Although x-ray crystallography can reveal the structure of molecules, numerous molecules cannot be crystallized and are not found naturally in crystallized form. A relatively new technique called x-ray diffraction microscopy is compatible with noncrystalline samples. However, this technique mostly has been restricted to national government laboratories because it requires light sources such as synchrotrons and free-electron and x-ray lasers, which cost millions of dollars and are so large that they span a football field. A team of researchers developed this lensless tabletop soft x-ray microscope that uses a computer algorithm and lasers that the group developed with a commercial x-ray CCD camera to achieve 70-nm resolution. Images reprinted with permission of PNAS.Therefore, tabletop diffraction microscopy systems have been developed that use laserlike soft x-ray sources based on electric discharge or on femtosecond laser emission through a capillary containing argon gas and an x-ray CCD camera. Because lenses can block some of the diffraction pattern from reaching the detector, lensless imaging systems based on these sources promise to achieve diffraction-limited resolution below 10 nm.However, lensless imaging systems have strict requirements and, thus, have until now not come close to the resolution of their large and expensive counterparts. A tabletop lensless imaging system that can achieve 70-nm resolution has been developed by researchers at JILA in Boulder, Colo., at Colorado State University in Fort Collins, at the University of California, Los Angeles, and at Lawrence Berkeley National Laboratory in Berkeley, Calif. In lensless imaging, an image-processing algorithm replaces the optics. It iteratively guesses which portion of the sample produced the scattered x-rays and constructs the image by refining those guesses. Because the algorithm reconstructs the image in this way, rather than capturing and leaving each image as is, the system is extremely insensitive to vibration. The researchers achieved the record-breaking resolution largely by developing this algorithm.The tabletop soft x-ray microscope imaged this simple figure with 70-nm resolution.Other factors that influence the resolution of lensless imaging include the coherence of the source, the scatter and the sampling ratio. To increase the coherence, the researchers lengthened the capillary tube used for the soft x-ray sources. The emission traveled through a Lebow low-bandpass aluminum filter and a pinhole in a box that reduced unwanted scatter. Mirrors built at Berkeley relayed the beam to the sample and out through a beam block built at JILA that reduced the intensity so as not to saturate the CCD camera. The sample was moved to the best diffraction angle with a Physik Instrumente piezo stage. Finally, the diffraction pattern was collected by an Andor Technology x-ray CCD camera. Each diffraction speckle was sampled with more than one pixel of the CCD chip. With the electrically generated laser, the researchers used the system to capture images of a simple figure, which were comparable in appearance to those taken with scanning electron microscopy. Measuring a line across parts of the image showed that the system achieved the record 71-nm resolution. With the source based on the femtosecond laser, they achieved 94-nm resolution, which is more than two times better than previously achieved with this source. The researchers said that the microscope likely will be broadly applicable to nanoscale investigations in materials science and biology. Principal investigator Margaret M. Murnane said, “It is possible that in 10 to 20 years, when this lensless x-ray microscope is fully developed, every hospital may have one for diagnosing disease via high-resolution images of single cells.”PNAS, Jan. 8, 2008, pp. 24-27.