The biomedical researchers realized that astronomers had already made great strides in solving a problem very similar to their own — isolating and analyzing one dot (in this case a star) in a crowded field of light. They hypothesized that a computer system designed for stellar photometry, a branch of astronomy focused on measuring the brightness of stars, could hold the solution to their problem.
Now, Georgia Tech and Emory researchers have created a technology based on stellar photometry software that provides more precise images of single molecules tagged with nanoprobes, particles specially designed to bind with a certain type of cell or molecule and illuminate when the target is found. The clearer images allow researchers to collect more detailed information about a single molecule, such as how the molecule is binding in a gene sequence, taking scientists a few steps closer to truly personalized and predictive medicine as well as more complex biomolecular structural mapping.
In addition to biomedical applications, the system could be used to clarify other types of nanoparticle probes, including tagged particles or molecules.
The research is detailed in this week’s online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).
“As more powerful imaging technologies are developed, scientists face a real challenge to quantitatively analyze and interpret these new mountains of data,” said May Wang, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “This PNAS paper is only a start, but I expect that innovative computing and data processing will be increasingly used to reveal detailed and quantitative features not currently available to biomedical researchers.”
“This work is pointing to a new era in light microscopy in which single molecule detection is achieved at nanometer resolution,” said Dr. Shuming Nie, a professor of biomedical engineering and chemistry and also the director of the Emory-Georgia Tech Cancer Nanotechnology Center. “This is also an example of interdisciplinary research in which advanced computing meets nanotechnology. I envision major applications not only for single-molecule imaging, but also for ultrasensitive medical diagnostics.”
Because scientists frequently use several different colors of nanoprobes to color code genes and proteins, a blended color dot is a common challenge when analyzing images. For every few green or red dots in an image, there could be a few yellow dots as well, indicating that at least two dots are clustering to create the appearance of a new color.
While less than precise nanoprobe images yield valuable information, the Georgia Tech and Emory research team knew that better technology was needed to pinpoint the exact distance in nanometers between probes to reveal important information about the size and binding geometry of targeted molecules.
“We had no way of knowing for sure if we were looking at one molecule or two or three molecules very near one another,” said Wang. “The fuzzy dot images were not precise enough on the nanometer level to truly tell us how these markers reflect DNA, but this system allows us to collect quantitative data and prove — not hypothesize — how genes are behaving.”
Instead of starting from scratch to create a system to isolate the clumped nanoprobe images, the Georgia Tech and Emory researchers pursued their stellar photometry idea by adapting DAOPHOT, a program written by Peter Stetson at the Dominion Astrophysical Observatory designed to handle crowded fields of stars.
After adapting DAOPHOT, the research team used color-coded nanoparticles to beat the traditional diffraction limit by nearly two orders of magnitude, allowing routine super-resolution imaging at one nanometer resolution. And by using DNA molecules, two color-coded nanoparticles are designed to recognize two binding sites on a single target. Then the particles are brought together within nanometer distances after target binding.
These distances are sorted out by highly efficient image processing technology, leading to detection and identification of individual molecules based on the target’s geometric size.
Compared to other single molecule imaging methods, the Georgia Tech and Emory system allows for higher-speed detection involving much larger sample volumes (microliter to milliliters).
Collaborators on the project include Amit Agrawal and Geoffrey Wang from the Departments of Biomedical Engineering and Chemistry at Emory and Georgia Tech, and Rajesh Deo from the Department of Physics and Astronomy at Georgia State University.
The research was funded by the National Institutes of Health, the Department of Energy Genomes to Life Program and the Georgia Cancer Coalition. Computer support was also provided by Microsoft and Hewlett-Packard.
The Georgia Institute of Technology is one of the nation's premiere research universities. Ranked seventh among U.S. News & World Report's top public universities, Georgia Tech's more than 18,000 students are enrolled in its Colleges of Architecture, Computing, Engineering, Liberal Arts, Management and Sciences. Tech is among the nation's top producers of women and African-American engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 100 interdisciplinary units plus the Georgia Tech Research Institute.
Megan McRainey | EurekAlert!
Spintronics: Researchers show how to make non-magnetic materials magnetic
06.08.2020 | Martin-Luther-Universität Halle-Wittenberg
Manifestation of quantum distance in flat band materials
05.08.2020 | Institute for Basic Science
Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.
Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...
An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.
Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...
Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
06.08.2020 | Earth Sciences
06.08.2020 | Power and Electrical Engineering
06.08.2020 | Life Sciences