Tiny Machines Research Articles

A Revolution in Cellular Aging: A Narrative Review of the Promising Role of Nanorobots in Diagnosis, Treatment, and Regenerative Medicine

Nanorobots, also known as nanobots, are promising medical structures with significant potential for revolutionizing medical treatments and preventing their onset. Nanorobotics shows promise for diagnosing, treating, and regenerating age-related diseases. These tiny machines can repair cellular damage, deliver drugs, stimulate tissue regeneration, and monitor treatments. However, their application in controlling cellular aging is in its early stages, requiring more research to fully understand their potential and address safety concerns. Despite this, the benefits of nanorobots in age-related disease management justify further investigation. This narrative review article provides an overview of recent developments in nanorobotics, specifically focusing on its medical applications. PubMed and Google Scholar were utilized to conduct a comprehensive search using relevant keywords including "nanorobots", "cellular aging", "drug delivery systems", "cellular repair", "therapeutics", and "diagnosis". Only articles published between 2005-2023 were selected to support the arguments with up-to-date evidence. The extracted information includes nanorobot design, fabrication methods, applications, and key findings. A quality assessment was performed, and the data were categorized thematically to identify patterns and trends. The article concludes with an examination of the current state and future prospects of nanorobotics in different fields. Our research showed that nanorobots have significant potential in the diagnosis, treatment, and regenerative medicine of age-related diseases. They can detect and repair cellular damage caused by aging, targeting DNA damage and cellular protein misfolding. Nanorobots can also deliver drugs directly to affected areas, reducing side effects. Furthermore, they stimulate tissue regeneration and the growth of new blood vessels by delivering growth factors. Nanorobots can also monitor treatment effectiveness by measuring drug concentration in tumor cells. However, there are concerns about their safety in long-term use that require further research. Overall, nanorobots present an innovative approach to addressing cellular changes in aging, but more research is needed to understand their full potential and address safety concerns. The use of nanorobots in treating cellular aging has opened new possibilities in diagnosing and treating age-related diseases and it is a rapidly evolving field with the potential to revolutionize age-related disease treatment and improve the quality of life globally.

Electromechanical Energy-Based 3D-Controllable Motion of Small Matter toward Tiny Machines

Is it possible to remotely operate a tiny piece of matter or a less-than-one-centimeter machine to perform a medical task in life? Especially given that in the present technology, neither the mechanism nor battery is small enough to be set up inside the structure of such a tiny machine. Yet, if the powered matter is magnetically responsive, then a magnetic field, as one of the potential power sources, can be applied to power it promisingly. Herein, the concept of electromechanical energy conversion is utilized through a specific configuration consisting of eight solenoids arranged together as a nest. The device converts electrical energy into an electromagnetic field, and finally, into mechanical energy, respectively, resulting in magnetic manipulation. Since electric energy is supplied to the configuration, eight solenoids generate the controllable magnetic field in both direction and magnitude by means of the superposition technique. The device can magnetically navigate tiny motorless matter to release mechanical energy through the 3D-controllable motion to arbitrary positions effectively and physical interactions with the surrounding environment as if operating a tiny machine. The experimental results report the feasibility of the device to control the 6-DOF locomotion of small matter precisely. The contribution of the concept based on this work leads to a promising protocol to remotely power small machines, micro-engines, micro-propellers, micro-turbines, etc.

Programmable Modular Acoustic Microrobots.

Microrobots have emerged as promising tools for biomedical and in vivo applications, leveraging their untethered actuation capabilities and miniature size. Despite extensive research on diversifying multi-actuation modes for single types of robots, these tiny machines tend to have limited versatility while navigating different environments or performing specific tasks. To overcome such limitations, self-assembly microstructures with on-demand reconfiguration capabilities have gained recent attention as the future of biocompatible microrobotics, as they can address drug delivery, microsurgery, and organoid development processes. Reversible modular reconfiguration structures require specific arrangements of particles that can assume several shapes when external fields are applied. We show how magnetic interaction can be used to assemble cylindrical microrobots into modular microstructures with different shapes. The motion actuation of the formed microstructure happens due to an external acoustic field, which generates responsive forces in the air bubbles trapped in the inner cavity of the robots. An external magnetic field can also steer these structures. We illustrate these capabilities by assembling the robots into different shapes that can swim and be steered, showing the potential to perform biomedical applications. Furthermore, we confirm the biocompatibility of the cylindrical microrobot used as the building blocks of our microstructure. Exposing Chinese Hamster Ovary cells to our microrobots for 24 hours demonstrates cell viability when in contact with the microrobot.

