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).

HUNT

The thumping, scuttling sounds retreated to the back of the storage room on the upper floor. The man stirred in the darkness, listening to the last, faint steps echoing away before stretching his legs and easing the stiffness in his knees. The edge of the wardrobe dug into his ribs, and the cold floor seeped into his weary bones. He broke the silence with a hushed gasp at the stabbing pain in his back — it had been years since he found himself crouched down on the floor for so long. He paused once more to listen, straining his ears for any sound from upstairs. The dimness in the bedroom began to lift, and his eyes wandered around the surroundings, before resting upon a framed photograph of himself and his wife. He smiled, his tense body relaxing for a brief instance. 

A door slammed with a crash, and the haunting pitter-patter of steps dashed to the other side of the house. He could hear and feel the slight quiver of the walls as each step landed on the floor just above him. He could make out the route his stalker took: out of the storage room, through the corridor, and into the library. The library. Dorothy! Peter shook away his thoughts and pushed past the pain. He crawled out of his hiding spot with caution and urgency — the image of his wife, hidden and alone, spurring him forward. As he emerged from behind the wardrobe, his foot caught the leg of the nightstand, toppling over a lamp as it fell to the ground with a loud crash. The footsteps came to an abrupt halt. A moment’s hesitation followed. The stalker’s attention had been distracted. 

Peter froze. In a flash, he heard the footsteps race back out into the corridor, before tumbling down the stairs with a ferocious will, until a faint light came streaming in through the bedroom door. Peter crawled forward, squeezing himself under the wooden frame of the bed. The effort proved too strenuous. His chest rose up and down, brushing against the floor. He felt trapped — stuck between the floor tiles and the bed slats digging deep into his back. The noise from outside the room rumbled on closer. A shadow flew across the door as the light dimmed momentarily. The stalker had made its way to the bedroom and now loomed in the silence — an ominous shape looking into the darkness before it. It paused there, considering, assessing, waiting. Peter’s lungs struggled to inhale in such a tight space. He winced, trying to deaden the sounds of his breathing. 

The presence stood there. He could hear its soft breath and see its bare feet, restless  — the soles tapping against the floor with impatience. It took a step forward, then hesitated, doubtful. 

A shout from upstairs caused it to spin round swiftly and dash back up with a loud banding noise. Peter heard a mocking laugh escape from its mouth as it reached the floor above once again. A shout soon followed, and then a cacophony of wails and cries curdled his blood. He thought of his wife once more. The old man pushed himself out from under the bed and staggered up, trying to regain his balance. In the dead silence, he felt the vicious pounding of his heart inside his chest and the blood rushing to his ears. His legs and back ached, but he forced himself towards the door and peered out into the dim light of the corridor. The doors leading into other rooms had been opened and left ajar. Peter’s spine tingled at the thought of some unseen presence lurking and hiding behind one of them — readying to pounce on top of him as he emerged. He leaned against the doorpost and eyed the sinister staircase just a few steps away in front of him, as it rose upwards towards an impenetrable blackness. His mind harked back to the image of his wife and the disturbance from a few moments earlier. Everything had gone quiet again. He took another cautious look at the corridor and quietly approached the stairs. 

He thought he heard a door creak from one of the rooms. He paused a moment to 

listen. Peter held on to the handrail, his grasp failing him as his hand trembled. The wooden planks groaned. His ascent felt endless, and having abandoned the light behind him, he plunged into the engulfing darkness on the top floor. Suddenly, before him stood a ghastly face staring right at him. The old man’s heart thumped faster than ever, and his legs felt faint. His mind wavered and struggled to fight off a wave of dizziness. As his eyes adjusted to the dark, the face before him became more clear. It morphed into the smooth and subtle brushstrokes of his grandfather’s portrait painting. He cursed under his breath and regained his stance, but had barely stepped off the last set of stairs when the scuttling sound came dashing round the corner. It was somewhat louder, more confused, and faster. It had taken him only a few moments to realise …  there’s two of them! More clear than ever, he could hear the fall of another pair of footsteps hurtling towards him, like some four-legged beast, ravenous in its pursuit of its prey.

Peter rounded the end of the staircase and dashed into the gloom of the library. 

‘Dororthy!’ he whispered. He pressed himself behind the open door, against the wall, a faint line of light visible in the slit between the hinges and the door frame. Peter heard the footsteps falter and come to an abrupt halt. Its breathing was heavy and hushed. A shadow appeared by the entrance before being joined by another — of the same size and height as the first. They moved forward together, stalking the inside of the library. Peter’s sweating hands grabbed the handle, pulling the door further in towards him. He glanced once more at the slit of light and recoiled in horror at the sudden appearance of another, much larger shadow than the other two — brooding and towering over the entrance. 

He felt the horror of it all overwhelm him and resigned himself to the idea of what was about to happen. He felt the door being snatched away from his grasp. He closed his eyes shut and waited …

‘Got you!’ a shrill voice screamed. 

He felt hands tugging at his clothes, pulling him and shouting. He opened his eyes as the lights in the library sprang to life.

‘Not so hidden, eh?’ said Peter. He allowed himself a sigh of relief and laughed at the sight of his grandchildren, waving and dancing in triumph at their discovery in the middle of the library.

‘So they found you too huh?’ he said, emerging from behind the door and dusting off his jumper. He looked at his wife and smiled.

‘Exactly where they found you,’ said Dorothy, arranging his shirt collar and patting him lovingly on the shoulders.

As they headed back downstairs, Peter’s hand slid without effort along the handrail. He dismounted the last step and smiled, as he heard once more the familiar footsteps of the children running around on the floor above. He had left his wife in the library to look up a book whilst he headed towards the bedroom — oblivious of the clawed hand pushing the door at the far end of the corridor wide open.

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