Zika virus is primarily transmitted through Aedes aegypti mosquitoes. Although the disease is largely asymptomatic or results in mild symptoms in adults, it causes developmental disorders in newborn babies if their mothers are infected during early pregnancy. Currently, the virus is circulating in more than 87 countries, infecting thousands of people annually, necessitating better testing and control measures.

“Mosquito-borne viruses cause serious diseases, but they have similar symptoms. If you have Zika, malaria, dengue, or chikungunya, you just might show up to the doctor with a fever and they won’t know why,” said Brian Cunningham (CGD Director/MMG), the Intel Alumni Endowed Chair of Electrical and Computer Engineering. “But it’s important to know whether it’s Zika, especially if the patient is a pregnant woman, because the consequences to a developing fetus are really severe.”

Zika virus infections are currently detected through polymerase chain reaction tests performed in a laboratory, which can amplify the genetic material of the virus, allowing scientists to detect it. In the new study, researchers used Loop-Mediated Isothermal Amplification to detect the virus in the blood samples using an approach suitable for point-of-care clinics. While PCR requires 20-40 repeated temperature shifts to amplify the genetic material, LAMP only requires one temperature — 65 °C — making it easier to control. Additionally, PCR tests are very sensitive to the presence of contaminants, especially the other components in a blood sample. As a result, the sample is first purified before it can be used. On the other hand, LAMP does not require any such purification step.

A cartridge, that contains reagents required to detect the virus, is inserted into the instrument to perform the test while the instrument is clipped onto a smartphone. Once the patient adds a drop of blood, one set of chemicals break open the viruses and the blood cells within five minutes. A heater below the cartridge heats it up to 65 °C. A second set of chemicals then amplifies the viral genetic material, and the liquid inside the cartridge fluoresces bright green if the blood sample contains the Zika virus. The entire process takes 25 minutes.

“The other cool aspect is that we’re doing the readout with a smartphone,” Cunningham said. “We’ve designed a clip-on device so that the smartphone’s rear camera is looking at the cartridge while the amplification occurs. When there’s a positive reaction, you see little green blooms of fluorescence that eventually fill up the entire cartridge with green light.”

The researchers are now developing similar devices to simultaneously detect other mosquito-borne viruses and are working on making the devices even smaller. “Although our clip-on detector is pretty small, a lot of the space is taken up by the batteries. In the next version, it will be powered by the phone’s battery,” Cunningham said.

The study “Smartphone clip-on instrument and microfluidic processor for rapid sample-to-answer detection of Zika virus in whole blood using spatial RT-LAMP” was published in the journal Analyst and can be found at 10.1039/d2an00438k.

The work was carried out in collaboration with Rashid Bashir (CGD/M-CELS), an Abel Bliss Professor of Engineering; Enrique Valera, a research assistant professor of bioengineering; Minh Do, a Thomas and Margaret Huang Endowed Professor of Electrical and Computer Engineering; and William King, a professor of electrical and computer engineering. The study was funded by the National Institutes of Health and the National Science Foundation Partnership for Innovation program.

In order to survive, biological organisms have to react to their environment. Whereas humans or animals possess a complex nervous system to sense their surroundings and to make conscious decisions, unicellular organisms developed different strategies. In biology, small organisms such as parasites and bacteria for example navigate through narrow channels such as blood vessels. They often do so in a regular, oscillating manner based on hydrodynamic interactions with the confining wall of the channel. “In our experiments, we could confirm the theoretical model that describes the specific dynamics of the microswimmer based on its size and the interactions with the channel wall” comments Corinna Maass, principal investigator of the studies. These regular movement patterns could also be used to develop mechanisms for targeted drug delivery, even transporting cargo against the current as also indicated in a previous study.

A trail of used fuel

In another study, the researchers investigated how moving microswimmers mutually affect each other. In their experimental model, small oil droplets in a soapy solution move autonomously by budding off little amounts of oil generating propulsion. Like a plane leaves behind contrails, the microswimmers generate a trace of used fuel which can repel others. This way, microswimmers are able to detect if another swimmer has been at the same place shortly before. “Interestingly, this causes a self-avoiding movement for individual microswimmers, whereas an ensemble of them results in droplets being caged between the trails of one another” reports Babak Vajdi Hokmabad, first author of the study. The repelling of the second droplet at the trajectory of a previously passing one depends on its approaching angle and the time passed after the first swimmer. These experimental findings also confirm the theoretical work in the field, previously conducted by Ramin Golestanian, managing director of the MPI-DS. The research was conducted in the scope of the Max Planck Center for Complex Fluid Dynamic, a joint research center composed of the MPI-DS, the MPI for Polymer Research and the University of Twente.

