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Raman spectroscopy predicts radiation resistance

Researchers from Johns Hopkins University and the University of Arkansas have demonstrated that Raman spectroscopy can identify tumours that will be responsive to radiotherapy, paving the way for simple, cost-effective patient stratification (Cancer Research 10.1158/0008-5472.CAN-18-2732).

Santosh Paidi, a graduate research assistant and lead author on this study, has produced the most convincing evidence yet that Raman spectroscopy could be key to reducing patient burden in cases of radiotherapy-resistant tumours.

Raman spectroscopy is a label-free, non-ionizing tool that examines the frequency components of laser light backscattered from an irradiated sample. The spectra contain molecular fingerprints that are sensitive to rotational and vibrational molecular motions in tissue and can therefore detect biophysical changes in the tumour microenvironment.

Unlike previous studies, Paidi’s research compared multiple types of cancer under a clinically relevant dose fractionation scheme. The team showed that Raman spectra could be used not only to measure treatment effectiveness, but also as a possible means of predicting tumour response. “I could foresee a clinical laboratory device employing Raman spectroscopy in the not-too-distant future,” says senior author Ishan Barman.

The animal model

The researchers injected human-derived lung and head-and-neck tumour cells into immunosuppressed mice, using both radiosensitive cells and cells that were rendered resistant to radiation. In this way, they created four groups of mice: with sensitive and with non-responsive tumours, both treated and untreated with radiotherapy. The team excised the tumours at the point in time when most untreated control tumours reached a volume of 1500 mm³.

The researchers collected Raman spectra from the excised tumours using a custom built, portable fibre-optic probe. They identified significant increases in signal from lipid, collagen and glycogen in both lung and head-and-neck tumours after treatment with radiation, and also saw larger signals from radiation-sensitive tumours. This finding demonstrated the consistency of Raman-derived biomarkers in these cancers.

Furthermore, the researchers used the spectra from all tumour groups to train a support vector machine algorithm to differentiate untreated radiosensitive tumours from untreated resistive tumours. They reported a 97% classification success rate for their support vector machine-derived classifier — suggesting that differences in tissue microenvironment prior to radiotherapy may be sufficient to stratify tumours.

Looking to the future

Paidi and colleagues have demonstrated that Raman spectroscopy provides an effective way to monitor radiotherapy efficacy, as well as perhaps identify patients most likely to benefit from such treatment. But how far away are we from clinical tumour stratification?

“The ability to integrate spectroscopic sensing with existing endoscopic platforms has been demonstrated by us and others in other contexts earlier,” says Barman. “The challenge resides in demonstrating the accuracy of these molecular markers in early identification of treatment-resistant head-and-neck squamous cell carcinoma. Systematic accomplishment of these goals is expected to take five years.”

“Our work in this article paves the way for our next set of animal model studies for comprehensive characterization of radiation, as well as chemotherapeutic, responses,” Barman tells Physics World. “Using a non-invasive optical probe, we will then evaluate the feasibility of this method for in vivo tumour monitoring in an effort to harness the predictive power of Raman measurements to personalize chemoradiation therapy in head-and-neck cancer patients.”

Calculations provide insight into why sound waves carry ‘negative mass’

A new theoretical study has revealed how sound waves transfer small amounts of mass as they travel. Angelo Esposito, Rafael Krichevsky and Alberto Nicolis at Columbia University in the US have calculated that the transfer occurs even when both quantum and relativistic effects are ignored. Their result implies that current interpretations of the properties of sound waves may need to be rethought.

Physicists had widely accepted that sound waves carry energy and momentum, but not mass. In 2018, however, Riccardo Penco at Carnegie Mellon University and Niciolis and made an astonishing discovery when observing particle-like sound waves (called phonons) propagating through superfluid helium, cooled close to absolute zero.

They found that the phonons moved in upward trajectories, against gravity. Contrary to classical models of sound waves, this implied that the phonons were coupled to gravity, allowing them to carry minuscule amounts of “negative effective gravitational mass” as they travelled.

