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Published August 5, 2008 | Published
Journal Article Open

Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging


Low-cost and high-resolution on-chip microscopes are vital for reducing cost and improving efficiency for modern biomedicine and bioscience. Despite the needs, the conventional microscope design has proven difficult to miniaturize. Here, we report the implementation and application of two high-resolution (≈0.9 μm for the first and ≈0.8 μm for the second), lensless, and fully on-chip microscopes based on the optofluidic microscopy (OFM) method. These systems abandon the conventional microscope design, which requires expensive lenses and large space to magnify images, and instead utilizes microfluidic flow to deliver specimens across array(s) of micrometer-size apertures defined on a metal-coated CMOS sensor to generate direct projection images. The first system utilizes a gravity-driven microfluidic flow for sample scanning and is suited for imaging elongate objects, such as Caenorhabditis elegans; and the second system employs an electrokinetic drive for flow control and is suited for imaging cells and other spherical/ellipsoidal objects. As a demonstration of the OFM for bioscience research, we show that the prototypes can be used to perform automated phenotype characterization of different Caenorhabditis elegans mutant strains, and to image spores and single cellular entities. The optofluidic microscope design, readily fabricable with existing semiconductor and microfluidic technologies, offers low-cost and highly compact imaging solutions. More functionalities, such as on-chip phase and fluorescence imaging, can also be readily adapted into OFM systems. We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications.

Additional Information

© 2008 by the National Academy of Sciences. Freely available online through the PNAS open access option. Communicated by Amnon Yariv, California Institute of Technology, Pasadena, CA, May 13, 2008 (received for review March 31, 2008). Published online before print July 28, 2008, doi: 10.1073/pnas.0804612105. We are grateful for the constructive discussions with and the generous help from Professor Axel Scherer, Jigang Wu, Dr. Zahid Yaqoob, Dr. Claudiu Giurumescu, Oren Schaedel and Dr. Xiaoyan Robert Bao. We appreciate the assistance of the Caltech Watson clean-room. This work is funded by DARPA's Center of Optofluidic Integration, the Wallace Coulter Foundation, National Science Foundation Career Award BES-0547657, and National Institutes of Health Grant R21 PA03-107. L.M.L. thanks the Croucher Scholarship for financial support. P.W.S. is an Investigator of the Howard Hughes Medical Institute. Author contributions: X.C., P.W.S., D.P., and C.Y. designed research; X.C., L.M.L., X.H., and W.Z. performed research; X.C. and L.M.L. analyzed data; and X.C., L.M.L., X.H., W.Z., P.W.S., D.P., and C.Y. wrote the paper. X.C. and L.M.L. contributed equally to this work. The authors declare no conflict of interest.

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