Promising evidence for the existence of a hypothetical dark matter particle has been uncovered in an experiment done by a team led by Vladan Vuletić at the Massachusetts Institute of Technology. However, a related measurement by Michael Drewsen at Aarhus University in Denmark and colleagues found no signs of the so-called “dark boson”.
Physicists know that the Standard Model of particle physics cannot be complete in its current form. For one thing, it does not describe dark matter – an elusive substance that has a profound influence on the evolution of galaxies and larger-scale structures in the universe. Current theoretical candidates for dark matter include hypothetical particles like axions and WIMPs – but decades-long attempts at the direct detection of such particles have come up short.
If dark matter particles behave in a broadly similar manner to known massive particles such as electrons, then interactions between dark matter particles should be mediated by a dark boson. In June 2020, physicists on the XENON dark matter detector observed excess light flashes in an underground liquid-xenon chamber, which may have been related to a dark boson.
Interacting neutrons and electrons
It is possible that a dark boson could mediate interactions between known particles – for example between neutrons and electrons in an atom. This would have a tiny effect on the energy levels of the atom, which could be revealed by making high-precision spectroscopy measurements.
Now, the Vuletić and Drewsen teams have searched for evidence a dark boson in the atomic spectra of isotopes of ytterbium and calcium, respectively. Isotopes were used because their nuclei have different numbers of neutrons and therefore potentially different dark-boson interactions with electrons.
Using high-resolution spectroscopy, each team measured shifts in the atomic spectra of five different isotopes of the atoms, as their electrons transitioned between two specific hyperfine energy levels. They then produced “King plots” of these transitions – which graph the observed frequency of one transition against that of the other.
According to the Standard Model, these King plots should be perfectly linear – which is what Drewson and colleagues found in their study of calcium isotopes. However, Vuletić and colleagues measured a distinct shift from linearity with a statistical significance of 3σ – which is much too low to be considered a discovery. The team says that the shift could be evidence for the existence of dark bosons, but that it is also in line with another proposed modification of the Standard Model.
Both teams now plan to make more accurate measurements of hyperfine electron transitions.
The studies are described in papers in Physical Review Letters by the Vuletić and Drewsen teams.
As tumours progress and grow, they undergo mechanical alterations such as changes in extracellular matrix rigidity and build-up of compressive stress. A European research team has now proposed that this compression of solid tumours may help explain why some cancers are resistant to chemotherapy drugs.
To test their hypothesis, the researchers examined tumour spheroids formed from pancreatic cancer cells. Under normal free-growth conditions, the spheroids increased in size to reach diameters of hundreds of microns. They also embedded spheroids in agarose gel. This confinement reduced cell proliferation, slowed the spheroid growth and after a few days, led to growth-induced pressure in the kilopascals range.
“We chose to work on pancreatic cancer because it is both one of the deadliest cancers, and one where the impact of compressive stress is very important, as pancreatic tumours are highly compressed,” explains Morgan Delarue from LAAS-CNRS. “We chose to examine the link between mechanical stress and chemotherapy efficacy.”
In a study described in Physical Review Letters, Delarue and colleagues – also from HZI, Claude Bernard Lyon 1 University and CRCT – treated both types of spheroid with 10 μM of the chemotherapy drug gemcitabine. They found that compressed spheroids were less sensitive to the drug than freely growing ones. The unconfined spheroids decreased in size by 30–40% after drug exposure, while spheroids treated after two days of confined growth shrank by less than 10%.
As gemcitabine targets proliferating cells, this reduced drug efficacy under compression may well be due to the decrease in cell proliferation. However, compression could also trigger mechanosensitive pathways that act directly on the drug, such that it does not reach the cells, is exported out of the cells or de-activated by the cell, for example.
To explore these potential mechanisms, the researchers developed a mathematical model to predict the combined effect of compression and drug exposure on spheroid growth. The model made two assumptions: that cell growth rate is affected by pressure; and that the drug only kills proliferating cells, with a killing rate that does not depend on pressure.
“We could not selectively test all these parameters experimentally, so we opted for a mathematical model with just two ingredients,” Delarue explains. “We can calibrate both parameters independently: proliferation under pressure, and drug killing without pressure. We also assumed a linear coupling between growth and drug-induced death.”
