The Rice lab of mechanical engineer Peter Lillehoj has developed a stamp-sized microfluidic chip that measures the concentration of SARS-CoV-2 nucleocapsid (N) protein in blood serum from a standard finger prick. The nanobeads bind to SARS-CoV-2 N protein, a biomarker for COVID-19, in the chip and transport it to an electrochemical sensor that detects minute amounts of the biomarker.

The researchers argued their process simplifies sample handling compared to swab-based PCR tests that are widely used to diagnose COVID-19 and need to be analyzed in a laboratory.

“What’s great about this device is that doesn’t require a laboratory,” Lillehoj said. “You can perform the entire test and generate the results at the collection site, health clinic or even a pharmacy. The entire system is easily transportable and easy to use.”

The research appears in the American Chemical Society journal ACS Sensors.

Lillehoj and Rice graduate student and lead author Jiran Li took advantage of existing biosensing tools and combined them with their own experience in developing simple diagnostics, like a microneedle patch introduced last year to diagnose malaria.

The new tool relies on a slightly more complex detection scheme but delivers accurate, quantitative results in a short amount of time. To test the device, the lab relied on donated serum samples from people who were healthy and others who were COVID-19-positive.

Lillehoj said a longer incubation yields more accurate results when using whole serum. The lab found that 55 minutes was an optimum amount of time for the microchip to sense SARS-CoV-2 N protein at concentrations as low as 50 picograms (billionths of a gram) per milliliter in whole serum. The microchip could detect N protein in even lower concentrations, at 10 picograms per milliliter, in only 25 minutes by diluting the serum fivefold.

Paired with a Google Pixel 2 phone and a plug-in potentiostat, it was able to deliver a positive diagnosis with a concentration as low as 230 picograms for whole serum.

“There are standard procedures to modify the beads with an antibody that targets a particular biomarker,” Lillehoj said. “When you combine them with a sample containing the biomarker, in this case SARS-CoV-2 N protein, they bond together.”

A capillary tube is used to deliver the sample to the chip, which is then placed on a magnet that pulls the beads toward an electrochemical sensor coated with capture antibodies. The beads bind to the capture antibodies and generate a current proportional to the concentration of biomarker in the sample.

The potentiostat reads that current and sends a signal to its phone app. If there are no COVID-19 biomarkers, the beads do not bind to the sensor and get washed away inside the chip.

Lillehoj said it would not be difficult for industry to manufacture the microfluidic chips or to adapt them to new COVID-19 strains if and when that becomes necessary.

The National Institutes of Health, the National Science Foundation and the Rice University COVID-19 Research Fund supported the research.

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The unexpected visitor belongs to a class of icy bodies found in space between Jupiter and Neptune. Called “Centaurs,” they become active for the first time when heated as they approach the Sun, and dynamically transition into becoming more comet-like.

Visible-light snapshots by NASA’s Hubble Space Telescope reveal that the vagabond object shows signs of comet activity, such as a tail, outgassing in the form of jets, and an enshrouding coma of dust and gas. Earlier observations by NASA’s Spitzer Space Telescope gave clues to the composition of the comet-like object and the gasses driving its activity.

“Only Hubble could detect active comet-like features this far away at such high detail, and the images clearly show these features, such as a roughly 400,000-mile-long broad tail and high-resolution features near the nucleus due to a coma and jets,” said lead Hubble researcher Bryce Bolin of Caltech in Pasadena, California.

Describing the Centaur’s capture as a rare event, Bolin added, “The visitor had to have come into the orbit of Jupiter at just the right trajectory to have this kind of configuration that gives it the appearance of sharing its orbit with the planet. We’re investigating how it was captured by Jupiter and landed among the Trojans. But we think it could be related to the fact that it had a somewhat close encounter with Jupiter.”

The team’s paper appears in the February 11, 2021 issue of The Astronomical Journal.

The research team’s computer simulations show that the icy object, called P/2019 LD2 (LD2), probably swung close to Jupiter about two years ago. The planet then gravitationally punted the wayward visitor to the Trojan asteroid group’s co-orbital location, leading Jupiter by about 437 million miles.

