A novel microfluidic resistive pulse sensor with multiple voltage input channels and a side sensing gate for particle and cell detection

Traditionally, a resistive pulse sensor (also known as Coulter counter) works by letting a particle pass through a small orifice in an electrolyte solution. The detection sensitivity mainly relies on the volume ratio of the particle to the orifice. This paper presents a novel resistive pulse sensor which has a sensing orifice located on the side wall of a microchannel. In this way, the sensor can detect and count particles (or cells) without requiring particles (or cells) passing through the sensing gate. An equation was derived to relate the magnitudes of the detected signals and the electrical resistances. Results show that the magnitudes of the detected signals can be increased by applying voltages from more than one voltage input channels simultaneously. Under the same conditions, the magnitudes of the detected signals become larger when the diameters of particles are larger. Higher detection sensitivity can be obtained simply by increasing either the magnitudes of the applied voltages or the number of the voltage input channels, or reducing the opening of the side sensing gate to a size that is even smaller than the diameter of the particle. Due to the high detection sensitivity, detection of 1 mu m particles by a relatively large sensing gate of 5 x 10 x 10 mu m (width x length x height) was successfully demonstrated with a signal to noise ratio (S/N) of approximately 3. This sensor was also applied to detect and count human red blood cells and lymphocyte cells. Results show that this method can clearly distinguish the cells with different sizes based on the pre-determined-thresholds. Because this sensor does not require cells to pass through the sensing gate, the channel clogging problem can be avoided. More importantly, the detection sensitivity can be tuned by applying different voltages without fabricating a smaller sensing gate. (C) 2018 Elsevier B.V. All rights reserved.