Malaria remains a serious health concern, with annual deaths increasing yearly since 2019 and almost half of the world’s population at risk of infection. Existing diagnostic tests are less than optimal and all rely on obtaining an invasive blood sample. Now, a research collaboration from USA and Cameroon has demonstrated a device that can non-invasively detect this potentially deadly infection without requiring a single drop of blood.
Currently, malaria is diagnosed using optical microscopy or antigen-based rapid diagnostic tests, but both methods have low sensitivity. Polymerase chain reaction (PCR) tests are more sensitive, but still require blood sampling. The new platform – Cytophone – uses photoacoustic flow cytometry (PAFC) to rapidly identify malaria-infected red blood cells via a small probe placed on the back of the hand.
PAFC works by delivering low-energy laser pulses through the skin into a blood vessel and recording the thermoacoustic signals generated by absorbers in circulating blood. Cytophone, invented by Vladimir Zharov from the University of Arkansas for Medical Science, was originally developed as a universal diagnostic platform and first tested clinically for detection of cancerous melanoma cells.
“We selected melanoma because of the possibility of performing label-free detection of circulating cells using melanin as an endogenous biomarker,” explains Zharov. “This avoids the need for in vivo labelling by injecting contrast agents into blood.” For malaria diagnosis, Cytophone detects haemozoin, an iron crystal that accumulates in red blood cells infected with malaria parasites. These haemozoin biocrystals have unique magnetic and optical properties, making them a potential diagnostic target.
Photoacoustic detection Schematic of the focused ultrasound transducer array assessing a blood network. (Courtesy: Nat. Commun. 10.1038/s41467-024-53243-z)
“The similarity between melanin and haemozoin biomarkers, especially the high photoacoustic contrast above the blood background, motivated us to bring a label-free malaria test with no blood drawing to malaria-endemic areas,” Zharov tells Physics World. “To build a clinical prototype for the Cameroon study we used a similar platform and just selected a smaller laser to make the device more portable.”
The Cytophone prototype uses a 1064 nm laser with a linear beam shape and a high pulse rate to interrogate fast moving blood cells within blood vessels. Haemozoin nanocrystals in infected red blood cells absorb this light (more strongly than haemoglobin in normal red blood cells), heat up and expand, generating acoustic waves. These signals are detected by an array of 16 tiny ultrasound transducers in acoustic contact with the skin. The transducers have focal volumes oriented in a line across the vessel, which increases sensitivity and resolution, and simplifies probe navigation.
In vivo testing
Zharov and collaborators – also from Yale School of Public Health and the University of Yaoundé I – tested the Cytophone in 30 Cameroonian adults diagnosed with uncomplicated malaria. They used data from 10 patients to optimize device performance and assess safety. They then performed a longitudinal study in the other 20 patients, who attended four or five times at up to 37 days following antimalarial therapy, contributing 94 visits in total.
Photoacoustic waveforms and traces from infected blood cells have a particular shape and duration, and a different time delay to that of background skin signals. The team used these features to optimize signal processing algorithms with appropriate averaging, filtration and gating to identify true signals arising from infected red blood cells. As the study subjects all had dark skin with high melanin content, this time-resolved detection also helped to avoid interference from skin melanin.
On visit 1 (the day of diagnosis), 19/20 patients had detectable photoacoustic signals. Following treatment, these signals consistently decreased with each visit. Cytophone-positive samples exhibited median photoacoustic peak rates of 1.73, 1.63, 1.18 and 0.74 peaks/min on visits 1–4, respectively. One participant had a positive signal on visit 5 (day 30). The results confirm that Cytophone is sensitive enough to detect low levels of parasites in infected blood.
The researchers note that Cytophone detected the most common and deadliest species of malaria parasite, as well as one infection by a less common species and two mixed infections. “That was a really exciting proof-of-concept with the first generation of this platform,” says co-lead author Sunil Parikh in a press statement. “I think one key part of the next phase is going to involve demonstrating whether or not the device can detect and distinguish between species.”
