Ahmet F Coskun

All Publications

• Dense transcript profiling in single cells by image correlation decoding NATURE METHODS Coskun, A. F., Cai, L. 2016; 13 (8): 657-?

  Abstract

  Sequential barcoded fluorescent in situ hybridization (seqFISH) allows large numbers of molecular species to be accurately detected in single cells, but multiplexing is limited by the density of barcoded objects. We present correlation FISH (corrFISH), a method to resolve dense temporal barcodes in sequential hybridization experiments. Using corrFISH, we quantified highly expressed ribosomal protein genes in single cultured cells and mouse thymus sections, revealing cell-type-specific gene expression.

  View details for DOI 10.1038/NMETH.3895

  View details for Web of Science ID 000385188700020

  View details for PubMedID 27271198

  View details for PubMedCentralID PMC4965285

• Cellular identity at the single-cell level MOLECULAR BIOSYSTEMS Coskun, A. F., Eser, U., Islam, S. 2016; 12 (10): 2965-2979

  Abstract

  A single cell creates surprising heterogeneity in a multicellular organism. While every organismal cell shares almost an identical genome, molecular interactions in cells alter the use of DNA sequences to modulate the gene of interest for specialization of cellular functions. Each cell gains a unique identity through molecular coding across the DNA, RNA, and protein conversions. On the other hand, loss of cellular identity leads to critical diseases such as cancer. Most cell identity dissection studies are based on bulk molecular assays that mask differences in individual cells. To probe cell-to-cell variability in a population, we discuss single cell approaches to decode the genetic, epigenetic, transcriptional, and translational mechanisms for cell identity formation. In combination with molecular instructions, the physical principles behind cell identity determination are examined. Deciphering and reprogramming cellular types impact biology and medicine.

  View details for DOI 10.1039/c6mb00388e

  View details for Web of Science ID 000384405400002

  View details for PubMedID 27460751

• Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view SCIENTIFIC REPORTS Coskun, A. F., Cetin, A. E., Galarreta, B. C., Alvarez, D. A., Altug, H., Ozcan, A. 2014; 4

  Abstract

  We demonstrate a high-throughput biosensing device that utilizes microfluidics based plasmonic microarrays incorporated with dual-color on-chip imaging toward real-time and label-free monitoring of biomolecular interactions over a wide field-of-view of >20 mm(2). Weighing 40 grams with 8.8 cm in height, this biosensor utilizes an opto-electronic imager chip to record the diffraction patterns of plasmonic nanoapertures embedded within microfluidic channels, enabling real-time analyte exchange. This plasmonic chip is simultaneously illuminated by two different light-emitting-diodes that are spectrally located at the right and left sides of the plasmonic resonance mode, yielding two different diffraction patterns for each nanoaperture array. Refractive index changes of the medium surrounding the near-field of the nanostructures, e.g., due to molecular binding events, induce a frequency shift in the plasmonic modes of the nanoaperture array, causing a signal enhancement in one of the diffraction patterns while suppressing the other. Based on ratiometric analysis of these diffraction images acquired at the detector-array, we demonstrate the proof-of-concept of this biosensor by monitoring in real-time biomolecular interactions of protein A/G with immunoglobulin G (IgG) antibody. For high-throughput on-chip fabrication of these biosensors, we also introduce a deep ultra-violet lithography technique to simultaneously pattern thousands of plasmonic arrays in a cost-effective manner.

