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Scientists around the world have long aimed to produce miniature robots that can be controlled inside the human body to aid doctors in identifying and treating diseases. Such microrobots hold the potential to access hard-to-reach areas of the body through the natural lumina. Wireless access has the potential to overcome drawbacks of systemic therapy, as well as to enable completely new minimally invasive procedures. The aim of this review is fourfold: first, to provide a collection of valuable anatomical and physiological information on the target working environments together with engineering tools for the design of medical microrobots; second, to provide a comprehensive updated survey of the technological state of the art in relevant classes of medical microrobots; third, to analyze currently available tracking and closed-loop control strategies compatible with the in-body environment; and fourth, to explore the challenges still in place, to steer and inspire future research. [ABSTRACT FROM AUTHOR]

Minimally invasive endovascular procedures rely heavily on catheter devices. However, traditional catheters lack active steering requiring considerable skill on the surgeon's part to accurately position the tip. While catheter tips could be made steerable using tendon-driven and Pneumatic Artificial Muscle (PAM) approaches, remote magnetic actuation is uniquely suited for this task due to its safety, controllability, and intrinsic miniaturization capabilities. Soft composite magnetic materials feature embedding distributed magnetic microparticles compared with attaching discrete permanent magnets proving beneficial in steerability and control. This work demonstrates the fabrication of a soft hollow magnetic tip that can be attached to a catheter to make the assembly steerable. The catheter tip is extensively characterized in terms of bending hysteresis, bending force, and dynamic response. The catheter showed average hysteresis between 5% and 10% and bending forces up to 0.8 N. It also showed a good dynamic response by changing its bending angle in <200 ms under a step response. [ABSTRACT FROM AUTHOR]

Soft magnetic structures having a non‐uniform magnetization profile can achieve multimodal locomotion that is helpful to operate in confined spaces. However, incorporating such magnetic anisotropy into their body is not straightforward. Existing methods are either limited in the anisotropic profiles they can achieve or too cumbersome and time‐consuming to produce. Herein, a 3D printing method allowing to incorporate magnetic anisotropy directly into the printed soft structure is demonstrated. This offers at the same time a simple and time‐efficient magnetic soft robot prototyping strategy. The proposed process involves orienting the magnetized particles in the magnetic ink used in the 3D printer by a custom electromagnetic coil system acting onto the particles while printing. The resulting structures are extensively characterized to confirm the validity of the process. The extent of orientation is determined to be between 92% and 99%. A few examples of remotely actuated small‐scale soft robots that are printed through this method are also demonstrated. Just like 3D printing gives the freedom to print a large number of variations in shapes, the proposed method also gives the freedom to incorporate an extensive range of magnetic anisotropies. [ABSTRACT FROM AUTHOR]

Microrobots (MRs) have attracted growing interest for their potentialities in diagnosis and noninvasive intervention in hard-to-reach body areas. The safe operation of biomedical MRs requires fine control capabilities, which strongly depend on precise and robust feedback about their position over time. Ultrasound acoustic phase analysis (US-APA) may allow for a reliable feedback strategy for MR imaging and tracking in tissue. In this article, we combine task-specific magnetic actuation and related US-APA motion tracking to achieve closed-loop navigation of a magnetic MR, rolling on the boundary of a lumen in a tissue-mimicking phantom. A C-arm system attached to a robotic platform is used to precisely position the magnetic actuation source and US-APA detection unit within the workspace, thus enabling MR visual-servoing. In the first place, the proposed approach allows to perform supervised localization of the MR without any a-priori knowledge of its position. After localization, a robust real-time tracking enables closed-loop MR teleoperation in the phantom lumina over a travel distance of 80 mm (145 body lengths), both in static and counter flow, thus achieving an average position tracking error of 368 micron (0.67 body lengths). For the first time, our results validate US-APA as a reliable feedback strategy for visual-servoing control of MRs in simulated in-body environment. [ABSTRACT FROM AUTHOR]

Creating fully implantable robots that replace or restore physiological processes is a great challenge in medical robotics. Restoring blood glucose homeostasis in patients with type 1 diabetes is particularly interesting in this sense. Intraperitoneal insulin delivery could revolutionize type 1 diabetes treatment. At present, the intraperitoneal route is little used because it relies on accessing ports connecting intraperitoneal catheters to external reservoirs. Drug-loaded pills transported across the digestive system to refill an implantable reservoir in a minimally invasive fashion could open new possibilities in intraperitoneal delivery. Here, we describe PILLSID (PILl-refiLled implanted System for Intraperitoneal Delivery), a fully implantable robotic device refillable through ingestible magnetic pills carrying drugs. Once refilled, the device acts as a programmable microinfusion system for precise intraperitoneal delivery. The robotic device is grounded on a combination of magnetic switchable components, miniaturized mechatronic elements, a wireless powering system, and a control unit to implement the refilling and control the infusion processes. In this study, we describe the PILLSID prototyping. The device key blocks are validated as single components and within the integrated device at the preclinical level. We demonstrate that the refilling mechanism works efficiently in vivo and that the blood glucose level can be safely regulated in diabetic swine. The device weights 165 grams and is 78 millimeters by 63 millimeters by 35 millimeters, comparable with commercial implantable devices yet overcoming the urgent critical issues related to reservoir refilling and powering. [ABSTRACT FROM AUTHOR]