Fresh point of view

Now, Nicolis and colleagues at Columbia have analysed this intriguing property through theoretical calculations of sound waves in solids and ordinary fluids. The team normally work on theories of particle physics and say that this expertise allowed them to approach the problem from a fresh point of view. They derived an equation relating the mass carried by a sound wave to the wave’s energy, the mass density of the material, and the speed of sound inside it.

True to Niciolis and Penco’s previous observation, the team’s equation showed that sound waves carry a negative mass, meaning they deplete mass as they travel. This also meant that sound waves must interact with Earth’s gravitational feel, moving upwards like a buoyant object in water.

Entangled Hawking radiation spotted in analogue black hole

Photograph of Jeff Steinhauer in his lab at Technion

The result seems to imply that a small fraction of material travels in the opposite direction to the sound wave. While it is easy to imagine how this could occur in a gas or liquid, it is difficult to envision in a solid. Niciolis and colleagues suggest that waves of elastic compression could shift small amounts of matter in one direction, but more research would be needed to confirm this prediction.

Currently, physicists use linear models to study sound waves. This approximation is suitable for most applications, but Niciolis and colleagues believe that when more accurate results are needed, linear models should be adapted to account for mass transfer.

The team now hope to explore mass transfer in more detail in materials including Bose-Einstein condensates, and, on much larger scales, through the Earth as a result of earthquakes.

The research is described in Physical Review Letters.

Thermal transport goes ballistic across 2D thin films

Ballistic thermal transport across thin films of van der Waals layered semiconductors — First experimental evidence of “ballistic” thermal transport across thin films of van der Waals layered semiconductors (in this case MoS₂). Courtesy: A Sood, Stanford University

Researchers at Stanford University and the University of California, Davis, in the US are reporting on the first experimental evidence for ballistic thermal transport across thin films of van der Waals layered semiconductors. The unexpected result will have implications for thermal management in thin-film 2D electronics.

Layered semiconductors, like the molybdenum disulphide studied in this work, are highly anisotropic because of weak van der Waals interactions between the material layers. They conduct heat poorly in the direction normal to the layers as compared to along them.

“The ability of a material to conduct heat is directly related to how far thermal vibrations (phonons) in it can travel without decaying, and is measured by their mean free path,” explains Aditya Sood, who is co-lead author of this study. “In our work, we have shown that even though these layers are weakly bonded and conduct heat poorly in the film-normal direction, the mean free paths of thermal vibrations are, surprisingly, still quite large. This means that heat is not transported through localized oscillations of the layers, but through coherent vibrations that travel long distances across hundreds of layers before decaying.”

“It is generally thought that the weakly bonded layers vibrate in a decoupled manner when heat flows across the material, but our result suggests otherwise,” he adds.

The result will have implications for thermal management in thin-film 2D electronics. “While the thermal coupling of single-layer 2D materials is limited by their interfaces, we have found that few-layer 2D materials have a ballistic phonon resistance, quantified here for the first time,” says co-team leader Eric Pop.

The finding could be exploited to make materials with tuneable or ultra-low thermal conductivity by inserting defects between the MoS₂layers, because these could impede the flow of ballistic phonons. “Indeed, we have already demonstrated an application of this phenomenon recently by engineering a thermal transistor based on lithium intercalation in MoS₂thin films”, adds Sood.

Ultrafast thermal metrology

In their present experiments, the researchers used an optical technique called time-domain thermoreflectance, which can sensitively measure the thermal properties of thin films down to nanometre thickness. “We heat up our film with short pulses of laser light and monitor the temperature at the top surface by measuring its reflectivity as the heat from each pulse diffuses through the sample,” explains Sood. “By analysing how fast this cooling occurs (typically within nanoseconds), we can determine the thermal conductivity of the film.”