  View details for DOI 10.1038/srep06789

  View details for Web of Science ID 000343979000004

  View details for PubMedID 25346102

  View details for PubMedCentralID PMC4209447

• Single-cell in situ RNA profiling by sequential hybridization NATURE METHODS Lubeck, E., Coskun, A. F., Zhiyentayev, T., Ahmad, M., Cai, L. 2014; 11 (4): 360-361

  View details for DOI 10.1038/nmeth.2892

  View details for Web of Science ID 000333749900006

  View details for PubMedID 24681720

  View details for PubMedCentralID PMC4085791

• Handheld high-throughput plasmonic biosensor using computational on-chip imaging LIGHT-SCIENCE & APPLICATIONS Cetin, A. E., Coskun, A. F., Galarreta, B. C., Huang, M., Herman, D., Ozcan, A., Altug, H. 2014; 3

  View details for DOI 10.1038/lsa.2014.3

  View details for Web of Science ID 000331998400002

• Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses NATURE PHOTONICS Mudanyali, O., McLeod, E., Luo, W., Greenbaum, A., Coskun, A. F., Hennequin, Y., Allier, C. P., Ozcan, A. 2013; 7 (3): 247-254

  Abstract

  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(2). As a proof-of-concept demonstration, we report on-chip detection of individual polystyrene nanoparticles, adenoviruses and influenza A (H1N1) viral particles.

  View details for DOI 10.1038/NPHOTON.2012.337

  View details for Web of Science ID 000316154700021

  View details for PubMedID 24358054

  View details for PubMedCentralID PMC3866034

• Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy NATURE METHODS Greenbaum, A., Luo, W., Su, T., Goeroecs, Z., Xue, L., Isikman, S. O., Coskun, A. F., Mudanyali, O., Ozcan, A. 2012; 9 (9): 889-895

  Abstract

  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.

  View details for DOI 10.1038/nmeth.2114

  View details for Web of Science ID 000308497800020

  View details for PubMedID 22936170

  View details for PubMedCentralID PMC3477589

• 3D-printed smartphone-based point of care tool for fluorescence- and magnetophoresis-based cytometry. Lab on a chip Knowlton, S., Joshi, A., Syrrist, P., Coskun, A. F., Tasoglu, S. 2017

  Abstract

  In developing countries, there are often limited resources available to provide important medical diagnostics, which severely limits our ability to diagnose conditions and administer proper treatment, leading to high mortality rates for treatable conditions. Here, we propose a multiplex tool capable of density-based cell sorting via magnetic focusing in parallel with fluorescence imaging to provide highly specific clinical assays. While many cell sorting techniques and fluorescence microscopes generally are costly and require extensive user training, limiting accessibility and usability in developing countries, this device is compact, low-cost, and portable. The device can separate cells on the basis of density, which can be used to identify cell type and cell activity, and image the cells in either brightfield, darkfield, or fluorescent imaging modes using the built-in smartphone camera. The combination of these two powerful and versatile techniques - magnetic focusing and fluorescence imaging - will make this platform broadly applicable to a range of biomedical assays. Clinical applications include cell cytometry and immunocytochemistry-based assays in limited-resource settings, which can ultimately help to improve worldwide accessibility to medical diagnostics.

  View details for DOI 10.1039/c7lc00706j

  View details for PubMedID 28726914

• Art on the Nanoscale and Beyond ADVANCED MATERIALS Yetisen, A. K., Coskun, A. F., England, G., Cho, S., Butt, H., Hurwitz, J., Kolle, M., Khademhosseini, A., Hart, A. J., Folch, A., Yun, S. H. 2016; 28 (9): 1724-1742

  Abstract

  Methods of forming and patterning materials at the nano- and microscales are finding increased use as a medium of artistic expression, and as a vehicle for communicating scientific advances to a broader audience. While sharing many attributes of other art forms, miniaturized art enables the direct engagement of sensory aspects such as sight and touch for materials and structures that are otherwise invisible to the eye. The historical uses of nano-/microscale materials and imaging techniques in arts and sciences are presented. The motivations to create artwork at small scales are discussed, and representations in scientific literature and exhibitions are explored. Examples are presented using semiconductors, microfluidics, and nanomaterials as the artistic media; these utilized techniques including micromachining, focused ion beam milling, two-photon polymerization, and bottom-up nanostructure growth. Finally, the technological factors that limit the implementation of artwork at miniature scales are identified, and potential future directions are discussed. As research marches toward even smaller length scales, innovative and engaging visualizations and artistic endeavors will have growing implications on education, communication, policy making, media activism, and public perception of science and technology.