The model accurately predicted the experimental data – implying that tumour resistance arises solely from the effect of compression on cell proliferation. “We observed an outstanding prediction,” says Delarue. “This strongly suggests the aforementioned mechanism, as other impacts of the mechanics on the drug would not be predicted by this model.”
This interpretation also implies that lowering compressive stress should increase cell proliferation and thus improve drug efficacy. To test this, the researchers examined gel-embedded spheroids treated over 6–7 days, after which time they had decreased in size such that they were no longer compressed. The model captured the experimental data exactly: a slow initial death velocity during compression, followed by a faster one in the unconfined phase.
This mechanical form of drug resistance should be independent of the type of drug used and the type of mechanical stress applied. The researchers confirmed both of these predictions. Firstly they treated spheroids with a different chemotherapeutic, docetaxel. The model accurately predicted the experimental results, with docetaxel efficacy reduced in compressed spheroids.
They next applied a different kind of mechanical stress: osmotic compression with dextran. Osmotically compressed spheroids treated with gemcitabine showed a similar modulation of drug efficacy as seen with growth-induced pressure. Again, the model accurately predicted these effects, further reinforcing the premise that mechanics decreases drug efficacy by modulating cell proliferation.
The team is continuing to work on this question of how compressive stress impacts cancer progression and treatment. “Additionally, we are seeking to understand how exactly compressive stress plays a role on cell proliferation,” Delarue tells Physics World. “We know it stops proliferation, but how? Understanding this point would help us to develop coupled therapies: a drug which would force cells to proliferate under pressure, plus a chemotherapeutic to kill them.”
ILL has been upgraded continuously since 2000. What enhancements have been made and how are they currently being exploited by researchers?
Our Millennium upgrade programme ran from 2000 to 2016 and had a budget €100m. To put this into context, we were spending close to 10% of our overall budget every year on upgrades. Millennium was a continuous process of upgrading the services we provide to our users in terms of instrumentation and software. An example of one instrument that was upgraded is WASP, which is a spin echo spectrometer. We gained orders of magnitude in performance, which allowed our users to do completely new kinds of experiments.
We are currently in the Endurance upgrade programme, which began in 2016. It will see €60m invested over eight years ending in 2023 – again, that is about 10% of our total budget spent on upgrades each year.
The continuous upgrading of instrumentation is essential because technology changes rapidly – you wouldn’t buy a car today that had the performance of a 2000 model. Also, the scientific problems that our users tackle are becoming increasingly more complex. As a result, users expect equipment to deliver higher throughput; achieve shorter measuring times; study faster kinetic processes; smaller samples; and much more. We are in an international competition with other neutron facilities – as well as other probes of matter such as X-ray sources and electron microscopes – so upgrading keeps us highly competitive.
We have nearly 40 instruments at ILL – 28 of these are public instruments and the rest are what we call collaborating research group instruments. All together they support about 800 experiments and 1500 scientists per year. The lifetime of an instrument is about 10 years – then it needs a major upgrade or a complete rebuild. Sometimes an instrument is phased out because the science moves on and we replace it with a new instrument for a different community. This is what we did during the Millennium upgrade and we will continue to do in Endurance.
How do you plan for upgrades?
We run ILL a bit like a business. When planning the Endurance upgrade, we had to anticipate the needs of our future scientific clients. For example, neutron imaging had not been done at ILL but we realized that it is becoming increasingly relevant. We were able to gain competence in imaging from other facilities such as BER II in Berlin, which has just shut down, or the local university here in Grenoble. We plan to install some BER II instrument components here and aim to have a top-notch neutron-imaging facility here at the ILL – hopefully the best in the world.
Another thing that we identified in the consultation for Endurance is the need to support more research in structural biology. We have an instrument called LADI that did some nice work on the HIV virus, for example. We are now in the process of installing a second upgraded version of LADI, called DALI, that should be ready for the users as soon as our neutron source has started up after the lockdown. We will use that instrument immediately to do COVID-19-related research.
Our neutron source is a reactor, which must be maintained and upgraded to ensure that it is compliant with the highest safety standards. While this is less visible to our user community, we have spent ?30m over 2000–2016 keeping the reactor in the best possible shape.
Grenoble is also home to the European Synchrotron Radiation Facility (ESRF). What are the benefits to science of having these facilities right next to each other?
It’s definitely a benefit to have such facilities on the same site and many of our users also use X-rays at ESRF. This co-location has been copied in several places around the world including the UK and Switzerland.
