Faculty Research

Rapid Virus Test Being Studied in Zhang Group will Differentiate SARS-CoV-2 from Other Respiratory Viruses

Yi Zhang Group
(from left to right) Guangfu Wu, Huijie Li, and Zhengyan Weng, advised by Professor Yi Zhang, are checking an array of graphene field-effect transistors.

In recent years, from H1N1 and now to SARS-CoV-2, global pandemics caused by highly contagious viral species have been threatening human life and putting tremendous pressure on healthcare services as well as the economy. Rapid testing and timely interventions for asymptomatic or mild infections caused by SARS-CoV-2, for example, would enable efficient quarantine of infected patients, thus significantly reducing the spread rate of the virus. Importantly, SARS-CoV-2 is expected to continue in the future fall/winter seasons, when it will coincide with the seasonal outbreak of other infectious respiratory diseases, including those caused by influenza virus and respiratory syncytial virus, which have similar signs and symptoms in the early stages. Considering the overlap in the seasonal peaks, symptoms, and underlying risk factors of these illnesses, having a rapid test to detect and differentiate SARS-CoV-2 from other infectious respiratory viruses will be clinically important.

In response to this clinical need, the Institute of Materials Science and Biomedical Engineering Assistant Professor Yi Zhang led the development of the most sensitive amplification-free SARS-CoV-2 diagnostic platform, the CRISPR Cas13a graphene field-effect transistor. This study, entitled “Amplification-Free Detection of SARS-CoV-2 and Respiratory Syncytial Virus Using CRISPR Cas13a and Graphene Field-Effect Transistors,” was published online on May 12, 2022, in the journal Angewandte Chemie International Edition.

“The key features of viral diagnostics are rapidness and sensitivity,” said Zhang. According to Zhang, most virus detection techniques, including the gold-standard RT-PCR, relies on viral sequence amplification, which can dramatically complicate the detection process and increase the risk of cross-contamination, therefore subject to elevated false-positive rates. However, current amplification-free methods are still limited by compromised sensitivity. “Our work revolutionized the field of amplification-free nucleic acid diagnostics by introducing a biosensing platform with sensitivity comparable with RT-PCR,” he said.

Yi Zhang
Dr. Yi Zhang

Derived from adaptive immunity in prokaryotes, Nobel-winning clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) technology leverages nucleic acid base pair complementarity between a guide RNA and targeted nucleic acid sequence and affords high target specificity capable of discriminating single mismatches. Recently, several CRISPR/Cas systems, including Cas13a, were found to perform cleavage of nonspecific bystander nucleic acid probes triggered by target detection, known as “collateral cleavage.” Such collateral cleavage demonstrates a multi-turnover behavior, turning a single target recognition event into multiple probe cleavage events, and therefore leads to signal amplification.

“The idea of our biosensor design originates from exploiting the signal amplification by translating CRISPR technology onto an ultrasensitive detection platform,” said Huijie Li, a Ph.D. student in Zhang’s lab; she is also the leading first author of the study. Graphene, as a two-dimensional material, exhibits extraordinary charge carrier mobility and thus high electrical conductivity. Thanks to its atomic thickness, graphene, when constructed into biosensors as a sensing material, is highly sensitive to the interaction with biological analytes. In this study, by immobilizing probes on graphene-based field-effect transistors and allowing Cas13a collateral cleavage of these probes activated by target detection, SARS-CoV-2 down to 1 aM level in both spiked and clinical samples, was successfully detected within a 30 min detection time.

Simply by changing the guide RNA design, CRISPR Cas13a graphene field-effect transistor platform was reconfigured to target respiratory syncytial virus with the same attomolar sensitivity. “As the COVID-19 pandemic wanes, our virus diagnostic tool can be easily adapted to combat the future outbreak of unknown viral species,” Guangfu Wu, a Postdoc in Zhang’s lab; he is the co-first author of this work, said.

This study marks a significant milestone towards our goal of developing an integrated point-of-care biosensing platform for viral diagnostics. “We are aiming to offer patients a fast, ultrasensitive all-in-one tool that can streamline sample treatment and analysis and deliver results without any specialized training,” said Zhengyan Weng, a Ph.D. student in Zhang’s lab; he is also the co-first author of this study.

 

This research is supported by the University of Connecticut start-up and the National Science Foundation under the award number CBET-2103025. The collaborators of this work include Dr. Xue Gao at Rice University (co-corresponding author), Drs. Kevin D. Dieckhaus and Lori Avery at UConn Health, and Dr. Yupeng Chen in the Department of Biomedical Engineering at UConn.

Yao Lin Receives Multi-Year NSF Grant

Yao Lin
Dr. Yao Lin

Professor Yao Lin has been awarded a five-year NSF grant (DMR #2210590, $719,664), for his research project, “Advancing Processability and Material Performance of Synthetic Polyamino Acids with Transformable Secondary Structures.”

