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Clues into "Blinking” Phenomena Could Improve Biologic Imaging

By MedImaging staff writers
Posted on 31 Jul 2008
A new study provides new insights into one of the remaining unsolved mysteries of quantum mechanics.

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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90 (56.028366088867): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=293510000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
91 (31.948089599609): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=293510000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
92 (38.14697265625): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
93 (77.962875366211): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (52.928924560547): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (46.014785766602): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (73.909759521484): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (37.193298339844): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (!!!!! 3479.9575805664): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (101.80473327637): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1
106 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1
107 (115.15617370605): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
108 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
109 (73.909759521484): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=293510000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
110 (555.03845214844): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=293510000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (106.0962677002): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
112 (!!!!! 2956.8672180176): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
113 (62.942504882812): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=293510000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
114 (556.94580078125): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=293510000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
115 (!!!!! 3731.0123443604): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
116 (544.07119750977): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
117 (127.07710266113): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
118 (83.92333984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
119 (75.817108154297): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
120 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
121 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
122 (68.187713623047): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
123 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
124 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
125 (313.99726867676): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
126 (!!!!! 47061.920166016): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
127 (!!!!! 4169.9409484863): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=293510000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=293510000 AND type='deeppockets_item' AND published='1' LIMIT 1
128 (!!!!! 17540.93170166): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
129 (89.883804321289): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
130 (45.061111450195): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
131 (32.901763916016): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
132 (42.200088500977): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
133 (32.186508178711): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
134 (330.92498779297): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
135 (50.067901611328): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
136 (38.862228393555): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
137 (31.948089599609): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
138 (512.12310791016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
139 (328.06396484375): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
140 (61.988830566406): SELECT name FROM jos_deeppockets WHERE id=215
141 (75.101852416992): SELECT name FROM jos_deeppockets WHERE id=215
142 (637.05444335938): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
143 (537.87231445312): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
144 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
145 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
146 (!!!!! 28042.078018188): TRUNCATE TABLE jos_trademed_module
147 (80.108642578125): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=293510000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
148 (56.028366088867): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=293510000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
149 (!!!!! 2192.0204162598): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
150 (84.877014160156): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
151 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
152 (44.107437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
153 (!!!!! 1224.9946594238): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
154 (144.00482177734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
155 (131.13021850586): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
156 (53.882598876953): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=293510000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=293510000 AND type='deeppockets_item' AND published='1' LIMIT 1
157 (36.001205444336): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=215 or channel_id is null)
158 (30.040740966797): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=215 or channel_id is null)
159 (32.901763916016): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
160 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
161 (44.107437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=293510000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=293510000 AND published='1' LIMIT 1
162 (35.04753112793): select jos_twitters.link from jos_twitters where cat=10
163 (29.087066650391): select jos_facebook.link from jos_facebook where cat=10
164 (29.087066650391): select jos_google_plus.link from jos_google_plus where cat=10
165 (29.087066650391): select jos_linkedin.link from jos_linkedin where cat=10