  View details for DOI 10.1002/adma.201502382

  View details for Web of Science ID 000372176200001

  View details for PubMedID 26671704

• Bioart. Trends in biotechnology Yetisen, A. K., Davis, J., Coskun, A. F., Church, G. M., Hyun Yun, S. 2015; 33 (12): 724-734

  Abstract

  Bioart is a creative practice that adapts scientific methods and draws inspiration from the philosophical, societal, and environmental implications of recombinant genetics, molecular biology, and biotechnology. Some bioartists foster inter- disciplinary relationships that blur distinctions between art and science. Others emphasize critical responses to emerging trends in the life sciences. Since bioart can be combined with realistic views of scientific developments, it may help inform the public about science. Artistic responses to biotechnology also integrate cultural commentary resembling political activism. Art is not only about ‘responses’, however. Bioart can also initiate new science and engineer- ing concepts, foster openness to collaboration and increasing scientific literacy, and help to form the basis of artists’ future relationships with the communities of biology and the life sciences.

  View details for PubMedID 26617334

• Entrepreneurship LAB ON A CHIP Yetisen, A. K., Volpatti, L. R., Coskun, A. F., Cho, S., Kamrani, E., Butt, H., Khademhosseini, A., Yun, S. H. 2015; 15 (18): 3638-3660

  Abstract

  High-tech businesses are the driving force behind global knowledge-based economies. Academic institutions have positioned themselves to serve the high-tech industry through consulting, licensing, and university spinoffs. The awareness of commercialization strategies and building an entrepreneurial culture can help academics to efficiently transfer their inventions to the market to achieve the maximum value. Here, the concept of high-tech entrepreneurship is discussed from lab to market in technology-intensive sectors such as nanotechnology, photonics, and biotechnology, specifically in the context of lab-on-a-chip devices. This article provides strategies for choosing a commercialization approach, financing a startup, marketing a product, and planning an exit. Common reasons for startup company failures are discussed and guidelines to overcome these challenges are suggested. The discussion is supplemented with case studies of successful and failed companies. Identifying a market need, assembling a motivated management team, managing resources, and obtaining experienced mentors lead to a successful exit.

  View details for DOI 10.1039/c5lc00577a

  View details for Web of Science ID 000360114300003

  View details for PubMedID 26245815

• Computational imaging, sensing and diagnostics for global health applications CURRENT OPINION IN BIOTECHNOLOGY Coskun, A. F., Ozcan, A. 2014; 25: 8-16

  Abstract

  In this review, we summarize some of the recent work in emerging computational imaging, sensing and diagnostics techniques, along with some of the complementary non-computational modalities that can potentially transform the delivery of health care globally. As computational resources are becoming more and more powerful, while also getting cheaper and more widely available, traditional imaging, sensing and diagnostic tools will continue to experience a revolution through simplification of their designs, making them compact, light-weight, cost-effective, and yet quite powerful in terms of their performance when compared to their bench-top counterparts.

  View details for DOI 10.1016/j.copbio.2013.08.008

  View details for Web of Science ID 000331505800003

  View details for PubMedID 24484875

• Spectral Demultiplexing in Holographic and Fluorescent On-chip Microscopy SCIENTIFIC REPORTS Sencan, I., Coskun, A. F., Sikora, U., Ozcan, A. 2014; 4