The team measured the film-normal thermal conductivity of MoS₂films with different thicknesses and found that the conductivity decreases with decreasing thickness. “Thanks to detailed atomistic calculations performed by our colleagues at UC Davis, we realized that this effect was in fact a direct consequence of the ballistic transport of thermal vibrations with mean free paths longer than the film thickness,” Sood tells Physics World. “These modes cannot carry much heat because of strong scattering at the film boundaries, which leads to an overall suppression in thermal conductivity.”

It is this boundary scattering of ballistic phonons that imposes a lower limit on the temperature increase in a device, he says.

The researchers, co-led by Ken Goodson and Yi Cui at Stanford and Davide Donadio at UC Davis, say they would now like to leverage the effects they have observed to engineer synthetic layered materials with extremely low conductivity. “As mentioned, inserting layers of a second material with a different atomic mass should result in scattering of ballistic phonons, leading to a dramatic suppression in heat transport,” explains Sood. “Such artificial solids could have exciting applications as thermal insulators on spacecraft, for example.”

The present study is detailed in Nano Letters 10.1021/acs.nanolett.8b05174.

Evidence for dark matter could be trapped in ancient rocks

Ancient rocks hidden deep underground could hold important clues about the nature of dark matter – according to physicists in Sweden and Poland. The idea is that dark-matter collisions should create nanoscale defects in the crystalline structure of rock – and this damage could be measured using modern microscopy techniques. Indeed, the team estimates that hundreds of thousands of defects could be present in just one cubic centimetre of rock.

A wealth of astronomical and cosmological evidence suggests that dark matter accounts for about 85% of matter in the universe, however, physicists have yet to make a direct detection of dark-matter particles. One possible candidate for dark matter are the weakly-interacting massive particles (WIMPs), hypothetical particles that only interact with normal matter through weak or gravitational forces.

While physicists have built a number of WIMPs detectors worldwide, none have managed to observe the elusive particles. These detectors tend to use large volumes of material and run over several years in the hope of seeing just a handful of collisions between WIMPs at atomic nuclei.

Now, Patrick Stengel at Stockholm University and his colleagues propose a simpler approach. They suggest that over billion-year timescales, WIMPs could have interacted many times with ancient rocks. The nuclear recoils induced by these interactions would have left characteristic, nanometre-wide damage tracks in the rocks, which are then preserved for billions of years.

This is not a new idea, but just like conventional dark-matter detectors, background radiation from cosmic rays and nuclear fission creates huge numbers of tracks that are difficult to discern from those created by dark matter. To minimize this background, Stengel and colleagues want to look at rock extracted from deep boreholes (about 10 km underground) to obtain samples that have been shielded for significant amounts of time from cosmic radiation. WIMP-induced tracks would also be easier to observe in materials like marine sediments and ultrabasic rocks, which are largely free of radioactive contaminants and can be found at suitable depths.

In addition, Stengel’s team show that detection techniques have vastly improved since earlier experiments. Using helium-ion beam microscopy, the physicists demonstrate that milligram-sized samples can be imaged at the nanometre-scale; providing the resolution needed to detect the tracks left by lower-mass WIMPs. Evidence for heavier WIMPs could also be found using small-angle X-ray scattering; although this would provide lower resolutions, tracks left by higher-mass particles could be found in samples as large as 100 g.

Strengel and colleagues concluded that a rock-based search would be many orders of magnitude more sensitive to lower-mass WIMPs than current detectors, and around 100 times more effective for heavier particles.

The proposal is described in Physical Review D.

Nanocrystals show near-perfect photoluminescence

Researchers have succeeded in chemically synthesizing cadmium selenide nanocrystals in a flask that are as perfect as materials grown at higher temperatures and in very controlled environments. They have also measured the exceptional photoluminescence efficiency of the materials using a new measurement technique called photothermal threshold quantum yield. The crystals could find use in advanced applications such as luminescent solar concentrators (LSCs) and optical refrigerators.

