Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System.

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord ex vivo, demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging.

MagnetoSuture: Tetherless Manipulation of Suture Needles.

This paper demonstrates the feasibility of ligation and tissue penetration for surgical suturing tasks using magnetically actuated suture needles. Manipulation of suture needles in minimally invasive surgery involves using articulated manual/robotic tools for needle steering and controlling needle-tissue or thread-tissue interactions. The large footprints of conventional articulated surgical tools significantly increase surgical invasiveness, potentially leading to longer recovery times, tissue damage, scarring, or associated infections. Aiming to address these issues, we investigate the feasibility of using magnetic fields to tetherlessly steer suture needles. The primary challenge of such a concept is to provide sufficient force for tissue penetration and ligation. In this work, we demonstrate proof-of-concept capabilities using the MagnetoSuture™ system, performing tissue penetration and ligation tasks using ex vivo tissues, customized NdFeB suture needles with attached threads, and remote-controlled magnetic fields. To evaluate the system performance, we conducted experiments demonstrating tetherless recreation of a purse string suture pattern, ligation of an excised segment of a rat intestine, and penetration of rat intestines.

Magnetically Aligned Nanorods in Alginate Capsules (MANiACs): Soft Matter Tumbling Robots for Manipulation and Drug Delivery.

Soft, untethered microrobots composed of biocompatible materials for completing micromanipulation and drug delivery tasks in lab-on-a-chip and medical scenarios are currently being developed. Alginate holds significant potential in medical microrobotics due to its biocompatibility, biodegradability, and drug encapsulation capabilities. Here, we describe the synthesis of MANiACs-Magnetically Aligned Nanorods in Alginate Capsules-for use as untethered microrobotic surface tumblers, demonstrating magnetically guided lateral tumbling via rotating magnetic fields. MANiAC translation is demonstrated on tissue surfaces as well as inclined slopes. These alginate microrobots are capable of manipulating objects over millimeter-scale distances. Finally, we demonstrate payload release capabilities of MANiACs during translational tumbling motion.

Towards Independent Control of Multiple Magnetic Mobile Microrobots.

In this paper, we have developed an approach for independent autonomous navigation of multiple microrobots under the influence of magnetic fields and validated it experimentally. We first developed a heuristics based planning algorithm for generating collision-free trajectories for the microrobots that are suitable to be executed by an available magnetic field. Second, we have modeled the dynamics of the microrobots to develop a controller for determining the forces that need to be generated for the navigation of the robots along the trajectories at a suitable control frequency. Next, an optimization routine is developed to determine the input currents to the electromagnetic coils that can generate the required forces for the navigation of the robots at the controller frequency. We then validated our approach by simulating an electromagnetic system that contains an array of sixty-four magnetic microcoils designed for generating local magnetic fields suitable for simultaneous independent actuation of multiple microrobots. Finally, we prototyped an m m -scale version of the system and present experimental results showing the validity of our approach.

The interplay of cell-cell and cell-substrate adhesion in collective cell migration.

Collective cell migration often involves notable cell-cell and cell-substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell-substrate adhesion and cell-cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells (Dictyostelium discoideum), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell-cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell-cell contacts. To further investigate cell-cell/cell-substrate interactions, we used optical micromanipulation to form cell-substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell-substrate contact.

Optical micromanipulation of active cells with minimal perturbations: direct and indirect pushing.

The challenge to wide application of optical tweezers in biological micromanipulation is the photodamage caused by high-intensity laser exposure to the manipulated living systems. While direct exposure to infrared lasers is less likely to kill cells, it can affect cell behavior and signaling. Pushing cells with optically trapped objects has been introduced as a less invasive alternative, but the technique includes some exposure of the biological object to parts of the optical tweezer beam. To keep the cells farther away from the laser, we introduce an indirect pushing-based technique for noninvasive manipulation of sensitive cells. We compare how cells respond to three manipulation approaches: direct manipulation, pushing, and indirect pushing. We find that indirect manipulation techniques lessen the impact of manipulation on cell behavior. Cell survival increases, as does the ability of cells to maintain shape and wiggle. Our experiments also demonstrate that indirect pushing allows cell-cell contacts to be formed in a controllable way, while retaining the ability of cells to change shape and move.

Survey on indirect optical manipulation of cells, nucleic acids, and motor proteins.

Optical tweezers have emerged as a promising technique for manipulating biological objects. Instead of direct laser exposure, more often than not, optically-trapped beads are attached to the ends or boundaries of the objects for translation, rotation, and stretching. This is referred to as indirect optical manipulation. In this paper, we utilize the concept of robotic gripping to explain the different experimental setups which are commonly used for indirect manipulation of cells, nucleic acids, and motor proteins. We also give an overview of the kind of biological insights provided by this technique. We conclude by highlighting the trends across the experimental studies, and discuss challenges and promising directions in this domain of active current research.