Upstream mobility and swarming of light activated micromotors.

Micromotors have been proposed for applications such as targeted drug delivery, thrombolysis, or sensing. However, single micrormotors are limited in the amount of payload they can deliver or force they can exert. Swarms of micromotors can overcome many of these challenges, however creating and controlling such swarms presents many challenges of its own. In particular, utilizing swarms in fluid flows is of significant importance for biomedical or lab-on-chip applications. Here, the upstream mobility and swarm formation of light driven micromotors in microchannel flows is demonstrated with maximum speeds around 0.1 mm s-1. Additionally, the light actuated microrobots operate in fairly low concentrations of hydrogen peroxide of approximately 1%. The micromotors form swarms at the boundary of the locally applied light pattern and the swarms can be moved by translating the light up or downstream.

Fabrication of three-lobed magnetic microrobots for cell transportation.

Mobile microrobots have the potential to transform medical treatments based on therapeutic delivery. Specifically, microrobots are promising candidates for cell transportation in cell-based therapies. Despite recent progress in cellular manipulation by microrobots, there is a significant need to design and fabricate microrobots to advance the field further. In this work, we present a facile approach to manufacturing three-lobed microrobots by a bench-top procedure. The microrobots are actuated by a harmless magnetic field which makes them biofriendly. Chemically, these microrobots are made of organosilica. The microrobots showed equally good control in both the open-loop and closed-loop settings. The three-lobed microrobots have two modes of motion during the open-loop control experiments. We employed these two modes for single-cell transportation. Our results show that the three-lobed microbots are very promising for cell transportation in a fluid.

Doxorubicin-Loaded Microrobots for Targeted Drug Delivery and Anticancer Therapy.

Micro-sized magnetic particles (also known as microrobots [MRs]) have recently been shown to have potential applications for numerous biomedical applications like drug delivery, microengineering, and single cell manipulation. Interdisciplinary studies have demonstrated the ability of these tiny particles to actuate under the action of a controlled magnetic field that not only drive MRs in a desired trajectory but also precisely deliver therapeutic payload to the target site. Additionally, optimal concentrations of therapeutic molecules can also be delivered to the desired site which is cost-effective and safe especially in scenarios where drug dose-related side effects are a concern. In this study, MRs are used to deliver anticancer drugs (doxorubicin) to cancer cells and subsequent cell death is evaluated in different cell lines (liver, prostate, and ovarian cancer cells). Cytocompatibility studies show that MRs are well-tolerated and internalized by cancer cells. Doxorubicin (DOX) is chemically conjugated with MRs (DOX-MRs) and magnetically steered toward cancer cells using the magnetic controller. Time-lapsed video shows that cells shrink and eventually die when MRs are internalized by cells. Taken together, this study confirms that microrobots are promising couriers for targeted delivery of therapeutic biomolecules for cancer therapy and other non-invasive procedures that require precise control.

ModMag: A modular magnetic micro-robotic manipulation device.

Electromagnetic systems have been used extensively for the control of magnetically actuated objects, such as in microrheology and micro- robotics research. Therefore, optimizing the design of such systems is highly desirable. Some of the features that are lacking in most cur- rent designs are compactness, portability, and versatility. Portability is especially relevant for biomedical applications in which in vivo or in vitro testing may be conducted in locations away from the laboratory microscope. This document describes the design, fabrication, and imple- mentation of a compact, low-cost, versatile, and user-friendly device (the ModMag) capable of controlling multiple electromagnetic setups, includ- ing a two-dimensional 4-coil configuration, a 3-dimensional Helmholtz configuration, a 2-dimensional magnetic tweezer configuration, and a piezoelectric transducer for producing acoustic waves. All electronics for powering the systems are contained in a compact 10″x6"x3" case, which includes a 10″ touchscreen. A graphical user interface provides additional ease of use. The system can also be controlled remotely, allowing for more flexibility and the ability to interface with other software running on the remote computer such as proprietary camera software. Aside from the software and circuitry, we also describe the design of the electromagnetic coil setups and provide examples of the use of the ModMag in experiments.•Low cost and portable magnetic micro-robot manipulation device•Compatible with the 3 most common coil configurations (traditional, Helmholtz, tweezer).

Spatial Patterning of Micromotor Aggregation and Flux.

Using a spatially varying light pattern with light activated semi-conductor based magnetic TiO2 micromotors, we study the difference in micromotor flux between illuminated and non-illuminated regions in the presence and absence of an applied magnetic field. We find that the magnetic field enhances the flux of the motors which we attribute to a straightening of the micromotor trajectories which decreases the time they spend in the illuminated region. We also demonstrate spatially patterned light-induced aggregation of the micromotors and study its time evolution at various micromotor concentrations. Although light induced aggregation has been observed previously, spatial patterning of aggregation demonstrates a further means of control which could be relevant to swarm control or self-assembly applications. Overall, these results draw attention to the effect of trajectory shape on the flux of active colloids as well as the concentration dependence of aggregation and its time dependence within a spatially patterned region, which is not only pertinent to self-assembly and swarm control, but also provides insight into the behavior of active matter systems with spatially varying activity levels.

