Researchers in Australia have developed a nanosensor that can detect the onset of gestational diabetes with 95% accuracy. Demonstrated by a team led by Carlos Salomon at the University of Queensland, the superparamagnetic “nanoflower” sensor could enable doctors to detect a variety of complications in the early stages of pregnancy.

Many complications in pregnancy can have profound and lasting effects on both the mother and the developing foetus. Today, these conditions are detected using methods such as blood tests, ultrasound screening and blood pressure monitoring. In many cases, however, their sensitivity is severely limited in the earliest stages of pregnancy.

“Currently, most pregnancy complications cannot be identified until the second or third trimester, which means it can sometimes be too late for effective intervention,” Salomon explains.

To tackle this challenge, Salomon and his colleagues are investigating the use of specially engineered nanoparticles to isolate and detect biomarkers in the blood associated with complications in early pregnancy. Specifically, they aim to detect the protein molecules carried by extracellular vesicles (EVs) – tiny, membrane-bound particles released by the placenta, which play a crucial role in cell signalling.

In their previous research, the team pioneered the development of superparamagnetic nanostructures that selectively bind to specific EV biomarkers. Superparamagnetism occurs specifically in small, ferromagnetic nanoparticles, causing their magnetization to randomly flip direction under the influence of temperature. When proteins are bound to the surfaces of these nanostructures, their magnetic responses are altered detectably, providing the team with a reliable EV sensor.

“This technology has been developed using nanomaterials to detect biomarkers at low concentrations,” explains co-author Mostafa Masud. “This is what makes our technology more sensitive than current testing methods, and why it can pick up potential pregnancy complications much earlier.”

Previous versions of the sensor used porous nanocubes that efficiently captured EVs carrying a key placental protein named PLAP. By detecting unusual levels of PLAP in the blood of pregnant women, this approach enabled the researchers to detect complications far more easily than with existing techniques. However, the method generally required detection times lasting several hours, making it unsuitable for on-site screening.

In their latest study, reported in Science Advances, Salomon’s team started with a deeper analysis of the EV proteins carried by these blood samples. Through advanced computer modelling, they discovered that complications can be linked to changes in the relative abundance of PLAP and another placental protein, CD9.

Based on these findings, they developed a new superparamagnetic nanosensor capable of detecting both biomarkers simultaneously. Their design features flower-shaped nanostructures made of nickel ferrite, which were embedded into specialized testing strips to boost their sensitivity even further.

Using this sensor, the researchers collected blood samples from 201 pregnant women at 11 to 13 weeks’ gestation. “We detected possible complications, such as preterm birth, gestational diabetes and preeclampsia, which is high blood pressure during pregnancy,” Salomon describes. For gestational diabetes, the sensor demonstrated 95% sensitivity in identifying at-risk cases, and 100% specificity in ruling out healthy cases.

Based on these results, the researchers are hopeful that further refinements to their nanoflower sensor could lead to a new generation of EV protein detectors, enabling the early diagnosis of a wide range of pregnancy complications.

“With this technology, pregnant women will be able to seek medical intervention much earlier,” Salomon says. “This has the potential to revolutionize risk assessment and improve clinical decision-making in obstetric care.”

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The COVID-19 pandemic provided a driving force for researchers to seek out new disinfection methods that could tackle future viral outbreaks. One promising approach relies on the use of nanoparticles, with several metal and metal oxide nanoparticles showing anti-viral activity against SARS-CoV-2, the virus that causes COVID-19. With this in mind, researchers from Sweden and Estonia investigated the effect of such nanoparticles on two different virus types.

Aiming to elucidate the nanoparticles’ mode of action, they discovered a previously unknown antiviral mechanism, reporting their findings in Nanoscale.

The researchers – from the Swedish University of Agricultural Sciences (SLU) and the University of Tartu – examined triethanolamine terminated titania (TATT) nanoparticles, spherical 3.5-nm diameter titanium dioxide (titania) particles that are expected to interact strongly with viral surface proteins.

They tested the antiviral activity of the TATT nanoparticles against two types of virus: swine transmissible gastroenteritis virus (TGEV) – an enveloped coronavirus that’s surrounded by a phospholipid membrane and transmembrane proteins; and the non-enveloped encephalomyocarditis virus (EMCV), which does not have a phospholipid membrane. SARS-CoV-2 has a similar structure to TGEV: an enveloped virus with an outer lipid membrane and three proteins forming the surface.

