There is an urgent need for faster and more cost-effective diagnostic tools to curb the spread of mpox and to prepare for the possibility of a future global pandemic. Researchers from University of California School of Medicine, Boston University, and their colleagues have now developed an optical biosensor that can rapidly detect monkeypox, the virus that causes mpox. The technology could allow clinicians to diagnose the disease at the point of care rather than wait for lab results. The study was published on November 14, 2024 in Biosensors and Bioelectronics.

In the clinic, mpox symptoms such as fever, pain, rashes and lesions resemble those of many other viral infections, says Partha Ray, an associate project scientist at UC San Diego School of Medicine and co-principal investigator on the study. “So just by looking at the patient, it is not easy for clinicians to distinguish monkeypox from these other diseases.”

What’s more, polymerase chain reaction (PCR) is currently the only approved method of diagnosing mpox. It is expensive, requires a laboratory, and can take days or weeks to get results. “A deadly combination when there is a fast-spreading epidemic or pandemic,” said Ray.

The search for a better molecular diagnostic for mpox draws on more than 10 years of research in the lab of Selim Ünlü, a distinguished professor of engineering at Boston University (BU) and co-principal investigator on the study. The lab has developed optical biosensors for detecting the viruses that cause Ebola hemorrhagic fever and COVID-19, among others. Ray’s team at UC San Diego collaborated with Ünlü’s lab, providing biological expertise and authenticated samples to Ünlü’s engineering team.

The study, led by first author Mete Aslan, a Ph.D. student in electrical and electronics engineering at BU, used a digital detection platform called Pixel-Diversity interferometric reflectance imaging sensor, or PD-IRIS, to detect the virus.

The researchers used samples collected from the lesions of a patient at UC San Diego Health with laboratory-confirmed mpox. They briefly incubated the samples with monoclonal monkeypox antibodies provided by Ray’s lab that bind to proteins on the surface of the virus. The virus-antibody complex was then transferred into tiny chambers on the surface of silicon chips on the sensor that were treated to fix these nanoparticles.

Shining precise wavelengths of red and blue light simultaneously on the chips caused interference, which resulted in slightly different responses when the virus-antibody nanoparticles were present. A color camera was used to detect this small signal and count individual particles with high sensitivity.

“You’re not trying to see the scattered light from the virus particle itself, but you’re looking at the interferometric signature of the field of scattered light mixed with the field that is reflected from the surface of the chip,” said Ünlü. He likens the process to FM radio, which mixes a weak signal containing information with a more powerful carrier signal at the same frequency, which, in turn, amplifies the weak signal.

The scientists also analyzed herpes simplex virus and cowpox virus samples, which have similar clinical presentations to mpox. The biosensor assay easily discriminated mpox samples from these other viruses, demonstrating that the specificity of the assay is essential for distinguishing mpox from these common viral diseases.

“Within two minutes, we can tell whether someone has monkeypox or not,” said Ray. “From collecting the virus samples to getting the real-time data takes around 20 minutes.”

In the clinic, the rapidity of the test would allow healthcare providers to diagnose mpox cases much more quickly than sending samples out to a lab. This is especially important for slowing community spread in countries where healthcare resources are sparse. Clinicians could also start treatment, if available, more quickly.

Ray envisions the tests being mass-produced as kits and sold to clinics, further reducing costs. A single boxed kit could be used to test for a variety of viruses, such as syphilis or HIV.

“The chip would be the same,” said Ray. “The only thing that would be different here is the binding antibody that would be specific for a particular virus.”

Ray and Ünlü are working together toward the goal of commercialization, not only to address the urgent need for rapid mpox tests in the Democratic Republic of the Congo but also to keep outbreaks from turning into pandemics. However, the researchers say this effort will require government support because there is little market for diagnostics addressing future threats.

“If we don’t take care of this particular epidemic right now, it is not going to be limited within Africa,” said Ray.

Additional co-authors on the study include: Howard Brickner, Alex E. Clark, Aaron F. Carlin, UC San Diego; Elif Seymour, iRiS Kinetics, Boston University Business Incubation Center; Michael B. Townsend, Panayampalli S. Satheshkumar, Centers for Disease Control and Prevention; Iris Celebi, Boston University; Megan Riley, axiVEND.

The study was funded, in part, by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (P30 AI036214), and the National Science Foundation (NSF-TT PFI 2329817).

“Laser light casting a shadow was previously thought impossible since light usually passes through other light without interacting,” said research team leader Raphael A. Abrahao from Brookhaven National Laboratory, previously at the University of Ottawa. “Our demonstration of a very counter-intuitive optical effect invites us to reconsider our notion of shadow.”