Sometimes users make separate research proposals to each facility. Some measurements, however, must be made in a very co-ordinated way. In small-angle scattering, for example, it could be advantageous to do the neutron measurements after the X-ray measurements. In such cases scientists can make a joint proposal for beam time at both facilities. Grenoble is home to the Partnership for Soft Condensed Matter and the Partnership for Structural Biology, which encourage research that uses both ILL and ESRF.
When it comes to structural biology, Grenoble hosts a site of the European Molecular Biology Laboratory (EMBL) and the French Institute for Structural Biology (IBS). These institutes have complementary capabilities in microscopy and nuclear magnetic resonance (NMR).
It is also very important that we have strong links to academia and industry, both in Grenoble and throughout Europe. We currently have 40 PhD students at ILL and about 20 of those are linked to industry.
Helmut Schober “We had to anticipate the needs of our future scientific clients.” (Courtesy: ILL)
The European Spallation Source of neutrons will open in Sweden in 2023. What roles will the ILL and the ESS play in the European and international neutron communities?
Europe today has the highest performing neutron community in the world because of the high quality of its national and international facilities. It is very important that the ESS succeeds in becoming a flagship facility for Europe. The Spallation Neutron Source (SNS) in the US is up to full performance and is currently engaged in boosting the power of its accelerator while equally talking about a second target station. The Americans are also thinking about either upgrading or replacing their High Flux Isotope Reactor (HFIR). Elsewhere, the Chinese have just commissioned their spallation source and Japan has a powerful spallation source. In this competition, Europe must not lose out.
The ESS will have its first neutrons around 2023. Routine operation with a large part of the instruments in place should occur by 2025. It is crucial, therefore, that ILL maintains a high-quality service to Europe’s neutron community until at least 2030. User communities can be volatile and if there is a shortage of neutron capacity, scientists will turn to other probes to get the information they need.
Unfortunately, several reactor-based national and regional neutron sources have closed recently worldwide. Should these facilities be replaced, or does the future lie in upgrading major international sources like ILL?
Regional neutron sources are definitely needed but there is a political dimension to the closure issue – it depends on whether or not a country is still willing to build a reactor. Europe has a great deal of expertise in building and operating research reactors and this must be preserved because there are some neutron experiments that simply can’t be done using spallation sources. This is the approach that the US, Japan and China are taking. Furthermore, research reactors fulfil a very important role in society because they make medical isotopes.
In Europe, no single country can afford to have it all so it is important that we share the load. We already do this because both the ESS and ILL rely on financial input from many countries. However, there is a danger that when a country runs into financial difficulties and cuts back on spending on neutron research their research communities will suffer.
A case in point is Italy, which has a strong neutron community, but for various financial reasons is not currently able to contribute to ILL in a way that would allow Italian scientists to develop their full potential. Fortunately for us, this missing income has been compensated by contributions from other countries and the financial damage was limited. It is really tough, though, for Italian scientists because we have to turn down their excellent research proposals. I regret this as a scientist, but we cannot separate scientific strategy from the financial and political environments.
Bright idea SuperSUN is a new high-density source of ultracold neutrons at ILL. (Courtesy: ILL/L Thion)
COVID-19 could result in a short-term crisis in scientific funding that could impact both direct funding of ILL and the funding of your user community. What worries you the most?
Both worry me. In the recession of 2007–2009, university funding was cut in some European countries. We noticed, for example, that demand from Spain’s large and high performing neutron community was going down. Access to ILL was guaranteed because Spain is a partner, but the community did not have enough PhD grants and other research funds – so scientific activity was reduced. We also had a budget cut after 2009 at ILL and this delayed the Millennium programme, which finished a bit later than originally planned.
In the face of a possible recession, we must ensure that ILL is properly funded so we can provide neutrons to our users – and we must also ensure that the ESS is not delayed by cutbacks. We operate in a research ecosystem and if financial difficulties occur in one area, it can affect the whole system. We need to limit the negative effects that this crisis could have on science budgets across Europe. This includes doing a holistic analysis of national facilities used by our community because delays in upgrades to national facilities could have significant overall effects on how ILL is used. It is really a complex matter.
On a positive note, COVID-19 has made governments realize how important research is. I hope that the promises that have been given in terms of maintaining research budgets will materialize. Also, I hope that this money is not directed only to research related to the virus – because the next crisis may be completely different.
