Publications by authors named "Onur Mudanyali"

23 Publications

  • Page 1 of 1

A Smartphone-Based Rapid Telemonitoring System for Ebola and Marburg Disease Surveillance.

ACS Sens 2019 01 28;4(1):61-68. Epub 2018 Dec 28.

Division of Molecular and Translational Sciences , United States Army Medical Research Institute of Infectious Diseases , Frederick , Maryland 21702 , United States.

We have developed a digital and multiplexed platform for the rapid detection and telemonitoring of infections caused by Ebola and Marburg filoviruses. The system includes a flow cell assay cartridge that captures specific antibodies with microarrayed recombinant antigens from all six species of filovirus, and a smartphone fluorescent reader for high-performance interpretation of test results. Multiplexed viral proteins, which are expandable to include greater numbers of probes, were incorporated to obtain highest confidence results by cross-correlation, and a custom smartphone application was developed for data analysis, interpretation, and communication. The smartphone reader utilizes an opto-electro-mechanical hardware attachment that snaps at the back of a Motorola smartphone and provides a user interface to manage the operation, acquire test results, and communicate with cloud service. The application controls the hardware attachment to turn on LEDs and digitally record the optically enhanced images. Assay processing time is approximately 20 min for microliter amounts of blood, and test results are digitally processed and displayed within 15 s. Furthermore, a secure cloud service was developed for the telemonitoring of test results generated by the smartphone readers in the field. Assay system results were tested with sera from nonhuman primates that received a live attenuated EBOV vaccine. This integrated system will provide a rapid, reliable, and digital solution to prevent the rapid overwhelming of medical systems and resources during EVD or MVD outbreaks. Further, this disease-monitoring system will be useful in resource-limited countries where there is a need for dispersed laboratory analysis of recent or active infections.
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http://dx.doi.org/10.1021/acssensors.8b00842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350200PMC
January 2019

Automated single-cell motility analysis on a chip using lensfree microscopy.

Sci Rep 2014 Apr 17;4:4717. Epub 2014 Apr 17.

1] Bioengineering Department, University of California Los Angeles, Los Angeles, California, United States of America [2] California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, United States of America [3] Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, United States of America.

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.
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http://dx.doi.org/10.1038/srep04717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989554PMC
April 2014

Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses.

Nat Photonics 2013 Mar;7(3)

Electrical Engineering Department, University of California, Los Angeles, California 90095, USA ; Bioengineering Department, University of California, Los Angeles, California 90095, USA ; California NanoSystems Institute, University of California, Los Angeles, California 90095, USA ; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.

The direct observation of nanoscale objects is a challenging task for optical microscopy because the scattering from an individual nanoparticle is typically weak at optical wavelengths. Electron microscopy therefore remains one of the gold standard visualization methods for nanoparticles, despite its high cost, limited throughput and restricted field-of-view. Here, we describe a high-throughput, on-chip detection scheme that uses biocompatible wetting films to self-assemble aspheric liquid nanolenses around individual nanoparticles to enhance the contrast between the scattered and background light. We model the effect of the nanolens as a spatial phase mask centred on the particle and show that the holographic diffraction pattern of this effective phase mask allows detection of sub-100 nm particles across a large field-of-view of >20 mm. As a proof-of-concept demonstration, we report on-chip detection of individual polystyrene nanoparticles, adenoviruses and influenza A (H1N1) viral particles.
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http://dx.doi.org/10.1038/nphoton.2012.337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866034PMC
March 2013

Cellphone-based devices for bioanalytical sciences.

Anal Bioanal Chem 2014 May 28;406(14):3263-77. Epub 2013 Nov 28.

HSG-IMIT - Institut für Mikro- und Informationstechnik, Georges-Koehler-Allee 103, 79110, Freiburg, Germany.