“From the optical perspective, these materials are nearly perfect,” says Alberto Salleo of Stanford University, who co-led this research effort with Paul Alivisatos of the Lawrence Berkeley National Laboratory. “The British theoretical physicist Sir Charles Frank famously stated that ‘crystals are like people, it’s the defects in them that make them interesting’. So, in this sense, these materials are ‘boring’ because they are so perfect, but they do, however, have unprecedented photoluminescence performance.”

Efficient photoluminescence needed for applications

Many optical applications, including solid-state lighting, colour displays and bioimagers, rely on efficient photoluminescence (the absorption and reemission of light), and the quantum yield of this process is extremely important. Indeed, when it approaches 100%, advanced devices like LSCs and spectrum-shifting greenhouses become possible.

Photoluminescence occurs when an absorbed photon excites an electron from a ground state into a higher-energy excited state, leaving behind a hole. Both charge carriers then quickly relax, in a matter of picoseconds, to the band edges by emitting thermal phonons into the crystal lattice. A few nanoseconds later, the thermalized electron and hole recombine, bringing the material back to its ground state, and this final transition can be either radiative or nonradiative (that is, mediated by defects by emitting more heat).

The performance of devices is measured using the photoluminescence quantum yield (PLQY), which is determined by the competition between radiative relaxation of the photoexcited charge carriers and nonradiative loss. The highest values recorded to date are 99.5 and 99.7 for rare-earth-doped high-bandgap single crystals and epitaxially-deposited thin films, respectively.

Thin films good, nanocrystals better

For commercial applications, it would be better to use nanocrystals (quantum dots), however, because they are more stable and cheaper than their bulk/thin-film counterparts and can be easily placed inside a host of composites, fluids, polymers and even biological environments. They can also be processed over large areas and their light absorption and emission can be tuned.

The PLQY for CdSe/CdS, which is the main core-shell quantum dot studied in research labs today can reach 95%. While high, this is not good enough for applications in which only an absolute minimum amount of light energy should be lost as heat. Indeed, optical refrigeration, thermophotovoltaic engines and thermal energy storage in optical cavities all require PLQYs of more than 99%, with negligible nonradiative losses.

Alivisatos’ team says that it has now succeeded in achieving such PLQYs by growing a 4- to 11-monoloyer CdS shell around a CdSe core using a modified version of a technique reported on in 2013 that produced a material with few surface traps while maintaining a high radiative efficiency.

Photothermal threshold quantum yield

The researchers had to overcome a problem first though to measure the photoluminescence efficiency of their materials: existing techniques do not have the accuracy needed to measure very high PLQYs, and often suffer from at least 2 to 5% uncertainty. To overcome this shortfall, they developed a measurement of the PLQY that does not rely on measuring photon flux but instead makes use of the quantization of light in a process analogous to the photoelectric effect.

“The technique is based on accurately measuring the instances where electron-hole recombination actually occurs nonradiatively and produces heat,” Salleo tells Physics World. “In a perfect emitter, electron-hole pairs at the band edges are expected to recombine without emitting any heat. Deviation from this expected ideal behaviour can be detected very sensitively, which makes our method, which we have called the photothermal threshold quantum yield (PTQY), very accurate.”

The team, reporting its work in Science 10.1126/science.aat3803, says it measured a PTQY of as high as 99.6 +/- 0.2%. “This value indicates that only 0.4% of the electron-hole pairs that are photoexcited recombine by giving off heat – that is, there is almost complete suppression of nonradiative PL decay channels. In other words, for every 1000 photons absorbed, the nanocrystals re-emit 996 photons, which can then be exploited in advanced optoelectronic devices.”

The researchers say they are now looking at the quantum yield of other materials recently made in Alivisatos’ lab.