Some physicists might be surprised to hear that ILL also has fundamental physics programme. What does that entail?
Our reactor produces large quantities of neutrinos and we have an experiment called STEREO that measures neutrino oscillations with the hope of discovering a fourth type of neutrino called a sterile neutrino. We are currently considering a proposal for an experiment called RICHOCHET that would measure how neutrinos scatter from nuclei in a solid target.
We also do fundamental physics by creating beams of cold neutrons – and by trapping and storing ultracold neutrons. This allows us to make very precise measurements of the neutron lifetime, which is important because the decay of the neutron to a proton offers the cleanest way to study the weak interaction. We can also measure the electric dipole moment of the neutron. This should be zero according to the Standard Model of particle physics, so a non-zero measurement would be very significant. And last but not least, the precise determination of the neutron’s gravitational states is a valuable test bed for models trying to explain dark matter or dark energy.
In these tough times of the COVID-19 pandemic, one of the safest ways of mixing with friends is to meet up in a local park. But what 2D configuration, lattice or otherwise, offers the best way to maintain the appropriate social distance? Many years ago, I did a PhD on properties of 2D atomic lattices, so I thought I might have the answer to that question – how wrong I was. My rather unsatisfactory answer is, “it depends”.
One criterion you might consider when advising people where to sit is simplicity – after all, most folks are not familiar with crystallography and may not be able (or indeed willing) to create a 2D Bravais lattice in their local park. So, perhaps it is best to go with a familiar square lattice. But there are two problems here – one is that you only have four nearest neighbours to chat with, and if you extend your social circle out to next-nearest neighbours, there are just four of those as well. The second problem is that a square lattice does not make efficient use of our precious green space – it delivers a 78% efficiency when it comes to packing in personal bubbles of fixed diameter.
In contrast, a hexagonal lattice makes use of 91% of available space – which is why this is called a “close-packed” arrangement. The hexagonal lattice is also 50% more social than a square lattice, because everyone has six nearest neighbours. There’s also more room for the party to grow, because you also have six next-nearest neighbours. A possible downside of this structure is that it could be more difficult for people to arrange themselves in a hexagonal lattice – ensuring that your six nearest neighbours are all at 60˚ from each other seems trickier than arranging your four nearest neighbours at right angles. However, if everyone carried a metre-stick, then you could take advantage of the close-packed nature of the lattice by having people trace out a circle around them so that their circle touched on the circles of six other people.
Just as we have 2 m markers on the floor to tell us how to space ourselves in a 1D queue, humans probably need a bit of help to crystallize in 2D
Just as we have 2 m markers on the floor to tell us how to space ourselves in a 1D queue, humans probably need a bit of help to crystallize in 2D. I think social distancing in a park is best done as an epitaxial process, where someone from the parks department provides a suitable substrate by painting a lattice of close-packed circles on the grass before everyone arrives with their picnic baskets. But human epitaxy has its challenges because interactions between individuals could cause something akin to a surface reconstruction. This occurs when atoms deposited on a surface sit where they want, rather than adhering to the underlying lattice structure. This process is referred to as “relaxation”, which is exactly the sort of thing you would expect to occur on a sunny Saturday afternoon in the park after the consumption of many gins-in-a-tin.
So, if you want to socially distance in an efficient way with 12 friends, then a hexagonal lattice is the winner. But are there downsides to close packing? How would you, for example, join a group of friends in the middle of a busy park who have kindly left a space for you? If the park is not too full, you might be able to hop like a highly correlated electron from one empty lattice site to the next. I’m not sure if a partially full square or hexagonal lattice is the easiest to navigate in this way – I will leave that calculation to you – but one way of getting through a partially full park would be to rearrange people back and forth as you move through, much like those moving-tile puzzles of numbered squares that you find in Christmas crackers. I don’t know if such a solution can be computed, but working out the best route and rearrangement of people on a 2D lattice is probably best addressed by a quantum annealer.
On a warm sunny afternoon, however, hopping like an electron through a crowded park is impossible. The lattice is in the insulator state, and the only way to get to your friends is to defy the laws of physics, and social-distancing, and charge on through. This is where the square lattice could offer an advantage because the lower packing density means you could manage to stay further away from people than you could in a hexagonal lattice – but you would still break the 2 m rule.