Collective movement through cooperation

Finally, the group also investigated the collective hydrodynamic behavior of multiple microswimmers. They found that multiple droplets can form clusters that spontaneously start to float like hovercrafts or rise and rotate like microscopic helicopters. The rotation of the cluster is based on cooperative coupling between the individual droplets which leads to coordinated behavior — although individual droplets alone do not comprise such movement. These arrangements represent thus another physical principle of how microswimmers are able to navigate their way — without using brains or muscles.

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Materials provided by Max Planck Institute for Dynamics and Self-Organization. Note: Content may be edited for style and length.

Chimpanzees don’t only forage for fruit, from time to time they also seek out opportunities to acquire protein-rich meat. To catch their agile monkey prey in the canopy, chimpanzees are better off having companions hunting alongside them. Scientists have found for the first time that communication is key to recruiting group members to join the hunt.

Hunting barks make the chase more effective

By studying more than 300 hunting events recorded over the last 25 years at the Kanyawara chimpanzee community in Uganda, researchers from the University of Zurich (UZH) and Tufts University in Boston have discovered that by making bark vocalizations, the wild apes catalyze group hunting, rendering this form of cooperative behavior more effective. “Chimps who produce hunting barks provide information to those nearby about their motivation to hunt, and this information may persuade reluctant individuals to join, boosting the overall chances of success,” says Joseph Mine, PhD student at the Department of Comparative Language Science of UZH, who led the study.

Hunting monkeys as a group in dense tropical rainforest where visibility is restricted can be challenging. Vocal communication allows more efficient group work. “Strikingly, following the production of hunting barks, we observed more hunters joining, greater speed in beginning the chase, and a shorter time to make the first capture,” says study co-last author Zarin Machanda from Tufts University, who heads up the Kanyawara Chimpanzee Project.

Although hunts are more effective following a bark, more research is needed to find out why the barks have this effect. “At the moment it is still unclear if these barks are given intentionally to coordinate the precise actions of the group, or whether these barks simply advertise an individual’s decision to hunt, which in turn, increases the likelihood of others joining them and with more hunters they are more effective,” adds UZH professor Simon Townsend, who helped lead the study.

Co-evolution of communication and cooperation

The evolutionary biologists considered a wide array of other factors that may affect the outcome of a hunt, including the presence of skilled hunters as well as potential distractions, but the occurrence of hunting barks retained a key role. “Communication plays a key role in coordinating complex acts of cooperation in humans, and this is the first indication that vocal communication might also facilitate group cooperation in our closest living relatives,” says Townsend.

It is widely accepted that communication and cooperation are tightly linked and co-evolved in humans. Over time, as one became more complex, so did the other, generating a feedback cycle which ultimately led to language and the uniquely complex forms of cooperation modern humans engage in.

Evolutionary roots at least 7 million years old

However, it was unknown how far back into humans’ evolutionary past this relationship between group cooperation and communication can be traced. Joseph Mine concludes: “Our results indicate that the relationship between vocal communication and group-level cooperation is ancient. This link seems to have been in place for at least 7 million years, since our last common ancestor with chimpanzees.”

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Materials provided by University of Zurich. Note: Content may be edited for style and length.

The optimized method is particularly important for odorant analysis. Odorants contribute significantly to the sensory profile of food and have a major influence on eating pleasure. Knowing the key odorants that shape the aroma of a food is therefore of interest both for analytical quality control and for targeted product development in the food industry.

Isolating volatile compounds from food — anything but trivial

However, isolating volatile compounds from food is not trivial. Many established methods lead to losses of labile odorants as well as to odor-active artifacts and are therefore unsuitable for odorant research. The manual SAFE technique developed in 1999 made it possible for the first time to easily isolate even thermally labile odorants from food without artifact formation. “This is an important prerequisite for using further analytical methods to identify the key odorants,” says Philipp Schlumpberger, who contributed equally to the study with Christine Stübner. Both are currently working on their doctorates at LSB.