Bucket Brigade

The nomadic object was discovered in early June 2019 by the University of Hawaii’s Asteroid Terrestrial-impact Last Alert System (ATLAS) telescopes located on the extinct volcanoes, one on Mauna Kea and one on Haleakala. Japanese amateur astronomer Seiichi Yoshida tipped off the Hubble team to possible comet activity. The astronomers then scanned archival data from the Zwicky Transient Facility, a wide-field survey conducted at Palomar Observatory in California, and realized that the object was clearly active in images from April 2019.

They followed up with observations from the Apache Point Observatory in New Mexico, which also hinted at the activity. The team observed the comet using Spitzer just days before the observatory’s retirement in January 2020, and identified gas and dust around the comet nucleus. These observations convinced the team to use Hubble to take a closer look. Aided by Hubble’s sharp vision, the researchers identified the tail, coma structure and the size of the dust particles and their ejection velocity. These images helped them confirm that the features are due to relatively new comet-like activity.

Although LD2’s location is surprising, Bolin wonders whether this pit stop could be a common pull-off for some sunward-bound comets. “This could be part of the pathway from our solar system through the Jupiter Trojans to the inner solar system,” he said.

The unexpected guest probably will not stay among the asteroids for very long. Computer simulations show that it will have another close encounter with Jupiter in about another two years. The hefty planet will boot the comet from the system, and it will continue its journey to the inner solar system.

“The cool thing is that you’re actually catching Jupiter flinging this object around and changing its orbital behavior and bringing it into the inner system,” said team member Carey Lisse of the Johns Hopkins University Applied Physics Laboratory (APL) in Laurel, Maryland. “Jupiter controls what’s going on with comets once they get into the inner system by altering their orbits.”

The icy interloper is most likely one of the latest members of the so-called “bucket brigade” of comets to get kicked out of its frigid home in the Kuiper belt and into the giant planet region through interactions with another Kuiper belt object. Located beyond Neptune’s orbit, the Kuiper belt is a haven of icy, leftover debris from our planets’ construction 4.6 billion years ago, containing millions of objects, and occasionally these objects have near misses or collisions that drastically alter their orbits from the Kuiper belt inward into the giant planet region.

The bucket brigade of icy relics endure a bumpy ride during their journey sunward. They bounce gravitationally from one outer planet to the next in a game of celestial pinball before reaching the inner solar system, warming up as they come closer to the Sun. The researchers say the objects spend as much or even more time around the giant planets, gravitationally pulling on them — about 5 million years — than they do crossing into the inner system where we live.

“Inner system, ‘short-period’ comets break up about once a century,” Lisse explained. “So, in order to maintain the number of local comets we see today, we think the bucket brigade has to deliver a new short-period comet about once every 100 years.”

An Early Bloomer

Seeing outgassing activity on a comet 465 million miles away from the Sun (where the intensity of sunlight is 1/25th as strong as on Earth) surprised the researchers. “We were intrigued to see that the comet had just started to become active for the first time so far away from the Sun at distances where water ice is barely starting to sublimate,” said Bolin.

Water remains frozen on a comet until it reaches about 200 million miles from the Sun, where heat from sunlight converts water ice to gas that escapes from the nucleus in the form of jets. So the activity signals that the tail might not be made of water. In fact, observations by Spitzer indicated the presence of carbon monoxide and carbon dioxide gas, which could be driving the creation of the tail and jets seen on the Jupiter-orbiting comet. These volatiles do not need much sunlight to heat their frozen form and convert them to gas.

Once the comet gets kicked out of Jupiter’s orbit and continues its journey, it may meet up with the giant planet again. “Short-period comets like LD2 meet their fate by being thrown into the Sun and totally disintegrating, hitting a planet, or venturing too close to Jupiter once again and getting thrown out of the solar system, which is the usual fate,” Lisse said. “Simulations show that in about 500,000 years, there’s a 90% probability that this object will be ejected from the solar system and become an interstellar comet.”

Video: https://www.youtube.com/watch?v=x-Ikmr5IPys&feature=emb_logo

“If there was a COVID-like pandemic occurring in important bacterial populations it would be difficult to tell, because before this study, we lacked the affordable and accurate tools necessary to study viral infections in uncultured bacterial populations,” said study corresponding author Sarah Preheim, a Johns Hopkins assistant professor of environmental health and engineering.

The findings were published today in Nature Microbiology.