Gold-hyaluranic acid micromotors and cold atmospheric plasma for enhanced drug delivery and therapeutic applications

Micro/nanomotors have emerged as promising platforms for various applications, including drug delivery and controlled release. These tiny machines, built from nanoscale materials such as carbon nanotubes, graphene, metal nanoparticles, or nanowires, can convert different forms of energy into mechanical motion. In the field of medicine, nanomotors offer potential for targeted drug delivery and diagnostic applications, revolutionizing areas such as cancer treatment and lab-on-a-chip devices. One prominent material used in drug delivery is hyaluronic acid (HA), known for its biocompatibility and non-immunogenicity. HA-based drug delivery systems have shown promise in improving the efficacy and reducing the toxicity of chemotherapeutic agents like doxorubicin (DOX). Additionally, micro/nanomotors controlled by external stimuli enable precise drug delivery to specific areas of the body. Cold atmospheric plasma (CAP) has also emerged as a promising technology for drug delivery, utilizing low-temperature plasma to enhance drug release and bioavailability. CAP offers advantages such as localized delivery and compatibility with various drug types. However, further research is needed to optimize CAP drug delivery systems and understand their mechanisms. In this study, gold-hyaluronic acid (Au-HA) micromotors were synthesized for the first time, utilizing acoustic force for self-motion. The release profile of DOX, a widely used anticancer drug, was investigated in pH-dependent conditions, and the effect of CAP on drug release from the micromotors was examined. Following exposure to the CAP jet for 1 min, the micromotors released approximately 29 μg mL−1 of DOX into the PBS (pH 5), which is significantly higher than the 17 μg mL−1 released without CAP. The research aims to minimize side effects, increase drug loading and release efficiency, and highlight the potential of HA-based micromotors in cancer therapy. This study contributes to the advancement of micro-motor technology and provides insights into the utilization of pH and cold plasma technology for enhancing drug delivery systems.

Molecular motor may help design tiny machines

Molecular motor may help design tiny machines

Intelligent sensing based on active micro/nanomotors.

In the microscopic world, synthetic micro/nanomotors (MNMs) can convert a variety of energy sources into driving forces to help humans perform a number of complex tasks with greater ease and efficiency. These tiny machines have attracted tremendous attention in the field of drug delivery, minimally invasive surgery, in vivo sampling, and environmental management. By modifying their surface materials and functionalizing them with bioactive agents, these MNMs can also be transformed into dynamic micro/nano-biosensors that can detect biomolecules in real-time with high sensitivity. The extensive range of operations and uses combined with their minuscule size have opened up new avenues for tackling intricate analytical difficulties. Here, in this review, various driving methods are briefly introduced, followed by a focus on intelligent detection techniques based on MNMs. And we discuss the distinctive advantages, current issues, and challenges associated with MNM-based intelligent detection. It is believed that the future advancements of MNMs will greatly impact the diagnosis, treatment, and prevention of diseases.

A review/survey paper on Nanobots in Medical Applications for brain tumor detections

This study is a review or survey on the use of nanobots in medicine. Designing and creating tiny machines, particularly robotic machines, is the field of nanorobotics. Any "smart" structure that is able to act, sense, signal, process information, think, manipulate, and exhibit swarm behaviour at the nanoscale is a nanorobot (10-9m). More specifically, the term "nanorobotics" (as opposed to "micro robotics") refers to the engineering field of nanotechnology that focuses on designing and creating nanorobots with devices that range in size from 0.1 to 10 micrometres and are made of components that are either nanoscale or molecular. Nanomedicine is one of the first practical applications of nanotechnology. Cancer cells are recognised and eliminated using biological devices. The project shown here was undertaken by an electronics and communication engineering post-graduate student in the department's second year at Bangalore's Dayananda Sagar College of Engineering. It was completed as part of the course requirements.

Nanobots: Future and Development

This review paper gives overview of the present status and further development in nanorobotics. Nanobots are very tiny machines designed to perform a specific task whose components are at or close to the scale of a nanometer. As consequence of nanotechnology, new technique consisting of device coming into market among these nanobots fields opportunity in cure of human illness. This bots are made of a single strand of DNA folded into desired shape. Bots will have two states – an “off” position, where the clamshells are closed tightly to bypass healthy cell without any damage and an “on” position, where clamshell opens up to expose cancerous cell from human body. In this paper included about method of working, composition, types, challenges in development and properties of nanobots.

