Vanderbilt engineer develops tiny tweezers to trap nanoscale molecules as small as proteins

An assistant professor of electrical engineering has developed the first-ever opto-thermo-electrohydrodynamic tweezers, optical nanotweezers that can trap and manipulate objects as small as proteins and viruses.

The technique, developed by Justus Ndukaife and two graduate students in his group, gives researchers a powerful new tool for the study and perhaps early detection of viruses, cancer and neurodegenerative diseases.

“The sky is the limit when it comes to the applications,” Ndukaife said.

Photos of Justus C. Ndukaife (Vanderbilt University)

“Stand-off trapping and manipulation of sub-10 nm objects and biomolecules using opto-thermo-electrohydrodynamic tweezers” was published online in the journal Nature Nanotechnology on August 31. The article was authored by Ndukaife and graduate students Chuchuan Hong and Sen Yang, who are conducting research in Ndukaife’s lab.

In 2018, one-half of the Nobel Prize was awarded to Arthur Ashkin, the physicist who developed optical tweezers, the use of a tightly focused laser beam to isolate and move micron-scale objects, which are the size of red blood cells. Micron-scale optical tweezers represent a significant advancement in biological research but are limited in the size of the objects they can manipulate.

The laser beam that acts as the pincer of an optical tweezer can only focus the laser light to a diameter about half the laser’s wavelength. In the case of red light with a wavelength of 700 nanometers, for example, the tweezer can focus on and manipulate only objects with a diameter of approximately 350 nanometers or greater using low power. While extremely small, it still leaves out smaller molecules such as viruses, which come in at 100 nanometers, or DNA and proteins that measure less than 10 nanometers.

The technique that Ndukaife established leaves several microns between the laser beam and its target, an important element of how these new, tiny tweezers work.

“We have developed a strategy that enables us to tweeze extremely small objects without exposing them to high-intensity light or heat that can damage a molecule’s function,” Ndukaife said. “The ability to trap and manipulate such small objects gives us the ability to understand the way our DNA and other biological molecules behave in great detail, on a singular level.”

Nanotweezer (Justus Ndukaife)

Until now, molecules such as extracellular vesicles could only be isolated using high-speed centrifuges, but the technology’s high cost has inhibited wide adoption. This new approach, on the other hand, has the potential to become broadly available to researchers with smaller budgets. The tweezers can also sort objects based on their size, which is important when looking for specific exosomes, extracellular vesicles secreted by cells that can cause cancers to metastasize. Exosomes range in size from 30 to 150 nanometers, and sorting and investigating specific exosomes has typically proven challenging.

Other applications Ndukaife envisions include detecting pathogens by trapping viruses for study and researching proteins that contribute to conditions associated with neurodegenerative diseases such as Alzheimer’s. Both applications could contribute to early detection of disease because the tweezers can effectively capture low levels of molecules, meaning a disease does not have to be full-blown before disease-causing molecules can be researched. The tweezer can be combined with other research techniques such as biofluorescence and spectroscopy.

“I am looking forward to seeing how other researchers harness its capabilities in their work,” said Ndukaife, who collaborated with the Center for Technology Transfer and Commercialization to file for patent protection on this technology.

The research was funded by NSF grant ECCS-1933109 and Vanderbilt University.