Team work The researchers from the USA and Cameroon are using photoacoustic flow cytometry to rapidly detect malaria infection. (Courtesy: Sunil Parikh)
Performance comparison
Compared with invasive microscopy-based detection, Cytophone demonstrated 95% sensitivity at the first visit and 90% sensitivity during the follow-up period, with 69% specificity and an area under the ROC curve of 0.84, suggesting excellent diagnostic performance. Cytophone also approached the diagnostic performance of standard PCR tests, with scope for further improvement.
Staff required just 4–6 h of training to operate Cytophone, plus a few days experience to achieve optimal probe placement. And with minimal consumables required and the increasing affordability of lasers, the researchers estimate that the cost per malaria diagnosis will be low. The study also confirmed that the safety of the Cytophone device. “Cytophone has the potential to be a breakthrough device allowing for non-invasive, rapid, label-free and safe in vivo diagnosis of malaria,” they conclude.
The researchers are now performing further malaria-related clinical studies focusing on asymptomatic individuals and children (for whom the needle-free aspect is particularly important). Simultaneously, they are continuing melanoma trials to detect early-stage disease and investigating the use of Cytophone to detect circulating blood clots in stroke patients.
“We are integrating multiple innovations to further enhance Cytophone’s sensitivity and specificity,” says Zharov. “We are also developing a cost-effective wearable Cytophone for continuous monitoring of disease progression and early warning of the risk of deadly disease.”
Quantized vortices – one of the defining features of superfluidity – have been seen in a supersolid for the first time. Observed by researchers in Austria, these vortices provide further confirmation that supersolids can be modelled as superfluids with a crystalline structure. This model could have variety of other applications in quantum many body physics and Austrian team now using it to study pulsars, which are rotating and magnetized neutron stars.
A superfluid is a curious state of matter that can flow without any friction. Superfluid systems that have been studied in the lab include helium-4; type-II superconductors; and Bose–Einstein condensates (BECs) – all of which exist at very low temperatures.
More than five decades ago, physicists suggested that some systems could exhibit crystalline order and superfluidity simultaneously in a unique state of matter called a supersolid. In such a state, the atoms would be described by the same wavefunction and are therefore delocalized across the entire crystal lattice. The order of the supersolid would therefore be defined by the nodes and antinodes of this wavefunction.
In 2004, Moses Chan of the Pennsylvania State University in the US and his PhD student Eun-Seong Kim reported observing a supersolid phase in superfluid helium-4. However, Chan and others have not been able to reproduce this result. Subsequently, researchers including Giovanni Modugno at Italy’s University of Pisa and Francesca Ferlaino at the University of Innsbruck in Austria have demonstrated evidence of supersolidity in BECs of magnetic atoms.
Irrotational behaviour
But until now, no-one had observed an important aspect of superfluidity in a supersolid: that a superfluid never carries bulk angular momentum. If a superfluid is placed in a container and the container is rotated at moderate angular velocity, it simply flows freely against the edges. As the angular momentum of the container increases, however, it becomes energetically costly to maintain the decoupling between the container and the superfluid. “Still, globally, the system is irrotational,” says Ferlaino; “So there’s really a necessity for the superfluid to heal itself from rotation.”
In a normal superfluid, this “healing” occurs by the formation of small, quantized vortices that dissipate the angular momentum, allowing the system to remain globally irrotational. “In an ordinary superfluid that’s not modulated in space [the vortices] form a kind of triangular structure called an Abrikosov lattice, because that’s the structure that minimizes their energy,” explains Ferlaino. It was unclear how the vortices might sit inside a supersolid lattice.
In the new work, Ferlaino and colleagues at the University of Innsbruck utilized a technique called magnetostirring to rotate a BEC of magnetic dysprosium-164 atoms. They caused the atoms to rotate simply by rotating the magnetic field. “That’s the beauty: it’s so simple but nobody had thought about this before,” says Ferlaino.
