The Microscopic World in Sharp Focus

The Leica Thunder Imaging System not only lives up to its grandiose name, it also exceeds it in its purpose. At first glance, the system looks just like your traditional microscope with a flatscreen monitor connected to it. THINK finds itself in the Motor Neuron Disease laboratory at the Centre for Molecular Medicine and Biobanking at the University of Malta. The dim lighting around the setup creates an impressive atmosphere. Images flash on the attached screen, and the sophisticated high-tech features of this specialised microscope become clearer. ‘There is no other microscope like this,’ says Mr Zachary Muscat, Accounts Manager at Evolve Ltd. — suppliers of this equipment to the University. 

While traditional microscopes have no issue focusing on normal cells, they tend to struggle with tissue samples. Tissue samples are somewhat thicker, and a typical microscope causes blurring at the centre of the projected image. Clarity and sharpness are critical in a field that requires precise analysis of samples, and the distortions caused by such image processing can severely limit the researcher. 

Being only one out of a hundred currently in use worldwide, the Leica Thunder Imaging System is capable of removing this blurring in real-time. Prof. Ruben J Cauchi, who leads the laboratory, explains the concept behind this piece of technology. ‘It looks like a normal microscope,’ he says. ‘The difference is that it has a tower with a powerful processor, and this is its core facility.’ Its high processing power, combined with technology typically used for gaming, allows for the enhancement of images beyond the capabilities of a standard microscope. While traditional microscopes use natural light, the Leica Thunder Imaging System splits natural light into different wavelengths to excite different fluorescent stains, and the processor captures the illumination of these stains independently, while the software compiles the images to produce razor-sharp results.

The laboratory’s primary research focuses on motor neuron diseases such as ALS (Amyotrophic Lateral Sclerosis), by utilising fruit flies as specimens under the microscope’s powerful lens. These insects serve as a model organism of ALS by removing genes causing the disease. ALS flies typically end up with weakness of the muscles used for flight. Prof. Cauchi emphasises the impact of the Thunder microscope for such research. ‘What we can do now is dissect the organism and see what is actually happening at a molecular level in the neurons and muscles. Previously, that was difficult to do.’

Muscles of a fruit fly stained for motor neuron terminals using the Leica Thunder Imager

Besides ALS, the laboratory is also focusing on projects concerning COVID-19. Research is being conducted on the ACE2 receptor, that same receptor which coronavirus particles bind themselves to before entering human cells. ‘So with the microscope, we are also looking at the location of this receptor and how we can actually find therapeutic approaches that decrease the levels of this receptor.’ In the long run, this will have a significant impact on the health sector by providing it with crucial information for the creation of specific drugs which can be used not only for COVID-19 but also potentially for future pandemics.

Equipment supplied by Evolve Ltd. through collaboration with the University of Malta, and made possible with funding from the Malta Council for Science & Technology COVID-19 R&D Fund (Project COV.RD.2020–22).

A precious living library

Matthew Camilleri in the lab

Author: Dr Ruben J. Cauchi

Fruit flies (Drosophila melanogaster) have helped scientists discover innumerable secrets about humanity. Over 1,000 types of these flies are living at the University of Malta’s (UM) Motor Neuron Disease (MND) Laboratory. Each type or ‘stock’ is unique, and UM researchers have generated the majority of stocks through genetic engineering over the last 11 years. Flies need constant care, fly food needs to be freshly prepared, and stocks must be monitored to avoid overpopulation and sudden death. The COVID-19 pandemic has forced universities worldwide to close campuses, leaving researchers to work and teach from home. But research activities, especially the care of living organisms, have to continue even in the face of a shutdown.

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Steam, Ships, and Emissions

Gozo lighthouse

Author: Chris Styles

On one of the highest spots in Gozo there proudly stands a lighthouse. Built in 1840, it continues to warn nearby ships away from the shallows. After a long night shift, the lighthouse has another crucial role to play. A team of researchers from the University of Malta, led by Prof. Raymond Ellul, has converted this historic piece of Malta’s heritage into a remote laboratory.

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Redesigned hip joints need a simulator

People are living longer than ever. But a long life has its price. With age come more diseases and health issues, such as hip problems that can limit a person’s mobility. 

