June 12, 2006
Smart Petri Dish Monitors Live Cells in Real Time
Using nanostructured photonic silicon crystals as a surface for cell growth, researchers in the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer at the University of California, San Diego, have created a straightforward method for observing changes in cell structure in real time. This “smart Petri dish” could enable new methods of high-throughput screening for preclinical safety testing or drug discovery studies.
Michael Sailor, Ph.D., and Sangeeta Bhatia, Ph.D., led the team of investigators that explored the use of photonic crystals as real-time sensors of cell biology. The key idea underpinning this work is that these nanoengineered crystals scatter light around a narrowly defined range of frequencies in a manner that is sensitive to changes in cell structure. Being able to observe changes in this optical signature without the use of any biochemical labels translates into a system that can monitor cell growth and health in real time and without the use of any equipment other than a standard reflectance microscope.
To prepare this smart Petri dish, the researchers coated porous silicon crystals with the polymer polystyrene. The polymer fills pores in the silicon crystal, creating a surface similar to that of conventional Petri dishes. The investigators then seeded this surface with primary hepatocytes, or liver cells; hepatocytes are used commonly to study drug metabolism. They then treated the cells with cadmium, a known toxin, and observed over 85 minutes. As cadmium exerted its toxic effect, scattering from the regions of the crystal underneath, cells grew noticeably brighter. In particular, cell nuclei and cell boundaries exhibited sharp changes in contrast.
The investigators also performed control experiments using conventional polystyrene Petri dishes and using a phase-contrast microscope and cell staining. The results were consistent with those observed using the nanostructured silicon plates, confirming that the cells were not affected by the surface on which they were grown. However, the increased sensitivity afforded by measuring changes in light scattering enabled the investigators to spot toxicity-related changes approximately two hours earlier than was possible using phase-contrast microscopy and staining.
This work, which was funded in part by the National Cancer Institute, is detailed in a paper titled, “The smart Petri dish: a nanostructured photonic crystal for real-time monitoring of living cells.” Since participating in this study, Dr. Bhatia has moved to the Massachusetts Institute of Technology, where she will work with both the UCSD Center and the MIT-Harvard Center of Cancer Nanotechnology Excellence. This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s web site.