Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications.

Independent control of microrobots is a cardinal challenge for manipulation at micro/nano scale. In this paper, we design and assemble an electromagnetic setup to overcome some of the major obstacles in the independent control of microrobots. The demanding magnetic requirements are met by the presented experimental testbed that is able to produce magnetic fields and gradients of, respectively, 160 mT and 3.6 T/m at the center of the workspace. Through the design process of this testbed, we analyze the importance of design parameters and derive a quantitative analysis of the requirements for the dissipation of the generated heat. Further, we present and develop the model and software infrastructure, capable of running at 25 Hz, necessary for independent control of multiple microrobots. We also introduce two novel techniques for current-minimizing mapping of the desired forces into currents at the electromagnet. Finally, the capabilities of the setup are demonstrated through independent control of two, both identical and nonidentical, soft-magnetic microspheres in three-dimensional space-with average root mean square errors of 102 µm and peak velocities of up to 331 µm/s.

Ultrasound B-mode imaging has been employed to monitor single agents and collective swarms of microrobots in-vitro and ex-vivo, in controlled experimental conditions. However, low contrast and spatial resolution still limit the effective employment of such method in a medical microrobotic scenario. Dopplerbased ultrasound appears as a promising tool for tracking microrobots in echogenic and dynamic environments as biological tissues. In this letter we demonstrate that microrobot displacements can be used as a special signature for their visualization within echogenic media, where B-mode fails. To this aim, we induced vibrations of a magnetic soft microrobot through alternated magnetic fields and used ultrasound phase analysis to derive microrobot features such as size and position over time. By exploiting vibrations, we were able to perform imaging and tracking of a low contrast microrobot both in tissuemimicking phantom and in chicken breast. Axial resolution was 38µm, that is four times smaller than the B-mode resolution with the employed equipment. We also performed real-time tracking of the microrobot's positions along linear trajectories with a linear velocity up to 1mm/s. Overall, the reported results pave the way to the application of the proposed approach for the robust monitoring of medical microrobots in tissue.

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.

Microrobots (MRs) have attracted significant interest for their potentialities in diagnosis and non-invasive intervention in hard-to-reach body areas. Fine control of biomedical MRs requires real-time feedback on their position and configuration. Ultrasound (US) imaging stands as a mature and advantageous technology for MRs tracking, but it suffers from disturbances due to low contrast resolution. To overcome these limitations and make US imaging suitable for monitoring and tracking MRs, we propose a US contrast enhancement mechanism for MR visualization in echogenic backgrounds (e.g., tissue). Our technique exploits the specific acoustic phase modulation produced by the MR characteristic motions. By applying this principle, we performed real-time visualization and position tracking of a magnetic MR rolling on a lumen boundary, both in static flow and opposing flow conditions, with an average error of 0.25 body-lengths. Overall, the reported results unveil countless possibilities to exploit the proposed approach as a robust feedback strategy for monitoring and tracking biomedical MRs in-vivo.