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Updated: Oct 27, 2025

Semi-Automated Phenotypic Analysis of Functional 3D Spheroid Cell Cultures
Published on: August 18, 2023
SpheroidPicker for automated 3D cell culture manipulation using deep learning
Istvan Grexa1,2, Akos Diosdi1,3, Maria Harmati1
1Synthetic and Systems Biology Unit, Biological Research Centre (BRC), Eötvös Loránd Research Network (ELKH), Temesvári körút 62, Szeged, 6726, Hungary.
Abstract:
Recent statistics report that more than 3.7 million new cases of cancer occur in Europe yearly, and the disease accounts for approximately 20% of all deaths. High-throughput screening of cancer cell cultures has dominated the search for novel, effective anticancer therapies in the past decades. Recently, functional assays with patient-derived ex vivo 3D cell culture have gained importance for drug discovery and precision medicine. We recently evaluated the major advancements and needs for the 3D cell culture screening, and concluded that strictly standardized and robust sample preparation is the most desired development. Here we propose an artificial intelligence-guided low-cost 3D cell culture delivery system. It consists of a light microscope, a micromanipulator, a syringe pump, and a controller computer. The system performs morphology-based feature analysis on spheroids and can select uniform sized or shaped spheroids to transfer them between various sample holders. It can select the samples from standard sample holders, including Petri dishes and microwell plates, and then transfer them to a variety of holders up to 384 well plates. The device performs reliable semi- and fully automated spheroid transfer. This results in highly controlled experimental conditions and eliminates non-trivial side effects of sample variability that is a key aspect towards next-generation precision medicine.
Insights
A new AI-guided system automates 3D cell culture transfer for cancer research. This innovation standardizes sample preparation, crucial for developing effective anticancer therapies and advancing precision medicine.
Area of Science:
- Oncology
- Biotechnology
- Medical Technology
Background:
- Cancer affects millions in Europe, with high-throughput screening of cell cultures dominating anticancer therapy research.
- Patient-derived ex vivo 3D cell cultures are increasingly vital for drug discovery and precision medicine.
- Standardized sample preparation is a critical unmet need in 3D cell culture screening for drug development.
Purpose of the Study:
- To introduce an artificial intelligence-guided, low-cost 3D cell culture delivery system.
- To address the need for standardized and robust sample preparation in 3D cell culture screening.
- To enhance experimental control and reduce sample variability in cancer research.
Main Methods:
- Development of an AI-guided system integrating a light microscope, micromanipulator, syringe pump, and computer.
- Implementation of morphology-based feature analysis for spheroid selection based on size and shape.
- Automated transfer of spheroids from standard holders (Petri dishes, microwell plates) to various formats up to 384-well plates.
Main Results:
- The system enables reliable semi- and fully automated spheroid transfer.
- Morphology-based analysis allows for the selection of uniform spheroids.
- The device facilitates controlled experimental conditions by minimizing sample variability.
Conclusions:
- The AI-guided 3D cell culture delivery system offers a standardized approach to sample preparation.
- This technology is poised to reduce non-trivial side effects from sample variability in drug discovery.
- The system represents a significant step towards next-generation precision medicine in oncology.

