Modern biology is driven by technology, explains Philip J. Lee, Ph.D., co-founder, president, and director of research at CellASIC a five-year-old company that develops microfluidic technologies for cell culture.
“While the last 50 years were dominated by gene and protein analysis, the current emphasis is to understand the cell as a system, and the next 50 years will focus on how cells interact to form functional tissues. CellASIC’s motivation is to determine how the need for cell-relevant environments for biologic studies can be met by engineering.”
In 2003 Dr. Lee and CellASIC co-founder Paul Hung, Ph.D., were graduate students in the laboratory of Luke Lee, Ph.D., a professor in the bioengineering department at the University of California, Berkeley. They began to utilize microfabrication methods to improve laboratory cell culture methods. What began as a quest to engineer a “better Petri dish” eventually led to experimenting with a continuous perfusion system that mimicked physiological tissue transport conditions with the ultimate goal of improving live-cell imaging.
“Live-cell imaging is the best way to monitor cells in vitro, because it allows for intracellular resolution and kinetic and spatial detail,” Dr. Philip Lee says. “While cells are dynamic systems that respond to changes in their environment, most studies cannot apply precise time-varying stimuli.”
Borrowing tools and technology from the semiconductor industry, CellASIC’s founders developed the capability to engineer structures on a microscale. They discovered that microfluidic technology enables the delivery of nanoliter volumes to individual units of an array, providing microenvironment control, reduction of sample volumes, inexpensive process automation, and the optical quality to monitor cell conditions in vitro. While microfluidic culture is “fundamentally different from dish-based cell culture,” it adapts to existing biological protocols, according to Dr. Lee.
“Advantages of microfluidic cell culture include creating better microenvironments that serve as models for complex cell behaviors, enabling integration and increased complexity in cell biology, and making live-cell studies easier with novel types of experimentation and more uniform experiment conditions, reduced cost, labor, and reagent use.”
In 2005 CellASIC rented a small laboratory near the university and obtained funding by writing research grants. While the company still gets a large portion of its funding from SBIRs, it is now generating product revenue from its first product, ONIX, launched in 2007. The ONIX microfluidic perfusion platform delivers a high level of control for live-cell imaging experiments. The platform integrates with users’ existing inverted microscope systems to enable dynamic time-lapse experiments. Its flow control system allows for computer-controlled dynamic flow switching for time-lapsed live-cell microscopy.
The ONIX platform’s single-use microfluidic plates work with two independent flow units with identical flow properties to enable simultaneous imaging of two sets of cell/medium combinations. The yeast cell microfluidic plate is optimized for time-lapsed imaging of yeast cells with solution exchange. The microfluidic cell-trapping region holds yeast cells in a uniform focal plane for time-lapse cell microscopy during perfusion flow. The mammalian cell microfluidic plate enables time-lapsed imaging of cultured mammalian cells with solution switching. The microfluidic cell culture region ensures optimal cell health during long-term microscopy studies.
Dr. Lee says the ONIX system is easy to use, with less than 10 minutes required to start collecting data. It is also compatible with existing cell culture workflow. To use ONIX, the researcher pipettes the cell suspension onto a microfluidic plate using capillary-driven cell loading, cultures the cells in a standard incubator via gravity-driven perfusion if desired, pipettes the media and solutions into flow inlet wells, seals them to the ONIX manifold, places the plate on an inverted microscope stage, specifies the solution exposure profile, and performs live-cell imaging.