Increasingly Intelligent Micromachines

Intelligent micromachines, with dimensions ranging from a few millimeters down to hundreds of nanometers, are miniature systems capable of performing specific tasks autonomously at small scales. Enhancing the intelligence of micromachines to tackle the uncertainty and variability in complex microenvironments has applications in minimally invasive medicine, bioengineering, water cleaning, analytical chemistry, and more. Over the past decade, significant progress has been made in the construction of intelligent micromachines, evolving from simple micromachines to soft, compound, reconfigurable, encodable, multifunctional, and integrated micromachines, as well as from individual to multiagent, multiscale, hierarchical, self-organizing, and swarm micromachines. The field leverages two important trends in robotics research—the miniaturization and intelligentization of machines—but a compelling combination of these two features has yet to be realized. The core technologies required to make such tiny machines intelligent include information media, transduction, processing, exchange, and energy supply, but embedding all of these functions into a system at the micro- or nanoscale is challenging. This article offers a comprehensive introduction to the state-of-the-art technologies used to create intelligence for micromachines and provides insight into the construction of next-generation intelligent micromachines that can adapt to diverse scenarios for use in emerging fields.

Enzyme-powered micro- and nano-motors: key parameters for an application-oriented design.

Nature has inspired the creation of artificial micro- and nanomotors that self-propel converting chemical energy into mechanical action. These tiny machines have appeared as promising biomedical tools for treatment and diagnosis and have also been used for environmental, antimicrobial or sensing applications. Among the possible catalytic engines, enzymes have emerged as an alternative to inorganic catalysts due to their biocompatibility and the variety and bioavailability of fuels. Although the field of enzyme-powered micro- and nano-motors has a trajectory of more than a decade, a comprehensive framework on how to rationally design, control and optimize their motion is still missing. With this purpose, herein we performed a thorough bibliographic study on the key parameters governing the propulsion of these enzyme-powered devices, namely the chassis shape, the material composition, the motor size, the enzyme type, the method used to incorporate enzymes, the distribution of the product released, the motion mechanism, the motion media and the technique used for motion detection. In conclusion, from the library of options that each parameter offers there needs to be a rational selection and intelligent design of enzymatic motors based on the specific application envisioned.

Biohybrid Micro- and Nanorobots for Intelligent Drug Delivery.

Biohybrid micro- and nanorobots are integrated tiny machines from biological components and artificial components. They can possess the advantages of onboard actuation, sensing, control, and implementation of multiple medical tasks such as targeted drug delivery, single-cell manipulation, and cell microsurgery. This review paper is to give an overview of biohybrid micro- and nanorobots for smart drug delivery applications. First, a wide range of biohybrid micro- and nanorobots comprising different biological components are reviewed in detail. Subsequently, the applications of biohybrid micro- and nanorobots for active drug delivery are introduced to demonstrate how such biohybrid micro- and nanorobots are being exploited in the field of medicine and healthcare. Lastly, key challenges to be overcome are discussed to pave the way for the clinical translation and application of the biohybrid micro- and nanorobots.

