The fundamental bottleneck of any bioprocess is the lack of real -time, online, in situ , quantitative information with respect to cellular behaviors in cultures. As a result, control, optimization, and scale -up of bioprocesses are essentially manual (empirical) -which results in suboptimal productivity (i.e., inadequate cell expansion) and product quality. To harness the immense potential of stem cells in terms of their plasticity and expansion capabilities, the physiological activity in relation to local culture parameters, such as pH, dissolved oxygen, nutrient and metabolite concentrations, and growth factor concentrations, needs to be recorded quantitatively with the required level of accuracy. Subsequently, it must be evaluated in a biologically meaningful manner, which, in the long run, could allow the systematic development of clinically relevant culture systems and methodologies, leading to the engineering of reproducible, well -characterized, regenerated " designer " tissues and organs that meet the strict regulatory criteria for clinical applications.This chapter will discuss the acquirement of quantitative information of the cell culture bioprocess using biosensors. The interfacing for a single potentiometric biosensor and for a single amperometric biosensor will be discussed fi rst, and then followed by the discussion on building a multichannel, PC -based, real -time measurement system. An up to 128 -channel, multiparametric physiological measurement system for monitoring stem cell culture process will be described in detail as an example.