A Study About Biochip Combined with Micro Mixer and Reactor for DNA Ligation

마이크로 혼합기와 반응기로 구성된 DNA 결찰용 바이오칩에 관한 연구

  • 강도형 (한양대학교 대학원 기계공학과) ;
  • 안유민 (한양대학교 기계공학과) ;
  • 황승용 (한양대학교 분자생명과학부)
  • Published : 2008.08.01


In this research, we developed new PDMS-glass based microbiochip consisted of the micromixer and microreactor for DNA ligation. The micromixer was composed of a straight channel integrated with nozzles and pillars, and the microreactor was composed of a serpentine channel. We coated the PDMS chip surface with the 0.25wt.% PVP solution to prevent the bubble generation which was caused by the hydrophobicity of the PDMS. The new micomixer was passive type and the mixing was enhanced by a convective diffusion using the nozzle and pillar. The 10.33mm long micromixer showed the good mixing efficiency of 87.7% at 500 l/min flow rate. We could perform the DNA ligation successfully in the microbiochip, and the ligation time was shortened from 4 hours in conventional laboratory method to 5 min in the microbiochip.


Microbiochip;Micromixer;PVP Coating;DNA Ligation


  1. Burns, M. A., Johnson, B. N, Brahmasandra, S. N., Handique, K., Webster, J. R., Krishnan, M., Sammarco, T. S., Man, P. M., Jones, D., Heldsinger, D., Mastrangelo, C. H. and Burke, D. T., 1998, “An Integrated Nanoliter DNA Analysis Device,” Science, Vol. 282, pp. 484-487
  2. Cho, C.-H., Cho, W., Ahn, Y. and Hwang, S.-Y., 2006, “PDMS/Glass Serpentine Microchannel Chip for PCR with Bubble Suppression in Sample Injection,” Trans. of the KSME (A), Vol. 30, No. 10, pp. 1261-1268
  3. Jayaraj, S., Kang, S. M. and Suh, Y. K., 2007, “ A Review on the Analysis and Experiment of Fluid Flow and Mixing in Micro-Channels,” Journal of Mechanical Science and Technology, Vol. 21, No. 3, pp. 536-548
  4. LU, L. H., Ryu, K. S. and Liu, C., 2002, “A Magnetic Microstirrer and Array for Microfluidic Mixing,” J. Microelectromech. Syst., Vol. 11, pp. 462-469
  5. Tsai, J. H. and Lin, L. W., 2002, “Active Microfluidic Mixer and Gas Bubble Filter Driven by Thermal Bubble Micropump,” Sensors Actuators A, Vol. 97-98, pp. 665-671
  6. Kim, D. S., Lee, S. H., Kwon, T. H. and Ahn, C. H., 2005, “A Serpentine Laminating Micromixer Combining Splitting/Recombination and Advection,” Lab Chip, Vol. 5, pp. 739-747
  7. Hong , C. C., Choi, J. W. and Ahn, C. H., 2004, “A Novel In-Plane Passive Microfluidic Mixer with Modified Telas Structures,” Lab Chip, Vol. 4, pp. 109-113
  8. Liu. R. H., Stremler, M. A., Sharp, K. V., Olsen, M. G., Santiago, J. G., Adrian, R. J., Aref, J. H. and Beebe, D. J., 2000, “Passive Mixing in a Three–Dimensional Serpentine Microchannel,” J. Microelectromech. Syst., Vol. 9, pp. 190-197
  9. Stroock, A. D., Dertinger, S. K. W., Ajdari, A., Mezic, I., Stone, H. A. and Whitesides, G. M., 2002, “Chaotic Mixer for Microchannels,” Science, Vol. 295, pp. 647-651
  10. Kim, K.-m., Shin, Y-s., Lee, D. and Ahn, Y.-m., 2007, “Mixing Efficiency Evaluation in Y-channel Micromixer Using LIF Confocal Microscope,” Trans. of the KSME (B), Vol. 31, No. 2, pp. 159-166
  11. Giordano, B. C., Copeland, E. R., Landers, J. P., 2001, “Towards Dynamic Coating of Glass Microchip Chambers for Amplifying DNA via the Polymerase Chain Reaction,” Electrophoresis, Vol. 22, pp. 334-340<334::AID-ELPS334>3.0.CO;2-O
  12. Wilkinson, A., Smith, A., Bullard, D., Lavesa-Curto, M., Sayer, H., Bonner, A., Hemmings, A. and Bowater, R., 2005, “Analysis of Ligation and DNA Binding by Escherichia Coli DNA Ligase (LigA),” BBA-Proteins Proteomics, Vol. 1749, pp. 113-122
  13. Joseph Sambrook and David W. Russell, 2001, Molecular Cloning (third edition), CSHL PRESS, Vol. 1, pp.1.84-1.87
  14. Deng, H. Y., Zhang, X. E., Mang, Y., Zhang, Z. P., Zhou, Y. F., Liu, Q., Lu, H. B. and Fu, Z. J., 2004, “Oligonucleotide Ligation Assay-Based DNA Chip for Multiplex Detection of Single Nucleotide Polymorphism,” Biosens. Bioelectron., Vol. 19, pp. 1277-1283
  15. Hessel V., Lowe, H., Schonfeld, F., 2005, “Micromixers - A Review on Passive and Active Mixing Principles,” Chem. Eng. Sci., Vol. 60, pp. 2479-2501
  16. Lin, C. H., Tsai, C. H. and Fu, L. M., 2005, “A Rapid Three-Dimensional Vortex Micromixer Utilizing Self-Rotation Effects under Low Reynolds Number Conditions,” J. Micromech. Microeng., Vol. 15, pp. 935-943
  17. Suh, Y. K. and Heo, H. S., 2002, “A Numerical Study on Stirring Characteristics in a Microchannel with Various Arrangement of Blocks,” Trans. of the KSME (B), Vol. 27, No.7, pp. 901-908
  18. Lee, S. W, Kim, D. S., Lee, S. S and Kwon, T. H., 2006, “A Split and Recombination Micromixer Fabricated in a PDMS Three-Dimensional Structure,” J. Micromech. Microeng. Vol. 16, pp. 1067-1072