  Abstract

  Lensfree on-chip imaging and sensing platforms provide compact and cost-effective designs for various telemedicine and lab-on-a-chip applications. In this work, we demonstrate computational solutions for some of the challenges associated with (i) the use of broadband, partially-coherent illumination sources for on-chip holographic imaging, and (ii) multicolor detection for lensfree fluorescent on-chip microscopy. Specifically, we introduce spectral demultiplexing approaches that aim to digitally narrow the spectral content of broadband illumination sources (such as wide-band light emitting diodes or even sunlight) to improve spatial resolution in holographic on-chip microscopy. We also demonstrate the application of such spectral demultiplexing approaches for wide-field imaging of multicolor fluorescent objects on a chip. These computational approaches can be used to replace e.g., thin-film interference filters, gratings or other optical components used for spectral multiplexing/demultiplexing, which can form a desirable solution for cost-effective and compact wide-field microscopy and sensing needs on a chip.

  View details for DOI 10.1038/srep03760

  View details for Web of Science ID 000329850400001

  View details for PubMedID 24441627

• Albumin testing in urine using a smart-phone LAB ON A CHIP Coskun, A. F., Nagi, R., Sadeghi, K., Phillips, S., Ozcan, A. 2013; 13 (21): 4231-4238

  Abstract

  We demonstrate a digital sensing platform, termed Albumin Tester, running on a smart-phone that images and automatically analyses fluorescent assays confined within disposable test tubes for sensitive and specific detection of albumin in urine. This light-weight and compact Albumin Tester attachment, weighing approximately 148 grams, is mechanically installed on the existing camera unit of a smart-phone, where test and control tubes are inserted from the side and are excited by a battery powered laser diode. This excitation beam, after probing the sample of interest located within the test tube, interacts with the control tube, and the resulting fluorescent emission is collected perpendicular to the direction of the excitation, where the cellphone camera captures the images of the fluorescent tubes through the use of an external plastic lens that is inserted between the sample and the camera lens. The acquired fluorescent images of the sample and control tubes are digitally processed within one second through an Android application running on the same cellphone for quantification of albumin concentration in the urine specimen of interest. Using a simple sample preparation approach which takes ~5 min per test (including the incubation time), we experimentally confirmed the detection limit of our sensing platform as 5-10 μg mL(-1) (which is more than 3 times lower than the clinically accepted normal range) in buffer as well as urine samples. This automated albumin testing tool running on a smart-phone could be useful for early diagnosis of kidney disease or for monitoring of chronic patients, especially those suffering from diabetes, hypertension, and/or cardiovascular diseases.

  View details for DOI 10.1039/c3lc50785h

  View details for Web of Science ID 000325369700011

  View details for PubMedID 23995895

• Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array LAB ON A CHIP Navruz, I., Coskun, A. F., Wong, J., Mohammad, S., Tseng, D., Nagi, R., Phillips, S., Ozcan, A. 2013; 13 (20): 4015-4023

  Abstract

  We demonstrate a cellphone based contact microscopy platform, termed Contact Scope, which can image highly dense or connected samples in transmission mode. Weighing approximately 76 grams, this portable and compact microscope is installed on the existing camera unit of a cellphone using an opto-mechanical add-on, where planar samples of interest are placed in contact with the top facet of a tapered fiber-optic array. This glass-based tapered fiber array has ~9 fold higher density of fiber optic cables on its top facet compared to the bottom one and is illuminated by an incoherent light source, e.g., a simple light-emitting-diode (LED). The transmitted light pattern through the object is then sampled by this array of fiber optic cables, delivering a transmission image of the sample onto the other side of the taper, with ~3× magnification in each direction. This magnified image of the object, located at the bottom facet of the fiber array, is then projected onto the CMOS image sensor of the cellphone using two lenses. While keeping the sample and the cellphone camera at a fixed position, the fiber-optic array is then manually rotated with discrete angular increments of e.g., 1-2 degrees. At each angular position of the fiber-optic array, contact images are captured using the cellphone camera, creating a sequence of transmission images for the same sample. These multi-frame images are digitally fused together based on a shift-and-add algorithm through a custom-developed Android application running on the smart-phone, providing the final microscopic image of the sample, visualized through the screen of the phone. This final computation step improves the resolution and also removes spatial artefacts that arise due to non-uniform sampling of the transmission intensity at the fiber optic array surface. We validated the performance of this cellphone based Contact Scope by imaging resolution test charts and blood smears.

