On-Chip Flow Cytometry Utilizing the Di-Electrophoresis and Ring Oscillator-Based Capacitive Sensor

Flow Cytometry (FC) is a powerful technique used to detect and measure various cellular characteristics, including size, count, morphology, and DNA content. It plays a vital role in clinical diagnostics and biomedical research, with widespread use in hospitals and medical institutions worldwide. In this work, an on-chip, capacitance-based flow cytometer is developed to manipulate, characterize, detect, and quantify microbeads based on their electrical properties, specifically, capacitance. The proposed biochip consists of two primary subsystems: a manipulation system for directing particles and a detection system for characterizing them. The manipulation system integrates a microfluidic flow control design with dielectrophoresis (DEP) microelectrodes. DEP enables label-free particle manipulation in non-uniform electric fields by inducing polarization, allowing for precise control of particle trajectories with minimal sample preparation. The detection system employs a capacitive sensor array coupled with a ring oscillator-based readout circuit for real-time electrical sensing. Capacitance-based biosensors offer rapid, accurate, and efficient detection without the need for bulky optical equipment or chemical labeling. Leveraging printed circuit board (PCB) technology, the DEP electrodes and capacitive sensors are seamlessly integrated into a compact, low-cost, and scalable platform. The inclusion of a gold surface further enhances electrical conductivity and biocompatibility, making the system suitable for biological applications. Experimental and simulation results confirm that the integrated manipulation and sensing components effectively characterize and quantify carboxylate polystyrene microbeads. The sensor exhibits high sensitivity, achieving 184 fF per 1% w/v concentration change, and demonstrates excellent linearity with a coefficient of determination (R2) of 0.9755, indicating a reliable and consistent response. The use of a 7-stage Miller ring oscillator enables precise capacitance-to-frequency conversion with minimal error, achieving a root mean square error (RMSE) of 0.57 across a capacitance range of 1–100 pF. This allows for reliable detection of concentrations as low as 0.15625% w/v.