Live cell imaging

Live cell imaging is the study of living cells using time-lapse microscopy. It is used by scientists to obtain a better understanding of biological function through the study of cellular dynamics. Live cell imaging was pioneered in first decade of the 20th century. One of the first time-lapse microcinematographic films of cells ever made was made by Julius Ries, showing the fertilization and development of the sea urchin egg. Since then, several microscopy methods have been developed which allow researchers to study living cells in greater detail with less effort. A newer type of imaging utilizing quantum dots have been used as they are shown to be more stable.

Before the introduction of the phase contrast microscope it was difficult to observe living cells. As living cells are translucent they must be stained to be visible in a traditional light microscope. Unfortunately, the process of staining cells generally kill the cells. With the invention of the phase contrast microscopy it became possible to observe unstained living cells in detail. After its introduction in the 1940s, live cell imaging rapidly became popular using phase contrast microscopy. The phase contrast microscope was popularized through a series of time-lapse movies (Video 1), recorded using a photographic film camera. Its inventor, Frits Zernike, was awarded the Nobel Prize in 1953. Other later phase contrast techniques used to observe unstained cells are Hoffman modulation and differential interference contrast microscopy.

Phase contrast microscopy does not have the capacity to observe specific proteins or other organic chemical compounds which form the complex machinery of a cell. Synthetic and organic fluorescent stains have therefore been developed to label such compounds, making them observable by fluorescent microscopy (Video 2). Fluorescent stains are, however, phototoxic, invasive and bleach when observed. This limits their use when observing living cells over extended periods of time. Non-invasive phase contrast techniques are therefore often used as a vital complement to fluorescent microscopy in live cell imaging applications.

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