Saturday, May 14, 2022

New Smartphone-Powered Microchip Opens the Door for Faster, Cheaper At-Home Medical Testing

A University of Minnesota Twin Cities research team has developed a new microfluidic chip for diagnosing diseases that uses a minimal number of components and can be powered wirelessly by a smartphone. The innovation opens the door for faster and more affordable at-home medical testing.

The researchers' paper is published in Nature Communications, a peer-reviewed, open access, scientific journal published by Nature Research. Researchers are also working to commercialize the technology.

Microfluidics involves the study and manipulation of liquids at a very small scale. One of the most popular applications in the field is developing "lab-on-a-chip" technology, or the ability to create devices that can diagnose diseases from a very small biological sample, blood or urine, for example.

Scientists already have portable devices for diagnosing some conditions-;rapid COVID-19 antigen tests, for one. However, a big roadblock to engineering more sophisticated diagnostic chips that could, for example, identify the specific strain of COVID-19 or measure biomarkers like glucose or cholesterol, is the fact that they need so many moving parts.

Chips like these would require materials to seal the liquid inside, pumps and tubing to manipulate the liquid, and wires to activate those pumps-;all materials that are difficult to scale down to the micro level. Researchers at the University of Minnesota Twin Cities were able to create a microfluidic device that functions without all of those bulky components.

Many lab-on-a-chip technologies work by moving liquid droplets across a microchip to detect the virus pathogens or bacteria inside the sample. The University of Minnesota researchers' solution was inspired by a peculiar real-world phenomenon with which wine drinkers will be familiar-;the "legs," or long droplets that form inside a wine bottle due to surface tension caused by the evaporation of alcohol.

Using a technique pioneered by Oh's lab in the early 2010s, the researchers placed tiny electrodes very close together on a 2 cm by 2 cm chip, which generate strong electric fields that pull droplets across the chip and create a similar "leg" of liquid to detect the molecules within.

Because the electrodes are placed so closely together (with only 10 nanometers of space between), the resulting electric field is so strong that the chip only needs less than a volt of electricity to function. This incredibly low voltage required allowed the researchers to activate the diagnostic chip using near-field communication signals from a smartphone, the same technology used for contactless payment in stores.

This is the first time researchers have been able to use a smartphone to wirelessly activate narrow channels without microfluidic structures, paving the way for cheaper, more accessible at-home diagnostic devices.

"This is a very exciting, new concept," said Christopher Ertsgaard, lead author of the study and a recent CSE alumnus (ECE Ph.D. '20). "During this pandemic, I think everyone has realized the importance of at-home, rapid, point-of-care diagnostics. And there are technologies available, but we need faster and more sensitive techniques. With scaling and high-density manufacturing, we can bring these sophisticated technologies to at-home diagnostics at a more affordable cost."

Oh's lab is working with Minnesota startup company GRIP Molecular Technologies, which manufactures at-home diagnostic devices, to commercialize the microchip platform. The chip is designed to have broad applications for detecting viruses, pathogens, bacteria, and other biomarkers in liquid samples.

"To be commercially successful, in-home diagnostics must be low-cost and easy-to-use," said Bruce Batten, founder and president of GRIP Molecular Technologies. "Low voltage fluid movement, such as what Professor Oh's team has achieved, enables us to meet both of those requirements. GRIP has had the good fortune to collaborate with the University of Minnesota on the development of our technology platform. Linking basic and translational research is crucial to developing a pipeline of innovative, transformational products."

In addition to Oh and Ertsgaard, the research team included University of Minnesota Department of Electrical and Computer Engineering alumni Daniel Klemme (Ph.D. '19) and Daehan Yoo (Ph.D. '16) and Ph.D. student Peter Christenson.

