locomotion for its ubiquity as a propulsion mechanism adopted by many swimming bacteria and artificial microswimmers. We show that the additional resistance can have qualitatively different effects on various scenarios of helical locomotion: (1) a helical propeller driven by an external torque, (2) a free swimming bacterium consisting of a helical flagellum and a head, and (3) a cargo-carrying helical propeller driven by an external torque. Our results elucidate the subtle and significant differences between torqued helical propulsion versus force-free and torque-free swimming in a porous medium. We also remark on the limitations as well as potential connections of our results with experimental measurements of bacterial swimming speeds in polymeric solutions.

Squirming in a viscous fluid enclosed by a Brinkman medium.

Cell motility plays important roles in a range of biological processes, such as reproduction and infections. Studies have hypothesized that the ulcer-causing bacterium Helicobacter pylori invades the gastric mucus layer lining the stomach by locally turning nearby gel into sol, thereby enhancing its locomotion through the biological barrier. In this work, we present a minimal theoretical model to investigate how heterogeneity created by a swimmer affects its own locomotion. As a generic locomotion model, we consider the swimming of a spherical squirmer in a purely viscous fluid pocket (representing the liquified or degelled region) surrounded by a Brinkman porous medium (representing the mucus gel). The use of the squirmer model enables an exact, analytical solution to this hydrodynamic problem. We obtain analytical expressions for the swimming speed, flow field, and power dissipation of the swimmer. Depending on the details of surface velocities and fluid properties, our results reveal the existence of a minimum threshold size of mucus gel that a swimmer needs to liquify in order to gain any enhancement in swimming speed. The threshold size can be as much as approximately 30% of the swimmer size. We contrast these predictions with results from previous models and highlight the significant role played by the details of surface actuations. In addition to their biological implications, these results could also inform the design of artificial microswimmers that can penetrate into biological gels for more effective drug delivery.

Medical micro/nanorobots in complex media.

Medical micro/nanorobots have received tremendous attention over the past decades owing to their potential to be navigated into hard-to-reach tissues for a number of biomedical applications ranging from targeted drug/gene delivery, bio-isolation, detoxification, to nanosurgery. Despite the great promise, the majority of the past demonstrations are primarily under benchtop or in vitro conditions. Many developed micro/nanoscale propulsion mechanisms are based on the assumption of a homogeneous, Newtonian environment, while realistic biological environments are substantially more complex. Moving toward practical medical use, the field of micro/nanorobotics must overcome several major challenges including propulsion through complex media (such as blood, mucus, and vitreous) as well as deep tissue imaging and control in vivo. In this review article, we summarize the recent research efforts on investigating how various complexities in biological environments impact the propulsion of micro/nanoswimmers. We also highlight the emerging technological approaches to enhance the locomotion of micro/nanorobots in complex environments. The recent demonstrations of in vivo imaging, control and therapeutic medical applications of such micro/nanorobots are introduced. We envision that continuing materials and technological innovations through interdisciplinary collaborative efforts can bring us steps closer to the fantasy of "swallowing a surgeon".

A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat.

Wearable sweat sensors have the potential to provide continuous measurements of useful biomarkers. However, current sensors cannot accurately detect low analyte concentrations, lack multimodal sensing or are difficult to fabricate at large scale. We report an entirely laser-engraved sensor for simultaneous sweat sampling, chemical sensing and vital-sign monitoring. We demonstrate continuous detection of temperature, respiration rate and low concentrations of uric acid and tyrosine, analytes associated with diseases such as gout and metabolic disorders. We test the performance of the device in both physically trained and untrained subjects under exercise and after a protein-rich diet. We also evaluate its utility for gout monitoring in patients and healthy controls through a purine-rich meal challenge. Levels of uric acid in sweat were higher in patients with gout than in healthy individuals, and a similar trend was observed in serum.

Sorting by interfacial tension (SIFT): Label-free enzyme sorting using droplet microfluidics.

