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Chemiluminescence lateral flow immunoassay cartridge with integrated amorphous silicon photosensors array for human serum albumin detection in urine samples

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Abstract

A novel and disposable cartridge for chemiluminescent (CL)-lateral flow immunoassay (LFIA) with integrated amorphous silicon (a-Si:H) photosensors array was developed and applied to quantitatively detect human serum albumin (HSA) in urine samples. The presented analytical method is based on an indirect competitive immunoassay using horseradish peroxidase (HRP) as a tracer, which is detected by adding the luminol/enhancer/hydrogen peroxide CL cocktail. The system comprises an array of a-Si:H photosensors deposited on a glass substrate, on which a PDMS cartridge that houses the LFIA strip and the reagents necessary for the CL immunoassay was optically coupled to obtain an integrated analytical device controlled by a portable read-out electronics. The method is simple and fast with a detection limit of 2.5 mg L−1 for HSA in urine and a dynamic range up to 850 mg L−1, which is suitable for measuring physiological levels of HSA in urine samples and their variation in different diseases (micro- and macroalbuminuria). The use of CL detection allowed accurate and objective analyte quantification in a dynamic range that extends from femtomoles to picomoles. The analytical performances of this integrated device were found to be comparable with those obtained using a charge-coupled device (CCD) as a reference off-chip detector. These results demonstrate that integrating the a-Si:H photosensors array with CL-LFIA technique provides compact, sensitive and low-cost systems for CL-based bioassays with a wide range of applications for in-field and point-of-care bioanalyses.

A novel integrated portable device was developed for direct quantitative detection of human serum albumin (HSA) in urine samples, exploiting a chemiluminescence lateral flow immunoassay (LFIA). The device comprises a cartridge that holds the LFIA strip and all the reagents necessary for the analysis, an array of amorphous silicon photosensors, and a custom read-out electronics

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References

  1. Wong RC, Tse HY. Lateral flow immunoassay. New York: Humana Press; 2009.

    Book  Google Scholar 

  2. Anfossi L, Calderara M, Baggiani C, Giovannoli C, Arletti E, Giraudi G. Development and application of a quantitative lateral flow immunoassay for fumonisins in maize. Anal Chim Acta. 2010;682:104–9.

    Article  CAS  Google Scholar 

  3. Smith JP, Sammons DL, Robertson SA, Snawder JE. Enhanced performance of methamphetamine lateral flow cassettes using an electronic lateral flow reader. J Occup Environ Hyg. 2015;12:45–50.

    Article  CAS  Google Scholar 

  4. Lee S, Kim G, Moon J. Development of a smartphone-based reading system for lateral flow immunoassay. J Nanosci Nanotechnol. 2014;14:8453–7.

    Article  CAS  Google Scholar 

  5. Adhikari M, Strych U, Kim J, Goux H, Dhamane S, Poongavanam MV, et al. Aptamer-phage reporters for ultrasensitive lateral flow assays. Anal Chem. 2015;87:11660–5.

    Article  CAS  Google Scholar 

  6. Cho I-H, Bhunia A, Irudayaraj J. Rapid pathogen detection by lateral-flow immunochromatographic assay with gold nanoparticle-assisted enzyme signal amplification. Int J Food Microbiol. 2015;206:60–6.

    Article  CAS  Google Scholar 

  7. Liang RL, Xu XP, Liu TC, Zhou JW, Wang XG, Ren ZQ, et al. Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium(III) chelate microparticles-based lateral flow test strips. Anal Chim Acta. 2015;891:277–83.

    Article  CAS  Google Scholar 

  8. Chen YQ, Chen Q, Han MM, Liu JY, Zhao P, He LD, et al. Near-infrared fluorescence-based multiplex lateral flow immunoassay for the simultaneous detection of four antibiotic residue families in milk. Biosens Bioelectron. 2016;79:430–4.

    Article  CAS  Google Scholar 

  9. Di Nardo F, Anfossi L, Giovannoli C, Passini C, Goftman VV, Goryacheva IY, et al. A fluorescent immunochromatographic strip test using quantum dots for fumonisins detection. Talanta. 2016;150:463–8.

    Article  Google Scholar 

  10. Sinawang PD, Rai V, Ionescu RE, Marks RS. Electrochemical lateral flow immunosensor for detection and quantification of dengue NS1 protein. Biosens Bioelectron. 2016;77:400–8.