Hip replacement procedures have become common, although implants have a lifespan too. It might happen that a hip replacement you get at 60 needs to be replaced at 75. This is not the ideal scenario.

To minimise these cases, researchers are testing new materials and designs to prolong prostheses’ lifespans. These potential solutions need to be tested, but each test costs tens of thousands of euro. Enter, the University of Malta’s hip joint simulator.

Hip joint simulator in all its glory.

The hip joint simulator is a machine that replicates the joint movements and loads imposed on the human hip. To do so, the simulator uses three stainless steel frames, each of which can be controlled independently using motors. These motors act as the ‘muscles’ of the hip, programmed to replicate the walking cycle during testing.

When it comes to simulating load and forces, a mechanism can load the implants with weights of up to 300kg in a fraction of a second. This emulates what happens while walking, when the weight of the body rests on one leg due to the body’s shift in the centre of gravity. While running, inertial forces can cause the hip to sometimes take five times a person’s body weight.

Finally, to simulate the environment inside the human body, researchers use a specialised solution that mimics the bodily fluids surrounding the hip joint. They even warm the fluid to imitate body temperature. 

The hip joint simulator forms part of the MaltaHip project that intends to radically redesign hip implants to give them the longer lifespan patients want and need. Watch this space for more.  

The MALTAHIP project is funded by the Malta Council for Science and Technology through FUSION: The R&I Technology Development Programme 2016 (R&I-2015-023T).

Heat for health

Over 10% of the Maltese population lives with type 2 diabetes mellitus. This means the local risk for peripheral arterial disease, the one that usually leads to amputation, is alarmingly high. But now, a team of researchers from the Faculty of Health Sciences (University of Malta) has its hands on a new high-tech camera that can be used to detect foot complications before it’s too late. 

A common symptom of peripheral arterial disease is a gradual temperature increase in a person’s foot. The change is very mild, making it difficult to detect manually. So Dr Alfred Gatt and his team are using the state-of-the-art thermographic FLIR thermal camera to hone in on these temperature variations from type 2 diabetes mellitus.

The camera uses infrared light in the same way a regular camera uses visible light to produce an image. Yes, puppy pictures are still possible, but they definitely won’t look as cute. Its ability to measure emitted heat means it is non-invasive, reducing risks of infection completely. So while the €30,000 price tag may seem high to some, it will save money in the long run.

The applications of this piece of equipment go above and beyond diabetes. It is being used for multiple research projects and contributing to medical knowledge related to other vascular diseases and physiological processes. Its true cost? Priceless.  

Up, up and away!

How do aerospace research engineers test new cockpit technologies without having to actually fly a plane Answer: flight simulators. These machines give pilots and engineers a safe, controlled environment in which to practise their flying and test out new technologies. In 2016 the team at the Institute of Aerospace Technologies at the University of Malta (IAT) started work on its first-ever flight simulator—SARAH (Simulator for Avionics Research and Aircraft HMI). Its outer shell was already available, having been constructed a few years back by Prof Carmel Pulé. From there, the team built the flight deck hardware and simulation software, and installed all the wiring as well as side sticks, pedals, a Flight Control Unit (FCU) and a central pedestal. The team constructing the simulator faced many hurdles. The biggest challenge was coordinating amongst everyone involved in the build: students, suppliers, and academic and technical staff. Careful planning was crucial.

The result is a simulator representative of an Airbus aircraft. However, it can also be easily reconfigured to simulate other aircraft, making it ideal for research purposes and experimentation. The Instructor Operating Station (IOS) also makes it possible to select a departure airport and change weather conditions.

One of the first uses of SARAH was to conduct research on technology that enables pilots to interact with cockpit automation using touchscreen gestures and voice commands. This research was conducted as part of the TOUCH-FLIGHT 2 research and innovation project (read more about this in Issue 19).

Going beyond the original aim of SARAH being used for research purposes, the IAT is also using the technology to educate graduates and young children in the hope of sparking an interest in the field. Earlier this year, a group of secondary school students flew their own virtual planes under the guidance of a professional airline pilot.

