HKUST co-develops robotic nanoprobe for precise mitochondria extraction charting new directions in research on therapies for neurodegenerative diseases and cancer

Mitochondrial dysfunction is associated with various chronic diseases and cancers, including neurodegenerative diseases and metabolic syndrome. Gently extracting a single mitochondrion from within a living cell—without causing damage and without the guidance of fluorescent makers—has long been a challenge akin to threading a needle in a storm for scientists.

A team led by Prof. Richard GU Hongri, Assistant Professor in the Division of Integrative Systems and Design of the Academy of Interdisciplinary Studies at The Hong Kong University of Science and Technology (HKUST), in collaboration with experts in mechanical engineering and biomedicine, has developed an automated robotic nanoprobe. This device can navigate within living cell, sense metabolic whispers in real time, and pluck an individual mitochondrion for analysis or—all without the need for fluorescent labeling. It is the world’s first cell-manipulation nanoprobe that integrates both sensors and actuators at its tip, enabling a micro-robot to autonomously navigate inside live cells. The breakthrough holds great promise for advancing future treatment strategies for chronic diseases and cancer.

From Seeing to Sensing
The mitochondrion is not much bigger than a bacterium, yet inside every living cell it carries out the essential chemistry that sustain life. Traditional intracellular “microsurgery” relies heavily on manual operations and fluorescent signals: tagging the target, flooding the sample with light, and following the glow. However, intense illumination can cause bleaching, heat and photochemical reactions may damage the cell, and fluorescent labels can interfere with downstream assays. To overcome these limitations, the research team adopted a different approach: instead of attempting to visualize mitochondria, they developed a method to sense them.

At the tip of the glass-fine nanoprobe are two nanoelectrodes that detect fleeting surges of reactive oxygen and nitrogen species (ROS/RNS), which are by-products of mitochondrial metabolism. Combined with an automated platform, the tip can track these signals in real time within living cells. Once the signal exceeds a defined threshold, the same tip switches function: tiny dielectrophoretic “nanotweezers” generate a non-uniform electric field that captures a nearby mitochondrion within approximately a hundred nanometers, enabling its extraction at a submicrometric scale with minimal disturbance. The key is colocalization: the sensor and actuator share the very same nanoscale point of action – where the signal is measured is precisely where the organelle is extracted. 

Revolutionizing Cell Manipulation with Precision 
Equally important is what happens outside the cell. The team has integrated the nanoprobe into a robotic workflow that standardizes and records each step: approaching the target cell, detecting the cell surface, piercing the cell membrane, tracking electrochemical currents, engaging the dielectrophoretic trap, and safely withdrawing. This procedure reduces invasiveness and enables repeated sampling of the same cell. The system’s automated positioning provides a clearer and more standardized operating workflow, eliminating the need for ad-hoc adjustments.

Ensuring Mitochondrial Functionality and Health
To confirm the presence of extracted mitochondria, quantitative PCR was performed to verify the mitochondrial genetic content. Notably, when transplanted into recipient cells, the imported mitochondria fused with the host network and underwent fission, demonstrating hallmark behaviors of healthy organelles. In other words, the extracted mitochondria can not only return to the cell but also remain functional. 

Prof. Gu stated, “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. The system also enables organelle transplantation, advancing the long-imagined ability of assembling ‘designer’ cells from living components.”

A Platform for the Future 
Since metabolic or ionic signatures can guide the probe to other organelles, and since the dielectrophoretic traps can be tuned and the robotic protocol retrained, this technology is highly versatile and applicable for extracting of mitochondria from various organelles. Looking ahead, the team plans to expand the library of label-free targets, improve 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.

The study was recently published in the prestigious multidisciplinary journal Science Advances. Prof. Gu and Prof. HU Chengzhi, a tenured associate professor in the Department of Mechanical and Energy Engineering at the Southern University of Science and Technology, are the corresponding authors. They collaborated with scholars from the City University of Hong Kong and the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, on this research.