Volume 20, Issue 8 (August 2020)
Modares Mechanical Engineering 2020, 20(8): 1943-1950 |
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1- Department of Mechanical Engineering, Faculty of Mechanical Engineering, Sharif University of Technology, Tehran, Iran
2- Department of Mechanical Engineering, Faculty of Gas and Petroleum, Yasouj University, Gachsaran, Iran
3- Department of Mechanical Engineering, Faculty of Mechanical Engineering, Sharif University of Technology, Tehran, Iran ,mssaidi.sharif@yahoo.com
2- Department of Mechanical Engineering, Faculty of Gas and Petroleum, Yasouj University, Gachsaran, Iran
3- Department of Mechanical Engineering, Faculty of Mechanical Engineering, Sharif University of Technology, Tehran, Iran ,
Abstract: (4367 Views)
Research on DNA is particularly important in the diagnosis, control, and treatment of many diseases, including cancer. Today, the use of digital droplet polymerase chain reaction (ddPCR) for different DNA tests has attracted much researchers’ attention. A large number of micron-sized droplets are required to perform ddPCR. In the present study, a ddPCR system was designed, fabricated, and evaluated using a microfluidic chip. The system comprises a microfluidic chip for droplet generation and a thermal cycling device needed for PCR. The droplet generation in the microchip was simulated in 3D. The simulation results were validated. The average error is about 5% in the radius of the droplets. The constructed thermal cycling device controls the chip temperature with a precision of ±1.5°C. The in-chip PCR process was successfully performed by applying 25 heat cycles. The fluorescent property was observed in most droplets that prove the thermal cycling device can provide the conditions for DNA proliferation in the laboratory. The images were processed, and different levels of fluorescent light were identified in the droplets. The coefficient of variation of the selected droplets is 2.5%, which gives a good accuracy compared to the acceptable amount for these types of systems (less than 8%). The results obtained from this fully native device can be used in many fields, including cancer detection, examination of malignant tissue, and evaluation of the success in tissue surgery.
Article Type: Original Research |
Subject:
Mechatronics
Received: 2019/11/12 | Accepted: 2020/05/3 | Published: 2020/08/15
Received: 2019/11/12 | Accepted: 2020/05/3 | Published: 2020/08/15
References
1. Shemer R, Magenheim J, Dor Y. Digital droplet PCR for monitoring tissue‐specific cell death using DNA methylation patterns of circulating cell‐free DNA. Current Protocols in Molecular Biology. 2019;127(1):90. [Link] [DOI:10.1002/cpmb.90]
2. Cho SM, Shin S, Kim Y, Song W, Hong SG, Jeong SH, et al. A novel approach for tuberculosis diagnosis using exosomal DNA and droplet digital PCR. Clinical Microbiology and Infection. 2019. [Link]
3. Li C, He Q, Liang H, Cheng B, Li J, Xiong S, et al. Diagnostic accuracy of droplet digital PCR (ddPCR) and amplification refractory mutation system PCR (ARMS-PCR) for detecting EGFR mutation in cell-free DNA of advanced lung cancer: A meta-analysis. Annals of Oncology. 2020;10:290. [Link] [DOI:10.3389/fonc.2020.00290]
4. Olmedillas-López S, García-Arranz M, García-Olmo D. Current and emerging applications of droplet digital PCR in oncology. Molecular Diagnosis & Therapy. 2017;21(5):493-510. [Link] [DOI:10.1007/s40291-017-0278-8]
5. Chang CH, Mau-Hsu D, Chen KC, Wei CW, Chiu CY, Young TH. Evaluation of digital real-time PCR assay as a molecular diagnostic tool for single-cell analysis. Scientific Reports. 2018;8(1):1-12. [Link] [DOI:10.1038/s41598-018-21041-5]
6. Miao G, Zhang L, Zhang J, Ge S, Xia N, Qian S, et al. Free convective PCR: From principle study to commercial applications-a critical review. Analytica Chimica Acta. 2020;1108:177-197. [Link] [DOI:10.1016/j.aca.2020.01.069]
7. Kalinina O, Lebedeva I, Brown J, Silver J. Nanoliter scale PCR with TaqMan detection. Nucleic Acids Research. 1997;25(10):1999-2004. [Link] [DOI:10.1093/nar/25.10.1999]
8. Vogelstein B, Kinzler KW. Digital PCR. Proceedings of the National Academy of Sciences. 1999;96(16):9236-9241. [Link] [DOI:10.1073/pnas.96.16.9236]
9. Pekin D, Skhiri Y, Baret JC, Le Corre D, Mazutis L, Ben Salem C, et al. Quantitative and sensitive detection of rare mutations using droplet-based microfluidics. Lab on a Chip. 2011;11(13):2156-2166. [Link] [DOI:10.1039/c1lc20128j]
10. Perkins G, Lu H, Garlan F, Taly V. Droplet-based digital PCR: Application in cancer research. Advances in Clinical Chemistry. 2017;79:43-91. [Link] [DOI:10.1016/bs.acc.2016.10.001]
11. Cordova C, Syeda MM, Corless B, Wiggins JM, Patel A, Kurz SC, et al. Plasma cell-free circulating tumor DNA (ctDNA) detection in longitudinally followed glioblastoma patients using TERT promoter mutation-specific droplet digital PCR assays. Journal of Clinical Oncology. 2019;37(15):2026. [Link] [DOI:10.1200/JCO.2019.37.15_suppl.2026]
