Clues into "Blinking” Phenomena Could Improve Biologic Imaging

More than 100 years ago, at the beginning of contemporary quantum mechanics, the Nobel Prize-winning physicist Neils Bohr predicted so-called "quantum jumps.” He predicted that these jumps would be caused by electrons making transitions between distinct energy levels of individual atoms and molecules. Although controversial in Bohr's time, such quantum jumps were experimentally observed, and his prediction confirmed, in the 1980s. More recently, with the development of single molecule imaging techniques in the early 1990s, it has been possible to observe similar jumps in individual molecules.

In research terms, these quantum jumps translate to discrete interruptions of the continuous emission from single molecules, revealing a phenomenon known as florescent intermittency or "blinking.” However, while specific instances of blinking can be directly ascribed to Bohr's original quantum jumps, many more cases exist where the observed fluorescence intermittency does not follow his predictions. Particularly, in systems as varied as fluorescent proteins, single-light harvesting complexes, single organic fluorophores, and, most recently, individual inorganic nanostructures, distinct deviations from Bohr's predictions occur.

Consequently, virtually all know fluorophores, including fluorescent quantum dots and molecules, exhibit unexplainable episodes of intermittent blinking in their emission. The underlying quantum mechanical process responsible for this phenomenon is a continuing mystery in modern chemical physics.

In an article appearing in the July 2, 2008, issue of the journal Nature Physics, University of Notre Dame (Notre Dame, IN, USA) physicist Dr. Bolizsar Janko and his coworkers presented a progress report on recent research, including their own, that has been geared at solving the mysteries of these fluorescent molecules or flourophores. They hope the article will help initiate further experimental and theoretical activity to clarify the ambiguity of fluorescence intermittency.

Finding the answer could lead to powerful imaging probes that will enable future researchers to better monitor disease-related molecules within cells. "Fluorescent molecules could be of fundamental importance in imaging biological systems and monitoring dynamic processes in vivo,” Dr. Jankó said. "One of the most attractive types of flourophores today are semiconductor nanocrystal quantum dots [NQD]. Their small size, brightness, photo stability, and highly tunable fluorescent color make them vastly superior to organic dyes.”

The blinking phenomenon, however, presents a great difficulty in using these dots, particularly for such applications as single-molecule biologic imaging, where a single NQD is used as a fluorescent label. "The NQD is fluorescent for some time, a so-called "on-time,” and then becomes optically inactive, experiencing an "off-time,” whereupon it turns on again,” Dr. Jankó reported.

If the blinking process could be regulated, quantum dots could, for instance, provide better, more stable, multi-color imaging of cancer cells or provide researchers with real-time images of a viral infection, such as HIV, within a cell. "It is very important to elucidate the origin of this phenomenon and to identify ways to control the blinking process,” Dr. Jankó said.

Dr. Jankó's Notre Dame research group already has taken a strong first step toward understanding the phenomenon through research by group member Dr. Masaru Kuno, an assistant professor of chemistry and biochemistry at the University. Dr. Kuno has discovered that the on- and off-time intervals of intermittent nanocrystal quantum dots follow a universal power law distribution. This discovery has provided Notre Dame researchers and others with the first clues into developing a deeper insight into the physical mechanism behind the vast range of on- and off-times in the intermittency.


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