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A 3-D electrical impedance tomography (EIT) is an emerging technique for real-time and non-destructive 3-D cell culture imaging. This paper presents a pioneering study of scaffold-based 3-D cell culture imaging using a miniature planar EIT sensor. A 17-electrode miniature-planar EIT sensor equipped with a regular-shape 3-D printed scaffold was manufactured, modeled, and characterized. In addition, an efficient 3-D image reconstruction method based on 3-D isotropic total variation and ${l}$ 1 joint regularization was proposed. The numerical simulation on scaffold phantoms and the experimental study on time-varying distribution of MCF-7 cancer cell suspension within the scaffold were performed. Both the simulation and experiment results suggest that using the miniature EIT sensor and the developed 3-D image reconstruction algorithms are able to achieve high quality, non-destructive scaffold-based 3-D cell culture imaging.

Electrical impedance tomography (EIT) has the potential to be an alternative technique to microscopy for many biological applications. It is a novel approach to monitor cell viability, proliferation, or drug response with high temporal resolution in a label-free, non-toxic, and non-destructive way. To limit measurement errors, only time-difference EIT is currently used for biological imaging. Still, the need for constant background reference limits its uses in long-term imaging. A novel equivalent circuit model was developed to analyze the errors in frequency-difference EIT (FDEIT) measurements. Based on the circuit model, the calibrated FDEIT (CFDEIT) method has been derived to compensate the measurement errors. The simulation results show that the voltage variations introduced by the leakage current are correctly modeled by the equivalent circuit. Significant improvements in the image quality are observed in both simulation and experimental results after the application of CFDEIT. It indicates that this paper improves the accuracy of FDEIT and makes it feasible for 3D tissue culture monitoring.

Real-time quantitative imaging is becoming highly desirable to study nondestructively the biological behavior of 3-D cell culture systems. In this paper, we investigate the feasibility of quantitative imaging/monitoring of 3-D cell culture processes via electrical impedance tomography (EIT), which is capable of generating conductivity images in a non-destructive manner with high temporal resolution. To this end, a planar miniature EIT sensor amenable to standard cell culture format is designed, and a 3-D forward model for the sensor is developed for 3-D imaging. Furthermore, a novel 3-D-Laplacian and sparsity joint regularization algorithm is proposed for enhanced 3-D image reconstruction. Simulation phantoms with spheres at various vertical and horizontal positions were imaged for 3-D performance evaluation. In addition, experiments on human breast cancer cell spheroid and a triangular breast cancer cell pellet were carried out for experimental verification. The results have shown that the stable measurement on high conductive cell culture medium and the significant improvement of image quality based on the proposed regularization method are achieved. It demonstrates the feasibility of using the miniature EIT sensor and 3-D image reconstruction algorithm to visualize 3-D cell cultures, such as spheroids or artificial tissues and organs. The established work would expedite real-time quantitative imaging of 3-D cell culture for assessment of cellular dynamics.