A ‘lab on a chip’ can measure protein and DNA interactions

Double stranded DNA fragment. Credit: Vcpmartin/Wikimedia/CC BY-SA 4.0

New nanophotonic tweezers developed by Cornell researchers can fit a chip less than one square inch, making it easier and more efficient to manipulate single molecules with light in order to examine biological systems.

In new research, Michelle Wang, James Gilbert White University Distinguished Professor of Physical Sciences in the College of Arts and Sciences, and her lab demonstrate that her nanoscale device, the nano-standard wave trap (nSWAT), can use enough power to perform a range of standard single-molecule experiments, including : stretching DNA molecules, decompressing DNA molecules, and disrupting and mapping protein-DNA interactions.

Their result was the first demonstration of a nanophotonic platform – rather than a massive tabletop setup – for such high-strength single-molecule manipulation. A successful demonstration paves the way for commercial availability, which could lead to its use in medical research.

The paper, “Nanophotonic Resonator Standing Wave Array for Single-molecule Processing and Measurement,” was published Jan. 10 in Nature Communications. Lead author is Fan Yi, a postdoctoral researcher in Wang’s lab with contributions from lab members James Inman, research specialist; and doctoral students Yifeng Hong and Porter Hall.

Previously, treating molecules with light — a technique known as optical trapping — required expensive, specialized equipment on a tabletop and could be inefficient, as researchers scanned one DNA molecule at a time.

“Nanophoton tweezers contain all the optical components of a tabletop, and they’ve been minimized to the nano-size but have the same functions,” said Wang, an investigator at Howard Hughes Medical Institute (HHMI).

In 2014, Wang and her lab announced the invention of nSWAT as a prototype, Wang said.

The main function of this generation of nSWAT sanctuaries is the power to understand and animate single molecules. The researchers show that nSWAT can apply the force needed to complete a set of precise experiments that biophysicists routinely perform while studying specific DNA-binding proteins.

James Inman, a research specialist in Wang’s lab, said macro-optical tweezers — a tabletop setup — can make very precise nanoscale measurements. The drawback, however, is that researchers have to look at one molecule of DNA at a time. Other technologies, including magnetic tweezers, offer higher throughput, Inman said, but they lack the required precision.

“If you can balance the process, you can get more information much more quickly,” Inman said.

Using nSWAT, researchers can manipulate a group of molecules simultaneously using tiny plastic beads arranged in a line. The light flows through the waveguides, and leaks out from the main places to catch the small beads. Each is about half a micron wide, and these beads are the knobs used to grab DNA molecules in order to apply force.

“You can trap a bead in each of those knots along that line, trapping dozens to maybe 100 beads at a time,” Inman said. Then we put a second copy nearby.

A line of small beads joined together by a long, thin DNA molecule. The molecule is now in a position to allow researchers to run it through standard experiments: stretching, unwinding, and mapping interactions.

The nSWAT chip does not contain a light source, Inman said. To use nSWAT, the lab must be equipped with a laser as a source of light and electricity and contacts to connect the electrodes and microscopes.

Also: water. The “lab-on-a-chip” works in an aqueous solution and is very small, Inman said, requiring only one drop.

This work was performed at the Cornell Science and Technology NanoScale (CNF) facility, one of the world’s leading nanofabrication facilities.

“[Here at CNF,] We have complex setups in soundproofed rooms on isolated optical tables,” Inman said. We hope to make single-molecule biophysics – and optical tweezers in particular – more popular. It produced a nanophotonic tweezer chip that cost only a few thousand dollars, he said.

“The hope is that this kind of basic research can be used to target proteins and treatment mechanisms,” Inman said.


Engineers make micron-scale optical tweezers


more information:
Fan Ye et al, Nano-resonant standing-wave array trap for single-molecule processing and measurement, Nature Communications (2022). DOI: 10.1038 / s41467-021-27709-3

Presented by Cornell University

the quote: ‘Lab on a Chip’ can measure protein-DNA interactions (2022, Jan 20) Retrieved Jan 21, 2022 from https://phys.org/news/2022-01-lab-chip-protein-dna-interactions .html

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