Closed Loop Control of Bubble-Propelled Microrobots.

Bubble-propelled microrobots have an advantage of relatively swift movement compared to most other types of microrobots, which makes them well suited for applications such as micromanipulation or movement in flows, but their high speed also poses challenges in precisely controlling their motion. This study proposes automated control of the microrobots using visual feedback and steering with uniform magnetic fields to constrain the microrobot's moving direction. The implementation of a closed-loop control mechanism ensures precise autonomous navigation along prescribed trajectories. Experimental results demonstrate that this approach achieves satisfactory tracking performance, with an average error of 6. 7 µm for a microrobot with a diameter of 24 µm.

Rolling Helical Microrobots for Cell Patterning.

Microrobots, untethered miniature devices capable of performing tasks at the microscale, have gained significant attention in the fields of robotics and biomedicine. These devices hold immense potential for various industrial and scientific applications, including targeted drug delivery and cell manipulation. In this study, we present a novel magnetic rolling helical microrobot specifically designed for bio-compatible cell patterning. Our microrobot incorporates both open-loop and closed-loop control mechanisms, providing flexible, precise, and rapid control for various applications. Through experiments, we demonstrate the microrobot's ability to manipulate cells by pushing them while rolling and arranging cells into desired patterns. This result is particularly significant as it has implications for diverse biological applications such as tissue engineering and organoid development. Moreover, we showcase the effectiveness of our microrobot in a closed-loop control system, where it successfully follows a predetermined path from an origin to a destination. The combination of cellular manipulation capabilities and trajectory-tracking performance underlines the versatility and potential of our magnetic rolling helical microrobot. The ability to control and navigate the microrobot with high precision opens up new possibilities for advanced biomedical applications. These findings contribute to the growing body of knowledge in microbotics and pave the way for further research and development in the field.

Programmable Modular Acoustic Microrobots.

Microrobots have emerged as promising tools for biomedical and in vivo applications, leveraging their untethered actuation capabilities and miniature size. Despite extensive research on diversifying multi-actuation modes for single types of robots, these tiny machines tend to have limited versatility while navigating different environments or performing specific tasks. To overcome such limitations, self-assembly microstructures with on-demand reconfiguration capabilities have gained recent attention as the future of biocompatible microrobotics, as they can address drug delivery, microsurgery, and organoid development processes. Reversible modular reconfiguration structures require specific arrangements of particles that can assume several shapes when external fields are applied. We show how magnetic interaction can be used to assemble cylindrical microrobots into modular microstructures with different shapes. The motion actuation of the formed microstructure happens due to an external acoustic field, which generates responsive forces in the air bubbles trapped in the inner cavity of the robots. An external magnetic field can also steer these structures. We illustrate these capabilities by assembling the robots into different shapes that can swim and be steered, showing the potential to perform biomedical applications. Furthermore, we confirm the biocompatibility of the cylindrical microrobot used as the building blocks of our microstructure. Exposing Chinese Hamster Ovary cells to our microrobots for 24 hours demonstrates cell viability when in contact with the microrobot.

Fabrication and open-loop control of three-lobed nonspherical Janus microrobots.

In this study, we propose a simple and efficient method to fabricate three-lobed nonspherical Janus microrobots. These microrobots can be actuated by a harmless magnetic field. Utilizing organosilica as the material of choice, we leverage its versatile silane chemistry to enable various surface modifications and functionalities. The fabricated microrobots demonstrate two distinct modes of motion, making them well-suited for cell transportation and drug delivery tasks. Their unique shape and motion characteristics allow for precise and targeted movement. Integrating these microrobots into therapeutic delivery platforms can revolutionize medical treatments, offering enhanced precision, efficiency, and versatility in delivering therapies to specific sites.

Multistimuli-responsive microrobots: A comprehensive review.

Untethered robots of the size of a few microns have attracted increasing attention for the potential to transform many aspects of manufacturing, medicine, health care, and bioengineering. Previously impenetrable environments have become available for high-resolution in situ and in vivo manipulations as the size of the untethered robots goes down to the microscale. Nevertheless, the independent navigation of several robots at the microscale is challenging as they cannot have onboard transducers, batteries, and control like other multi-agent systems, due to the size limitations. Therefore, various unconventional propulsion mechanisms have been explored to power motion at the nanoscale. Moreover, a variety of combinations of actuation methods has also been extensively studied to tackle different issues. In this survey, we present a thorough review of the recent developments of various dedicated ways to actuate and control multistimuli-enabled microrobots. We have also discussed existing challenges and evolving concepts associated with each technique.

Role of Surface Tension in Microrobot Penetration in Membranes.

cell-membrane fusion using microrobots can be a useful technique for delivering bioactive compounds to cellular systems. The role of membrane curvature and lipid ordering in the cell membrane penetration process is well known. However, once the fusion into the cell membrane is already initiated, the fluid dynamics of microrobot penetration based on tension difference of the microrobot solution and membrane curvature at the fusion pore has not been explored yet. Here, we demonstrate how surface tension difference among merging interfaces plays role in microrobot droplet penetration into a liquid bath, mimicking cell membrane fusion. The maximum penetration of a microrobot droplet into a liquid bath depends on the positive difference of surface tension between the droplet and liquid bath, longitudinal curvature of the bridge region, and the size of the droplet.

