In this project, we will design and test a novel system for assessing pathological skeletal muscle tissue in an animal model of Duchenne Muscle Dystrophy (DMD), to be used as a biosensor for drug testing and, as a long-term application, for patients¿ diagnosis. Microwave patch antennas allow the measurement of the dielectric properties of the material under test, and the sensors based on this technology represent a novel and interesting approach for the noninvasive measurement of biological tissues¿ properties. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells; the functions of muscle stem cells, namely satellite cells, become impeded, yielding to the substitution of myotubes with non-functional fibrotic tissue. In view of this, we aim at developing a sensor able to recognize pathological muscles based on the altered ratio between muscle fibers and fibrotic tissue. To reach this goal, we will initially develop a sensor able to distinguish, in vitro, a myoblast from a fibroblastic cell line. This first step will allow us to determine the basal difference between the two main cell populations involved in DMD pathogenesis of muscle tissue in a very controlled environment, yielding a precise assessment of the sensor metrological properties before moving to animal testing. Subsequently, the proposed sensor will be optimized to discern, ex vivo, control and pathological murine skeletal muscle. It is worth noting that skeletal muscle is a heterogeneous tissue, and that this second step will yield an improved sensor capable of recognizing an increase of fibrotic tissue in a more complex system. In parallel, morphological evaluations will be performed to assess the amount of differentiated myotubes and fibroblasts in the tested muscles. Finally, the sensor will be optimized to distinguish healthy and pathological skeletal muscles in vivo, which represents the most complex condition, only by placing the sensor in contact with the tissue of interest.
Microwave sensors have been proposed in the literature for both industrial and pharmaceutical applications. Since these sensors can enable non-destructive testing, they have a great potential for healthcare applications. One of the most prominent healthcare issues is the continuous monitoring of chronic diseases. In these conditions, the capability of promptly returning changes to pharmacological treatments may play a crucial role in patients¿ clinical course. In this context, a novel biosensor based on the non-invasive measurement of tissue¿s dielectric properties could represent a quick, accurate and easy-to-use approach for early continuous monitoring.
In addition, in recent years, progress in the ICT have facilitated the access to information contributing to a dramatic change of healthcare industry, helping patients to access their vital-sign information anywhere and anytime (es. Smartwatch). The response of a microwave sensor system could be therefore connected directly to a smartphone through a pocket-device and controlled via APP, enabling a continuous monitoring of the tissue decaying, and could be also easily merged with all the other vital signals acquired. In this context, microstrip resonators are a good candidate for these applications, since they are low-cost, portable, easy fabrication, and integration with the remaining circuitry. In theory, a cellular variation changes the dielectric properties of the biological tissue and consequently affects the response of the microstrip resonator. Based on this principle, antennas and microwave resonators can be used similarly to what already proposed in the literature to sense the changes in blood glucose levels, sweet or cancer.
Furthermore, nowadays biopsy has been established as a crucial technique to verify the amount of dystrophin in skeletal muscle tissue: it is straightforward, efficient, and accurate, but still invasive. As a long-term advance of this project, the use of microwave-based biosensors could represent a potential alternative or additional technique to detect various pathological tissues, thus allowing a non-invasive diagnostic outcome.
In view of this, this project aims to demonstrate how the proposed method is a viable tool for distinguishing between healthty and unhealthy tissue. In particular, in vitro, ex vivo end in vivo tests will be carried on with cells and animal models to assess the feasibility of this approach in a system with increasing complexity, to pave the way for application with human patients.