    Article  CAS  Google Scholar 

  11. Shi L, Wu F, Wen Y, Zhao F, Xiang J, Ma L. A novel method to detect Listeria monocytogenes via superparamagnetic lateral flow immunoassay. Anal Bioanal Chem. 2015;407:529–35.

    Article  CAS  Google Scholar 

  12. Seidel M, Niessner R. Chemiluminescence microarrays in analytical chemistry: a critical review. Anal Bioanal Chem. 2014;406:5589–612.

    Article  CAS  Google Scholar 

  13. Mirasoli M, Guardigli M, Michelini E, Roda A. Recent advancements in chemical luminescence-based lab-on-chip and microfluidic platforms for bioanalysis. J Pharm Biomed Anal. 2014;87:36–52.

    Article  CAS  Google Scholar 

  14. Faulstich K, Gruler R, Eberhard M, Lentzsch D, Haberstroh K. Handheld and portable reader devices for lateral flow immunoassays. In: Wong RC, Tse HY, editors. Lateral flow immunoassay. New York: Humana Press; 2009. p. 157–83.

    Google Scholar 

  15. Mirasoli M, Buragina A, Dolci LS, Simoni P, Anfossi L, Giraudi G, et al. Chemiluminescence based biosensor for fumonisins quantitative detection in maize samples. Biosens Bioelectron. 2012;32:283–7.

    Article  CAS  Google Scholar 

  16. Mirasoli M, Buragina A, Dolci LS, Guardigli M, Simoni P, Montoya A, et al. Development of a chemiluminescence-based quantitative lateral flow immunoassay for on-field detection of 2,4,6-trinitrotoluene. Anal Chim Acta. 2012;721:167–72.

    Article  CAS  Google Scholar 

  17. Zangheri M, Di Nardo F, Anfossi L, Giovannoli C, Baggiani C, Roda A, et al. A multiplex chemiluminescent biosensor for type B-fumonisins and aflatoxin B1 quantitative detection in maize flour. Analyst. 2015;140:358–65.

    Article  CAS  Google Scholar 

  18. Zangheri M, Cevenini L, Anfossi L, Baggiani C, Simoni P, Di Nardo F, et al. A simple and compact smartphone accessory for quantitative chemiluminescence-based lateral flow immunoassay for salivary cortisol detection. Biosens Bioelectron. 2015;64:63–8.

    Article  CAS  Google Scholar 

  19. Caputo D, de Cesare G, Dolci LS, Mirasoli M, Nascetti A, Roda A, et al. Microfluidic chip with integrated a-Si:H photodiodes for chemiluminescence-based bioassays. IEEE Sens J. 2013;13:2595–602.

    Article  CAS  Google Scholar 

  20. Pires NMM, Dong T. Measurement of salivary cortisol by a chemiluminescent organic-based immunosensor. Biomed Mater Eng. 2014;24:15–20.

    CAS  Google Scholar 

  21. de Cesare G, Caputo D, Nascetti A, Guiducci C, Riccò B. a-Si: H ultraviolet sensor for deoxyribonucleic acid analysis. Appl Phys Lett. 2006;88:083904–6.

    Article  Google Scholar 

  22. Caputo D, de Cesare G, Nascetti A, Negri R. Spectral tuned amorphous silicon p-i-n for DNA detection. J Non-Cryst Solids. 2006;352:2004–6.

    Article  CAS  Google Scholar 

  23. Caputo D, de Cesare G, Fanelli C, Nascetti A, Ricelli A, Scipinotti R. Amorphous silicon photosensors for detection of ochratoxin A in wine. IEEE Sens J. 2012;12:2674–9.

    Article  CAS  Google Scholar 

  24. Novo P, Prazeres DMF, Chu V, Conde JP. Microspot-based ELISA in microfluidics: chemiluminescence and colorimetry detection using integrated thin-film hydrogenated amorphous silicon photodiodes. Lab Chip. 2011;11:4063–71.

    Article  CAS  Google Scholar 

  25. Novo P, Moulas G, Prazeres DMF, Chu V, Conde JP. Detection of ochratoxin A in wine and beer by chemiluminescence-based ELISA in microfluidics with integrated photodiodes. Sensor Actuat B Chem. 2013;176:232–40.

    Article  CAS  Google Scholar 

  26. Caputo D, de Cesare G, Scipinotti R, Mirasoli M, Roda A, Zangheri M, et al. Chemiluminescence-based micro-total-analysis system with amorphous silicon photodiodes. Lect Notes Electr Eng. 2014;268:207–11.

