Under‐Oil Autonomously Regulated Oxygen Microenvironments: A Goldilocks Principle‐Based Approach for Microscale Cell Culture (Adv. Sci. 10/2022)

Abstract

Autonomously Regulated Oxygen Microenvironments In article number 2104510 , Chao Li, Ophelia S. Venturelli, David J. Beebe, and co‐workers introduce a Goldilocks principle‐based method, named autonomously regulated oxygen microenvironments (AROM), to recapitulate the oxygen homeostasis and kinetics seen in vivo in microscale cell culture. Fundamentally different from the traditional, operator‐centered oxygen control, i.e., the operator‐defined oxygen microenvironment to which the cells are exposed passively, AROM allows cells to self‐regulate (or autonomously regulate) and respond to the oxygen microenvironment via a supply‐demand balance.

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

“…In this work, we aim to leverage the ELR-empowered UOMS [12,[21][22][23][24][25][26][27][28] to establish an open microfluidic in vitro microtumor model with controlled, self-organized ECM microenvironments for studying tumor cell-ECM interactions and pre-screening of anti-metastasis strategies. Our design principle is driven by combined top down and bottom up for synergized controllability and efficiency.…”

“…This UOMS microtumor model can be further integrated with other UOMS-based technologies including autonomously regulated oxygen microenvironment (AROM), [12] microliter whole blood assay (μ-Blood), [44,45] microbial communities, [26,46] ELR-antimicrobial susceptibility testing (AST), [27] micro total analysis system (μTAS), [22] and label-free spectroscopies (e.g., multiphoton, [26] Raman, [28] and IR [47] ). Thanks to its natural alignment with the open system standard, the UOMS microtumor model is compatible with most the automated liquid handling tools (e.g., robotic pipetting/microtiter plate preparation systems) in biology and clinical laboratories.…”

“…Here, we leverage a newly introduced sub-branch in open microfluidics known as Exclusive Liquid Repellency (ELR)-empowered Under-oil Open Microfluidic System (UOMS) [12,[21][22][23][24][25][26][27][28] to establish an open microfluidic microtumor model with combined top down and bottom up. The ELR physics allows inherent (i.e., surface-texture and surfactant independent) and absolute liquid repellency (with Young's contact angle θ = 180 o ), [21,23] which lays the foundation for the top down fabrication of open microfluidic channels in UOMS with micrometer-scale spatial resolution and lossless sample processing.…”

“…[1] In vitro microtumor models provide a venue for using human cell lines or primary patient samples (distinct from animal models with a non-human environment) [2] to perform pathogenesis studies, diagnosis/prognosis, and drug/treatment screening. [3] In light of the value in both fundamental research and translational application, recently in vitro microtumor models got further developed to better mimic the in vivo physiopathological environments, witnessing the transition from the traditional two-dimensional (2D) cell culture [i.e., cells directly cultured on an artificial substrate such as polypropylene (PS) or glass] [4] to three-dimensional (3D) microtissues (e.g., spheroids, [5] organoids [6] ) supported by ECM [7] and microphysiological systems [8] with advanced structures [e.g., lumen, [9,10] microvascular networks (MVNs) [11] ] and mass transport (e.g., vital gasses, [12] soluble factors [13] ) controls.…”