Biological dielectrophoresis: Applications to the determination of the dielectric properties of cells, to cell sorting, and to fusion

Abstract

Dielectrophoresis (DEP), the motion of neutral bodies induced by nonuniform electric fields, is widely applicable in biological problems. The DEP force, and hence the relative polarizability of all cells in aqueous media varies strongly with the applied frequency. This gives rise to DEP spectra which we find to be unique even for individual cells. For example, single cells can be readily ‘levitated’ by ac fields to balance against gravitational force, so as to provide precise spectra of the dielectric properties. In other apparatus to be described, streams of cells are subjected to nonuniform ac fields and their deflection into or out of the regions of high field intensity are measured to provide dielectric spectra and comparisons of cell types or normalcy. Moreover, such apparatus is readily arranged to provide cell sorting based upon intrinsic dielectric properties of the passing cells Finally, the DEP phenomenon can be applied “in reverse” so to speak, and used to probe the ac fields generated by the cells themselves. Here, the DEP effect exerted by the nonuniform ac field of a cell is studied with the aid of tiny polarizable particles (Micro-Dielectrophoresis), Again, the application of external rf fields is found to evoke cellular spinning at sharply resonant frequencies. Using both micro-DEP and cellular spin resonance, natural rf oscillations are found in a wide range of cell types, from bacteria to mammalian, indicating that it is “universal”. DEP is also useful in evoking cell fusion. Biological particles such as cells or their parts can be made to move simply by applying a nonuniform electric field. This motion occurs even though the cells or their parts are electrically neutral, and by its means we can control cells so as to sort them, to fuse them together, and to even assess their electrical nature. The fundamental phenomenon concerned is “dielectrophoresis”. Dielectrophoresis, hereafter abbreviated to DEP, is defined as the motion of neutral, polarizable matter produced by a nonuniform (ac or dc) field. DEP should be distinguished from electrophoresis, which is the motion of charged particles in a static electric field. The DEP of many particle types has been examined, resulting in numerous applications. Aerosols, glasses, minerals, polymer molecules, living cells, organelles, and virus particles were made to respond with DEP. Among the numerous applications developed are agglomeration, orientation, sorting or separations, dielectric characterization, levitation, and materials handling such as pumping, precipitation and filtration [1]. The effects of DEP are easily produced, and large particles especially respond in many useful ways. DEP, which is a gentle effect, can how-ever be observed on particles ranging in size even down to the molecular level under special conditions. Sincethermal (Brownian motion) effects tend to disrupt ordering by gentle actions such as that of DEP, a practical lower limit of particle size in normal usage comes in at about the level of virus particle sizes. Particles such as cells, however, are easily handled by DEP.