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 (Ϸ0.9 m for the first and Ϸ0.8 m 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.optofluidic microscopy ͉ phenotype characterization ͉ microfluidic O ptical microscopy pervades almost all aspects of modern biomedicine and bioscience; to name a few key areas, optical microscopes are vital instruments in microorganism studies, cell biology, and clinical pathology. However, despite the long history of microscopy and the remarkable range of optical tools that have been developed since the invention of the first microscope in the early 1600s, the fundamental design of microscopes has undergone little change. A typical microscope still consists of an objective, space for relaying the image, and an eyepiece or an imaging lens to project a magnified image onto a person's retina or a camera. In addition to its relatively high implementation cost (precise and expensive lenses are needed), the conventional microscope design has also proven difficult to miniaturize (1, 2). A relatively modern invention-digital inline holographic microscopy (DIHM) (3)-showed that it is possible to render microscope-resolution images of objects without the use of lenses; however, as a method, DIHM requires significant postmeasurement computation and the use of a coherent light source. In 2005, Lange et al. (4) reported a direct projection method to implement compact and low-cost imaging systems. In Lange's method, the specimen is placed...