Hawking on a 50p coin, hype over ‘quantum time reversal’, pi record smashed on Pi Day

This week marks the first anniversary of the death of Stephen Hawking. To celebrate his remarkable life, the UK’s Royal Mint has created a new 50p coin that features a stylized black hole along with the Bekenstein–Hawking formula for the entropy of a black hole. It was designed by Edwina Ellis, who told the BBC, “I wanted to fit a big black hole on the tiny coin and wish [Hawking] was still here chortling at the thought”. I think her representation of a black hole looks fantastic. You can read more in “Prof Stephen Hawking commemorated on new 50p coin”.

“No, scientists didn’t just ‘reverse time” with a quantum computer” is the headline of a story that appeared this week in MIT Technology Review. It looks at the hype surrounding a recent paper in Science Advances called “Arrow of time and its reversal on the IBM quantum computer”.

In the abstract of the paper the authors say, “Using this algorithm on an IBM quantum computer enables us to experimentally demonstrate a backward time dynamics for an electron scattered on a two-level impurity,” so you can perhaps understand why several media outlets worldwide reported that the physicists had reversed time.

Yesterday was Pi Day, at least according to the US-style digital date 3/14/2019. It is fitting that the value of the pi has been calculated to a record-breaking length of 31 trillion digits. This was done by Emma Haruka Iwao, who works for Google in Japan. She used the her employer’s cloud computing service to calculate pi and shatter the previous record of 22 trillion digits. You can read more in “Emma Haruka Iwao smashes pi world record with Google help”.

Climate change could allow disease-carrying mosquitoes to spread across Western Europe

Climate change could allow disease-carrying Asian tiger mosquitoes to spread across Western Europe, say two independent groups of researchers. The insects are known to spread more than 20 diseases including yellow fever, chikungunya, dengue and Zika – which could become more common in the region.

According to a new study by Soeren Metelmann of the University of Liverpool and colleagues in the UK, almost all of England and Wales could be warm enough for the species by the 2060s. Meanwhile, an international team including Moritz Kraemer at the University of Oxford has done an independent study that predicts that the mosquito will spread throughout Europe over the next 30 years.

Successful invader

Originally from East Asia, the insect is a highly-successful invasive species and is now found on every continent except Antarctica. It has been spreading across Europe since the 1970s. It is established as far north as Germany and the mosquito has been spotted in south-east England. In the last decade there have been outbreaks of chikungunya in Italy, showing that the spread of such mosquito-borne viruses within Europe is possible.

To understand how the mosquito could spread further in the UK, Metelmann and colleagues created a model that combines detailed knowledge of the life cycle of the mosquito with UK climate predictions from NASA for the period 2060–2069. The climate data covers two carbon-emission scenarios: one sees emissions peak in 2040, while emissions continue to rise in the other.

Under median predicted temperature rises, the model indicates that southern England and the English Midlands could support populations of Asian tiger mosquitoes by the 2060s, for both emissions scenarios. If the higher emissions scenario occurs and NASA’s maximum predicted temperature rise happens, then all of England and Wales along with parts of Scotland and Ireland would be suitable for the mosquitoes.

In their study, Kraemer and colleagues predict the future global distribution of the mosquito using 17 climate change models combined with data on historical mosquito spread and forecasts of human movement.

Describing their results in Nature Microbiology , the team says that they expect the Asian tiger mosquito to have spread across Europe by 2050, encompassing large areas of France and Germany and also patches of England, Wales, Scandinavia and the Baltic states. Initially the expansion is expected to be independent of climate change, but later dispersals will be driven primarily by environmental change. By 2080 the team predict that the Asian tiger mosquito will be in 197 countries worldwide, with 20 of those detecting its presence for the first time.

Urbanization and humidity

Kraemer told Physics World that much of the expansion “can be attributed to increasing temperatures, but other factors like urbanization and humidity also play key roles”. He adds, “We show that human movements are of crucial importance. Humans transport mosquitoes in all stages – adult, eggs, larvae – to new locations where they can establish new populations.”

