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Three NSF RAPID Grants to Develop Quicker Test for COVID-19 for Holonyak Lab Faculty

Three Nick Holonyak Jr., Micro and Nanotechnology Lab (HMNTL) faculty members have received NSF Rapid Response Research (RAPID) program grants, all of which aim to shorten the amount of time it takes to process a COVID-19 test. Current tests can take as long as five days for results to be returned to the patient. Although more rapid nucleic acid tests that can give a result within an hour have become available, there are reports of a high rate of false negatives among these tests.

With the United States reaching the highest number of SARS-CoV-2 (this particular strain of coronavirus) cases out of any infected country, it is a national imperative to be able to test people before they show symptoms to reduce the spread of the deadly disease.

"As one of the only facilities in the country that incorporates both micro and nanofabrication cleanroom facilities and a BioNanotechnology Laboratory (BNL) under the same roof, HMNTL is proud to meet the moment and provide support to COVID-19 related essential research," said Xiuling Li, HMNTL interim director and Donald Biggar Willett Professor in Engineering.

Here is a more in-depth look at how HMNTL faculty are helping:

Rapid Electrical Detection of COVID-19 at Point-of-Care

A team led by Rashid Bashir, Dean of the Grainger College of Engineering, and Holonyak Lab faculty researcher, has proposed the development of a point-of-care device that uses nasal fluid samples to detect the presence of COVID-19 within 10 minutes.
Current tests are complex and labor-intensive, requiring each sample to be sent to a laboratory for confirmation. The test being developed by Bashir's group will simplify the process by eliminating the need to extract RNA from samples and simplify the test it as a whole. The new test will electrically detect specific nucleic acid molecules associated with the SARS-CoV2-2.

"Our approach can provide for a rapid electrical detection of the RNA amplification using graphene sensors and result in a miniaturized format for the test and also reduce the test's total processing time," said Bashir, Abel Bliss Professor of Engineering, professor of bioengineering, and member of the Center for Genomic Diagnostics.

The team hopes the proposed approach can be expanded beyond COVID-19 detection to become a global health technology that contributes to providing low-cost diagnostics of a number of viruses around the world in a portable and inexpensive way.

Rapid Single-Step Reagentless SARS-CoV-2 Viral Load Test by Detection of Intact Virus Particles

The next COVID-19 detection project combines capturing intact COVID-19 viruses with custom-designed DNA nanostructures so they can be immediately counted with a newly-invented type of biosensor imaging. This process could be completed and produce results in less than 15 minutes.

This new method would allow diagnostic facilities at the point of care to count each virus directly using a new form of ultrasensitive biosensor microscopy that amplifies the magnitude of light scattering produced by the virus when it is illuminated with a laser. To determine if the viewed virus is SARS-CoV-2, customized DNA nanostructure-based capture probes would be immobilized on a photonic crystal biosensor surface. When exposed to a sample, such as material eluted from a nasal swab, the DNA rhombus-shaped "virus net" would selectively attach the virus to the biosensor surface, while allowing all other materials to pass over the sensor without capture.

"Our approach would represent a new paradigm for virus diagnostics that does not require the chemical enzymatic amplification of nucleic acids, and so does not require temperature control, thermal cycles, viral lysis, nucleic acid purification, or fluorescent dyes," said Cunningham, Donald Biggar Willett Professor in Engineering and professor of electrical and computer engineering. "We just capture and count, so it is the simplest possible process, and our sensing method gives a result immediately as the viruses are captured."

The technology used in this method was recently demonstrated as a new form of biosensor microscopy called Photonic Resonator Interference Scattering Microscopy (PRISM), which allows researchers to detect and digitally count virus particles, protein molecules, and a variety of nanoparticles in real time without the use of additional labels or stains.

The team for this research also includes Xing Wang, associate professor of Chemistry, Taylor Canady, postdoc fellow at the Carl R. Woese Institute for Genomic Biology, and Nantao Li, Cunningham's ECE graduate student.

RAPID: Developing a Novel Biosensor for Rapid, Direct, and Selective Detection of COVID-19 using DNA Aptamer-Nanopore 

Holonyak Lab affiliate faculty member Yi Lu is working with Lijun Rong from the University of Illinois at Chicago to develop a biosensor that could detect and differentiate infectious SARS-CoV-2 from the SARS-CoV-2 that have been rendered noninfectious by patient's antibodies or disinfectants. This would allow patients to receive proper treatment in a timely manner, and would allow people who aren't infected or contagious to be released from quarantine.

The project aims to develop a modular and scalable sensor for direct detection of the intact coronavirus using DNA aptamers, short, single-stranded DNA molecules that can selectively bind infectious SARS-CoV-2. When coupled with nanopore, a pore of nanometer size, the result would be able to differentiate the infectious SARS-CoV-2 from the non-infectious forms or other viruses such as flu viruses with a high level of specificity.

"Achieving such a high level of specificity is very important for COVID-19 diagnostics," said Yi Lu, professor of chemistry and bioengineering. "This is because studies have shown that viral RNA levels that are being used in most COVID-19 diagnostic tests do not always correlate with viral transmissibility."

This technique is less resource-intensive than current methods due to not requiring pretreatment or RNA amplification. It also decreases the likelihood of cross contamination. It could also be used to test surface areas to ensure they have been properly sanitized after coming in contact with an infected patient.

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