Generating Nonlinear Concentration Gradients in Microfluidic Devices for Cell Studies

• Published in: Analytical chemistry (Washington) Vol. 83; no. 6; pp. 2020 - 2028
• Main Authors: Selimović, Šeila, Sim, Woo Young, Kim, Sang Bok, Jang, Yun Ho, Lee, Won Gu, Khabiry, Masoud, Bae, Hojae, Jambovane, Sachin, Hong, Jong Wook, Khademhosseini, Ali
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.03.2011
• Subjects: Animals; Applied fluid mechanics; Aqueous solutions; Cell Survival - drug effects; Cells; Cytological Techniques - instrumentation; Cytotoxins - toxicity; Diffusion; Dose-Response Relationship, Drug; Exact sciences and technology; Fluid dynamics; Fluidics; Fundamental areas of phenomenology (including applications); Hydrogen peroxide; Mice; Microfluidic Analytical Techniques; NIH 3T3 Cells; Nonlinear Dynamics; Nonnative species; Physics; Studies; Multiplexing; Mixing; Hydrogen peroxide; Scattering; Device; Concentration; Concentration ratio; Design; Storage; Asymmetry; Aqueous solutions; Fibroblasts; Arrays; Viability; Microfluidics; Concentration gradient
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/ac2001737

We describe a microfluidic device for generating nonlinear (exponential and sigmoidal) concentration gradients, coupled with a microwell array for cell storage and analysis. The device has two inputs for coflowing multiple aqueous solutions, a main coflow channel and an asymmetrical grid of fluidic channels that allows the two solutions to combine at intersection points without fully mixing. Due to this asymmetry and diffusion of the two species in the coflow channel, varying amounts of the two solutions enter each fluidic path. This induces exponential and sigmoidal concentration gradients at low and high flow rates, respectively, making the microfluidic device versatile. A key feature of this design is that it is space-saving, as it does not require multiplexing or a separate array of mixing channels. Furthermore, the gradient structure can be utilized in concert with cell experiments, to expose cells captured in microwells to various concentrations of soluble factors. We demonstrate the utility of this design to assess the viability of fibroblast cells in response to a range of hydrogen peroxide (H2O2) concentrations.