As the group increased the field’s rotation rate, they observed vortices forming in the condensate and migrating to the density minima. “Vortices are zeroes of density, so there it costs less energy to drill a hole than in a density peak,” says Ferlaino; “The order that the vortices assume is largely imparted by the crystalline structure – although their distance is dependent on the repulsion between vortices.”
Unexpected applications
The researchers believe the findings could be applicable in some unexpected areas of physics. Ferlaino tells of hearing a talk about the interior composition of neutron stars by the theoretical astrophysicist Massimo Mannarelli of Gran Sasso Laboratory in Italy. “During the coffee break I went to speak to him and we’ve started to work together.”
“A large part of the astrophysical community is convinced that the core of a neutron star is a superfluid,” Ferlaino says; “The crust is a solid, the core is a superfluid, and a layer called the inner crust has both properties together.” Pulsars are neutron stars that emit radiation in a narrow beam, giving them a well-defined pulse rate that depends on their rotation. As they lose energy through radiation emission, they gradually slow down.
Occasionally, however, their rotation rates suddenly speed up again in events called glitches. The researchers’ theoretical models suggest that the glitches could be caused by vortices unpinning from the supersolid and crashing into the solid exterior, imparting extra angular momentum. “When we impose a rotation on our supersolid that slows down, then at some point the vortices unpin and we see the glitches in the rotational frequency,” Ferlaino says. “This is a new direction – I don’t know where it will bring us, but for sure experimentally observing vortices was the first step.”
Theorist Blair Blakie of the University of Otago in New Zealand is excited by the research. “Vortices in supersolids were a bit of a curiosity in early theories, and sometimes you’re not sure whether theorists are just being a bit crazy considering things, but now they’re here,” he says. “It opens this new landscape for studying things from non-equilibrium dynamics to turbulence – all sorts of things where you’ve got this exotic material with topological defects in it. It’s very hard to predict what the killer application will be, but in these fields people love new systems with new properties.”
A City on Mars: Can We Settle Space, Should We Settle Space, and Have We Really Thought This Through? By Kelly and Zach Weinersmith
Husband-and-wife writing team Kelly and Zach Weinersmith were excited about human settlements in space when they started research for their new book A City on Mars. But the more they learned, the more sceptical they became. From technology, practicalities and ethics, to politics and the legal framework, they uncovered profound problems at every step. With humorous panache and plenty of small cartoons by Zach, who also does the webcomic Saturday Morning Breakfast Cereal, the book is a highly entertaining guide that will dent the enthusiasm of most proponents of settling space. Kate Gardner
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Einstein in Oxford By Andrew Robinson
“England has always produced the best physicists,” Albert Einstein once said in Berlin in 1925. His high regard for British physics led him to pay three visits to the University of Oxford in the early 1930s, which are described by Andrew Robinson in his charming short book Einstein in Oxford. Sadly, the visits were not hugely productive for Einstein, who disliked the formality of Oxford life. His time there is best remembered for the famous blackboard – saved for posterity – on which he’d written while giving a public lecture. Matin Durrani
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Pillars of Creation: How the James Webb Telescope Unlocked the Secrets of the Cosmos By Richard Panek
The history of science is “a combination of two tales” says Richard Panek in his new book charting the story of the James Webb Space Telescope (JWST). “One is a tale of curiosity. The other is a tale of tools.” He has chosen an excellent case study for this statement. Pillars of Creation combines the story of the technological and political hurdles that nearly sank the JWST before it launched with a detailed account of its key scientific contributions. Panek’s style is also multi-faceted, mixing technical explanations with the personal stories of scientists fighting to push the frontiers of astronomy. Katherine Skipper
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Quanta and Fields: the Biggest Ideas in the Universe By Sean Carroll
With 2025 being the International Year of Quantum Science and Technology, the second book in prolific science writer Sean Carroll’s “Biggest Ideas” trilogy – Quanta and Fields – might make for a prudent read. Following the first volume on “space, time and motion”, it tackles the key scientific principles that govern quantum mechanics, from wave functions to effective wave theory. But beware: this book is packed with equations, formulae and technical concepts. It’s essentially a popular-science textbook, in which Carroll does things like examine each term in the Schrödinger equation and delve into the framework for group theory. Great for physicists but not, perhaps, for the more casual reader. Tushna Commissariat
Oral phenylephrine was shown to be ineffective for treating nasal congestion over a year go. This week, the FDA took the first steps toward removing it from pharmacy shelves.
