Publications by authors named "Anthony Erlinger"

9 Publications

  • Page 1 of 1

Compact and light-weight automated semen analysis platform using lensfree on-chip microscopy.

Anal Chem 2010 Oct;82(19):8307-12

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

We demonstrate a compact and lightweight platform to conduct automated semen analysis using a lensfree on-chip microscope. This holographic on-chip imaging platform weighs ∼46 g, measures ∼4.2 × 4.2 × 5.8 cm, and does not require any lenses, lasers or other bulky optical components to achieve phase and amplitude imaging of sperms over ∼24 mm(2) field-of-view with an effective numerical aperture of ∼0.2. Using this wide-field lensfree on-chip microscope, semen samples are imaged for ∼10 s, capturing a total of ∼20 holographic frames. Digital subtraction of these consecutive lensfree frames, followed by appropriate processing of the reconstructed images, enables automated quantification of the count, the speed and the dynamic trajectories of motile sperms, while summation of the same frames permits counting of immotile sperms. Such a compact and lightweight automated semen analysis platform running on a wide-field lensfree on-chip microscope could be especially important for fertility clinics, personal male fertility tests, as well as for field use in veterinary medicine such as in stud farming and animal breeding applications.
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http://dx.doi.org/10.1021/ac101845qDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987715PMC
October 2010

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

Multi-angle lensless digital holography for depth resolved imaging on a chip.

Opt Express 2010 Apr;18(9):9690-711

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

A multi-angle lensfree holographic imaging platform that can accurately characterize both the axial and lateral positions of cells located within multi-layered micro-channels is introduced. In this platform, lensfree digital holograms of the micro-objects on the chip are recorded at different illumination angles using partially coherent illumination. These digital holograms start to shift laterally on the sensor plane as the illumination angle of the source is tilted. Since the exact amount of this lateral shift of each object hologram can be calculated with an accuracy that beats the diffraction limit of light, the height of each cell from the substrate can be determined over a large field of view without the use of any lenses. We demonstrate the proof of concept of this multi-angle lensless imaging platform by using light emitting diodes to characterize various sized microparticles located on a chip with sub-micron axial and lateral localization over approximately 60 mm(2) field of view. Furthermore, we successfully apply this lensless imaging approach to simultaneously characterize blood samples located at multi-layered micro-channels in terms of the counts, individual thicknesses and the volumes of the cells at each layer. Because this platform does not require any lenses, lasers or other bulky optical/mechanical components, it provides a compact and high-throughput alternative to conventional approaches for cytometry and diagnostics applications involving lab on a chip systems.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898907PMC
http://dx.doi.org/10.1364/OE.18.009690DOI Listing
April 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 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

Lensfree holographic imaging for on-chip cytometry and diagnostics.

Lab Chip 2009 Mar 5;9(6):777-87. Epub 2008 Dec 5.

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

We experimentally illustrate a lensfree holographic imaging platform to perform on-chip cytometry. By controlling the spatial coherence of the illumination source, we record a 2D holographic diffraction pattern of each cell or micro-particle on a chip using a high resolution sensor array that has approximately 2 microm pixel size. The recorded holographic image is then processed by using a custom developed decision algorithm for matching the detected hologram texture to existing library images for on-chip characterization and counting of a heterogeneous solution of interest. The holographic diffraction signature of any microscopic object is significantly different from the classical diffraction pattern of the same object. It improves the signal to noise ratio and the signature uniformity of the cell patterns; and also exhibits much better sensitivity for on-chip imaging of weakly scattering phase objects such as small bacteria or cells. We verify significantly improved performance of this holographic on-chip cytometry approach by automatically characterizing heterogeneous solutions of red blood cells, yeast cells, E. coli and various sized micro-particles without the use of any lenses or microscope objectives. This lensless on-chip holography platform will especially be useful for point-of-care cytometry and diagnostics applications involving e.g., infectious diseases such as HIV or malaria.
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http://dx.doi.org/10.1039/b813943aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931575PMC
March 2009

Multi-angle LUCAS for high-throughput on-chip cytometry.

Annu Int Conf IEEE Eng Med Biol Soc 2008 ;2008:1854-5

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

We illustrate that by recording under-sampled diffraction patterns of cells at different illumination angles, we can achieve high-throughput on-chip characterization of a heterogeneous cell solution over an ultra large volume of approximately 5 ml. This platform, termed multi-angle LUCAS, is especially promising for cost-effective point-of-care cell counting applications.
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http://dx.doi.org/10.1109/IEMBS.2008.4649543DOI Listing
May 2009

High-throughput lensfree imaging and characterization of a heterogeneous cell solution on a chip.

Biotechnol Bioeng 2009 Feb;102(3):856-868

Electrical Engineering Department, University of California, P.O. Box 951594, Los Angeles, California 90095.

A high-throughput on-chip imaging platform that can rapidly monitor and characterize various cell types within a heterogeneous solution over a depth-of-field of approximately 4 mm and a field-of-view of approximately 10 cm(2) is introduced. This powerful system can rapidly image/monitor multiple layers of cells, within a volume of approximately 4 mL all in parallel without the need for any lenses, microscope-objectives or any mechanical scanning. In this high-throughput lensless imaging scheme, the classical diffraction pattern (i.e., the shadow) of each micro-particle within the entire sample volume is detected in less than a second using an opto-electronic sensor chip. The acquired shadow image is then digitally processed using a custom developed "decision algorithm" to enable both the identification of the particle location in 3D and the characterization of each micro-particle type within the sample volume. Through experimental results, we show that different cell types (e.g., red blood cells, fibroblasts, etc.) or other micro-particles all exhibit uniquely different shadow patterns and therefore can be rapidly identified without any ambiguity using the developed decision algorithm, enabling high-throughput characterization of a heterogeneous solution. This lensfree on chip cell imaging platform shows a significant promise especially for medical diagnostic applications relevant to global health problems, where compact and cost-effective diagnostic tools are urgently needed in resource limited settings.
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http://dx.doi.org/10.1002/bit.22116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183348PMC
February 2009