Droplet microfluidics has the ability to greatly increase the throughput of screening and sorting of enzymes by carrying reagents in picoliter droplets flowing in inert oils. It was found with the use of a specific surfactant, the interfacial tension of droplets can be very sensitive to droplet pH. This enables the sorting of droplets of different pH when confined droplets encounter a microfabricated trench. The device can be extended to sort enzymes, as a large number of enzymatic reactions lead to the production of an acidic or basic product and a concurrent change in solution pH. The progress of an enzymatic reaction is tracked from the position of a flowing train of droplets. We demonstrate the sorting of esterase isoenzymes based on their enzymatic activity. This label-free technology, that we dub droplet sorting by interfacial tension (SIFT), requires no active components and would have applications for enzyme sorting in high-throughput applications that include enzyme screening and directed evolution of enzymes.

Effects of surfactant transport on electrodeformation of a viscous drop.

In this work we quantify the effects of surfactant transport on the deformation of a viscous drop under a DC electric field. We study how convective and diffusive transport of surfactants at drop surfaces influence the equilibrium and dynamic deformation of a leaky dielectric drop and a conducting drop. Focusing on the prolate drop shape (elongates along the electric field), we show the differences in equilibrium deformation and flow circulation between a leaky dielectric drop and a conducting drop. We quantify the drop electrodeformation via its dependence on the interior flow circulation and the dominant surfactant transport regime (characterized by the surface Péclet number Pe_{s}). For a leaky dielectric drop with dominant surfactant diffusion (Pe_{s}≪1), equator-to-pole (pole-to-equator) circulation yields smaller (larger) equilibrium deformation with increasing surfactant coverage, compared to a clean drop. However, when convection dominates (Pe_{s}≫1), the equilibrium drop deformation increases (decreases) with larger surfactant coverage for equator-to-pole (pole-to-equator) circulation. Larger equilibrium drop deformation is found for a leaky dielectric drop than a conducting drop when the interior flow is from equator to pole. For an interior flow from pole to equator, we identify cases where larger deformation is found for a conducting interior fluid. Finally, we study the effect of the surfactant transport on the dynamic evolution of drop shape. We found the drop undergoes an overshoot in the early deformation phase, before settling to its equilibrium shape-similar to the overshoot observed for unsteady Stokes flow.

A Rapid and Low-Cost Pathogen Detection Platform by Using a Molecular Agglutination Assay.

Rapid and low-cost pathogen diagnostic approaches are critical for clinical decision-making procedures. Cultivating bacteria often takes days to identify pathogens and provide antimicrobial susceptibilities. The delay in diagnosis may result in compromised treatment and inappropriate antibiotic use. Over the past decades, molecular-based techniques have significantly shortened pathogen identification turnaround time with high accuracy. However, these assays often use complex fluorescent labeling and nucleic acid amplification processes, which limit their use in resource-limited settings. In this work, we demonstrate a wash-free molecular agglutination assay with a straightforward mixing and incubation step that significantly simplifies procedures of molecular testing. By targeting the 16S rRNA gene of pathogens, we perform a rapid pathogen identification within 30 min on a dark-field imaging microfluidic cytometry platform. The dark-field images with low background noise can be obtained using a narrow beam scanning technique with off-the-shelf complementary metal oxide semiconductor (CMOS) imagers such as smartphone cameras. We utilize a machine learning algorithm to deconvolute topological features of agglutinated clusters and thus quantify the abundance of bacteria. Consequently, we unambiguously distinguish Escherichia coli positive from other E. coli negative among 50 clinical urinary tract infection samples with 96% sensitivity and 100% specificity. Furthermore, we also apply this quantitative detection approach to achieve rapid antimicrobial susceptibility testing within 3 h. This work exhibits easy-to-use protocols, high sensitivity, and short turnaround time for point-of-care testing uses.

Ellipsoidal Brownian self-driven particles in a magnetic field.

We study the two-dimensional Brownian dynamics of an ellipsoidal paramagnetic microswimmer moving at a low Reynolds number and subject to a magnetic field. Its corresponding mean-square displacement, showing the effect of a particles's shape, activity, and magnetic field on the microswimmer's diffusion, is analytically obtained. Comparison between analytical and computational results shows good agreement. In addition, the effect of self-propulsion on the transition time from anisotropic to isotropic diffusion of the ellipse is investigated.

