Micro- and nanoscale robots that can effectively convert diverse energy sources into movement and force represent a
rapidly emerging and fascinating robotics research area. Recent advances in the design, fabrication, and operation of micro/nanorobots have greatly enhanced their power, function, and versatility. The new capabilities of these tiny untethered machines indicate immense potential for a variety of biomedical applications. This article reviews recent progress and future perspectives of micro/nanorobots in biomedicine, with a special focus on their potential advantages and applications for directed drug delivery, precision surgery, medical diagnosis, and detoxification. Future success of this technology, to be realized through close collaboration between robotics, medical, and nanotechnology experts, should have a major impact on disease diagnosis, treatment, and prevention.

/pdf/micro-nanorobots-for-biomedicine-delivery-surgery-sensing-23eglg29gr.pdf

Micro/Nanorobots for Biomedicine: Delivery, Surgery, Sensing, and Detoxification.

Magnetic microrobots and nanorobots can be remotely controlled to propel in complex biological fluids with high precision by using magnetic fields. Their potential for controlled navigation in hard-to-reach cavities of the human body makes them promising miniaturized robotic tools to diagnose and treat diseases in a minimally invasive manner. However, critical issues, such as motion tracking, biocompatibility, biodegradation, and diagnostic/therapeutic effects, need to be resolved to allow preclinical in vivo development and clinical trials. We report biohybrid magnetic robots endowed with multifunctional capabilities by integrating desired structural and functional attributes from a biological matrix and an engineered coating. Helical microswimmers were fabricated from Spirulina microalgae via a facile dip-coating process in magnetite (Fe3O4) suspensions, superparamagnetic, and equipped with robust navigation capability in various biofluids. The innate properties of the microalgae allowed in vivo fluorescence imaging and remote diagnostic sensing without the need for any surface modification. Furthermore, in vivo magnetic resonance imaging tracked a swarm of microswimmers inside rodent stomachs, a deep organ where fluorescence-based imaging ceased to work because of its penetration limitation. Meanwhile, the microswimmers were able to degrade and exhibited selective cytotoxicity to cancer cell lines, subject to the thickness of the Fe3O4 coating, which could be tailored via the dip-coating process. The biohybrid microrobots reported herein represent a microrobotic platform that could be further developed for in vivo imaging-guided therapy and a proof of concept for the engineering of multifunctional microrobotic and nanorobotic devices.

Multifunctional biohybrid magnetite microrobots for imaging-guided therapy

Advances in bioinspired design principles and nanomaterials have led to tremendous progress in autonomously moving synthetic nano/micromotors with diverse functionalities in different environments. However, a significant gap remains in moving nano/micromotors from test tubes to living organisms for treating diseases with high efficacy. Here we present the first, to our knowledge, in vivo therapeutic micromotors application for active drug delivery to treat gastric bacterial infection in a mouse model using clarithromycin as a model antibiotic and Helicobacter pylori infection as a model disease. The propulsion of drug-loaded magnesium micromotors in gastric media enables effective antibiotic delivery, leading to significant bacteria burden reduction in the mouse stomach compared with passive drug carriers, with no apparent toxicity. Moreover, while the drug-loaded micromotors reach similar therapeutic efficacy as the positive control of free drug plus proton pump inhibitor, the micromotors can function without proton pump inhibitors because of their built-in proton depletion function associated with their locomotion. Nano- and micromotors have been demonstrated in vitro for a range of applications. Here the authors demonstrate the in-vivo therapeutic use of micromotors to treat H. pylori infection.

/pdf/micromotor-enabled-active-drug-delivery-for-in-vivo-23eam8vatg.pdf

Micromotor-enabled active drug delivery for in vivo treatment of stomach infection

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

Recently, tremendous progress in synthetic micro/nanomotors in diverse environment has been made for potential biomedical applications. However, existing micro/nanomotor platforms are inefficient for deep tissue imaging and motion control in vivo. Here, we present a photoacoustic computed tomography (PACT)–guided investigation of micromotors in intestines in vivo. The micromotors enveloped in microcapsules are stable in the stomach and exhibit efficient propulsion in various biofluids once released. The migration of micromotor capsules toward the targeted regions in intestines has been visualized by PACT in real time in vivo. Near-infrared light irradiation induces disintegration of the capsules to release the cargo-loaded micromotors. The intensive propulsion of the micromotors effectively prolongs the retention in intestines. The integration of the newly developed microrobotic system and PACT enables deep imaging and precise control of the micromotors in vivo and promises practical biomedical applications, such as drug delivery.

A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines in vivo

The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue p...

Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract

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Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract