Student 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.

Elyse Schriber Named NSF Graduate Research Fellow

ElyseElyse Schriber Schriber, a second-year materials science graduate student in the lab of assistant professor of chemistry J. Nathan “Nate” Hohman, was named among five UConn students to receive the prestigious National Science Foundation Graduate Research Fellowship (NSF GRFP).

Elyse began working with Hohman as an undergraduate research assistant in 2017, when he was a staff scientist at the Molecular Foundry at Lawrence Berkeley National Lab before coming to UConn.

She started working on method development for serial femtosecond chemical crystallography (SFCX) at an X-ray free electron laser (XFEL) facility in 2018. This is an X-ray crystallography technique that determines single crystal structures of materials from microcrystalline powders. She continues that work at UConn currently. The duo recently published their first paper on the method in Nature.

She plans to continue to work on different facets of the SFCX project in her graduate program, including studying ultrafast nonequilibrium excited state structural dynamics in materials.

“I started my undergraduate degree as a nontraditional student at the local community college and as a result, did not have a straightforward pathway into graduate school or academia,” says Schriber. “Being awarded the GRFP, especially with my background, makes me hopeful that more students with similar experiences can be empowered to believe that they can be successful, regardless of how they got their start.”  Read the full UConn Today Story

IMS Faculty Members Mentor 2022 SURF Award Winners

SURF AwardsWith the assistance of faculty mentors, UConn students in all majors, across all UConn campuses, conduct research or creative projects each year in pursuit of the Summer Undergraduate Research Fund (SURF) Award. 

UConn recently announced that 39 students had been awarded the 2022 SURF Award. Two Institute of Materials Science (IMS) faculty members served as mentor to winners for this year’s cohort of winners.

Dr. Helena Silva (Electrical and Computer Engineering) served as mentor for Derek Lefcort (’23, Electrical Engineering, ENG) for his project entitled Fabrication and Electrical Characterization of Multi-Contact PCM Toggle Device.

Dr. Linnaea Ostroff (Physiology and Neurobiology) served as mentor to Rebecca Tripp (’23, Physiology and Neurobiology, CLAS) for her project, Characterizing Neurons Containing Calcium-Binding Proteins in the Amygdala of Female and Male Rats.

IMS congratulates all the winners and commends Drs. Silva and Ostroff for their dedication in serving as mentors.

Read the full announcement

 

MSE Students’ Fluxtrol Research Makes Semifinals at National Heat Treat Society Conference

MSE Group Poster Wins
Dean’s group in front of their project at the Heat Treat Society Conference. From left to right: Ryan Gordon, Cole Accord, and Quenten Dean.

Two MSE students made it to semi-finals at the 31st Heat Treat Contest which took place Sept. 14 and 15 in St. Louis. This year, the student/emerging professional portion of the conference hosted the Fluxtrol Student Competition and the new ASM Heat Treating Society Strong Bar Student Competition.

The talented group of rising materials engineers from UConn consisted of three undergraduate students, three graduate students, and one recent graduate.

The Heat Treating Society as a whole serves professional and aspiring material engineers who work in thermal processing. The annual competition offers awards and widespread recognition to young innovative scientists. Through this, the program seeks to encourage the participation of younger generations in the ASM Heat Treating Society. It also provides a pipeline to worldwide opportunities in the thermal processing community.

Recent MSE graduate Brittany Nelson and MSE senior Ryan Gordon were the two participants from UConn who made it to the semi-final round of the Fluxtrol Student Research Contest. “Unfortunately, they did not make it to the final winner slot, but everyone did a great job and they had some steep competition,” their faculty advisor, MSE Assistant Professor Lesley Frame, says. Frame currently serves as the first female Vice President of the Heat Treat Society.  Read the full MSE Story.