In Optica, Optica Publishing Group’s journal for high-impact research, the researchers describe how they used a ruby crystal and specific laser wavelengths to show that a laser beam could block light and create a visible shadow due to a nonlinear optical process. This effect occurs when light interacts with a material in an intensity-dependent way and can influence another optical field.

“Our understanding of shadows has developed hand-in-hand with our understanding of light and optics,” said Abrahao. “This new finding could prove useful in various applications such as optical switching, devices in which light controls the presence of another light, or technologies that require precise control of light transmission, like high-power lasers.”

Lunch talk sparks idea

The new research is part of a larger exploration into how a light beam interacts with another light beam under special conditions and nonlinear optical processes. The idea started over a lunch conversation when it was pointed out that some experimental schematics made with 3D visualization software depict the shadow of a laser beam because they treat it as a cylinder without accounting for the physics of a laser beam. Some of the scientists wondered: Could this be done in a lab?

“What started as a funny discussion over lunch led to a conversation on the physics of lasers and the nonlinear optical response of materials,” said Abrahao. “From there, we decided to conduct an experiment to demonstrate the shadow of a laser beam.”

To do this, the researchers directed a high-power green laser through a cube made of standard ruby crystal and illuminated it with a blue laser from the side. When the green laser enters the ruby, it locally changes the material response to the blue wavelength. The green laser acts like an ordinary object while the blue laser acts like illumination.

The interaction between the two light sources created a shadow on a screen that was visible as a dark area where the green laser blocked the blue light. It met all the criteria for a shadow because it was visible to the naked eye, followed the contours of the surface it fell on and followed the position and shape of the laser beam, which acted as an object.

The laser shadow effect is a consequence of optical nonlinear absorption in the ruby. The effect occurs because the green laser increases the optical absorption of the blue illuminating laser beam, creating a matching region in the illuminating light with lower optical intensity. The result is a darker area that appears as a shadow of the green laser beam.

Shadow measurements

“This discovery expands our understanding of light-matter interactions and opens up new possibilities for utilizing light in ways we hadn’t considered before,” said Abrahao.

The researchers experimentally measured the dependence of the shadow’s contrast on the laser beam’s power, finding a maximum contrast of approximately 22%, similar to the contrast of a tree’s shadow on a sunny day. They also developed a theoretical model and showed that it could accurately predict the shadow contrast.

The researchers say that from a technological perspective, the effect they demonstrated shows that the intensity of a transmitted laser beam can be controlled by applying another laser. Next, they plan to investigate other materials and other laser wavelengths that can produce similar effects.

During early investigations of the Lafayette Meteorite, scientists discovered that it had interacted with liquid water while on Mars. Scientists have long wondered when that interaction with liquid water took place. An international collaboration of scientists including two from Purdue University’s College of Science have recently determined the age of the minerals in the Lafayette Meteorite that formed when there was liquid water. The team has published its findings in Geochemical Perspective Letters.

Marissa Tremblay, assistant professor with the Department of Earth, Atmospheric, and Planetary Sciences (EAPS) at Purdue University, is the lead author of this publication. She uses noble gases like helium, neon and argon, to study the physical and chemical processes shaping the surfaces of Earth and other planets. She explains that some meteorites from Mars contain minerals that formed through interaction with liquid water while still on Mars.

“Dating these minerals can therefore tell us when there was liquid water at or near the surface of Mars in the planet’s geologic past,” she says. “We dated these minerals in the Martian meteorite Lafayette and found that they formed 742 million years ago. We do not think there was abundant liquid water on the surface of Mars at this time. Instead, we think the water came from the melting of nearby subsurface ice called permafrost, and that the permafrost melting was caused by magmatic activity that still occurs periodically on Mars to the present day.”

In this publication, her team demonstrated that the age obtained for the timing of water-rock interaction on Mars was robust and that the chronometer used was not affected by things that happened to Lafayette after it was altered in the presence of water.

“The age could have been affected by the impact that ejected the Lafayette Meteorite from Mars, the heating Lafayette experienced during the 11 million years it was floating out in space, or the heating Lafayette experienced when it fell to Earth and burned up a little bit in Earth’s atmosphere,” she says. “But we were able to demonstrate that none of these things affected the age of aqueous alteration in Lafayette.”

Ryan Ickert, senior research scientist with Purdue EAPS, is a co-author of the paper. He uses heavy radioactive and stable isotopes to study the timescales of geological processes. He demonstrated that other isotope data (previously used to estimate the timing of water-rock interaction on Mars) were problematic and had likely been affected by other processes.

“This meteorite uniquely has evidence that it has reacted with water. The exact date of this was controversial, and our publication dates when water was present,” he says.

Found in a drawer

Thanks to research, quite a bit is known about the Lafayette Meteorite’s origin story. It was ejected from the surface of Mars about 11 million years ago by an impact event.

