Abstract
Previous diagnosing methods based on agglutination have a limitation in view of emergency and point-of-care diagnoses due to the requirement of large scale equipments and much agglutination time. In this paper, we propose a low cost microfluidic lab-on-a-chip for more efficient detection of agglutination. In the present lab-on-a-chip, two inlet microwells, flow guiding microchannels, chaotic micromixer and reaction microwell are fully integrated. Mold inserts for the lab-on-a-chip were manufactured by UV photolithography and nickel electroplating process. The complete lab-on-a-chip was realized by the microinjection molding of cyclic olefin copolymer and the subsequent thermal bonding. The improved serpentine laminating micromixer, developed by our group, integrated in the lab-on-a-chip showed the high-level of chaotic mixing, thereby enabling us to get a reliable mixing of sample and reagent. The performance of the fabricated lab-on-a-chip was demonstrated by agglutination experiments with simulated bloods of 10 μl and simulated sera of 10 μl. The results of agglutination inside the reaction microwell were clearly read by means of the level of light transmission. The present microfluidic lab-on-a-chip could be widely applied to various clinical diagnostics based on agglutination tests.
Similar content being viewed by others
References
Ahn CH, Choi J-W, Beaucage G, Nevin JH, Lee J-B, Puntambekar A et al (2004) Disposable smart lab on a chip for point-of-care clinical diagnostics. Proc IEEE 92:154–173. doi:10.1109/JPROC.2003.820548
Auroux P-A, Iossifidis D, Reyes DR, Manz A (2002) Micro total analysis systems. 2. Analytical standard operations and applications. Anal Chem 74:2637–2652. doi:10.1021/ac020239t
Bains W (1998) Simple DNA probe assays based on particle agglutination. Clin Chem 44:876–878
Becker H, Gärtner C (2000) Polymer microfabrication methods for microfluidic analytical applications. Electrophoresis 21:12–26. doi:10.1002/(SICI)1522-2683(20000101)21:1<12::AID-ELPS12>3.0.CO;2-7
Duffy DC, McDonald JC, Schueller OJA, Whitesides GM (1998) Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal Chem 70:4974–4984. doi:10.1021/ac980656z
Feng Y, Zhou Z, Ye X, Xiong J (2003) Passive valves based on hydrophobic microfluidics. Sens Actuat A 108:138–143. doi:10.1016/S0924-4247(03)00363-7
Gupta A, Chaudhary VK (2003) Whole-blood agglutination assay for on-site detection of human immunodeficiency virus infection. J Clin Microbiol 41:2814–2821. doi:10.1128/JCM.41.7.2814-2821.2003
Ise Y, Fukuda M, Suzuki T (1987) Interaction of hepatitis B surface antigen with serum albumin of various species on polystylene latex particles. Med Microbiol Immunol (Berl) 176:199–207. doi:10.1007/BF00196687
Kim DS, Lee SH, Kwon TH, Ahn CH (2005) A serpentine laminating micromixer combining splitting/recombination and advection. Lab Chip 5:739–747. doi:10.1039/b418314b
Kim DS, Lee SH, Ahn CH, Lee JY, Kwon TH (2006a) Disposable integrated microfluidic biochip for blood typing by plastic microinjection moulding. Lab Chip 6:794–802. doi:10.1039/b516495h
Kim DS, Lee HS, Lee B-K, Yang SS, Kwon TH, Lee SS (2006b) Replications and analysis of microlens array fabricated by a modified LIGA process. Polym Eng Sci 46:416–425. doi:10.1002/pen.20466
Kim DS, Lee HS, Han J, Lee SH, Ahn CH, Kwon TH (2008) Collapse-free thermal bonding technique for large area microchambers in plastic lab-on-a-chip applications. Microsyst Technol 14:179–184. doi:10.1007/s00542-007-0416-z
Lee SH, Han J, Kim DS, Kwon TH, Hwang CJ, Heo YM, et al (2004) A high precision self-assembly technique for multilayer polymer lab-on-a-chip. In: Proceedings micro total analysis systems 2004 (μTAS 2004), September 2004, Malmö, Sweden, 2: 413–415
Lee B-K, Hwang CJ, Kim DS, Kwon TH (2008) Replication quality of flow-through microfilters in microfluidic lab-on-a-chip for blood typing by microinjection molding. J Manuf Sci E–T ASME 130. doi:10.1115/1.2896142
Park JM, Kim DS, Kang TG, Kwon TH (2008) Improved serpentine laminating micromixer with enhanced local advection. Microfluid Nanofluid 4:513–523. doi:10.1007/s10404-007-0208-x
Reyes DR, Iossifidis D, Auroux P-A, Manz A (2002) Micro total analysis systems. 1. Introduction, theory, and technology. Anal Chem 74:2623–2636. doi:10.1021/ac0202435
Spindler JH, Klüter H, Kerowgan M (2001) A novel microplate agglutination method for blood grouping and reverse typing without the need for centrifugation. Transfusion 41:627–632. doi:10.1046/j.1537-2995.2001.41050627.x
Yager P, Edwards T, Fu E, Helton K, Nelson K, Tam MR et al (2006) Microfluidic diagnostic technologies for global public health. Nature 442:412–418. doi:10.1038/nature05064
Acknowledgment
The authors would like to thank the Korean Ministry of Commerce, Industry and Energy for financial support via the Development of Next-Generation New Technology Program (Development of Intelligent Robot Technologies for Laboratory Medicine by Applying Biotechnology) (10024719), and the author, DSK was partially supported by the Chung-Ang University Excellent Researcher Grant in 2008.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Choi, S.H., Kim, D.S. & Kwon, T.H. Microinjection molded disposable microfluidic lab-on-a-chip for efficient detection of agglutination. Microsyst Technol 15, 309–316 (2009). https://doi.org/10.1007/s00542-008-0689-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00542-008-0689-x