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 costeffective, 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 46 grams with dimensions smaller than 4.2cm × 4.2cm × 5.8cm that achieves sub-cellular resolution over a large field of view of ~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 optoelectronic 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.

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 ~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).

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 ~46 grams, achieves a numerical aperture of ~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.Water-associated diseases create major problems in the developing parts of the world where there is no reliable infrastructure for proper decontamination of water resources which also brings inadequate access to clean drinking water. The same danger also occurs during natural disasters and wars, where water treatment and sewage facilities lose their functionality. As a matter of fact, the occurrence of waterborne diseases has been dramatically increasing worldwide including in highly industrialized countries such as the United States. [2][3][4][5] Two widely spread examples of such diarrheal diseases include Giardiasis and Cryptosporidiosis which are caused by protozoan parasites, namely Giardia Lamblia and Cryptosporidium Parvum, respectively. 6 Unfortunately, these parasites can survive in cold water for several weeks and are resistant to most of the conventional water treatment methods such as chlorination. 7 Various approaches have been demonstrated so far for identification and quantification of pathogens in drinking and recreational water resources. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Traditional culture-based methods are time-consuming and have serious drawbacks due to lack of accurate enumeration methods as well as rapid transition of some of the species into non-culturable state after being released into freshwater. 11,12 To address the challenges of these laborious tools, culture-independent techniques have also been demonstrated, which utilize various technologies including polymerase chain reaction † Published as part of a special issue dedicated to To provide an alternative solution to this important problem, here we investigate the use of a field-portable lensfree holographic microscope (see Fig. 1) to image and automatically detect pathogenic protozoan parasites such as Giardia Lamblia and Cryptosporidium Parvum at low concentration levels of <400/mL without the use o...

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 mm 2 . 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.Caenorhabditis elegans (C. elegans) has been extensively studied as a model organism to better understand the underlying mechanisms of various human diseases. 1 It has several important features that justify this widespread use. First, C. elegans is easy to culture in laboratory environments, growing and reproducing rapidly and cost-effectively. Further, it is a transparent, optically accessible organism with well developed nervous and reproductive systems, intestine, skin and muscles. As a result, high-throughput phenotypical characterization of C. elegans samples, which primarily involves optical imaging in the form of conventional microscopy, has led to important discoveries in biomedical research and specifically in drug discovery, significantly impacting genetics, 2 oncology 3 and neurobiology. 4,5 Motivated by these advances, various high-throughput platforms were demonstrated for phenotypical screening of this model organism. [6][7][8][9] In these existing systems, phenotype characterization relies on conventional lens-based light microscopy, which has a limited imaging field-of-view, despite the use of bulky and expensive objective-lenses.Here we demonstrate color and monochrome on-chip imaging of C. elegans samples using an alternative optical microscopy platform that is especially suitable for high-throughput screening applications, also offering straightforward integration with microfluidics. When compared to the state of the art, our approach does not utilize any lenses, lasers or other bulky optical components or any mechanical scanning, making it highly compact and simple to use. Our on-chip imaging approach is based on incoherent lensless in-line holography 10 (see Fig. 1) which provides a significantly larger field-of-view (FOV), permitting simultaneous imaging of C. elegans samples over an area of >24 mm 2 , i.e., ~10 fold larger than a typical 10× objectivelens FOV. Digital reconstruction of the recorded lensless holograms rapidly creates the C. elegans images within less than 1 s; and by digitally combining these reconstructed images at three different wavelengths (red, green and blue) color images of the samples that are labeled with functional dyes are also acquired. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript requires almost no sensitive optical alignment, making it quite easy to operate, even for nontechnical personnel. Through its integration with micro-fluidic systems, this lensle...

We demonstrate a telemedicine microscopy platform which operates based on lensfree digital holography. It utilizes an incoherent light-source and an opto-electronic sensor-array to record lensfree holograms of micro-objects within a sample, which are then rapidly processed using custom-developed algorithms to provide microscopic images of the samples without the use of any lenses, lasers or other bulky optical/mechanical components. This holographic-microscope achieves sub-cellular resolution over a field-of-view of ~24 mm 2 which is >20 fold larger than a typical 10X objective-lens field-of-view. We implemented this lensfree microscopy platform on a compact stand-alone unit (~46 grams with dimensions of ~4.2 x 4.2 x 5.8 cm) as well as on a commercially-available cell-phone which is modified with a light-weight attachment (~38 grams). The imaging performance of these lensfree telemedicine-microscopes is demonstrated using several micro-objects including blood cells and water-borne parasites.