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.

Toxic and hazardous chemical species are ubiquitous, predominantly emitted by anthropogenic activities, and pose serious risks to human health and the environment. Thus, the sensing and subsequent capture of these chemicals, especially in the gas or vapor phase, are of extreme importance. To this end, metal–organic frameworks have attracted significant interest, as their high porosity and wide tunability make them ideal for both applications. These tailorable framework materials are particularly promising for the specific sensing and capture of targeted chemicals, as they can be designed to fit a diverse range of required conditions. This review will discuss the advantages of metal–organic frameworks in the sensing and capture of harmful gases and vapors, as well as principles and strategies guiding the design of these materials. Recent progress in the luminescent detection of aromatic and aliphatic volatile organic compounds, toxic gases, and chemical warfare agents will be summarized, and the adsorptive removal of fluorocarbons/chlorofluorocarbons, volatile radioactive species, toxic industrial gases and chemical warfare agents will be discussed.

Sensing and capture of toxic and hazardous gases and vapors by metal–organic frameworks

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

Micro-/nanorobots (m-bots) have attracted significant interest due to their suitability for applications in biomedical engineering and environmental remediation. Particularly, their applications in in vivo diagnosis and intervention have been the focus of extensive research in recent years with various clinical imaging techniques being applied for localization and tracking. The successful integration of well-designed m-bots with surface functionalization, remote actuation systems, and imaging techniques becomes the crucial step toward biomedical applications, especially for the in vivo uses. This review thus addresses four different aspects of biomedical m-bots: design/fabrication, functionalization, actuation, and localization. The biomedical applications of the m-bots in diagnosis, sensing, microsurgery, targeted drug/cell delivery, thrombus ablation, and wound healing are reviewed from these viewpoints. The developed biomedical m-bot systems are comprehensively compared and evaluated based on their characteristics. The current challenges and the directions of future research in this field are summarized.

Trends in Micro-/Nanorobotics: Materials Development, Actuation, Localization, and System Integration for Biomedical Applications.

After the tremendous advances over the past two decades, micro‐/nanorobots can effectively convert other forms of energy into propulsion and movement, as well as be navigated to targeted locations under physiological conditions and environments. They have been demonstrated to have the potential to load, transport, and deliver therapeutic payloads directly to disease sites, thereby improving the therapeutic efficacy and reducing systemic side effects of highly toxic drugs. In this feature article, the various propulsion modalities of micro‐/nanorobots ranging from chemical/biochemical reactions to external fields, and to motile microorganisms are summarized and commented in terms of driving forces required by the automotive motion in biological media, biocompatibility, as well as the corresponding advantages and limitations in terms of biomedical applications. Then, the latest developments of in vitro and in vivo active drug delivery based on micro‐/nanorobots are discussed in detail. The challenges and future prospects are also highlighted in the end. With ever booming research enthusiasm in this field and increasing multidisciplinary cooperation, micro‐/nanorobots with intelligence and multifunctions will emerge in the near future, which would have a profound impact on the treatment of diseases.

Micro-/Nanorobots at Work in Active Drug Delivery

The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Reported herein is a new microdevice, consisting of magnesium-based micromotors which can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, and the normal stomach pH is restored within 24 h post motor administration.

/pdf/micromotors-spontaneously-neutralize-gastric-acid-for-ph-4py1y2lnm9.pdf

Micromotors Spontaneously Neutralize Gastric Acid for pH‐Responsive Payload Release

Herein, we report that UiO-type (UiO = University of Oslo) metal–organic frameworks (MOFs) can be transformed into self-propelled micromotors by employing several different metal-based propulsion systems. Incorporation of a bipyridine ligand into the UiO-67 lattice transforms the crystallites, upon metalation, into single-site, metal-based catalytic “engines” to power the micromotors with chemical fuel. The “engine performance” (i.e., propulsion) of the single-site powered micromotors has been tuned by the choice of the metal ion utilized. In addition, a chemical “braking” system was achieved by adding chelating agents capable of sequestering the metal ion engines and thereby suppressing the catalytic activity, with different chelators displaying different deceleration capacities. These results demonstrate that MOFs can be powered by various engines and halted by different brakes, resulting in a high degree of motion design and control at the nanoscale.

Metal–Organic Frameworks as Micromotors with Tunable Engines and Brakes

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Micromotors Spontaneously Neutralize Gastric Acid for pH‐Responsive Payload Release

Metal–Organic Frameworks as Micromotors with Tunable Engines and Brakes