Lensless, microfluidic imaging of cells and tiny worms

In scanning microscopy, images are put together by sweeping a single narrow beam back and forth over a sample. If you had a wide array of multiple beams, one scan would suffice. And if the sample moved over the array, you wouldn’t need to scan at all. That idea is behind a new optofluidic imaging scheme developed for biological applications by Caltech’s Changhuei Yang and his colleagues. At the heart of the scheme is an off-the-shelf sensor whose CMOS pixels are read out individually. Contrast is achieved when a sample, under constant illumination, momentarily shadows the pixels as it passes over them in a microfluidic channel. At 10 × 10 μm², the pixel size is too big to resolve the parts of amoebae and other tiny organisms. To boost the resolution, Yang masks the pixels with a commensurate array of 1-μm-diameter holes. Although 99% of the sensor is masked, 100% of a sample is imaged because the sample’s path over the lines of holes is canted at a slight angle. Thanks to the angle, an organism or cell is scanned not only along but also across its whole body. The Caltech team built and demonstrated two types of imager; they differ in how they stabilize a sample’s orientation during a scan. In one type, suitable for imaging tiny worms and other elongated samples, gravity pulls the samples. Confinement suffices to prevent the samples from tumbling. In the other type, suitable for squatter, more rounded samples, pressure pushes the samples. Tumbling is forestalled by a strong DC electric field, which polarizes and aligns the samples. Both imagers are barely bigger than a US quarter and, as the accompanying images show, provide resolution comparable to that of a conventional optical microscope. (X. Cui et al., Proc. Natl. Acad. Sci. USA 105 , 10670, 2008 http://dx.doi.org/10.1073/pnas.0804612105 .)