Dynamic transition from helices to sheets in fibrous proteins facilitates a remarkable increase in the strength, stiffness, and energy dissipation capacity. Polyamino acids (PAAs), also known as synthetic polypeptides, can adopt analogous secondary structures. However, inducing the structural transitions in the solid PAA of high molecular weights (MWs) is a largely unmet challenge. As a result, many of the PAA materials either have poor thermomechanical properties or are incompatible with polymer processing techniques such as extrusion and compression molding. This project aims to develop a general strategy to significantly improve the thermomechanical properties and processability of synthetic PAAs by taking advantage of metastable, transformable structures of PAAs and control over their in-situ transition and hierarchical organization.

The findings from this project may enable the generation of polymeric systems that will approach the level of sophistication and versatility found in some of nature’s biomaterials. The research also provides a model system of synthetic polymers with intrinsic secondary structures in which the different partitioning of intramolecular and intermolecular networks determines the macroscopic properties of materials, enabling comparison of the experimental results with predictions from simulations and modeling.

Graduate and undergraduate students will be trained on bioinspired polymeric materials and acquire skills in polymer synthesis, material characterization, mechanics, and computer simulations.

Four IMS Faculty Members Receive OVPR Scholarship Facilitation Award

Scholarship Facilitation Award Winners
(l-r) Drs. Farhad Imani, Jasna Jankovic, Tomoyasu Mani, and Luyi Sun

The Scholarship Facilitation Fund program provides up to $2,000 to UConn faculty across all disciplines. The OVPR offers the competitive awards to promote, support, and enhance research, scholarship, and creative endeavors across UConn Storrs and regional campuses.

Four IMS faculty members were among the 67 faculty named as recipient of the award for Spring 2022:

  • Farhad Imani, Mechanical Engineering
    Brain-inspired Hyperdimensional Computing for Empowering Cognitive Additive Manufacturing
  • Jasna Jankovic, Material Science and Engineering
    STEAM Tree Earth Day Celebration
  • Tomoyasu Mani, Chemistry
    Stereoselective Control of Electron Transfer Reactions
  • Luyi Sun, Chemical and Biomolecular Engineering
    Publication in PNAS, a Premium Journal for Maximum Impact

IMS Congratulates these faculty members on this accomplishment.

Materials Research Society Features Nate Hohman in Podcast

MRS Bulletin PodcastNate Hohman is the feature of the Materials Research Society (MRS) podcast, MRS Bulletin. Laura Leay interviews Hohman about the structure of two chalcogenolates his group uncovered. By combining serial femtosecond crystallography —usually used to characterize large molecules—and a clique algorithm, Hohman’s group was able to analyze the structure of small molecules. With serial femtosecond crystallography, large molecules like proteins produce thousands of spots on the detector; in contrast, small molecule crystals only a produce a few spots. The algorithm uses the pattern that the spots make on the detector to determine the orientation of as many crystals in the liquid jet as possible. The data from each crystal can then be merged together to find the structure. Nate’s research is featured in the 2022 IMS Annual Newsletter.

Yang Cao in Collaboration on Project Funded by ARPA-E OPEN 2021

Yang Cao
Dr. Yang Cao

On February 14, 2022, ARPA-E announced $175 million for 68 OPEN 2021 research and development projects aimed at developing disruptive technologies to strengthen the nation’s advanced energy enterprise. These high-impact, high-risk technologies support novel approaches to clean energy challenges.

Associate Professor and Electrical Insulation Resource Center (EIRC) Director Yang Cao and fellow researchers from Virginia Polytechnic Institute and State University (Virginia Tech) will combine the functionality benefits of power electronics with the power density benefits of high-voltage cables to create a cohesive, all-in-one structure to replace bulky, inflexible power substations in today’s electrical grid. This “substation within a cable” design uses a cascade of coaxial power conversion cells to gradually step-down voltage to levels required by the loads. Virginia Tech’s module can achieve high power density and a form factor that enables seamless integration with the cable by mimicking a coaxial geometry design. This could eliminate the need for large and expensive power substations and enable simple integration of renewable energy sources, an electric vehicle fast-charging infrastructure, energy storage, and efficient direct current distribution lines.

The research project, Substation in a Cable for Adaptable, Low-cost Electrical Distribution (SCALED) has received $2,953,389 in funding support through the ARPA-E OPEN 2021 initiative.

Xueju “Sophie” Wang Receives NSF CAREER Award

Xueju "Sophie" WangMSE Assistant Professor Xueju “Sophie” Wang has been awarded the NSF Faculty Early Development Program CAREER Award for her proposal entitled “Mechanics of Active Polymers and Morphing structures: Determine the Role of Molecular Interactions and Stiffness Heterogeneity in Reversible Shape Morphing.” It is one of NSF’s most prestigious awards.

