Rapid Microfluidic Formation of Uniform Patient-Derived Breast Tumor Spheroids

Zhuhao Wu, Zhiyi Gong, Zheng Ao, Junhua Xu, Hongwei Cai, Maram Muhsen, Samuel Heaps, Maria Bondesson, Shishang Guo, Feng Guo

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Breast cancer is a highly complex, heterogeneous, and multifactorial disease that poses challenges for rapid and efficient treatment and development of personalized therapy. Here, we describe a rapid and reliable method to generate three-dimensional (3D) tumor spheroids in vitro that recapitulate an individual patient's tumor for testing treatments. By employing droplet microfluidics and scaffold materials, tumor cells were encapsulated into a large number of Matrigel-in-oil droplets with precise control over cell numbers and components per droplet. After removal of the oil, large numbers of uniform tumor spheroids were formed within a few hours via Matrigel-supported cell self-assembly. Our microfluidic technique produces uniform-sized tumor spheroids in less than 1 day. This method was used to reproducibly and rapidly generate uniform-sized tumor spheroids derived from patients' breast tumor tissues. As a proof-of-concept application, this method was used to quickly evaluate cancer treatments. We demonstrated that our microfluidic patient-derived tumor cultures not only preserve the genetic characteristics of the original tumor tissue but also provide heterogeneous responses to targeted therapies within 2 days. We believe this method will enable a timely and reliable 3D in vitro culture model, which may be applicable to personalized treatment prediction, drug discovery, and toxicity testing.

Original languageEnglish
Pages (from-to)6273-6283
Number of pages11
JournalACS Applied Bio Materials
Volume3
Issue number9
DOIs
StatePublished - 21 Sep 2020
Externally publishedYes

Keywords

  • 3D tumor cultures
  • breast cancer
  • microfluidics
  • personalized therapy
  • tumor spheroids

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