During the last decade, there has been a rapidly growing trend toward the use of cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have been used for digital microscopy, cytometry, read-out of immunoassays and lateral flow tests, electrochemical and surface plasmon resonance based bio-sensing, colorimetric detection and healthcare monitoring, among others. Cellphone can be considered as one of the most prospective devices for the development of next-generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare delivery and personalized medicine. With more than 6.5 billion cellphone subscribers worldwide and approximately 1.6 billion new devices being sold each year, cellphone technology is also creating new business and research opportunities. Many cellphone-based devices, such as those targeted for diabetic management, weight management, monitoring of blood pressure and pulse rate, have already become commercially-available in recent years. In addition to such monitoring platforms, several other CBDs are also being introduced, targeting e.g., microscopic imaging and sensing applications for medical diagnostics using novel computational algorithms and components already embedded on cellphones. This report aims to review these recent developments in CBDs for bioanalytical sciences along with some of the challenges involved and the future opportunities.
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http://dx.doi.org/10.1007/s00216-013-7473-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024356PMC
May 2014

Optical detection and sizing of single nanoparticles using continuous wetting films.

ACS Nano 2013 Sep 1;7(9):7601-9. Epub 2013 Aug 1.

CEA, LETI, MINATEC, 17 rue des martyrs, 38054 Grenoble cedex 9, France.

The physical interaction between nanoscale objects and liquid interfaces can create unique optical properties, enhancing the signatures of the objects with subwavelength features. Here we show that the evaporation on a wetting substrate of a polymer solution containing submicrometer or nanoscale particles creates liquid microlenses that arise from the local deformations of the continuous wetting film. These microlenses have properties similar to axicon lenses that are known to create beams with a long depth of focus. This enhanced depth of focus allows detection of single nanoparticles using a low-magnification microscope objective lens, achieving a relatively wide field-of-view, while also lifting the constraints on precise focusing onto the object plane. Hence, by creating these liquid axicon lenses through spatial deformations of a continuous thin wetting film, we transfer the challenge of imaging individual nanoparticles to detecting the light focused by these lenses. As a proof of concept, we demonstrate the detection and sizing of single nanoparticles (100 and 200 nm), CpGV granuloviruses, as well as Staphylococcus epidermidis bacteria over a wide field-of-view of 5.10 × 3.75 mm(2) using a 5× objective lens with a numerical aperture of 0.15. In addition to conventional lens-based microscopy, this continuous wetting-film-based approach is also applicable to lens-free computational on-chip imaging, which can be used to detect single nanoparticles over a large field-of-view of >20-30 mm(2). These results could be especially useful for high-throughput field analysis of nanoscale objects using compact and cost-effective microscope designs.
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http://dx.doi.org/10.1021/nn403431yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909561PMC
September 2013

Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses.

Lab Chip 2013 Jun;13(11):2028-35

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

The development of lensfree on-chip microscopy in the past decade has opened up various new possibilities for biomedical imaging across ultra-large fields of view using compact, portable, and cost-effective devices. However, until recently, its ability to resolve fine features and detect ultra-small particles has not rivalled the capabilities of the more expensive and bulky laboratory-grade optical microscopes. In this Frontier Review, we highlight the developments over the last two years that have enabled computational lensfree holographic on-chip microscopy to compete with and, in some cases, surpass conventional bright-field microscopy in its ability to image nano-scale objects across large fields of view, yielding giga-pixel phase and amplitude images. Lensfree microscopy has now achieved a numerical aperture as high as 0.92, with a spatial resolution as small as 225 nm across a large field of view e.g., >20 mm(2). Furthermore, the combination of lensfree microscopy with self-assembled nanolenses, forming nano-catenoid minimal surfaces around individual nanoparticles has boosted the image contrast to levels high enough to permit bright-field imaging of individual particles smaller than 100 nm. These capabilities support a number of new applications, including, for example, the detection and sizing of individual virus particles using field-portable computational on-chip microscopes.
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http://dx.doi.org/10.1039/c3lc50222hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813829PMC
June 2013

Lensfree computational microscopy tools for cell and tissue imaging at the point-of-care and in low-resource settings.

Stud Health Technol Inform 2013 ;185:299-323

Electrical Engineering Department, University of California, Los Angeles, CA, USA.

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, Papanicolaou (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.
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April 2014

Optical imaging techniques for point-of-care diagnostics.

Lab Chip 2013 Jan 9;13(1):51-67. Epub 2012 Oct 9.

