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Robotic Production of Cancer Cell Spheroids with an Aqueous Two-phase System for Drug Testing
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A Soft Microrobot for Single-Cell Transport, Spheroid Assembly, and Dual-Mode Drug Screening.

Philipp Harder1,2,3, Nergishan İyisan1,2,3, Yukun Wang1,2,3

  • 1Microrobotic Bioengineering Lab (MRBL), School of Computation, Information and Technology, Department of Electrical Engineering, Technical University of Munich (TUM), Hans-Piloty-Straße 1, 85748, Garching, Germany.

Advanced Materials (Deerfield Beach, Fla.)
|November 13, 2025
PubMed
Summary

Researchers developed a novel hydrogel microrobot for precise 3D cell manipulation. This adaptable technology enables targeted cell delivery, spheroid formation, and real-time sensing for advanced disease modeling and drug screening.

Keywords:
3D cell culturecell deliverydrug screeningphotothermal actuationsoft microrobot

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Area of Science:

  • Biotechnology
  • Materials Science
  • Cell Biology

Background:

  • Current 3D cell culture models face challenges like limited diffusion and lack of real-time adaptability.
  • Existing methods such as hydrogel scaffolds, 3D bioprinting, and microfluidics offer spatial control but lack dynamic responsiveness.

Purpose of the Study:

  • To introduce a soft, untethered hydrogel microrobot for advanced in vitro cellular applications.
  • To demonstrate capabilities including targeted single-cell delivery, spheroid self-assembly, photothermal actuation, and real-time sensing.

Main Methods:

  • Fabrication of uniform spherical microrobots using microfluidic encapsulation.
  • Incorporation of gold nanorods for photothermal heating and Rhodamine B for temperature sensing.
  • Locomotion via thermophoretic convection for precise 3D manipulation and controlled cell handling.

Main Results:

  • Demonstrated microrobot-mediated single-cell pick-up and spheroid formation using specialized surface coatings.
  • Microrobots successfully performed localized heating and real-time temperature sensing, modulating the cellular microenvironment.
  • Combined photothermal stimulation with drug testing to reduce fibrosarcoma cell invasiveness, validating its use in drug screening.

Conclusions:

  • The developed hydrogel microrobot offers a versatile platform for adaptable 3D cell culture and manipulation.
  • This technology enhances disease modeling and drug screening by providing precise control and real-time feedback.
  • The microrobot's capabilities represent a significant advancement in creating more physiologically relevant in vitro systems.