Broadband Dielectric Spectroscopy of Cell Cultures

Abstract

Broadband dielectric spectroscopy measurements of biological materials within RF/microwave range can reveal cellular information, which is of important value in biological and medical researches. Here we present a platform that combines a miniaturized coplanar waveguide (CPW) transmission line (TL) sensor and a special CPW fed interdigitated capacitor (IDC), which allows us to measure the complex permittivity of cell cultures from 300 kHz to 50 GHz. The CPW-TL sensor and the CPW-IDC sensor are integrated with an SU-8 microfluidic channel, enabling measurements of microliter or even nano-liter volumes of liquids and suspensions. Due to the accurate alignment of the SU-8 polymer and the reliable lift-off fabrication procedure, we are able to minimize the measurement errors caused by the sensors' dimension tolerance. To ensure accurate complex permittivity extraction of the tested material, related calibrations and de-embedding processes are explained. With the measurement of deionized water as a validation, the platform is used to measure the complex permittivity of both a yeast cell culture and a mammalian cell culture. We elaborate on the interesting findings and discuss future possibilities.

On-Chip Characterization of High-Loss Liquids Between 750 and 1100 GHz

“…This method is based on an electronic heterodyne technique, and benefits from having first-class frequency resolution (∼ 1 Hz), about 20 dB higher dynamic range than TDS systems at 1 THz [15], traceability to the International System of Units [16], and can use calibration techniques to move the reference plane to the region of interest [17]; whereas the downside is that the bandwidth is limited to a waveguide band. The frequency range of VNA measurements applied to biology has been typically restricted to microwave [18] and millimeter-wave frequencies [19], [20]. However, recent development in heterodyne technology has increased the maximum frequency of VNA analysis up to 1.5 THz [21] in rectangular waveguides, and up to 1.1 THz for onchip measurements using contact probes [22].…”

Biosensor Using a One-Port Interdigital Capacitor: A Resonance-Based Investigation of the Permittivity Sensitivity for Microfluidic Broadband Bioelectronics Applications

“…The recent advances in microwave dielectric spectroscopy along with the progress in micro-and nanotechnologies have stimulated the development of miniature microwave biosensors for liquid characterization, enabling development in the lab-on-a-chip devices [23,24]. Microwave biological sensors for microliter and even nanoliter liquid samples find applications in many research fields, such as chemical synthesis, biological analysis, and medical diagnosis [25][26][27][28][29][30][31][32]. There has therefore been great interest in recent years in the development of miniature biosensors based on microwave dielectric spectroscopy analysis for liquid characterization.…”

“…Nevertheless, different biological materials can show different dispersion properties at different frequency ranges, so it is necessary to analyze the spectroscopy of biological materials in a broad band. Broadband spectroscopy can be obtained by combing an IDC with a CPW line to avoid the onset of IDC self-resonance [28,47]. This method is time-consuming.…”

Numerical modeling of two microwave sensors for biomedical applications

“…Dielectric spectroscopy (DS) is a very powerful investigation technique that is based on studying the frequencydependent dielectric response of matter to applied electromagnetic (EM) fields, 1 thereby enabling analysis of the underlying dielectric properties of a wide variety of biological materials under test (MUTs) (eg, tissue, 2 blood, 3 proteins, 4 viruses, 5,6 and cultured cells 7,8 ). To characterize MUTs and to detect their dielectric properties at microwave frequencies, a plethora of different sensor topologies have been proposed over the years, finding various applications in life science, such as microwave diagnostics in medicine, [9][10][11][12] and each one with its own pros and cons.…”

“…To accomplish this tough task, different solutions have been recently developed by using coplanar waveguide (CPW) technology. As well known, the integration of CPW transmission lines (TLs) with microfluidic channels allows achieving broadband DS, 8,[24][25][26] but its applicability is limited to relatively high frequencies (generally larger than 100 MHz). This is because at lower frequencies, it is necessary to use very long TLs that result in a larger space consumption and a larger sample volume.…”