{"id":"M10-047","slug":"ph-responsive-fluorescent--M10-047","source":{"id":"M10-047","dataset":"techtransfer","title":"pH-responsive fluorescent false neurotransmitters for measuring secretory vesicle pH","description_":"<p>Optical imaging of neurons is a useful tool for the study of neurotransmission. Fluorescent false neurotransmitters (FFNs) mimic the body's neurotransmitters and allow researchers to visualize neurotransmission simultaneously with other fluorescent markers. This technology revises FFNs so that they can be pH responsive by exploiting fluorescence characteristics. Since the secretory vesicles of neurons are pH driven researchers utilizing this technology may now visualize not only neurotransmission, but also optically measure pH levels of these secretory vesicles. </p>\r\r<h2>A non-toxic, photostable, and simple way of measuring pH in synaptic vesicles</h2>\r\r<p>Previously, the only technologies that allowed researchers to visualize vesicular pH were cumbersome and time-consuming. For instance, in vitro visualization required transfections of vectors into cells, a technique that in large part fail to achieve very high efficiency. Moreover, transfections often kill cells and are difficult to succeed in ex vivo studies. Former in vivo experiments achieving optical measurements of pH could only be done via transgenic animal models, which can take years to generate, without guaranteed success. This technology offers a non-toxic, photostable, simple alternative: a pH-responsive, fluorescent false neurotransmitter. Cells incubated with the fluorescent compound showed selective uptake by VMAT vesicles, while pH measurements were performed using fluorescent microscopy, demonstrating the technology's ease of use. </p>\r\r<p>This technology has been tested in vitro using PC12 cells. </p>\r\r<h2>Lead Inventor:</h2>\r\r<p><a href=\"http://www.columbia.edu/cu/chemistry/groups/sames/dali.html\">Dalibor Sames, PhD</a></p>\r\r<h2>Applications:</h2>\r\r<ul>\r<li>Tool to measure pH of secretory vesicles of synapses for neuroscience research</li>\r<li>Can be used for neuropsychiatric diseases</li>\r<li>May be adapted as an in vitro diagnostic tool to measure neurotransmitter irregularities in neurodegenerative diseases such as Alzheimer's or Parkinson's</li>\r<li>May be adapted as a high throughput screening tool for pharmaceutical agents</li>\r</ul>\r\r<h2>Advantages:</h2>\r\r<ul>\r<li>Does not require cell transfection </li>\r<li>Does not require generation of transgenic animals </li>\r<li>Accurate and sensitive measurement of pH</li>\r<li>Photostable</li>\r<li>Non-toxic</li>\r<li>Targets VMAT-expressing secretory vesicles found in neurons and neuroendocrine cells </li>\r</ul>\r\r<h2>Patent information:</h2>\r\r<p>Patent issued (<a href=\"http://patentscope.wipo.int/search/en/WO2008013997\">WO2008013997 A3</a>)</p>\r\r<p>Tech Ventures Reference: IR M10-047</p>\r\r<h2>Related Publications:</h2>\r\r<ul>\r<li><a href=\"http://www.ncbi.nlm.nih.gov/pubmed/19423778\">Gubernator NG, Zhang H, Staal RG, Mosharov EV, Pereira DB, Yue M, Balsanek V, Vadola PA, Mukherjee B, Edwards RH, Sulzer D, Sames D. \" Fluorescent false neurotransmitters visualize dopamine release from individual presynaptic terminals. \" Science. 2009 Jun 12;324(5933):1441-4.</a></li>\r</ul>\r","tags":["Dopamine","Fluorescence microscope","Genetically modified animal","High-throughput screening","Medical optical imaging","Medication","Neurodegenerative disease","Neuroendocrine cell","Neuroscience","Neurotransmitter","Reuptake inhibitor","Synapse","Synaptic vesicle","Transfection"],"file_number":"M10-047","collections":[],"meta_description":"A non-toxic, photostable pH-responsive fluorescent probe (FFN) visualizes vesicle pH alongside neurotransmission in neurons.","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":3.0,\"scalability\":3.0,\"timeliness\":2.0},\"weighted_score\":3.35,\"risks\":[\"Patent/ freedom-to-operate uncertainty (older tech with potential prior art)\",\"possible safety/toxicity concerns for in vivo translation\",\"limited clinical/readout translation beyond research tool\",\"dependency on VMAT-specific vesicle targeting may limit universality\"],\"one_sentence_take\":\"The concept is novel and impactful as a research tool with a reasonable readiness trajectory but faces translational/timeliness constraints and potential scope limitations beyond specialized research use.\"}","inventors":["Dalibor Sames","David Sulzer Ph.D.","Minhee Lee","Niko Gubernator"],"manager":"Jerry Kokoshka","depts":["Chemistry","Psychiatry"],"divs":["Columbia University Medical Center (CUMC)","Faculty of the Arts & Sciences"],"date_released":"2014-08-25"},"highlight":{},"matched_queries":null,"score":0.0}