Universal Microfluidic System for Analysis and Control of Cell Dynamics

Abstract

SUMMARYDynamical control of the cellular microenvironment is highly desired for quantitative studies of stem cells and immune signaling. Here, we present an automated microfluidic system for high-throughput culture, differentiation and analysis of a wide range of cells in precisely defined dynamic microenvironments recapitulating cellular niches. This system delivers complex, time-varying biochemical signals to 1,500 independently programmable cultures containing either single cells, 2-D populations, or 3-D organoids, and dynamically stimulates adherent or non-adherent cells while tracking and retrieving them for end-point analysis. Using this system, we investigated the signaling landscape of neural stem cell differentiation under combinatorial and dynamic stimulation with growth factors. Experimental and computational analyses identified "cellular logic rules" for stem cell differentiation, and All rights reserved. No reuse allowed without permission.

Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis

“…The microenvironment of the cells plays critical roles in regulating cell fate choices. We used these resources and explored some of the signaling pathways defining logic in NSC differentiation using a high-throughput microfluidic approach (Zhang et al, 2019). This validation was the tip of the iceberg and together with the recent developments in the field, we provide a consolidated resource, a comprehensive and systematic characterization of major progenitor pools in cortical development.…”

Dynamic Environmental Control in Microfluidic Single‐Cell Cultivations: From Concepts to Applications

“…The functionality was demonstrated with fluorescence dye in five different concentrations. All square pulses had a temporal resolution of 30 s. Zhang et al [ 90 ] created a multilayer microfluidic chip with peristaltic pumps and valves for a high throughput live cell analysis under dynamical ligand conditions for example Jagged1, DLL1, EGF, PACAP, CXCL, and PDGF. They cultivated mouse fibroblast cells and HSCs under daily changing ligand combinations over 6 days and found synergistic and antagonistic signal interactions.…”