Mattia Dimitri

Purpose: Dynamic hand splints are rehabilitation orthoses equipped with elastic bands/springs that provide passive resistance to finger movements. To enable real-time controllability of rehabilitative exercises and potentially improve therapeutic outcomes, it would be advantageous to replace the elastic components with soft actuators, enabling finger movements to be exercised against controllable loads. The ideal soft actuators for dynamic hand splints should generate large displacements at moderate forces, have a compact size and low specific weight, and be electrically safe. Methods: Here, we describe a dynamic splint embedded with soft pneumatic actuators functioning as “inverse artificial muscles”, which elongate when pressurised, reducing the force that resists finger flexions. A prototype system was assembled using off-the-shelf materials. An actuator was fabricated and mounted on a forearm brace, connecting one extremity to a finger via a tendon and the other one to an onboard load cell, to monitor the force exerted during finger motions. The system was tested via two psychophysical tests. Results: A dynamic psychophysical test on perceptual differences in force demonstrated that subjects were able to reliably perceive force variations, with a sensitivity (slope of the psychometric curve) of ~ 110%/bar at 50% probability. In a static psychophysical test with a fully flexed finger, the maximum average force was ~ 5.2 N at 0 bar, whilst the minimum average force when subjects reported no perception of force, by progressively increasing the pressure, was as low as ~ 0.7 N at 3 bar, indicating good accuracy of the system. Conclusion: The developed active splint has the potential to enable dynamically controllable hand rehabilitation tasks.

Microwave (MW) ablation is a minimally invasive technique used to destroy pathological tissues through localized heating generated by a needle applicator. Internally cooled applicators using water circulation have long been the standard for high-power applications; however, water cooling introduces significant mechanical complexity. This work investigates the feasibility of a novel air-cooled coaxial thermal-ablation needle operating at 2.45 GHz up to 70 W. The system uses two concentric metal tubes—an outer 14 G stainless steel shaft (OD 2.1 mm) and an inner copper capillary (OD 1 mm, ID 0.7 mm)—serving simultaneously as the MW transmission line and cooling conduit, with dry air at room temperature (25 °C) flowing at 11 L/min under 5 bar input pressure. Experimental cooling efficiency tests demonstrated 78% efficiency for the shaft section in air and 32% for the section embedded in tissue. Electromagnetic and thermal simulations predicted ablation dimensions in a non-perfused liver of 35 mm short axis with ellipticity of 0.65 for the basic applicator, improving to 0.88 with an advanced PEEK-shaft design featuring a cancelling slot. A prototype was built and tested on exvivo bovine liver, achieving input matching better than −24 dB at 2.44 GHz and ablation dimensions (average of 5 tests) of 31 mm short axis and 45 mm long axis. Results confirm the feasibility of air cooling as a simpler, safer, and lower-cost alternative to water cooling for medium-power MW ablation.

This study investigates the impact of low-intensity continuous ultrasound (LICU) on pancreatic adenocarcinoma (PANC-1) spheroids, emphasizing morphological and volumetric transformations. PANC-1 spheroids were cultured and treated with LICU across frequencies from 1 to 5 MHz. Cell viability and mortality were analyzed through Calcein AM/PI staining, while volumetric and morphological changes were quantified across frequencies from 2 to 4 MHz using advanced imaging techniques and computational tools, including a custom Python OpenCv Library, AnaSP 3.0, a MATLAB based open source tool. Notably, a frequency of 3.5 MHz yielded optimal outcomes, also achieving a reduction in spheroid volume and mortality while minimizing disgregation, a factor linked to metastasis risk. These findings underscore LICU’s potential as an effective therapeutic strategy, balancing tumor reduction with the preservation of structural cohesion. The study establishes a methodological framework for optimizing LICU parameters, presenting a less invasive avenue for improving therapeutic outcomes in pancreatic cancer treatment.

Goal: Organ perfusion is a vast subject with several techniques, the most common being Hypothermic Machine Perfusion (HMP) and Normothermic Machine Perfusion (NMP). In this paper, a new machine developed at the Biolab of the University of Florence has been tested to validate its capability to perform a well-controlled Oxygenated Rewarming (COR) phase and maintain stability during the NMP phase. Methods: The tests (n = 5) were conducted on fresh porcine livers and evaluated according to liver perfusion standards. The developed machine is based on a previous version, with an integrated control and sensor system and a complete mechanical and electronic redesign. Results: The results demonstrate the excellent usability of the machine and its ability to effectively maintain the organs in good condition. The new system performed well, and the measures made on the livers were satisfactory for good preservation of the organ. Conclusion: This study showed the effectiveness of the developed machine. Future development of the system will include a more sophisticated control system to ensure the correct parameters for perfusion.

Sonoporation has garnered significant attention for its potential to temporarily permeabilize cell membranes through the application of ultrasound waves, thus enabling an efficient cellular uptake of molecules. Despite its promising applications, the precise control of sonoporation remains a complex and evolving challenge in the field of cellular and molecular biology. This review aims to address two key aspects central to advancing our understanding of sonoporation. Firstly, it underscores the necessity for the establishment of a standardized methodology to validate and quantify the successful entry of molecules into target cells. This entails a critical examination of existing techniques and the identification of best practices to ensure accurate, reliable, and reproducible results. By establishing a common framework for assessing sonoporation outcomes, researchers can enhance the reliability and comparability of their experiments, paving the way for more robust findings. Secondly, the review places particular emphasis on the detailed analysis of various acoustic parameters as reported in the papers selected from the literature. Among these parameters, acoustic intensity (specifically, ISPTA) emerges as a pivotal factor in sonoporation studies. Furthermore, this review delves into the exploration of the elastic modulus and its significance in sonoporation mechanisms and associated challenges. This knowledge can inform the development of more effective strategies to optimize sonoporation protocols. In summary, this review not only highlights the pressing need for a standardized approach to verify molecule entry into cells but also delves into the search for an effective frequency and acoustic intensity for in vivo and in vitro applications.

