AVS 54th International Symposium
    Biomaterial Interfaces Friday Sessions
       Session BI-FrM

Paper BI-FrM11
High Throughput Pharmacological Screening using Cell-Based Biosensors

Friday, October 19, 2007, 11:20 am, Room 609

Session: Microbioanalytical Systems
Presenter: K. Varghese, Medical University of South Carolina, University of Central Florida
Authors: K. Varghese, Medical University of South Carolina, University of Central Florida
P. Molnar, University of Central Florida
N. Bhargava, University of Central Florida
M. Das, University of Central Florida
M.S. Kindy, Medical University of South Carolina
J.J. Hickman, University of Central Florida, Medical University of South Carolina
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In drug development there is a large demand for a system capable of high throughput screening, as well as stable long-term recordings. Cell-based biosensors (CBBs) have the potential to address this demand. CBBs work on the principle of a direct interface between electronics and biological cells, such that the electronics make it possible to quantify a change in the cells’ immediate environment. The cell-electronics interface can be modified using different physical properties to vary the adhesive properties of cells. It then becomes possible to promote or inhibit cell adhesion, as well as support preferential attachment of one cell type over another. Cell-based electrophysiology can be broadly divided into two categories - 1) those based on intracellular potentials (e.g. use glass microelectrodes, as in patch clamping) and 2) those based on extracellular potentials. Our research focuses on the latter, wherein extracellular microelectrode arrays are used as a noninvasive and long-term approach for the measurement of biopotentials. The objective of this study is to develop a high throughput CBB where the cell-electronics interface is represented by neurons on Metal Microelectrode Arrays (MEAs). The sensor thus developed should be able to detect acute and chronic effects for a broad range of compounds, at a broad range of concentrations, on neuronal physiology. The inherent properties of this CBB also make it possible to obtain long-term recordings from the neurons. The CBB discussed here consists of a layer of cultured embryonic rat neurons on surface-modified MEAs. The interfaces were modified utilizing self-assembled monolayers and characterized utilizing XPS and contact angle measurements. This system was then used to study the time-dependant effects of Amyloid beta (a causative factor of Alzheimer’s Disease) on embryonic rat neurons. Since long-term recordings were relatively easy to obtain, it was possible to observe the effects of amyloid beta, at nanomolar concentrations, over a period of ten hours or more, without cell death. A quantitative description of the effect of this compound on the neuronal system utilizing extracellular recordings will be described. The cells were also characterized by morphology as well as immunocytochemical analysis. Intracellular electrophysiological controls were also performed and will be compared to the results obtained with the solid-state devices.