An Iowa State University and the Ames Laboratory research team has developed new microscope technology to study biological molecules. The new technology allows researchers to make 3-D measurements of single molecules with unprecedented accuracy and precision. The technology could be useful for medical researchers and other biology researchers who need very high-resolution data from microscopes.

The team led by Sanjeevi Sivasankar has blended optical and atomic force microscope technologies finding a way to complete 3-D measurements of single biological molecules with unprecedented accuracy and precision.

Sivasanker Yen Li at ISU

The existing technology allows researchers to measure single molecules on the x and y axes of a two dimensional plane. The new technology adds allowing researchers to make height measurements (the z axis) down to the nanometer – just a billionth of a meter – without custom optics or special surfaces for the samples.

Sivasankar, an Iowa State assistant professor of physics and astronomy and an associate of the U.S. Department of Energy’s Ames Laboratory said, “This is a completely new type of measurement that can be used to determine the z position of molecules.”

The full details of the technology have just been published by the journal Nano Letters.  Co-authors of the study are Sivasankar; Hui Li, an Iowa State post-doctoral research associate in physics and astronomy and an associate of the Ames Laboratory; and Chi-Fu Yen, an Iowa State doctoral student in electrical and computer engineering and a student associate of the Ames Laboratory.

Sivasankar’s research program has two objectives: to learn how biological cells adhere to each other and to develop new tools to study those cells. That’s why the new microscope technology – called standing wave axial nanometry (SWAN) – was developed in Sivasankar’s lab and backed by support from lab startup funds from Iowa State University and a $120 thousand dollar grant from the Grow Iowa Values Fund, a state economic development program.

Standing Wave Axial Nanometry Illustrated. Click image for the largest view. Use link to Nano Letters above for full details.

The short version of how the technology works is a researcher would attach a commercial atomic force microscope to a single molecule fluorescence microscope. The tip of the atomic force microscope is positioned over a focused laser beam, creating a standing wave pattern. A molecule that has been treated to emit light is placed within the standing wave. As the tip of the atomic force microscope moves up and down, the fluorescence emitted by the molecule fluctuates in a way that corresponds to its distance from the surface. That distance can be compared to a marker on the surface and measured, yielding the third dimensional value.

“We can detect the height of the molecule with nanometer accuracy and precision,” Sivasankar said.

The team’s paper reports that measurements of a molecule’s height are accurate to less than a nanometer.  They also report that measurements can be taken again and again to a precision of 3.7 nanometers.
Sivasankar’s research team used fluorescent nanospheres and single strands of DNA to calibrate, test and prove their new instrument.

Users who could benefit immediately from the technology include medical researchers who need high-resolution data from microscopes. Sivasankar thinks the technology has commercial potential and is confident it will advance his own work in single molecule biophysics.

“We hope to use this technology to move that research forward,” he said. “And in doing that, we’ll continue to invent new technologies.”

The biofuel crowd, the catalyst folks and the battery electrode people are going to love this, a lot sooner than the good folks in Ames Iowa realize.  The ability to see all three dimensions will help greatly, setting up the next jump, time elapsed images.

Way to go!  It’s a big improvement.


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