A First-Order Approach to Model Simultaneous Control of Multiple Microrobots.

The control of swarm systems is relatively well understood for simple robotic platforms at the macro scale. However, there are still several unanswered questions about how similar results can be achieved for microrobots. In this paper, we propose a modeling framework based on a dynamic model of magnetized self-propelling Janus microrobots under a global magnetic field. We verify our model experimentally and provide methods that can aim at accurately describing the behavior of microrobots while modeling their simultaneous control. The model can be generalized to other microrobotic platforms in low Reynolds number environments.

Cellular Manipulation Using Rolling Microrobots.

Many biomedical applications, such as targeted drug delivery or cell manipulation, are well suited for the deployment of microrobots, untethered devices that are capable of carrying out tasks at the microscale. One biocompatible means of driving microrobots relies on magnetic actuation. In particular, microrobots driven using rotating fields rather than magnetic field gradients are especially practical for real-word applications. Many biological applications involve enclosed environments, such as blood vessels, in which surfaces are abundant, therefore, surface rolling is a particularly pertinent method of transportation. In this paper we demonstrate manipulation and transportation of cells using two types of magnetically driven rolling microrobots. We find that the microrobots are able to manipulate the cells by physically pushing or by first adhering to the cells and then carrying them. Microrobots spinning at high rates also can transport cells via the induced fluid flows.

Harnessing catalytic pumps for directional delivery of microparticles in microchambers.

The directed transport of microparticles in microfluidic devices is vital for efficient bioassays and fabrication of complex microstructures. There remains, however, a need for methods to propel and steer microscopic cargo that do not require modifying these particles. Using theory and experiments, we show that catalytic surface reactions can be used to deliver microparticle cargo to specified regions in microchambers. Here reagents diffuse from a gel reservoir and react with the catalyst-coated surface. Fluid density gradients due to the spatially varying reagent concentration induce a convective flow, which carries the suspended particles until the reagents are consumed. Consequently, the cargo is deposited around a specific position on the surface. The velocity and final peak location of the cargo can be tuned independently. By increasing the local particle concentration, highly sensitive assays can be performed efficiently and rapidly. Moreover, the process can be repeated by introducing fresh reagent into the microchamber.

Boundaries can steer active Janus spheres.

The advent of autonomous self-propulsion has instigated research towards making colloidal machines that can deliver mechanical work in the form of transport, and other functions such as sensing and cleaning. While much progress has been made in the last 10 years on various mechanisms to generate self-propulsion, the ability to steer self-propelled colloidal devices has so far been much more limited. A critical barrier in increasing the impact of such motors is in directing their motion against the Brownian rotation, which randomizes particle orientations. In this context, here we report directed motion of a specific class of catalytic motors when moving in close proximity to solid surfaces. This is achieved through active quenching of their Brownian rotation by constraining it in a rotational well, caused not by equilibrium, but by hydrodynamic effects. We demonstrate how combining these geometric constraints can be utilized to steer these active colloids along arbitrary trajectories.

Synthetic Nano- and Micromachines in Analytical Chemistry: Sensing, Migration, Capture, Delivery, and Separation.

Synthetic nano- and microscale machines move autonomously in solution or drive fluid flows by converting sources of energy into mechanical work. Their sizes are comparable to analytes (sub-nano- to microscale), and they respond to signals from each other and their surroundings, leading to emergent collective behavior. These machines can potentially enable hitherto difficult analytical applications. In this article, we review the development of different classes of synthetic nano- and micromotors and pumps and indicate their possible applications in real-time in situ chemical sensing, on-demand directional transport, cargo capture and delivery, as well as analyte isolation and separation.

Chemotactic separation of enzymes.

We demonstrate a procedure for the separation of enzymes based on their chemotactic response toward an imposed substrate concentration gradient. The separation is observed within a two-inlet, five-outlet microfluidic network, designed to allow mixtures of active (ones that catalyze substrate turnover) and inactive (ones that do not catalyze substrate turnover) enzymes, labeled with different fluorophores, to flow through one of the inlets. Substrate solution prepared in phosphate buffer was introduced through the other inlet of the device at the same flow rate. The steady-state concentration profiles of the enzymes were obtained at specific positions within the outlets of the microchannel using fluorescence microscopy. In the presence of a substrate concentration gradient, active enzyme molecules migrated preferentially toward the substrate channel. The excess migration of the active enzyme molecules was quantified in terms of an enrichment coefficient. Experiments were carried out with different pairs of enzymes. Coupling the physics of laminar flow of liquid and molecular diffusion, multiphysics simulations were carried out to estimate the extent of the chemotactic separation. Our results show that, with appropriate microfluidic arrangement, molecular chemotaxis leads to spontaneous separation of active enzyme molecules from their inactive counterparts of similar charge and size.