Wang’s NSF CAREER award will support her research on fundamental studies of the mechanics of innovative active polymers and morphing structures. Soft active polymers that can change their shapes and therefore functionalities upon exposure to external stimuli are promising for many applications, including soft robotics, artificial muscles and tissue repair. This research project aims to establish the missing correlations across the molecular, material and structural levels of novel active polymers for their rational design, manufacturing and applications, by using liquid crystal elastomers as a model material system.

“I am very grateful and honored to receive this prestigious award, and I look forward to working with my students to address challenges in innovative active polymers and to apply them in emerging fields like soft robotics,” Wang said.

Read the full Department of Materials Science and Engineering Story

Rajeswari Kasi to Serve on Editorial Board of Micromolecules

Rajeswari Kasi
Dr. Rajeswari Kasi

Professor of Chemistry Rajeswari (Raji) Kasi has accepted an appointment to the editorial board of Macromolecules, a peer-reviewed scientific journal published by the American Chemical Society. The publication was first published in 1968 on a bi-monthly basis but has, over the years, moved from monthly to bi-weekly publication.

Kasi’s research encompasses all aspects of materials design including synthesis of hierarchically structured polymers and polymer-hybrid materials with tailored architecture, functionality, and composition; investigation of self-assembly and structure at various length scales; and evaluation of unique macroscopic material properties. She will serve a three-year term on the editorial board.

IMS Faculty Members Receive Department of Education GAANN Award

Drs. Bryan Huey and Lesley Frame
Drs. Bryan Huey (l) and Lesley Frame

Drs. Bryan Huey (IMS/MSE) and Lesley Frame (IMS/MSE) are recent recipients of the Department of Education (ED) Graduate Assistance in Areas of National Need (GAANN) grant.

Drs. Huey and Frame collaboratively applied for the award which provides fellowships, through academic departments and programs, to assist graduate students with excellent records who demonstrate financial need and plan to pursue the highest degree available in their course study at the institution in a field designated as an area of national need.

Their Careers in Advanced Materials Engineering Research and Academia (CAMERA) GAANN program will provide world-class educational, research, advising, and professional training experiences and opportunities, beyond MSE courses and laboratory research taught by established experts in a range of materials engineering specialties. They will utilize the funding to support five Ph.D. fellowships focusing on increasing the number of highly trained Ph.D. scholars from populations traditionally underrepresented in STEM.

Drs. Huey and Frame plan to provide primary and secondary faculty advisors for candidates selected for the fellowship. Each Fellow will earn credits through a novel ‘Academia Lab’ created by MSE in conjunction with the school of engineering and the UConn Center for Excellence in Teaching and Learning in order to incorporate instruction and workshops in educational pedagogy and practice, scientific writing and presenting, and mentorship skills.

The grant of ~$760K will be supplemented by funding from the School of Engineering, the Office of the Vice President for Research, the Office of the Provost, and The Graduate School.

Research Project Aims to Eradicate Use of Harmful Gas

Yang CaoThe gas sulfur hexafluoride (SF6) has been keeping our electrical grid safe from dangerous arcing and explosions since its introduction to the public in the 1930s. Developed in a General Electric lab, sulfur hexafluoride is one of the most widely used insulation gases by electrical utility companies because of its reliability and safety, but remains relatively unknown by the general public.

Starting in the 1960s, as greenhouse gases and their effect on the environment became more widely known, sulfur hexafluoride has been identified as one of the largest causes of global warming. While most educational and legislative efforts have been focused on CO2, or carbon dioxide, emissions as a big offender, sulfur hexafluoride has flown under the radar despite its staggering global warming potential: 25,200 times that of carbon dioxide.

Because of that, University of Connecticut Electrical and Computer Engineering Professor Yang Cao has been selected to receive $2.7 million in funding over three years from the U.S. Department of Energy’s Advanced Research Projects Agency-Energy (ARPA-E) to develop a lifecycle management framework, with innovations in physics based aging modeling, aging byproducts fixation, and a low-cost, high-fidelity multi-gas leak sensor with GE Research, to help utilities make a smooth transition to a new, SF6– free electrical grid.  Read the full UConn Today story.

Dr. Heidi Dierssen is Conducting Research to Improve Remote Sensing of Microplastics on the Ocean’s Surface

Dr. Heidi DierssenProfessor of marine sciences and geography, Heidi Dierssen, has received a nearly $577,000 grant from NASA to study better methods for remote sensing of surface microplastics using satellites. The project will involve a collaboration with a visual artist to advance community understanding of this problem.

Dierssen’s lab, Coastal Ocean Lab for Optics and Remote Sensing (COLORS), conducted previous research on the optical properties of microplastics, providing the necessary background information to determine the best approaches for remote detection. Understanding the optical properties of microplastics is the first step in determining whether satellites can detect and quantify floating microplastics from space.

Dierssen has assembled a diverse scientific team of experts from NASA Goddard Space Flight Center, Colombia University, University of Maryland, Baltimore County, and Terra Research Inc.

Read the full story from UConn Today