“We collaborated with the University of Tartu in studies of antiviral materials,” explains lead author Vadim Kessler from SLU. “They had found strong activity from cerium dioxide nanoparticles, which acted as oxidants for membrane destruction. In our own studies, we saw that TATT formed appreciably stable complexes with viral proteins, so we could expect potentially much higher activity at lower concentration.”

In this latest investigation, the team aimed to determine whether one of these potential mechanisms – blocking of surface proteins, or membrane disruption via oxidation by nanoparticle-generated reactive oxygen species – is the likely cause of TATT’s antiviral activity. The first of these effects usually occurs at low (nanomolar to micromolar) nanoparticle concentrations, the latter at higher (millimolar) concentrations.

Mode of action

To assess the nanoparticle’s antiviral activity, the researchers exposed viral suspensions to colloidal TATT solutions for 1 h, at room temperature and in the dark (without UV illumination). For comparison, they repeated the process with silicotungstate polyoxometalate (POM) nanoparticles, which are not able to bind strongly to cell membranes.

The nanoparticle-exposed viruses were then used to infect cells and the resulting cell viability served as a measure of the virus infectivity. The team note that the nanoparticles alone showed no cytotoxicity against the host cells.

Measuring viral infectivity after nanoparticle exposure revealed that POM nanoparticles did not exhibit antiviral effects on either virus, even at relatively high concentrations of 1.25 mM. TATT nanoparticles, on the other hand, showed significant antiviral activity against the enveloped TGEV virus at concentrations starting from 0.125 mM, but did not affect the non-enveloped EMCV virus.

Based on previous evidence that TATT nanoparticles interact strongly with proteins in darkness, the researchers expected to see antiviral activity at a nanomolar level. But the finding that TATT activity only occurred at millimolar concentrations, and only affected the enveloped virus, suggests that the antiviral effect is not due to blocking of surface proteins. And as titania is not oxidative in darkness, the team propose that the antiviral effect is actually due to direct complexation of nanoparticles with membrane phospholipids – a mode of antiviral action not previously considered.

“Typical nanoparticle concentrations required for effects on membrane proteins correspond to the protein content on the virus surface. With a 1:1 complex, we would need maximum nanomolar concentrations,” Kessler explains. “We saw an effect at about 1 mM/l, which is far higher. This was the indication for us that the effect was on the whole of membrane.”

Verifying the membrane effect

To corroborate their hypothesis, the researchers examined the leakage of dye-labelled RNA from the TGEV coronavirus after 1 h exposure to nanoparticles. The fluorescence signal from the dye showed that TATT-treated TGEV released significantly more RNA than non-exposed virus, attributed to the nanoparticles disrupting the virus’s phospholipid membrane.

Finally, the team studied the interactions between TATT nanoparticles and two model phospholipid compounds. Both molecules formed strong complexes with TATT nanoparticles, while their interaction with POM nanoparticles was weak. This additional verification led the researchers to conclude that the antiviral effect of TATT in dark conditions is due to direct membrane disruption via complexation of titania nanoparticles with phospholipids.

“To the best of our knowledge, [this] proves a new pathway for metal oxide nanoparticles antiviral action,” they write.

Importantly, the nanoparticles are non-toxic, and work at room temperature without requiring UV illumination – enabling simple and low-cost disinfection methods. “While it was known that disinfection with titania could work in UV light, we showed that no special technical measures are necessary,” says Kessler.

Kessler suggests that the nanoparticles could be used to coat surfaces to destroy enveloped viruses, or in cost-effective filters to decontaminate air or water. “[It should be] possible to easily create antiviral surfaces that don’t require any UV activation just by spraying them with a solution of TATT, or possibly other oxide nanoparticles with an affinity to phosphate, including iron and aluminium oxides in particular,” he tells Physics World.

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A new graphene nanostructure could become the basis for the first ferromagnets made purely from carbon. Known as an asymmetric or “Janus” graphene nanoribbon after the two-faced god in Roman mythology, the opposite edges of this structure have different properties, with one edge taking a zigzag form. Lu Jiong , a researcher at the National University of Singapore (NUS) who co-led the effort to make the structure, explains that it is this zigzag edge that gives rise to the ferromagnetic state, making the structure the first of its kind.

