Oguzhan Yaglidere

Lensfree microscopy on a cellphone

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).

Optofluidic Fluorescent Imaging Cytometry on a Cell Phone

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.

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

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.

Distributed medical image analysis and diagnosis through crowd-sourced games: a malaria case study.

In this work we investigate whether the innate visual recognition and learning capabilities of untrained humans can be used in conducting reliable microscopic analysis of biomedical samples toward diagnosis. For this purpose, we designed entertaining digital games that are interfaced with artificial learning and processing back-ends to demonstrate that in the case of binary medical diagnostics decisions (e.g., infected vs. uninfected), with the use of crowd-sourced games it is possible to approach the accuracy of medical experts in making such diagnoses. Specifically, using non-expert gamers we report diagnosis of malaria infected red blood cells with an accuracy that is within 1.25% of the diagnostics decisions made by a trained medical professional.

Field-portable reflection and transmission microscopy based on lensless holography

We demonstrate a lensfree dual-mode holographic microscope that can image specimens in both transmission and reflection geometries using in-line transmission and off-axis reflection holography, respectively. This field-portable dual-mode holographic microscope has a weight of ~200 g with dimensions of 15 x 5.5 x 5cm, where a laser source is powered by two batteries. Based on digital in-line holography, our transmission microscope achieves a sub-pixel lateral resolution of ≤2 µm over a wide field-of-view (FOV) of ~24 mm2 due to its unit fringe magnification geometry. Despite its simplicity and ease of operation, in-line transmission geometry is not suitable to image dense or connected objects such as tissue slides since the reference beam gets distorted causing severe aberrations in reconstruction of such objects. To mitigate this challenge, on the same cost-effective and field-portable assembly we built a lensless reflection mode microscope based on digital off-axis holography where a beam-splitter is used to interfere a tilted reference wave with the reflected light from the object surface, creating an off-axis hologram of the specimens on a CMOS sensor-chip. As a result of the reduced space-bandwidth product of the off-axis geometry compared to its in-line counterpart, the imaging FOV of our reflection mode is reduced to ~9 mm2, while still achieving a similar sub-pixel resolution of ≤2 µm. We tested the performance of this compact dual-mode microscopy unit by imaging a US-air force resolution test target, various micro-particles as well as a histopathology slide corresponding to skin tissue. Due to its compact, cost-effective, and lightweight design, this dual-mode lensless holographic microscope might especially be useful for field-use or for conducting microscopic analysis in resource-poor settings.

Lensfree On-Chip Microscopy and Tomography for Biomedical Applications

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 study, 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.

Wide-field fluorescent microscopy on a cell-phone

We demonstrate wide-field fluorescent imaging on a cell-phone, using compact and cost-effective optical components that are mechanically attached to the existing camera unit of the cell-phone. Battery powered light-emitting diodes (LEDs) are used to side-pump the sample of interest using butt-coupling. The pump light is guided within the sample cuvette to excite the specimen uniformly. The fluorescent emission from the sample is then imaged with an additional lens that is put in front of the existing lens of the cell-phone camera. Because the excitation occurs through guided waves that propagate perpendicular to the detection path, an inexpensive plastic color filter is sufficient to create the dark-field background needed for fluorescent imaging. The imaging performance of this light-weight platform (∼28 grams) is characterized with red and green fluorescent microbeads, achieving an imaging field-of-view of ∼81 mm2 and a spatial resolution of ∼10 μm, which is enhanced through digital processing of the captured cell-phone images using compressive sampling based sparse signal recovery. We demonstrate the performance of this cell-phone fluorescent microscope by imaging labeled white-blood cells separated from whole blood samples as well as water-borne pathogenic protozoan parasites such as Giardia Lamblia cysts.

Handheld, lensless microscope identifies malaria parasites

Optical microscopy is an indispensable tool in science and medicine. However, the size and cost of conventional optical microscopes limit their use in rugged field-settings or in remote areas to assist in tasks such as medical tests, disease diagnostics, or monitoring of water quality. In recent years, there has been widespread interest in reducing the size and cost of microscopes and making them more suited for point-of-care and telemedicine applications, or for tackling global health problems. These approaches range from miniaturizing traditional microscope designs and attaching them to cell phones, to eliminate lenses altogether

Field-Portable Lensless Holographic Microscope using Pixel Super-Resolution

We report a portable lensless holographic microscope utilizing pixel super-resolution to achieve <1um resolution and 24mm2 field-of-view. The performance of this light-weight (95g) microscope is validated by imaging malaria parasites in blood-smears.

Fluorescent flow-cytometry on a cell-phone

We demonstrate fluorescent imaging flow-cytometry that is integrated on a cell-phone. The cellphone based flow-cytometer was used to measure the density of white-blood-cells in blood samples, providing a decent match to the hematology analyzer.