Over the past half century, electrical engineers have honed their skills in the race to build ever tinier microprocessors. Now their expertise is being directed toward developing a new type of chip: one that contains a miniature, state-of-the-art biology lab. "To do biological experiments, you want the biological counterparts of logic gates, inputs, and outputs," says Ming Wu. "You need to be able to move cells around."
Optoelectronic Tweezers: EECS Professor Ming Wu is holding a light-actuated microfluidic chip. When combined with a digital light projector, the chip can perform a wide variety of user-programmed microfluidic functions, such as trapping and tracking 10,000 individual cells. (Photo by Peg Skorpinski) Moving cells around is Wu's specialty. Together with his students, he has developed a new technology to enable biology researchers to individually manipulate and control large numbers of particles at once. The technology, called "optoelectronic tweezers," is still in the laboratory stage, but Wu is working with biotechnology companies to develop "labs-on-a-chip" that feature it. "We want to make it simple enough, general enough so that anyone can use it," he says.
Industrial-scale biology experiments typically feature giant machines piping liquid and robots carrying out parallel test tube operations. Labs-on-a-chip would enable researchers to do on-the-spot lab experiments using tiny samples and minuscule amounts of reagent, notes Wu. Health workers could perform a full spectrum of blood tests with less than a drop of blood, and field workers could quickly and efficiently determine whether a water source has been contaminated or compromised.
Over the past decade or so, other technologies for labs-on-a-chip have been introduced, but none of them feature the combination of precision and scale of Wu's optoelectronic tweezers. Optical tweezers, which use laser beams to move cells, use 100,000 times more energy than Wu's technology and have a limited manipulation area, so they cannot move large numbers of cells at once. Electrokinetic tools, which work by creating electrical fields that attract or repel particles, can efficiently move large numbers of particles but lack the flexibility and resolution needed to manipulate individual cells.
Optoelectronic tweezers combine the best features of both technologies, allowing researchers enough precision to manipulate single cells while, at the same time, enabling them to control an array of tens of thousands of cells at once. Wu's labs-on-a-chip are also reprogrammable. "Our circuit is like a piece of blank paper and we can write the circuit on the paper," says Wu.
In Wu's optoelectronic tweezer experiments, particles suspended in fluid are sandwiched between two layers of glass, the lower of which has been coated with a photoconductive material. A red light-emitting diode illuminates a digital micromirror device—the picture-creating technology used in modern televisions and projectors. The pattern is projected onto the photoconductive surface where it excites virtual electrodes, creating non-uniform electric fields that pull particles away from the illuminated areas, entrapping them in the dark zones.
Because the forces act differently on cells depending on their properties, the technology can also be used to sift out a small number of cells or particles of a certain type, such as white blood cells or stem cells, or to separate dead cells from living ones. Wu and his students have even managed to create a sort of optical conveyor belt that sorts cells by diameter. "Most experiments are done with a population of cells and by measuring an average response," Wu says. "Researchers can use our technology to separate out only the cells that have positive response, say, to a drug. They can then perform genomic analyses of the cells or try to control the cells interactively by varying the drugs.
The technology could also be used to create a series of precisely defined environments for drug discovery, Wu suggests. For instance, pharmaceutical researchers trying to find the optimal combination of several drugs for attacking a particular type of bacteria or virus could create a chip on which the relative proportion of the drugs changes gradually over a series of sites.
The group is currently working with biotechnology companies, as well as with the National Institutes of Health Nanomedicine Development Centers at Berkeley and UCLA, to fine-tune the technology.