By exploiting the nanometer sensitivity of the confocal response to the position of an in-focus reflecting surface, we measured the bending rigidity of lipid-bilayer vesicles with a noninvasive all-optical method. The vesicles were weakly deformed with femtonewton optical force, and the bending rigidity was measured continuously from the $L_{\alpha }$ through the $P_{{\beta }^{\prime }}$ to the $L_{{\beta }^{\prime }}$ phases on the same specimen for the first time. The bending modulus is found to increase by an order of magnitude from the $L_{\alpha }$ phase to the $L_{{\beta }^{\prime }}$ phase, as a result of the increasing area-compressibility modulus and bilayer thickness. The dips of bending modulus give precisely the main-transition and pretransition temperatures, which supports the recently proposed chain-melting model of pretransition.

We use a microfluidic cell culture chip equipped with pneumatic microvalves to analyze the paracrine loop between lung cancer cells and fibroblasts. In order to assess the cellular responses in the paracrine loop, we measure the migration speeds of cancer cells and the aspect ratios of fibroblasts which reflect the phenotype of myofibroblasts. With well-controlled interaction sequences between these two types of cells, we verify that the cytokines from cancer cells effectively stimulate the fibroblasts into myofibroblasts. The cytokines from myofibroblasts, rather than fibroblasts, increase the migration speeds of cancer cells. We confirm that the transforming growth factor-β1 (TGF-β1) is involved in the interaction between cancer cells and fibroblasts, and we also interrupt this paracrine loop in the cell culture chip by inhibiting the TGF-β1 receptors on fibroblasts.

Applying the principle of differential confocal microscopy to wide-field optically sectioning microscopy, we develop a noninterferometric optical profilometer without scanning mechanisms. Depth resolution of 2 nm is achieved with a power-regulated tungsten-halogen lamp as the light source and a 14-bit CCD camera as the detector. The effects of inhomogeneous surface reflectivity are removed from topographic measurements by arithmetic division. The whole system can be constructed on a single silicon chip for use as a miniaturized optical profiler.

We combine a micro-fluidic electric-field cell-culture (MEC) chip with structured-illumination nano-profilometry (SINAP) to quantitatively study the variations of cancer cell filopodia under external direct-current electric field (dcEF) stimulations. Because the lateral resolution of SINAP is better than 150 nm in bright-field image modality, filopodia with diameters smaller than 200 nm can be observed clearly without fluorescent labeling. In the MEC chip, a homogeneous EF is generated inside the culture area that simulates the endogenous EF environment. With this MEC chip–SINAP system, we directly observe and quantify the biased growth of filopodia of lung cancer cells toward the cathode. The epidermal growth factor receptors around the cell edges are also redistributed to the cathodal side. These results suggest that cancer-cell filopodia respond to the changes in EFs in the microenvironment.

We measure the temporal evolution of three-dimensional membrane topography on living fibroblasts and characterize the propagation of membrane waves using a wide-field optical profiling technique. The measured membrane profiles are compared with the numerical results calculated by the active membrane model recently proposed by Shlomovitz and Gov. After the treatments of blebbistatin and latrunculin A separately, the membrane waves disappear and the membrane surfaces are flattened, verifying that the membrane waves are driven by the interactions between myosin II and actin polymerization.