Label-free quantification of asymmetric cancer-cell filopodium activities in a multi-gradient chip.

We use novel super-resolution bright-field optical microscopy to observe the filopodium activities of human lung cancer cells in a multi-gradient cell culture chip. Temporal variations of the filopodium numbers are measured without fluorescent labelling. By carefully designing the fluidic field inside the culture chip, we establish stable concentration gradients of the injected reagents. The reagents are injected via a separated central inlet, and the concentration gradients are different at different positions in the chip. The same chip can be used for both control and treated experiments. Using epidermal growth factor as the treatment, we verify that the protrusions of filopodia indicate the direction of concentration gradients experienced by a living cancer cell; while the treatment of bovine serum albumin shows no specific effect on the growth of filopodia. The combination of label-free, high-resolution optical microscopy and a micro cell culture chip establishes a convenient and versatile platform for dynamical cancer-cell analyses.