  View details for DOI 10.1039/c3lc50589h

  View details for Web of Science ID 000324752100005

  View details for PubMedID 23939637

• A personalized food allergen testing platform on a cellphone LAB ON A CHIP Coskun, A. F., Wong, J., Khodadadi, D., Nagi, R., Tey, A., Ozcan, A. 2013; 13 (4): 636-640

  Abstract

  We demonstrate a personalized food allergen testing platform, termed iTube, running on a cellphone that images and automatically analyses colorimetric assays performed in test tubes toward sensitive and specific detection of allergens in food samples. This cost-effective and compact iTube attachment, weighing approximately 40 grams, is mechanically installed on the existing camera unit of a cellphone, where the test and control tubes are inserted from the side and are vertically illuminated by two separate light-emitting-diodes. The illumination light is absorbed by the allergen assay, which is activated within the tubes, causing an intensity change in the acquired images by the cellphone camera. These transmission images of the sample and control tubes are digitally processed within 1 s using a smart application running on the same cellphone for detection and quantification of allergen contamination in food products. We evaluated the performance of this cellphone-based iTube platform using different types of commercially available cookies, where the existence of peanuts was accurately quantified after a sample preparation and incubation time of ~20 min per test. This automated and cost-effective personalized food allergen testing tool running on cellphones can also permit uploading of test results to secure servers to create personal and/or public spatio-temporal allergen maps, which can be useful for public health in various settings.

  View details for DOI 10.1039/c2lc41152k

  View details for Web of Science ID 000313971300017

  View details for PubMedID 23254910

• Giga-Pixel Lensfree Holographic Microscopy and Tomography Using Color Image Sensors PLOS ONE Isikman, S. O., Greenbaum, A., Luo, W., Coskun, A. F., Ozcan, A. 2012; 7 (9)

  Abstract

  We report Giga-pixel lensfree holographic microscopy and tomography using color sensor-arrays such as CMOS imagers that exhibit Bayer color filter patterns. Without physically removing these color filters coated on the sensor chip, we synthesize pixel super-resolved lensfree holograms, which are then reconstructed to achieve ~350 nm lateral resolution, corresponding to a numerical aperture of ~0.8, across a field-of-view of ~20.5 mm(2). This constitutes a digital image with ~0.7 Billion effective pixels in both amplitude and phase channels (i.e., ~1.4 Giga-pixels total). Furthermore, by changing the illumination angle (e.g., ± 50°) and scanning a partially-coherent light source across two orthogonal axes, super-resolved images of the same specimen from different viewing angles are created, which are then digitally combined to synthesize tomographic images of the object. Using this dual-axis lensfree tomographic imager running on a color sensor-chip, we achieve a 3D spatial resolution of ~0.35 µm × 0.35 µm × ~2 µm, in x, y and z, respectively, creating an effective voxel size of ~0.03 µm(3) across a sample volume of ~5 mm(3), which is equivalent to >150 Billion voxels. We demonstrate the proof-of-concept of this lensfree optical tomographic microscopy platform on a color CMOS image sensor by creating tomograms of micro-particles as well as a wild-type C. elegans nematode.

