Technology

Holomic Rapid Diagnostic Reader (HRDR-200)

hrdr-200-smallRapid Diagnostic Tests (RDTs) take the center stage in point-of-care diagnostics; they have found widespread application at home (i.e. home pregnancy tests), physicians’ offices (thyroid RDT), and public health (HIV, malaria, influenza, drug screening and many others). Responding to the disease bio-markers in bodily fluids, color changes on RDTs indicate the presence of a particular condition that is generally evaluated via visual inspection by human eye. However, considering the fact that various types of RDTs might be used together, possibly each with different control and diagnosis instructions, this manual human reading process might be prone to errors. Moreover, the varying color variations cannot be observed and quantified during visual examination of RDTs by humans, especially under varying illumination and imaging conditions.

The Holomic Rapid Diagnostic Reader (HRDR) on a cellphone, together with its powerful software applications, solves all these problems. Offering quantitative, repeatable and accurate digital reading of RDTs, HRDR can enable large scale use of RDTs for better healthcare delivery, monitoring and real-time geo-mapping of emerging epidemics and other conditions, and help healthcare professionals and public health authorities with epidemics preparedness.

Launched in 2012 and available in the market, the HRDR-200 is compliant with ISO 9001/ISO 13485 and is registered with the FDA as Class 1 medical device.

Selected Publication:

- O. Mudanyali, S. Dimitrov, U. Sikora, S. Padmanabhan, I. Navruz, and A. Ozcan, Lab on a Chip (2012), DOI:10.1039/C2LC40235A (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2012/LC/c2lc40235a)

Cell-phone Microscope

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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 handheld tool for telemedicine applications to address various global health challenges. Weighing only 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 have evaluated the performance of this lensfree cellphone microscope by imaging various sized micro-particles, as well as red blood cells, white blood cells, platelets and waterborne parasites.

Selected Publication:

- D. Tseng, O. Mudanyali, C. Oztoprak, S.O. Isikman, I. Sencan, O. Yaglidere and A. Ozcan, Lab Chip (2010), Cover Article, DOI: 10.1039/C003477K (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2010/LC/c003477k)

Lensfree Holographic Microscope

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This lensfree microscope weighing only 46 grams with dimensions smaller than 4.2 cm x 4.2 cm x 5.8 cm can achieve sub-cellular resolution over a large field of view of 24 mm2. 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 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. It can provide a transformative solution to some of the unmet needs of cell biology and medical diagnostics.

Selected Publications:

- O. Mudanyali, D. Tseng, C. Oh, S.O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, Lab Chip (2010), DOI: 10.1039/C000453G (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2010/LC/c000453g)

- O. Mudanyali, C. Oztoprak, D. Tseng, A. Erlinger, and A. Ozcan, Lab on a Chip (2010), DOI: 10.1039/C004829A (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2010/LC/c004829a)

- T. Su, A. Erlinger, D. Tseng, and A. Ozcan, Analytical Chemistry (2010), DOI: 10.1021/AC101845Q (http://pubs NULL.acs NULL.org/doi/abs/10 NULL.1021/ac101845q)

Pixel Super Resolution Microscope

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Based on several years of breakthrough research in lensfree holographic microscopy (published in leading journals including Nature Photonics, Nature Methods, PNAS, Nature Scientific Reports, etc.), through advanced numerical techniques and rapid image reconstruction process our pixel super resolution microscopy platform can achieve diffraction limited resolution (~300 nm; capable of detecting single viruses and sub-100 nm particles) across an extremely large field of view of >20 mm2, which yields more than two orders of magnitude larger imaging area compared to other imaging techniques with comparable resolution. This performance is simply unmatched in terms of space bandwidth product and since we are not limited by any lenses (i.e., depth focusing is done through post-processing of holograms) a depth of field of >500 µm can be routinely achieved without the need for any mechanical alignment or micro-controller stages. These features make our platform (1) very throughput easily screening >10 micro-liters of volume with very high-sensitivity and (2) very compact and light-weight without the need for any bulky and expensive objective lenses or micro-alignment stages.

Selected Publications:

- W. Bishara, U. Sikora, O. Mudanyali, T. Su, O. Yaglidere, S. Luckhart, and A. Ozcan, Lab on a Chip (2011), DOI:10.1039/C0LC00684J (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2011/LC/c0lc00684j)

- O. Mudanyali, E. McLeod, W. Luo, A. Greenbaum, A.F. Coskun, Y. Hennequin, C. Allier, and A. Ozcan, Nature Photonics (2013), DOI:10.1038/NPHOTON.2012.337 (http://www NULL.nature NULL.com/nphoton/journal/v7/n3/abs/nphoton NULL.2012 NULL.337 NULL.html)

- A. Greenbaum, W. Luo, T-W. Su, Z. Göröcs, L. Xue, S.O. Isikman, A.F. Coskun, O. Mudanyali, and A. Ozcan, Nature Methods (2012), DOI:10.1038/NMETH.2114 (http://www NULL.nature NULL.com/nmeth/journal/v9/n9/full/nmeth NULL.2114 NULL.html)

- T-W. Su, L. Xue and A. Ozcan, Proceedings of the National Academy of Sciences (PNAS) (2012), DOI:10.1073/PNAS.1212506109 (http://www NULL.pnas NULL.org/content/109/40/16018)

