KINGSTON, R.I. – Dec. 12, 2019 – Every little kid who dreams of growing up to be a chemist envisions working with test tubes to discover a breakthrough that changes science.
Jason Dwyer, associate professor of chemistry at the University of Rhode Island, was one of those young dreamers. But Dwyer’s tool of choice is not a test tube. It’s a silicon nitride nanopore, a nano-sized hole that can identify substances at their smallest detectable level – a single molecule.
“Nanopores are probably one of the hottest technologies out there in all of science,” said Dwyer, whose research group focuses on design, fabrication, and use of single-molecule nanopore sensors for bioanalytical and biochemical research. “People talk about detecting parts per million toxins or impurities. The best you can ever do is to detect a single molecule. This is a test tube that holds a single molecule and we can do profoundly different things with it.”
Dwyer’s work in advancing nanopore sensing has earned him an internationally recognized Innovation Award from the Federation of Analytical Chemistry and Spectroscopy Societies at its annual SciX Conference in Palm Springs, California, in October. He was selected from among four finalists for the award, which is given for the most innovative and outstanding research advancements debuted at the conference.
“Professor Dwyer’s approach to functionalizing the silicon nitride surface of the nanopores used for molecular sensing will be game-changing,” said Christopher Harrison, one of the judges on the awards panel, an associate professor of chemistry at San Diego State University, and vice president of the AES Electrophoresis Society. “The ability to precisely control the surface chemistry of the nanopores will allow for more reproducible and accurate single-molecule measurements. Most importantly to the anticipated broad impact of the technology that Professor Dwyer has developed is the simplicity of the approach, which will allow others in the field to incorporate it in their own research.”
“I think what set us apart was that we are focused on science and technology from the birth of an idea to the delivery of a device,” said Dwyer. “The critical idea was that we replaced a chemical process with an electrical one. That has allowed us to create a device that works every single time. It allows us to do experiments we wouldn’t otherwise be able to do, look at molecules that might not otherwise have been acceptable to this. The nice thing about the award is the recognition of both the novelty of the fundamental work and its importance for enabling better clinical diagnostics.”
The medical benefits for solid-state nanopore sensing are many. It has enabled DNA sequencing, the detection of disease, and quality control of medicines down to the single molecule. Electronic sensing in medicine has led to such technologies as home blood glucose detection, Dwyer said.
“We want something that can detect and sequence DNA, proteins, sugars, biomarkers of disease, which can tell you if that bacteria that’s colonizing your skin is a problem,” said Dwyer. “Or in the pharmaceutical industry, whether the drug molecule they’ve made is contaminated and they need to go back and fix it.”
Nanopore sensors have been a prominent tool in single-molecule research for more than 20 years. Through a hole about one hundred thousandth times smaller than a human hair, the sensor measures molecules that pass through it. An ionic current, also passing through the hole, makes it possible to identify the molecule. Solid-state silicon nitride nanopores, however, still faced a problem with surface chemistry.
Dwyer’s innovation has helped solve that problem. His research group has developed a chemical method to tailor the nanopore to the application, using chemical surface coating on the basic nanopore.
“We basically provide the best way so far of painting the inside of this pore with a surface coating,” said Dwyer, who has filed for a patent on the method. “In some sense, we’re sort of creating a Marvel universe of pores. The regular pore is Peter Parker, and it has some properties that can do certain things. But once you put the Spider-Man outfit on it – the coating – you can do many more things.”
Coating of the nanopore with reactive chemicals helps in a number of ways. Sticking can be a problem when trying to cram a molecule through a like-sized nanopore, but coating can help tweak the size of the nanopore to match the molecule. It can also control how quickly the molecule moves through the pore, or change the electric charge of the nanopore to deal with like-charged molecules.
The method also eliminated a conventional step of pretreating the surface with a hazardous chemical, hydrofluoric acid – a process that also rendered useless the nanopores Dwyer created in his lab.
“Hydrofluoric acid is probably the only chemical I’m afraid of. It dissolves bone, and it interacts with calcium and affects heart function. It’s nasty stuff,” said Dwyer. “So, we took what everybody had done in the literature for 20 years. We said let’s leave out this step that everyone thinks is essential and replace it with this other thing. And that worked. And that worked every single time.”
Down the road, the innovation has the potential to lower the cost of analysis, making the process more accessible. “If we make DNA sequencing cheaper – and our painting can help with that – you could do sequencing at home,” Dwyer said. “If you can sequence the DNA inside single cells, you can see if something’s a tumor cell. You could also sequence the bacteria on your kitchen sponge and determine if it’s worrisome.”
The surface coating method also has the potential of leading to the development of nanopores with surface chemistry that matches the application, and the creation of sensing tools that mimic nanopores found in nature.
“We are at the beginning of demonstrating the capability of what we can do with this and now we start to play,” he said. “People really haven’t had the ability to understand what coatings they should put on the pore because they haven’t had the ability to do it.”
This material is based on work supported by the National Science Foundation CAREER award CBET-1150085 and NSF award CHE-1808344. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.