Glass on the grass
So do any other 2D arrangements offer benefits? One problem with lattices is that people tend to line up along specific directions, which means that your near neighbours tend to block your line of sight to friends who are further away. This could be a moot point because shouting across 4 m or more is not particularly sociable. But if you wanted a direct line of sight to lots of faraway neighbours, the solution could be a glass-like structure in which people are scattered about the park, at a minimum 2 m distance between individuals. I suspect that this arrangement would naturally emerge in a park if people sat where they wished. And perhaps there would be some sort of phase transition to a hexagonal lattice at a critical density?
The finite nature of a park also comes to bear on social distancing. Lattices, after all, are infinite constructs and a close-packed arrangement is not always the most efficient way to pack spheres within a confined space. If a square garden only has room for 12 people, for example, a hexagonal arrangement works best – but a garden with room for 16 is best filled by a square lattice. And between these two, the most efficient configurations are jumbled and do not have a lattice structure.
Park boundaries are a problem because they break a lattice’s translational symmetry – so why not choose a quasicrystal arrangement that does not have translational symmetry? I’ll leave that thought for the reader to ponder after a few cold ones in the blazing sunshine.
The US physicist Arthur Ashkin, who shared the 2018 Nobel Prize for Physics for his contributions to laser physics, died on 21 September aged 98. His most famous work concerned the use of laser light to manipulate microparticles, which led him in the 1980s to create “optical tweezers” that could be used to trap and control atoms, viruses and bacteria. For this development he shared the 2018 Nobel prize with Gérard Mourou and Donna Strickland for their “groundbreaking inventions in the field of laser physics”.
Ashkin was born on 2 September 1922 in New York City, US. He completed a degree in physics from Columbia University in 1947 followed by a PhD from Cornell University in 1952. After his PhD, he moved to Bell Labs in New Jersey where he remained for the rest of his career. It was at Bell Labs where he pioneered the use of laser to manipulate objects. In 1970 Ashkin showed that forces generated by laser beams can trap tiny dielectric particles in air or water. The scattering of light pushes the particles in the direction of beam propagation so two counter-propagating beams will stop a particle from moving along the axis of propagation.
A major improvement came 16 years later, when in 1986 Ashkin showed that it is possible to trap particles using just one laser beam – rather than a counter-propagating pair. This optical trap, known as optical tweezers, could hold particles ranging in size from tens of nanometres to tens of microns – a range that allowed the study of viruses, bacteria and other biological cells. To manipulate such living organisms in a way that would not damage them, Ashkin switched the laser light from green to infrared light. Optical tweezers have since proved invaluable to biophysicists, who have used them to measure the forces involved in biological processes such as the transport of organelles within living cells, how bacteria are propelled by rotating flagella and how forces affect large biological molecules such as DNA.
Ashkin retired in 1992 and held 47 patents through his career. In 2013 he was inducted into the US National Inventors Hall of Fame and in 2018, at 96, became the oldest person ever to receive the physics Nobel prize. Given Ashkin’s health, he was unable to attend the Nobel prize ceremony and his Nobel lecture was instead delivered by his colleague René-Jean Essiambre following a short video greeting by Ashkin.
On the nanoscale, objects warm up faster than they cool down. That is the surprising conclusion of Alessio Lapolla and Aljaž Godec at the Max Planck Institute of Biophysical Chemistry in Germany, who have predicted this asymmetry using mathematical models of confined nanoparticles.
One basic assumption in thermodynamics is that an object that is either hotter or colder than its surrounding environment will cool down or heat up, respectively, at the same rate. So, an object that is slightly warmer than room temperature will reach room temperature at the same time as an identical object that started slightly below room temperature.
Lapolla and Godec tested this principle in their study using a mathematical model of a tiny nanoparticle trapped inside a one-dimensional box. As the particle undergoes Brownian motion, its position is mapped using a probability distribution – which peaks at the centre of the box, where the particle is most likely to be found. Since Brownian motion increases with temperature, the duo predicted that heating should cause the probability distribution to spread out during heating, and become narrower during cooling. However, this was not expected to result in a difference in how hot and cold particles reached equilibrium with their surroundings.