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

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.
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http://dx.doi.org/10.1039/c2lc40864cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510351PMC
January 2013

Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy.

Nat Methods 2012 Sep 30;9(9):889-95. Epub 2012 Aug 30.

Electrical Engineering Department, University of California, Los Angeles, Los Angeles, California, USA.

We discuss unique features of lens-free computational imaging tools and report some of their emerging results for wide-field on-chip microscopy, such as the achievement of a numerical aperture (NA) of ∼0.8-0.9 across a field of view (FOV) of more than 20 mm(2) or an NA of ∼0.1 across a FOV of ∼18 cm(2), which corresponds to an image with more than 1.5 gigapixels. We also discuss the current challenges that these computational on-chip microscopes face, shedding light on their future directions and applications.
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http://dx.doi.org/10.1038/nmeth.2114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477589PMC
September 2012

Integrated rapid-diagnostic-test reader platform on a cellphone.

Lab Chip 2012 Aug 17;12(15):2678-86. Epub 2012 May 17.

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

We demonstrate a cellphone-based rapid-diagnostic-test (RDT) reader platform that can work with various lateral flow immuno-chromatographic assays and similar tests to sense the presence of a target analyte in a sample. This compact and cost-effective digital RDT reader, weighing only ~65 g, mechanically attaches to the existing camera unit of a cellphone, where various types of RDTs can be inserted to be imaged in reflection or transmission modes under light-emitting diode (LED)-based illumination. Captured raw images of these tests are then digitally processed (within less than 0.2 s per image) through a smart application running on the cellphone for validation of the RDT, as well as for automated reading of its diagnostic result. The same smart application then transmits the resulting data, together with the RDT images and other related information (e.g., demographic data), to a central server, which presents the diagnostic results on a world map through geo-tagging. This dynamic spatio-temporal map of various RDT results can then be viewed and shared using internet browsers or through the same cellphone application. We tested this platform using malaria, tuberculosis (TB) and HIV RDTs by installing it on both Android-based smartphones and an iPhone. Providing real-time spatio-temporal statistics for the prevalence of various infectious diseases, this smart RDT reader platform running on cellphones might assist healthcare professionals and policymakers to track emerging epidemics worldwide and help epidemic preparedness.
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http://dx.doi.org/10.1039/c2lc40235aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390446PMC
August 2012

Lensfree computational microscopy tools for cell and tissue imaging at the point-of-care and in low-resource settings.

Anal Cell Pathol (Amst) 2012 ;35(4):229-47

Electrical Engineering Department, University of California, Los Angeles, USA.

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.
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http://dx.doi.org/10.3233/ACP-2012-0057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684710PMC
October 2012

Portable and cost-effective pixel super-resolution on-chip microscope for telemedicine applications.

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:8207-10

Department of Electrical Engineering, University of California, Los Angeles 90095, USA.

We report a field-portable lensless on-chip microscope with a lateral resolution of <1 μm and a large field-of-view of ~24 mm(2). This microscope is based on digital in-line holography and a pixel super-resolution algorithm to process multiple lensfree holograms and obtain a single high-resolution hologram. In its compact and cost-effective design, we utilize 23 light emitting diodes butt-coupled to 23 multi-mode optical fibers, and a simple optical filter, with no moving parts. Weighing only ~95 grams, we demonstrate the performance of this field-portable microscope by imaging various objects including human malaria parasites in thin blood smears.
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http://dx.doi.org/10.1109/IEMBS.2011.6092024DOI Listing
May 2012

Lensfree super-resolution holographic microscopy using wetting films on a chip.

Opt Express 2011 Aug;19(18):17378-89

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

We investigate the use of wetting films to significantly improve the imaging performance of lensfree pixel super-resolution on-chip microscopy, achieving < 1 µm spatial resolution over a large imaging area of ~24 mm(2). Formation of an ultra-thin wetting film over the specimen effectively creates a micro-lens effect over each object, which significantly improves the signal-to-noise-ratio and therefore the resolution of our lensfree images. We validate the performance of this approach through lensfree on-chip imaging of various objects having fine morphological features (with dimensions of e.g., ≤0.5 µm) such as Escherichia coli (E. coli), human sperm, Giardia lamblia trophozoites, polystyrene micro beads as well as red blood cells. These results are especially important for the development of highly sensitive field-portable microscopic analysis tools for resource limited settings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258299PMC
http://dx.doi.org/10.1364/OE.19.017378DOI Listing
August 2011

Lensfree On-Chip Microscopy and Tomography for Bio-Medical Applications.

