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 mm 2 . 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. Keywords: computational imaging; lensfree microscopy; on-chip microscopy; synthetic aperture INTRODUCTIONWide field-of-view (FOV) and high-resolution imaging is crucial for various applications in biomedical and physical sciences. Such tasks demand microscopes to have large space-bandwidth products (SBPs) with minimal spatial aberrations that distort the utilization of the SBP of the imaging system. Conventional lens-based digital microscopes can achieve high-resolution imaging over a large FOV using mechanical scanning stages to capture multiple images from different parts of the specimen that are digitally stitched together. This scanning approach, however, demands a relatively bulky and expensive imaging set-up. In contrast, recent advances in digital components and computational techniques have enabled powerful imaging methods,

Development of inexpensive blood imaging systems: where are we now?

“…However, several improvements to this technique have since been reported. As in the shadow-imaging technology described above, changing the source position can give additional information to enable pixelsuper-resolution [71][72][73][74], with effective numerical apertures above 0.75 possible. An important feature of this improvement is that it enables lens-free on-chip imaging of dense and connected samples, such as pathology slides of tissue samples or thick blood smears.…”

“…The largest drawback is the requirement for complex computational methods that may be timeconsuming or not feasible given today's current computing power on portable, low-cost devices. The lens-free holographic microscopy takes about 46 min to reconstruct a 1  1 mm region (CPU: Intel Xeon E5-1620) [72]. The portable FP microscopy reconstructs a 1.1 mm  0.8 mm region in about 50 s with an i7 4-core CPU [78].…”

High-resolution On-chip Imaging using Synthetic Aperture

“…Here we report a new lensfree imaging technique that is based on synthetic aperture, which we term as LISA (Lensfree Imaging using Synthetic Aperture) [3]. In LISA, during the data acquisition, the specimen is sequentially illuminated from multiple angles, and at every angle, source shifting pixel super resolution technique is implemented to obtain high resolution diffraction patterns ( Fig.…”

Compact lensless phase imager

“…One of this phase retrieval technique uses a multi angle illumination [19,20]. During this process, several holograms are taken with different illumination directions.…”

“…Then, the amplitude and the phase are numerically reconstructed using all those holograms. This technique has been proposed with an optical fiber mounted on a rotational arm [7,19] or several light-emitting diodes (LEDs) coupled in a fiber-optic array [21]. In this system, the distance between the end of the fiber and the object has to be quite large (several cm) to obtain enough spatial coherence.…”