Investigating Dielectric Impedance Spectroscopy As a Non-Destructive Quality Assessment Tool for 3D Cellular Constructs

Abstract

In any three dimensional (3D) biofabrication process, assessing critical biological quality attributes of 3D constructs such as viable cell number, cell distribution and metabolic activity is critical to determine the suitability and success of the process. One major limitation in current state-of-the-art is the lack of appropriate methods to monitor these quality attributes in situ in a non-destructive, label-free manner. In this study, we investigate the feasibility of using dielectric impedance spectroscopy to address this gap. We first measured the relative permittivity of 3D alginate constructs with four different concentrations of encapsulated MG63 cells (1–6.5 million cells/mL) and found them to be statistically significantly different (p < 0.05). Within the tested range, the relationship between cell concentration and relative permittivity was noted to be linear (R2 = 0.986). Furthermore, we characterized the β-dispersion parameters for MG63-encapsulated in alginate (6.5 million cells/mL). These results demonstrate that dielectric impedance spectroscopy can be used to monitor critical quality attributes of cell-encapsulated 3D constructs. Owing to the measurement efficiency and non-destructive mode of testing, this method has tremendous potential as an in-process quality control tool for 3D biofabrication processes and the long-term monitoring of cell-encapsulated 3D constructs.

Enhancing quality control in bioprinting through machine learning

“…DIS is a non-image technique in which the constructs are stimulated with an alternating electric field at different frequencies and the permittivity is registered. The authors have observed that the difference in permittivity between the two peaks in the frequency range 150-2500 kHz correlates to the number of viable cells, thus providing a tool to monitor the viability during and after printing without using destructive and offline assessments [59].…”

Engineering next-generation bioinks with nanoparticles: moving from reinforcement fillers to multifunctional nanoelements

“…These new nanocomposite bioinks can be applied to provide the 3D bioprinted tissue/ organs with the capability to accurately monitor cells behavior during long-term culture studies without using invasive techniques. 116…”

Dielectric characterization of fiber‐ and nanofiller‐reinforced polymeric materials

“…This valuable information on cell morphology, proliferation, and differentiation aids in optimizing the tissue engineering process. [13][14][15][16] DS plays a vital role in cancer diagnosis and treatment as it also aids in characterizing the distinct dielectric properties of cancer cells, allowing for early detection, diagnosis, and treatment monitoring. [17][18][19][20][21] In addition, DS is useful in drug delivery, enabling the assessment of drug transport and distribution in tissues and organs.…”

“…DS also finds significant applications in biomedical engineering, particularly in tissue engineering, where measuring the dielectric properties of cells and extracellular matrices allows monitoring of tissue growth and development. This valuable information on cell morphology, proliferation, and differentiation aids in optimizing the tissue engineering process 13–16 . DS plays a vital role in cancer diagnosis and treatment as it also aids in characterizing the distinct dielectric properties of cancer cells, allowing for early detection, diagnosis, and treatment monitoring 17–21 .…”