This is not a new phenomenon. In the summer of 1865 there was an outbreak of yellow fever in South Wales, when a similar species of mosquito arrived on a boat from Cuba. At least 27 people were infected and 15 died. Metelmann says that it has always been possible for tropical mosquitoes to be introduced into the UK in warm summer months and survive – and even breed – for a few weeks before disappearing in the winter. But his team’s latest research shows that in the near future such introductions could lead to the establishment of resident populations that survive the winter.

Metelmann adds that the arrival of Asian tiger mosquitoes does not necessarily mean the arrival of the diseases they carry, but it makes it “more likely”. The biggest risk is mosquito-borne diseases brought in by travellers. “If this mosquitoes establishes in the UK and we get introductions by travelling cases of chikungunya, for example, and the mosquitoes bites the traveller it could then get transmitted locally,” Metelmann explains.

While current monitoring and control strategies are sensible, preventing the establishment of Asian tiger mosquitoes in the UK in the long term will become more and more challenging as conditions become more suitable, Metelmann says. He suggests that the future focus could instead be on techniques to stop the mosquitoes from transmitting viruses and other actions, such as vaccination.

3D printed piezoelectric materials line up for medical applications

“Hey, Cortana.” “Hey, Alexa.” “Hey, Lyra.” “Hey, Robin.” “Hey, Siri.”

If you’ve ever owned a quartz watch, received an ultrasound exam in a doctor’s office, or enjoyed a voice-controlled personal assistant like Siri, you have used piezoelectricity.

Researchers at Virginia Tech and Pennsylvania State University have now developed a method for 3D printing piezoelectric materials. These 3D printed structures look like sheets of tiny combs. Their properties are tunable, or directly assigned, ushering in a new era for medical devices and materials (Nature Mater. 10.1038/s41563-018-0268-1).

Piezoelectric effect production

If you stretch, squeeze or apply stress or pressure to a piezoelectric crystal, the structure will deform, pushing some atoms closer together and others further apart. Net electrical charge appears, and to rebalance themselves, the positive and negative charges align at the poles (opposite, outer faces) of the crystal. An electrical potential is created and can be harnessed for a variety of applications. This process is reversible, meaning that voltage can also be converted into mechanical energy.

Today, we rely on the piezoelectric effect for operating transducers, circuits and other systems, but the range of piezoelectric properties available for new applications remains limited, says Xiaoyu (Rayne) Zheng, senior author of the Nature Materials study. Crystal orientations are few, materials are brittle, and development and processing require a clean room.

To address these limitations, Zheng and his research team developed an additive manufacturing technique for piezoelectric materials. Rather than chemically synthesizing novel piezoelectric materials, their technique uses existing materials and a modified desktop 3D printer.

Printing stage for 3D printed piezoelectric materials. (Courtesy: Xiaoyu (Rayne) Zheng)

Put simply, these new, 3D printed piezoelectric materials are tunable, Zheng explains. “Unlike conventional piezoelectrics where electric charge movements are prescribed by the intrinsic crystals, the new method allows users to prescribe and program voltage responses to be magnified, reversed or suppressed in any direction,” he says.

Zheng’s team fabricated the piezoelectric materials through a three-stage process. First, they dispersed a surface-treated powder in a light-sensitive resin until a solid matrix formed. Then they exposed a thin deposit of resin to a patterned beam of light over and over to build a lattice. Finally, they exposed the lattice to intense electric fields to ensure that the poles aligned and responded collectively.

The future of piezoelectric materials

The tunability of 3D printed piezoelectric materials also enables multi-functionality. Zheng envisions their use in intelligent materials and devices, particularly in medicine. Adaptable stents in blood vessels will regulate and sense blood pressure changes. Self-sensing synthetic skin will record and detect pressure, pulse, joint movement, voice, breathing rate and motion. Wearables will sense dynamic pressure changes in the hands and feet, while ultrasound transducers will help medical personnel visualize tissues in different ways.

The advantages of 3D printed piezoelectric materials were precisely what made the project difficult, says Zheng. The research group faced two primary challenges: modelling the materials and their responses in tensor space, and making sure that the materials were printable.

