Enhanced ion tolerance of electrokinetic locomotion in polyelectrolyte-coated microswimmer.
ABSTRACT: Over the last decade, researchers have endeavored to mimic the naturally motile microorganisms and develop artificial nano/microswimmers, which propel themselves in aqueous media. However, most of these nano/microswimmers are propelled by the self-electrophoretic mechanism, which has one critical incompetency: the inability to operate in a high concentration electrolyte solution, such as the most important body fluid, blood. This ionic quenching behavior is well backed by the classical Helmholtz-Smoluchowski theory and seems to be an insurmountable challenge which has shadowed the otherwise promising biomedical applications for artificial nano/microswimmers. Here, we propose that the active nano/microswimmer's self-electrophoresis is fundamentally different from the passive nanoparticle electrophoresis. By significantly increasing the Dukhin number with polyelectrolyte coating and geometry optimization, a favorable deviation from the Helmholtz-Smoluchowski behavior can be realized, and ion tolerance is enhanced by over 100 times for a visible light-powered self-electrophoretic microswimmer.
Project description:Untethered mobile microrobots have the potential to leverage minimally invasive theranostic functions precisely and efficiently in hard-to-reach, confined, and delicate inner body sites. However, such a complex task requires an integrated design and engineering, where powering, control, environmental sensing, medical functionality, and biodegradability need to be considered altogether. The present study reports a hydrogel-based, magnetically powered and controlled, enzymatically degradable microswimmer, which is responsive to the pathological markers in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical architecture enabling volumetric cargo loading and swimming capabilities under rotational magnetic fields and a 3D-printed optimized 3D microswimmer (length = 20 ?m and diameter = 6 ?m) using two-photon polymerization from a magnetic precursor suspension composed from gelatin methacryloyl and biofunctionalized superparamagnetic iron oxide nanoparticles. At normal physiological concentrations, we show that matrix metalloproteinase-2 (MMP-2) enzyme could entirely degrade the microswimmer in 118 h to solubilized nontoxic products. The microswimmer rapidly responds to the pathological concentrations of MMP-2 by swelling and thereby boosting the release of the embedded cargo molecules. In addition to delivery of the drug type of therapeutic cargo molecules completely to the given microenvironment after full degradation, microswimmers can also release other functional cargos. As an example demonstration, anti-ErbB 2 antibody-tagged magnetic nanoparticles are released from the fully degraded microswimmers for targeted labeling of SKBR3 breast cancer cells in vitro toward a potential future scenario of medical imaging of remaining cancer tissue sites after a microswimmer-based therapeutic delivery operation.
Project description:Nano/microswimmers represent the persistent endeavors of generations of scientists towards the ultimate tiny machinery for device manufacturing, targeted drug delivery, and noninvasive surgery. In many of these envisioned applications, multiple microswimmers need to be controlled independently and work cooperatively to perform a complex task. However, this multiple channel actuation remains a challenge as the controlling signal, usually a magnetic or electric field, is applied globally over all microswimmers, which makes it difficult to decouple the responses of multiple microswimmers. Here, we demonstrate that a photoelectrochemically driven nanotree microswimmer can be easily coded with a distinct spectral response by loading it with dyes. By using different dyes, an individual microswimmer can be controlled and navigated independently of other microswimmers in a group. This development demonstrates the excellent flexibility of the light navigation method and paves the way for the development of more functional nanobots for applications that require high-level controllability.
Project description:Active self-propelled colloidal populations induce time-dependent three-dimensional fluid flows, which alter the rheological (viscoelastic) properties of their fluidic media. Researchers have also studied passive colloids mixed with bacterial suspensions to understand the hydrodynamic coupling between active and passive colloids. With recent developments in biological cell-driven biohybrid microswimmers, different type biological microswimmer (e.g., bacteria and algae) populations need to interact fluidically with each other in the same fluidic media, while such interactions have not been studied experimentally yet. Therefore, we report the swimming behavior of two opposite types of biological microswimmer (active colloid) populations: Chlamydomonas reinhardtii (C. reinhardtii) algae (puller-type microswimmers) population in coculture with Escherichia coli (E. coli) bacteria (pusher-type microswimmers) population. We observed noticeable fluidic coupling deviations from the existing understanding of passive colloids mixed with bacterial suspensions previously studied in the literature. The fluidic coupling among puller- and pusher-type microswimmers led to nonequilibrium fluctuations in the fluid flow due to their opposite swimming patterns. Such coupling could be the main reason behind the shift in motility behaviors of these two opposite-type swimmer populations suspended in the same fluidic media.
Project description:In this study, in a bio-hybrid microswimmer system driven by multiple Serratia marcescens bacteria, we quantify the chemotactic drift of a large number of microswimmers towards L-serine and elucidate the associated collective chemotaxis behavior by statistical analysis of over a thousand swimming trajectories of the microswimmers. The results show that the microswimmers have a strong heading preference for moving up the L-serine gradient, while their speed does not change considerably when moving up and down the gradient; therefore, the heading bias constitutes the major factor that produces the chemotactic drift. The heading direction of a microswimmer is found to be significantly more persistent when it moves up the L-serine gradient than when it travels down the gradient; this effect causes the apparent heading preference of the microswimmers and is the crucial reason that enables the seemingly cooperative chemotaxis of multiple bacteria on a microswimmer. In addition, we find that their chemotactic drift velocity increases superquadratically with their mean swimming speed, suggesting that chemotaxis of bio-hybrid microsystems can be enhanced by designing and building faster microswimmers. Such bio-hybrid microswimmers with chemotactic steering capability may find future applications in targeted drug delivery, bioengineering, and lab-on-a-chip devices.