Substituting the natural bladder with an artificial solution, after cancer and other pathologies, is an ambitious challenge in biomedical engineering. In this work we propose a fully implantable smart artificial bladder system (ABS) that collects urinary fluids and provides the subject with real-time feedback on the implant status. To achieve long term duration, the ABS was designed to be unstretchable in order to be treated with urine resistant coatings and included built-in passive check valves preventing reflux to kidneys. To estimate the amount of fluid collected, the ABS was provided with four electromagnetic distance sensing units and a control unit. An algorithm implemented on an embedded controller enabled the reconstruction of the bladder volume through sensors readings. A wireless data transfer system allows for providing a real-time feedback to the subject. Bench tests validated volume reconstruction accuracy and ex-vivo experiments verified the implantability of the proposed device on a human cadaver, proving the reliability of a Bluetooth data transmission system and paving the way towards an in-body/out-body communication. The proposed solution has the potential to overcome the limitations of currently available replacement strategies towards a new generation of implantable devices for lost organ functions replacement. [ABSTRACT FROM AUTHOR]

In recent years, magnetism has gained an enormous amount of interest among researchers for actuating different sizes and types of bio/soft robots, which can be via an electromagnetic‐coil system, or a system of moving permanent magnets. Different actuation strategies are used in robots with magnetic actuation having a number of advantages in possible realization of microscale robots such as bioinspired microrobots, tetherless microrobots, cellular microrobots, or even normal size soft robots such as electromagnetic soft robots and medical robots. This review provides a summary of recent research in magnetically actuated bio/soft robots, discussing fabrication processes and actuation methods together with relevant applications in biomedical area and discusses future prospects of this way of actuation for possible improvements in performance of different types of bio/soft robots. [ABSTRACT FROM AUTHOR]

Abstract: The clinical adoption of nanoscale agents for targeted therapy is still hampered by the quest for a balance between therapy efficacy and side effects on healthy tissues, due to nanoparticle biodistribution and undesired drug accumulation issues. Here, an intravascular catheter able to efficiently retrieve from the bloodstream magnetic nanocarriers not contributing to therapy, thus minimizing their uncontrollable dispersion and consequently attenuating possible side effects, is proposed. The device consists of a miniature module, based on 27 permanent magnets arranged in two coaxial series, integrated into a clinically used 12 French catheter. This device can capture ≈94% and 78% of the unused agents when using as carriers 500 and 250 nm nominal diameter superparamagnetic iron oxide nanoparticles, respectively. This approach paves the way to the exploitation of new “high‐risk/high‐gain” drug formulations and supports the development of novel therapeutic strategies based on magnetic hyperthermia or magnetic microrobots. [ABSTRACT FROM AUTHOR]

The bioartificial pancreas (BAP) represents a viable solution for the treatment of type 1 diabetes (T1D). By encapsulating pancreatic cells in a semipermeable membrane to allow nutrient, insulin and glucose exchange, the side effects produced by islets and whole organ transplantation-related immunosuppressive therapy can be circumvented. Several factors, mainly related to materials properties, capsule morphology and biological environment, play a key role in optimizing BAP systems. The BAP is an extremely complex delivery system for insulin. Despite considerable efforts, in some instances meeting with limited degree of success, a BAP capable of restoring physiological pancreas functions without the need for immunosuppressive drugs and of controlling blood glucose levels especially in large animal models and a few clinical trials, does not exist. The state of the art in terms of materials, fabrication techniques and cell sources, as well as the current status of commercial devices and clinical trials, are described in this overview from an interdisciplinary viewpoint. In addition, challenges to the creation of effective BAP systems are highlighted including future perspectives in terms of component integration from both a biological and an engineering viewpoint. [ABSTRACT FROM AUTHOR]

The aim of this study is to contribute to the advancement of the mechatronic implantable artificial organs field by demonstrating the feasibility of a mechatronic refilling module to be used with implantable artificial organs (and particularly suitable for an artificial pancreas), and permitting a completely noninvasive refilling procedure without the need for dedicated surgical interventions. We described a refilling module, chronically interfaced with the duodenum wall, based on a magnetic switchable device, and able to reversibly dock an ingestible insulin carrier, whenever required. The capsule was provided with sensors in order to reveal its approach. A punching system was also developed with the aim of assuring a safe transfer of the insulin from the capsule to an implanted reservoir. The key components of the system were developed and tested. Finally, they were integrated in a preliminary prototype. [ABSTRACT FROM PUBLISHER]