A new and practical approach to the low-noise amplification of weakened optical signals has been unveiled by researchers in Sweden. Drawing from the principles of four-wave mixing, Rasmus Larsson and colleagues at Chalmers University of Technology believe their approach could have promising implications for laser-based communication systems in space.
Until recently, space-based communication systems have largely relied on radio waves to transmit signals. Increasingly, however, these systems are being replaced with optical laser beams. The shorter wavelengths of these signals offer numerous advantages over radio waves. These include higher data transmission rates; lower power requirements; and lower risks of interception.
However, when transmitted across the vast distances of space, even a tightly focused laser beam will spread out significantly by the time its light reaches its destination. This will weaken severely the signal’s strength.
To deal with this loss, receivers must be extremely sensitive to incoming signals. This involves the preamplification of the signal above the level of electronic noise in the receiver. But conventional optical amplifiers are far too noisy to achieve practical space-based communications.
Phase-sensitive amplification
In a 2021 study, Larsson’s team showed how these weak signals can, in theory, be amplified with zero noise using a phase-sensitive optical parametric amplifier (PSA). However, this approach did not solve the problem entirely.
“The PSA should be the ideal preamplifier for optical receivers,” Larsson explains. “However, we don’t see them in practice due to their complex implementation requirements, where several synchronized optical waves of different frequencies are needed to facilitate the amplification.” These cumbersome requirements place significant demands on both transmitter and receiver, which limits their use in space-based communications.
To simplify preamplification, Larsson’s team used four-wave mixing. Here, the interaction between light at three different wavelengths within a nonlinear medium produces light at a fourth wavelength.
In this case, a weakened transmitted signal is mixed with two strong “pump” waves that are generated within the receiver. When the phases of the signal and pump are synchronized inside a doped optical fibre, light at the fourth wavelength interferes constructively with the signal. This boosts the amplitude of the signal without sacrificing low-noise performance.
Auxiliary waves
“This allows us to generate all required auxiliary waves in the receiver, with the transmitter only having to generate the signal wave,” Larsson describes. “This is contrary to the case before where most, if not all waves were generated in the transmitter. The synchronization of the waves further uses the same specific lossless approach we demonstrated in 2021.”
The team says that this new approach offers a practical route to noiseless amplification within an optical receiver. “After optimizing the system, we were able to demonstrate the low-noise performance and a receiver sensitivity of 0.9 photons per bit,” Larsson explains. This amount of light is the minimum needed to reliably decode each bit of data and Larsson adds, “This is the lowest sensitivity achieved to date for any coherent modulation format.”
This unprecedented sensitivity enabled the team to establish optical communication links between a PSA-amplified receiver and a conventional, single-wave transmitter. With a clear route to noiseless preamplification through some further improvements, the researchers are now hopeful that their approach could open up new possibilities across a wide array of applications – especially for laser-based communications in space.
“In this rapidly emerging topic, the PSA we have demonstrated can facilitate much higher data rates than the bandwidth-limited single photon detection technology currently considered.”
This ability would make the team’s PSA ideally suited for communication links between space-based transmitters and ground-based receivers. In turn, astronomers could finally break the notorious “science return bottleneck”. This would remove many current restrictions on the speed and quantity of data that can be transmitted by satellites, probes, and telescopes scattered across the solar system.
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