Off the walls
Contrary to expectations, however, Lapolla and Godec observed that warmer particles took longer to cool down than cooler objects did to warm up. To explain this asymmetry, the duo suggests that the more dynamic motion of a warmer particle means that it bounces off the walls of the box more often. As a result of this bouncing, the warm particle tends to drift towards the centre of the box more readily. This counteracts the spreading out due to Brownian motion – thereby narrowing the particle’s probability distributions to the centre of the box. In contrast, this bouncing became less pronounced at cooler temperatures. With less opposition to their Brownian motions, colder particles could relax to their equilibrium states more readily than their warmer counterparts.
Lapolla and Godec believe their results will improve our understanding of temperature changes in nanoscale systems. It could also provide fresh insights into phenomena like the Mpemba effect – whereby water appears to freeze more quickly when its starting temperature is warmer. The duo now hope to verify their results through practical experiments, which could be carried out relatively easily by confining particles within optical traps. The insights gained through these studies could also help to improve efficiency in devices including micromotors and heat pumps.
The announcement of the 2013 Nobel Prize for Physics is memorable for the hour-long delay in announcing the winners – François Englert and Peter Higgs – and for the long citation.
The pair won “for the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles, and which recently was confirmed through the discovery of the predicted fundamental particle, by the ATLAS and CMS experiments at CERN’s Large Hadron Collider”.
Theory, experiment or both?
I can vividly remember the morning of 8 October 2013 while I sat at my desk at Physics World headquarters waiting for the prize announcement. The Higgs boson had been discovered at CERN in July 2012, and it was pretty obvious that the 2013 prize would be related to the discovery. The big question was would it go to the theorists who predicted the Higgs back in 1964 or to the experimentalists who discovered it – or both?
Now when it comes to announcing the winners of each year’s Nobel prize, the Nobel Committee usually does so precisely at the scheduled time. But as the minutes ticked by, and no news was forthcoming, I started to wonder if 2013 was going to be the year when the committee finally dispensed with the rule that no more than three people can share the prize.
I imagined that, in an opulent, portrait-lined room at the Swedish Royal Academy of Sciences, a huge row had broken out about whether or not to give at least a portion of the award to the thousands of physicists working on ATLAS, CMS and the LHC. After all, the Higgs was not found by accident at CERN – there had been a decades-long sustained and focussed effort to detect the particle. Furthermore, modern science is highly collaborative, so recognizing the CERN physicists, I felt, would be the perfect way to update a prize that is more than a century old.
Out-and-about in Edinburgh
But alas, it wasn’t to be. The hour-long delay in announcing the prize merely occurred because the committee could not contact Peter Higgs. He was out-and-about in Edinburgh and in the end only heard about his win after lunch, several hours later, when he was congratulated in the street by a former neighbour.
What is more, I don’t think any scientific collaboration will be winning the Nobel Prize for Physics any time soon. Last year I interviewed Lars Brink – a Swedish particle theorist who served on the Nobel Committee for Physics on eight separate occasions and who served as chair for the 2013 award. Brink says that the Academy is hesitant to open the physics prize up to organizations or collaborations such as CERN. “We don’t want 5000 people calling themselves Nobel laureates,” he told me.
What the Nobel Committee did do, however, was to beef up that year’s citation. By mentioning ATLAS, CMS and the LHC, the committee did go at least some way to recognise the legion of experimentalists who confirmed calculations done by Higgs and independently by Englert and Robert Brout – the latter having died in 2011 and who therefore also missed out on the prize.
But given that the Higgs prediction and subsequent discovery is a classic example of how theory and experiment work hand in hand, I still think it is a shame that all those hard-working experimentalists were unable to share the prize. My fantasy citation for the 2013 prize would therefore have been “to François Englert, Peter Higgs and to all the physicists working on ATLAS, CMS and the LHC for the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles and the experimental discovery of the predicted fundamental particle”.
Still, who knows, perhaps the experimental discovery of the Higgs will be honoured this year after all – or in years to come.
In recent years, the pharmaceutical industry has been interested in biocatalysis (enzymes) for the production of drugs and drug intermediates due to the high selectivity of enzymes. However, many of these enzymes require expensive cofactors. Electrochemistry provides an opportunity to do cofactor regeneration to decrease the cost and the sustainability of biocatalysis for synthesis.
This webinar will introduce bioelectrocatalysis and discuss its current and future applications in electrosynthesis.