“We know this because once it was ejected from Mars, the meteorite experienced bombardment by cosmic ray particles in outer space, that caused certain isotopes to be produced in Lafayette,” Tremblay says. “Many meteoroids are produced by impacts on Mars and other planetary bodies, but only a handful will eventually fall to Earth.”

But once Lafayette hit Earth, the story gets a little muddy. It is known for certain that the meteorite was found in a drawer at Purdue University in 1931. But how it got there is still a mystery. Tremblay and others made strides in explaining the history of the post-Earth timeline in a recent publication.

“We used organic contaminants from Earth found on Lafayette (specifically, crop diseases) that were particularly prevalent in certain years to narrow down when it might have fallen, and whether the meteorite fall may have been witnessed by someone,” Tremblay says.

Meteorites: time capsules of the universe

Meteorites are solid time capsules from planets and celestial bodies from our universe. They carry with them bits of data that can be unlocked by geochronologists. They set themselves apart from rocks that may be found on Earth by a crust that forms from its descent through our atmosphere and often form a fiery entrance visible in the night’s sky.

“We can identify meteorites by studying what minerals are present in them and the relationships between these minerals inside the meteorite,” says Tremblay. “Meteorites are often denser than Earth rocks, contain metal, and are magnetic. We can also look for things like a fusion crust that forms during entry into Earth’s atmosphere. Finally, we can use the chemistry of meteorites (specifically their oxygen isotope composition) to fingerprint which planetary body they came from or which type of meteorite it belongs to.”

An international collab

The team involved with this publication included an international collaboration of scientists. The team also includes Darren F. Mark, Dan N. Barfod, Benjamin E. Cohen, Martin R. Lee, Tim Tomkinson and Caroline L. Smith representing the Scottish Universities Environmental Research Centre (SUERC), the Department of Earth and Environmental Science at the University of St Andrews, the School of Geographical and Earth Sciences at the University of Glasgow, the School of Earth Sciences at the University of Bristol, and the Science Group at The Natural History Museum in London.

“Before moving to Purdue, Ryan and I were both based at the Scottish Universities Environmental Research Centre, where the argon-argon isotopic analyses of the alteration minerals in Lafayette took place” Tremblay says. “Our collaborators at SUERC, the University of Glasgow, and the Natural History Museum have previously done a lot of work studying the history of Lafayette.”

Dating the alteration minerals in Lafayette and, more generally, in this class of meteorites from Mars called nakhlites, has been a long-term objective in planetary science because scientists know that the alteration happened in the presence of liquid water on Mars. However, these materials are especially difficult to date, and previous attempts at dating them had either been very uncertain and/or likely affected by processes other than aqueous alteration.

“We have demonstrated a robust way to date alteration minerals in meteorites that can be applied to other meteorites and planetary bodies to understand when liquid water might have been present,” Tremblay says.

Because of the Stahura Undergraduate Meteorite Fund, Tremblay and Ickert will be able to continue studying the geochemistry and histories of meteorites and undergraduates at Purdue EAPS will be able to assist in this research.

With the demand for donor organs far outstripping the supply, calls for changes in public policy are growing. An opt-out (‘presumed consent’) default policy is often seen as a promising approach. This policy stipulates that all adults are automatically considered potential organ donors after their death, unless they explicitly withdraw their consent during their lifetime. In contrast, the opt-in (‘explicit consent’) system requires potential donors to actively consent to donate their organs after they die. The discussion around implementing an opt-out policy has recently gained traction again in Germany, raising the question of whether such a change in policy would actually lead to an increase in the number of deceased organ donors.

A recent analysis of all member countries of the Organisation for Economic Co-operation and Development (OECD) found no significant difference in deceased donor rates between opt-in and opt-out countries, but significantly fewer living donors — individuals who voluntarily donate organs, like a kidney, while alive — in opt-out countries. However, such cross-sectional analyses cannot control for all country-specific factors like health infrastructure, culture, and religious issues — all of which can influence donation rates.

To address the limitations of prior research, the current study used a longitudinal approach, analyzing changes in deceased donor rates over time in five countries — Argentina, Chile, Sweden, Uruguay, and Wales — that had switched from an opt-in to an opt-out default policy. This method provided a more reliable assessment of the impact of opt-out policies by controlling for long-term trends and country-specific factors.

Data was collected from international databases, including the International Registry in Organ Donation and Transplantation (IRODaT) and the Global Observatory on Donation and Transplantation (GODT). Of the 39 countries that had changed from explicit to presumed consent by December 2019, only five could be included in the analysis due to a lack of historical data for changes made before the IRODaT database was launched in 1996 and because presumed consent practices often existed informally prior to formal legislation.