IEEE J Sel Top Quantum Electron 2011 Jul;18(3):1059-1072

Electrical Engineering Department at the University of California, Los Angeles, CA 90095, USA ( http://innovate.ee.ucla.edu/ ). California NanoSystems Institute (CNSI), at the University of California, Los Angeles, CA 90095, USA.

Lensfree on-chip holographic microscopy is an emerging technique that offers imaging of biological specimens over a large field-of-view without using any lenses or bulky optical components. Lending itself to a compact, cost-effective and mechanically robust architecture, lensfree on-chip holographic microscopy can offer an alternative toolset addressing some of the emerging needs of microscopic analysis and diagnostics in low-resource settings, especially for telemedicine applications. In this review, we summarize the latest achievements in lensfree optical microscopy based on partially coherent on-chip holography, including portable telemedicine microscopy, cell-phone based microscopy and field-portable optical tomographic microscopy. We also discuss some of the future directions for telemedicine microscopy and its prospects to help combat various global health challenges.
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http://dx.doi.org/10.1109/JSTQE.2011.2161460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902671PMC
July 2011

Lensfree on-chip holography facilitates novel microscopy applications.

SPIE Newsroom 2010 May

Electrical Engineering Department, University of California at Los Angeles (UCLA), Los Angeles, CA.

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http://dx.doi.org/10.1117/2.1201005.002947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107039PMC
May 2010

Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array.

Lab Chip 2011 Apr 1;11(7):1276-9. Epub 2011 Mar 1.

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

We report a portable lensless on-chip microscope that can achieve <1 µm resolution over a wide field-of-view of ∼ 24 mm(2) without the use of any mechanical scanning. This compact on-chip microscope weighs ∼ 95 g and is based on partially coherent digital in-line holography. Multiple fiber-optic waveguides are butt-coupled to light emitting diodes, which are controlled by a low-cost micro-controller to sequentially illuminate the sample. The resulting lensfree holograms are then captured by a digital sensor-array and are rapidly processed using a pixel super-resolution algorithm to generate much higher resolution holographic images (both phase and amplitude) of the objects. This wide-field and high-resolution on-chip microscope, being compact and light-weight, would be important for global health problems such as diagnosis of infectious diseases in remote locations. Toward this end, we validate the performance of this field-portable microscope by imaging human malaria parasites (Plasmodium falciparum) in thin blood smears. Our results constitute the first-time that a lensfree on-chip microscope has successfully imaged malaria parasites.
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http://dx.doi.org/10.1039/c0lc00684jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151573PMC
April 2011

Detection of waterborne parasites using field-portable and cost-effective lensfree microscopy.

Lab Chip 2010 Sep 9;10(18):2419-23. Epub 2010 Aug 9.

Electrical Engineering Department, UCLA, CA 90095, USA.

Protection of human health and well-being through water quality management is an important goal for both the developed and the developing parts of the world. In the meantime, insufficient disinfection techniques still fail to eliminate pathogenic contaminants in freshwater as well as recreational water resources. Therefore, there is a significant need for screening of water quality to prevent waterborne outbreaks and incidents of water-related diseases. Toward this end, here we investigate the use of a field-portable and cost-effective lensfree holographic microscope to image and detect pathogenic protozoan parasites such as Giardia Lamblia and Cryptosporidium Parvum at low concentration levels. This compact lensless microscope (O. Mudanyali et al., Lab Chip, 2010, 10, 1417-1428), weighing approximately 46 grams, achieves a numerical aperture of approximately 0.1-0.2 over an imaging field of view that is more than an order of magnitude larger than a typical 10X objective lens, and therefore may provide an important high-throughput analysis tool for combating waterborne diseases especially in resource limited settings.
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http://dx.doi.org/10.1039/c004829aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2942761PMC
September 2010

High-throughput lens-free blood analysis on a chip.