Flexible colonoscopy remains the prime mean of screening for colorectal cancer (CRC) and the gold standard of all population-based screening pathways around the world. Almost 60% of CRC deaths could be prevented with screening. However, colonoscopy attendance rates are affected by discomfort, fear of pain and embarrassment or loss of control during the procedure. Moreover, the emergence and global thread of new communicable diseases might seriously affect the functioning of contemporary centres performing gastrointestinal endoscopy. Innovative solutions are needed: artificial intelligence (AI) and physical robotics will drastically contribute for the future of the healthcare services. The translation of robotic technologies from traditional surgery to minimally invasive endoscopic interventions is an emerging field, mainly challenged by the tough requirements for miniaturization. Pioneering approaches for robotic colonoscopy have been reported in the nineties, with the appearance of inchworm-like devices. Since then, robotic colonoscopes with assistive functionalities have become commercially available. Research prototypes promise enhanced accessibility and flexibility for future therapeutic interventions, even via autonomous or robotic-assisted agents, such as robotic capsules. Furthermore, the pairing of such endoscopic systems with AI-enabled image analysis and recognition methods promises enhanced diagnostic yield. By assembling a multidisciplinary team of engineers and endoscopists, the paper aims to provide a contemporary and highly-pictorial critical review for robotic colonoscopes, hence providing clinicians and researchers with a glimpse of the major changes and challenges that lie ahead. [ABSTRACT FROM AUTHOR]

Over the past decade, there has been a growing interest in the development of an artificial pancreas for intraperitoneal insulin delivery. Intraperitoneal implantable pumps guarantee more physiological glycemic control than subcutaneous wearable ones, for the treatment of type 1 diabetes. In this work, a fully implantable artificial pancreas refillable by ingestible pills is presented. In particular, solutions enabling the communication between the implanted pump and external user interfaces and novel control algorithms to intraperitoneally release an adequate amount of insulin based on glycemic data are shown. In addition, the powering and the wireless battery recharging are addressed. Specifically, the design and optimization of a customized transcutaneous energy transfer with two independent wireless channels are presented. The system was tested in terms of recharging efficacy, possible temperature rise within the body, during the recharging process and reliability of the wireless connection in the air and in the presence of ex vivo tissues.Clinical Relevance- This work aims to improve the control, battery recharging, and wireless communication of a fully implantable artificial pancreas for type 1 diabetes treatment.

Octopus suckers that possess the ability to actively control adhesion through muscle actuation have inspired artificial adhesives for safe manipulation of thin and delicate objects. However, the design of adhesives with fast adhesion switching speed to transport cargoes in confined spaces remains an open challenge. Here, we present an untethered magnetic adhesive pad combining the functionality of fast adhesion switching and remotely controlled locomotion. The adhesive pad can be activated from low-adhesion state to high-adhesion state by near infrared laser within 30 s, allowing to fulfill a high-throughput task of retrieving and releasing objects. Moreover, under the guidance of external magnetic field, the proposed pad is demonstrated to transport thin and fragile electronic components across a tortuous path, thus indicating its potential for dexterous delivery in complex working environments., (© 2021 IOP Publishing Ltd.)

The invertebrates ability to adapt to the environment during motion represents an intriguing feature to inspire robotic systems. We analysed the sipunculid species Phascolosoma stephensoni (Sipunculidae, Annelida), and quantitatively studied the motion behaviour of this unsegmented worm. The hydrostatic skeleton and the muscle activity make the infaunal P . stephensoni able to extrude part of its body (the introvert) from its burrow to explore the environment by remaining hidden within the rocky substrate where it settled. The introvert protrusion is associated with changes in the body shape while keeping the overall volume constant. In this study, we employed a marker-less optical tracking strategy to quantitatively study introvert protrusion (i.e. kinematics, elongation percentage and forces exerted) in different navigation media. When P . stephensoni specimens were free in sea water (outside from the burrow), the worms reached lengths up to three times their initial ones after protrusion. Moreover, they were able to elongate their introvert inside a viscous medium such as agar-based hydrogel. In this case, the organisms were able to break the hydrogel material, exerting forces up to 3 N and then to navigate easily inside it, producing stresses of some tens of kPa. Our measurements can be used as guidelines and specifications to design and develop novel smart robotic systems., (© 2020 IOP Publishing Ltd.)

Micro dosing pumps are the beating heart of infusion systems. Among many technologies to inject micro quantities of fluids, peristaltic pumps show high precision and the possibility to not alter the fluid properties. However, in real drug delivery applications, the continuous release behavior of typical peristaltic pumps is not favorable. In this paper, we investigate the intermittent performance of two prototypes of peristaltic pumps, based on four and five rollers, used to occlude the tube. The pump performances are reported for different rotation speeds and lag times between consecutive infusions. The proposed pumps showed a good volumetric precision (2.88 μL for the five rollers pump and 4.11 μL for the four rollers pump) without any dependency on rotation speed and lag time.

Introduction: Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion., Areas Covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape., Expert Opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.