Microscopy has gotten a makeover. Scientists have redefined the concept of an optical microscope by removing the lens, resulting in an imaging system small enough to fit in the palm of a hand but powerful enough to create 3-D optical tomographic images of large volumes of minuscule samples. Before it was demonstrated in an experiment at the University of California, lens-free optical tomographic imaging on a chip had never been seen. The idea stemmed from the recent progress in miniaturizing life sciences tools with microfluidic and lab-on-a-chip technologies. Until now, optical microscopy had not kept pace with this trend, said Aydogan Ozcan, associate professor of electrical engineering at UCLA’s Henry Samueli School of Engineering and Applied Science. Invented more than 400 years ago, the optical microscope has grown larger and more complex during modifications to image ever smaller objects with better resolution. Addressing the lack of progress in miniaturization, Ozcan’s research group set out to develop a tomographic microscopy platform through lens-free imaging technology. A schematic of a lens-free tomography setup, depicting the angles of rotation for the light source to illuminate a sample. Images courtesy of UCLA. The new system takes advantage of the fact that organic structures are partially transparent, so that shining a light on a sample of these cells creates shadows that reveal not only its outline, but also details about its subcellular structure. Those details could be captured and analyzed by scientists if the shadow were directed onto a digital sensor array, the researchers say, resulting in an image taken without a lens. This lens-free system would act as one component in a lab-on-a-chip platform, Ozcan said, potentially fitting beneath a microfluidic chip used for precise control and manipulation of biological samples and fluids. The two tools would work in tandem, with the microfluidic chip depositing and subsequently removing a sample from the lens-free imager in an automated process. An artistic rendering of a sample being tomographically imaged, showing the individual sections. To create the platform’s 3-D images, the light source must be rotated to illuminate the samples from multiple angles, enabling the use of tomography. The result is a 3-D image without sacrificing resolution. In addition, the system offers a much larger field of view and depth of field because the imaging is done by a digital sensor array, rather than being constrained by a lens. An optical imaging system small enough to fit onto an optoelectronic chip could speed scientific work significantly, greatly affecting the fields of cell and developmental biology. The chip’s small size also could lead to cost savings on equipment.