Metal-organic frameworks for stimuli-responsive drug delivery.

Manipulation and navigation of micro and nanoswimmers in different fluid environments can be achieved by chemicals, external fields, or even motile cells Many researchers have selected magnetic fields as the active external actuation source based on the advantageous features of this actuation strategy such as remote and spatiotemporal control, fuel-free, high degree of reconfigurability, programmability, recyclability, and versatility This review introduces fundamental concepts and advantages of magnetic micro/nanorobots (termed here as "MagRobots") as well as basic knowledge of magnetic fields and magnetic materials, setups for magnetic manipulation, magnetic field configurations, and symmetry-breaking strategies for effective movement These concepts are discussed to describe the interactions between micro/nanorobots and magnetic fields Actuation mechanisms of flagella-inspired MagRobots (ie, corkscrew-like motion and traveling-wave locomotion/ciliary stroke motion) and surface walkers (ie, surface-assisted motion), applications of magnetic fields in other propulsion approaches, and magnetic stimulation of micro/nanorobots beyond motion are provided followed by fabrication techniques for (quasi-)spherical, helical, flexible, wire-like, and biohybrid MagRobots Applications of MagRobots in targeted drug/gene delivery, cell manipulation, minimally invasive surgery, biopsy, biofilm disruption/eradication, imaging-guided delivery/therapy/surgery, pollution removal for environmental remediation, and (bio)sensing are also reviewed Finally, current challenges and future perspectives for the development of magnetically powered miniaturized motors are discussed

Magnetically Driven Micro and Nanorobots

Magnetic microrobots were developed for three-dimensional culture and the precise delivery of stem cells in vitro, ex vivo, and in vivo. Hippocampal neural stem cells attached to the microrobots proliferated and differentiated into astrocytes, oligodendrocytes, and neurons. Moreover, microrobots were used to transport colorectal carcinoma cancer cells to tumor microtissue in a body-on-a-chip, which comprised an in vitro liver-tumor microorgan network. The microrobots were also controlled in a mouse brain slice and rat brain blood vessel. Last, microrobots carrying mesenchymal stem cells derived from human nose were manipulated inside the intraperitoneal cavity of a nude mouse. The results indicate the potential of microrobots for the culture and delivery of stem cells.

Magnetically actuated microrobots as a platform for stem cell transplantation.

Oriented liquid crystal networks (LCNs) can undergo reversible shape change at the macroscopic scale upon an order-disorder phase transition of the mesogens. This property is explored for developing soft robots that can move under external stimuli, such as light in most studies. Herein, electrically driven soft robots capable of executing various types of biomimetic locomotion are reported. The soft robots are composed of a uniaxially oriented LCN strip, a laminated Kapton layer, and thin resistive wires embedded in between. Taking advantage of the combined attributes of the actuator, namely, easy processing, reprogrammability, and reversible shape shift between two 3D shapes at electric power on and off state, the concept of a "Janus" soft robot is demonstrated, which is built from a single piece of the material and has two parts undergoing opposite deformations simultaneously under a uniform stimulation. In addition to complex shape morphing such as the movement of oarfish and sophisticated devices like self-locking grippers, electrically powered "Janus" soft robots can accomplish versatile locomotion modes, including crawling on flat surfaces through body arching up and straightening down, crawling inside tubes through body stretching and contraction, walking like four-leg animals, and human-like two-leg walking while pushing a load forward.

Biomimetic Locomotion of Electrically Powered “Janus” Soft Robots Using a Liquid Crystal Polymer

Advances in medical robots promise to improve modern medicine and the quality of life. Miniaturization of these robotic platforms has led to numerous applications that leverages precision medicine. In this review, the current trends of medical micro and nanorobotics for therapy, surgery, diagnosis, and medical imaging are discussed. The use of micro and nanorobots in precision medicine still faces technical, regulatory, and market challenges for their widespread use in clinical settings. Nevertheless, recent translations from proof of concept to in vivo studies demonstrate their potential toward precision medicine.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202002203

Medical Micro/Nanorobots in Precision Medicine.