THE FUTURE OF BODY IMPLANTS

There are around 415 million people suffering from diabetes around the globe, and they don't need to get their finger punctured every time their blood sugar is to be monitored or insulin to be delivered, thanks to the magical “Insulin Pumps”. All these tiny machines have is a needle and a small pump, the system is able to monitor the glucose levels, provide information to the pump and then determine the amount of insulin to be injected through the needle. But they have a catch: they're temporary. Within a few days, glucose sensors have to be moved and replaced. And it's not just glucose monitors and insulin pumps that have this problem, but all bodily implants, at different time scales. Plastic prosthetic knees have to be replaced after about 20 years. Other implants, such as those used for cosmetic reasons, can meet the same fate in about 10. That isn't just a nuisance: it can be expensive and risky. This inconvenience happens because of our bodies' immune systems. Honed by several hundred million years of evolution, these defensive fronts have become exceptionally good at identifying foreign objects. Our immune systems boast an impressivearsenal of tools to tackle, intercept, and destroy anything they believe shouldn't be there. But the consequence of this constant surveillance is that our bodies treat helpful implants, like insulin pumps, with the same suspicion as they would a harmful virus or bacteria. As soon as the insulin pump has been implanted in the skin, its presence triggers what's known as a “foreign body response.” This starts with free-floating proteins that stick themselves to the surface of the implant. Those proteins include antibodies, which attempt to neutralize the new object and send out a signal that calls other immune cells to the site to strengthen the attack. Early-responding inflammatory cells, like neutrophils and macrophages, respond to the emergency call. The needle of the pump is labeled as foreign object and attacked with tiny grains that are filled with enzymes, they try t deteriorate the surface of the insulin pump's needle. Macrophages secrete enzymes too, together with nitric oxide radicals, which create a chemical reaction that degrades the object over time. If the macrophages are unable to dispatch the foreign body rapidly, they fuse together, forming a mass of cells called a “giant cell.” At the same time, cells called fibroblasts travel to the site and begin to deposit layers of dense connective tissue. Those enclose the needle that the pump uses to deliver insulin and test for glucose levels. Over time this scaffolding builds up, forming a scar around the implant. The scar functions as an almost impenetrable wall that might start to block vital interactions between the body and the implant. For example, scarring around pacemakers (an electrically charged medical device to control heartbeat) can interrupt the electrical transmission that's crucial for their functioning. With time due to stress and workload, Synthetic knee joints might give out particles that trigger immune cells to come into action and inflame around these fragments. Unfortunately the work of immune system attack might sometime be fatal and endanger life. Research work is underway to trick the immune system into accepting the new devices that are introduced into our bodily tissues. There are implants coated with certain chemicals and drugs that somewhat downplay the response of immune system. Those basically make the implants invisible to the immune system. More implants are being made out of natural materials and in forms that directly mimic issues, so that the body launches a weaker attack than it would if it came across a completely artificial implant. Some medical treatments involve implants designed to regenerate lost or damaged tissues. In those cases, the implant is designed to contain ingredients that will release specific signals, and carefully tailor to bodies' immune reactions. In the future, this way of working alongside the immune system could help develop completely artificial organs, totally integrative prostheses, and self-healing wound therapies. These treatments might one day revolutionize medicine and transform, forever, thebodies we live in.

Fully Steerable Symmetric Thermoplasmonic Microswimmers.

A cornerstone of the directed motion of microscopic self-propelling particles is an asymmetric particle structure defining a polarity axis along which these tiny machines move. This structural asymmetry ties the orientational Brownian motion to the microswimmers directional motion, limiting their persistence and making the long time motion effectively diffusive. Here, we demonstrate a completely symmetric thermoplasmonic microswimmer, which is propelled by laser-induced self-thermophoresis. The propulsion direction is imprinted externally to the particle by the heating laser position. The orientational Brownian motion, thus, becomes irrelevant for the propulsion, allowing enhanced control over the particles dynamics with almost arbitrary steering capability. We characterize the particle motion in experiments and simulations and also theoretically. The analysis reveals additional noise appearing in these systems, which is conjectured to be relevant for biological systems. Our experimental results show that even very small particles can be precisely controlled, enabling more advanced applications of these micromachines.

Interactions between Biomedical Micro-/Nano-Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities.

Mobile micro- and nano-motors (MNMs) emerge as revolutionary platforms for biomedical applications, including drug delivery, biosensing, non-invasive surgery, and cancer therapy. While for applications in biomedical fields and practical clinical translation, the interactions of these untethered tiny machines with the immune system is an essential issue to be considered. This review highlights the recent approaches of surpassing immune barriers to prevent foreign motors from triggering immune responses. In addition to trials focusing on the function preservation of MNMs, examples of versatile MNMs working with the immune components (immune molecules, immune cells and the whole system) to achieve cancer immunotherapy, immunoassay, and detoxification are outlined. The immune interference part provides researchers an idea about what is the limit presented by the immune components. The coworking part suggests ways to bypass or even utilize the limit. With interdisciplinary cooperation of nanoengineering, materials science, and immunology field, the rationally designed functional MNMs are expected to provide novel opportunities for the biomedical field.

External Power-Driven Microrobotic Swarm: From Fundamental Understanding to Imaging-Guided Delivery.

