title: Microfluidic chip with integrated electrical cell-impedance sensing for monitoring single cancer cell migration in three-dimensional matrixes.
abstract: Cell migration has been recognized as one hallmark of malignant tumor progression. By integrating the method of electrical cell-substrate impedance sensing (ECIS) with the Boyden chamber design, the state-of-the-art techniques provide kinetic information about cell migration and invasion processes in three-dimensional (3D) extracellular matrixes. However, the information related to the initial stage of cell migration with single-cell resolution, which plays a unique role in the metastasis-invasion cascade of cancer, is not yet available. In this paper, we present a microfluidic device integrated with ECIS for investigating single cancer cell migration in 3D matrixes. Using microfluidics techniques without the requirement of physical connections to off-chip pneumatics, the proposed sensor chip can efficiently capture single cells on microelectrode arrays for sequential on-chip 2D or 3D cell culture and impedance measurement. An on-chip single-cell migration assay was successfully demonstrated within several minutes. Migration of single metastatic MDA-MB-231 cells in their initial stage can be monitored in real time; it shows a rapid change in impedance magnitude of approximately 10 Ω/s, whereas no prominent impedance change is observed for less-metastasis MCF-7 cells. The proposed sensor chip, allowing for a rapid and selective detection of the migratory properties of cancer cells at the single-cell level, could be applied as a new tool for cancer research.
authors.affiliation: Department of Microsystems Engineering, IMTEK, University of Freiburg , Georges-Koehler Allee 103, 79110 Freiburg, Germany.
authors.forename: Tien Anh
authors.initials: TA
authors.lastname: Nguyen
authors.forename: Tsung-I
authors.initials: TI
authors.lastname: Yin
authors.forename: Diego
authors.initials: D
authors.lastname: Reyes
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Urban
mesh_terms: D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D001943:Breast Neoplasms / Q000473:pathology*; D018929:Cell Culture Techniques; D002465:Cell Movement; D017097:Electric Impedance; D004566:Electrodes; D005260:Female; D006801:Humans; D046208:Microchip Analytical Procedures / Q000379:methods*; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D008991:Monitoring, Physiologic; D014407:Tumor Cells, Cultured