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      Field-portable reflection and transmission microscopy based on lensless holography

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          Abstract

          We demonstrate a lensfree dual-mode holographic microscope that can image specimens in both transmission and reflection geometries using in-line transmission and off-axis reflection holography, respectively. This field-portable dual-mode holographic microscope has a weight of ~200 g with dimensions of 15 x 5.5 x 5cm, where a laser source is powered by two batteries. Based on digital in-line holography, our transmission microscope achieves a sub-pixel lateral resolution of ≤2 µm over a wide field-of-view (FOV) of ~24 mm 2 due to its unit fringe magnification geometry. Despite its simplicity and ease of operation, in-line transmission geometry is not suitable to image dense or connected objects such as tissue slides since the reference beam gets distorted causing severe aberrations in reconstruction of such objects. To mitigate this challenge, on the same cost-effective and field-portable assembly we built a lensless reflection mode microscope based on digital off-axis holography where a beam-splitter is used to interfere a tilted reference wave with the reflected light from the object surface, creating an off-axis hologram of the specimens on a CMOS sensor-chip. As a result of the reduced space-bandwidth product of the off-axis geometry compared to its in-line counterpart, the imaging FOV of our reflection mode is reduced to ~9 mm 2, while still achieving a similar sub-pixel resolution of ≤2 µm. We tested the performance of this compact dual-mode microscopy unit by imaging a US-air force resolution test target, various micro-particles as well as a histopathology slide corresponding to skin tissue. Due to its compact, cost-effective, and lightweight design, this dual-mode lensless holographic microscope might especially be useful for field-use or for conducting microscopic analysis in resource-poor settings.

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          Most cited references43

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          A new microscopic principle.

          D. Gabor (1948)
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            Mobile Phone Based Clinical Microscopy for Global Health Applications

            Light microscopy provides a simple, cost-effective, and vital method for the diagnosis and screening of hematologic and infectious diseases. In many regions of the world, however, the required equipment is either unavailable or insufficiently portable, and operators may not possess adequate training to make full use of the images obtained. Counterintuitively, these same regions are often well served by mobile phone networks, suggesting the possibility of leveraging portable, camera-enabled mobile phones for diagnostic imaging and telemedicine. Toward this end we have built a mobile phone-mounted light microscope and demonstrated its potential for clinical use by imaging P. falciparum-infected and sickle red blood cells in brightfield and M. tuberculosis-infected sputum samples in fluorescence with LED excitation. In all cases resolution exceeded that necessary to detect blood cell and microorganism morphology, and with the tuberculosis samples we took further advantage of the digitized images to demonstrate automated bacillus counting via image analysis software. We expect such a telemedicine system for global healthcare via mobile phone – offering inexpensive brightfield and fluorescence microscopy integrated with automated image analysis – to provide an important tool for disease diagnosis and screening, particularly in the developing world and rural areas where laboratory facilities are scarce but mobile phone infrastructure is extensive.
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              Diffraction phase microscopy for quantifying cell structure and dynamics.

              We have developed diffraction phase microscopy as a new technique for quantitative phase imaging of biological structures. The method combines the principles of common path interferometry and single-shot phase imaging and is characterized by subnanometer path-length stability and millisecond-scale acquisition time. The potential of the technique for quantifying nanoscale motions in live cells is demonstrated by experiments on red blood cells.
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                Author and article information

                Journal
                Biomed Opt Express
                BOE
                Biomedical Optics Express
                Optical Society of America
                2156-7085
                30 August 2011
                01 September 2011
                30 August 2011
                : 2
                : 9
                : 2721-2730
                Affiliations
                [1 ]Electrical Engineering Department, University of California at Los Angeles, CA 90095, USA
                [2 ]Bioengineering Department, University of California at Los Angeles, CA 90095, USA
                [3 ]California NanoSystems Institute (CNSI), University of California at Los Angeles, CA 90095, USA
                Author notes
                Article
                150686
                10.1364/BOE.2.002721
                3184880
                21991559
                a9b20a76-d4cb-477f-bf27-005588b16cba
                ©2011 Optical Society of America

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License, which permits download and redistribution, provided that the original work is properly cited. This license restricts the article from being modified or used commercially.

                History
                : 7 July 2011
                : 11 August 2011
                : 11 August 2011
                Funding
                Funded by: NSF
                Award ID: CAREER Award
                Funded by: ONR
                Award ID: Young Investigator Award 2009
                Funded by: NIH
                Award ID: Director’s New Innovator Award DP2OD006427
                Funded by: Gates Foundation
                Funded by: Vodafone Americas Foundation
                Funded by: NSF BISH
                Award ID: 0754880
                Award ID: 0930501
                Categories
                Microscopy
                Custom metadata
                True
                0

                Vision sciences
                (180.0180) microscopy,(090.1995) digital holography,(170.1650) coherence imaging

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