A Power Compensation Strategy for Achieving Homogeneous Microstructures for 4D Printing Shape-Adaptive PNIPAM Hydrogels: Out-of-Plane Variations.

In the last decade, 3D printing has attracted significant attention and has resulted in benefits to many research areas. Advances in 3D printing with smart materials at the microscale, such as hydrogels and liquid crystalline polymers, have enabled 4D printing and various applications in microrobots, micro-actuators, and tissue engineering. However, the material absorption of the laser power and the aberrations of the laser light spot will introduce a decay in the polymerization degree along the height direction, and the solution to this problem has not been reported yet. In this paper, a compensation strategy for the laser power is proposed to achieve homogeneous and high aspect ratio hydrogel structures at the microscale along the out-of-plane direction. Linear approximations for the power decay curve are adopted for height steps, discretizing the final high aspect ratio structures. The strategy is achieved experimentally with hydrogel structures fabricated by two-photon polymerization. Moreover, characterizations have been conducted to verify the homogeneity of the printed microstructures. Finally, the saturation of material property is investigated by an indirect 3D deformation method. The proposed strategy is proved to be effective and can be explored for other hydrogel materials showing significant deformation. Furthermore, the strategy for out-of-plane variations provides a critical technique to achieve 4D-printed homogeneous shape-adaptive hydrogels for further applications.

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.

Towards a Comprehensive and Robust Micromanipulation System with Force-Sensing and VR Capabilities.

In this modern world, with the increase of complexity of many technologies, especially in the micro and nanoscale, the field of robotic manipulation has tremendously grown. Microrobots and other complex microscale systems are often to laborious to fabricate using standard microfabrication techniques, therefore there is a trend towards fabricating them in parts then assembling them together, mainly using micromanipulation tools. Here, a comprehensive and robust micromanipulation platform is presented, in which four micromanipulators can be used simultaneously to perform complex tasks, providing the user with an intuitive environment. The system utilizes a vision-based force sensor to aid with manipulation tasks and it provides a safe environment for biomanipulation. Lastly, virtual reality (VR) was incorporated into the system, allowing the user to control the probes from a more intuitive standpoint and providing an immersive platform for the future of micromanipulation.

A Tumbling Magnetic Microrobot System for Biomedical Applications.

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot's position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot's constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system's capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

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.

Design of Microscale Magnetic Tumbling Robots for Locomotion in Multiple Environments and Complex Terrains.

This paper presents several variations of a microscale magnetic tumbling ( µ TUM) robot capable of traversing complex terrains in dry and wet environments. The robot is fabricated by photolithography techniques and consists of a polymeric body with two sections with embedded magnetic particles aligned at the ends and a middle nonmagnetic bridge section. The robot's footprint dimensions are 400 µ m × 800 µ m. Different end geometries are used to test the optimal conditions for low adhesion and increased dynamic response to an actuating external rotating magnetic field. When subjected to a magnetic field as low as 7 mT in dry conditions, this magnetic microrobot is able to operate with a tumbling locomotion mode and translate with speeds of over 60 body lengths/s (48 mm/s) in dry environments and up to 17 body lengths/s (13.6 mm/s) in wet environments. Two different tumbling modes were observed and depend on the alignment of the magnetic particles. A technique was devised to measure the magnetic particle alignment angle relative to the robot's geometry. Rotational frequency limits were observed experimentally, becoming more prohibitive as environment viscosity increases. The µ TUM's performance was studied when traversing inclined planes (up to 60°), showing promising climbing capabilities in both dry and wet conditions. Maximum open loop straight-line trajectory errors of less than 4% and 2% of the traversal distance in the vertical and horizontal directions, respectively, for the µ TUM were observed. Full directional control of µ TUM was demonstrated through the traversal of a P-shaped trajectory. Additionally, successful locomotion of the optimized µ TUM design over complex terrains was also achieved. By implementing machine vision control and/or embedding of payloads in the middle section of the robot, it is possible in the future to upgrade the current design with computer-optimized mobility through multiple environments and the ability to perform drug delivery tasks for biomedical applications.

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.

Towards A Fully Automated High-Throughput Phototransfection System.

We have designed and implemented a framework for creating a fully automated high-throughput phototransfection system. Integrated image processing, laser target position calculation, and stage movements show a throughput increase of > 23X over the current manual phototransfection method while the potential for even greater throughput improvements (> 110X) is described. A software tool for automated off-line single cell morphological measurements, as well as real-time image segmentation analysis, has also been constructed and shown to be able quantify changes in the cell before and after the process, successfully characterizing them, using metrics such as cell perimeter, area, major and minor axis length, and eccentricity values.

Transcriptome transfer produces a predictable cellular phenotype.

Cellular phenotype is the conglomerate of multiple cellular processes involving gene and protein expression that result in the elaboration of a cell's particular morphology and function. It has been thought that differentiated postmitotic cells have their genomes hard wired, with little ability for phenotypic plasticity. Here we show that transfer of the transcriptome from differentiated rat astrocytes into a nondividing differentiated rat neuron resulted in the conversion of the neuron into a functional astrocyte-like cell in a time-dependent manner. This single-cell study permits high resolution of molecular and functional components that underlie phenotype identity. The RNA population from astrocytes contains RNAs in the appropriate relative abundances that give rise to regulatory RNAs and translated proteins that enable astrocyte identity. When transferred into the postmitotic neuron, the astrocyte RNA population converts 44% of the neuronal host cells into the destination astrocyte-like phenotype. In support of this observation, quantitative measures of cellular morphology, single-cell PCR, single-cell microarray, and single-cell functional analyses have been performed. The host-cell phenotypic changes develop over many weeks and are persistent. We call this process of RNA-induced phenotype changes, transcriptome-induced phenotype remodeling.