New electrochemical platform paves the way for advanced portable diagnostic tools

ASU, University of Toronto develop first direct gene-circuit-to-electrode interface

November 25, 2019

Scientists at Arizona State University and the University of Toronto have developed the first direct gene-circuit-to-electrode interface by combining cell-free synthetic biology with state-of-the-art nanostructured electrodes. Long inspired by concepts from the field of electronics, with its circuits and logic gates, synthetic biologists have sought to reprogram biological systems to carry out artificial functions for medical, environmental and pharmaceutical applications. This new work moves the field of synthetic biology toward biohybrid systems that can take advantage of benefits from each discipline. 

“This is the first example of a gene circuit being directly coupled to electrodes and is an exciting tool for the conversion of biological information into an electronic signal,” said Keith Pardee, assistant professor in the Department of Pharmaceutical Sciences at the University of Toronto's Leslie Dan Faculty of Pharmacy. Biotech The direct gene-circuit-to-electrode interface unites biology’s ability to sense with the memory and decision-making capabilities of electronic systems. Photo by Steven Southon, University of Toronto Download Full Image

Study results were published today in Nature ChemistryThe interdisciplinary effort to create the new system brought together expertise in cell-free synthetic biology from the Pardee lab and electrochemistry from the Kelley lab at the University of Toronoto and sensor design from the Green lab in the Biodesign Center for Molecular Design and Biomimetics at ASU. 

“This new system enables us to detect many different signals simultaneously, which is essential for diagnostics and monitoring systems,” said co-author Alexander A. Green, researcher at the Biodesign Institute at the Arizona State University and assistant professor in the School of Molecular Sciences. “The electronic output means that in the future it can be readily interfaced with technologies like smartphones and distributed sensing arrays that could be brought directly to a patient’s bedside.”

Pardee, whose research group specializes in developing cell-free diagnostic technologies that can be used safely outside the lab, and Green, whose research group engineers molecular sensors, received widespread attention in 2016 when they and collaborators released a platform for the rapid, portable and low-cost detection of the Zika virus using paper-based synthetic gene networks.

“In our previous work detecting the Zika virus, we showed how you could embed the cellular machinery on a piece of paper, a nonbiological environment, to detect pathogens at very low cost,” Green said. “With this new work, we’re showing how you can connect the same cellular machinery to an electronic interface and detect multiple independent signals at the same time.” 

“With these hybrid biological-electronic systems we have the chance to take full advantage of biology’s ability to sense along with the capacity of electronic systems to process huge amounts of information, which should enable us to make more advanced and broadly useful diagnostics going forward,” he said.

Overcoming practical limits of optical signaling

Bringing the capacity to detect the Zika virus outside of the clinic and to the point of need was a crucial step forward, but the approach relied on conventional optical signaling — a change in color to indicate that the virus had been detected. This posed a challenge for practical implementation in countries like Brazil where viruses with similar symptoms require health care providers to screen for several different pathogens in order to correctly identify the source of a patient’s infection. 

This highlighted the need for a portable system that could accommodate many sensors in the same diagnostic test, a capability known as multiplexing. The challenge was that multiplexing with color-based signaling is not practical.

“Once you get beyond three color signals, you run out of bandwidth for unambiguous detection. Moving into the electrochemical space gives us significantly more bandwidth for reporting and signalling. We’ve now shown that distinct electrochemical signals can operate in parallel and without crosstalk, which is a much more promising approach for scaling up,” Pardee said.  

The new biohybrid system uses nonoptical reporter enzymes contained within 16 microliters of liquid, about a third the size of a water droplet, which pair specifically with micropatterned electrodes hosted on a small chip no more than one inch in length. Within this chip, gene circuit-based sensors monitor for the presence of specific nucleic acid sequences, which, when activated, trigger the production of one of a panel of the reporter enzymes. The enzymes then react with reporter DNA sequences that set off an electrochemical response on the electrode sensor chip.

Detecting antibiotic resistant genes

As a proof of concept, the team applied the new approach to detecting colistin antibiotic resistance genes that have recently been identified in livestock globally and represent a serious threat to the use of the antibiotic as a last resort treatment for infection. Four separate resistance genes were detected, demonstrating the ability of the system to effectively identify and report each gene independently, and also in combination.

For synthetic biologists, this new approach represents a potential technical leap forward. Conventional synthetic biology requires that logic calculations be encoded into the DNA of the gene circuit. This can be painstaking, taking months or years to build complex circuits. 

“What makes this combined approach so powerful is that the underlying connectivity of the gene circuit sensor outputs can be reprogrammed at will by simply modifying the code at the level of the software rather than at the level of the DNA which is much more difficult and time consuming,” said Shana Kelley, a university professor in the Department of Pharmaceutical Sciences at teh University of Toronto whose research group specializes in the development of highly sensitive electrochemical sensors. Bringing biology-based sensing together with electronic-based logic, memory and response elements, has the potential to transform medicine, biotech, academic research, food safety, and other practical applications, she said.

A powerful tool kit for the future

“In the future I think we’ll see these systems deployed in the field for diagnostics that detect panels of different pathogens based on the geographic region or the crops being cultivated to combat disease and increase food production,” Green said. “They’ll also be able to interface with smartphones to automatically analyze test results and gain critical information on how a pathogen is spreading over time.”

In Toronto, Pardee and his research group are excited to see where others in the synthetic biology field will take the system. “We’ve essentially created a new set of tools and opened up a new venue for signaling. Synthetic biology applications are limited at the reporting step and this has been a significant challenge. With this new combined approach, we think we can really accelerate the field and its capacity to improve lives.”