Today, manual SAFE is established worldwide as a standard procedure in aroma research. Nevertheless, the research team saw a need for optimization in ease of use, in the yields achieved, and in reducing the risk of transferring nonvolatile material, which can significantly interfere with subsequent analytical steps.

The valve is critical

“As we discovered, the problems are mainly associated with the manual operation of the valve on the dropping funnel. Therefore, we replaced it with an electronically controlled pneumatic valve. To fully automate the SAFE apparatus, we optionally extended it with an automatic liquid nitrogen refill system as well as an endpoint detection and shutdown system,” explains Martin Steinhaus, section and working group leader at LSB.

As the team’s study now shows, the installation of the automatic valve increased yields, particularly for lipid-rich food extracts and for odorants with comparatively high boiling points. In addition, operator errors, which can lead to contamination of isolates with nonvolatile substances in the manual version, are eliminated with the automated SAFE.

“In the meantime, automated SAFE has replaced the manual variant in our laboratories. Other academic and industrial research groups are already following our example,” says principal investigator Martin Steinhaus.

Quantum computers are hugely powerful devices with a capacity for speed and calculation which is well beyond the reach of classical, or binary, computing. Instead of a binary system of zeroes and ones, it operates through superpositions, which may be zeroes, ones or both at the same time.

The continuously-evolving development of quantum computing has reached the point of having an advantage over classical computers for an artificial problem. It could have future applications in a wide range of areas. One promising class of problems involves the simulation of quantum systems, with potential applications such as developing materials for batteries, industrial catalysis and nitrogen fixing.

The paper, published in Nature, explores near- and medium-term possibilities for quantum simulation on analogue and digital platforms to help evaluate the potential of this area. It has been co-written by researchers from Strathclyde, the Max Planck Institute of Quantum Optics, Ludwig Maximilians University in Munich, Munich Center for Quantum Science and Technology, the University of Innsbruck, the Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, and Microsoft Corporation.

Professor Andrew Daley, of Strathclyde’s Department of Physics, is lead author of the paper. He said: “There has been a great deal of exciting progress in analogue and digital quantum simulation in recent years, and quantum simulation is one of the most promising fields of quantum information processing. It is already quite mature, both in terms of algorithm development, and in the availability of significantly advanced analogue quantum simulation experiments internationally.

“In computing history, classical analogue and digital computing co-existed for more than half a century, with a gradual transition towards digital computing, and we expect the same thing to happen with the emergence of quantum simulation.

“As a next step along the development of this technology, it is now important to discuss ‘practical quantum advantage,’ the point at which quantum devices will solve problems of practical interest that are not tractable for traditional supercomputers.

“Many of the most promising short-term applications of quantum computers fall under the umbrella of quantum simulation: modelling the quantum properties of microscopic particles that are directly relevant to understanding modern materials science, high-energy physics and quantum chemistry.

“Quantum simulation should be possible in the future on fault-tolerant digital quantum computers with more flexibility and precision, but it can also already be done today for specific models through special-purpose analogue quantum simulators. This happens in an analogous way to the study of aerodynamics, which can be conducted either in a wind tunnel or through simulations on a digital computer. Where aerodynamics often use a smaller scale model to understand something big, analogue quantum simulators often take a larger scale model to understand something even smaller.

“Analogue quantum simulators are now moving from providing qualitative demonstrations of physical phenomena to providing quantitative solutions for native problems. A particularly exciting way forward in the near term is the development of a range of programmable quantum simulators hybridising digital and analogue techniques. This holds great potential because it combines the best advantages of both sides by making use of the native analogue operations to produce highly entangled states.”

The University of Strathclyde and all of the partners on this perspective article have large, active programmes involving both theory of architectures and algorithms, as well as development of platforms for analogue quantum simulation and digital quantum computing. The partners have been collaborating as part of the Horizon 2020 EU Quantum Technologies Flagship project PASQuanS. At Strathclyde, research in this area is strongly embedded in the UK’s national quantum technology programme, and has received substantial funding from UK Research and Innovation.

