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Biologists want to see more details and get more information about various processes, and they are pushing the limits of microscopy by developing new methods to do just this.
Australian scientists have used a combination of immunoelectron, fluorescence and 3D structured illumination super resolution microscopy to capture malaria parasites in the act of invading red blood cells. The researchers from the Walter and Eliza Hall Institute of Medical Research and the University of Technology, Sydney, achieved enough detail to analyze cellular and molecular events underlying each discrete step of malaria invasion. They then used this information to propose a comprehensive model for the molecular basis of parasite invasion. Some of these steps are shown in the images, with the red blood cell superimposed for context. The parasite (nucleus in blue) forms a tight junction (green) that is like a window that it inserts into the red blood cell to gain entry. The secretory organelle (red) secretes its contents through the tight junction (green), creating a vacuole in which the parasite lives inside the red blood cell. Once invasion is complete the window is closed and will later break down. This work was published in a Cell Host & Microbe paper. Read more about what super resolution microscopy can do in the primer, Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells.
UCLA neuroscientists are gaining insight into a form of autism thanks to a new technique called multifocal two-photon microscopy with spatiotemporal excitation-emission multiplexing (STEM). The neuroscientists collaborated with physicists to modify a two-photon laser-scanning microscope, splitting the main laser beam into four smaller beamlets. This allowed them to record four times as many brain cells as the earlier version of the microscope, or they could record four times faster. They also used a different beam to record neurons at various depths inside the brain, giving a 3-D effect, which had never been done previously. Using the technique for calcium imaging produces a high-resolution 3-D video of neuronal circuit activity in a living animal. Carlos Portera-Cailliau, a member of the research team who studies a form of autism known as Fragile X syndrome, has already used the technique to compare the cortex of a normal mouse with a Fragile X mutant mouse and observed the misfiring that occurs in the Fragile X brain. The work is published in a Nature Methods paper.
Nongjian (N.J.) Tao and his colleagues at the Biodesign Institute at Arizona State University have developed an electrochemical impedance microscope that adds spatial information to electrochemical impedance spectroscopy (EIS). In EIS, AC voltage is applied to an electrode and the current response is measured. Impedance can be used to detect processes such as a molecular binding event and apoptosis of cells taking place on the electrode surface. The new electrochemical impedance microscope uses surface plasmon resonance to measure impedance with submicrometre spatial resolution. The researchers used the microscope to monitor the dynamics of apoptosis and electroporation in individual cells with millisecond time resolution, reporting the work in a Nature Chemistry paper. The technique's spatial and temporal resolution allow the study of individual cells as well as subcellular structures and processes without labels and a ~2 pS detection limit in terms of admittance (inverse of impedance). [source]
Next time you’re taking a break from the microscope, take a moment to appreciate the beauty and art of your own microscopic images or get some inspiration from others by browsing through the latest Materials Research Society “Science as Art” competition.
Photo Credits:
Malaria image: David Riglar and Jacob Baum, Walter and Eliza Hall Institute, with support from Cynthia Whitchurch and Lynne Turnbull of the University of Technology, Sydney.
STEM microscope: UCLA