Design, Fabrication, and Application of a Microfluidic Device for Investigating Physical Stress-Induced Behavior in Yeast and Microalgae

Abstract

Purpose:The development of an efficient in vitro cell culture device to process various cells would represent a major milestone in biological science and engineering. However, the current conventional macro-scale in vitro cell culture platforms are limited in their capacity for detailed analysis and determination of cellular behavior in complex environments. This paper describes a microfluidic-based culture device that allows accurate control of parameters of physical cues such as pressure. Methods: A microfluidic device, as a model microbioreactor, was designed and fabricated to culture Saccharomyces cerevisiae and Chlamydomonas reinhardtii under various conditions of physical pressure stimulus. This device was compatible with live-cell imaging and allowed quantitative analysis of physical cue-induced behavior in yeast and microalgae. Results: A simple microfluidic-based in vitro cell culture device containing a cell culture channel and an air channel was developed to investigate physical pressure stress-induced behavior in yeasts and microalgae. The shapes of Saccharomyces cerevisiae and Chlamydomonas reinhardtii could be controlled under compressive stress. The lipid production by Chlamydomonas reinhardtii was significantly enhanced by compressive stress in the microfluidic device when compared to cells cultured without compressive stress. Conclusions: This microfluidic-based in vitro cell culture device can be used as a tool for quantitative analysis of cellular behavior under complex physical and chemical conditions.

Topographical extracellular matrix cues on anticancer drug‐induced cytotoxicity in stem cells

“…4,13 For example, it was reported that biomimetic microsystem of the the human alveolar capillary interface of the lung (called as lung-on-a-chip) showed great potentials as a platform for understanding lung functions and diseases. 5 Despite a considerable amount of ongoing research, it is still important challenges to fully mimic the cellular or tissue environments for the manipulation of biomimetic systems. 5 Despite a considerable amount of ongoing research, it is still important challenges to fully mimic the cellular or tissue environments for the manipulation of biomimetic systems.…”

“…[1][2][3] Unfortunately, due to the fundamental similarities between cancer cells and normal tissue, non-specific cytotoxicity and other offtarget effects of small-molecule drugs present additional complications for patient survival and quality of life during a course of treatment. [4][5][6] We argue that it would therefore be desirable to have a supplementary in vitro platform, which to directly test the side effects of chemotherapeutic agents on various types of human tissue under conditions that mimic, as closely as possible, the endogenous conditions of each tissue line. [4][5][6] We argue that it would therefore be desirable to have a supplementary in vitro platform, which to directly test the side effects of chemotherapeutic agents on various types of human tissue under conditions that mimic, as closely as possible, the endogenous conditions of each tissue line.…”

“…For example, Kim et al, proposed and developed a cytotoxicity assay using a microfluidic device with microwells and a distributive microfluidic channel network, 11 which induced the formation of cancer cell spheroids that could mimic the threedimensional (3D) tumor tissues in vitro to improve the prediction of the cytotoxicity on cells due to the use of anticancer drug. [4][5][6] Proper mimicry can be critical for ensuring the accurate behavior of these on-chip tissues or organ system, thus it allows one to extrapolate observations of cell-drug interactions (e.g., cytotoxicity) to other animal models or human patients. In particular, we note that the local geometry and the well-defined features of the extracellular matrix (ECM) [7][8][9][10][11][12][13] and the influence of these nanoscale topographic features have thus far been ignored in most on-chip systems reported in the literatures.…”