Pixel-size limitation of lensfree on-chip microscopy can be circumvented by utilizing pixel-super-resolution techniques to synthesize a smaller effective pixel, improving the resolution. Here we report that by using the two-dimensional pixel-function of an image sensor-array as an input to lensfree image reconstruction, pixel-super-resolution can improve the numerical aperture of the reconstructed image by ~3 fold compared to a raw lensfree image. This improvement was confirmed using two different sensor-arrays that significantly vary in their pixel-sizes, circuit architectures and digital/optical readout mechanisms, empirically pointing to roughly the same space-bandwidth improvement factor regardless of the sensor-array employed in our set-up. Furthermore, such a pixel-count increase also renders our on-chip microscope into a Giga-pixel imager, where an effective pixel count of ~1.6–2.5 billion can be obtained with different sensors. Finally, using an ultra-violet light-emitting-diode, this platform resolves 225 nm grating lines and can be useful for wide-field on-chip imaging of nano-scale objects, e.g., multi-walled-carbon-nanotubes.

We introduce the use of a birefringent crystal with lensless digital holography to create an on-chip differential interference contrast (DIC) microscope. Using an incoherent source with a large aperture, in-line holograms of micro-objects are created, which interact with a uniaxial crystal and an absorbing polarizer, encoding differential interference contrast information of the objects on the chip. Despite the fact that a unit fringe magnification and an incoherent source with a large aperture have been used, holographic digital processing of such holograms rapidly recovers the differential phase contrast image of the specimen over a large field-of-view of ~24 mm2.

We introduce the use of nanostructured surfaces for lensfree on-chip microscopy. In this incoherent on-chip imaging modality, the object of interest is directly positioned onto a nanostructured thin metallic film, where the emitted light from the object plane, after being modulated by the nanostructures, diffracts over a short distance to be sampled by a detector-array without the use of any lenses. The detected far-field diffraction pattern then permits rapid reconstruction of the object distribution on the chip at the subpixel level using a compressive sampling algorithm. This imaging modality based on nanostructured substrates could especially be useful to create lensfree fluorescent microscopes on a compact chip.

We demonstrate lensfree on-chip sensing within a microfluidic channel using plasmonic nanoapertures that are illuminated by a partially coherent quasimonochromatic source. In this approach, lensfree diffraction patterns of metallic nanoapertures located at the bottom of a microfluidic channel are recorded using an optoelectronic sensor-array. These lensfree diffraction patterns can then be rapidly processed, using phase recovery techniques, to back propagate the optical fields to an arbitrary depth, creating digitally focused complex transmission patterns. Cross correlation of these patterns enables lensfree on-chip sensing of the local refractive index surrounding the near-field of the plasmonic nanoapertures. Based on this principle, we experimentally demonstrate lensfree sensing of refractive index changes as small as ∼2×10(-3). This on-chip sensing approach could be quite useful for development of label-free microarray technologies by multiplexing thousands of plasmonic structures on the same microfluidic chip, which can significantly increase the throughput of sensing.

The conventional optical microscope is an inherently two-dimensional (2D) imaging tool. The objective lens, eyepiece and image sensor are all designed to capture light emitted from a 2D ‘object plane’. Existing technologies, such as confocal or light sheet fluorescence microscopy have to utilize mechanical scanning, a time-multiplexing process, to capture a 3D image. In this paper, we present a 3D optical microscopy method based upon simultaneously illuminating and detecting multiple focal planes. This is implemented by adding two diffractive optical elements to modify the illumination and detection optics. We demonstrate that the image quality of this technique is comparable to conventional light sheet fluorescent microscopy with the advantage of the simultaneous imaging of multiple axial planes and reduced number of scans required to image the whole sample volume.