We report a fast and effective lens-free imaging platform for optical diffraction tomography (ODT). Using single wavelength illumination from only 4 angular directions and a lensless inline holographic imaging setup to directly capture the resulting diffraction patterns, our method can reconstruct high quality 3D images of biological samples at micron-scale resolution across a cubic-millimeter-level volume with a compact, scalable and inexpensive system. To achieve this, we developed a compressive tomographic reconstruction algorithm to solve the inverse problem of lens-free ODT by combining Wirtinger derivatives and primal-dual splitting. This fast and inexpensive lens-free tomographic microscopy system provides a promising 3D imaging approach for high throughput biomedical applications.
Lens-free imaging (LFI) has become an important microscopy tool in many life science and industrial applications. Due to the absence of optical lenses (such as objectives) and accompanying lens aberrations (such as chromatic aberrations), the LFI modality is well suited for optical inspection of microscopic objects in a wide spectral range. However, the relatively restricted spectral sensitivity of CMOS imagers, i.e. from visible (~400 nm) up to near-infrared range (~900 nm), limits the wide spectral use of the technique. Many microscopic samples contain valuable information both in the visible and in the short wave infra-red (SWIR), sometimes in addition to visible (VIS) and near-infrared (NIR). With the recent emergence of cost-effective image sensor technologies such as quantum-dot and graphene-based image sensors with high quantum efficiency in SWIR, new lens-free imaging opportunities are emerging for wideband and high throughput microscopy. We demonstrate for the first time an LFI system based on a quantum-dot image sensor, capable of operating in both the visible and short-wave infrared range. The holograms of the samples are obtained through multiple partially coherent illumination sources in both visible and short-wave infrared (ranging from 405 nm to 1550 nm). The captured holograms are reconstructed to obtain images of the sample in focus. We demonstrate an optical resolution of 3.48 micron in a field of view of 9.6 mm2 over the whole spectral range. Our technique mitigates the need for bulky and expensive achromatic imaging optics and offers significant improvements in cost, field-of-view, scalability, and optical resolution to achieve microscopic imaging in both the visible and short-wave infrared spectral range with a simple imaging system. We present in this paper a performance analysis of the system and several potential applications and use cases.
Fluorescence microscopy is an indispensable tool in biology and medicine, fuelling many breakthrough discoveries in a wide set of sub-domains. Yet, the resolution is intrinsically restricted by the diffraction limit. The last two decades have witnessed the emergence of several super-resolution fluorescence microscopy techniques that are breaking this limit (cfr. Nobel Prize in Chemistry 2014). Structured illumination microscopy (SIM) is one of such techniques that has gained much popularity and is available in commercial systems. In SIM, a biological sample is illuminated by a spatially structured light field — a sinusoidal interference pattern — which causes normally inaccessible high-resolution information to be encoded into the observed image due to the Moiré effect. Typically, the illumination patterns are generated by a grating or SLM and focused onto the sample through an objective lens to excite the fluorophores. Next, the fluorescence is transmitted to the imager through the same lens. Multiple images are taken under certain illumination patterns and used to reconstruct a single super-resolved image. However, making use of free space optics, state-of-the-art SIM systems require multiple bulky and precision optical components that give these systems the drawbacks of high cost and cumbersome size.
In this talk, a structured illumination microscopy system based on a photonic integrated circuit (PIC) is presented. The unique properties of photonic integrated circuits allow us to create truly innovative microscopy systems that have the potential to go well beyond the current state-of-the-art: higher resolution due to the use of high refractive index materials, easier alignment with on-chip illumination light path, large field of view, a compact form factor resulting from on-chip integration, and lower cost due to compatibility with CMOS chip fabrication.