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Open Access Publications from the University of California

Scholarly Works (7 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2012)

Despite the rapid progress in optical imaging, most of the advanced microscopy modalities still require complex and costly set-ups that unfortunately limit their use beyond well-equipped laboratories. To provide affordable and easy-to-use microscopes for resource-limited settings, I developed a holographic on-chip imaging technology that utilizes cost-effective and compact optoelectronic components to enable the digital reconstruction of microscopic amplitude and phase images for biological cells with sub-micron resolution over a field-of-view of >24 mm^2. Without the need for any lenses, bulky optical components or coherent sources such as lasers, this partially-coherent computational imaging modality can automatically analyze thousands of cells in parallel for their cell type, concentration, structure, and dynamics. As being compact, light-weight, cost-effective, high-throughput, and highly-sensitive, this lensfree imaging technology is especially suitable for field diagnostics applications involving global health problems such as HIV, malaria, infectious diarrhea, or male infertility.

Based on this lensfree imaging technology, I also devised a dual-angle dual-color holographic scheme to achieve sub-micron accuracy and sub-12-minisecond resolution for three-dimensional tracking of >1,500 human sperms in a field-of-view of >17 mm^2 and a depth-of-field of >0.5 mm. The high accuracy and high throughput of this lensfree imaging platform enabled the first observation of human sperms' tight (1-6um wide), fast (3-20 r/sec), and rare (4- 5%) helical trajectories, which surprisingly are dominated by right-handed ones (~90%) and can be significantly suppressed by seminal plasma. Such a high-throughput 3D tracking platform can also be a valuable tool for observing the statistical swimming patterns of various microorganisms, leading to new insights in their 3D dynamics.

