Smartphone Instrument for Portable Enzyme- Linked Immunosorbent Assays

We demonstrate the utilization of a smartphone camera as a spectrometer that is capable of measuring Enzyme Linked Immunosorbent Assays (ELISA) at biologically-relevant concentrations with the aid of a custom cradle that aligns a diffraction grating and a collimating lens between a light source and the imaging sensor. Two example biomarkers are assayed using conventional ELISA protocols: IL-6, a protein used diagnostically for several types of cancer, and Ara h 1, one of the principle peanut allergens. In addition to the demonstration of limits of detection at medically-relevant concentrations, a screening of various cookies was completed to measure levels of peanut cross-contamination in local bakeries. The results demonstrate the utility of the instrument for quantitatively performing broad classes of homogeneous colorimetric assays, in which the endpoint readout is the color change of a liquid sample.

Hojeong Yu | Kenneth D Long | Brian T Cunningham | J. Blache | G. Whitesides | H. Klocker | N. Switz | S. Shevkoplyas | M. Mawatari | E. Goillot | K. Long | Hojeong Yu | B. Cunningham | L. Gurrin | D. G. Altman | D. Sheffield | D. Moneret-vautrin | J. Nordlee | R. Helm | G. Bannon | B. Remington | E. Knol | C. Bruijnzeel‐Koomen | E. van Hoffen | W. Shreffler | L. Bentolila | J. Kampeera | W. Kiatpathomchai | A. Galas | S. Koppelman | J. Delpero | Z. Culig | B. Withyachumnarnkul | S. Hefle | K. J. Allen | D. Sehy | Z. Göröcs | V. Moutardier | A. Muñoz-Furlong | A. Mercatello | Y. Merrouche | A. DunnGalvin | D. Mokart | M. Sonohata | J. Han | S. Négrier | A. Tsay | M. Hoekstra | J. Kabourek | P. Kolodziejczyk | E. Walewska | L. Ścisło | A. Czupryna | A. Sannini | T. Flaim | I. Eder | J. Brun | F. Knotek | C. Xu | A. Penninks | U. Bartelt | A. Ravault | B. Tookdee | R. Maamari | S. Attali | S. Cheng | A. Burks | A. C. Knulst | S. Someya | G. Bartsch | M. L. Mathai | A. Volpe | Wong | E. Dubovi | R. Caire | W. Horninger | R. Richards-Kortum | J. Tourani | J. Kulig | D. Di Carlo | A. Puntambekar | S. G. Pasmans | T. Hotokebuchi | G. Houvenaeghel | J. Moskovtchenko | J Y Blay | J. Wong | H. Yu | R. Crevel | J. Godbold | M. Gupta | A. Ozcan | W. Luo | S H Sicherer | Hojeong Yu | B. T. Cunningham | A L Litster | B. Pressler | R G Norkus | J. Maurer | N. A. Schultz | J. D. Stuart | G. A. Robbins | R. D. Bristol | G Bansal | W. Zhou | P. J. Barlow | P. S. Joshi | H. L. Lo | Y. K. Chung | R Suebsing | W. Turner | C C Huang | P. Y. Lee | P. Y. Chen | T. Y. Liu | D N Breslauer | W. A. Lam | D. A. Fletcher | Q Wei | H. Qi | D. Tseng | S. J. Ki | Z. Wan | T.-T Wu | R. Sun | D. Gallegos | H. Yu | P. P. Clark | Y. Lin | S. George | P. Nath | Label-Free | A F Coskun | D. Khodadadi | R. Nagi | A. Tey | K. Sadeghi | S. Feng | E. Yan | D J Guerrero | W. DiMenna | R. Mercado | S. Sun | J Kai | N. Santiago | S. H. Lee | V. Moore | C. H. Ahn | F Poulsen | K. B. Jensen | E Cauchon | S. Liu | S. E. Percival | D. Rowland | P. Binkert | J.-P Strickner | Falgueyret | J Brown | L. Theis | L. Kerr | N. Zakhidova | K. O 'connor | M. Uthman | Z. M. Oden | A J Mach | J. H. Kim | A. Arshi | S. C. Hur | N M Pham | H Kugisaki | M. Komine | K. Tsunoda | H. Honke | M. Merlin | W.-S Wong | J. Yu | L.-H Wong | H.-Y Chan | S.-H Chu | K.-O Ng | K. Chan | J.-Y Sung | Y. Chan | A Hobisch | T. Putz | V. Combaret | A E Flinterman | C. F. Den | Hartog Jager | H. Sampson | A M Szczepanik | T. Scully | M. Siedlar | M. Lenart | M. Rutkowska | S L Taylor | J. Baumert | A Pomés | M. D. Chapman | M. Morisset | P. Dumont | Y. Meijer | M Wensing | G A Zurzolo | S. L. Taylor | M. L. Tang | J. O. Hourihane | J M Bland | M Enders | K. Bunn | S. Strobel | K. Dietz | G. Enders | L. Wong

[1]  R. Lequin Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). , 2005, Clinical chemistry.

[2]  C. Ahn,et al.  A novel microfluidic microplate as the next generation assay platform for enzyme linked immunoassays (ELISA). , 2012, Lab on a chip.

[3]  Klaus Dietz,et al.  Performance of the Elecsys Rubella IgG Assay in the Diagnostic Laboratory Setting for Assessment of Immune Status , 2013, Clinical and Vaccine Immunology.

[4]  Ying Sun,et al.  A smartphone-based platform for analyzing physiological audio signals , 2012, 2012 38th Annual Northeast Bioengineering Conference (NEBEC).

