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Magnetic swArms for liver chemoeMBOlization

Periodic Reporting for period 2 - MAMBO (Magnetic swArms for liver chemoeMBOlization)

Reporting period: 2022-09-01 to 2023-08-31

MAMBO aims at enforcing the employment of robotic technologies in the field of medicine, towards the development of robotically-enabled high efficiency therapeutic strategies and towards the strengthening of the EU leadership in this field. Cancer is one of the three main causes of mortality worldwide and current therapeutic approaches produce severe side-effects or incomplete eradication. Controverting the standard paradigms by penetrating into the hard-to-reach areas of the human body and selectively performing therapy in a controllable fashion appears as the holy grail in cancer treatment. Untethered microrobots wirelessly activated through magnetic fields could help in this direction. However, before any microrobot-based therapeutic paradigm can reach the clinical practice, several challenges still need to be faced.
MAMBO (Magnetic swArms for liver chemoeMBOlization) proposes the use of swarms of drug-loaded, US-responsive, magnetic microrobots for targeted liver chemoembolization. The proposal stems from the idea to improve cancer chemotherapy and existing chemoembolization procedures by using magnetic forces to collect chemotherapeutics in the target region (through swarm control methods) and to controllably and stably embolize tumor blood vessels. Drug loaded soft magnetic microrobots featured by responsiveness to ultrasound are being developed to this aim. The responsivity to US enables microrobot swelling and controlled vessel occlusion and at the same time allows their ultrasound-based imaging to guarantee their tracking in vivo. Magnetic swarm control techniques are employed to enable microrobots locomotion in biologically-relevant fluids. US-mediated phase transition mechanisms is employed to trigger embolization and drug release, whereas advanced ultrasound imaging techniques will be employed during the overall procedure to enable sub-resolution tracking of the swarm and performances evaluation (Figure 1).
MAMBO aims to train the proponent for developing novel technologies to enable the employment of swarms of magnetic, echogenic drug-loaded microrobots for optimized chemoembolization. To accomplish this goal, three sub-objectives were identified:
- Development of the multifunctional magnetic microrobots. They should (i) present swarm behavior, (ii) swell on demand to enable vessel embolization, (iii) encapsulate and release drugs and (iv) enable ultrasound-based imaging.
- Magnetic swarm control strategy compatible with navigation in the blood to enable target blood vessels reaching and in situ accumulation.
- Ultrasound based imaging of the microrobots swarm to monitor its action.
During the 36 months of the project, corresponding to the Outgoing phase taking place at the Chinese University of Hong Kong and Return Phase at Scuola Superiore Sant’Anna, key research and training steps were carried out to accomplish MAMBO objectives.
As a first step, the fabrication process allowing to obtain microrobots responsive to Ultrasound and Magnetic Fields was engineered and optimized. Modulating magnetic fields allows to control swarms of microrobots towards the target location. The results accomplished in terms of microrobots fabrication, US stimulation and swarm control are extremely encouraging and represent an important milestone with respect on the state of the art.
In parallel, together with colleagues both at the Host and Partner Institution, I’ve been working on the development of new methods for optimized US-based imaging at small-scales. Indeed, traditional US-based imaging (typically defined ad B-mode) features non-sufficient spatial resolution and fails in allowing microrobots imaging in tissue-mimicking environment. To overcome this limitation, we developed (and published models, methods and results) a new imaging method based on US signals phase analysis. This method allows to exploit microrobot motion as specific signatures for their detection thus being independent from the contrast of the working environment and as a consequence extremely efficient in soft tissues. By exploiting such method, we demonstrated the possibility to monitor vibrating, rolling and bacteria-like microrobots and to use this type of imaging feedback for closed-loop microrobots magnetic control. The use of artificial intelligence has also allowed to enhance imaging and tracking performance by leveraging on anatomical information and making the developed methods closed to real medical applications.
The results accomplished led to several publications (seven journals papers accepted, one submitted). Furthermore, the results accomplished were also disseminated through talks (1 plenary, 1 keynote and 4 invited talks, 1 invited lecture) I gave in relevant International Conferences and Research Institutes.
The results obtained in the framework of the Action are well beyond the state of the art, both in terms of multifunctional microrobots fabrication and in terms of imaging at small scales.
In the last 12 months of the project, the results obtained in the Outgoing phase were consolidated by focusing on furtherly characterizing microrobots US-induced volumetric transition and in enhancing their Ultrasound-based imaging and tracking.
Through numerous publications, conference presentations and the management of projects and students, I have demonstrated a high level of professional maturity as a researcher. With the MAMBO project I had the chance to enrich my background with swarm control and imaging skills thus completing the set of competences useful to identify and conceive new therapeutic solutions based on microrobots. Furthermore, the possibility to work abroad for two years in a completely different environment, has significantly strengthened my capability to work in an international environment and deepen my experience in project management.
In particular, I think that the skills acquired in terms of magnetic control and imaging in the framework of the MAMBO project will have a main impact for two main reasons: first because they represent transversal competences to enable robot-assisted interventional/medical procedures; second because they will reveal themselves extremely important to steer future research lines and to train/supervise students at different levels.
MAMBO also played a significant impact on my career by allowing me to be appointed as a Tenure Track Assistant Professor at Scuola Superiore Sant’Anna where I will start my own research Group and keep working in the field of microrobotics.
In addition to the impact on my academic career, MAMBO results could significantly impact the society. Based on cancer epidemiology and on the limitations of available therapeutic strategies, it is almost straightforward to identify the potential impact that micro-technologies for targeted therapy will have in the ageing European society. In this sense, MAMBO results prove an important starting point to support the employment of microrobots in the clinical practice.
The results obtained look promising both overall – with the final application in mind – and in terms of technological blocks developed and physical principle exploited. They all pave the way to a more established research field where I will keep being active and also, in the future, to the clinical and industrial exploitation of micro-technologies in medicine.
MAMBO concept overview