    Cover page: Lensfree Holographic On-Chip Imaging and Three-Dimensional Tracking
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2010)
    We demonstrate lensfree holographic microscopy on a chip to achieve approximately 0.6 microm spatial resolution corresponding to a numerical aperture of approximately 0.5 over a large field-of-view of approximately 24 mm2. By using partially coherent illumination from a large aperture (approximately 50 microm), we acquire lower resolution lensfree in-line holograms of the objects with unit fringe magnification. For each lensfree hologram, the pixel size at the sensor chip limits the spatial resolution of the reconstructed image. To circumvent this limitation, we implement a sub-pixel shifting based super-resolution algorithm to effectively recover much higher resolution digital holograms of the objects, permitting sub-micron spatial resolution to be achieved across the entire sensor chip active area, which is also equivalent to the imaging field-of-view (24 mm2) due to unit magnification. We demonstrate the success of this pixel super-resolution approach by imaging patterned transparent substrates, blood smear samples, as well as Caenoharbditis Elegans.
      Cover page: Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2010)
      We demonstrate the use of a compressive sampling algorithm for on-chip fluorescent imaging of sparse objects over an ultra-large field-of-view (>8 cm(2)) without the need for any lenses or mechanical scanning. In this lensfree imaging technique, fluorescent samples placed on a chip are excited through a prism interface, where the pump light is filtered out by total internal reflection after exciting the entire sample volume. The emitted fluorescent light from the specimen is collected through an on-chip fiber-optic faceplate and is delivered to a wide field-of-view opto-electronic sensor array for lensless recording of fluorescent spots corresponding to the samples. A compressive sampling based optimization algorithm is then used to rapidly reconstruct the sparse distribution of fluorescent sources to achieve approximately 10 microm spatial resolution over the entire active region of the sensor-array, i.e., over an imaging field-of-view of >8 cm(2). Such a wide-field lensless fluorescent imaging platform could especially be significant for high-throughput imaging cytometry, rare cell analysis, as well as for micro-array research.
        Cover page: Lensless wide-field fluorescent imaging on a chip using compressive decoding of sparse objects
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2014)
        Quantitative cell motility studies are necessary for understanding biophysical processes, developing models for cell locomotion and for drug discovery. Such studies are typically performed by controlling environmental conditions around a lens-based microscope, requiring costly instruments while still remaining limited in field-of-view. Here we present a compact cell monitoring platform utilizing a wide-field (24 mm(2)) lensless holographic microscope that enables automated single-cell tracking of large populations that is compatible with a standard laboratory incubator. We used this platform to track NIH 3T3 cells on polyacrylamide gels over 20 hrs. We report that, over an order of magnitude of stiffness values, collagen IV surfaces lead to enhanced motility compared to fibronectin, in agreement with biological uses of these structural proteins. The increased throughput associated with lensfree on-chip imaging enables higher statistical significance in observed cell behavior and may facilitate rapid screening of drugs and genes that affect cell motility.
          Cover page: Automated single-cell motility analysis on a chip using lensfree microscopy
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2011)
          We demonstrate lensfree on-chip fluorescent imaging of transgenic Caenorhabditis elegans (C. elegans) over an ultra-wide field-of-view (FOV) of e.g., >2-8 cm(2) with a spatial resolution of ∼10 µm. This is the first time that a lensfree on-chip platform has successfully imaged fluorescent C. elegans samples. In our wide-field lensfree imaging platform, the transgenic samples are excited using a prism interface from the side, where the pump light is rejected through total internal reflection occurring at the bottom facet of the substrate. The emitted fluorescent signal from C. elegans samples is then recorded on a large area opto-electronic sensor-array over an FOV of e.g., >2-8 cm(2), without the use of any lenses, thin-film interference filters or mechanical scanners. Because fluorescent emission rapidly diverges, such lensfree fluorescent images recorded on a chip look blurred due to broad point-spread-function of our platform. To combat this resolution challenge, we use a compressive sampling algorithm to uniquely decode the recorded lensfree fluorescent patterns into higher resolution images, demonstrating ∼10 µm resolution. We tested the efficacy of this compressive decoding approach with different types of opto-electronic sensors to achieve a similar resolution level, independent of the imaging chip. We further demonstrate that this wide FOV lensfree fluorescent imaging platform can also perform sequential bright-field imaging of the same samples using partially-coherent lensfree digital in-line holography that is coupled from the top facet of the same prism used in fluorescent excitation. This unique combination permits ultra-wide field dual-mode imaging of C. elegans on a chip which could especially provide a useful tool for high-throughput screening applications in biomedical research.
            Cover page: Lensfree Fluorescent On-Chip Imaging of Transgenic Caenorhabditis elegans Over an Ultra-Wide Field-of-ViewCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2013)
            We report the discovery of an entirely new three-dimensional (3D) swimming pattern observed in human and horse sperms. This motion is in the form of 'chiral ribbons', where the planar swing of the sperm head occurs on an osculating plane creating in some cases a helical ribbon and in some others a twisted ribbon. The latter, i.e., the twisted ribbon trajectory, also defines a minimal surface, exhibiting zero mean curvature for all the points on its surface. These chiral ribbon swimming patterns cannot be represented or understood by already known patterns of sperms or other micro-swimmers. The discovery of these unique patterns is enabled by holographic on-chip imaging of >33,700 sperm trajectories at >90-140 frames/sec, which revealed that only ~1.7% of human sperms exhibit chiral ribbons, whereas it increases to ~27.3% for horse sperms. These results might shed more light onto the statistics and biophysics of various micro-swimmers' 3D motion.
              Cover page: Sperm Trajectories Form Chiral Ribbons
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2012)
              The recent revolution in digital technologies and information processing methods present important opportunities to transform the way optical imaging is performed, particularly toward improving the throughput of microscopes while at the same time reducing their relative cost and complexity. Lensfree computational microscopy is rapidly emerging toward this end, and by discarding lenses and other bulky optical components of conventional imaging systems, and relying on digital computation instead, it can achieve both reflection and transmission mode microscopy over a large field-of-view within compact, cost-effective and mechanically robust architectures. Such high throughput and miniaturized imaging devices can provide a complementary toolset for telemedicine applications and point-of-care diagnostics by facilitating complex and critical tasks such as cytometry and microscopic analysis of e.g., blood smears, Pap tests and tissue samples. In this article, the basics of these lensfree microscopy modalities will be reviewed, and their clinically relevant applications will be discussed.
                Cover page: Modern Trends in Imaging VIII: Lensfree Computational Microscopy Tools for Cell and Tissue Imaging at the Point‐of‐Care and in Low‐Resource SettingsCreative Commons 'BY' version 4.0 license
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