Sick bacteria are stymied in their function as decomposers and as part of the foundation of the food web in the Chesapeake Bay and other waterways. Determining viral infections in bacteria traditionally relies on culturing both bacteria and virus, which misses 99% of bacteria found in the environment because they cannot be grown in culture, Preheim says, adding that tests of viral infections in uncultured bacteria are expensive and difficult to apply widely, not unlike the early stages of COVID-19 testing.

The key to making a test of viral infections for uncultured bacteria faster and more affordable was to isolate single bacterial cells in a small bubble (i.e. an emulsion droplet) and fuse the genes of the virus and bacteria together once inside.

“The fused genes act like name tags for the bacteria and viruses,” said lead author Eric Sakowski, a former postdoctoral researcher in Preheim’s laboratory who is now an assistant professor at Mount St. Mary’s University. “By fusing the genes together, we are able to identify which bacteria are infected, as well as the variant of the virus that is causing the infection.”

The resulting test provides a novel way to screen for viral infections in a subset of bacterial populations. The test allows researchers to identify a link between environmental conditions and infections in Actinobacteria, one of the most abundant bacterial groups in the Chesapeake Bay and one that plays a crucial role in decomposing organic matter, making nutrients available to plants and photosynthetic algae.

Though the researchers developed this tool studying the Chesapeake Bay, they say their approach could be widely applied across aquatic ecosystems, shedding light on viral ecology and helping predict — and even prevent — devastating environmental impacts.

“This testing tool allows us to track viral infections more easily, so we can monitor these infections to see when they are most likely to have important environmental consequences,” Preheim said.

Sakowski said the new test could someday also affect how we treat bacterial infections.

“Viruses show potential for treating infections caused by antibiotic-resistant bacteria,” he said. “Knowing which viruses most effectively infect bacteria will be critical to this type of treatment.”

Preheim’s team also included Johns Hopkins doctoral student Keith Arora-Williams, and Funing Tian, Ahmed A. Zayed, Olivier Zablocki, and Matthew B. Sullivan, all from the Ohio State University.

Support was provided by the National Science Foundation and the Gordon E. and Betty I. Moore Foundation.

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For the study, researchers at NCI, part of the National Institutes of Health, collaborated with two health care data analytics companies (HealthVerity and Aetion, Inc.) and five commercial laboratories. The findings were published on Feb. 24 in JAMA Internal Medicine.

“While cancer research and cancer care remain?the?primary?focus of NCI’s work, we were eager to lend our expertise in serological sciences to help address the global COVID-19 pandemic, at the request of Congress,” said NCI Director Norman E. “Ned” Sharpless, M.D., who was one of the coauthors on the study. “We hope that these results, in combination with those of other studies, will inform future public health efforts and help in setting policy.”

“The data from this study suggest that people who have a positive result from a commercial antibody test appear to have substantial immunity to SARS-CoV-2, which means they may be at lower risk for future infection,” said Lynne Penberthy, M.D., M.P.H., associate director of NCI’s Surveillance Research Program, who led the study. “Additional research is needed to understand how long this protection lasts, who may have limited protection, and how patient characteristics, such as comorbid conditions, may impact protection. We are nevertheless encouraged by this early finding.”

Antibody tests — also known as serology tests — detect serum antibodies, which are immune system proteins made in response to a specific foreign substance or infectious agent, such as SARS-CoV-2.

This study was launched in an effort to better understand whether, and to what degree, detectable antibodies against SARS-CoV-2 protect people from reinfection with the virus. Working with HealthVerity and Aetion, NCI aggregated and analyzed patient information collected from multiple sources, including five commercial labs (including Quest Diagnostics and Labcorp), electronic medical records, and private insurers. This was done in a way that protects the privacy of an individual’s health information and is compliant with relevant patient privacy laws.

The researchers ultimately obtained antibody test results for more than 3 million people who had a SARS-CoV-2 antibody test between Jan. 1 and Aug. 23, 2020. This represented more than 50% of the commercial SARS-CoV-2 antibody tests conducted in the United States during that time. Nearly 12% of these tests were antibody positive; most of the remaining tests were negative, and less than 1% were inconclusive.