Adapted from story by Kate Richards, University of Toronto. Written by Dianne Price.

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Next-gen cybersecurity workforce spotlighted at two ASU-led events

November 25, 2019

Russian grid hacking. Cyberinfiltration of U.S. universities. Rampant data exposures. Spy tool-breaching. Shadow Brokers. And more.

These challenges — including cyberthreats, disinformation and privacy in the age of big data — are just a few of the big global cybersecurity challenges being tackled by faculty, researchers, scientists and students at Arizona State University’s Global Security Initiative. Last week, two ASU-hosted events put a critical spotlight on cybersecurity and the preparation and training of the industry’s future workforce.

The marquee event was the 10th annual meeting of the National Initiative for Cybersecurity Education, a conference in downtown Phoenix that brought together thought leaders from industry, government, academia and nonprofit organizations to address the community's cybersecurity education, training and workforce needs. Hosted by ASU, Florida International University and New America, the NICE Conference and Expo — “Reimagining the Future of the Cybersecurity Workforce: Adapting to a Changing Landscape” — provided an opportunity to share best practices from around the world and across sectors in order to build the workforce needed to confront cybersecurity risks now and in the future.

“Cybersecurity will play an increasingly important role in the future of work, particularly as automation permeates industries of all types,” said Sethuraman Panchanathan, executive vice president of ASU Knowledge Enterprise and the university’s chief research and innovation officer. “Interagency cooperation and collaboration with leading research institutions allows us to create ecosystems of education around this key issue.”

A keystone event at the NICE gathering was the “Future of Cybersecurity Education” panel discussion facilitated by FIU Chief Information Officer Robert Grillo, featuring Tina Thorstenson, ASU chief information security officer and deputy CIO for IT Governance, Policy and Information Security; Anne-Marie Slaughter, New America CEO; and Lee Lambert, Pima (Arizona) Community College chancellor.

“It is clear that the future of delivering better cybersecurity starts by improving the pipeline and qualifications of people who will become the front line of defense to address the myriad security threats that face us as a nation,” said Slaughter, who heads New America, a 20-year-old nonprofit think tank focused on the challenges caused by rapid technological and social change.

“By seeing firsthand the innovations put forward by Arizona State University and Florida International University in knowledge development, and seeing how it complements the work that New America is doing on cybersecurity and the cyber workforce, it really gives me hope that, though the cyber threats we face continue to multiply exponentially, we are training the next generation of cybersecurity experts who will challenge these threats,” she said.

Jamie Winterton, who moderated a cybersecurity careers panel during last weekend’s “Cyber Day 4 Girls” at the West campus and served as the academic co-chair of the NICE Conference, says ASU’s role in the two events is a reflection of the university’s standing in the industry and its advancement of a well-prepared cybersecurity workforce in the future.

“Ensuring the security of our internet-connected society – from protecting an individual’s personal information to ensuring the seamless operation of our electrical grid — is a tough challenge,” said Winterton, director of strategy for ASU’s Global Security Initiative, where she coordinates and participates in defense- and security-related research.

“The tough challenge is constantly evolving," she said. "ASU brings an innovative, mission-driven mindset to the problem, which is also reflected in how we approach cybersecurity education. ASU’s cybersecurity offerings can be found across the university — in computer science, IT, applied computing, business, law, politics and global studies and more. And we partner closely with community colleges, the local business community and government to address real-world threats.”

Slaughter, who was the first woman to serve as director of policy planning for the U.S. Department of State, says the NICE Conference was important to ensuring that the cybersecurity workforce remains a focus moving forward.

“We cannot adequately protect the nation from all of the cybersecurity threats that exist if we do not take care to ensure that we are mobilizing a workforce that reflects our entire population. ASU, FIU and other innovative universities are at the heart of making sure we're preparing appropriately for the future of cybersecurity threats.

“With cybersecurity, when time is of the essence to respond to these threats, it is important to fill critical positions quickly from a qualified and diverse workforce that can adapt to the cyberdangers of the moment,” Slaughter said.

To that end, ASU’s New College of Interdisciplinary Arts and Science partnered with IBM and GSI to host nearly 200 middle school girls from 14 schools around the Greater Phoenix area at its recent Cyber Day 4 Girls event. Cyber Day featured industry experts and panel discussions designed to give the students a greater understanding of cybersecurity issues such as the protection of personal information, the internet of things and the career opportunities that exist within the field.

Panchanathan says the university’s Global Security Initiative provides many of the answers and solutions to challenges in the field of security, including cybersecurity. As an initiative of the university’s Knowledge Enterprise, GSI has developed practical mission-relevant approaches and effective decision-oriented tools while working with defense, security and diplomacy communities. A prepared workforce for the future is one of those challenges.

“Exploring various aspects of security and identifying the specific skill sets and mindsets that will be crucial to this type of work in the future will help ensure we can proactively address challenges.”

Top photo: Speakers on the “Future of Cybersecurity Education” panel discussion converse during the 10th annual meeting of the National Initiative for Cybersecurity Education in downtown Phoenix on Nov. 19, 2019. Left to right, the panel consisted of Florida International Univeristy Chief Information Officer Robert Grillo; Pima (Arizona) Community College Chancellor Lee Lambert; New America CEO Anne-Marie Slaughter and ASU Chief Information Security Officer and Deputy CIO for IT Governance, Policy and Information Security Tina Thorstenson. Photo by Andy DeLisle

By Steve Des Georges