Measurement of extracellular signals from cells and tissues provides vital information in determining cellular excitability and conductive mechanisms. These signals are produced mostly by flow of ions like calcium (Ca+), sodium (Na+), potassium (K+), and chloride (Cl−) through cell membrane channels.
In vitro tissue biosynthesis is an invaluable resource not only for tissue-organ replacement, but also for studies of disease mechanisms as well as for building high-throughput cell bioassay systems or biochips for pharmacological and proteomic studies. In vitro biosynthesis of three-dimensional (3D) multi-cellular structures that resemble adult or differentiated tissue has been tried for many years with limited success, mostly because organs enclose more than one cell type and because the existing amorphous bio-compatible materials do not permit pre-arrangement of different cell types with their appropriate functional architecture.
Multi-Electrode Array (MEA) devices have facilitated recordings of extracellular electrical activity simultaneously from multiple sites, in vitro and in vivo. Current MEA devices are designed for culturing and recording from cells of one type or a mixture of different cell types combined in a two dimensional scheme. While a major fraction of bodily tissues are composed of two or more cell types (e.g. glia and neurons in the brain, fibroblasts, smooth muscle cells, endothelial cells and myocytes in the heart and endothelial and smooth muscle cells in the arteries), there are no viable systems for studying the three-dimensional interactions between such cells.
Electrical recordings in heart muscle can be made at surface cells using optical mapping or impaling glass microelectrodes. However, measurements at deeper layers require the use of plunge electrodes, which can induce tissue damage.
There are similar challenges associated with physiological studies of agonists, antagonists, and their corresponding receptors, such as in high-throughput drug screenings. Conventionally, such studies require the use of freshly isolated tissue samples, and results of the studies can be adversely impacted by ischemia and other factors.
Thus, there is a need for systems of studying preparations where two or more cell types can be co-cultured in a three-dimensional, controlled manner. There is a further need for using such systems in improving the understanding of cell interaction mechanisms and to improve the artificial development of tissues. There is still a further need for an in vitro reconstituted system in which the architecture for multiple cell layers and types is produced with an electrical recording system already in place. There is still a further need for a cell-based assay that permits performance of the high-throughput drug screenings and other physiological studies while avoiding the need for fresh tissue samples and limiting the likelihood of events that adversely affect such studies.