  View details for DOI 10.1371/journal.pone.0045044

  View details for Web of Science ID 000308738500108

  View details for PubMedID 22984606

• High-throughput screening of large volumes of whole blood using structured illumination and fluorescent on-chip imaging LAB ON A CHIP Arpali, S. A., Arpali, C., Coskun, A. F., Chiang, H., Ozcan, A. 2012; 12 (23): 4968-4971

  Abstract

  Undiluted blood samples are difficult to image in large volumes since blood constitutes a highly absorbing and scattering medium. As a result of this limitation, optical imaging of rare cells (e.g., circulating tumour cells) within unprocessed whole blood remains a challenge, demanding the use of special microfluidic technologies. Here we demonstrate a new fluorescent on-chip imaging modality that can rapidly screen large volumes of absorbing and scattering media, such as undiluted whole blood samples, for detection of fluorescent micro-objects at low concentrations (for example ≤50-100 particles/mL). In this high-throughput imaging modality, a large area microfluidic device (e.g., 7-18 cm(2)), which contains for example ~0.3-0.7 mL of undiluted whole blood sample, is directly positioned onto a wide-field opto-electronic sensor-array such that the fluorescent emission within the microchannel can be detected without the use of any imaging lenses. This microfluidic device is then illuminated and laterally scanned with an array of Gaussian excitation spots, which is generated through a spatial light modulator. For each scanning position of this excitation array, a lensfree fluorescent image of the blood sample is captured using the opto-electronic sensor-array, resulting in a sequence of images (e.g., 144 lensfree frames captured in ~36 s) for the same sample chip. Digitally merging these lensfree fluorescent images based on a maximum intensity projection (MIP) algorithm enabled us to significantly boost the signal-to-noise ratio (SNR) and contrast of the fluorescent micro-objects within whole blood, which normally remain undetected (i.e., hidden) using conventional uniform excitation schemes, involving plane wave illumination. This high-throughput on-chip imaging platform based on structured excitation could be useful for rare cell research by enabling rapid screening of large volume microfluidic devices that process whole blood and other optically dense media.

  View details for DOI 10.1039/c2lc40894e

  View details for Web of Science ID 000310916500005

  View details for PubMedID 23047492

• Optofluidic Fluorescent Imaging Cytometry on a Cell Phone ANALYTICAL CHEMISTRY Zhu, H., Mavandadi, S., Coskun, A. F., Yaglidere, O., Ozcan, A. 2011; 83 (17): 6641-6647

  Abstract

  Fluorescent microscopy and flow cytometry are widely used tools in biomedical sciences. Cost-effective translation of these technologies to remote and resource-limited environments could create new opportunities especially for telemedicine applications. Toward this direction, here we demonstrate the integration of imaging cytometry and fluorescent microscopy on a cell phone using a compact, lightweight, and cost-effective optofluidic attachment. In this cell-phone-based optofluidic imaging cytometry platform, fluorescently labeled particles or cells of interest are continuously delivered to our imaging volume through a disposable microfluidic channel that is positioned above the existing camera unit of the cell phone. The same microfluidic device also acts as a multilayered optofluidic waveguide and efficiently guides our excitation light, which is butt-coupled from the side facets of our microfluidic channel using inexpensive light-emitting diodes. Since the excitation of the sample volume occurs through guided waves that propagate perpendicular to the detection path, our cell-phone camera can record fluorescent movies of the specimens as they are flowing through the microchannel. The digital frames of these fluorescent movies are then rapidly processed to quantify the count and the density of the labeled particles/cells within the target solution of interest. We tested the performance of our cell-phone-based imaging cytometer by measuring the density of white blood cells in human blood samples, which provided a decent match to a commercially available hematology analyzer. We further characterized the imaging quality of the same platform to demonstrate a spatial resolution of ~2 μm. This cell-phone-enabled optofluidic imaging flow cytometer could especially be useful for rapid and sensitive imaging of bodily fluids for conducting various cell counts (e.g., toward monitoring of HIV+ patients) or rare cell analysis as well as for screening of water quality in remote and resource-poor settings.

