Browsing by Author "Ye, Fan"

Now showing 1 - 6 of 6
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    Deep imaging in scattering media with selective plane illumination microscopy
    (SPIE, 2016) Pediredla, Adithya Kumar; Zhang, Shizheng; Avants, Ben; Ye, Fan; Nagayama, Shin; Chen, Ziying; Kemere, Caleb; Robinson, Jacob T.; Veeraraghavan, Ashok; Bioengineering; Electrical and Computer Engineering; Computer Science
    In most biological tissues, light scattering due to small differences in refractive index limits the depth of optical imaging systems. Two-photon microscopy (2PM), which significantly reduces the scattering of the excitation light, has emerged as the most common method to image deep within scattering biological tissue. This technique, however, requires high-power pulsed lasers that are both expensive and difficult to integrate into compact portable systems. Using a combination of theoretical and experimental techniques, we show that if the excitation path length can be minimized, selective plane illumination microscopy (SPIM) can image nearly as deep as 2PM without the need for a high-powered pulsed laser. Compared to other single-photon imaging techniques like epifluorescence and confocal microscopy, SPIM can image more than twice as deep in scattering media (∼10 times the mean scattering length). These results suggest that SPIM has the potential to provide deep imaging in scattering media in situations in which 2PM systems would be too large or costly.
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    Generalized method to design phase masks for 3D super-resolution microscopy
    (Optical Society of America, 2019) Wang, Wenxiao; Ye, Fan; Shen, Hao; Moringo, Nicholas A.; Dutta, Chayan; Robinson, Jacob T.; Landes, Christy F.
    Point spread function (PSF) engineering by phase modulation is a novel approach to three-dimensional (3D) super-resolution microscopy, with different point spread functions being proposed for specific applications. It is often not easy to achieve the desired shape of engineered point spread functions because it is challenging to determine the correct phase mask. Additionally, a phase mask can either encode 3D space information or additional time information, but not both simultaneously. A robust algorithm for recovering a phase mask to generate arbitrary point spread functions is needed. In this work, a generalized phase mask design method is introduced by performing an optimization. A stochastic gradient descent algorithm and a Gauss-Newton algorithm are developed and compared for their ability to recover the phase masks for previously reported point spread functions. The new Gauss-Newton algorithm converges to a minimum at much higher speeds. This algorithm is used to design a novel stretching-lobe phase mask to encode temporal and 3D spatial information simultaneously. The stretching-lobe phase mask and other masks are fabricated in-house for proof-of-concept using multi-level light lithography and an optimized commercially sourced stretching-lobe phase mask (PM) is validated experimentally to encode 3D spatial and temporal information. The algorithms’ generalizability is further demonstrated by generating a phase mask that comprises four different letters at different depths.
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    Implantable integrated nanophotonic probes with light sheet illumination for deep imaging
    (2019-08-08) Ye, Fan; ROBINSON, JACOB
    Optical techniques to record and stimulate neural activity are becoming increasingly powerful and effective, but delivering light to specific regions deep within the brain is limited by the scattering of neural tissue. By focusing light to a single illumination plane, researchers can perform high-speed volumetric imaging or optically stimulate cells within specific layers of tissue. This single plane illumination, which is called light sheet illumination, also reduces the background from out-of-plane fluorescence creating images with higher contrast. However, conventional light sheet microscopy based on discrete optical components is incompatible with large living animals. To overcome this limitation, I have designed and fabricated two different kind of miniature, implantable silicon-based photonic probes that act as light sheet illumination devices. The first probe consists of a properly designed planar metallic microlens integrated onto aluminum nitride (AlN) waveguide gratings on a thermal oxide silicon substrate. Light diffraction by the metallic slit microlens can be considered as the interference between quasi-cylindrical waves and the finite-difference time-domain (FDTD) simulations match the experimental measurements. These results have verified that a single metallic slit is an efficient nanophotonic element for light sheet illumination. Furthermore, I have integrated the microlens onto the aluminum nitride resonant waveguide gratings on a silicon-based probe and the properly designed waveguide gratings can radiate the guided visible light vertically. Subsequently, the diffraction field radiated from the gratings will be focused by the microlens to achieve light sheet illumination that can be used for deep brain imaging. The second probe is as thin as 20 μm that can also produce a thin layer of illumination from the properly designed aluminum nitride waveguide gratings without using the microlens. I have theoretically and experimentally verified that the aluminum nitride resonant waveguide gratings are effective for producing light sheet illumination. I also show that three dimensional imaging, is possible by scanning the light sheet illumination plane. Compared to single photon imaging techniques like epi-fluorescence microscopy and confocal microscopy, the nanophotonic integrated light sheet microscopy can image more than twice the depth in a brain tissue phantom, which is confirmed experimentally. Compared to table-top systems and multi-photon microscopy, this implantable photonic probe enables a low-cost, small-form solution for light sheet illumination and deep brain imaging.
