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!
Move over, lasers: Scientists can now create holograms from neutrons, too
21.10.2016 | National Institute of Standards and Technology (NIST)
Finding the lightest superdeformed triaxial atomic nucleus
20.10.2016 | The Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences