Advanced Cell Chip Technologies for 3D Model Drug Screening and Therapy Development

Our laboratory has developed highly compatible cell chips and devices for three-dimensional (3D) models, including cancer spheroids and full-thickness skin. These 3D models closely mimic human organs, enabling potential predictions for new drug screening and human metabolized products that may inhibit cancer or improve wound healing.

Concurrently, we are advancing therapies by applying nanotechnology, such as nanocarriers, to support and enhance treatment efficacy. Furthermore, we utilize hydrogel technology to promote 3D architecture development.

We have successfully fabricated cell chips incorporating polydopamine (PDA) integrated with polydimethylsiloxane (PDMS) microwells and indium tin oxide (ITO) microelectrodes. This design allows for direct 3D spheroid generation and real-time monitoring of spheroid growth over extended periods. Employing graphene quantum dot-based nanocarriers, we developed a combined cryptotanshinone-graphene quantum dots (CPT-GQDs) nanocomposite that exhibits remarkable anticancer properties. The viability of 3D spheroids was significantly reduced after exposure to 6 μg/ml of CPT and CPT-GQDs, with viability rates of 28% and 22%, respectively. By combining traditional techniques (molecular and cellular analysis) with impedance data, we determined the half-maximal inhibitory concentration (IC₅₀) to be 1.47 ± 0.16 μg/mL.

Additionally, we have fabricated a novel trans-epithelial electrical resistance (TEER) device that offers convenient and flexible measurements of full-thickness skin tissues. We synthesized hydrogels incorporating native components such as collagen and alginate, cross-linked with CaCl₂, enabling the formation of uniform 3D skin with full layers, including a dermal fibroblast layer and an epidermal layer composed of melanocytes and keratinocytes. This new TEER device facilitates long-term monitoring of 3D skin reconstruction differentiation.
This innovative combination of nanotechnology, hydrogel engineering, and state-of-the-art cell impedance measurement opens up new avenues for expedited drug discovery and the potential development of novel therapies.

Acknowledgment
This research was supported by National Research Foundation of Korea (NRF-2020M3A9E4104385, 2023R1A2C1003669), and Korea Environment Industry & Technology Institute (KEITI) through "Technology Development Project for Biological Hazards Management in Indoor Air" Project, funded by Korea Ministry of Environment (MOE)(G232021010381).

Keyword:
PDMS microwell, ITO microelectrodes, TEER device, 3D model, nanocomposite, real-time monitoring.