A Quantum Technology Cluster is embedded in the Glasgow City Innovation District, an initiative driven by Strathclyde along with Glasgow City Council, Scottish Enterprise, Entrepreneurial Scotland and Glasgow Chamber of Commerce. It is envisaged as a global place for quantum industrialisation, attracting companies to co-locate, accelerate growth, improve productivity and access world-class research technology and talent at Strathclyde.

The University of Strathclyde is the only academic institution that has been a partner in all four EPSRC-funded Quantum Technology Hubs in both phases of funding. The Hubs are in: Sensing and Timing; Quantum Enhanced Imaging; Quantum Computing and Simulation, and Quantum Communications Technologies.

When a small amount of water is added, the salts within the paper dissolve and charged ions are released, thus making the electrolyte ionically conductive. These ions activate the battery by dispersing through the paper, resulting in zinc in the ink at the anode being oxidized thereby releasing electrons. By closing the (external) circuit these electrons can then be transferred from the zinc-containing anode — via the graphite- and carbon black-containing ink, the wires and the device — to the graphite cathode where they are transferred to — and hence reduce — oxygen from ambient air. These redox reactions (reduction and oxidation) thus generate an electrical current that can be used to power an external electrical device.

Proof of concept: a sustainable energy source for low-power electronics

To demonstrate the ability of their battery to run low-power electronics, Nyström’s team combined two cells into one battery to increase the operating voltage and used it to power an alarm clock with a liquid crystal display. Analysis of the performance of a one-cell battery revealed that after two drops of water were added, the battery activated within 20 seconds and, when not connected to an energy-consuming device, reached a stable voltage of 1.2 volts. The voltage of a standard AA alkaline battery is 1.5 volts.

After one hour, the one-cell battery’s performance decreased significantly due to the paper drying. However, after the researchers added two extra drops of water, the battery maintained a stable operating voltage of 0.5 volts for more than one additional hour.

The researchers propose that the biodegradability of paper and zinc could enable their battery to minimize the environmental impact of disposable, low-power electronics. “What’s special about our new battery is that, in contrast many metal air batteries using a metal foil that is gradually consumed as the battery is depleted, our design allows to add only the amount of zinc to the ink that is actually needed for the specific application,” says Nyström. Metal foils were more difficult to control and not always fully consumed leading to a waste of materials. So the more zinc the ink contains, the longer the battery is able to operate.

A more critical point of the battery’s current design with water activation, Nyström adds, is the time it takes for the battery to dry out. “But I am sure this can be engineered differently to get around this problem.” For environmental sensing applications at a certain humidity or in wet environments, however, the drying of the paper would not be an issue.

Two complementary technologies

Previously, Nyström’s team had already developed a paper-based degradable super capacitor that could be charged and discharged thousands of times without losing efficiency. Compared to batteries of the same weight, supercapacitors have an energy density that is around 10 times lower — while at the same time having a power density that is around ten to one hundred times greater. Supercapacitors can therefore be charged and discharged much faster. They can also withstand many more charge and discharge cycles. “So the two devices are actually complementary,” says Nyström. The idea behind the new water-activated battery was to be able to manufacture devices that are fully charged and that only release this energy after the triggering of a stimulus, in this case simply a drop of water.

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Materials provided by Swiss Federal Laboratories for Materials Science and Technology (EMPA). Original written by Michael Hagmann. Note: Content may be edited for style and length.

In this new study, the international team describe how they created a DNA repair vehicle to genetically fix faulty podocin, a common genetic cause of inheritable Steroid Resistant Nephrotic Syndrome (SRNS).*

Podocin is a protein normally located on the surface of specialised kidney cells and is essential for kidney function. Faulty podocin, however, remains stuck inside the cell and never makes it to the surface, terminally damaging the podocytes. Since the disease cannot be cured with medications, gene therapy which repairs the genetic mutations causing the faulty podocin offers hope for patients.

Typically, human viruses have been utilised in gene therapy applications to carry out genetic repairs. These are used as a ‘Trojan Horse’ to enter cells carrying the errors. Currently dominating systems include lentivirus (LV), adenovirus (AV) and adeno-associated virus (AAV), which are all relatively harmless viruses that readily infect humans. However, these viruses all share the same limitation in that they are restricted in space within their viral shells. This in turn constrains the amount of cargo they can deliver, namely the DNA kit required for efficient genetic repair, which significantly limits the scope of their application in gene therapy.