Consistent with previous cross-sectional analyses, the study found that switching the default from opt-in to opt-out did not lead to any increase in organ donation rates in the five countries considered. Moreover, the results indicated that the opt-out default did not cause even a slight upward curve in organ donations: the long-term trend remained the same, showing no change in the rate following the switch. As expected, the results did show a reduction in deceased donations with the onset of the COVID-19 pandemic, with only a slow recovery observed by 2022.

“Simply switching to an opt-out system does not automatically lead to more organ donations,” states author Mattea Dallacker, who led the project at the Center for Adaptive Rationality at the Max Planck Institute for Human Development. “Without accompanying measures, such as investments in the healthcare system and public awareness campaigns, a shift to an opt-out default is unlikely to increase organ donations. There is no easy solution to the complex challenge of boosting organ donation rates,” she continues.

The study also underscores the crucial role of relatives in organ donation decisions. Even in presumed consent systems, where individuals are considered donors unless they opt out, families are often consulted and can override the presumed consent. Since many people do not talk about their donation wishes with loved ones, presumed consent can lead to uncertainty and hesitation among families, potentially resulting in refusals.

“A possible alternative to the opt-out system is a mandatory choice system,” says Ralph Hertwig, Director at the Center for Adaptive Rationality at the Max Planck Institute for Human Development. “This would allow citizens to explicitly register their consent or objection to organ donation, when applying for a driver’s license or ID card, for example. This active choice system could prompt people to make an informed decision, which would eliminate the perceived ambiguity about their preference that appears to lead to higher family refusal rates. Good and accessible information about organ donation is essential for informed choice,” Hertwig continues.

“It’s a very weird event, called AT 2021hdr, that keeps recurring every few months,” said Lorena Hernández-García, an astrophysicist at the Millennium Institute of Astrophysics, the Millennium Nucleus on Transversal Research and Technology to Explore Supermassive Black Holes, and University of Valparaíso in Chile. “We think that a gas cloud engulfed the black holes. As they orbit each other, the black holes interact with the cloud, perturbing and consuming its gas. This produces an oscillating pattern in the light from the system.”

A paper about AT 2021hdr, led by Hernández-García, was published Nov. 13 in the journal Astronomy and Astrophysics.

The dual black holes are in the center of a galaxy called 2MASX J21240027+3409114, located 1 billion light-years away in the northern constellation Cygnus. The pair are about 16 billion miles (26 billion kilometers) apart, close enough that light only takes a day to travel between them. Together they contain 40 million times the Sun’s mass.

Scientists estimate the black holes complete an orbit every 130 days and will collide and merge in approximately 70,000 years.

AT 2021hdr was first spotted in March 2021 by the Caltech-led ZTF (Zwicky Transient Facility) at the Palomar Observatory in California. It was flagged as a potentially interesting source by ALeRCE (Automatic Learning for the Rapid Classification of Events). This multidisciplinary team combines artificial intelligence tools with human expertise to report events in the night sky to the astronomical community using the mountains of data collected by survey programs like ZTF.

“Although this flare was originally thought to be a supernova, outbursts in 2022 made us think of other explanations,” said co-author Alejandra Muñoz-Arancibia, an ALeRCE team member and astrophysicist at the Millennium Institute of Astrophysics and the Center for Mathematical Modeling at the University of Chile. “Each subsequent event has helped us refine our model of what’s going on in the system.”

Since the first flare, ZTF has detected outbursts from AT 2021hdr every 60 to 90 days.

Hernández-García and her team have been observing the source with Swift since November 2022. Swift helped them determine that the binary produces oscillations in ultraviolet and X-ray light on the same time scales as ZTF sees them in the visible range.

The researchers conducted a Goldilocks-type elimination of different models to explain what they saw in the data.

Initially, they thought the signal could be the byproduct of normal activity in the galactic center. Then they considered whether a tidal disruption event — the destruction of a star that wandered too close to one of the black holes — could be the cause.

Finally, they settled on another possibility, the tidal disruption of a gas cloud, one that was bigger than the binary itself. When the cloud encountered the black holes, gravity ripped it apart, forming filaments around the pair, and friction started to heat it. The gas got particularly dense and hot close to the black holes. As the binary orbits, the complex interplay of forces ejects some of the gas from the system on each rotation. These interactions produce the fluctuating light Swift and ZTF observe.

Hernández-García and her team plan to continue observations of AT 2021hdr to better understand the system and improve their models. They’re also interested in studying its home galaxy, which is currently merging with another one nearby — an event first reported in their paper.

“As Swift approaches its 20th anniversary, it’s incredible to see all the new science it’s still helping the community accomplish,” said S. Bradley Cenko, Swift’s principal investigator at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. “There’s still so much it has left to teach us about our ever-changing cosmos.”