- A. Greenbaum, W. Luo, B. Khademhosseinieh, T-W. Su, A.F. Coskun, and A. Ozcan, Scientific Reports (Nature Publishing Group) (2013), DOI:10.1038/SREP01717 (http://www NULL.nature NULL.com/srep/2013/130424/srep01717/full/srep01717 NULL.html)

Blood Analysis on a Cell-phone

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This cell-phone based Blood Analyzer is a compact imaging cytometry platform installed on a cell-phone for the measurement of the density of red and white blood cells as well as hemoglobin concentration in human blood samples. Fluorescent and bright-field images of blood samples are captured using separate optical attachments to the cell-phone and are rapidly processed through a custom-developed smart application running on the phone for counting of blood cells and determining hemoglobin density. We evaluated the performance of this cell-phone based blood analysis platform using anonymous human blood samples and achieved comparable results to a standard bench-top hematology analyser. Test results can either be stored on the cell-phone memory or be transmitted to a central server, providing remote diagnosis opportunities even in field settings.

Selected Publication:

-H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, Lab on a Chip (2013), DOI:10.1039/C3LC41408F (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2013/LC/C3lc41408f)

Allergen Testing Platform on a Cellphone

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This personalized food allergen testing platform 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 compact attachment, weighing ~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 that 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 sec 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 platform using different types of commercially available cookies, where the existence of peanuts was accurately quantified after a simple sample preparation. It can be also employed for a variety of other allergens, including e.g., almond, egg, gluten, hazelnut, lupine, mustard, sesame, crustacean, soy as well as milk. 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.

Selected Publication:

-A.F. Coskun, J. Wong, D. Khodadadi, R. Nagi, A. Tey, and A. Ozcan, Lab on a Chip (2012), DOI:10.1039/C2LC41152K (http://pubs NULL.rsc NULL.org/en/content/articlelanding/2012/LC/C2LC41152K)

Fluorescent Imaging Cytometry and E.Coli Detection on a Cell-phone

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We introduce the integration of imaging cytometry and fluorescent microscopy on a cell-phone using a compact, light-weight 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 the imaging volume through a disposable micro-fluidic channel that is positioned above the existing camera unit of the cell-phone. The same micro-fluidic device also acts as a multi-layered optofluidic waveguide and efficiently guides the excitation light, which is butt-coupled from the side facets of our micro-fluidic channel using 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 micro-channel. 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.

Using a similar fluorescent imaging design and a capillary array, it is also possible to detect E. Coli in liquid samples. This fluorescent cell-phone based Escherichia coli (E. coli) detection utilizes anti-E. coli O157:H7 antibody functionalized glass capillaries as solid substrates to perform a quantum dot based sandwich assay for specific detection of E. coli O157:H7 in liquid samples.

Selected Publications:

-H. Zhu, O. Yaglidere, T. Su, D. Tseng, and A. Ozcan, Lab on a Chip (2010), DOI: 10.1039/C0LC00358A (http://pubs NULL.rsc NULL.org/en/content/articlelanding/2011/lc/c0lc00358a)

-H. Zhu, S. Mavandadi, A.F. Coskun, O. Yaglidere, and A. Ozcan, Analytical Chemistry (2011), DOI:10.1021/AC201587A (http://pubs NULL.acs NULL.org/doi/abs/10 NULL.1021/ac201587a)

-H. Zhu, U. Sikora, and A. Ozcan, Analyst (2012), DOI: 10.1039/C2AN35071H (http://pubs NULL.rsc NULL.org/en/Content/ArticleLanding/2012/AN/c2an35071h)

Lensfree Tomographic Microscope

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This field-portable lensfree tomographic microscope can achieve sectional imaging of a large volume (20 mm3) on a chip with an axial resolution of <7 micro-meters. In this compact tomographic imaging platform (weighing only 110 grams), multiple light-emitting diodes (LEDs) are controlled through a micro-processor to sequentially illuminate the sample from different angles to record lensfree holograms of the sample that is placed on the top of a digital sensor array. These lensfree holograms obtained over an angular range of +50/-50 degrees are rapidly reconstructed to yield projection images of the sample, which can then be processed to compute tomograms of the objects on the sensor-chip. The performance of this compact and light-weight lensfree tomographic microscope is validated by imaging micro-beads of different dimensions as well as a Hymenolepis nana egg, which is an infectious parasitic flatworm. Achieving a decent three-dimensional spatial resolution, this field-portable on-chip optical tomographic microscope might provide a useful toolset for telemedicine and high-throughput imaging applications.

Selected Publications:

-S.O. Isikman, W. Bishara, S. Mavandadi, F.W. Yu, S. Feng, R. Lau and A. Ozcan, Proceedings of the National Academy of Sciences (PNAS) (2011), DOI:10.1073/PNAS.1015638108 (http://www NULL.pnas NULL.org/content/early/2011/04/15/1015638108 NULL.full NULL.pdf)

-S.O. Isikman, W. Bishara, U. Sikora, O. Yaglidere, J. Yeah, and A. Ozcan, Lab on a Chip (2011), DOI:10.1039/C1LC20127A (http://pubs NULL.rsc NULL.org/en/content/articlelanding/2011/lc/c1lc20127a)

-S.O. Isikman, W. Bishara, H. Zhu, and A. Ozcan, Applied Physics Letters (2011), DOI:10.1063/1.3548564 (http://apl NULL.aip NULL.org/resource/1/applab/v98/i16/p161109_s1?bypassSSO=1)