This paper presents innovative designs for 3D-printed tumbling microrobots, specifically engineered for targeted in vivo drug delivery applications. The microrobot designs, created using stereolithography 3D printing technologies, incorporate permanent micro-magnets to enable actuation via a rotating magnetic field actuator system. The experimental framework encompasses a series of locomotion characterization tests to evaluate microrobot performance under various conditions. Testing variables include variations in microrobot geometries, actuation frequencies, and environmental conditions, such as dry and wet environments, and temperature changes. The paper outlines designs for three drug loading methods, along with comprehensive assessments thermal drug release using a focused ultrasound system, as well as biocompatibility tests. Animal model testing involves tissue phantoms and in vivo rat models, ensuring a thorough evaluation of the microrobots' performance and compatibility. The results highlight the robustness and adaptability of the proposed microrobot designs, showcasing the potential for efficient and targeted in vivo drug delivery. This novel approach addresses current limitations in existing tumbling microrobot designs and paves the way for advancements in targeted drug delivery within the large intestine.

Deep Reinforcement Learning-Based Semi-Autonomous Control for Magnetic Micro-robot Navigation with Immersive Manipulation Y udong Mao, Dandan Zhang Abstract -- Magnetic micro-robots have demonstrated immense potential in biomedical applications, such as in vivo drug delivery, non-invasive diagnostics, and cell-based therapies, owing to their precise maneuverability and small size. However, current micromanipulation techniques often rely solely on a two-dimensional (2D) microscopic view as sensory feedback, while traditional control interfaces do not provide an intuitive manner for operators to manipulate micro-robots. These limitations increase the cognitive load on operators, who must interpret limited feedback and translate it into effective control actions. T o address these challenges, we propose a Deep Reinforcement Learning-Based Semi-Autonomous Control (DRL-SC) framework for magnetic micro-robot navigation in a simulated microvascular system. Our framework integrates Mixed Reality (MR) to facilitate immersive manipulation of micro-robots, thereby enhancing situational awareness and control precision. Simulation and experimental results demonstrate that our approach significantly improves navigation efficiency, reduces control errors, and enhances the overall robustness of the system in simulated microvascular environments. I NTRODUCTION Over the past few decades, significant advancements have been made in the manipulation of magnetic micro-robots, facilitating precise drug delivery [1]-[3], non-invasive diagnostics [4], and cell-based therapies [5]-[7]. Magnetic micro-robots are typically small, enabling them to navigate complex and narrow spaces within the human body in a non-contact manner [8].

Small-scale robots offer significant potential in minimally-invasive medical procedures. Due to the nature of soft biological tissues, however, robots are exposed to complex environments with various challenges in locomotion, which is essential to overcome for useful medical tasks. A single mini-robot often provides insufficient force on slippery biological surfaces to carry medical instruments, such as a fluid catheter or an electrical wire. Here, for the first time, we report a team of millirobots (TrainBot) that can generate around two times higher actuating force than a TrainBot unit by forming a convoy to collaboratively carry long and heavy cargos. The feet of each unit are optimized to increase the propulsive force around three times so that it can effectively crawl on slippery biological surfaces. A human-scale permanent magnetic set-up is developed to wirelessly actuate and control the TrainBot to transport heavy and lengthy loads through narrow biological lumens, such as the intestine and the bile duct. We demonstrate the first electrocauterization performed by the TrainBot to relieve a biliary obstruction and open a tunnel for fluid drainage and drug delivery. The developed technology sheds light on the collaborative strategy of small-scale robots for future minimally-invasive surgical procedures.

