The first draft of the human genome took more than a decade of research and cost some $3 billion. Today, new techniques for high-speed DNA sequencing have radically reduced the time and cost to decrypt roughly 3 billion base pairs that form the blueprint for human life.
Yet the human genome is far from the whole story. To fully understand the biological underpinnings of health and disease, scientists must probe the world of proteins — large, complex molecules required for the structure, function and regulation of the body’s tissues and organs. 
Chao Wang, a researcher with the Biodesign Center for Molecular Design and Biomimetics at Arizona State University, and his colleagues are advancing an ambitious project: developing new methods for sequencing individual protein molecules using a rapid, accurate and inexpensive method. Download Full Image
Now, Chao Wang, a researcher with the Biodesign Center for Molecular Design and Biomimetics at Arizona State University, and his colleagues are advancing an ambitious project: developing new methods for sequencing individual protein molecules using a rapid, accurate and inexpensive method.
Single-molecule protein sequencing of this kind holds the potential to revolutionize diagnostic medicine through the identification of protein biomarkers for cancer and other deadly diseases, provide earlier and more accurate diagnoses and deepen our understanding of how healthy cells function.
“Sequencing proteins and analyzing their post-translational modifications are particularly important for the studies of heart disease, cancer, neurodegenerative diseases and diabetes,” says Wang, who is also an associate professor in the School of Electrical, Computer and Energy Engineering at ASU. “One important future use of this technology is single-cell level proteomic analysis, which can have profound impact on both disease diagnostics and therapeutics.”
Wang’s work combines nanoscience with biotechnology and focuses on nanofabrication, nanoelectronics, nanofluidics, plasmonics and biosensing.
Multipurpose building blocks
In addition to maintaining proper biological functioning of cells and tissues throughout the body, protein interactions are implicated in many diseases. Ideally, researchers would like to read protein sequences with the ease of current DNA sequencing methods, investigating the complexities of protein behavior and finding new therapies for a broad range of protein-linked maladies, including cystic fibrosis, diabetes, cancer, Alzheimer’s disease and Parkinson’s disease.
Until now however, the goal has proved challenging and elusive.
Chao Wang is a researcher with the Biodesign Center for Molecular Design and Biomimetics at Arizona State University and an associate professor in the School of Electrical, Computer and Energy Engineering.
Chao Wang is a researcher with the Biodesign Center for Molecular Design and Biomimetics at Arizona State University and an associate professor in the School of Electrical, Computer and Energy Engineering.
Unlike DNA, which is composed of just four nucleotide letters, proteins are made up of some 20 different amino acids, which bind together to form sequences, before folding into complex 3D configurations. These 20 amino acids arrange themselves to form tens of thousands of proteins in the body.
To further this research, Wang has received the prestigious NIH Director’s New Innovator Award. In 2022, the NIH awarded over $200 million to support transformative biomedical research projects under four research categories. The NIH Director’s New Innovator Award was established in 2007 as part of its High-Risk, High-Reward Research program to “accelerate the pace of biomedical, behavioral and social science discoveries by supporting exceptionally creative scientists with highly innovative research.”
“This award is indeed a great honor and surprise. The opportunities ASU provided to me during the past few years have really allowed me to work across disciplinary boundaries to pursue crazy but scientifically meaningful ideas,” Wang says. “This award certainly marks a new beginning for my journey ahead. It provides not only the funds that are otherwise difficult to obtain for this project, but also more confidence to continue my multidisciplinary path in both research and education.”
Stephen Phillips, director of the School of Electrical, Computer and Energy Engineering, notes that electrical engineers don’t often earn this award.
“Chao Wang’s challenging work across several disciplines in engineering, biology and health reflects the impressive level of innovation and creativity that this award is intended to further,” Phillips says. “His ongoing efforts to leverage transdisciplinary ideas to accomplish new results is sure to inspire others to follow his lead.”
