Enhanced Electrical Impedance Sensing of Biological Cells Using Travelling Wave Dielectrophoresis Manipulation

Abstract

Electrokinetics involves techniques of applying forces and torques to fluids or suspended microscopic particles like biological cells, by exploiting their electrical properties and their interactions with electric fields. This has been demonstrated many times to have significant applications in lab-on-a-chip systems. Biological cells and other microparticles are dielectrically-heterogeneous structures, and therefore each different particle has a distinct dielectric frequency-response signature. This dielectric distinction allows sub-populations of particles to be separated by different criteria such as cell species or physiological state, by applying alternating current (AC) electric fields at frequencies where the responses differ between sub-populations.

Electrokinetic manipulation in the form of dielectrophoresis (DEP) can be used to selectively (usually by species or physiological state) trap biological microparticles to a set of electrodes through which impedance sensing can be used to sense their concentration. This technique has been demonstrated many times in the literature, and has been called Dielectrophoretic Impedance Measurement (DEPIM). This is most effective when a particle suspension is flowing past the electrodes so that the particles can be trapped out of the fluid as it passes, due to the local nature of the DEP forces.

Travelling wave dielectrophoresis (TWD) is a technique which can be used to move cells in a more continuous manner over a large array of electrodes, to a subset of electrodes, or to regions adjacent to an array of electrodes, within a stationary suspending medium. Travelling wave dielectrophoresis has been demonstrated in the literature to be useful for concentrating suspended particles such as biological cells, using single-layer fabricated microelectrodes with spiral geometries, to a single area from a particle suspension. This concentration can also be done selectively, as different particles have different responses versus applied phase-quadrature signal frequency.

Absent from the literature, are devices which take advantage of this concentration ability in conjunction with impedance sensing or impedance spectroscopy, to sense the suspended particles as they are concentrated.

This thesis presents microfabricated devices, and associated electronic systems which use techniques involving travelling wave dielectrophoresis, as-opposed to dielectrophoresis, to selectively concentrate particles within a stationary fluid, to a subset of electrodes through which electrical impedance spectroscopy is used to determine particle sub-population concentrations.

Several different device designs are briefly outlined and discussed, as well as associated signal processing electronic systems. A final single device design is described and testing of operation detailed. Testing of several different modes of operation of this device are discussed, including sensing the concentration of a single type of cell using a single phase-quadrature signal frequency, as well as using multiple phase-quadrature signal frequencies to separateand sense two different cell sub-populations.

These or similar devices could be used as sensors which could potentially be more selective and sensitive than DEPIM devices, and without requiring a fluid flow, such as that generated by a microfluidic system.