There are highly sensitive analytical techniques for probing cellular and molecular events in very small volumes. The development of microtools for effective sample handling and separation in such volumes remains a challenge. Most devices developed so far use electrophoretic and chromatographic separation methods. We show that forces generated by ac fields under conditions of negative dielectrophoresis (DEP) can also be used. Miniaturized electrode arrays are housed in a microchannel and driven with high-frequency ac. A laminar liquid flow carries particles past the electrodes. Modification of the ac drive changes the particle trajectories. We have handled latex particles of micrometer size and living mammalian cells in a device which consists of the following four elements: a planar funnel which concentrates particles from a 1-mm-wide stream to a beam of about 50-micron width, an aligner which narrows the beam further and acts to break up particle aggregates, a field cage which can be used to trap particles, and a switch which can direct particles into one of two output channels. The electrodes are made from platinum/titanium and indium tin oxide (ITO) on glass substrates. Particle concentration and switching could be achieved for linear flow velocities up to about 10 mm s-1. The combination of this new method with high-performance optical detection offers prospects for miniaturized flow cytometry.

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We demonstrate that micrometre and sub-micrometre particles can be trapped, aggregated and concentrated in planar quadrupole electrode configurations by positive and negative dielectrophoresis. For particles less than in diameter, concentration is driven by thermal gradients, hydrodynamic effects and sedimentation forces. Liquid streaming is induced by the AC field itself via local heating and results, under special conditions, in vortices which improve the trapping efficiency. Microstructures were fabricated by electron-beam lithography and modified by UV laser ablation. They had typical gap dimensions between 500 nm and several micrometres. The theoretical and experimental results illustrate the basic principles of particle behaviour in ultra-miniaturized field traps filled with aqueous solutions. The smallest single particle that we could stably trap was a Latex bead of 650 nm. The smallest particles which were concentrated in the central part of the field trap were 14 nm in diameter. At high frequencies (in the megahertz range), field strengths up to 56 MV can be applied in the narrow gaps of 500 nm. Further perspectives for microparticle and macromolecular trapping are discussed.

Replacing dysfunctional endocrine tissues (eg, islets) with healthy, nonautologous material protected against the immune defense of the patient could soon become a reality. Recent advances have resulted in the development of alginate-based microcapsules that meet the demands of biocompatibility, long-term integrity, and function. Focus on the development of good manufacturing practice-conforming microfluidic chip technology for generation of immunoisolated transplants and on cryopreservation technology will bring the cell-based therapy to the market and clinics.

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