A compact, lightweight, dual-mode microscope that uses holograms instead of lenses could prove to be a boon for global health initiatives. The palm-size device, developed at UCLA, costs only $50 to $100 to make. It features a transmission mode that can be used to probe relatively large volumes of blood or water, and a reflection mode that can image denser, opaque samples. The spatial resolution for both modes is less than 2 μm — comparable to that achieved by bulkier microscopes with low- to medium-power lenses. In reflection mode, the holographic microscope can create images of dense, opaque materials such as water filters. (a-b) Laser light from a laser diode (LD) is projected through a pinhole (PH) and then split into two beams by a beam cube (BC). One beam of light hits the sample; the other does not. The beams are then reunited to form an interference pattern, which is recorded on a CMOS image sensor. (c) This photograph shows the microscope in reflection mode, with its cover removed. (The inset shows what the microscope looks like with its cover on.) The 200-g device is 15 cm long, 5.5 cm high and 5 cm wide. (Images: Ozcan BioPhotonics Group, UCLA/Biomedical Optics Express. “This is the first demonstration of essentially a handheld version of a microscope that can do dual-mode imaging within a very compact and cost-effective form,” said co-developer Aydogan Ozcan, senior author of the Biomedical Optics Express paper that describes the device. With just a small amount of training, doctors could use devices like these to improve health care in remote areas of the world with little access to diagnostic equipment, Ozcan said. The microscope could help ensure water quality, test patients’ blood for harmful bacteria, and even be used to measure the quality of livestock semen on farms. It could also prove useful in health crises such as Europe’s recent outbreak of E. coli. These pictures compare a piece of skin tissue imaged with the holographic microscope to the same piece of tissue imaged with a conventional microscope. The top two images (a-b) show the raw, unprocessed hologram — the light interference pattern — that is collected by the microscope’s sensor in reflection mode; the second image (b) is a zoomed-in version of the first (a). A computer-reconstructed image of this skin tissue is at the bottom left (c). The bottom right (d) shows a picture of the same specimen taken with a conventional objective-lens microscope. “It’s a very challenging task to detect E. coli in low concentrations in water and food,” Ozcan said. “This microscope could be part of a solution for field investigation of water or food, or maybe pathogens in blood.” Part of the device’s success is the weight it shed when researchers got rid of the bulkier, heavier, more expensive pieces that most microscopes rely on for collecting and focusing light: the lenses. Instead of lenses, this microscope uses holograms. Holograms are formed when light bouncing off (or passing through) a three-dimensional object is made to interfere with a “reference beam,” or light that has not hit the object. In the device, an inexpensive light source is divided into two beams — one that interacts with microscopic cells or particles in the sample, and one that does not. The beams then pass to an adjacent sensor chip, where their interference pattern is recorded. Software analyzes that pattern and recreates the path taken by the light that passed through or bounced off the objects being imaged. Each component of the device is fairly inexpensive, Ozcan said. The laser light could come from a $5 laser pointer. The sensor chip that collects that light is the same as the detectors in the back of an iPhone or Blackberry and costs less than $15 per chip. And the whole image-collecting system runs on two AA batteries. Where the researchers have reduced weight and expense in doing away with lenses, they have added the power of the cloud. The microscope captures raw data, but a computer is required to reconstruct the images. Users in the field could employ their laptops to process the information or send it over the Internet or mobile phone networks to a remote server. Ozcan has founded a company that is developing this technology with the goal of making a version of the microscope that can be manufactured and sold to health care workers and hobbyists. For more information, visit: www.ucla.edu