Vascular diseases such as thrombosis, atherosclerosis, and aneurysm, which can lead to blockage of blood flow or blood vessel rupture, are common and life-threatening. Conventional minimally invasive treatments utilize catheters, or long tubes, to guide small devices or therapeutic agents to targeted regions for intervention. Unfortunately, catheters suffer from difficult and unreliable navigation in narrow, winding vessels such as those found in the brain. Magnetically actuated untethered robots, which have been extensively explored as an alternative, are promising for navigation in complex vasculatures and vascular disease treatments. Most current robots, however, cannot swim against high flows or are inadequate in treating certain conditions. Here, we introduce a multifunctional and magnetically actuated milli-spinner robot for rapid navigation and performance of various treatments in complicated vasculatures. The milli-spinner, with a unique hollow structure including helical fins and slits for propulsion, generates a distinct flow field upon spinning. The milli-spinner is the fastest-ever untethered magnetic robot for movement in tubular environments, easily achieving speeds of 23 cm/s, demonstrating promise as an untethered medical device for effective navigation in blood vessels and robotic treatment of numerous vascular diseases.

Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine of Cornell University, New York, NY, USA Abstract Nanorobotics offers an emerging frontier in biomedicine, holding the potential to revolutionize diagnostic and therapeutic applications through its unique capabilities in manipulating biological systems at the nanoscale. Following PRISMA guidelines, a comprehensive literature search was conducted using IEEE Xplore and PubMed databases, resulting in the identification and analysis of a total of 414 papers. The studies were filtered to include only those that addressed both nanorobotics and direct medical applications. Our analysis traces the technology's evolution, highlighting its growing prominence in medicine as evidenced by the increasing number of publications over time. Applications ranged from targeted drug delivery and single-cell manipulation to minimally invasive surgery and biosensing. Despite the promise, limitations such as biocompatibility, precise control, and ethical concerns were also identified. This review aims to offer a thorough overview of the state of nanorobotics in medicine, drawing attention to current challenges and opportunities, and providing directions for future research in this rapidly advancing field. Introduction Nanorobotics, a field merging nanotechnology with teleoperated and autonomous robotics, presents groundbreaking solutions that are unattainable with conventional robotics. A nanorobot, also known as a nanomachine, is a miniature mechanical or electromechanical device designed to perform specific tasks at the nanoscale level [1]. Contrary to nanorobotics, nanoparticles are tiny particles with unique properties, used for applications like drug delivery. Nanorobotics involves designing molecular-scale robots for tasks such as targeted medical procedures.

In recent years, the medical industry has witnessed a growing interest in minimally invasive procedures, with magnetic microrobots emerging as a promising approach. These micro-robots possess the ability to navigate through various media, including viscoelastic and non-Newtonian fluids, enabling targeted drug delivery and medical interventions. Many current designs, inspired by micro-swimmers in biological systems like bacteria and sperm, employ a contact-based method for transporting a payload. Adhesion between the cargo and the carrier can make release at the target site problematic. In this project, our primary objective was to explore the potential of a helical micro-robot for non-contact drug or cargo delivery. We conducted a comprehensive study on the shape and geometrical parameters of the helical microrobot, specifically focusing on its capability to transport passive filaments. Based on our analysis, we propose a novel design consisting of three sections with alternating handedness, including two pulling and one pushing microhelices, to enhance the capture and transport of passive filaments in Newtonian fluids using a non-contact approach. We then simulated the process of capturing and transporting the passive filament, and tested the functionality of the newly designed micro-robot. Our findings offer valuable insights into the physics of helical micro-robots and their potential for medical procedures and drug delivery. Furthermore, the proposed non-contact method for delivering filamentous cargo could lead to the development of more efficient and effective microrobots for medical applications.

