A new chip-based platform developed by researchers at UC Santa Cruz integrates nanopores and optofluidic technology with a feedback control system. In a paper published today in Nature Communications, the researchers report using the device to control the delivery of individual biomolecules—including ribosomes, DNA, and proteins—into a fluid-filled channel on a chip. They also showed that the device can be used to sort different types of molecules, enabling selective analysis of target molecules from a mixture.
The capabilities of the programmable nanopore-optofluidic device point the way toward a novel research tool for high-throughput single-molecule analysis on a chip. “We can bring a single molecule into a fluidic channel where it can then be analyzed using integrated optical waveguides or other techniques,” says senior author Holger Schmidt of UC Santa Cruz. “The idea is to introduce a particle or molecule, hold it in the channel for analysis, then discard the particle, and easily and rapidly repeat the process to develop robust statistics of many single-molecule experiments.”
The new device builds on the team’s previous work to develop optofluidic chip technology combining microfluidics with integrated optics for optical analysis of single molecules. The addition of nanopores allows controlled delivery of molecules into the channel, as well as the opportunity to analyze the electrical signal produced as a molecule passes through the pore.
With the feedback control system in the new device, real-time analysis of the current turns the nanopore into a ‘smart gate’ that can be programmed by the user to deliver molecules into the channel in a predetermined manner. The gate can be closed as soon as a single molecule has passed through, and opened again after a set time. The team even showed the device’s potential to selectively activate the gating function in response to a target molecule (e.g., DNA).
“The use of nanopores as ‘smart gates’ is a key step toward a single-molecule analysis system that is user-friendly and can work at high throughput,” Schmidt said. “It allows user-programmable control over the number of molecules that are being delivered to a fluidic channel for further analysis or processing, selective gating of different types of single molecules, and the ability to deliver single molecules into a chip at record rates of many hundreds per minute.”