Showing papers by "Alon Greenbaum published in 2015"

Synthetic aperture-based on-chip microscopy

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.

High-Throughput and Label-Free Single Nanoparticle Sizing Based on Time-Resolved On-Chip Microscopy

Abstract: Sizing individual nanoparticles and dispersions of nanoparticles provides invaluable information in applications such as nanomaterial synthesis, air and water quality monitoring, virology, and medical diagnostics. Several conventional nanoparticle sizing approaches exist; however, there remains a lack of high-throughput approaches that are suitable for low-resource and field settings, i.e., methods that are cost-effective, portable, and can measure widely varying particle sizes and concentrations. Here we fill this gap using an unconventional approach that combines holographic on-chip microscopy with vapor-condensed nanolens self-assembly inside a cost-effective hand-held device. By using this approach and capturing time-resolved in situ images of the particles, we optimize the nanolens formation process, resulting in significant signal enhancement for the label-free detection and sizing of individual deeply subwavelength particles (smaller than λ/10) over a 30 mm2 sample field-of-view, with an accuracy o...

Device and method for iterative phase recovery based on pixel super-resolved on-chip holography

Abstract: A method for lens-free imaging of a sample or objects within the sample uses multi-height iterative phase retrieval and rotational field transformations to perform wide FOV imaging of pathology samples with clinically comparable image quality to a benchtop lens-based microscope. The solution of the transport-of-intensity (TIE) equation is used as an initial guess in the phase recovery process to speed the image recovery process. The holographically reconstructed image can be digitally focused at any depth within the object FOV (after image capture) without the need for any focus adjustment, and is also digitally corrected for artifacts arising from uncontrolled tilting and height variations between the sample and sensor planes. In an alternative embodiment, a synthetic aperture approach is used with multi-angle iterative phase retrieval to perform wide FOV imaging of pathology samples and increase the effective numerical aperture of the image.

Wide-field pathology imaging using on-chip microscopy.

Abstract: As the primary imaging tool to assist the examination of pathological samples, the conventional light microscope suffers from limited throughput, relatively high cost, bulky size, lack of portability, and requirement for focus adjustment. All of these drawbacks partially limit the use of light microscopy tools in resource-limited settings. Lens-free on-chip microscopy can help to address these drawbacks and achieve high-throughput pathology slide imaging without using lenses or objectives. Here, we review the performance of this lens-free imaging platform by showing examples of its performance with various samples including normal and sickle-cell disease blood smears and human carcinoma of the breast. This lens-free computational microscopy platform is a promising tool that can serve high-throughput pathology needs especially in resource-poor settings.

High throughput on-chip analysis of high-energy charged particle tracks using lensfree imaging

Abstract: We demonstrate a high-throughput charged particle analysis platform, which is based on lensfree on-chip microscopy for rapid ion track analysis using allyl diglycol carbonate, i.e., CR-39 plastic polymer as the sensing medium. By adopting a wide-area opto-electronic image sensor together with a source-shifting based pixel super-resolution technique, a large CR-39 sample volume (i.e., 4 cm × 4 cm × 0.1 cm) can be imaged in less than 1 min using a compact lensfree on-chip microscope, which detects partially coherent in-line holograms of the ion tracks recorded within the CR-39 detector. After the image capture, using highly parallelized reconstruction and ion track analysis algorithms running on graphics processing units, we reconstruct and analyze the entire volume of a CR-39 detector within ∼1.5 min. This significant reduction in the entire imaging and ion track analysis time not only increases our throughput but also allows us to perform time-resolved analysis of the etching process to monitor and optimize the growth of ion tracks during etching. This computational lensfree imaging platform can provide a much higher throughput and more cost-effective alternative to traditional lens-based scanning optical microscopes for ion track analysis using CR-39 and other passive high energy particle detectors.

Wide-field Imaging of Pathology Slides using Lensfree On-chip Microscopy

Abstract: Three-dimensional lensfree imaging of pathology slides over a large field-of-view is achieved using multi-height phase recovery that incorporates transport-of-intensity equation and rotational field transformations to overcome stagnation in iterative image reconstruction.

High-numerical-aperture lens-free on-chip imaging using synthetic aperture

Abstract: The high-resolution optical inspection of a specimen across a large area is critical for the examination of rare events or abnormal objects in a variety of scientific disciplines, including biology, medicine, and materials science. Conventional lens-based microscopes are, however, limited by the trade-off between spatial resolution and field of view (FOV). Maintaining a high resolution over a large FOV requires expensive and bulky optical components or mechanical scanning stages, which limits widespread use, particularly in resource-limited settings. The rapid evolution of modern detection, sampling, and computing technologies has enabled new imaging methods that do not require lenses. These lensless approaches are not limited by the same trade-off between resolution and FOV. In particular, lens-free holographic on-chip imaging provides a wide-field and high-resolution imaging platform, coupled with a design that enables the development of compact and costeffective devices.1, 2 The optical setup of a lens-free on-chip microscope can be quite simple, constituting a partially coherent light source (e.g., an LED) and an image sensor chip. The specimen is placed slightly above the active area of the chip (100– 500 m). Light from the partially coherent source is incident on the specimen, and the resulting holographic diffraction pattern is recorded and digitized by an image sensor chip for further reconstruction. Running at unit magnification, a lens-free on-chip microscope possesses an FOV that is equal to the image sensor active area (20–30mm2), typically >100 times larger than a lens-based microscope with comparable resolution. To mitigate the relatively low spatial-sampling rate of the image sensor pixels, sourceor sample-shifting-based pixel super-resolution is performed to Figure 1. (a) Optical setup of our lens-free imaging method using a synthetic aperture. Partially coherent light is coupled to a single mode fiber with a spectral bandwidth of 2.5nm. Inset: A rotational arm is mounted on a two-axis linear stage so that the light source can be laterally shifted to perform pixel super-resolution. (b) Close-up showing the placement of the sample above the image sensor. (c) Optical schematic. The sample is placed above the image sensor by a small distance (0.1–1mm). The fiber tip is mounted on the rotational arm so that it can be scanned across a dome above the sample plane.

High-throughput lensfree ion-track analysis for laser-driven accelerators

Abstract: We report a lensfree imaging based high-throughput ion-track analysis platform for laser driven accelerators. This computational on-chip imaging platform, owing to its large field-of-view of 18 cm2, provides >20-fold improved imaging speed than lens-based analysis systems.

High-resolution on-chip imaging using synthetic aperture

Abstract: We report a synthetic-aperture-based on-chip lensfree microscope. Having a wide field-of-view of ∼20.5 mm2, this technique sets the largest numerical aperture (1.4) for on-chip microscopy.

Field-portable nanoparticle and virus sizing enabled by on-chip microscopy and vapor-condensed nanolenses

Abstract: Vapor-condensed nanolenses make label-free lensfree holographic microscopy sensitive to individual particles 40 nm and larger. Detected signals correlate with particle size with accuracy ±11 nm. Automated image processing measures >105 particles within a single field-of-view.