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      Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens

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          Abstract

          The increasing capabilities and ubiquity of mobile phones and their associated digital cameras offer the possibility of extending low-cost, portable diagnostic microscopy to underserved and low-resource areas. However, mobile phone microscopes created by adding magnifying optics to the phone's camera module have been unable to make use of the full image sensor due to the specialized design of the embedded camera lens, exacerbating the tradeoff between resolution and field of view inherent to optical systems. This tradeoff is acutely felt for diagnostic applications, where the speed and cost of image-based diagnosis is related to the area of the sample that can be viewed at sufficient resolution. Here we present a simple and low-cost approach to mobile phone microscopy that uses a reversed mobile phone camera lens added to an intact mobile phone to enable high quality imaging over a significantly larger field of view than standard microscopy. We demonstrate use of the reversed lens mobile phone microscope to identify red and white blood cells in blood smears and soil-transmitted helminth eggs in stool samples.

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          Most cited references4

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          Laboratory medicine in Africa: a barrier to effective health care.

          Providing health care in sub-Saharan Africa is a complex problem. Recent reports call for more resources to assist in the prevention and treatment of infectious diseases that affect this population, but policy makers, clinicians, and the public frequently fail to understand that diagnosis is essential to the prevention and treatment of disease. Access to reliable diagnostic testing is severely limited in this region, and misdiagnosis commonly occurs. Understandably, allocation of resources to diagnostic laboratory testing has not been a priority for resource-limited health care systems, but unreliable and inaccurate laboratory diagnostic testing leads to unnecessary expenditures in a region already plagued by resource shortages, promotes the perception that laboratory testing is unhelpful, and compromises patient care. We explore the barriers to implementing consistent testing within this region and illustrate the need for a more comprehensive approach to the diagnosis of infectious diseases, with an emphasis on making laboratory testing a higher priority.
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            Cell-Phone-Based Platform for Biomedical Device Development and Education Applications

            In this paper we report the development of two attachments to a commercial cell phone that transform the phone's integrated lens and image sensor into a 350× microscope and visible-light spectrometer. The microscope is capable of transmission and polarized microscopy modes and is shown to have 1.5 micron resolution and a usable field-of-view of 150×150 with no image processing, and approximately 350×350 when post-processing is applied. The spectrometer has a 300 nm bandwidth with a limiting spectral resolution of close to 5 nm. We show applications of the devices to medically relevant problems. In the case of the microscope, we image both stained and unstained blood-smears showing the ability to acquire images of similar quality to commercial microscope platforms, thus allowing diagnosis of clinical pathologies. With the spectrometer we demonstrate acquisition of a white-light transmission spectrum through diffuse tissue as well as the acquisition of a fluorescence spectrum. We also envision the devices to have immediate relevance in the educational field.
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              Cost-effective and compact wide-field fluorescent imaging on a cell-phone.

              We demonstrate wide-field fluorescent and darkfield imaging on a cell-phone with compact, light-weight and cost-effective optical components that are mechanically attached to the existing camera unit of the cell-phone. For this purpose, we used battery powered light-emitting diodes (LEDs) to pump the sample of interest from the side using butt-coupling, where the pump light was guided within the sample cuvette to uniformly excite the specimen. The fluorescent emission from the sample was then imaged using an additional lens that was positioned right in front of the existing lens of the cell-phone camera. Because the excitation occurs through guided waves that propagate perpendicular to our detection path, an inexpensive plastic colour filter was sufficient to create the dark-field background required for fluorescent imaging, without the need for a thin-film interference filter. We validate the performance of this platform by imaging various fluorescent micro-objects in 2 colours (i.e., red and green) over a large field-of-view (FOV) of ∼81 mm(2) with a raw spatial resolution of ∼20 μm. With additional digital processing of the captured cell-phone images, through the use of compressive sampling theory, we demonstrate ∼2 fold improvement in our resolving power, achieving ∼10 μm resolution without a trade-off in our FOV. Further, we also demonstrate darkfield imaging of non-fluorescent specimen using the same interface, where this time the scattered light from the objects is detected without the use of any filters. The capability of imaging a wide FOV would be exceedingly important to probe large sample volumes (e.g., >0.1 mL) of e.g., blood, urine, sputum or water, and for this end we also demonstrate fluorescent imaging of labeled white-blood cells from whole blood samples, as well as water-borne pathogenic protozoan parasites such as Giardia Lamblia cysts. Weighing only ∼28 g (∼1 ounce), this compact and cost-effective fluorescent imaging platform attached to a cell-phone could be quite useful especially for resource-limited settings, and might provide an important tool for wide-field imaging and quantification of various lab-on-a-chip assays developed for global health applications, such as monitoring of HIV+ patients for CD4 counts or viral load measurements.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                22 May 2014
                : 9
                : 5
                : e95330
                Affiliations
                [1]Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, California, United States of America
                McGill University, Canada
                Author notes

                Competing Interests: The authors have the following interests: This study was funded in part by Microsoft Research and Intel Corporation. Daniel Fletcher and Neil Switz are inventors on US Patent Application 20110009163, “High Numerical Aperture Telemicroscopy Apparatus”, filed January 13th, 2011. Co-author Daniel Fletcher is a co-founder of CellScope, Inc., a company commercializing a cellphone-based otoscope. Co-authors Daniel Fletcher and Neil Switz hold shares in CellScope, Inc. The shares belonging to Neil Switz are held by The Regents of the University of California and disposition is determined by them according to a fixed formula. Cellscope, Inc. neither had nor has any involvement with the project described in this paper. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: NAS MVD DAF. Performed the experiments: NAS MVD. Analyzed the data: NAS MVD DAF. Wrote the paper: NAS MVD DAF.

                Article
                PONE-D-13-50181
                10.1371/journal.pone.0095330
                4031072
                24854188
                993d3b67-8f23-42a3-a80a-7ca91d04d17a
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 November 2013
                : 26 March 2014
                Page count
                Pages: 7
                Funding
                This work was supported by grants from Microsoft Research, Intel Corporation, the Bill and Melinda Gates Foundation, and the Blum Center at UC Berkeley. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biotechnology
                Bioengineering
                Medical Devices and Equipment
                Engineering and Technology
                Medicine and Health Sciences
                Diagnostic Medicine
                Pathology and Laboratory Medicine
                Public and Occupational Health
                Global Health
                Health Screening
                Physical Sciences
                Physics
                Condensed Matter Physics
                Optics

                Uncategorized
                Uncategorized

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