Microfluidic Resistance sensing for single cell growth rate measurements and cell separation characterization.

Abstract

This dissertation presents the development of two microfluidic resistance sensing schemes and demonstrates their applications for (1) volume growth rate measurements of single budding yeast cells, and (2) performance characterization of size-based on-chip direct current dielectrophoretic (DC-DEP) cell separation. The first sensing scheme is based on the MOSFET-based microfluidic resistive-pulse sensing, which amplifies the percentage modulation of resistance pulses of the sensing microchannel when microparticles or cells are translocated through it. By reversing the electroosmotic flow direction through alternating the polarity of the applied electric potential, a selected yeast cell can be moved back and forth through the sensing aperture, which allows for direct measurement of cell volume growth over a whole cell cycle. The measured volume growth curve shows a sigmoid profile. Data analysis strongly suggests a local exponential volume growth phenomenon, while globally the growth can be represented equally well by a piecewise linear and two non-linear models. The second sensing scheme, a reference-channel based resistance sensing, consists of a sensing channel and a reference channel aligned in a serial manner. Introduction of the reference channel allows for elimination of the effects of baseline ionic current drift because the same ionic current flows through both the sensing and the reference channel and the ratio of the voltage drops across the two channels is only related to the ratio of the electrical resistance of the two channels. We demonstrate this sensing scheme through measuring the volume growth of a single yeast cell inside the sensing channel in real-time over 2.5 hours. We further demonstrate the possibility of integrating the MOSFET-based resistive-pulse sensing with DC-DEP separation to simultaneously separate cells and characterize the separation performance. The characterization results of cells with continuous size distribution are analyzed using the receiver operator characteristics method. It is shown that the DC-DEP separation performance of different sized polystyrene beads, yeast colony, and 4T1 breast cancer cells and bone marrow cells highly depends on the particle/cell flow rate.