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    Implanted Nanophotonic Probes for Deep Imaging in Scattering Media
    (2018-04-26) Ye, Fan; ROBINSON , JACOB
    Optical imaging techniques that measure changes in calcium or voltage provide a promising route toward to large-scale measurement of neural activity and high spatial resolution to resolve individual neurons. However, acquiring images through significant depths of the brain is difficult since brain tissue is extremely heterogeneous, which results in strong scattering by the various tissue components and limited penetration depth as well as achievable imaging resolution. To overcome the effects of scattering, optical imaging measurement techniques have been proposed ranging from laser scanning microscopy of submicron structures to diffuse optical tomography of large volumes of tissue. Recent advances in imaging technology such as light-sheet microscopy have enabled high-speed, high-resolution, three-dimensional volumetric imaging of large volumes of neural tissue. However, the light sheet microscopy technique fails to be compatible with opaque or scattering samples and has a limitation of the sample size by the two compact orthogonal illumination and detection objectives. In this work, I will show an implantable light sheet photonic probe integrated with a microlens that can produce a thin layer of illumination. With this planar illumination, the probe can image more than 500 microns deep below the surface of a brain tissue phantom, which is confirmed experimentally. First, I will make an introduction of the current optical imaging techniques, such as epi-fluorescence microscopy, laser scanning confocal microscopy, two-photon microscopy and conventional light sheet microscopy. Also, I will discuss the limitations and drawbacks of each method. Second, I will present the design and principle of the integrated light sheet photonic probe with a microlens that can produce a thin layer of light illumination perpendicular to the device plane. In addition, I will show the structure of the photonic probe and components of the imaging setup. Also, I will numerically and experimentally illustrate the light sheet can be created by a microlens diffraction. Then I will show the imaging result of inserting the photonic probe inside the brain tissue phantom and compare it to the conventional wide field microscopy. Finally, I will make a summary of my work and then talk about the future work of my research.
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    Integrated light-sheet illumination using metallic slit microlenses
    (Optical Society of America, 2018) Ye, Fan; Avants, Benjamin W.; Veeraraghavan, Ashok; Robinson, Jacob T.
    Light sheet microscopy (LSM) - also known as selective plane illumination microscopy (SPIM) - enables high-speed, volumetric imaging by illuminating a two-dimensional cross-section of a specimen. Typically, this light sheet is created by table-top optics, which limits the ability to miniaturize the overall SPIM system. Replacing this table-top illumination system with miniature, integrated devices would reduce the cost and footprint of SPIM systems. One important element for a miniature SPIM system is a flat, easily manufactured lens that can form a light sheet. Here we investigate planar metallic lenses as the beam shaping element of an integrated SPIM illuminator. Based on finite difference time domain (FDTD) simulations, we find that diffraction from a single slit can create planar illumination with a higher light throughput than zone plate or plasmonic lenses. Metallic slit microlenses also show broadband operation across the entire visible range and are nearly polarization insensitive. Furthermore, compared to meta-lenses based on sub-wavelength-scale diffractive elements, metallic slit lenses have micron-scale features compatible with low-cost photolithographic manufacturing. These features allow us to create inexpensive integrated devices that generate light-sheet illumination comparable to tabletop microscopy systems. Further miniaturization of this type of integrated SPIM illuminators will open new avenues for flat, implantable photonic devices for in vivo biological imaging.
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    Single-frame 3D fluorescence microscopy with ultraminiature lensless FlatScope
    (AAAS, 2017) Adams, Jesse K.; Boominathan, Vivek; Avants, Benjamin W.; Vercosa, Daniel G.; Ye, Fan; Baraniuk, Richard G.; Robinson, Jacob T.; Veeraraghavan, Ashok; Nanophotonic Computational Imaging and Sensing Laboratory
    Modern biology increasingly relies on fluorescence microscopy, which is driving demand for smaller, lighter, and cheaper microscopes. However, traditional microscope architectures suffer from a fundamental trade-off: As lenses become smaller, they must either collect less light or image a smaller field of view. To break this fundamental trade-off between device size and performance, we present a new concept for three-dimensional (3D) fluorescence imaging that replaces lenses with an optimized amplitude mask placed a few hundred micrometers above the sensor and an efficient algorithm that can convert a single frame of captured sensor data into high-resolution 3D images. The result is FlatScope: perhaps the world's tiniest and lightest microscope. FlatScope is a lensless microscope that is scarcely larger than an image sensor (roughly 0.2 g in weight and less than 1 mm thick) and yet able to produce micrometer-resolution, high-frame rate, 3D fluorescence movies covering a total volume of several cubic millimeters. The ability of FlatScope to reconstruct full 3D images from a single frame of captured sensor data allows us to image 3D volumes roughly 40,000 times faster than a laser scanning confocal microscope while providing comparable resolution. We envision that this new flat fluorescence microscopy paradigm will lead to implantable endoscopes that minimize tissue damage, arrays of imagers that cover large areas, and bendable, flexible microscopes that conform to complex topographies.