Anal Chem 2010 Jun;82(11):4621-7

Electrical Engineering Department, University of California, Los Angeles, California 90095, USA.

We present a detailed investigation of the performance of lens-free holographic microscopy toward high-throughput on-chip blood analysis. Using a spatially incoherent source that is emanating from a large aperture, automated counting of red blood cells with minimal sample preparation steps at densities reaching up to approximately 0.4 x 10(6) cells/muL is presented. Using the same lens-free holographic microscopy platform, we also characterize the volume of the red blood cells at the single-cell level through recovery of the optical phase information of each cell. We further demonstrate the measurement of the hemoglobin concentration of whole blood samples as well as automated counting of white blood cells, also yielding spatial resolution at the subcellular level sufficient to differentiate granulocytes, monocytes, and lymphocytes from each other. These results uncover the prospects of lens-free holographic on-chip imaging to provide a useful tool for global health problems, especially by facilitating whole blood analysis in resource-poor environments.
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http://dx.doi.org/10.1021/ac1007915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892055PMC
June 2010

Lensfree microscopy on a cellphone.

Lab Chip 2010 Jul 6;10(14):1787-92. Epub 2010 May 6.

UCLA Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

We demonstrate lensfree digital microscopy on a cellphone. This compact and light-weight holographic microscope installed on a cellphone does not utilize any lenses, lasers or other bulky optical components and it may offer a cost-effective tool for telemedicine applications to address various global health challenges. Weighing approximately 38 grams (<1.4 ounces), this lensfree imaging platform can be mechanically attached to the camera unit of a cellphone where the samples are loaded from the side, and are vertically illuminated by a simple light-emitting diode (LED). This incoherent LED light is then scattered from each micro-object to coherently interfere with the background light, creating the lensfree hologram of each object on the detector array of the cellphone. These holographic signatures captured by the cellphone permit reconstruction of microscopic images of the objects through rapid digital processing. We report the performance of this lensfree cellphone microscope by imaging various sized micro-particles, as well as red blood cells, white blood cells, platelets and a waterborne parasite (Giardia lamblia).
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http://dx.doi.org/10.1039/c003477kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941438PMC
July 2010

Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications.

Lab Chip 2010 Jun 19;10(11):1417-28. Epub 2010 Apr 19.

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

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. In the meantime, microscopy in resource-limited settings has requirements significantly different from those encountered in advanced laboratories, and such imaging devices should be cost-effective, compact, light-weight and appropriately accurate and simple to be usable by minimally trained personnel. Furthermore, these portable microscopes should ideally be digitally integrated as part of a telemedicine network that connects various mobile health-care providers to a central laboratory or hospital. Toward this end, here we demonstrate a lensless on-chip microscope weighing approximately 46 grams with dimensions smaller than 4.2 cm x 4.2 cm x 5.8 cm that achieves sub-cellular resolution over a large field of view of approximately 24 mm(2). This compact and light-weight microscope is based on digital in-line holography and does not need any lenses, bulky optical/mechanical components or coherent sources such as lasers. Instead, it utilizes a simple light-emitting-diode (LED) and a compact opto-electronic sensor-array to record lensless holograms of the objects, which then permits rapid digital reconstruction of regular transmission or differential interference contrast (DIC) images of the objects. Because this lensless incoherent holographic microscope has orders-of-magnitude improved light collection efficiency and is very robust to mechanical misalignments it may offer a cost-effective tool especially for telemedicine applications involving various global health problems in resource limited settings.
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http://dx.doi.org/10.1039/c000453gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902728PMC
June 2010

Color and monochrome lensless on-chip imaging of Caenorhabditis elegans over a wide field-of-view.

Lab Chip 2010 May 19;10(9):1109-12. Epub 2010 Mar 19.

Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA.

