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Magnetically actuated microgripper has enabled real-time force-controlled handling of fragile cell spheroids, offering a route to assemble complex multicellular tissue models
Researchers have developed a force-sensitive microscopic robot capable of manipulate delicate three-dimensional cell spheroids without causing structural damage – a development that could improve the construction of complex engineered tissues.
A study by a team at Purdue University, West Lafayette, Indiana, USA, has introduced a mobile microgripper (MMG) designed to handle spheroids with controlled force and high spatial precision. These spheroids, which are compact aggregates of living cells, have become central to tissue engineering because they can replicate key biological interactions between cells and their surrounding matrix. However, their fragility has posed a persistent technical challenge, particularly during transfer and assembly.
Conventional handling approaches – including suction-based manipulation such as with micropipettes – have often imposed mechanical stress that compromises spheroid integrity. This limitation has constrained efforts to assemble multicellular constructs that more closely resemble native tissues where multiple cell types coexist and interact in structured arrangements.
“Other techniques for cell spheroid bioassembly can affect the tissue construct and/or apply limited manipulation forces,” said Dr. David Cappelleri, professor of mechanical engineering and biomedical engineering at Purdue.
“The force-sensing MMG … addresses these current issues by allowing the safe bioassembly of different spheroids into a single construct,” he said.
The MMG device has drawn inspiration from macroscopic claw mechanisms. It consists of two articulated arms connected by a hinge, which allows controlled closure to grasp spheroids with minimal applied force. Crucially, the system operates under magnetic actuation. External magnetic fields have enabled both locomotion of the device and precise control of the opening and closing of its gripping jaws. This design choice has avoided direct mechanical contact from bulky instrumentation and has maintained compatibility with biological environments.
“This was a big part of the design – to figure out a way to use magnetic fields for both locomotion and for control of the opening and closing of the gripper jaws,” Cappelleri added.
A defining feature of the system lies in its real-time force sensing capability. The MMG continuously monitors the force exerted on the spheroids and adjusts its grip dynamically, which allows the operator to accommodate variability in spheroid size, composition, and mechanical resilience. This feedback-controlled approach has reduced the risk of deformation or rupture during handling.
Following computational modelling to evaluate mechanical performance, the researchers have conducted in vitro experiments that demonstrated the device’s ability to reposition and organise spheroids into defined spatial arrangements. The team has confirmed that the magnitude of force applied during manipulation remained within a range that preserved spheroid viability after transfer.
The integration of multiple spheroids into a single construct represents a critical step towards the fabrication of physiologically relevant tissues. In vivo tissues typically comprise heterogeneous cell populations arranged in complex architectures. To replicate such systems in vitro, researchers must combine distinct spheroid types without compromise to their biological function.
At present, the MMG has enabled assembly of spheroids into planar cellular sheets, which serve as a foundational architecture for more elaborate constructs. The research team has indicated that future work will aim to extend this capability towards three-dimensional tissue fabrication, with the longer-term objective to build fully functional engineered tissues.
The authors have also outlined plans to transition from manual operation to automated control. Automation could allow higher throughput assembly and improved reproducibility, both of which remain essential for translational applications such as regenerative medicine, drug testing and disease modelling.
Taken together, the development of a magnetically actuated, force-sensitive MMG has addressed a longstanding bottleneck in spheroid-based tissue engineering. By enable precise and gentle manipulation, the technology has opened a route towards more sophisticated and biologically faithful tissue constructs.
For further reading please visit: 10.1063/5.0304932
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