대한방사성의약품학회지 (Journal of Radiopharmaceuticals and Molecular Probes)

  • 제8권2호
  • /
  • Pages.95-101
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  • 2022
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  • 2384-1583(pISSN)
  • /
  • 2508-3848(eISSN)
대한방사성의약품학회 (Korean Society of Radiopharmaceuticals and Molecular Probes)
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Development of Microfluidic Radioimmunoassay Platform for High-throughput Analysis with Reduced Radioactive Waste

  • Jin-Hee Kim (Radioisotope Research Division, Korea Atomic Energy Research Institute) ;
  • So-Young Lee (Radioisotope Research Division, Korea Atomic Energy Research Institute) ;
  • Seung-Kon Lee (Radioisotope Research Division, Korea Atomic Energy Research Institute)
  • 투고 : 2022.12.10
  • 심사 : 2022.12.23
  • 발행 : 2022.12.30
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초록

Microfluidic radioimmunoassay (RIA) platform called µ-RIA spends less reagent and shorter reaction time for the analysis compared to the conventional tube-based radioimmunoassay. This study reported the design of µ-RIA chips optimized for the gamma counter which could measure the small samples of radioactive materials automatically. Compared with the previous study, the µ-RIA chips developed in this study were designed to be compatible with conventional RIA test tubes. And, the automatic gamma counter could detect radioactivity from the 125I labeled anti-PSA attached to the chips. Effects of the multi-layer microchannels and two-phase flow in the µ-RIA chips were investigated in this study. The measured radioactivity from the 125I labeled anti-PSA was linearly proportional to the number of stacked chips, representing that the radioactivity in µ-RIA platform could be amplified by designing the chips with multi-layers. In addition, we designed µ-RIA chip to generate liquid-gas plug flow inside the microfluidic channel. The plug flow can promote binding of the biomolecules onto the microfluidic channel surface with recirculation in the liquid phase. The ratio of liquid slug and air slug length was 1 : 1 when the 125I labeled anti-PSA and the air were injected at 1 and 35 µL/min, respectively, exhibiting 1.6 times higher biomolecule attachment compared to the microfluidic chip without the air injection. This experimental result indicated that the biomolecular reaction was improved by generating liquid-gas slugs inside the microfluidic channel. In this study, we presented a novel µ-RIA chips that is compatible with the conventional gamma counter with automated sampler. Therefore, high-throughput radioimmunoassay can be carried out by the automatic measurement of radioactivity with reduced radiowaste generation. We expect the µ-RIA platform can successfully replace conventional tube-based radioimmunoassay in the future.

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과제정보

이 연구는 한국원자력연구원 주요사업(방사성동위원소 응용 표준화기술 개발, 524440-23)의 지원을 받아 수행되었음.

