Rounding up wayward cells and particles under a microscope slide can be as difficult as corralling wild horses on the range, particularly if there’s a need to separate a single individual from the group.
But now, a new device dubbed an “optoelectronic tweezer” developed by UC Berkeley engineers and primarily funded by UCLA’s Institute for Cell Mimetic Space Exploration, will enable researchers to easily manipulate large numbers of single cells and particles using optical images projected on a glass slide coated with photoconductive materials.
“This is the first time a single light-emitting diode has been used to trap more than 10,000 microparticles at the same time,” said Ming Wu, UC Berkeley professor of electrical engineering and computer sciences and principal investigator of the study.
“Optoelectronic tweezers can produce instant microfluidic circuits without the need for sophisticated microfabrication techniques.”
This technique, reported in the July 21 issue of the journal Nature, has an advantage over existing methods of manipulating cells, such as optical tweezers that use focused laser beams to “trap” small molecules. Such devices require high-powered lasers, and their tight focusing requirements fundamentally limit the number of cells that can be moved at the same time.
A large part of Wu’s research was conducted while he was an electrical engineering professor at UCLA, and a co-principal investigator at NASA’s Institute for Cell Mimetic Space Exploration, housed at UCLA’s Henry Samueli School of Engineering and Applied Science.
Wu and his graduate students, Pei Yu Chiou and Aaron Ohta, also improved upon other cell manipulation tools that use electrokinetic forces to create electric fields that either repel or attract particles in order to move them. Dielectrophoresis, for instance, can move larger numbers of particles. However, it lacks the resolution and flexibility of optical tweezers.
The engineers found a way to get the best of both worlds by transforming optical energy to electrical energy through the use of a photoconductive surface. The idea is similar to that used in the ubiquitous office copier machine. In xerography, a document is scanned and transferred onto a photosensitive drum, which attracts dyes of carbon particles that are rolled onto a piece of paper to reproduce the image.
In this case, the researchers use a photosensitive surface made of amorphous silicon, a common material used in solar cells and flat-panel displays. Microscopic polystyrene particles suspended in a liquid were sandwiched between a piece of glass and the photoconductive material. Wherever light would hit the photosensitive material, it would behave like a conducting electrode, while areas not exposed to light would behave like a non-conducting insulator. Once a light source is removed, the photosensitive material returns to normal.
Depending upon the properties of the particles or cells being studied, they will either be attracted to or repelled by the electric field generated by the optoelectronic tweezer. Either way, the researchers can use that behavior to scoot particles where they want them to go.
There are many reasons why researchers would want the ability to easily manipulate cells. Biologists may want to isolate and study the fetal cells that can be found in a mother’s blood sample, for instance, or sort out abnormally shaped organisms from healthy ones.
“This sorting process is now painstakingly done by hand,” said Wu, who is also co-director of the Berkeley Sensor and Actuator Center. “A technician finds the cell of interest under a microscope and literally cuts out the piece of glass where the cell is located, taking care not to cut the sample.”
“Our design has a strong practical advantage in that, unlike optical tweezers, a simple light source, such as a light-emitting diode or halogen lamp, is powerful enough,” said Chiou, a Ph.D. student in electrical engineering and computer sciences and lead author of the paper. “That is about 100,000 times less intense than the power required for optical tweezers.”
In addition, because the optoelectronic tweezers generate patterns through projected light, an almost limitless range of patterns are possible.
“We can almost change these patterns on the fly,” said Ohta, also a Ph.D. student in electrical engineering and computer sciences. “For other manipulation tools, changing these electrode patterns meant fabricating a new chip. Now, we can just project a new image to generate any type of pattern we want.”
The researchers are now studying ways to combine this technology with computer pattern recognition so that the sorting process could be automated. “We could design the program to separate cells by size, luminescence, texture, fluorescent tag and basically any characteristic that can be distinguished visually,” said Wu.
This research is also supported by the Defense Advanced Research Project Agency, the Graduate Research and Education in Adaptive Bio-Technology training program, and the National Science Foundation.