    Article  Google Scholar 

  27. Mirasoli M, Nascetti A, Caputo D, Zangheri M, Scipinotti R, Cevenini L, et al. Multiwell cartridge with integrated array of amorphous silicon photosensors for chemiluminescence detection: development, characterization and comparison with cooled-CCD luminograph. Anal Bioanal Chem. 2014;406:5645–56.

    Article  CAS  Google Scholar 

  28. Zangheri M, Mirasoli M, Nascetti A, Caputo D, Bonvicini F, Gallinella G, et al. Microfluidic cartridge with integrated array of amorphous silicon photosensors for chemiluminescence detection of viral DNA. Sens Biosens Res. 2016;7:127–32.

    Google Scholar 

  29. Miller GW, Bruns DE, Hortin GL, Sandberg S, Aakre KM, McQueen MJ, et al. Current issues in measurement and reporting of urinary albumin excretion. Clin Chem. 2009;55:24–38.

    Article  CAS  Google Scholar 

  30. Seegmiller JC, Barnidge DR, Burns BE, Larson TS, Lieske JC, Kumar R. Quantification of urinary albumin by using protein cleavage and LC-MS/MS. Clin Chem. 2009;55:1100–7.

    Article  CAS  Google Scholar 

  31. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32:64–78.

    Article  Google Scholar 

  32. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2003;26:S33–50.

    Article  Google Scholar 

  33. Burtis CA, Ashwood Tietz ER. Textbook of clinical chemistry. 3rd ed. W.B. Saunders Company; 1999.

  34. Adachi H. Microalbuminuria is an independent prognostic information for cardiovascular disease. Atherosclerosis. 2014;237:106–7.

    Article  CAS  Google Scholar 

  35. Basi S, Fesler P, Mimran A, Lewis JB. Microalbuminuria in type 2 diabetes and hypertension. Diabetes Care. 2008;31:S194–201.

    Article  CAS  Google Scholar 

  36. Miró-Casas E, Farré Albaladejo M, Covas M-I, Rodriguez JO, Menoyo Colomer E, Lamuela Raventós RM, et al. Capillary gas chromatography–mass spectrometry quantitative determination of hydroxytyrosol and tyrosol in human urine after olive oil intake. Anal Biochem. 2001;294:63–72.

    Article  Google Scholar 

  37. Caputo D, Forghieri U, Palma F. Low-temperature admittance measurement in thin film amorphous silicon structures. J Appl Phys. 1997;82:733–41.

    Article  CAS  Google Scholar 

  38. Caputo D, de Angelis A, Lovecchio N, Nascetti A, Scipinotti R, de Cesare G. Amorphous silicon photosensors integrated in microfluidic structures as a technological demonstrator of a Lab-on-Chip system. Sens Biosens Res. 2015;3:98–104.

    Google Scholar 

  39. Brown MC. Evolution in lateral flow-based immunoassay systems. In: Wong RC, Tse HY, editors. Lateral flow immunoassay. New York: Humana Press; 2009. p. 1–33.

    Chapter  Google Scholar 

  40. O’Farrell B. Antibodies: key to a robust lateral flow immunoassay. In: Wong RC, Tse HY, editors. Lateral flow immunoassay. New York: Humana Press; 2009. p. 59–74.

    Google Scholar 

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Acknowledgments

We are very grateful to Scriba Nanotecnologie S.r.l. (www.scriba-nanotec.com) for strict collaboration and fruitful scientific discussion related to the design and production of the polydimethylsiloxane cartridge.

Financial support was provided by the Italian Ministry of Instruction, University and Research: PRIN 2010 project prot. 20108ZSRTR “ARTEMIDE (Autonomous Real Time Embedded Multi-analyte Integrated Detection Environment): a fully integrated lab-on-chip for early diagnosis of viral infections” and by the Italian Space Agency, agreement n. 2015-037-R.0 “PLEIADES (Planetary Life Explorer with Integrated Analytical Detection and Embedded Sensors)”.

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Correspondence to Mara Mirasoli.

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The authors declare that they have no conflict of interest.

Clinical samples were available for research purposes according to Italian privacy law (decree 196/ 2003, 1110).

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Published in the topical collection Highlights of Analytical Chemical Luminescence with guest editors Aldo Roda, Hua Cui and Chao Lu.

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Zangheri, M., Di Nardo, F., Mirasoli, M. et al. Chemiluminescence lateral flow immunoassay cartridge with integrated amorphous silicon photosensors array for human serum albumin detection in urine samples. Anal Bioanal Chem 408, 8869–8879 (2016). https://doi.org/10.1007/s00216-016-9991-0

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