  View details for DOI 10.1021/ac201587a

  View details for Web of Science ID 000294322100031

  View details for PubMedID 21774454

• Lensless fluorescent microscopy on a chip. Journal of visualized experiments : JoVE Coskun, A. F., Su, T., Sencan, I., Ozcan, A. 2011

  Abstract

  On-chip lensless imaging in general aims to replace bulky lens-based optical microscopes with simpler and more compact designs, especially for high-throughput screening applications. This emerging technology platform has the potential to eliminate the need for bulky and/or costly optical components through the help of novel theories and digital reconstruction algorithms. Along the same lines, here we demonstrate an on-chip fluorescent microscopy modality that can achieve e.g., <4 μm spatial resolution over an ultra-wide field-of-view (FOV) of >0.6-8 cm(2) without the use of any lenses, mechanical-scanning or thin-film based interference filters. In this technique, fluorescent excitation is achieved through a prism or hemispherical-glass interface illuminated by an incoherent source. After interacting with the entire object volume, this excitation light is rejected by total-internal-reflection (TIR) process that is occurring at the bottom of the sample micro-fluidic chip. The fluorescent emission from the excited objects is then collected by a fiber-optic faceplate or a taper and is delivered to an optoelectronic sensor array such as a charge-coupled-device (CCD). By using a compressive-sampling based decoding algorithm, the acquired lensfree raw fluorescent images of the sample can be rapidly processed to yield e.g., <4 μm resolution over an FOV of >0.6-8 cm(2). Moreover, vertically stacked micro-channels that are separated by e.g., 50-100 μm can also be successfully imaged using the same lensfree on-chip microscopy platform, which further increases the overall throughput of this modality. This compact on-chip fluorescent imaging platform, with a rapid compressive decoder behind it, could be rather valuable for high-throughput cytometry, rare-cell research and microarray-analysis.

  View details for DOI 10.3791/3181

  View details for PubMedID 21876522

• Lensfree Fluorescent On-Chip Imaging of Transgenic Caenorhabditis elegans Over an Ultra-Wide Field-of-View PLOS ONE Coskun, A. F., Sencan, I., Su, T., Ozcan, A. 2011; 6 (1)

  Abstract

  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.

  View details for DOI 10.1371/journal.pone.0015955

  View details for Web of Science ID 000286511900031

  View details for PubMedID 21253611

• Wide-field lensless fluorescent microscopy using a tapered fiber-optic faceplate on a chip ANALYST Coskun, A. F., Sencan, I., Su, T., Ozcan, A. 2011; 136 (17): 3512-3518

  Abstract

  We demonstrate lensless fluorescent microscopy over a large field-of-view of ~60 mm(2) with a spatial resolution of <4 µm. In this on-chip fluorescent imaging modality, the samples are placed on a fiber-optic faceplate that is tapered such that the density of the fiber-optic waveguides on the top facet is >5 fold larger than the bottom one. Placed on this tapered faceplate, the fluorescent samples are pumped from the side through a glass hemisphere interface. After excitation of the samples, the pump light is rejected through total internal reflection that occurs at the bottom facet of the sample substrate. The fluorescent emission from the sample is then collected by the smaller end of the tapered faceplate and is delivered to an opto-electronic sensor-array to be digitally sampled. Using a compressive sampling algorithm, we decode these raw lensfree images to validate the resolution (<4 µm) of this on-chip fluorescent imaging platform using microparticles as well as labeled Giardia muris cysts. This wide-field lensfree fluorescent microscopy platform, being compact and high-throughput, might provide a valuable tool especially for cytometry, rare cell analysis (involving large area microfluidic systems) as well as for microarray imaging applications.

  View details for DOI 10.1039/c0an00926a

  View details for Web of Science ID 000293644200016

  View details for PubMedID 21283900

• Lensfree Fluorescent On-Chip Imaging using Compressive Sampling. Optics and photonics news Coskun, A. F., Su, T., Sencan, I., Ozcan, A. 2010; 21 (12): 27-?

