Measuring and visualizing cell surface charge plays a significant role instudying intercellular signaling, metabolism, and cell differentiation, etc. Cell surfacecharge distribution differs among species, cell types, benign cells, or differentiationstates. Therefore, it can be used for cell analysis and diagnostics. Surface chargecharacteristics of cancer cells are also considered as novel biomarkers for cancerdetection and treatments. It has also been widely confirmed that cell surface chargeimpacts many cell membrane-regulated cell functions such as endocytosis, muscle cellcontraction, nutrient transport: However, the direct relationship and underlyingmechanism between cell surface charge and cell phenotype or induced cell responsehave been less studied because measurement and mapping of cell surface charge remaina significant challenge due to the lack of robust techniques capable of micro-and nanoscale measurements in complex environments.In this dissertation, I first presented a cell surface charge mapping method viaelectrostatic cell–nanoparticle (NP) interactions. The fluorescent nanoparticles (NPs)with opposite charges were electrostatically bonded to the cell surface and were usedas the marker to investigate single cells’ surface charge distribution. A stack offluorescence distribution on a cell’s surface at a series of vertical focusing distanceswas imaged to estimate the profile of NPs distribution. By establishing a relationshipbetween fluorescent light intensity and the number of nanoparticles, cells’ surfacecharge distribution was quantified from the fluorescence distribution. Microparticleswere firstly used to validate the method. From the measured surface charge density of microparticles (MPs), the average zeta potentials agreed with that measured by thestandard electrophoretic light scattering. Two types of cells, human umbilical veinendothelial cells (HUVECs) and HeLa cells, were tested as well, from which HUVECand Hela cells have distinct surface charge distribution, suggesting the potential ofusing cell surface charge distribution as a new criterion for cell type identification andcell detection.Furthermore, I presented a cell surface charge mapping method viaoptoelectronic interactions. This method could measure the surface charge distributionof a single cell without affecting the chemistry or physics of the cell or its membrane.The light reflected from the electrodes on the indium tin oxide substrate (ITO) surfacechanged under the influence of the applied voltage bias and the surface charge. A cellis placed an array of microelectrodes fabricated on a transparent ITO (indium tin oxide)surface. An incident light irradiates ITO surface from the backside. Because of theinfluence of the cell surface charge (or zeta potential), the photocurrent and absorptionof the incident light is changed, causing a magnitude change of the reflected light.Hence the cell surface charge distribution can be quantified by analyzing the reflectedlight intensity. This method does not need physical or chemical modification of the cellsurface. I validated this method using charged microparticles and two types of cells,Human Dermal Fibroblast Cells (HDFs) and Human Mesenchymal Stem Cells (hMSC).The measured average zeta potentials were in good agreement with standardelectrophoresis light scattering method.