The research team is confident that their results will hold as they explore novel applications for their 3D printed piezoelectric materials. They used simulations and experiments to verify their theory, designs and materials using classical piezoelectric crystal geometries, and verified the expected behaviours and responses of the 3D printed materials experimentally.

What’s next for the research team? Designing appropriate piezoelectric sensitivities, developing methods for 3D electronic integration, and investigating more biologically friendly piezoelectric materials for embedded device applications.

Young forests use carbon most effectively

For forests, it really does help to be young. British scientists who have identified the vital factor that shows what makes a forest a good carbon sink say young forests use carbon best and absorb it most efficiently.

A new study in the Proceedings of the National Academy of Sciences seems on the face of it to settle an old puzzle with an unsurprising answer. New and young forests make the most efficient and effective carbon sinks.

Humans burn fossil fuels and emit vast quantities of greenhouse gases such as carbon dioxide into the atmosphere. The felling, burning and clearing of natural forest releases ever more carbon.

But green plants absorb CO₂ to make tissue and turn the gas into root and branch, leaf and bark, trunk and fruit. So scientists, led by Tom Pugh of the University of Birmingham in England, addressed the question: what kind of forest is best as a carbon sink?

They gathered data about forest age, devised computer models and looked at the estimates of carbon intake between 2001 and 2010 in old, long-established areas of forest. Then they looked at the data from younger stands of timber that had colonised areas once logged, or damaged by forest fire, or farmed and then abandoned.

They identified an age effect in stands of timber less than 140 years old: big enough to account for 25% of forest carbon uptake from the atmosphere.

And although the great tropical rainforests are regarded as the “lungs” of the planet, and invaluable resources and homes for biodiversity, in fact the most efficient carbon dioxide consumers were forests in the middle and high latitudes: these included areas of land once farmed in the US eastern states, and then left to become part of the US National Forest, and farmland abandoned during the worldwide economic depression of the 1930s.

The finding seems reasonable, if only because the carbon appetite that turns a sapling into a full-grown tree would seem to be more demanding than that of mature or very old trees. But nothing about the notorious “carbon budget problem” is simple.

Uncertain response

It is an axiom of global response to climate change that forests should be protected and restored. But the nature and the mechanisms of forest carbon uptake can be difficult to establish.

In theory forests may absorb around a third of all carbon emissions, but the way trees could respond to the extra carbon dioxide available is still not certain.

As carbon dioxide ratios in the atmosphere increase, the planet warms and climates change: it could be possible for some forests, some of the time, to actually release more carbon than they absorb.

And while it might seem obvious that young trees would be greedier than old ones, precise measurement of the forest giants doesn’t necessarily tell the same story. Although the importance of forests is not in question, researchers keep making the point that forests are not enough.

Drastic cuts needed

Humans must still find ways to drastically cut fossil fuel use, and greenhouse gas emissions. But as of 2019, there is no sign that this is happening.

But the latest research confirms the value of some investments. It suggests that the vast reforestation programmes launched in China, and the huge boreal forests of Canada, Russia and Europe, are playing an important role in climate management.

“It’s important to get a clear sense of where and why this carbon uptake is happening, because it helps us make targeted and informed decisions about forest management,” Pugh said.

“The amount of CO₂ that can be taken up by forests is a finite amount; ultimately reforestation programmes will only be effective if we simultaneously work to reduce our emissions.”

This article first appeared at Climate News Network

Multipole magnetic tweezers measure organelle mechanical properties

Being able to directly probe organelles (specialized structures inside biological cells) and measure their properties is important for understanding subcellular activity, diagnosing diseases associated with this activity and developing new therapies. Doing this is no easy task, however. A team of researchers in Canada, China and the US has now developed a new magnetic tweezer system that can measure the mechanical properties of organelles for the first time. The device makes use of a magnetic bead placed inside the cell that can be used to precisely manipulate intracellular structures at any location in 3D and apply a controllable force of up to 60 piconewtons to them for long periods. By relating the applied force and the amount by which the organelle deforms as a result, the nanobot can measure properties such as viscoelasticity and plasticity of the cell nucleus, mitochondria and endoplasmic reticulum.

