title: Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging.
abstract: 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 (approximately 0.9 microm for the first and approximately 0.8 microm 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.
authors.affiliation: Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Xiquan
authors.initials: X
authors.lastname: Cui
authors.forename: Lap Man
authors.initials: LM
authors.lastname: Lee
authors.forename: Xin
authors.initials: X
authors.lastname: Heng
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhong
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.forename: Demetri
authors.initials: D
authors.lastname: Psaltis
authors.forename: Changhuei
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000648:ultrastructure*; D002477:Cells / Q000648:ultrastructure*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D010641:Phenotype