Shelley Minteer is a USTAR Professor in the departments of chemistry, and materials science and engineering at the University of Utah. She received her PhD in analytical chemistry at the University of Iowa in 2000 under the direction of Professor Johna Leddy. After receiving her PhD, she spent 11 years as a faculty member in the Department of Chemistry at Saint Louis University before moving to the University of Utah in 2011. She is also an Associate Editor for the Journal of the American Chemical Society. She has published more than 350 publications and more than 450 presentations at national and international conferences and universities. She has won several awards, including the Luigi Galvani Prize of the Bioelectrochemical Society, the Missouri Inventor of the Year, International Society of Electrochemistry Tajima Prize, Fellow of The Electrochemical Society, and the Society of Electroanalytical Chemists’ Young Investigator Award. Her research interests focus on electrocatalysis and bioanalytical electrochemistry. She has expertise in biosensors, biofuel cells, and bioelectronics.
Sometimes, the answers to difficult questions are within plain sight. That is what researchers at the University of Southern California realised as they looked for new ways to find and see cancer cells inside the human body and discovered that the dyes they could use are all around us every day.
Early detection of cancerous cells gives patients the best chance of successful treatment and survival. However, finding those cells can be challenging. In their latest research, reported in Biomaterials Science, Cristina Zavaleta and her team found that they could use common dyes and pigments, like food colouring and tattoo ink, combined with nanoparticles to essentially paint cancer cells – making them easy to spot when compared with normal cells.
Paint by cell type
Finding cancer cells without imaging agents is a difficult job. “For instance, if the problem is colon cancer, this is detected via endoscopy,” Zavaleta explains. “But an endoscope is literally just a flashlight on the end of a stick, so it will only give information about the structure of the colon – you can see a polyp and know you need to take a biopsy.”
But with imaging agents that can specifically paint the cancerous cells, medical professionals have a much easier job. “If we could provide imaging tools to help doctors see whether that particular polyp is cancerous or just benign, maybe they don’t even need to take it,” says Zavaleta.
Inspiration for this work came from an unusual source: Zavaleta’s imagination was sparked in an animation class with Pixar artists. “I was thinking about how these really high-pigment paints were bright in a way I hadn’t seen before,” she says. This led to a trip to a tattoo artist and the realization that these everyday inks could have exciting properties for medical imaging.
Putting the pieces together
The researchers created optical imaging agents using liposomal nanoparticles. These nanoparticles are tiny spheres made of a membrane of lipid, or fat, molecules – the same kind of structures that form the boundaries of human cells – and the colourful dyes can be housed inside. Using nanoparticles made of fats and dyes that are already FDA-approved and used in everyday life is a clever approach for potentially accelerating their clinical translation.
The researchers found that not only do nanoparticles containing these common dyes exhibit improved fluorescence signals compared with the clinical dyes, because more of the dye can be loaded into each nanoparticle, but that they are also significantly more visible inside tumours than in adjacent normal cells. The researchers suggest that this is because the tumours have leakier blood vessels feeding them, letting in the nanoparticles, which cannot enter into normal cells.
The new dyes also have unique spectral fingerprints, which could aid in their specific detection. It could even be possible to use multiple different dyes together to paint different types of cells in unique ways.
Whilst the initial findings in mice models are encouraging, there is still some way to go until this work might help patients in the clinic. However, Zavaleta and her colleagues are hopeful that this study could provide a foundation towards better cancer detection in the future.
Awe struck Linn Hobbs’ fascination with materials extends to those used in the many clocks at his home on the outskirts of Boston, Massachusetts. (Courtesy: Robert P Crease)
If you want to get a sense of the power and beauty of materials science, there are few better places to start than a chat with Linn Hobbs. Living in retirement in a three-storey house on the outskirts of Boston, US, Hobbs spent most of his career at the nearby Massachusetts Institute of Technology and retains an almost child-like enthusiasm for materials science. “[It] explores the kinds of things you can find in an average 10-year-old’s pocket,” he claims. “Salt, sand, string, rust and bone.”
Born in 1944 in Detroit, Hobbs’ interest in science started early. He was a licensed ham-radio operator at 11, later built his own communications equipment and these days still broadcasts from the top floor of his house. In 1962 Hobbs went to study engineering science at Northwestern University in Illinois, where the first book he read was on metals. “I was astounded that so much science could be applied to so much of the world around us,” he told me when I visited last summer. “I read the book like a novel, cover to cover in three days.”