“The mechanical properties of the biggest organelle inside a cell – the nucleus – are altered in cancer cells, cells with progeria, and cells infected with malaria,” explains lead author of this research study Xian Wang of the University of Toronto. “Directly probing the mechanical properties of the cell nucleus inside single cells would thus help us better understand the structural differences between diseased and healthy cells.”

Current techniques to manipulate subcellular structures often use invasive tools like micropipettes that can damage organelles. Optical tweezers that use laser beams are also popular, but the force that they generate is not high enough to mechanically move organelles.

Sub-micron bead

The new tweezer consists of six magnetic coils with sharp poles placed in different planes around a microscope coverslip seeded with live cells. The researchers apply electric current to each of the coils to generate a high magnetic gradient in the workspace. They then place a magnetic bead, with a diameter smaller than 1 micron, onto the coverslip, where the cells easily take it up through endocytosis. The bead can be pushed in different directions inside the cell by applying varying magnetic fields and so be made to “probe” the insides of the cell.

The device is integrated in a confocal microscope so that it can be imaged with high resolution. By observing the confocal microscope images in real time, the researchers were able to measure the elasticity and viscosity of a cell’s nucleus and observe variations in stiffness along different parts of the organelle. For example, they found that the nuclei of late-stage bladder cancer cells that they studied were less stiff when poked compared to early-stage ones.

Generalized predictive control algorithm

The device provides a way to directly quantify the mechanical properties of intracellular organelles without having to freeze-dry and cut them up into slices first, explains Wang. What is more, we can exert forces of around 50 pN, which is an order of magnitude higher than that possible with lasers. And thanks to a generalized predictive control (GPC) algorithm, we can precisely control its position inside the cell to within a couple of hundred nanometres down the Brownian limit.

“When the magnetic bead is small, we require a high-resolution imaging tool to observe it and so control its position based on image feedback,” says Wang. “However, the problem is that high resolution means low imaging speed, which results in a large positioning errors using a traditional control algorithm.”

To overcome this problem, the researchers adapted this algorithm for a sub-micron bead and developed their GPC, which predicts the bead position when no image feedback is available based on the previous camera frame. “This is how we are able to control it with an average of 0.4 microns (about half the bead’s body length),” says Wang.

“The idea of multipole magnetic tweezers is not new,” he tells Physics World. “We have simply further developed this concept and the method for sub-micron position control and pico-Newton force control on the smallest bead ever in this kind of study.”

Mechanical load during metastasis

In their experiments, the researchers found that the cell nucleus stiffens after repeated applied mechanical load. This type of load is what the cell experiences during metastasis, when it has to squeeze through the tiny spaces between the endothelium cells of blood vessels.

“Previous research has revealed that nuclear deformation determines whether the cell can pass through a confined space,” explains Wang. “Nuclei of cancer cells are usually softer than those of healthy ones, which means they can do this and metastasize to other organs in the body. In our work, we discovered that late-stage cancer cells do not stiffen much after a force is applied to them, so they can continue to move invasively.”

This study focused on characterising the biophysical properties of intracellular organelles and the researchers say they are now looking to apply their technology to diagnosis and treatment. “Based on our current results, early-stage and late-stage cancer cell nuclei have distinct mechanical properties and these might potentially be used as a marker for diagnosis when no apparent physiological or morphological difference is present.

“For treatment, we are working on understanding and developing large scale tools – foe example, applying a large force intracellularly to trigger cell apoptosis, for targeted cancer therapies.”

The team, reporting its work in Science Robotics 10.1126/scirobotics.aav6180, includes Helen McNeil and Yonit Tsatskis at Mount Sinai Hospital and Sevan Hopyan at The Hospital for Sick Children (SickKids).

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