title: Assembly of multiple cell gradients directed by three-dimensional microfluidic channels.
abstract: Active control over the cell gradient is essential for understanding biological systems and the reconstitution of the functionality of many types of tissues, particularly for organ-on-a-chip. Here, we propose a three-dimensional (3D) microfluidic strategy for generating controllable cell gradients. In this approach, a homogeneous cell suspension is loaded into a 3D stair-shaped PDMS microchannel to generate a cell gradient within 10 min by sedimentation. We demonstrate that cell gradients of various profiles (exponential and piecewise linear) can be achieved by precisely controlling the height of each layer during the fabrication. With sequential seeding, we further demonstrate the generation of two overlapping cell gradients on the same glass substrate with pre-defined designs. The cell gradient-based QD cytotoxicity assay also demonstrated that cell behaviors and resistances were regulated by the changes in cell density. These results reveal that the proposed 3D microfluidic strategy provides a simple and versatile means for establishing controllable gradients in cell density, opening up a new avenue for reconstructing functional tissues.
authors.affiliation: Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. bfliu@mail.hust.edu.cn.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Feng
authors.forename: Yachao
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Bi-Feng
authors.initials: BF
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003584:Cytological Techniques / Q000295:instrumentation* / Q000379:methods*; D004867:Equipment Design; D005456:Fluorescent Dyes / Q000737:chemistry / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D041681:NIH 3T3 Cells; D045663:Quantum Dots / Q000737:chemistry / Q000633:toxicity
chemical_list: D005456:Fluorescent Dyes