From the cellular perspective: exploring differences in the cellular baseline in macroscale and microfluidic cultures

Abstract

Microfluidic devices for cell culture based assays provide new types of engineered microenvironments and new methods for controlling and quantifying cellular responses to these microenvironments. However, without an understanding of the effects of the microenvironments present in microdevices from a cellular perspective, it will be challenging to integrate work done in microdevices with biological data obtained via traditional methods. With the adaptation and validation of In Cell Westerns (ICWs) and in situ analysis techniques to microfluidic devices, we can begin to look at a variety of cellular responses to microcultures. Here we observe several differences in proliferation, glucose metabolism, signaling pathway activation and protein expression levels between cells cultured in traditional macroscale cultures and in microfluidic cultures. The issues of glucose starvation, growth factor restriction, volume density and effects of interactions with poly(dimethylsiloxane) (PDMS) were examined to determine the relative importance of each to cell behavior. Changes in glucose metabolism, insensitivity to volume density or media supplementation, and finally reduced proliferation as the exposure to PDMS increased, suggests that perhaps interactions between media/cells and this commonly employed polymer may be significant for some cell based assays. The differences between cells in macroscale and microfluidic cultures suggest that the cellular baseline may be substantially altered in microcultures due to both inherent differences in scale as well as material differences. The observations highlight the need to biologically validate micofluidic devices for cell based assays in order to accurately interpret the data obtained with them in the context of traditional macroculture data. Additional areas of study that will further characterize and validate microscale culture are discussed.

Polymer-Based Microfluidic Devices for Pharmacy, Biology and Tissue Engineering

“…Furthermore, non-brittle PDMS-based microfluidic systems are physically robust. However, one drawback of using PDMS is the hydrophobicity of the polymer which complicates the investigation of drug metabolism and toxicity, since hydrophobic substrates can interact with the material [382][383][384]. To overcome this adsorption problem, a number of PDMS surface treatments have been developed.…”

Microfluidic devices for cell cultivation and proliferation

“…13 Uniform cell distribution inside the scaffolds is an important issue, which has been addressed by approaches such as surface acoustic wave actuations with an amplitude of a few tens of nanometres. 14 There are numerous excellent reviews of microfluidic cell culture platforms, [15][16][17][18][19] stem cell studies in microenvironments, [20][21][22][23][24] the design of microfluidic devices for biological research, [25][26][27][28] the potential of microfluidic chips for investigating neurological diseases, 29,30 and biomolecular gradients in cell culture systems. 31,32 In this paper, recent innovations in microfluidic platforms for cell patterning, culturing, and proliferation are examined, with discussion divided into: microperfusion and cell cultivation (first for different cell lines and then with particular focus on stem cells), gradient-generator microfluidic devices that provide cell culture microenvironments in which cells are exposed to a gradient of bimolecular cues and finally, cell patterning and positioning prior to cultivation.…”

Current Application of Micro/Nano-Interfaces to Stimulate and Analyze Cellular Responses

“…8,35,40 Furthermore, current technological advances in microinterface systems have allowed scientists to examine biological systems at unprecedented levels of detail in cell biology, synthetic biology, and bacterial physiology. 8,10,58 Microscale experimental techniques have opened a path to characterize how a population of cells respond to their environment, communicate with each other, or undergo complex processes such as gene expression and gene network dynamics. These technologies have already made significant contributions not only to the study of multiple cells but also to the study of single cells.…”