<p dir="ltr">Cell polarity as defined by biologists is the cell ability to sense, determine its direction and orient itself in specific direction (e.g., front and back, top and bottom, and inside and outside). Recent studies have shown that loss of cell polarity at the tissue-level is a signature of a tumor. Detecting tumor cells based on their polarization, i.e., their electrical permittivity at the single-cell level could open the door for potential new diagnosing tools. Developing sensitive tools that are affordable and can perform fast reading is an after-sought goal. Currently, biochemical techniques are the adapted methods for research and analysis. These techniques include fluorescence-based, affinity-based, electrochemistry-based, and optical-based methods. The main disadvantages of these methods are their bulky size, and high cost due to the use of the complex pre-labeling and cannot handle small numbers of cells. On the other hand, biophysical sensing techniques for single cell focus on the whole cell intrinsic properties such as molecular compositions, volume, mass, electrical properties (i.e., conductivity and permittivity), mechanical properties. Biophysical sensing based on electrical methods would be non-invasive, fast, safe for the cells, and affordable. </p><p dir="ltr">In this thesis, novel sensors for single-cell detection are presented. Design, simulation, fabrication, and in some cases, experimental characterization of these proposed microfluidic sensors are discussed in details. The use of low and high frequency readouts for cell detection as well as the long-term goal of integration as a CMOS sensing platform are demonstrated. Detection and counting of air-bubbles on mm-sized RF ring resonator are demonstrated as a first proof of concept. Miniaturized RF ring resonator and co-planar-waveguide (CPW) devices that are integrated with microfluidic channels to characterize single-cells are then discussed. Furthermore, a novel CMOS capacitor sensor for cell detection is proposed for the first time. The idea of the proposed sensor is based on a perforated MIM capacitor that allows the detection of cells by a change in the dielectric constant of the capacitor perforated with a micro-channel.</p>