Untethered micro/nanorobots have been widely investigated owing to their potential in performing various tasks in different environments. The significant progress in this emerging interdisciplinary field has benefited from the distinctive features of those tiny active agents, such as wireless actuation, navigation under feedback control, and targeted delivery of small-scale objects. In recent studies, collective behaviors of these tiny machines have received tremendous attention because swarming agents can enhance the delivery capability and adaptability in complex environments and the contrast of medical imaging, thus benefiting the imaging-guided navigation and delivery. In this review, we summarize the recent research efforts on investigating collective behaviors of external power-driven micro/nanorobots, including the fundamental understanding of swarm formation, navigation, and pattern transformation. The fundamental understanding of swarming tiny machines provides the foundation for targeted delivery. We also summarize the swarm localization using different imaging techniques, including the imaging-guided delivery in biological environments. By highlighting the critical steps from understanding the fundamental interactions during swarm control to swarm localization and imaging-guided delivery applications, we envision that the microrobotic swarm provides a promising tool for delivering agents in an active, controlled manner.

Scalable and integrated flow synthesis of triple-responsive nano-motors via microfluidic Pickering emulsification

Artificial micro-/nano-motors are tiny machines as newly emerging tools capable of achieving numerous tasks. In principle, the self-phoretic motions require asymmetric structures in geometry and chemistry. However, conventional production techniques suffered from complex and time consuming multi-step process in low uniformity, and difficult to endow multi-functions into motors. This work disclosed a continuous-flow synthesis of triple-responsive (thermophoretic, chemical and magnetic movement) nano-motors (m-SiO2/Fe3O4-Pdop/Pt) via microfluidic Pickering emulsification in a process of integrated and scalable manner. The droplet microfluidic process allows efficient self-assembly of the silica nanoparticles surrounding the spherical interface of resin droplet, rendering excellent Pickering efficiency and reproducibility, and followed by anisotropic decoration of polydopamine (Pdop) and Pt catalyst in a serial flow process. The obtained Janus nanoparticles reveal double- or triple-responsive self-propulsions with synergic mobility by combining thermophoresis powered by light, catalytic driven motion in H2O2 or magnetic movement by magnet. Further, a non-metallic polydopamine based thermophoretic motion as well as an automated nano-cleaner for rapid water purification by dye removal are convincingly functioned. Finally, this novel integrated flow strategy proves a scalable manufacturing production (> 0.7 g hr−1) of the nano-motors using inexpensive single microreactor, fulfilling quantitative and qualitative needs for versatile applications.

Microscopic robot takes its first steps

have the potential to explore worlds too small to see with the human eye. But making tiny machines that combine moving parts with onboard electronics has been a significant challenge. Researchers a...

Ultrasound Imaging and Tracking of Micro/Nanorobots: From Individual to Collectives

The rapid development of untethered micro/nanorobots enables them to be applied in biomedical tasks, such as targeted delivery, localized diagnostics, and minimally invasive surgery. However, many challenges remain before applying these tiny machines to perform therapeutics and intervention in a living body. Among them, one critical issue is the integration of medical imaging systems with micro/nanorobotics to acquire precise feedback in vivo . Ultrasound imaging, as one of the widely used mature imaging technologies, shows great potential for providing real-time feedback of micro/nanorobots in 2-D and 3-D space. In this mini-review, the recent progress and challenges on the imaging and tracking of micro/nanorobots using established medical ultrasound imaging technologies are surveyed and summarized. The limitations together with future research opportunities in the real-time navigation of micro/nanorobots in vivo and their collectives are discussed.

Shape-morphing microbots take wing

Researchers have made tiny shape-shifting machines that morph into different forms one after another in response to magnetic fields (Nature 2019, DOI: 10.1038/s41586-019-1713-2). This sophisticated...

Mimicking Sub-Structures Self-Organization in Microtubules.

Microtubules (MTs) are highly dynamic polymers distributed in the cytoplasm of a biological cell. Alpha and beta globular proteins constituting the heterodimer building blocks combine to form these tubules through polymerization, controlled by the concentration of Guanosine-triphosphate (GTPs) and other Microtubule Associated Proteins (MAPs). MTs play a crucial role in many intracellular processes, predominantly in mitosis, organelle transport and cell locomotion. Current research in this area is focused on understanding the exclusive behaviors of self-organization and their association with different MAPs through organized laboratory experiments. However, the intriguing intelligence behind these tiny machines resulting in complex self-organizing structures is mostly unexplored. In this study, we propose a novel swarm engineering framework in modeling rules for these systems, by combining the principles of design with swarm intelligence. The proposed framework was simulated on a game engine and these simulations demonstrated self-organization of rings and protofilaments in MTs. Analytics from these simulations assisted in understanding the influence of GTPs on protofilament formation. Also, results showed that the population density of GTPs rather than their bonding probabilities played a crucial role in polymerization in forming microtubule substructures.