About 11% of the seropositive individuals and 9.5% of the seronegative individuals later received a nucleic acid amplification test (NAAT) — sometimes referred to as a PCR test — for SARS-CoV-2. The research team looked at what fraction of individuals in each group subsequently had a positive NAAT result, which may indicate a new infection. The study team reviewed NAAT results at several intervals: 0-30 days, 31-60 days, 61-90 days, and >90 days because some people who have recovered from a SARS-CoV-2 infection can still shed viral material (RNA) for up to three months (although they likely do not remain infectious during that entire period).

The team found that, during each interval, between 3% and 4% of the seronegative individuals had a positive NAAT test. But among those who had originally been seropositive, the NAAT test positivity rate declined over time. When the researchers looked at test results 90 or more days after the initial antibody test (when any coronavirus detected by NAAT is likely to reflect a new infection rather than continued virus shedding from the original infection), only about 0.3% of those who had been seropositive had a positive NAAT result — about one-tenth the rate in those who had been seronegative.

Although these results support the idea that having antibodies against SARS-CoV-2 is associated with protection from future infection, the authors note important limitations to this study. In particular, the findings come from a scientific interpretation of real-world data, which are subject to biases that may be better controlled for in a clinical trial. For example, it is not known why people who had tested antibody positive went on to have a PCR test. In addition, the duration of protection is unknown; studies with longer follow-up time are needed to determine if protection wanes over time.

To continue to comprehensively address this important research question, NCI is supporting clinical studies that monitor infection rates in large populations of people whose antibody status is known. These are known as “seroprotection” studies. NCI is also sponsoring ongoing studies using real-world data to assess the longer-term effect of antibody positivity on subsequent infection rates.

This research is part of a $306 million effort that NCI has taken on at the request of Congress to develop, validate, improve, and implement serological testing and associated technologies applicable to COVID-19. Through this appropriation, NCI is working with the Department of Health and Human Services; the National Institute of Allergy and Infectious Diseases, another part of NIH; and other government agencies to apply its expertise and advanced research capabilities to respond to this pandemic, including efforts to rigorously characterize the performance of serology assays.

A team of researchers from the University of Exeter’s flagship Living Systems Institute has discovered how the model alga Chlamydomonas is seemingly able to scan the environment by constantly spinning around its own body axis in a corkscrewing movement. This helps it respond to light, which it needs for photosynthesis.

The tiny alga, which is found abundantly in fresh-water ponds across the world, swims by beating its two flagella, hair-like structures that adopt a whip-like movement to move the cell. These flagella beat in much the same way as the cilia in the human respiratory system.

Chlamydomonas cells are able to sense light through a red eye spot and can react to it, known as phototaxis. The cell rotates steadily as it propels itself forwards using a sort of breaststroke, at a rate of about once or twice a second, so that its single eye can scan the local environment.

However, the intricate mechanism that allows the alga to achieve this helical swimming has been previously unclear.

IN the new study, the researchers first performed experiments which revealed that the two flagella in fact beat in planes that are slightly skewed away from each other.

Then, creating a sophisticated computer model of Chlamydomonas, they were able to simulate the flagella movement and reproduce the observed swimming behaviour.

The researchers discovered that the flagella were able to move the Chlamydomonas in a clockwise fashion with each power stroke, and then anticlockwise on the reverse stroke — akin to how a swimmer rocks back and forth when switching from one arm to another. Except here the cell feels no inertia.

Furthermore, they also deduced how simply by exerting slightly different forces on the two flagella, the alga can even steer, rather than just move in a straight line.

The researchers were able to show that by adding in an additional influence, such as light, the alga can navigate left or right by knowing which flagellum to stroke harder than the other.

Dr Kirsty Wan, who led the study said: “The question of how a cell makes these types of precise decisions can be a matter of life or death. It’s quite a remarkable feat of both physics and biology, that a single cell with no nervous system to speak of is able to do this…It’s an age-old mystery that my group is currently working hard to solve.”

For the study, the researchers were able to test various scenarios to determine which variables were influencing the trajectory. Their study showed that by varying different parameters, such as if one flagella is slightly stronger than another, the tilt plane of the flagella or its beat pattern, the algae can manipulate its own movement.

Team member Dr Dario Cortese added: “The agreement of our model with the experiments is surprising really, that we could effectively capture the complex 3D beat of the flagella with a very simple movement of a bead going around in circles.”

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