“The work is the first demonstration of the concept of a Janus graphene nanoribbon (JGNR) strand featuring a single ferromagnetic zigzag edge,” Lu says.

Graphene nanostructures with zigzag-shaped edges show much promise for technological applications thanks to their electronic and magnetic properties. Zigzag GNRs (ZGNRs) are especially appealing because the behaviour of their electrons can be tuned from metal-like to semiconducting by adjusting the length or width of the ribbons; modifying the structure of their edges; or doping them with non-carbon atoms. The same techniques can also be used to make such materials magnetic. This versatility means they can be used as building blocks for numerous applications, including quantum and spintronics technologies.

Previously, only two types of symmetric ZGNRs had been synthesized via on-surface chemistry: 6-ZGNR and nitrogen-doped 6-ZGNR, where the “6” refers to the number of carbon rows across the nanoribbon’s width. In the latest work, Lu and co-team leaders Hiroshi Sakaguchi of the University of Kyoto, Japan and Steven Louie at the University of California, Berkeley, US sought to expand this list.

 “It has been a long-sought goal to make other forms of zigzag-edge related GNRs with exotic quantum magnetic states for studying new science and developing new applications,” says team member Song Shaotang, the first author of a paper in Nature about the research.

ZGNRs with asymmetric edges

Building on topological classification theory developed in previous research by Louie and colleagues, theorists in the Singapore-Japan-US collaboration predicted that it should be possible to tune the magnetic properties of these structures by making ZGNRs with asymmetric edges. “These nanoribbons have one pristine zigzag edge and another edge decorated with a pattern of topological defects spaced by a certain number m of missing motifs,” Louie explains. “Our experimental team members, using innovative z-shaped precursor molecules for synthesis, were able to make two kinds of such ZGNRs. Both of these have one edge that supports a benzene motif array with a spacing of m = 2 missing benzene rings in between. The other edge is a conventional zigzag edge.”

Crucially, the theory predicted that the magnetic behaviour – ranging from antiferromagnetism to ferrimagnetism to ferromagnetism – of these JGNRs could be controlled by varying the value of m. In particular, says Louie, the configuration of m = 2 is predicted to show ferromagnetism – that is, all electron spins aligned in the same direction – concentrated entirely on the pristine zigzag edge. This behaviour contrasts sharply with that of symmetric ZGNRs, where spin polarization occurs on both edges and the aligned edge spins are antiferromagnetically coupled across the width of the ribbon.

Precursor design and synthesis

To validate these theoretical predictions, the team synthesized JGNRs on a surface. They then used advanced scanning tunnelling microscope (STM) and atomic force microscope (AFM) measurements to visualize the materials’ exact real-space chemical structure. These measurements also revealed the emergence of exotic magnetic states in the JGNRs synthesized in Lu’s lab at the NUS.

In the past, Sakaguchi explains that GNRs were mainly synthesized using symmetric precursor chemical structures, largely because their asymmetric counterparts were so scarce. One of the challenges in this work, he notes, was to design asymmetric polymeric precursors that could undergo the essential fusion (dehydrogenation) process to form JGNRs. These molecules often orient randomly, so the researchers needed to use additional techniques to align them unidirectionally prior to the polymerization reaction. “Addressing this challenge in the future could allow us to produce JGNRs with a broader range of magnetic properties,” Sakaguchi says.

Towards carbon-based ferromagnets

According to Lu, the team’s research shows that JGNRs could become the first carbon-based spin transport channels to show ferromagnetism. They might even lead to the development of carbon-based ferromagnets, capping off a research effort that began in the 1980s.

However, Lu acknowledges that there is much work to do before these structures find real-world applications. For one, they are not currently very robust when exposed to air. “The next goal,” he says, “is to develop chemical modifications that will enhance the stability of these 1D structures so that they can survive under ambient conditions.”

A further goal, he continues, is to synthesize JGNRs with different values of m, as well as other classes of JGNRs with different types of defective edges. “We will also be exploring the 1D spin physics of these structures and [will] investigate their spin dynamics using techniques such as scanning tunnelling microscopy combined with electron spin resonance, paving the way for their potential applications in quantum technologies.”

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