PillarX: A Microfluidic Device to Profile Circulating Tumor Cell Clusters Based on Geometry, Deformability, and Epithelial State

Brenda J. Green*, Margherita Marazzini, Ben Hershey, Amir Fardin, Qingsen Li, Zongjie Wang, Giovanni Giangreco, Federica Pisati, Stefano Marchesi, Andrea Disanza, Emanuela Frittoli, Emanuele Martini, Serena Magni, Galina V. Beznoussenko, Claudio Vernieri, Riccardo Lobefaro, Dario Parazzoli, Paolo Maiuri, Kristina Havas, Mahmoud LabibSara Sigismund, Pier Paolo Di Fiore, Rosalind H. Gunby, Shana O. Kelley, Giorgio Scita

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating tumor cell (CTC) clusters are associated with increased metastatic potential and worse patient prognosis, but are rare, difficult to count, and poorly characterized biophysically. The PillarX device described here is a bimodular microfluidic device (Pillar-device and an X-magnetic device) to profile single CTCs and clusters from whole blood based on their size, deformability, and epithelial marker expression. Larger, less deformable clusters and large single cells are captured in the Pillar-device and sorted according to pillar gap sizes. Smaller, deformable clusters and single cells are subsequently captured in the X-device and separated based on epithelial marker expression using functionalized magnetic nanoparticles. Clusters of established and primary breast cancer cells with variable degrees of cohesion driven by different cell-cell adhesion protein expression are profiled in the device. Cohesive clusters exhibit a lower deformability as they travel through the pillar array, relative to less cohesive clusters, and have greater collective invasive behavior. The ability of the PillarX device to capture clusters is validated in mouse models and patients of metastatic breast cancer. Thus, this device effectively enumerates and profiles CTC clusters based on their unique geometrical, physical, and biochemical properties, and could form the basis of a novel prognostic clinical tool.

Original languageEnglish (US)
Article number2106097
JournalSmall
Volume18
Issue number17
DOIs
StatePublished - Apr 27 2022

Keywords

  • breast cancer
  • deformability
  • diagnostics
  • microfluidics
  • nanoparticles

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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