Magnetic resonance imaging (MRI)-guided robotic systems offer great potential for new minimally invasive medical tools, including MRI-powered miniature robots. By re-purposing the imaging hardware of an MRI scanner, the magnetic miniature robot could be navigated into the remote part of the patient's body without needing tethered endoscopic tools. However, the state-of-art MRI-powered magnetic miniature robots have limited functionality besides navigation. Here, we propose an MRI-powered magnetic miniature capsule robot benefiting from acoustic streaming forces generated by MRI-guided high-intensity focus ultrasound (HIFU) for controlled drug release. Our design comprises a polymer capsule shell with a submillimeter-diameter drug-release hole that captures an air bubble functioning as a stopper. We use the HIFU pulse to initiate drug release by removing the air bubble once the capsule robot reaches the target location. By controlling acoustic pressure, we also regulate the drug release rate for multiple location targeting during navigation. We demonstrated that the proposed magnetic capsule robot could travel at high speed up to 1.13 cm/s in ex vivo porcine small intestine and release drug to multiple target sites in a single operation, using a combination of MRI-powered actuation and HIFU-controlled release. The proposed MRI-guided microrobotic drug release system will greatly impact minimally invasive medical procedures by allowing on-demand targeted drug delivery.

We are living amid a technological revolution that is transforming the globe. Changes are visible in all aspects of our lives from transportation, health, and communications. As the adage states, yesterday's science fiction is today's science. We are now expanding our capabilities in every area of science, chemistry, biology, physics, and engineering. That includes heightened spae exploration, as well as building smart cities, new manufacturing hubs, and developing artificial intelligence and quantum technologies. The rapid pace of technological change is clearly visible, but much of what you may not see, the exceedingly small physical components of change called nanotechnologies, are catalyzing the revolution. While there are many nanotech uses, three areas of nanotech are paving the way to our future: Materials Science, Nanomedicine and Device Engineering.

Tiny robots that can climb slopes, move against the flow of fluids and travel over obstacles could one day deliver drugs to specific areas in the human body. A team of scientists, led by Weinberg Medical Physics in Maryland, have designed soft robots called MANiACs that are controlled by an external magnetic field to deliver medication to exact locations. Findings, published in Frontiers in Robotics and Ai, show how the MANiACs (magnetically aligned nanorods in alginate capsules) could perform as drug delivery vehicles inside parts of the human body that are hard to reach by oral or intravenous medication. This is the first study to test how microrobots perform in the central nervous system (CNS). The MANiACs' technology is reminiscent of the premise in the 1966 sci-fi film'Fantastic Voyage,' in which a group of scientists shrink a submarine and themselves to travel inside a patient's brain.

Duchenne muscular dystrophy (DMD), a rare genetic disease usually diagnosed in young boys, gradually weakens muscles across the body until the heart or lungs fail. Symptoms often show up by age 5; as the disease progresses, patients lose the ability to walk around age 12. Today, the average life expectancy for DMD patients hovers around 26. It was big news, then, when Cambridge, Massachusetts-based Sarepta Therapeutics announced in 2019 a breakthrough drug that directly targets the mutated gene responsible for DMD. The therapy uses antisense phosphorodiamidate morpholino oligomers (PMO), a large synthetic molecule that permeates the cell nucleus in order to modify the dystrophin gene, allowing for production of a key protein that is normally missing in DMD patients. It's not very good at entering cells," says Carly Schissel, a PhD candidate in MIT's Department of Chemistry. To boost delivery to the nucleus, researchers can affix cell-penetrating peptides (CPPs) to the drug, thereby helping it cross the cell and nuclear membranes to reach its target. Which peptide sequence is best for the job, however, has remained a looming question. MIT researchers have now developed a systematic approach to solving this problem by combining experimental chemistry with artificial intelligence to discover nontoxic, highly-active peptides that can be attached to PMO to aid delivery. By developing these novel sequences, they hope to rapidly accelerate the development of gene therapies for DMD and other diseases. Results of their study have now been published in the journal Nature Chemistry in a paper led by Schissel and Somesh Mohapatra, a PhD student in the MIT Department of Materials Science and Engineering, who are the lead authors. Rafael Gomez-Bombarelli, assistant professor of materials science and engineering, and Bradley Pentelute, professor of chemistry, are the paper's senior authors. Other authors include Justin Wolfe, Colin Fadzen, Kamela Bellovoda, Chia-Ling Wu, Jenna Wood, Annika Malmberg, and Andrei Loas. "Proposing new peptides with a computer is not very hard.