Project description:Biohybrid microswimmers, which are realized through the integration of motile microscopic organisms with artificial cargo carriers, have a significant potential to revolutionize autonomous targeted cargo delivery applications in medicine. Nonetheless, there are many open challenges, such as motility performance and immunogenicity of the biological segment of the microswimmers, which should be overcome before their successful transition to the clinic. Here, we present the design and characterization of a biohybrid microswimmer, which is composed of a genetically engineered peritrichously flagellated Escherichia coli species integrated with red blood cell-derived nanoliposomes, also known as nanoerythrosomes. Initially, we demonstrated nanoerythrosome fabrication using the cell extrusion technique and characterization of their size and functional cell membrane proteins with dynamic light scattering and flow cytometry analyses, respectively. Then, we showed the construction of biohybrid microswimmers through the conjugation of streptavidin-modified bacteria with biotin-modified nanoerythrosomes by using non-covalent streptavidin interaction. Finally, we investigated the motility performance of the nanoerythrosome-functionalized biohybrid microswimmers and compared it with the free-swimming bacteria. The microswimmer design approach presented here could lead to the fabrication of personalized biohybrid microswimmers from patients' own cells with high fabrication efficiencies and motility performances.
Project description:Acoustic actuation of bioinspired microswimmers is experimentally demonstrated. Microswimmers are fabricated in situ in a microchannel. Upon acoustic excitation, the flagellum of the microswimmer oscillates, which in turn generates linear or rotary movement depending on the swimmer design. The speed of these bioinspired microswimmers is tuned by adjusting the voltage amplitude applied to the acoustic transducer. Simple microfabrication and remote actuation are promising for biomedical applications.
Project description:Microscale swimming may be intuited to be dominated by background flows, sweeping away any untethered bodies with the prevalent flow direction. However, it has been observed that many microswimmers utilize ambient flows as guidance cues, in some cases resulting in net motion upstream, contrary to the dominant background fluid direction and our accompanying intuition. Thus the hydrodynamic response of small-scale motile organisms requires careful analysis of the complex interaction between swimmer and environment. Here we investigate the effects of a Newtonian shear flow on monoflagellated swimmers with specified body symmetry, representing, for instance, the Leishmania mexicana promastigote, a parasitic hydrodynamic puller that inhabits the microenvironment of a sandfly vector midgut and is the cause of a major and neglected human tropical disease. We observe that a lack of symmetry-breaking cellular geometry results in the periodic tumbling of swimmers in the bulk, with the rotations exhibiting a linear response to changes in shearing rate enabling analytic approximation. In order to draw comparisons with the better-studied pushers, we additionally consider virtual Leishmania promastigotes in a confined but typical geometry, that of a no-slip planar solid boundary, and note that in general stable guided taxis is not exhibited amongst the range of observed behaviors. However, a repulsive boundary gives rise to significant continued taxis in the presence of shearing flow, a phenomenon that may be of particular pertinence to the infective lifecycle stage of such swimmers subject to the assumption of a Newtonian medium. We finally propose a viable and general in vitro method of controlling microswimmer boundary accumulation using temporally evolving background shear flows, based on the analysis of phase-averaged dynamics and verified in silico.
Project description:Fission and fusion processes of particle clusters occur in many areas of physics and chemistry from subnuclear to astronomic length scales. Here we study fission and fusion of magnetic microswimmer clusters as governed by their hydrodynamic and dipolar interactions. Rich scenarios are found that depend crucially on whether the swimmer is a pusher or a puller. In particular a linear magnetic chain of pullers is stable while a pusher chain shows a cascade of fission (or disassembly) processes as the self-propulsion velocity is increased. Contrarily, magnetic ring clusters show fission for any type of swimmer. Moreover, we find a plethora of possible fusion (or assembly) scenarios if a single swimmer collides with a ringlike cluster and two rings spontaneously collide. Our predictions are obtained by computer simulations and verifiable in experiments on active colloidal Janus particles and magnetotactic bacteria.
Project description: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.
Project description:Selective actuation of a single microswimmer from within a diverse group would be a first step toward collaborative guided action by a group of swimmers. Here we describe a new class of microswimmer that accomplishes this goal. Our swimmer design overcomes the commonly-held design paradigm that microswimmers must use non-reciprocal motion to achieve propulsion; instead, the swimmer is propelled by oscillatory motion of an air bubble trapped within the swimmer's polymer body. This oscillatory motion is driven by the application of a low-power acoustic field, which is biocompatible with biological samples and with the ambient liquid. This acoustically-powered microswimmer accomplishes controllable and rapid translational and rotational motion, even in highly viscous liquids (with viscosity 6,000 times higher than that of water). And by using a group of swimmers each with a unique bubble size (and resulting unique resonance frequencies), selective actuation of a single swimmer from among the group can be readily achieved.