[5]  H. Sampson,et al.  Peanut allergy: emerging concepts and approaches for an apparent epidemic. , 2007, The Journal of allergy and clinical immunology.

[6]  E. Dubovi,et al.  Accuracy of a point-of-care ELISA test kit for predicting the presence of protective canine parvovirus and canine distemper virus antibody concentrations in dogs. , 2012, Veterinary journal.

[7]  Chih-Chung Huang,et al.  Design and implementation of a smartphone-based portable ultrasound pulsed-wave doppler device for blood flow measurement , 2012, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[8]  J D Stuart,et al.  Field examination of ground water quality as an indicator of microbiological activity at gasoline contaminated sites. , 1996, Chemosphere.

[9]  Vincent Wai-Sun Wong,et al.  High serum interleukin‐6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B , 2009, International journal of cancer.

[10]  Rebecca Richards-Kortum,et al.  A Hand-Powered, Portable, Low-Cost Centrifuge for Diagnosing Anemia in Low-Resource Settings , 2011, The American journal of tropical medicine and hygiene.

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

[12]  J. Falgueyret,et al.  Development of a homogeneous immunoassay for the detection of angiotensin I in plasma using AlphaLISA acceptor beads technology. , 2009, Analytical biochemistry.

[13]  Dino Di Carlo,et al.  Automated cellular sample preparation using a Centrifuge-on-a-Chip. , 2011, Lab on a chip.

[14]  T. Mandrup-Poulsen,et al.  Interleukin-6 and diabetes: the good, the bad, or the indifferent? , 2005, Diabetes.

[15]  George M Whitesides,et al.  Egg beater as centrifuge: isolating human blood plasma from whole blood in resource-poor settings. , 2008, Lab on a chip.

[16]  Derek Tseng,et al.  Fluorescent imaging of single nanoparticles and viruses on a smart phone. , 2013, ACS nano.

[17]  D. Altman,et al.  Measuring agreement in method comparison studies , 1999, Statistical methods in medical research.

[18]  Henrik Eliasson Color calibration of a CMOS digital camera for mobile imaging , 2010, Electronic Imaging.

[19]  R. Helm,et al.  Monitoring peanut allergen in food products by measuring Ara h 1. , 2003, The Journal of allergy and clinical immunology.

[20]  P. Nath,et al.  Label-free biodetection using a smartphone. , 2013, Lab on a chip.

[21]  Steve L. Taylor,et al.  Threshold dose for peanut: risk characterization based upon published results from challenges of peanut-allergic individuals. , 2009, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[22]  A. Knulst,et al.  Determination of no-observed-adverse-effect levels and eliciting doses in a representative group of peanut-sensitized children. , 2006, The Journal of allergy and clinical immunology.

[23]  J. Godbold,et al.  US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. , 2010, The Journal of allergy and clinical immunology.

[24]  M. Mawatari,et al.  Serum concentrations of interleukin-6 in patients following unilateral versus bilateral total knee arthroplasty , 2009, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[25]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[26]  J. Blache,et al.  Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery. , 2005, British journal of anaesthesia.

[27]  J. Blay,et al.  Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. , 1992, Cancer research.

[28]  Derek K. Tseng,et al.  Detection and Spatial Mapping of Mercury Contamination in Water Samples Using a Smart-Phone , 2014, ACS nano.

[29]  Steve L. Taylor,et al.  Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol , 2013, Allergy, Asthma & Clinical Immunology.

[30]  F. Poulsen,et al.  A Luminescent Oxygen Channeling Immunoassay for the Determination of Insulin in Human Plasma , 2007, Journal of biomolecular screening.

[31]  J. Kampeera,et al.  Evaluation of colorimetric loop‐mediated isothermal amplification assay for visual detection of Streptococcus agalactiae and Streptococcus iniae in tilapia , 2013, Letters in applied microbiology.

[32]  H. Klocker,et al.  Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. , 1998, Cancer research.

[33]  Douglas J. Guerrero,et al.  Dyed red, green, and blue photoresist for manufacture of high-resolution color filter arrays for image sensors , 2003, IS&T/SPIE Electronic Imaging.

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

[35]  David Sheffield,et al.  Threshold dose for peanut: Risk characterization based upon diagnostic oral challenge of a series of 286 peanut-allergic individuals. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[36]  I. Gust,et al.  Evaluation of enzyme-linked immunosorbent assays: a method of data analysis. , 1988, Journal of virological methods.

[37]  Li Shen,et al.  Point-of-care colorimetric detection with a smartphone. , 2012, Lab on a chip.

[38]  Heike Knüpfer,et al.  Significance of interleukin-6 (IL-6) in breast cancer (review) , 2007, Breast Cancer Research and Treatment.

[39]  M. Rutkowska,et al.  IL-6 serum levels predict postoperative morbidity in gastric cancer patients , 2011, Gastric Cancer.

[40]  N. M. Pham Blood Filtration for Multiplexed Point-of-care Diagnostic Devices , 2012 .

[41]  A. Knulst,et al.  Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time , 2007, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[42]  Weibiao Zhou,et al.  Review of Rapid Tests Available for Measuring the Quality Changes in Frying Oils and Comparison with Standard Methods , 2010, Critical reviews in food science and nutrition.

[43]  A. Knulst,et al.  The distribution of individual threshold doses eliciting allergic reactions in a population with peanut allergy. , 2002, The Journal of allergy and clinical immunology.

[44]  C. Galli Modeling systematic errors: polychromatic sources of Beer-Lambert deviations in HPLC/UV and nonchromatographic spectrophotometric assays. , 2001, Journal of pharmaceutical and biomedical analysis.