| Cells are Nature's nano-machines and the result of millions of years of natural selection. We ourselves are assemblies of these nano-machines. As such, developing cell-based biosensors is at the frontier of nanotechnology and aims to take advantage of these highly advanced nano-machines by integrating living cells with microelectronics. To realize such devices, two key issues need to be addressed: what kind of cells can be used for biosensor applications and how to convert cellular responses into physically interpretable signals. In this thesis, we explored the use of an FT cell-line and its endogenous ATP receptors as the basis for a living cell-based biosensor. Both a calcium imaging based optical method and an amperometry based electrochemical method were investigated as the detection mechanism. Results indicate both methods are feasible for biosensor applications. Moreover, microfluidics was also studied to enable on-chip cell transport and system level integration of cell-based biosensors.; This thesis consists of 7 chapters. Chapter 1 reviews the state of the art of BioMEMS and cell-based biosensors. Chapter 2 describes the working principles of the cell-based biosensor and the relevant biological background information. Chapter 3 lays out in detail the theory behind electrochemical detection on chips using Cr/Au microelectrodes. In Chapter 4, a living cell-based biosensor is investigated using an electrochemical method of detecting the cellular response. In Chapter 5, a calcium imaging based optical method is discussed followed by a re-investigation of the electrochemical method for comparison. Chapter 6 describes two microfluidic devices we have fabricated to enable fast on-chip cell transport and drug delivery. Finally, Chapter 7 summarizes the major findings in this thesis and discusses possible future research directions for living cell-based biosensors. |
