Mitochondrial dysfunction is a critical factor in numerous chronic diseases, including neurodegenerative disorders and metabolic syndrome. The challenge of extracting a single mitochondrion from a living cell without causing damage or relying on fluorescent markers has been a formidable obstacle for scientists. However, a groundbreaking development from The Hong Kong University of Science and Technology (HKUST) promises to change this landscape.
A team led by Prof. Richard GU Hongri, Assistant Professor in the Division of Integrative Systems and Design at HKUST, has unveiled an automated robotic nanoprobe. This innovative device can navigate within living cells, detect metabolic signals in real-time, and extract individual mitochondria for analysis—all without fluorescent labeling. This breakthrough, which marks the world’s first cell-manipulation nanoprobe integrating both sensors and actuators at its tip, holds significant potential for advancing treatments for chronic diseases and cancer.
From Seeing to Sensing
The mitochondrion, though not much larger than a bacterium, performs essential functions within every living cell. Traditional intracellular “microsurgery” relies heavily on manual operations and fluorescent signals, which can damage cells and interfere with assays. To address these challenges, the HKUST research team adopted a novel approach: sensing rather than visualizing mitochondria.
At the tip of the glass-fine nanoprobe are two nanoelectrodes that detect fleeting surges of reactive oxygen and nitrogen species (ROS/RNS), by-products of mitochondrial metabolism. Combined with an automated platform, the tip tracks these signals in real time. Upon exceeding a defined threshold, the tip’s function switches, and tiny dielectrophoretic “nanotweezers” capture a nearby mitochondrion, enabling its extraction with minimal disturbance.
Revolutionizing Cell Manipulation with Precision
Equally important is the process outside the cell. The research team has integrated the nanoprobe into a robotic workflow that standardizes each step: approaching the target cell, detecting the cell surface, piercing the membrane, tracking electrochemical currents, engaging the dielectrophoretic trap, and safely withdrawing. This automated procedure reduces invasiveness and allows for repeated sampling of the same cell, providing a clearer and more standardized operating workflow.
Ensuring Mitochondrial Functionality and Health
To verify the presence of extracted mitochondria, quantitative PCR was used to confirm mitochondrial genetic content. Notably, when transplanted into recipient cells, the mitochondria fused with the host network and underwent fission, demonstrating hallmark behaviors of healthy organelles. Prof. Gu emphasized the potential of this technology:
“Researchers can now sample mitochondria from single living cells without the confounding effects of fluorescent labels. These samples can then be combined with genomics or biochemical assays, providing new insights for minimally invasive surgical research on mitochondrial dysfunction diseases, including neurodegenerative diseases and metabolic syndrome.”
A Platform for the Future
This technology’s versatility is underscored by its ability to guide the probe to other organelles using metabolic or ionic signatures. The dielectrophoretic traps can be tuned, and the robotic protocol retrained, making it applicable for extracting mitochondria from various organelles. Looking ahead, the team plans to expand the library of label-free targets, enhance probe efficiency, and integrate post-extraction analytics.
This initial demonstration marks a more standardized operating procedure for single-cell “microsurgery,” paving the way for transformative advancements in cellular research and therapeutic applications. As the scientific community continues to explore the potential of this technology, it may soon revolutionize our understanding and treatment of diseases linked to mitochondrial dysfunction.