Hobbs tried to major in materials science, but was informed that Northwestern had no major in the subject. All it had was a graduate materials-science department, which had been set up by the Advanced Research Projects Agency (ARPA) just two years earlier. ARPA itself had been established as a panic measure by the US government, which realized it lagged the Soviet Union in missile technology following the launch of Sputnik – the world’s first artificial satellite – in 1957. ARPA was designed to foster the study of metal alloys, ceramics and other compounds that could withstand the extreme pressures and temperatures of missiles and spacecraft.
When Hobbs arrived at Northwestern, even the university’s grad students in materials science had little prior training in the new discipline.
So when Hobbs arrived at Northwestern, even the university’s grad students in materials science had little prior training in the new discipline. Undeterred, Hobbs learned alongside them, despite his status as a lowly undergraduate. With his electronics experience as a radio operator, he ended up building equipment to study the motion of dislocation defects in lithium fluoride, which has a crystal structure identical to that of table salt.
After graduating from Northwestern in 1966, Hobbs went to the UK on a Marshall Scholarship, winding up at the University of Oxford, which then was a world-leader in the electron microscopy of materials. Hobbs’ subsequent career leant heavily on this tool, using it in a constantly widening set of applications that were turning materials science into an ever more unified field.
Hobbs’ hobbies
During his decade at Oxford, Hobbs took up a series of life-long hobbies, each involving different facets of materials science and reflecting a growing fascination with historical artefacts.
One hobby was antiquarian horology, instigated by his purchase of an old clock in an Oxfam charity shop for £10. On my visit to his house, our conversation was periodically punctuated by bright, high-timbre chimes from many of his subsequently acquired clocks. Hobbs explained the role of various clock materials – wood, iron, steel, brass, bell-metal, even sapphire – and discussed how they drove the history of these devices. Material behaviour was also critical for the forte pianos (an early kind of piano) in Hobbs’ collection of these instruments.
At Oxford, Hobbs became the wine steward at Wolfson College. This was a prestigious gig: Oxbridge colleges take their wine very seriously and Hobbs now owns a 2500-bottle wine cellar. As he showed me round it, Hobbs stopped to explain the structure of Champagne bottles; the indent at the bottom, called a punt, is mechanical reinforcement. He also explained the different colours of glass bottles – their silicate glass deriving from sand – with green being so common as the iron impurities causing it are the hardest to remove. A stack of skis next to the wine cellar then led Hobbs to explain why his knowledge of their component materials saw him becoming a consultant for a ski company.
Linn Hobbs is keenly aware just how integral materials science is to different fields of research.
Hobbs is keenly aware just how integral materials science is to different fields of research. He told me how he once listened to a young biologist describing difficulties with in vitro studies of cellular processes in bone formation. These studies were being carried out in Petri dishes, prompting Hobbs to enquire as to the nature of the glass substrate. Looking at him blankly, the biologist exclaimed in frustration: “Glass is glass!” Hobbs replied, “No, it’s not,” and explained that there are many types of glass, whose composition, surface chemistry, topography and defects all affect biological processes.
During his career, Hobbs has also studied the materials science of natural polymer fibres used by ancient cultures – the “string” in the child’s pocket – as well as metal corrosion processes, such as the rusting of iron. As for bone, Hobbs and his research group used electron microscopes to study bone biomineralization processes. In collaboration with the Royal National Orthopaedic Hospital in London, he also examined how bone bonds to orthopaedic implants, discovering that bone mineralization can begin after just three days.
The critical point
Few American materials scientists, it is safe to say, have been awarded an OBE (Order of the British Empire), which Hobbs received for his long involvement with the Marshall Scholarship programme and other Anglo-American educational initiatives. As for our conversation, it left me with an appreciation for two aspects of the history of materials science. One is that it is driven by society’s demands for better materials in everything from housing, clothing and transport to defence, art and medicine. The other is the role of scientific instruments in advancing our understanding of materials. This has simultaneously extended materials science into previously separate fields – notably metallurgy, ceramics and glass, polymers, biology and medicine – and unified much scientific research in these varied disciplines.
In recent years, the pharmaceutical industry has been interested in biocatalysis (enzymes) for the production of drugs and drug intermediates due to the high selectivity of enzymes. However, many of these enzymes require expensive cofactors. Electrochemistry provides an opportunity to do cofactor regeneration to decrease the cost and the sustainability of biocatalysis for synthesis.
