Opto-fluidics based microscopy and flow cytometry on a cell phone for blood analysis.

Blood analysis is one of the most important clinical tests for medical diagnosis. Flow cytometry and optical microscopy are widely used techniques to perform blood analysis and therefore cost-effective translation of these technologies to resource limited settings is critical for various global health as well as telemedicine applications. In this chapter, we review our recent progress on the integration of imaging flow cytometry and fluorescent microscopy on a cell phone using compact, light-weight and cost-effective opto-fluidic attachments integrated onto the camera module of a smartphone. In our cell-phone based opto-fluidic imaging cytometry design, fluorescently labeled cells are delivered into the imaging area using a disposable micro-fluidic chip that is positioned above the existing camera unit of the cell phone. Battery powered light-emitting diodes (LEDs) are butt-coupled to the sides of this micro-fluidic chip without any lenses, which effectively acts as a multimode slab waveguide, where the excitation light is guided to excite the fluorescent targets within the micro-fluidic chip. Since the excitation light propagates perpendicular to the detection path, an inexpensive plastic absorption filter is able to reject most of the scattered light and create a decent dark-field background for fluorescent imaging. With this excitation geometry, the cell-phone camera can record fluorescent movies of the particles/cells 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 solution under test. With a similar opto-fluidic design, we have recently demonstrated imaging and automated counting of stationary blood cells (e.g., labeled white blood cells or unlabeled red blood cells) loaded within a disposable cell counting chamber. We tested the performance of this cell-phone based imaging cytometry and blood analysis platform by measuring the density of red and white blood cells as well as hemoglobin concentration in human blood samples, which showed a good match to our measurement results obtained using a commercially available hematology analyzer. Such a cell-phone enabled opto-fluidics microscopy, flow cytometry, and blood analysis platform could be especially useful for various telemedicine applications in remote and resource-limited settings.

[1]  G. Whitesides,et al.  Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. , 2008, Analytical chemistry.

[2]  Roger Detels,et al.  Plasma Viral Load and CD4+ Lymphocytes as Prognostic Markers of HIV-1 Infection , 1997, Annals of Internal Medicine.

[3]  A. Ozcan,et al.  Ultra wide-field lens-free monitoring of cells on-chip. , 2008, Lab on a chip.

[4]  P. Kiesel,et al.  Fluorescence spectrometer-on-a-fluidic-chip. , 2007, Lab on a chip.

[5]  D. Filippini,et al.  Surface plasmon resonance chemical sensing on cell phones. , 2012, Angewandte Chemie.

[6]  Hongying Zhu,et al.  Cost-effective and compact wide-field fluorescent imaging on a cell-phone. , 2011, Lab on a chip.

[7]  Rainer Hofmann-Wellenhof,et al.  Telemedicine and teledermatology: Past, present and future , 2008, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[8]  Keiichi Abe,et al.  Topological structural analysis of digitized binary images by border following , 1985, Comput. Vis. Graph. Image Process..

[9]  Monitoring CD4 in whole blood with an opto‐fluidic detector based on spatially modulated fluorescence emission , 2011, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[10]  Aydogan Ozcan,et al.  A personalized food allergen testing platform on a cellphone. , 2013, Lab on a chip.

[11]  Hongying Zhu,et al.  Cost-effective and rapid blood analysis on a cell-phone. , 2013, Lab on a chip.

[12]  David N Breslauer,et al.  Mobile Phone Based Clinical Microscopy for Global Health Applications , 2009, PloS one.

[13]  Derek Tseng,et al.  Lensfree microscopy on a cellphone. , 2010, Lab on a chip.

[14]  A. Ozcan,et al.  Quantum dot enabled detection of Escherichia coli using a cell-phone. , 2012, The Analyst.

[15]  Amy L. Gryshuk,et al.  Cell-Phone-Based Platform for Biomedical Device Development and Education Applications , 2011, PloS one.

[16]  Joshua Balsam,et al.  Thousand-fold fluorescent signal amplification for mHealth diagnostics. , 2014, Biosensors & bioelectronics.

[17]  Aydogan Ozcan,et al.  Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array. , 2013, Lab on a chip.

[18]  David J. You,et al.  Cell-phone-based measurement of TSH using Mie scatter optimized lateral flow assays. , 2013, Biosensors & bioelectronics.

[19]  Aydogan Ozcan,et al.  Integrated rapid-diagnostic-test reader platform on a cellphone. , 2012, Lab on a chip.

[20]  Hongying Zhu,et al.  Optofluidic fluorescent imaging cytometry on a cell phone. , 2011, Analytical chemistry.