Gold nanostructure-integrated conductive microwell arrays for uniform cancer spheroid formation and electrochemical drug screening.

Cancer spheroids, which mimic distinct cell-to-cell and cell-extracellular matrix interactions of solid tumors in vitro, have emerged as a promising tumor model for drug screening. However, owing to the unique characteristics of spheroids composed of three-dimensionally densely-packed cells, the precise characterizations of cell viability and function with conventional colorimetric assays are challenging. Herein, we report gold nanostructure-integrated conductive microwell arrays (GONIMA) that enable both highly efficient uniform cancer spheroid formation and precise electrochemical detection of cell viability. A nanostructured gold on indium tin oxide (ITO) substrate facilitated the initial cell aggregation and further 3D cell growth, while the non-cytophilic polymer microwell arrays restricted the size and shape of the spheroids. As a result, approximately 150 human glioblastoma spheroids were formed on a chip area of 1.13 cm2 with an average diameter of 224 µm and a size variation of only 5% (±11.36 µm). The high uniformity of cancer spheroids contributed to the stability of electrical signals measuring cell viability. Using the fabricated GONIMA, the effects of a representative chemotherapeutic agent, hydroxyurea, on the glioblastoma spheroids were precisely monitored under conditions of varying drug concentrations (0-0.3 mg/mL) and incubation times (24-48 h). Therefore, we conclude that the newly developed platform is highly useful for rapid and precise in vitro drug screening, as well as for the pharmacokinetic analyses of specific drugs using 3D cellular cancer models.

Recent Advances in Electrochemical Biosensors for Monitoring Animal Cell Function and Viability.

Redox reactions in live cells are generated by involving various redox biomolecules for maintaining cell viability and functions. These qualities have been exploited in the development of clinical monitoring, diagnostic approaches, and numerous types of biosensors. Particularly, electrochemical biosensor-based live-cell detection technologies, such as electric cell-substrate impedance (ECIS), field-effect transistors (FETs), and potentiometric-based biosensors, are used for the electrochemical-based sensing of extracellular changes, genetic alterations, and redox reactions. In addition to the electrochemical biosensors for live-cell detection, cancer and stem cells may be immobilized on an electrode surface and evaluated electrochemically. Various nanomaterials and cell-friendly ligands are used to enhance the sensitivity of electrochemical biosensors. Here, we discuss recent advances in the use of electrochemical sensors for determining cell viability and function, which are essential for the practical application of these sensors as tools for pharmaceutical analysis and toxicity testing. We believe that this review will motivate researchers to enhance their efforts devoted to accelerating the development of electrochemical biosensors for future applications in the pharmaceutical industry and stem cell therapeutics.