Maximizing propulsive thrust of a driven filament at low Reynolds number via variable flexibility.

At low Reynolds numbers the locomotive capability of a body can be dramatically hindered by the absence of inertia. In this work, we show how propulsive performance in this regime can be significantly enhanced by employing spatially varying flexibility. As a prototypical example, we consider the propulsive thrust generated by a filament periodically driven at one end. The rigid case leads to zero propulsion, as so constrained by Purcell's scallop theorem, while for uniform filaments there exists a bending stiffness maximizing the propulsive force at a given frequency; here we demonstrate explicitly how considerable further improvement can be achieved by simply varying the stiffness along the filament. The optimal flexibility distribution is strongly configuration-dependent: while increasing the flexibility towards the tail-end enhances the propulsion of a clamped filament, for a hinged filament decreasing the flexibility towards the tail-end is instead favorable. The results reveal new design principles for maximizing propulsion at low Reynolds numbers, potentially useful for developing synthetic micro-swimmers requiring large propulsive force for various biomedical applications.

Propulsion via flexible flapping in granular media.

Biological locomotion in nature is often achieved by the interaction between a flexible body and its surrounding medium. The interaction of a flexible body with granular media is less understood compared with viscous fluids partially due to its complex rheological properties. In this work, we explore the effect of flexibility on granular propulsion by considering a simple mechanical model in which a rigid rod is connected to a torsional spring that is under a displacement actuation using a granular resistive force theory. Through a combined numerical and asymptotic investigation, we characterize the propulsive dynamics of such a flexible flapper in relation to the actuation amplitude and spring stiffness, and we compare these dynamics with those observed in a viscous fluid. In addition, we demonstrate that the maximum possible propulsive force can be obtained in the steady propulsion limit with a finite spring stiffness and large actuation amplitude. These results may apply to the development of synthetic locomotive systems that exploit flexibility to move through complex terrestrial media.

Swimming efficiency in a shear-thinning fluid.

Micro-organisms expend energy moving through complex media. While propulsion speed is an important property of locomotion, efficiency is another factor that may determine the swimming gait adopted by a micro-organism in order to locomote in an energetically favorable manner. The efficiency of swimming in a Newtonian fluid is well characterized for different biological and artificial swimmers. However, these swimmers often encounter biological fluids displaying shear-thinning viscosities. Little is known about how this nonlinear rheology influences the efficiency of locomotion. Does the shear-thinning rheology render swimming more efficient or less? How does the swimming efficiency depend on the propulsion mechanism of a swimmer and rheological properties of the surrounding shear-thinning fluid? In this work, we address these fundamental questions on the efficiency of locomotion in a shear-thinning fluid by considering the squirmer model as a general locomotion model to represent different types of swimmers. Our analysis reveals how the choice of surface velocity distribution on a squirmer may reduce or enhance the swimming efficiency. We determine optimal shear rates at which the swimming efficiency can be substantially enhanced compared with the Newtonian case. The nontrivial variations of swimming efficiency prompt questions on how micro-organisms may tune their swimming gaits to exploit the shear-thinning rheology. The findings also provide insights into how artificial swimmers should be designed to move through complex media efficiently.

Gating of a mechanosensitive channel due to cellular flows.

A multiscale continuum model is constructed for a mechanosensitive (MS) channel gated by tension in a lipid bilayer membrane under stresses due to fluid flows. We illustrate that for typical physiological conditions vesicle hydrodynamics driven by a fluid flow may render the membrane tension sufficiently large to gate a MS channel open. In particular, we focus on the dynamic opening/closing of a MS channel in a vesicle membrane under a planar shear flow and a pressure-driven flow across a constriction channel. Our modeling and numerical simulation results quantify the critical flow strength or flow channel geometry for intracellular transport through a MS channel. In particular, we determine the percentage of MS channels that are open or closed as a function of the relevant measure of flow strength. The modeling and simulation results imply that for fluid flows that are physiologically relevant and realizable in microfluidic configurations stress-induced intracellular transport across the lipid membrane can be achieved by the gating of reconstituted MS channels, which can be useful for designing drug delivery in medical therapy and understanding complicated mechanotransduction.