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Alon Greenbaum

Bio: Alon Greenbaum is an academic researcher from California Institute of Technology. The author has contributed to research in topics: Microscopy & Microscope. The author has an hindex of 26, co-authored 58 publications receiving 3453 citations. Previous affiliations of Alon Greenbaum include Tel Aviv University & University of California, Los Angeles.


Papers
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Journal ArticleDOI
TL;DR: When used with cell-type-specific promoters and enhancers, these AAVs enable efficient and targetable genetic modification of cells throughout the nervous system of transgenic and non-transgenic animals.
Abstract: Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1 × 1011 vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1 × 1012 vg of AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons. The efficiency of these vectors facilitates robust cotransduction and stochastic, multicolor labeling for individual cell morphology studies. To support such efforts, we provide methods for labeling a tunable fraction of cells without compromising color diversity. Furthermore, when used with cell-type-specific promoters and enhancers, these AAVs enable efficient and targetable genetic modification of cells throughout the nervous system of transgenic and non-transgenic animals.

822 citations

Journal ArticleDOI
TL;DR: Unique features of lens-free computational imaging tools are discussed and some of their emerging results for wide-field on-chip microscopy, such as the achievement of a numerical aperture of ∼0.8–0.9 across a field of view (FOV) of more than 20 mm2, which corresponds to an image with more than 1.5 gigapixels.
Abstract: In this perspective, the authors present the basic features of lens-free computational imaging tools and report performance comparisons with conventional microscopy methods. They also discuss the challenges that these computational on-chip microscopes face for their wide-scale biomedical application.

486 citations

Journal ArticleDOI
TL;DR: A review of state-of-the-art optical imaging techniques that can have a significant impact on global health by facilitating effective and affordable POC diagnostics is presented in this article.
Abstract: Improving access to effective and affordable healthcare has long been a global endeavor. In this quest, the development of cost-effective and easy-to-use medical testing equipment that enables rapid and accurate diagnosis is essential to reduce the time and costs associated with healthcare services. To this end, point-of-care (POC) diagnostics plays a crucial role in healthcare delivery in both developed and developing countries by bringing medical testing to patients, or to sites near patients. As the diagnosis of a wide range of diseases, including various types of cancers and many endemics, relies on optical techniques, numerous compact and cost-effective optical imaging platforms have been developed in recent years for use at the POC. Here, we review the state-of-the-art optical imaging techniques that can have a significant impact on global health by facilitating effective and affordable POC diagnostics.

271 citations

Journal ArticleDOI
TL;DR: The performance of a computational lens-free, holographic on-chip microscope that uses the transport-of-intensity equation, multi-height iterative phase retrieval, and rotational field transformations to perform wide-FOV imaging of pathology samples with comparable image quality to a traditional transmission lens-based microscope is illustrated.
Abstract: Optical examination of microscale features in pathology slides is one of the gold standards to diagnose disease. However, the use of conventional light microscopes is partially limited owing to their relatively high cost, bulkiness of lens-based optics, small field of view (FOV), and requirements for lateral scanning and three-dimensional (3D) focus adjustment. We illustrate the performance of a computational lens-free, holographic on-chip microscope that uses the transport-of-intensity equation, multi-height iterative phase retrieval, and rotational field transformations to perform wide-FOV imaging of pathology samples with comparable image quality to a traditional transmission lens-based microscope. The holographically reconstructed image can be digitally focused at any depth within the object FOV (after image capture) without the need for mechanical focus adjustment and is also digitally corrected for artifacts arising from uncontrolled tilting and height variations between the sample and sensor planes. Using this lens-free on-chip microscope, we successfully imaged invasive carcinoma cells within human breast sections, Papanicolaou smears revealing a high-grade squamous intraepithelial lesion, and sickle cell anemia blood smears over a FOV of 20.5 mm(2). The resulting wide-field lens-free images had sufficient image resolution and contrast for clinical evaluation, as demonstrated by a pathologist's blinded diagnosis of breast cancer tissue samples, achieving an overall accuracy of ~99%. By providing high-resolution images of large-area pathology samples with 3D digital focus adjustment, lens-free on-chip microscopy can be useful in resource-limited and point-of-care settings.

257 citations

Journal ArticleDOI
TL;DR: In this article, a synthetic aperture-based on-chip microscope was proposed to achieve a very large effective numerical aperture of 1.4 over a field-of-view (FOV) of >20 mm2.
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.

202 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: An imaging method, termed Fourier ptychographic microscopy (FPM), which iteratively stitches together a number of variably illuminated, low-resolution intensity images in Fourier space to produce a wide-field, high-resolution complex sample image, which can also correct for aberrations and digitally extend a microscope's depth-of-focus beyond the physical limitations of its optics.
Abstract: We report an imaging method, termed Fourier ptychographic microscopy (FPM), which iteratively stitches together a number of variably illuminated, low-resolution intensity images in Fourier space to produce a wide-field, high-resolution complex sample image. By adopting a wavefront correction strategy, the FPM method can also correct for aberrations and digitally extend a microscope’s depth of focus beyond the physical limitations of its optics. As a demonstration, we built a microscope prototype with a resolution of 0.78 µm, a field of view of ∼120 mm^2 and a resolution-invariant depth of focus of 0.3 mm (characterized at 632 nm). Gigapixel colour images of histology slides verify successful FPM operation. The reported imaging procedure transforms the general challenge of high-throughput, high-resolution microscopy from one that is coupled to the physical limitations of the system’s optics to one that is solvable through computation.

1,363 citations

Journal ArticleDOI
07 Sep 2018-Science
TL;DR: 3D-printed D2NNs are created that implement classification of images of handwritten digits and fashion products, as well as the function of an imaging lens at a terahertz spectrum.
Abstract: Deep learning has been transforming our ability to execute advanced inference tasks using computers. Here we introduce a physical mechanism to perform machine learning by demonstrating an all-optical diffractive deep neural network (D2NN) architecture that can implement various functions following the deep learning-based design of passive diffractive layers that work collectively. We created 3D-printed D2NNs that implement classification of images of handwritten digits and fashion products, as well as the function of an imaging lens at a terahertz spectrum. Our all-optical deep learning framework can perform, at the speed of light, various complex functions that computer-based neural networks can execute; will find applications in all-optical image analysis, feature detection, and object classification; and will also enable new camera designs and optical components that perform distinctive tasks using D2NNs.

1,145 citations

Journal ArticleDOI
TL;DR: The fundamentals of AAV and vectorology are discussed, focusing on current therapeutic strategies, clinical progress and ongoing challenges.
Abstract: Adeno-associated virus (AAV) vectors are the leading platform for gene delivery for the treatment of a variety of human diseases. Recent advances in developing clinically desirable AAV capsids, optimizing genome designs and harnessing revolutionary biotechnologies have contributed substantially to the growth of the gene therapy field. Preclinical and clinical successes in AAV-mediated gene replacement, gene silencing and gene editing have helped AAV gain popularity as the ideal therapeutic vector, with two AAV-based therapeutics gaining regulatory approval in Europe or the United States. Continued study of AAV biology and increased understanding of the associated therapeutic challenges and limitations will build the foundation for future clinical success.

1,041 citations