Programmable acoustic modular microrobots.

The field of microrobotics has emerged as a promising area of research with significant applications in biomedicine, both in vitro and in vivo, such as targeted cargo delivery, microsurgery, and cellular manipulation. Microrobots actuated with multiple modalities have the potential for greater adaptability, robustness, and capability to perform various tasks. Modular units that can reconfigure into various shapes, create structures that may be difficult to fabricate as one whole unit, and be assembled on-site, could provide more versatility by assembly and disassembly of units on demand. Such multi-modal modular microrobots have the potential to address challenging applications. Here, we present a biocompatible cylindrical microrobot with a dome-shaped cavity. The microrobot is actuated by both magnetic and acoustic fields and forms modular microstructures of various shapes. We demonstrate the use of these microrobots for cellular manipulation by creating patterns on a surface. Supplementary Information: The online version contains supplementary material available at 10.1007/s12213-024-00175-y.

Learning a Tracking Controller for Rolling µbots.

Micron-scale robots (µbots) have recently shown great promise for emerging medical applications. Accurate control of µbots, while critical to their successful deployment, is challenging. In this work, we consider the problem of tracking a reference trajectory using a µbot in the presence of disturbances and uncertainty. The disturbances primarily come from Brownian motion and other environmental phenomena, while the uncertainty originates from errors in the model parameters. We model the µbot as an uncertain unicycle that is controlled by a global magnetic field. To compensate for disturbances and uncertainties, we develop a nonlinear mismatch controller. We define the model mismatch error as the difference between our model's predicted velocity and the actual velocity of the µbot. We employ a Gaussian Process to learn the model mismatch error as a function of the applied control input. Then we use a least-squares minimization to select a control action that minimizes the difference between the actual velocity of the µbot and a reference velocity. We demonstrate the online performance of our joint learning and control algorithm in simulation, where our approach accurately learns the model mismatch and improves tracking performance. We also validate our approach in an experiment and show that certain error metrics are reduced by up to 40%.

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 for a Heterogeneous Group of Magnetically-actuated Microrobots.

The development of magnetically-actuated micro-robots is of great interest for emerging medical applications due to their inherent safety, low cost to manufacture, and flexibility. In many practical applications, precise control over the motion of the microrobots is a strong requirement. In these contexts, closed-loop control is a practical tool to adjust the microrobots' control inputs in real time. In this work, we describe a process to quickly fabricate a large number of heterogeneous microrobots using colloidal synthesis. We simultaneously develop a closed-loop control law that drives the microrobots to a desired formation in the plane. In addition, we prove that heterogeneity in the microrobot dynamics is necessary to generate arbitrary formations. Finally, using experimental data, we show in simulation that N = 4 microrobots can be driven to any arbitrary formation using our control law.

Targeted Vibration-Induced Necrosis in Liver Cancer Cells using Paramagnetic Microrobots.

Therapeutic delivery of anti-cancer drugs is a major goal of modern medicine. However, developing methods to target cancer cells for more effective treatment and reduced side effects is a significant ongoing challenge. Microrobots have recently been studied for their ability to navigate difficult-to-reach regions in the human body to deliver therapeutics for microscopically localized interventions. Using microrobots for targeted and local therapy therefore, is a promising revolutionary treatment method. In this study, magnetic microrobots were used to target and kill cancer cells via localized magnetic oscillations, resulting in magnetolysis of the cancer cells. The magnetic microrobots were selectively moved to Hepatocarcinoma cells (HepG2 cells) using a custom magnetic system which applied rotating magnetic fields. After internalization of the microrobots by the cancer cells, magnetic oscillation of varying dosages was applied, resulting in cell death.

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.

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.