Current developments in medical technology have focused on therapeutic treatments that selectively and effectively address specific pathological areas, minimizing side effects on healthy tissues. In this regard, many procedures have been developed to provide non-invasive therapy, for example therapeutic ultrasound (US). In the medical field, in particular in cancer research, it has been observed how ultrasounds can cause cell death and inhibit cell proliferation of cancer cells, while preserving healthy ones with almost negligible side effects. Various studies have shown that low intensity pulse ultrasound (LIPUS) and low intensity continuous ultrasound (LICUS) regulate the proliferation, cell differentiation and cavitation phenomena. Nowadays, there are poorly known aspects of low intensity US treatment, in terms of biophysical and biomechanical effects on target cells. The aim of this study is to set up an innovative apparatus for US treatment of pancreatic ductal adenocarcinoma (PDAC) cells, monitoring parameters such as acoustic intensity, acoustic pressure, stimulation frequency and treatment protocol. To this purpose, we have developed a custom-made set up for the US stimulation at 1.2 and 3 MHz of tridimensional (3D) cultures of PDAC cells (PANC-1, Mia Paca-2 and BxPc3 cells). Images of the 3D cultures were acquired, and the Calcein/PI assay was applied to detect US-induced cell death. Overall, the setup we have presented paves the way to an innovative protocol for tumor treatment. The system can be used either alone or in combination with small molecules or recombinant antibodies in order to propose a novel combined therapeutic approach.

Introduction: During the last two decades, many surgical procedures have evolved from open surgery to minimally invasive surgery (MIS). This limited invasiveness has motivated the development of robotic assistance platforms to obtain better surgical outcomes. Nowadays, the da Vinci robot is a commercial tele-robotic platform widely used for different surgical applications. Material and methods: In this work, the da Vinci Research Kit (dVRK), namely the research version of the da Vinci, is used to manipulate a novel microwave device in a teleoperation scenario. The dVRK provides an open source platform, so that the novel microwave tool, dedicated to prevention bleeding during hepatic resection surgery, is mechanically integrated on the slave side, while the software interface is adapted in order to correctly control tool pose. Tool integration is validated through in-vitro and ex-vivo tests performed by expert surgeons, meanwhile the coagulative efficacy of the developed tool in a perfused liver model was proved in in-vivo tests. Results and conclusions: An innovative microwave tool for liver robotic resection has been realized and integrated into a surgical robot. The tool can be easily operated through the dVRK without limiting the intuitive and friendly use, and thus easily reaching the hemostasis of vessels.

Ex vivo testing is a fundamental step in the development of new medical devices; indeed without it, it is impossible to proceed with in vivo tests. At the University of Florence, a robotic tool for microwave thermal ablation is under development. Up to now, the thermoablation tests for the validation of the tool were carried out on non-perfused ex vivo livers, providing results that inevitably differ from those obtainable with an in vivo liver. The aim is to design, and consequently create, a compact and transportable system which allows to perfuse a swine liver with physiological solution and heparin. This device should also allow the organ to be transported from the explantation place to the laboratory, keeping it under normothermal condition. The perfusor was designed to simulate the physiological flow within the liver in the most realistic way possible. The design, construction, and optimization of the perfusor have been addressed using the physiological values of hepatic flow and pressure identified in the literature, neglecting in the first instance any load losses. Therefore, open circuit tests were conducted, validated through perfusion tests on freshly explanted pig liver; during these tests, the surface temperature of the organ was recorded using an infrared camera, and the fluid temperature was verified using an immersion probe. The perfusion test showed a good alignment with the open circuit tests, demonstrating the validity of the simplifications adopted to treat the complex vascular structure of the liver.

Purpose: Bleeding from parenchyma transection during a robotic hepatic surgery remains the most critical point affecting postoperative recovery and long-term survival. Various robotic devices with different types of energies have been proposed; however, each of these lack in steerability, efficacy, or accuracy. The aim of this work is to evaluate the feasibility and performance of a new steerable microwave resection device intended for minimizing intraoperative blood loss during laparoscopic and robotic liver resections. Methods: The new device operating at 2.45 GHz was designed to accommodate the engineering constraints derived from its use for robotic surgery or laparoscopy, in which a steerable head is required and the internal cooling of forced gas or water is undesirable. The device design, analysis, and optimization were addressed using the most advanced commercial electromagnetic and thermal solvers to achieve the best results. To experimentally validate the results of the numerical analysis, many ablations were performed on a freshly explanted bovine liver by using a single device prototype with three levels of energy supplied to the tissue. During the ablation procedures, the time, temperature, and shape of the thermal lesion were recorded using thermocouples and an infra-red thermos camera. Summary: Ex vivo tests showed good agreement with the numerical simulations, demonstrating the validity of the simplifications adopted to deal with the complex phenomena involved in the extreme hyperthermia of a living tissue. The high performance, thermal reliability, and robustness of the developed device were also demonstrated along with the possibility of reducing operation time and blood loss.