Label-free biodetection using a smartphone.

Utilizing its integrated camera as a spectrometer, we demonstrate the use of a smartphone as the detection instrument for a label-free photonic crystal biosensor. A custom-designed cradle holds the smartphone in fixed alignment with optical components, allowing for accurate and repeatable measurements of shifts in the resonant wavelength of the sensor. Externally provided broadband light incident upon an entrance pinhole is subsequently collimated and linearly polarized before passing through the biosensor, which resonantly reflects only a narrow band of wavelengths. A diffraction grating spreads the remaining wavelengths over the camera's pixels to display a high resolution transmission spectrum. The photonic crystal biosensor is fabricated on a plastic substrate and attached to a standard glass microscope slide that can easily be removed and replaced within the optical path. A custom software app was developed to convert the camera images into the photonic crystal transmission spectrum in the visible wavelength range, including curve-fitting analysis that computes the photonic crystal resonant wavelength with 0.009 nm accuracy. We demonstrate the functionality of the system through detection of an immobilized protein monolayer, and selective detection of concentration-dependent antibody binding to a functionalized photonic crystal. We envision the capability for an inexpensive, handheld biosensor instrument with web connectivity to enable point-of-care sensing in environments that have not been practical previously.

[1]  Ingemar Lundström,et al.  Bioanalysis with surface plasmon resonance , 1991 .

[2]  M. Natan,et al.  Colloidal Au-enhanced surface plasmon resonance immunosensing. , 1998, Analytical chemistry.

[3]  Lin He,et al.  Colloidal Au-Enhanced Surface Plasmon Resonance for Ultrasensitive Detection of DNA Hybridization , 2000 .

[4]  D. Diamond,et al.  Development and application of surface plasmon resonance-based biosensors for the detection of cell-ligand interactions. , 2000, Analytical biochemistry.

[5]  R. Weil,et al.  Limitations on the quantitative determination of telomerase activity by the electrophoretic and ELISA based TRAP assays. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[6]  R. Mage,et al.  A comparison of ELISA and flow microsphere-based assays for quantification of immunoglobulins. , 2002, Journal of immunological methods.

[7]  B. Cunningham,et al.  A label-free optical technique for detecting small molecule interactions. , 2002, Biosensors & bioelectronics.

[8]  Marek Piliarik,et al.  Multi-analyte surface plasmon resonance biosensing. , 2005, Methods.

[9]  Brian T. Cunningham,et al.  A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation , 2007, Apoptosis.

[10]  Charles J. Choi,et al.  Single-step fabrication and characterization of photonic crystal biosensors with polymer microfluidic channels. , 2006, Lab on a chip.

[11]  Brian T. Cunningham,et al.  Self-referenced assay method for photonic crystal biosensors: Application to small molecule analytes , 2007 .

[12]  Hirotsugu Ogi,et al.  Concentration dependence of IgG-protein A affinity studied by wireless-electrodeless QCM. , 2007, Biosensors & bioelectronics.

[13]  P. Fauchet,et al.  Two-dimensional silicon photonic crystal based biosensing platform for protein detection. , 2007, Optics express.

[14]  Charles J. Choi,et al.  A 96-well microplate incorporating a replica molded microfluidic network integrated with photonic crystal biosensors for high throughput kinetic biomolecular interaction analysis. , 2007, Lab on a chip.

[15]  C. Pannuti,et al.  Sensitivity and specificity of three ELISA-based assays for discriminating primary from secondary acute dengue virus infection. , 2007, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[16]  Martin Kristensen,et al.  Photonic-crystal waveguide biosensor. , 2007, Optics express.

[17]  G. Kuchel,et al.  ELISA and multiplex technologies for cytokine measurement in inflammation and aging research. , 2008, The journals of gerontology. Series A, Biological sciences and medical sciences.

[18]  Brian T. Cunningham,et al.  Label free biosensor incorporating a replica-molded, vertically emitting distributed feedback laser , 2008 .

[19]  Brian T. Cunningham,et al.  High sensitivity photonic crystal biosensor incorporating nanorod structures for enhanced surface area , 2008 .

[20]  Lance G. Laing,et al.  Advantages and application of label-free detection assays in drug screening , 2008, Expert opinion on drug discovery.

[21]  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.

[22]  Arunas Ramanavicius,et al.  Surface plasmon resonance biosensor for direct detection of antibodies against human growth hormone. , 2009, The Analyst.

[23]  B. Cunningham,et al.  Label-Free Photonic Crystal Biosensor Integrated Microfluidic Chip for Determination of Kinetic Reaction Rate Constants , 2009, IEEE Sensors Journal.

[24]  A. Limaye,et al.  Surface plasmon resonance detection using antibody-linked magnetic nanoparticles for analyte capture, purification, concentration, and signal amplification. , 2009, Analytical chemistry.

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

[26]  Rashid Bashir,et al.  A detection instrument for enhanced-fluorescence and label-free imaging on photonic crystal surfaces. , 2009, Optics express.

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

[28]  Sanjeeva Srivastava,et al.  Label‐free detection techniques for protein microarrays: Prospects, merits and challenges , 2009, Proteomics.

[29]  Naomi J. Halas,et al.  Label-free detection of DNA hybridization using surface enhanced Raman spectroscopy. , 2010, Journal of the American Chemical Society.

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

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

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

[33]  Martina Gerken,et al.  Photonic crystal biosensors towards on‐chip integration , 2012, Journal of biophotonics.

[34]  Xiaowei Guo Surface plasmon resonance based biosensor technique: A review , 2012, Journal of biophotonics.

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