RELATED: ASU professor to study new genome editing tools with NIH Innovator Award
Sequence of innovations
Currently, the gold standard for sequencing proteins is mass spectrometry, but the method has a variety of limitations. For many applications, mass spectrometry is simply not sensitive enough. The technique, which requires bulky, expensive machinery and technological expertise, requires about a million protein copies in a sample to make an accurate detection.
Researchers would like to identify individual protein molecules, which would allow the ferreting out of details particular to each separate protein, including modifications that may affect the protein’s function.
To make single-molecule protein sequencing an affordable and practical tool, several difficulties plaguing current efforts must be overcome. These include sensing system reliability, slow readout, high noise and high cost.
The new project addresses these issues with the design of an on-chip integrated, electronic system. The proteins are read sequentially using a low noise nanopore composed of sapphire for greater accuracy.
The device is outfitted with additional photonic nanostructures, electronic device components, and circuit elements capable of translating single-molecule protein fingerprints into electronic signals. This synchronous recording will improve the accuracy, potentially enabling the identification of all 20 amino acids at a higher throughput than existing methods.
The researchers will further improve protein identification using deep-learning algorithms. The result is a portable device capable of rapid, accurate, inexpensive protein sequencing, poised to improve data throughput by two to three orders of magnitude.
Novel nanopores
The idea of using nanopores for sequencing has been around awhile, and several variants of the method have been used successfully for DNA sequencing. The technique feeds sequences of DNA nucleotides or, in the case of proteins, amino acids, through a very narrow pore, much like a length of thread passing through a needle’s eyelet. The nanopore must be fabricated a few billionths of a nanometer in diameter. A detector then scans each member of the DNA or protein sequence as it passes through the nanopore.
The new single-molecule protein sequencing technique makes use of a very low-noise, all-sapphire nanopore fluidic device, as well as two different sensing modes, which combined dramatically improve the accuracy of the amino acid identifications. The use of sapphire also provides improved structural stability over other materials, a crucial consideration for a device that must be engineered to exacting standards at nanoscale dimensions.
Although the amino acids in the protein sequence are fluorescently tagged, the method does not require expensive and labor-intensive fluorescent microscopy to read the signals, which are picked up by the optoelectronic channel of the circuit.
The use of advanced semiconductor chip design and manufacturing technologies has the potential to lower the costs, decrease the instrument size and directly digitize data for biology and health care use. Such advances can accelerate translation between bench and bedside.
The single-molecule protein sequencing device is Wang’s latest nanobiotechnology creation. In earlier research, he demonstrated the power of combining semiconductor and nanophotonic technologies to design faster, more accurate, less expensive and more broadly accessible biosensing technologies, including portable devices for the detection of infectious agents, such as Ebola and SARS CoV-2, as well as for African swine fever.
Grant ID: DP2-GM149552
Science writer, Biodesign Institute at ASU
480-727-0378 richard.harth@asu.edu
In 1880, the Grand Canyon was a mystery.Oh, people might have read John Wesley Powell’s 1875 book, ultimately titled “The Exploration of the Colorado River and Its Canyons,” but the book wasn’t so much a deep dive into the size, beauty and geology of the Grand Canyon as much as it was a tale of the Wild West.“It was meant to be a geological treatise, but it was actually written more as a…
In 1880, the Grand Canyon was a mystery.
Oh, people might have read John Wesley Powell’s 1875 book, ultimately titled “The Exploration of the Colorado River and Its Canyons,” but the book wasn’t so much a deep dive into the size, beauty and geology of the Grand Canyon as much as it was a tale of the Wild West.
“It was meant to be a geological treatise, but it was actually written more as an adventure novel because he needed to sell it and get more appropriations from Congress,” said Matthew Toro, director of maps, imagery and geospatial services at the ASU Library.
A portrait of Clarence Dutton is on display as part of the ASU Library’s “Dutton’s Atlas” exhibit. Photo by Charlie Leight/ASU News
It was Dutton, Powell’s protege, who forever changed the perception of the Grand Canyon. In 1882, Dutton published the “Tertiary History of the Grand Canyon District with Atlas,” a geological “masterpiece,” Toro said, that used literary prose, science, landscape illustrations from Thomas Moran and Williams Henry Holmes, and a collection of topographic and geologic maps to transform the perception of the Grand Canyon.
