2. Academic Validation
  3. Multi-Inlet Spheroid Generator for High-Throughput Combinatorial Drug Screening Based on the Tumor Microenvironment

Multi-Inlet Spheroid Generator for High-Throughput Combinatorial Drug Screening Based on the Tumor Microenvironment

  • ACS Appl Mater Interfaces. 2023 May 26. doi: 10.1021/acsami.3c02439.
Seokgyu Han 1,  Sein Kim 2,  Hye Kyung Hong 3,  Yong Beom Cho 3 4,  Hyo Eun Moon 5 6,  Sun Ha Paek 5 6 7 8,  Sungsu Park 1 2 9
Affiliations

Affiliations

  • 1 School of Mechanical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Korea.
  • 2 Department of Biomedical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Korea.
  • 3 Department of Surgery, Samsung Medical Center, School of Medicine, Seoul 06351, Korea.
  • 4 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University (SKKU), Seoul 06351, Korea.
  • 5 Department of Neurosurgery, Seoul National University Hospital (SNUH), Seoul 03080, Korea.
  • 6 Cancer Research Institute, Seoul National University Hospital (SNUH), Seoul 03080, Korea.
  • 7 Hypoxia Ischemia Disease Institute, Seoul National University Hospital (SNUH), Seoul 03080, Korea.
  • 8 Advanced Institute of Convergence Technology, Seoul National University (SNU), Suwon 16229, Korea.
  • 9 Department of Biophysics, Institute of Quantum Biophysics (IQB), Sungkyunkwan University (SKKU), Suwon 16419, Korea.
PMID: 37234040 DOI: 10.1021/acsami.3c02439
Abstract

Tumor spheroids are powerful tools for drug screening and understanding tumor physiology. Among spheroid formation methods, the hanging drop method is considered most suitable for high-throughput screening (HTS) of Anticancer drugs because it does not require surface treatment. However, it still needs to increase the liquid-holding capacity because hanging drops often fall due to the increased pressure caused by the addition of drugs, cells, etc. Here, we report a multi-inlet spheroid generator (MSG) enabling the stable addition of liquid-containing drugs or cells into a spheroid through its side inlet. The MSG was able to load additional solutions through the side inlet without increasing the force applied to the hanging drop. The volume of the additional liquid was easily controlled by varying the diameter of the side inlet. Furthermore, the sequences of the solution injections were manipulated using multiple side inlets. The feasibility of the MSG in clinical application was demonstrated by testing the efficacy of drugs in patient-derived Cancer (PDC) cells and controlling the stromal cell ratio in the tumor microenvironment (TME) containing spheroids. Our results suggest that the MSG is a versatile platform for HTS of Anticancer drugs and recapitulating the TME.

Keywords

drug screening; hanging drop; multi-inlet; tumor spheroid; volume control.

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