Lab-on-a-Chip for Monitoring the Quality of Raw Milk

  • Choi Jeong-Woo (Department of Chemical and Biomolecular Engineering, and Interdisciplinary Program of Integrated Biotechnology, Sogang University) ;
  • Kim Young-Kee (Department of Chemical Engineering, Hankyong National University) ;
  • Kim Hee-Joo (Department of Chemical and Biomolecular Engineering, and Interdisciplinary Program of Integrated Biotechnology, Sogang University) ;
  • Lee Woo-Chang (Department of Chemical Engineering, Hankyong National University) ;
  • Seong Gi-Hun (Department of Applied Chemistry, Hanyang University)
  • Published : 2006.08.01

Abstract

A lab-on-a-chip (LoC) was designed for simultaneous monitoring of microorganisms, antibiotic residues, somatic cells, and pH in raw milk. The LoC was fabricated from polydimethylsiloxane (PDMS) using microelectromechanical system (MEMS) technology, which consisted of two parts; a protein array and microchannel. The protein array was fabricated by immobilizing five types of antibodies corresponding to two microorganisms, two antibiotic residues, and somatic cells. A sol-gel film was deposited on a glass substrate to immobilize the antibodies. The target analytes in raw milk could be bound with the corresponding antibody by an immunoreaction, and the antigen-antibody complex was detected using fluorescence microscopy. SNARF-dextran was used as a pH indicator, and the SNARF-entrapped hydrogel was attached to the microchannel in the chip. After injecting the milk sample into the channel, the pH was measured by monitoring the change in fluorescence intensity by fluorescence microscopy. The on-chip simultaneous assay of two microorganisms (E. coli O157:H7 and Streptococcus agalactiae), two antibiotic residues (penicillin G and dihydrostreptomycin), and neutrophils was successfully accomplished using the proposed LoC system.