Motile metal-organic frameworks (MOFs) are potential candidates to serve as small-scale robotic platforms for applications in environmental remediation, targeted drug delivery, or nanosurgery. Here, magnetic helical microstructures coated with a kind of zinc-based MOF, zeolitic imidazole framework-8 (ZIF-8), with biocompatibility characteristics and pH-responsive features, are successfully fabricated. Moreover, it is shown that this highly integrated multifunctional device can swim along predesigned tracks under the control of weak rotational magnetic fields. The proposed systems can achieve single-cell targeting in a cell culture media and a controlled delivery of cargo payloads inside a complex microfluidic channel network. This new approach toward the fabrication of integrated multifunctional systems will open new avenues in soft microrobotics beyond current applications.

/pdf/mofbots-metal-organic-framework-based-biomedical-microrobots-2g39tvv0m6.pdf

MOFBOTS: Metal-Organic-Framework-Based Biomedical Microrobots.

Biocompatibility and high responsiveness to magnetic fields are fundamental requisites to translate magnetic small-scale robots into clinical applications. The magnetic element iron exhibits the highest saturation magnetization and magnetic susceptibility while exhibiting excellent biocompatibility characteristics. Here, a process to reliably fabricate iron microrobots by means of template-assisted electrodeposition in 3D-printed micromolds is presented. The 3D molds are fabricated using a modified two-photon absorption configuration, which overcomes previous limitations such as the use of transparent substrates, low writing speeds, and limited depth of field. By optimizing the geometrical parameters of the 3D molds, metallic structures with complex features can be fabricated. Fe microrollers and microswimmers are realized that demonstrate motion at ≈20 body lengths per second, perform 3D motion in viscous environments, and overcome higher flow velocities than those of "conventional 3D printed helical microswimmers." The cytotoxicity of these microrobots is assessed by culturing them with human colorectal cancer (HCT116) cells for four days, demonstrating their good biocompatibility characteristics. Finally, preliminary results regarding the degradation of iron structures in simulated gastric acid liquid are provided.

/pdf/3d-fabrication-of-fully-iron-magnetic-microrobots-36yljcgzld.pdf

3D Fabrication of Fully Iron Magnetic Microrobots

/pdf/indirect-3d-and-4d-printing-of-soft-robotic-microstructures-3ylp3y1nst.pdf

Indirect 3D and 4D Printing of Soft Robotic Microstructures

Metals and polymers are dissimilar materials in terms of their physicochemical properties, but complementary in terms of functionality. As a result, metal-organic structures can introduce a wealth of novel applications in small-scale robotics. However, current fabrication techniques are unable to process three-dimensional metallic and polymeric components. Here, we show that hybrid microstructures can be interlocked by combining 3D lithography, mold casting, and electrodeposition. Our method can be used to achieve complex multi-material microdevices with unprecedented resolution and topological complexity. We show that metallic components can be combined with structures made of different classes of polymers. Properties of both metals and polymers can be exploited in parallel, resulting in structures with high magnetic responsiveness, elevated drug loading capacity, on-demand shape transformation, and elastic behavior. We showcase the advantages of our approach by demonstrating new microrobotic locomotion modes and controlled agglomeration of swarms. Mechanically interlocking dissimilar materials, such as metals and polymers, is a challenging yet promising pathway for designing and fabricating complex systems on the small scale. Here, the authors report a novel interlocking fabrication scheme and showcase the fabrication of microrobots via 3D-lithography.

/pdf/mechanically-interlocked-3d-multi-material-micromachines-2vrnt3mnv6.pdf

Mechanically interlocked 3D multi-material micromachines.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201970192

Carlos C. J. Alcântara

Papers

MOFBOTS: Metal-Organic-Framework-Based Biomedical Microrobots.

3D Fabrication of Fully Iron Magnetic Microrobots

Indirect 3D and 4D Printing of Soft Robotic Microstructures

Mechanically interlocked 3D multi-material micromachines.

MOF‐Based Microrobots: MOFBOTS: Metal–Organic‐Framework‐Based Biomedical Microrobots (Adv. Mater. 27/2019)