We demonstrate color and monochrome on-chip imaging of Caenorhabditis elegans samples over a wide field-of-view using incoherent lensless in-line holography. Digital reconstruction of the recorded lensless holograms rapidly creates the C. elegans images within <1 s over a field-of-view of >24 mm2. By digitally combining the reconstructed images at three different wavelengths (red, green and blue), color images of dyed samples are also acquired. This wide field-of-view and compact on-chip imaging modality also permits straightforward integration with microfluidic systems.
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http://dx.doi.org/10.1039/c001200aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869489PMC
May 2010

Lensfree holographic imaging of antibody microarrays for high-throughput detection of leukocyte numbers and function.

Anal Chem 2010 May;82(9):3736-44

Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.

Characterization of leukocytes is an integral part of blood analysis and blood-based diagnostics. In the present paper, we combine lensless holographic imaging with antibody microarrays for rapid and multiparametric analysis of leukocytes from human blood. Monoclonal antibodies (Abs) specific for leukocyte surface antigens (CD4 and CD8) and cytokines (TNF-alpha, IFN-gamma, IL-2) were printed in an array so as to juxtapose cell capture and cytokine detection antibody (Ab) spots. Integration of Ab microarrays into a microfluidic flow chamber (4 muL volume) followed by incubation with human blood resulted in capture of CD4 and CD8 T-cells on specific Ab spots. On-chip mitogenic activation of these cells induced release of cytokine molecules that were subsequently captured on neighboring anticytokine Ab spots. The binding of IL-2, TNF-alpha, and IFN-gamma molecules on their respective Ab spots was detected using horseradish peroxidase (HRP)-labeled anticytokine Abs and a visible color reagent. Lensfree holographic imaging was then used to rapidly ( approximately 4 s) enumerate CD4 and CD8 T-lymphocytes captured on Ab spots and to quantify the cytokine signal emanating from IL-2, TNF-alpha, and IFN-gamma spots on the same chip. To demonstrate the utility of our approach for infectious disease monitoring, blood samples of healthy volunteers and human immunodeficiency virus (HIV)-infected patients were analyzed to determine the CD4/CD8 ratio, an important HIV/AIDS diagnostic marker. The ratio obtained by lensfree on-chip imaging of CD4 and CD8 T-cells captured on Ab spots was in close agreement with conventional microscopy-based cell counting. The present paper, describing tandem use of Ab microarrays and lensfree holographic imaging, paves the way for future development of miniature cytometry devices for multiparametric blood analysis at the point of care or in a resource-limited setting.
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http://dx.doi.org/10.1021/ac100142aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864520PMC
May 2010

Lensless on-chip imaging of cells provides a new tool for high-throughput cell-biology and medical diagnostics.

J Vis Exp 2009 Dec 14(34). Epub 2009 Dec 14.

Electrical Engineering Department, University of California, Los Angeles, CA, USA.

Conventional optical microscopes image cells by use of objective lenses that work together with other lenses and optical components. While quite effective, this classical approach has certain limitations for miniaturization of the imaging platform to make it compatible with the advanced state of the art in microfluidics. In this report, we introduce experimental details of a lensless on-chip imaging concept termed LUCAS (Lensless Ultra-wide field-of-view Cell monitoring Array platform based on Shadow imaging) that does not require any microscope objectives or other bulky optical components to image a heterogeneous cell solution over an ultra-wide field of view that can span as large as approximately 18 cm(2). Moreover, unlike conventional microscopes, LUCAS can image a heterogeneous cell solution of interest over a depth-of-field of approximately 5 mm without the need for refocusing which corresponds to up to approximately 9 mL sample volume. This imaging platform records the shadows (i.e., lensless digital holograms) of each cell of interest within its field of view, and automated digital processing of these cell shadows can determine the type, the count and the relative positions of cells within the solution. Because it does not require any bulky optical components or mechanical scanning stages it offers a significantly miniaturized platform that at the same time reduces the cost, which is quite important for especially point of care diagnostic tools. Furthermore, the imaging throughput of this platform is orders of magnitude better than conventional optical microscopes, which could be exceedingly valuable for high-throughput cell-biology experiments.
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http://dx.doi.org/10.3791/1650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149969PMC
December 2009