Keywords

References

  1. Albracht, J. H. and M. S. De Wit. 1987. Analysis of gentamicin in raw material in pharmaceutical preparations by high-performance liquid chromatography. J. Chrornatogr. 389:306-311 https://doi.org/10.1016/S0021-9673(01)94439-5
  2. Arenkow, P., A. Kukhtin, S. Voloshchuk, V. Chupeeva, and A. Mirzabekov. 2000. Protein microchips: Use for immunoassay and enzymatic reactions. Anal. Biochern. 278: 123-131 https://doi.org/10.1006/abio.1999.4363
  3. Baxter, G. A., J. P. Ferguson, M. C. O'Conner, and C. T. Elliott. 2001. Detection of streptomycin residues in whole milk using an optical immunobiosensor. J. Agric. Food Chem. 49: 3204-3207 https://doi.org/10.1021/jf001484l
  4. Cahill, D. J. 2000. Protein arrays: A high-throughput solution for proteomics research? Trends Biotechnol. 18: 47 -51 https://doi.org/10.1016/S0167-7799(00)00006-8
  5. Choi, J. W., Y. S. Nam, and M. Fujihira. 2004. Nanoscale fabrication of biomolecular layer and its application to biodevices. Biotechnol. Bioprocess Eng. 9: 76-85 https://doi.org/10.1007/BF02932988
  6. Chow, A. W. 2002. Lab-on-a-chip: Opportunities for chemical engineering. AIChE J. 48: 1590-1595 https://doi.org/10.1002/aic.690480802
  7. Eva, G., B. Peter, and S. Ase. 2002. Biosensor analysis of penicillin G in milk based on the inhibition of carboxypeptidase activity. Anal. Chim. Acta 468: 153-159 https://doi.org/10.1016/S0003-2670(02)00599-8
  8. Fujii, T. 2002. PDMS-based microfluidic devices for biomedical applications. Microelectr. Engin. 61-62: 907-914 https://doi.org/10.1016/S0167-9317(02)00494-X
  9. Gaudin, V., J. Fontaine, and P. Maris. 2001. Screening of penicillin residues in milk by a surface plasmon resonancebased biosensor assay: Comparison of chemical and enzymatic sample pre-treatment. Anal. Chim. Acta. 436: 191-198 https://doi.org/10.1016/S0003-2670(01)00948-5
  10. Gerhardt, G. C., C. D. C. Salisburg, and J. D. Macneil. 1994. Analysis of streptomycin and dihydrostreptomycin in milk by liquid chromatography. J. AOAC Int. 77: 765-767
  11. Guggisberg, D. and H. Koch. 1995. Method for the quantitative determination of gentamicin in meat, liver and kidney by HPLC and post-column derivatization. Mitteilungen aus dem Gebiete der Lebensmitteluntersuchung und Hygiene 86: 14-28
  12. Haasnoot, W., G. Cazemier, M. Koets, and A. Van Amerongen. 2003. Single biosensor immunoassay for the detection of five aminoglycosides in reconstituted skimmed milk. Anal. Chim. Acta 488: 53-60 https://doi.org/10.1016/S0003-2670(03)00628-7
  13. Haasnoot, W., E. E. M. G. Loomans, G. Cazemier, R. Dietrich, R. Verheijen, A. A. Bergwerff, and R. W. Stephany. 2002. Direct versus competitive biosensor immunoassays for the detection of (dihydro )streptomycin residues in milk. Food Agric. Immunol. 14: 15-28 https://doi.org/10.1080/09540100220137637
  14. Haasnoot, W., P. Stouten, G. Cazemier, A. Lommen, J. F. M. Nouws, and H. J. Keukens. 1999. Immunochemical detection of aminoglycosides in milk and kidney. Analyst 124: 301-305 https://doi.org/10.1039/a807846g
  15. Jacques, N., E. Harry, S. lise, L. Gerard, S. Jan, and S. Henk. 1999. A microbiological assay system for assessment of raw milk exceeding EU maxium residue levels. Int. Dairy J. 9: 85-90 https://doi.org/10.1016/S0958-6946(99)00026-6
  16. Kelvin, H. L. 2001. Proteomics: A technology-driven and technology limited discovery science. Trends Biotechnol. 19: 217-222 https://doi.org/10.1016/S0167-7799(01)01639-0
  17. Kodadek, T. 2001. Protein microarrays: Prospects and problems. Chern. Biol. 8: 105-115 https://doi.org/10.1016/S1074-5521(00)90067-X
  18. Kukar, T., S. Eckenrode, Y. Gu, W. Lian, M. Megginson, J.-X. She, and D. Wu. 2002. Protein microarrays to detect protein-protein interactions using red and green fluorescent proteins. Anal. Biochem. 306: 50-54 https://doi.org/10.1006/abio.2002.5614
  19. Kwak, B.-Y., B.-J. Kwon, C.-H. Kweon, and D.-H. Shon. 2004. Detection of Aspergillus, Penicillium, and Fusarium species by sandwich enzyme-linked immunosorbent assay using mixed monoclonal antibodies. J. Microbiol. Biotechnol. 14: 385-389
  20. Oh, B.-K., Y. K. Kim, Y. M. Bae, W. H. Lee, and J. W. Choi. 2002. Detection of Escherichia coli O157:H7 using immunosensor based on surface plasmon resonance. J. Microbiol. Biotechnol. 12: 780-786
  21. Oh, B.-K., Y. K. Kim, W. Lee, Y. M. Bae, W. H. Lee, and J. W. Choi. 2003. Immunosensor for detection of Legionella pneumophila using surface plasmon resonance. Biosens. Bioelectron. 18: 605-611 https://doi.org/10.1016/S0956-5663(03)00032-0
  22. Oh, B.-K., W. Lee, B.-S. Chun, Y. M. Bae, W. H. Lee, J. W. Choi. 2005. The fabrication of protein chip based on surface plasmon resonance for detection of pathogens. Biosens. Bioelectron. 20: 1847-1850 https://doi.org/10.1016/j.bios.2004.05.010
  23. Park, I. S., D. K. Kim, and N. Kim. 2004. Characterization and food application of a potentiometric biosensor measuring $\beta$-lactam antibiotics. J. Microbiol. Biotechnol. 14: 698-706
  24. Schaeferling, M., S. Schiller, H. Paul, M. Kruschinan, P. Pavlickova, M. Meerkamp, C. Giammasi, and D. Kambhampati. 2002. Application of self assembly techniques in the design ofbiocompatible protein microarray surfaces. Electrophoresis 23: 3097-3105 https://doi.org/10.1002/1522-2683(200209)23:18<3097::AID-ELPS3097>3.0.CO;2-G
  25. Schnappinger, P, E. Usleber, E. Martlbauer, and G. Terplan. 1993. Enzyme immunoassay for the detection of streptomycin and dihydrostreptomycin in milk. Food Agric. Immunol. 5: 67-74 https://doi.org/10.1080/09540109309354785
  26. Setford, S. J., R. M. Van Es, Y. F. Blankwater, and S. Kroger. 1999. Receptor binding protein amperometric affinity sensor for rapid $\beta$-Iactam quantification in milk. Anal. Chim. Acta 398: 13-22 https://doi.org/10.1016/S0003-2670(99)00383-9
  27. Strasser, A., R. Dietrich, E. Usleber, and E. Martlbauer. 2003. Immunochemical rapid test for multiresidue analysis of antimicrobial drugs in milk using monoclonal antibodies and hapten-glucose oxidase conjugates. Anal. Chim. Acta 495: 11-19 https://doi.org/10.1016/j.aca.2003.08.024
  28. Verheijen, R., I. K. Osswald, R. Dietrich, and W. Haasfoot. 2000. Development of a one step strip test for the detection of (dihydro)streptomycin residues in raw milk. Food Agric. Immunol. 12: 31-40 https://doi.org/10.1080/09540100099607
  29. Vinet, F., P. Chaton, and Y. FouilIet. 2002. Microarrays and microtluidic devices: Miniaturized systems for biological analysis. Microelectr. Engin. 61-62: 41-47 https://doi.org/10.1016/S0167-9317(02)00458-6