Biologists introduced some years ago an intermediate biological model between 2D cell culture and 3D in vivo tissues, called microtissues or spheroids. To study such 3D models, techniques are currently applied, including electromagnetic waves-based methods at low frequencies. This frequency range does not allow the penetration of the waves inside the cells, conversely to the microwaves. There is consequently a strong interest to develop an appropriate microwave-based sensor dedicated to microtissues analysis. This constitutes the topic of this paper with the introduction of a new microwave sensor, suitable for the dielectric characterization of microtissues. An analytic method is proposed to extract their electrical parameters. The evaluation of the biosensor is performed, while measuring large polystyrene beads with known dielectric properties, followed then by the dielectric evaluation of fixed spheroids from 500MHz to 20GHz.

Accurate characterization of biological matter, for example, in tissue, cells, and biological fluids, is of high importance. For example, early and correct detection of abnormalities, such as cancer, is essential as it enables early and effective type-specific treatment, which is crucial for mortality reduction [1]. Moreover, it is imperative to investigate the effectiveness and toxicity of pharmaceutical treatments before administration in clinical practice [2]. However, biological matter characterization still faces many challenges. State-of-the-art imaging and characterization methods have drawbacks, such as the requirement to attach difficult-to-find and costly labels to the biological target (e.g., COVID-19 rapid test), expensive equipment (e.g., magnetic resonance imaging or MRI), low accuracy (e.g., ultrasound), use of ionizing radiation (e.g., X-rays), and invasiveness [3]. The characterization of biological matter using microwave (µW), millimeter wave (mmW), and Terahertz (THz) spectroscopy is a promising alternative: it is label-free, does not require ionizing radiation, and can be non-invasive.Moreover, there is a significant difference in how different biological materials absorb, reflect, and transmit electromagnetic (EM) waves [4] that is due to the difference in their dielectric properties. The dielectric properties are described by the frequency-dependent material parameter called the complex permittivity 𝜺(𝒇), which expresses how the material

Microwave dielectric spectroscopy is a promising technique that allows intracellular, non-invasive, label-free and cost-effective biological studies. To complement the sensing possibilities of this technique at this frequency range, which have been previously demonstrated at the single cell, cellular suspensions and organs levels, a microwave-based sensor is designed, fabricated and evaluated to dielectrically characterize 3D biological microtissues. Such a biological model is indeed of high interest for biological investigations, as it constitutes an intermediate entity between 2D cell cultures and organs, exhibiting a biological response close to the one obtained with tissue physiology. The proposed sensor here the development of one of the first microfabricated device for spheroids studies. A discussion on the way of analyzing the data is proposed thanks the measurements of different fixed spheroids and polystyrene beads.