High-throughput and real-time cell contraction monitoring based on optical Fourier transform

Forces generated by cells are critical regulators of cell adhesion and function. Polymeric micropillar arrays have been widely used for measuring cellular traction forces, however, the sub-micron scale deflections of micropillars are typically measured with a high power microscope, leading to a limited field-of-view and reducing the measurement efficiency. Herein, we reports a typical 4F system used to monitor cell contraction force based on optical Fourier transform (OFT). Compared to conventional microscopy, with a field-of-view on the scale of millimeters and instant acquisition of the force map, this method makes high-throughput and real-time cell contraction monitoring possible. The cells growing on micropillar arrays were placed on the object plane of a typical 4F system, illuminated by a monochromatic plane wave. OFT was performed on the light field as it passed through the first Fourier lens. The spatial spectrum that consists of discrete light spots was projected on the back focal plane of the first Fourier lens and was then filtered by an optical stop, eliminating the extraneous frequency components while allowing the frequency spots corresponding to the period of the micropillar arrays to pass through the aperture. Inverse OFT was conducted as the filtered light passed through the second Fourier lens and an image was reconstructed on the image plane of the 4F system, which was recorded by a CCD camera with a 20X objective. The light intensity of the image directly represents the degree of periodicity of the micropillar arrays, in which low-intensity areas indicated that the micropillars in this area were deflected while high-intensity areas indicate the presence of uniform micropillar arrays. Using this method, cell contraction forces could be directly visualized based on the intensity distribution at the image plane with no need for further image post-processing, enabling direct visualization of cell contraction in a larger field-of-view.