TFT sensor array for real-time cellular characterization, stimulation, impedance measurement and optical imaging of in-vitro neural cells

Real-time in-vitro multi-modality characterization of neuronal cell ensemble involves highly complex interdependent phenomena and processes. Although a variety of microelectrode arrays (MEAs) have been reported, diagnosis techniques are limited in term of sensing area, optical transparency, resolution and number of modalities. This paper presents an optically transparent thin-film-transistor (TFT) array biosensor chip for neuronal ensemble investigation, in which TFT electrodes are used for six modalities including extracellular voltage recording of both action potential (AP) and local field potential (LFP), current or voltage stimulation, chemical stimulation, electrical impedance measurement, and optical imaging. The sensor incorporates a large sensing area (15.6 mm x 15.6 mm) with a 200 x 150 array of indium-tin-oxide (ITO) electrodes placed at a 50 mu m or 100 mu m pixel pitch and with 10 ms temporal resolution; these performances are comparable to the state-of-theart MEA devices. The TFT electrode array is designed based on the switch matrix architecture. The reliability and stability of TFTs are examined by measuring their electrical characteristics. Impedance spectroscopy function is verified by mapping the neuron position and the status (cells alive or dead, contamination) on the electrodes, which facilitates the biochemical studies in electrical domain that adds quantitative views to visual observation of cells through the optical microscopy. An in-vitro neuron culture is studied using electrophysiological, electrochemical, and optical characterization. Detailed signal analysis is demonstrated to prove the capability of bioassay.