Looking ahead, the IAT plans to incorporate more state-of-the-art equipment into SARAH to increase its capabilities and make the user experience even more realistic. There are also plans to build other simulators—including a full-motion flight simulator and an Air Traffic Control simulator—and to connect them together to simulate more complex scenarios involving pilots and air traffic controllers; a scenario that would more closely resemble the experience of a real airport.Project TOUCH-FLIGHT 2 was financed by the Malta Council for Science & Technology, for and on behalf of the Foundation for Science and Technology, through the FUSION: R&I Technology Development Programme.

Author: Abigail Galea

Luminex xMAP®: Enhanced lab efficiency

Stereotypical depictions of researchers involve crazy hair, oversized goggles, shabby lab coats, and loads of test tubes. While the first three may be exaggerated, the sheer volume of tubes and wells needed in a lab cannot be overstated, especially when the lab is dedicated to anything biological.

One tissue sample can be used for a gamut of tests, all of them attempting to identify something different in it, be they antibodies, DNA, or RNA (biomarkers). Often, many samples are required due to all the tests needed to highlight the variations in those biomarkers. But the size of samples is now decreasing thanks to machines like the Luminex System running xMAP technology.

The Luminex System is a research/clinical diagnostics platform that allows detection of multiple analytes in a single well of a microtiter plate—100 or more reactions using a single drop of fluid.

Multiplex assays are widely used in experiments investigating the characteristics of molecules within a biological sample. This approach can be used to see whether an experimental treatment works, or what changes a DNA mutation causes in the molecules or molecular pathways within cells.

In real terms, this machine allows for analyses to be done to determine whether or not a patient has a particular disease or gene variant in their blood that would prevent a drug from being effective. It also allows them to determine the ideal dosage for those drugs. The machine can also be used to identify and characterise viral infections.

A particular research group at the University of Malta, headed by Prof. Godfrey Grech, has used Luminex xMAP technology to develop novel markers which are allowing them to classify a subset of triple-negative breast cancer
patients.

By identifying these biomarkers, it may be possible in future to detect the disease earlier and give patients better-targeted therapy.

Prof. Godfrey Grech and his team of researchers.

Author: Prof. Godfrey Grech

Mobile Air Quality Laboratory (MAQL)

The Mobile Air Quality Laboratory (MAQL) is the first of its kind on the Maltese Islands. Run by a team of geoscientists at the University of Malta, the MAQL can assess the quality of the air by continuously monitoring particulate and gaseous air toxics.

​The particulates it can detect vary in size. The finer particles (PM1 and PM2.5) are usually the most dangerous respirable fraction but the instrumentation can also measure coarser sized particles (PM4 and PM10). The suite of gaseous pollutants that can be checked are sulfur dioxide, oxides of nitrogen, carbon monoxide, ozone, Volatile Organic Compounds (VOCs), organic and elemental carbon, and radon.

Mobile Air Quality Laboratory (MAQL)

Quick Specs:

  • Power consumption (including cooling system):
    2.5 kW
  • Particulate limit of detection: 1 ug/m3
  • VOCs measurement frequency:
  • 1 sample/30 minutes
  • Gaseous pollutants measurement frequency:
    1 minute
  • Gaseous pollutants limit of detection: < 0.5 ppb
  • Cost: €0.60 million

The MAQL is able to compare the air in indoor and outdoor spaces while recording meteorological conditions onsite. The comparison helps scientists understand from where the pollution originates. Is there so much pollution in our environs because of all the cars outside our window? Or is it because of the new sofa the family next door just bought? Or perhaps it is a result of the redecoration the building down the road recently underwent. Such data is vital for scientists to be able to figure out the root of a problem, to create a model of personal exposure to the pollutants, and to develop safer measures for the general public.

The MAQL facility will help scientists develop a clearer picture of the indoor air quality across the Maltese Islands. It will help other scientists interpret older data, and enable them to design new studies. Medics can match such data with population studies and assess disease rates around Malta. The MAQL can determine the sources of pollution inside buildings with the help of lifestyle and meteorological data, providing enough information for the construction of dwellings which have cleaner and safer air for everyone.

Magnets, Spinning Nuclei, and Light

An NMR (Nuclear Magnetic Resonance) spectrometer is a vital machine for the organic chemist. Using its powerful magnet the type, number of atoms, and how they are connected can be figured out. This is key for understanding the structure of organic chemicals such as drugs, pharmaceuticals, and those used in chemical computers.

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