참고문헌

  1. Schaffer FL, Soergel ME. Liquid scintillation radioassay in disposable microcentrifuge tubes: Radioimmune precipitates and other applications. Applied Microbiology 1974;28(2):280-7. https://doi.org/10.1128/am.28.2.280-287.1974
  2. Darwish IA. Immunoassay methods and their applications in pharmaceutical analysis: Basic methodology and recent advances. International Journal of Biomedical Science 2006;2(3):217-35.
  3. Landon J, Moffat A. The radioimmunoassay of drugs. A review. Analyst 1976;101(1201):225-43. https://doi.org/10.1039/an9760100225
  4. Arnaud CD, Tsao HS, Littledike T. Radioimmunoassay of human parathyroid hormone in serum. The Journal of Clinical Investigation 1971;50(1): 21-34. https://doi.org/10.1172/JCI106476
  5. Yoo S, Yoon M, Park UJ, Han H S, Kim JH, Hwang HJ. A radioimmunoassay method for detection of DNA based on chemical immobilization of anti-DNA antibody. Experimental & Molecular Medicine 1999;31(3):122-5. https://doi.org/10.1038/emm.1999.20
  6. Kim J, Lee S, Lee S. Development of novel lab-on-a-chip platform for high-throughput radioimmunoassay. Applied Radiation and Isotopes 2021;168:109526.
  7. Convery N, Gadegaard N. (2019). 30 years of microfluidics. Micro and Nano Engineering 2019;2:76-91.
  8. Heyries KA, Mandon CA, Ceriotti L, Ponti J, Colpo P, Blum LJ, Marquette CA. "Macromolecules to PDMS transfer" as a general route for PDMS biochips. Biosensors and Bioelectronics 2009;24(5):1146-52. https://doi.org/10.1016/j.bios.2008.06.042
  9. Hashimoto M, Kaji H, Kemppinen ME, Nishizawa M. Localized immobilization of proteins onto microstructures within a preassembled microfluidic device. Sensors and Actuators B: Chemical 2008;28(2):545-51.
  10. Phillips KS, Cheng Q. Microfluidic immunoassay for bacterial toxins with supported phospholipid bilayer membranes on poly (dimethylsiloxane). Analytical Chemistry 2005;77(1):327-34. https://doi.org/10.1021/ac049356+
  11. Sia SK, Whitesides GM. Microfluidic devices fabricated in poly (dimethylsiloxane) for biological studies. Electrophoresis 2003;24(21):3563-76. https://doi.org/10.1002/elps.200305584
  12. Lin C, Wang J, Wu H, Lee G. Microfluidic immunoassays. Journal of the Association for Laboratory Automation 2010;15(3):253-74. https://doi.org/10.1016/j.jala.2010.01.013
  13. Meldrum DR, Holl MR. Microscale bioanalytical systems. Science 2002;297 2002;297(5584):1197-8. https://doi.org/10.1126/science.297.5584.1197
  14. Qin D, Xia Y, Whitesides GM. Soft lithography for micro-and nanoscale patterning. Nature Protocols 2010;5(3):491.
  15. Gokaltun A, Yarmush ML, Asatekin A, Usta OB. Recent advances in nonbiofouling PDMS surface modification strategies applicable to microfluidic technology. Technology 2017;5(01):1-12. https://doi.org/10.1142/S2339547817300013
  16. Trantidou T, Elani Y, Parsons E, Ces O. Hydrophilic surface modification of PDMS for droplet microfluidics using a simple, quick, and robust method via PVA deposition. Microsystems & Nanoengineering 2017;3(1):1-9.
  17. Liao Q, Zhao S, Cai B, He R, Rao L, Wu, Y, Zhao X. Biocompatible fabrication of cell-laden calcium alginate microbeads using microfluidic double flow-focusing device. Sensors and Actuators A: Physical 2018;79:313-20.
  18. Deshpande S, Caspi Y, Meijering AE, Dekker C. Octanol-assisted liposome assembly on chip. Nature Communications 2016;7(1):1-9.
  19. Rossier JS, Girault HH. Enzyme linked immunosorbent assay on a microchip with electrochemical detection. Lab on a Chip 2001;1(2):153-7. https://doi.org/10.1039/b104772h
  20. Garstecki P, Fuerstman MJ, Stone HA, Whitesides GM. Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up. Lab on a Chip 2006;6(3):437-46. https://doi.org/10.1039/b510841a
  21. Garstecki P, Fischbach MA, Whitesides GM. Design for mixing using bubbles in branched microfluidic channels. Applied Physics Letters 2005;86(24):244108
  22. Abadie T, Aubin J, Legendre D, Xuereb C. Hydrodynamics of gas-liquid taylor flow in rectangular microchannels. Microfluidics and Nanofluidics 2012;12(1):355-69. https://doi.org/10.1007/s10404-011-0880-8
  23. Tice JD, Song H, Lyon AD, Ismagilov RF. Formation of droplets and mixing in multiphase microfluidics at low values of the reynolds and the capillary numbers. Langmuir 2003;19(22):9127-33. https://doi.org/10.1021/la030090w