research highlights

Lab-on-a-chip High-tech Petri dishes

A self-imaging Petri dish monitors cultures as they grow in the . In a scientist’s dream world, one would be able to sit quietly at the desk, browse the jour- nals and read research highlights, even think, while still keeping an eye on the cell cultures growing in the incubator. The cell cultures would be imaged automatically and project- ed live on the screen of a computer, and there would be no need to shuttle the cultures back and forth from the incubator to the micro- scope, to monitor their growth. This would not only make things easier for the scientist, The ePetri dish. Image courtesy of Guoan Zheng. it would also help reduce contaminations and perturbations to the culture that are caused Among the advantages of this lens-less by manual movement. approach is that the field of Guoan Zheng, Changhuei Yang and their view is as large as the sensor, and it does not colleagues at the California Institute of require focusing. Technology, have now made this dream a The authors used ePetri to culture an reality. In recent work, they built a Petri dish, embryonic stem cell line and track its growth ePetri, smart enough to autonomously image directly from the incubator. An Ethernet the biological sample plated on it. To build cable connected ePetri from the incubator ePetri, the authors capitalized on the cheap to a personal computer, and it took only a availability of high-pixel-number so-called couple of minutes to reconstruct the entire complementary metal–oxide semiconduc- high-resolution image of the culture dish. tor or CMOS imaging sensors that are com- The resolution of ePetri was equivalent to the mon in cell-phone cameras. They glued a type of image you would get from a conven- commercial CMOS sensor to the bottom of tional under the 40× objective a homemade square well and plated lens and was sufficient to follow changes in mammalian cells directly on its surface. For the cells’ morphology during differentiation Nature America, Inc. All rights reserved. All rights Inc. America, Nature 1 illumination, they used the LED screen of a and reconstruct cell lineage trees. cell phone supported with Lego blocks. Yang’s group is working hard to produce

© 201 Whereas building ePetri could have been several prototypes of ePetri to distribute to part of a middle-school science project, collaborators and other scientists. Additional retrieving high-resolution images from it work is needed to test whether the resolution required nontrivial microscopy methods. of ePetri is not affected by different types of “The current CMOS sensors have rather culture dish coatings and whether it can sup- large pixels, so when you put the cells direct- port growth of primary cells. Scientists can ly on them and strike a light, you get images also use ePetri to generate one single snap- that are intrinsically coarse,” explains Zheng. shot of an entire tissue, culture or organism. Zheng, Yang and colleagues devised a way Future developments could also integrate to work around this by reconstructing high- ePetri into other sophisticated lab-on-a-chip resolution images from a collection of lower designs and enable additional automation of quality ones. They directed the illuminating culture maintenance. light at different angles onto the cells and Perhaps the biggest limitation of the cur- took sequential images in which the cells’ rent version of ePetri is that it cannot be used shadow had moved by a fraction smaller for fluorescence imaging but Yang assures than a pixel. They then combined all the low- that a fluorescence-compatible version of resolution shadow images to generate one ePetri is soon to come. single high-resolution image of the entire E rika Pastrana culture dish using pixel super-resolution algorithms. “People have used these kinds of RESEARCH PAPERS Zheng G. et al. The ePetri dish, an on-chip cell algorithms to generate high-quality images of imaging platform based on subpixel perspective the moon taken from a collection of lower- sweeping microscopy (SPSM). Proc. Natl. Acad. Sci. resolution images,” Yang says. USA 108, 16889–16894 (2011).

nature methods | VOL.8 NO.12 | DECEMBER 2011 | 999