Synthetic aperture-based on-chip microscopy

Abstract

Wide field-of-view (FOV) and high-resolution imaging requires microscopy modalities to have large space-bandwidth products. Lensfree on-chip microscopy decouples resolution from FOV and can achieve a space-bandwidth product greater than one billion under unit magnification using state-of-the-art opto-electronic sensor chips and pixel super-resolution techniques. However, using vertical illumination, the effective numerical aperture (NA) that can be achieved with an on-chip microscope is limited by a poor signal-to-noise ratio (SNR) at high spatial frequencies and imaging artifacts that arise as a result of the relatively narrow acceptance angles of the sensor's pixels. Here, we report, for the first time, a synthetic aperture-based on-chip microscope in which the illumination angle is scanned across the surface of a dome to increase the effective NA of the reconstructed lensfree image to 1.4, achieving e.g., ∼250-nm resolution at 700-nm wavelength under unit magnification. This synthetic aperture approach not only represents the largest NA achieved to date using an on-chip microscope but also enables color imaging of connected tissue samples, such as pathology slides, by achieving robust phase recovery without the need for multi-height scanning or any prior information about the sample. To validate the effectiveness of this synthetic aperture-based, partially coherent, holographic on-chip microscope, we have successfully imaged color-stained cancer tissue slides as well as unstained Papanicolaou smears across a very large FOV of 20.5 mm2. This compact on-chip microscope based on a synthetic aperture approach could be useful for various applications in medicine, physical sciences and engineering that demand high-resolution wide-field imaging. An on-chip microscope that offers both a high-resolution and a wide field of view looks set to benefit the biological and physical sciences. The lensfree imaging device, developed by researchers at the University of California at Los Angeles, CA, USA, makes use a synthetic aperture approach to provide a very large effective numerical aperture of 1.4 over a field of view of >20 mm2; this is a much larger numerical aperture than previous lensfree approaches had realized (<0.9). Consequently, very high spatial resolution (for example, 250 nm at a wavelength of 700 nm) was achieved. By illuminating samples with light of three different wavelengths (470 nm, 532 nm and 632 nm), the researchers also obtained lens-free color images of samples such as breast cancer tissue.