A versatile cancer cell trapping and 1D migration assay in a microfluidic device

Abstract

Highly migratory cancer cells often lead to metastasis and recurrence and are responsible for the high mortality rates in many cancers despite aggressive treatment. Recently, the migratory behavior of patient-derived glioblastoma multiforme cells on microtracks has shown potential in predicting the likelihood of recurrence, while at the same time, antimetastasis drugs have been developed which require simple yet relevant high-throughput screening systems. However, robust in vitro platforms which can reliably seed single cells and measure their migration while mimicking the physiological tumor microenvironment have not been demonstrated. In this study, we demonstrate a microfluidic device which hydrodynamically seeds single cancer cells onto stamped or femtosecond laser ablated polystyrene microtracks, promoting 1D migratory behavior due to the cells' tendency to follow topographical cues. Using time-lapse microscopy, we found that single U87 glioblastoma multiforme cells migrated more slowly on laser ablated microtracks compared to stamped microtracks of equal width and spacing (p < 0.05) and exhibited greater directional persistence on both 1D patterns compared to flat polystyrene (p < 0.05). Single-cell morphologies also differed significantly between flat and 1D patterns, with cells on 1D substrates exhibiting higher aspect ratios and less circularity (p < 0.05). This microfluidic platform could lead to automated quantification of single-cell migratory behavior due to the high predictability of hydrodynamic seeding and guided 1D migration, an important step to realizing the potential of microfluidic migration assays for drug screening and individualized medicine.

Classification of Preeclamptic Placental Extracellular Vesicles Using Femtosecond Laser-fabricated Nanoplasmonic Sensors and Machine Learning

“…Furthermore, fs-laser ablation naturally results in the generation of particle debris which often redeposits onto the patterned surface. 57 For SERS applications, these redeposited gold or silver nanoparticles could theoretically produce even greater Raman signal enhancement than the base nanopattern alone.…”

Latest Updates on the Advancement of Polymer-Based Biomicroelectromechanical Systems for Animal Cell Studies

“…[ Microtracks allowed guiding cell migration with high predictability and precise positioning. [38] 8…”

“…The device improved the reproducibility of cell trapping and enhanced the clinical applicability of in vitro single-cell migration assays. This device benefited from automatic analysis of single-cell migration behavior to predict treatment outcomes and antimetastasis drug screening [38]. In another study, a multiarray microchip developed by Huang et al allowed studying mechanically induced physiological changes in cells through a side-stretching mechanism and a controllable pneumatic trap which were used to encapsulate and discharge suspended cells (Table 3).…”

“…Cell isolation and/or trapping is another essential step in cell-related studies. BioMEMS commonly uses passive capturing or hydrodynamic force for cell isolation and/or trapping purposes [32,35,38,89]. These techniques face challenges including selective capturing of cells and further release of the trapped cells.…”

Classification of Preeclamptic Placental Extracellular Vesicles Using Femtosecond Laser Fabricated Nanoplasmonic Sensors

“…Furthermore, femtosecond laser ablation naturally results in the generation of particle debris which often redeposits onto the patterned surface. 60 For SERS applications, this redeposited gold or silver nanoparticle debris could produce even greater Raman signal enhancement than the base pattern alone.…”