  View details for PubMedID 21546979

• Lensfree sensing on a microfluidic chip using plasmonic nanoapertures APPLIED PHYSICS LETTERS Khademhosseinieh, B., Biener, G., Sencan, I., Su, T., Coskun, A. F., Ozcan, A. 2010; 97 (22)

  Abstract

  We demonstrate lensfree on-chip sensing within a microfluidic channel using plasmonic nanoapertures that are illuminated by a partially coherent quasimonochromatic source. In this approach, lensfree diffraction patterns of metallic nanoapertures located at the bottom of a microfluidic channel are recorded using an optoelectronic sensor-array. These lensfree diffraction patterns can then be rapidly processed, using phase recovery techniques, to back propagate the optical fields to an arbitrary depth, creating digitally focused complex transmission patterns. Cross correlation of these patterns enables lensfree on-chip sensing of the local refractive index surrounding the near-field of the plasmonic nanoapertures. Based on this principle, we experimentally demonstrate lensfree sensing of refractive index changes as small as ∼2×10(-3). This on-chip sensing approach could be quite useful for development of label-free microarray technologies by multiplexing thousands of plasmonic structures on the same microfluidic chip, which can significantly increase the throughput of sensing.

  View details for DOI 10.1063/1.3521390

  View details for Web of Science ID 000284965000007

  View details for PubMedID 21203381

• Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution OPTICS EXPRESS Bishara, W., Su, T., Coskun, A. F., Ozcan, A. 2010; 18 (11): 11181-11191

  Abstract

  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.

  View details for DOI 10.1364/OE.18.011181

  View details for Web of Science ID 000278512300031

  View details for PubMedID 20588977

• Lensless wide-field fluorescent imaging on a chip using compressive decoding of sparse objects OPTICS EXPRESS Coskun, A. F., Sencan, I., Su, T., Ozcan, A. 2010; 18 (10): 10510-10523

  Abstract

  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.

  View details for DOI 10.1364/OE.18.010510

  View details for Web of Science ID 000277560000076

  View details for PubMedID 20588904

• Lensfree on-chip imaging using nanostructured surfaces APPLIED PHYSICS LETTERS Khademhosseinieh, B., Sencan, I., Biener, G., Su, T., Coskun, A. F., Tseng, D., Ozcan, A. 2010; 96 (17)

  Abstract

  We introduce the use of nanostructured surfaces for lensfree on-chip microscopy. In this incoherent on-chip imaging modality, the object of interest is directly positioned onto a nanostructured thin metallic film, where the emitted light from the object plane, after being modulated by the nanostructures, diffracts over a short distance to be sampled by a detector-array without the use of any lenses. The detected far-field diffraction pattern then permits rapid reconstruction of the object distribution on the chip at the subpixel level using a compressive sampling algorithm. This imaging modality based on nanostructured substrates could especially be useful to create lensfree fluorescent microscopes on a compact chip.

  View details for DOI 10.1063/1.3405719

  View details for Web of Science ID 000277242000006

  View details for PubMedID 20502644

• Wide field-of-view lens-free fluorescent imaging on a chip LAB ON A CHIP Coskun, A. F., Su, T., Ozcan, A. 2010; 10 (7): 824-827

  Abstract

  We demonstrate an on-chip fluorescent detection platform that can simultaneously image fluorescent micro-objects or labeled cells over an ultra-large field-of-view of 2.5 cm x 3.5 cm without the use of any lenses, thin-film filters and mechanical scanners. Such a wide field-of-view lensless fluorescent imaging modality, despite its limited resolution, might be very important for high-throughput screening applications as well as for detection and counting of rare cells within large-area microfluidic devices.

  View details for DOI 10.1039/b926561a

  View details for Web of Science ID 000275757600005

  View details for PubMedID 20379564

• Spectral tuning of liquid microdroplets standing on a superhydrophobic surface using electrowetting APPLIED PHYSICS LETTERS Kiraz, A., Karadag, Y., Coskun, A. F. 2008; 92 (19)

  View details for DOI 10.1063/1.2927373

  View details for Web of Science ID 000256564200004