A simple and compact smartphone accessory for quantitative chemiluminescence-based lateral flow immunoassay for salivary cortisol detection.

We have developed a simple and accurate biosensor based on a chemiluminescent (CL)-lateral flow immunoassay (LFIA) method integrated in a smartphone to quantitatively detect salivary cortisol. The biosensor is based on a direct competitive immunoassay using peroxidase-cortisol conjugate, detected by adding the chemiluminescent substrate luminol/enhancer/hydrogen peroxide. The smartphone camera is used as light detector, for image acquisition and data handling via a specific application. We 3D-printed simple accessories to adapt the smartphone. The system comprises a cartridge, which houses the LFIA strip, and a smartphone adaptor with a plano-convex lens and a cartridge-insertion slot. This provides a mini-darkbox and aligned optical interface between the camera and the LFIA membrane for acquiring CL signals. The method is simple and fast, with a detection limit of 0.3 ng/mL. It provides quantitative analysis in the range of 0.3-60 ng/mL, which is adequate for detecting salivary cortisol in the clinically accepted range. It could thus find application in the growing area of home-self-diagnostic device technology for clinical biomarker monitoring, overcoming the current difficulties in achieving sensitive and quantitative information with conventional systems taking the advantage of smartphone connectivity and the enhanced performance of the included camera.

[1]  Á. Montoya,et al.  Development of a chemiluminescence-based quantitative lateral flow immunoassay for on-field detection of 2,4,6-trinitrotoluene. , 2012, Analytica chimica acta.

[2]  Dan Du,et al.  Quantum dot-based immunochromatographic fluorescent biosensor for biomonitoring trichloropyridinol, a biomarker of exposure to chlorpyrifos. , 2010, Analytical chemistry.

[3]  César Fernández-Sánchez,et al.  Disposable noncompetitive immunosensor for free and total prostate-specific antigen based on capacitance measurement. , 2004, Analytical chemistry.

[4]  B. Kudielka,et al.  Salivary cortisol as a biomarker in stress research , 2009, Psychoneuroendocrinology.

[5]  Rudolf Krska,et al.  A rapid lateral flow test for the determination of total type B fumonisins in maize , 2009, Analytical and bioanalytical chemistry.

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

[7]  Edward M. Barrett,et al.  Integrated thin-film polymer/fullerene photodetectors for on-chip microfluidic chemiluminescence detection. , 2007, Lab on a chip.

[8]  Hongying Zhu,et al.  Optical imaging techniques for point-of-care diagnostics. , 2013, Lab on a chip.

[9]  Aldo Roda,et al.  Chemiluminescent detection systems of horseradish peroxidase employing nucleophilic acylation catalysts. , 2008, Analytical biochemistry.

[10]  A. Roda,et al.  Chemiluminescent low-light imaging of biospecific reactions on macro- and microsamples using a videocamera-based luminograph. , 1996, Analytical chemistry.

[11]  A. Roda,et al.  Development of a sensitive enzyme immunoassay for plasma and salivary steroids. , 1984, Talanta.

[12]  Robert Salter,et al.  Interlaboratory study of the Charm ROSA Safe Level Aflatoxin M1 Quantitative lateral flow test for raw bovine milk. , 2006, Journal of AOAC International.

[13]  Giyoung Kim,et al.  Performance Improvement of the One-Dot Lateral Flow Immunoassay for Aflatoxin B1 by Using a Smartphone-Based Reading System , 2013, Sensors.

[14]  Xilin Zhao,et al.  Lateral flow immunoassay using europium chelate-loaded silica nanoparticles as labels. , 2009, Clinical chemistry.

[15]  Geertruida A. Posthuma-Trumpie,et al.  Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey , 2009, Analytical and bioanalytical chemistry.

[16]  Zhenpeng Qin,et al.  Significantly improved analytical sensitivity of lateral flow immunoassays by using thermal contrast. , 2012, Angewandte Chemie.

[17]  Il-Hoon Cho,et al.  Plastic ELISA-on-a-chip based on sequential cross-flow chromatography. , 2006, Analytical chemistry.

[18]  E. Alocilja,et al.  A conductometric biosensor for biosecurity. , 2003, Biosensors & bioelectronics.

[19]  G. Whitesides,et al.  Diagnostics for the developing world: microfluidic paper-based analytical devices. , 2010, Analytical chemistry.

[20]  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.

[21]  Aldo Roda,et al.  Microtiter format for simultaneous multianalyte detection and development of a PCR-chemiluminescent enzyme immunoassay for typing human papillomavirus DNAs. , 2002, Clinical chemistry.

[22]  Laura Anfossi,et al.  Development and application of a quantitative lateral flow immunoassay for fumonisins in maize. , 2010, Analytica chimica acta.

[23]  A. Nascetti,et al.  Microfluidic Chip With Integrated a-Si:H Photodiodes for Chemiluminescence-Based Bioassays , 2013, IEEE Sensors Journal.

[24]  Weian Zhao,et al.  Lab on paper. , 2008, Lab on a chip.

[25]  Xuena Zhu,et al.  Paper based point-of-care testing disc for multiplex whole cell bacteria analysis. , 2011, Biosensors & bioelectronics.

[26]  Elisa Michelini,et al.  A portable bioluminescence engineered cell-based biosensor for on-site applications. , 2011, Biosensors & bioelectronics.

[27]  Xu Li,et al.  Patterned paper and alternative materials as substrates for low-cost microfluidic diagnostics , 2012 .

[28]  L J Kricka,et al.  Chemiluminescent methods for detecting and quantitating enzyme activity. , 2000, Methods in enzymology.

[29]  Ashok Mulchandani,et al.  Label-free, chemiresistor immunosensor for stress biomarker cortisol in saliva. , 2011, Biosensors & bioelectronics.

[30]  Elisa Michelini,et al.  Peer Reviewed: Analytical Bioluminescence and Chemiluminescence , 2003 .

[31]  A. Roda,et al.  Chemiluminescence-based biosensor for fumonisins quantitative detection in maize samples. , 2012, Biosensors & bioelectronics.

[32]  Ying Wang,et al.  Rapid and sensitive detection of protein biomarker using a portable fluorescence biosensor based on quantum dots and a lateral flow test strip. , 2010, Analytical chemistry.

[33]  N. Ahuja,et al.  The Smartphone in Medicine: A Review of Current and Potential Use Among Physicians and Students , 2012, Journal of medical Internet research.

[34]  Aldo Roda,et al.  Portable device based on chemiluminescence lensless imaging for personalized diagnostics through multiplex bioanalysis. , 2011, Analytical chemistry.