The mechanistic understanding of the molecular biology of cells including stem cells is an active area of research that is fundamental to all of the biological sciences. It is well known that transformation of cells in culture by toxic agents can lead to a wide range of changes in cellular properties, including loss of growth control, altered morphology, increased mobility of surface lectin receptors and changes in cytoskeleton organization. Considerable evidence has suggested that alternations in the cell surface may be responsible for many of these observations. In this poster presentation, we will show a few examples to study cell-substrate interactions using real time non invasive label free sensor technology (i.e. Quartz Crystal Microbalance, Surface Plasmon resonance and potentiometry). Several new sensor recognition elements (i.e. recombinant antibodies, peptides, lectins, carbohydrates) and their use for studying cell-substrate interactions with label free transducers will be discussed. This presentation will illustrate the advantages of developing a label free microarray format for high throughput measurement of cell-substrate interactions in a quantitative, real time manner with high sensitivity and specificity but limited size, weight and power consumption. It can be easily implemented in a microarray system that reduces reagent use, increases sensitivity, improves measurement speed, and allows for high sample throughput for understanding of stem cell biology. 1. Yanyan Wang, Qiang Chen, Xiangqun Zeng*, Potentiometric Biosensor for Studying Hydroquinone Cytotoxicity in vitro, Biosensors and Bioelectronics, 2010, 25,1356-1362. 2. Weilian Qiu, Xiangqun Zeng*, Conductive Polymer as Controlled Microenvironment for Potentiometric High Throughput Evaluation of Ionic Liquid Cell Toxicity, Analytical and Bioanalytical Chemistry, 2008, 392, 203-213. 3. Shen Z., Huang M., Xiao C., Zhang Y., Zeng X*, Wang G. P.*, Nonlabeled Quartz Crystal Microbalance Biosensor for Bacterial Detection Using Carbohydrate and Lectin Recognition, Anal. Chem. 2007, 79(6) 2312-2319. 4. Single Chain Fragment Variable Recombinant Antibody as a Template for Fc Sensors , Heping Yan, Zhihong Shen, Ray Mernaugh, Xiangqun Zeng*, Submitted to Anal. Chem. In Review.