Integrated circuit/microfluidic chip to programmably trap and move cells and droplets with dielectrophoresis

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Original entry: Nan Niu, APPHY 226, Spring 2009

by Thomas P. Hunt, David Issadore and R. M. Westervelt

Abstract

This article presents an advanced topic in technology and is directly related to soft matters. The essence of this paper is a device built by Professor Westervelts group utilizing both electrical and fluidic devices for the manipulation of soft matters, such as cells, vesicles, and droplets. Such kind of lab-on-a-chip device is one of the most advanced biomedical device because it combined the programmability of CMOS technology with the current microfluidic technology therefore allowing varieties of applications. This integrated circuit/microfluidic chip can trap and move individual living biological cells and chemical droplets along programmable paths using dielectrophoresis (DEP). Moreover, the chip is capable of simultaneously and independently controlling the location of thousands of dielectric objects. Using this hybrid chip, the authors have moved yeast and mammalian cells through a microfluidic chamber at speeds up to 30 mm sec-1. According to the authors, thousands of cells can be individually trapped and simultaneously positioned in controlled patterns. For the more advanced function, the chip can trap and move pL droplets of water in oil, split one droplet into two, and mix two droplets into one.

Experiment

Integrated circuit architecture

IC Block Diagram
Schematic Diagram

Experimental set-up

Experimental set-up

Dielectrophoresis theory

Dielectrophoresis is the motion of a dielectric object in a nonuniform electric field. A non-uniform electric field creates an induced electric dipole in a dielectric that feels a force in the non-uniform field. By applying an appropriate local electric field pattern, any particle with a dielectric constant different to that of the surrounding medium can be manipulated with DEP. The DEP force on a spherical particle is:

  • <math>F_\mathrm{DEP} = 2\pi r^3\varepsilon_m \textrm{Re}\left\{\frac{\varepsilon^*_p - \varepsilon^*_m}{\varepsilon^*_p + 2\varepsilon^*_m}\right\}\nabla \left|\vec{E}\right|^2</math>

Experimental Result

Simulation
Experiment

The simulation pictures shows electric field magnitude and the force field for an 8 mm diameter sphere above the chip with the dielectric properties of a cell in a water bath. The simulation geometry was modelled on an actual chip geometry beneath a 200 mm deep microfluidic chamber filled with water. In the simulation, two pixels were set to 5 V, leaving all the other pixels at ground as shown in a) of the simulation picture. Simulation picture b) shows the electric field, from which the DEP forces were calculated and shown in simulation picture c). As the authors calculated for experiment, an 8 mm diameter cell above one electrode would be subject to a DEP force of approximately 5 pN when a neighbouring electrode was energized.

The experiment picture a) shows the time sequence of the DEP manipulation of yeast cells. Pixels are energized in sequence to move first one cell alone and then all three together. The maximum speed of a yeast cell was approximately 30 mm sec-1. Picture b) shows the complex pattern of thousands of yeast cells patterned by DEP. Pixels across the array were energized to spell out "Lab on a Chip", attracting cells toward the local maxima of the electric field. Picture c) shows the time sequence of yeast and rat alveolar macrophages manipulated with DEP. Pixels on the chip were energizedto independently move the two cells and then bring them together. Picture d) shows the splitting, moving and combining water drops in oil with DEP with the energized pixels highlighted in white. Droplets were deformed by energizing multiple sets of pixels. Holding a droplet in place with two energized pixels, another set of pixels was energized to stretch the droplet. As it was stretched, the single droplet elongated and pinched in the middle to form two separate droplets. The droplets recombined when they were brought into contact.