By applying synthetic biology techniques, the team led by Dr Francesco Aulicino and Professor Imre Berger from Bristol’s School of Biochemistry, re-engineered baculovirus, a for humans harmless insect virus which is no longer constrained by limited cargo capacity.

“What sets apart baculovirus from LV, AV, and AAV is the lack of a rigid shell encapsulating the cargo space.” said Dr Francesco Aulicino, who led the study. The shell of baculovirus resembles a hollow stick — it simply becomes longer when the cargo increases. This means a lot more sophisticated tool-kit to repair a genetic defect can be delivered by the baculovirus, making it much more versatile than commonly-used systems.

First, baculovirus had to be equipped to penetrate human cells which it normally would not do. “We decorated the baculovirus with proteins that enabled it to enter human cells very efficiently.” explained Dr Aulicino. This modified baculovirus is considered safe, as it could only multiply in the insect, but not in human cells. The scientists then used their engineered baculovirus to deliver much larger DNA pieces than was previously possible, and build these into the genomes of a whole range of human cells.

The DNA in the human genome comprises 3 billion base-pairs making up ~25,000 genes, which encode for the proteins that are essential for cellular functions. If faulty base-pairs occur in our genes, faulty proteins are made which can make us ill, resulting in hereditary disease. Gene therapy promises repair of hereditary disease at its very root, by rectifying such errors in our genomes. Gene editing approaches, in particular CRISPR/Cas-based methods, have greatly advanced the field by enabling genetic repair with base-pair precision.

The team used patient-derived podocytes carrying the disease-causing error in the genome to demonstrate the aptitude of their technology. By creating a DNA repair kit, comprising protein-based scissors and the nucleic acid molecules that guide them — and the DNA sequences to replace the faulty gene, the team delivered with a single engineered baculovirus a healthy copy of the podocin gene concomitant with the CRISPR/Cas machinery to insert it with base-pair precision into the genome. This was able to reverse the disease-causing phenotype and restore podocin to the cell surface.

Professor Imre Berger explains: “We had previously used baculovirus to infect cultured insect cells to produce recombinant proteins for studying their structure and function.” This method, called MultiBac, developed by the Berger laboratory, has been highly successful to make very large multiprotein complexes with many subunits, in laboratories world-wide. “MultiBac already exploited the flexibility of the baculovirus shell to deliver large pieces of DNA into the cultured insect cells, instructing them to assemble the proteins we were interested in.” When the scientists realised that the same property could potentially transform gene therapy in human cells, they went to work to create their new system described in their publication.

Dr Aulicino added: “There are many avenues to utilise our system. In addition to podocin repair, we could show that we can simultaneously correct many errors in very different places in the genome efficiently, by using our single baculovirus delivery system and the most recent editing techniques available.”

“SRNS is one of the more common genetic diseases affecting the kidney” said Professor Moin Saleem, a leading expert in the gene therapy of hereditary kidney disease at Bristol Renal. “SRNS is characterised by kidney failure at an early age, leading to severe loss in quality of life for those affected.”

Professor Gavin Welsh, Professor of Renal Cell Biology at Bristol Renal, concluded: “These results are very encouraging. This new approach pioneered by the Berger team holds promise not only for SRNS, but also for a range of other genetic diseases of the kidney, where efficient genetic repair is not feasible with current technology. It is a long road ahead to implement a new vector system for clinical applications, but we believe the advantages offered make this a very worthwhile undertaking.”

This research received funding from the European Research Councial (ERC), Kidney Research UK (KRUK), and the EPSRC/BBSRC Bristol Research Centre for Synthetic Biology BrisSynBio.

*About Steroid Resistant Nephrotic Syndrome (SRNS)

Hereditary SRNS is a devastating kidney disease affecting children and young adults. It is caused by mutations in genes that are important in the function of the specialised filtration cell of the kidney, called the podocyte. These disorders currently have no available therapy, and result in rapid onset of kidney failure, requiring dialysis and transplantation.