Abstract

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 <xref ref-type="bibr" rid="ref1" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">[1]</xref> . Moreover, it is imperative to investigate the effectiveness and toxicity of pharmaceutical treatments before administration in clinical practice <xref ref-type="bibr" rid="ref2" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">[2]</xref> . 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 tests), expensive equipment (e.g., magnetic resonance imaging), low accuracy (e.g., ultrasound), use of ionizing radiation (e.g., X-rays), and invasiveness <xref ref-type="bibr" rid="ref3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">[3]</xref> . The characterization of biological matter using microwave ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">µ</i> W), millimeter-wave (mmW), and terahertz (THz) spectroscopy is a promising alternative: it is label-free, does not require ionizing radiation, and can be noninvasive. Moreover, there is a significant difference in how different biological materials absorb, reflect, and transmit electromagnetic (EM) waves <xref ref-type="bibr" rid="ref4" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">[4]</xref> 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 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\mathbf{\varepsilon}\left({\mathbf{f}}\right){,}$</tex-math></inline-formula> which expresses how the material responds to an external oscillating electric field. The complex permittivity of a material determines how the material absorbs, reflects, and transmits EM waves at different frequencies ( <xref ref-type="fig" rid="fig1" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Figure 1</xref> ). Since each biological material’s permittivity spectrum is different, it acts as an EM fingerprint. A material’s complex permittivity can be calculated from the reflection and transmission of EM waves through the material, described by the S-parameters, which can be measured using a vector network analyzer (VNA) transmitting and receiving EM waves over a range of frequencies. The amplitude and phase of the transmitted and reflected EM waves at different frequencies are influenced by different underlying biological effects at different scales. That causes the entire spectrum to provide information from the supracellular to the molecular and even atomic scale.

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