This research was supported by the National Science Foundation (NSF). Oh received support from the Sanford P. Bordeau Endowed Chair at the University of Minnesota and the McKnight University Professorship. Device fabrication was performed in the Minnesota Nano Center at the University of Minnesota, which is supported by NSF through the National Nanotechnology Coordinated Infrastructure (NNCI).

Source: University of Minnesota

Journal reference: Ertsgaard, C. T., et al. (2022) Open-channel microfluidics via resonant wireless power transfer. Nature Communications.

New Rapid Virus Test uses Gold Particles and is 150 Times More Accurate than Standard Tests

University of Texas at Dallas researchers have developed a rapid virus test using gold particles and lasers that promises to deliver results as accurate as lab tests in a fraction of the time.

The technology, called digital plasmonic nanobubble detection—or Diamond for short—is 150 times more accurate than standard rapid tests, according to a study published in Nature Communications last month. Its accuracy is comparable to polymerase chain reaction (PCR) tests, which take hours to perform.

The team of UTD scientists that authored the study, led by associate professor of mechanical engineering Dr. Zhenpeng Qin, tested Diamond against respiratory syncytial virus, although the researchers say the technology can be used to detect other prominent viruses, like COVID-19 and influenza.

"For the [PCR] COVID test, we drive through the pharmacy and give the sample. Getting the sample tested usually takes two to four hours before we get the results," said Haihang Ye, a UTD research associate in mechanical engineering. "Our technology can reduce the sample testing time to 30 minutes, but the sensitivity can be as good as those molecular tests."

Faster, cheaper and more effective virus tests are in high demand as the U.S. shifts into a new normal in the coronavirus pandemic. Though case counts are near all-time lows in North Texas, the highly contagious BA.2 variant continues to spread locally and across the country.

The cost of a COVID-19 test varies widely depending on location and type of test. A study of the largest hospitals in every state done by the Peterson Center of Healthcare and Kaiser Family Foundation Health System Tracker found coronavirus test prices ranged anywhere from $20 to more than $1,400. Only 3% of the hospitals surveyed listed testing prices below $50.

A Diamond test, which Ye said can be produced for around $15, mixes a patient sample from a nasal swab with gold nanoparticles attached to antibodies for the virus being tested. The antibodies, marked by the gold nanoparticles, then bind with proteins on the virus' surface if the virus is present in the sample.

Researchers then inject the sample mixed with labeled antibodies into a narrow tube mounted on a glass slide. As the liquid passes through the tube, it's hit by the beams of two lasers, one of which activates the gold nanoparticles, causing them to expand.

If the expansion is strong enough, the nanoparticle will boil the water around it and create vapor bubbles. Large nanobubbles mean the virus is present in the sample.

"If there's no virus, there will be a tiny nanobubble signal from the particle only so we can differentiate the sample's status," said Yaning Liu, a UTD mechanical engineering doctoral student and co-first author of the Diamond study.

Diamond is the product of years of research and millions of dollars in grant funding, including $2.5 million in grants from the National Institute of Allergy and Infectious Diseases and a $293,000 grant from the Department of Defense's Congressionally Directed Medical Research Programs.

To test different viruses using the technology, all researchers need to do is change the associated antibodies, Ye said. Though Diamond has the potential to expand testing options for a number of viruses, it requires researchers to know what they're testing for.

"One of the challenges with the current tests is that providers have to kind of have an idea of what they're looking for," said Elitza Theel, associate professor of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minn.

A less-targeted approach using a technology called metagenomic next-generation sequencing allows scientists to sequence all of the genetic material in a sample to identify which infectious pathogens are present. The technology is already in use, but the process is expensive and takes days to return results, Theel said.

"It's not really helpful in the immediate acute setting," she said.

While Diamond must be approved by the Food and Drug Administration before it can be used publicly, the scientists behind the technology launched a company called Avsana Labs to hopefully commercialize it. Qin serves as president of the company, which was created through UTD's Venture Development Center.