“It’s really the first comprehensive work of Grand Canyon geology,” Toro added.
To celebrate the 140th anniversary of Dutton’s work, the ASU Library, along with support from Arizona State University’s Institute for Humanities Research, the School of Geographical Sciences and Urban Planning, the School of Earth and Space Exploration, and a grant from Arizona Humanities, has created an interactive exhibit titled “Dutton’s Atlas: How Cartography Helped the Canyon Become Grand.”
The exhibit, which includes digitized versions of Dutton’s six maps and complementary physical items from the canyon, will be available for public viewing beginning Oct. 22, on the first floor of the Hayden Library on ASU’s Tempe campus.
A symposium featuring several speakers on topics such as geology and photography of the canyon will be held at the exhibit kickoff that Saturday, from 11 a.m. to 4 p.m., and the physical exhibit will be open at least through the end of this semester and possibly into the spring semester, Toro said.
The digital replica of the exhibit is available here.
The exhibit was designed by Amy Watson, who leads the design team for the ASU Library, and included work by Toro, the project’s director, Stephen Pyne, professor emeritus at the School of Life Sciences, Steven Semken, professor at the School of Earth and Space Exploration, and Julie Tanaka, formerly the curator for rare books and manuscripts of the ASU Library.
Several students also worked on the project, most notably Paityn Schlosser, a senior geology major who admitted she really had no idea what she was getting into when she saw the 20-hours a week job pop up on an email chain.
“I didn’t think I had any chance,” Schlosser said. “I applied and Matt emailed me on a Friday and said, ‘Can you come in at 4 p.m. for an interview?’
“I was like, ‘Screw it. What do I have to do lose?’ And then (at the interview), he said, ‘Do you know anything about Clarence Dutton?’ I said, ‘No.’”
She does now.
Map and Geospatial Hub student workers Giovanni Catanzaro (left) and Paityn Schlosser and staff member Eric Friesenhahn (right) discuss aspects of the “Dutton Atlas” exhibit on Tuesday, Oct. 18, in the lobby of the Hayden Library on ASU’s Tempe campus. Photo by Charlie Leight/ASU News
The exhibit will highlight Dutton’s work in a variety of ways, including the prose he used to describe the canyon. In one writing, he begins, “The Grand Canyon of the Colorado is a great innovation in modern ideas of scenery and in our conceptions of the beauty and power of nature.”
Viewers of the exhibit will also see the three illustrations from Holmes’ Panorama from Point Sublime, a 3D-printed and hand-painted map puzzle, and three rocks from the Grand Canyon collected by Semken, and have the opportunity to use an interactive online multimedia exhibit that curates the atlas with maps, images and video.
“You can literally come and touch and feel the rocks. You can see what the state of geographical knowledge was back in the late 19th century,” Toro said. “The most important part, really, is that we’ve digitized all of the actual maps from Dutton’s Atlas and put them into real-world geographical coordinates. So the user will have the option to overlay these maps with modern geological data on a touch screen. They can really see the way the state of geological knowledge has evolved over the last 140 years.”
Schlosser said she hopes that when people see the exhibit, “they get the enjoyment of geology and they understand the importance of understanding what’s beneath us.”
“A lot of people commonly associate geology with just a blow-off science,” Schlosser added. “This is one of the most informational-based sciences that you could ever do. I hope it piques some people’s interest and hopefully more people will go to the Grand Canyon and get to see what it’s all about.”
Map and Geospatial Hub Director Matthew Toro (left) talks with student worker Giovanni Catanzaro, a second-year geography student, at the “Dutton Atlas” exhibit on Tuesday, Oct. 18, in the lobby of Hayden Library on ASU’s Tempe campus. Photo by Charlie Leight/ASU News
Reporter , ASU News
Scott.Bordow@asu.edu
Contact us