Microfluidic chip containing porous gradient for chemotaxis study

Abstract

We have developed a new porous gradient microfluidic device based on in situ Gtn-HPA/CMC-Tyr hydrogel that comprises gelatin hydroxyphenylpropionic acid (Gtn-HPA) conjugate and carboxymethyl cellulose tyramine (CMC-Tyr) conjugate. The device is fabricated using a soft lithographic technique, in which microstructures were patterned on a thin layer of polydimethylsiloxane (PDMS) using a polymeric mold. Human fibrosarcoma cells (HT1080) were employed as invasive cancer cell model. Porosity gradients were generated by flowing pore etching fluid in the gradient generator network. Results suggested that spatial control of the porosity can be obtained, which mimics the 3-dimensional microenvironment in vivo for cell-based screening applications including real time chemotaxis, cytotoxicity, and continuous drug-response monitoring. A chemoattractant gradient is then generated and cell migration is monitored in real time using fluorescence microscopy. The viability of cells was evaluated using calcien AM stain. Herein, we successfully monitored the chemotactic responses of cancer cells, confirmed the validity of using in situ porous hydrogels as a construction material for a microchemotaxis device, and demonstrated the potential of the hydrogel with tunable porosity based microfluidic device in biological experiments. This device will also be practical in controlling the chemical and mechanical properties of the surroundings during the formation of tissue engineered constructs.

Bioconjugated Hydrogels for Tissue Engineering and Regenerative Medicine

“…A gradient of gelatin-HPA hydrogels was also fabricated in a microfluidic channel. 173 This gradient was used to record the chemotactic response of human cancerous cells in a high-throughput and cost-effective manner. In general, gradient systems aim to recapitulate the anisotropic structural and chemical properties of the native ECM.…”

Use of Microfluidic Technology for Cell Separation

“…Abboodi and coworkers have developed a hydrogel-based microfluidic chip for chemotaxis studies [66]. The device consists of three chambers in this study, the middle chamber is filled with a 3D porous hydrogel structure that contains the cell culture; here fibrosarcoma cell line HT1080 was used as an invasive cancer cell model.…”