Just last week, another North Texas company had its COVID-19 test approved by the FDA. Frisco-based InspectIR Systems invented a breathalyzer apparatus, the first coronavirus test of its kind to get federal approval, that can yield results in less than three minutes.

Yaning Liu et al, Digital plasmonic nanobubble detection for rapid and ultrasensitive virus diagnostics, Nature Communications (2022). DOI: 10.1038/s41467-022-29025-w

Rapid Method Shown to Detect Infection in Cystic Fibrosis

Rapid method shown to detect infection in cystic fibrosis: Southampton researchers have demonstrated a quick and accurate method to diagnose bacterial infections. The technique has the potential to detect infections in cystic fibrosis patients in minutes rather than days.

In future, the simple analysis could be performed on hospital wards to deliver faster and more effective treatment.

The approach could also be expanded to target a variety of diseases and counter anti-microbial resistance.

Cystic fibrosis is an inherited condition that causes sticky mucus to build up in the lungs and digestive system. This causes lung infections and problems with digesting food.

It affects around 1 in every 10,000 births in the UK.

Treatments are available to help reduce the problems caused by the condition. Yet recurring infections still dramatically reduce the quality and length of life.

The current methods for diagnosing immediate (acute) and longer-term (chronic) infections are complex and time-consuming in the laboratory. For biofilm infections, it can take days from collecting and processing a patient’s sample to achieving a result. This delays effective treatments and impacts patient outcomes.

A multi-disciplinary team from the University of Southampton and University Hospital Southampton set out to develop a diagnostic tool that would be rapid, accurate and simple-to-use for doctors.

They have developed a new chemical analysis technique called multi-excitation Raman spectroscopy. This non-invasive method emits a scattering of multiple colours of light into a patient’s sample.

Prof Sumeet Mahajan, Head of Chemical Biology and the Associate Director of Institute for Life Sciences at the University of Southampton, explained:

“When light is applied to a sample’s molecules they can vibrate which helps us understand their characteristics. By using different colours of light, a different set of such vibrations can be triggered meaning we can get more information about their composition than previously possible.

“This then allows ‘finger-printing’ that can be used to identify the properties of the pathogens that cause cystic fibrosis. In many current techniques, a reagent needs to be added to a sample or a tag needs to be attached to the molecules of interest to analyse their composition. This is not required under this new approach which uses natural properties of the molecules to analyse them.”

Professor Mahajan continued: “Our new Raman spectroscopy based method offers many advantages over resource-intensive, culture-based methods, allowing rapid and label-free analysis. It is reagentless and avoids complex sample-preparation steps with sophisticated equipment. Here, we have developed a method that is highly accurate yet rapid and neither requires nanoscale materials for enhancing signals nor fluorophores for detection.”

Long term infections in the lungs of people with cystic fibrosis are extremely hard to treat . There is evidence that the Pseudomonas aeruginosa bacteria exists as biofilms in the body, protecting the bacteria from antibiotic action and driving antimicrobial resistance. This increases the urgency for rapid and effective treatment.

The Southampton research, published in Analytical Chemistry, showed 99.75% accuracy at identifying Pseudomonas aeruginosa and Staphylococcus aureus across all studied strains. This included 100% accuracy for drug-sensitive and drug-resistant Staphylococcus aureus.

The project drew together expertise from the National Institute for Health and Care Research (NIHR) Southampton Biomedical Research Centre (BRC) and Southampton Clinical Research Facility (CRF), the National Biofilms Innovation Centre (NBIC), together with the University of Southampton’s School of Chemistry and Institute for Life Sciences (IfLS). It was led by Professor Mahajan, Professor Jeremy Webb and Professor Saul Faust.

Prof Faust, Director of NIHR Southampton CRF, said: “Our study demonstrates an important step toward a rapid and reagentless diagnostic tool requiring only simple or routine sample preparation.

“Such a platform could also prove useful in a variety of other disease areas and help address the mounting challenge of anti-microbial resistance.”