12. Ramírez JD, Herrera G, Hernandez C, Cruz-Saavedra L, Munoz M, Florez C, et al. Evaluation of the analytical and diagnostic performance of a digital droplet polymerase chain reaction (ddPCR) assay to detect Trypanosoma cruzi DNA in blood samples. PLoS Neglected Tropical Diseases. 2018;12(12):e0007063. [Link] [DOI:10.1371/journal.pntd.0007063]
13. Wu W, Zhou S, Hu J, Wang G, Ding X, Gou T, et al. A thermosetting oil for droplet‐based real‐time monitoring of digital PCR and cell culture. Advanced Functional Materials. 2018;28(39):1803559. [Link] [DOI:10.1002/adfm.201803559]
14. Pan Y, Ma T, Meng Q, Mao Y, Chu K, Men Y, et al. Droplet digital PCR enabled by microfluidic impact printing for absolute gene quantification. Talanta. 2020;211:120680. [Link] [DOI:10.1016/j.talanta.2019.120680]
15. Hatch AC, Fisher JS, Tovar AR, Hsieh AT, Lin R, Pentoney SL, et al. 1-Million droplet array with wide-field fluorescence imaging for digital PCR. Lab on a Chip. 2011;11(22):3838-3845. [Link] [DOI:10.1039/c1lc20561g]
16. Kiss MM, Ortoleva-Donnelly L, Beer NR, Warner J, Bailey CG, Colston BW, et al. High-throughput quantitative polymerase chain reaction in picoliter droplets. Analytical Chemistry. 2008;80(23):8975-8981. [Link] [DOI:10.1021/ac801276c]
17. Markey AL, Mohr S, Day PJR. High-throughput droplet PCR. Methods. 2010;50(4):277-281. [Link] [DOI:10.1016/j.ymeth.2010.01.030]
18. Mohr S, Zhang YH, Macaskill A, Day PJR, Barber RW, Goddard N, et al. Numerical and experimental study of a droplet-based PCR chip. Microfluidics and Nanofluidics. 2007;3(5):611-621. [Link] [DOI:10.1007/s10404-007-0153-8]
19. Ochoa A, Trejo F, Olguín LF. Droplet-based microfluidics methods for detecting enzyme inhibitors. In: Labrou N. Targeting enzymes for pharmaceutical development. New York: Springer; 2020. [Link] [DOI:10.1007/978-1-0716-0163-1_14]
20. Ergin FG, Watz BB, Gade-Nielsen NF. A review of planar PIV systems and image processing tools for lab-on-chip microfluidics. Sensors. 2018;18(9):3090. [Link] [DOI:10.3390/s18093090]
21. Gupta S, Ramesh K, Ahmed S, Kakkar V. Lab-on-chip technology: A review on design trends and future scope in biomedical applications. International Journal of Bio-Science and Bio-Technology. 2016;8(5):311-322. [Link] [DOI:10.14257/ijbsbt.2016.8.5.28]
22. Khoo BL, Grenci G, Lim YB, Lee SC, Han J, Lim CT. Expansion of patient-derived circulating tumor cells from liquid biopsies using a CTC microfluidic culture device. Nature Protocols. 2018;13(1):34-58. [Link] [DOI:10.1038/nprot.2017.125]
23. Lu J, Pang J, Chen Y, Dong Q, Sheng J, Luo Y, et al. Application of microfluidic chips in separation and analysis of extracellular vesicles in liquid biopsy for cancer. Micromachines. 2019;10(6):390. [Link] [DOI:10.3390/mi10060390]
24. Ingber DE. Integrated human organ-on-chip microphysiological systems [Internet]. Unknown publisher city: Google Patents; 2019 [Unknown Cited]. Available from: Unknown [Link]
25. Moghadas H, Saidi MS, Kashaninejad N, Nguyen NT. A high-performance polydimethylsiloxane electrospun membrane for cell culture in lab-on-a-chip. Biomicrofluidics. 2018;12(2):024117. [Link] [DOI:10.1063/1.5021002]
26. Kashaninejad N, Yaghoobi M, Pourhassan‐Moghaddam M, Bazaz SR, Jin D, Warkiani ME. Biological diagnosis based on microfluidics and nanotechnology. In: Jiang X, Bai C, Liu M. Nanotechnology and Microfluidic. Hoboken: John Wiley & Sons; 2020. [Link] [DOI:10.1002/9783527818341.ch7]
27. Opalski AS, Kaminski TS, Garstecki P. Droplet microfluidics as a tool for the generation of granular matters and functional emulsions. KONA Powder and Particle Journal. 2019;36:50-71. [Link] [DOI:10.14356/kona.2019004]
28. Chen R, Sun Z, Chen D. Droplet-based microfluidics for cell encapsulation and delivery. In: Santos H, Liu D, Zhang H. Microfluidics for pharmaceutical applications. Amsterdam: Elsevier; 2019. [Link] [DOI:10.1016/B978-0-12-812659-2.00011-9]
29. Ji Q, Zhang JM, Liu Y, Li X, Lv P, Jin D, et al. A modular microfluidic device via multimaterial 3D printing for emulsion generation. Scientific Reports. 2018;8(1):1-11. [Link] [DOI:10.1038/s41598-018-22756-1]
30. Jain V, Patrikar RM. A low-cost portable dynamic droplet sensing system for digital microfluidics Applications. IEEE Transactions on Instrumentation and Measurement. 2019;69(6):3623-3630. [Link] [DOI:10.1109/TIM.2019.2932526]
31. Orejuela JDA. Gas-liquid droplet microfluidics under confined 3D flow-focusing geometries for droplet generation under the jetting regime [dissertation]. Boston: Northeastern university; 2019. [Link]
32. Madic J, Zocevic A, Senlis V, Fradet E, Andre B, Muller S, et al. Three-color crystal digital PCR. Biomolecular Detection Quantification. 2016;10:34-46. [Link] [DOI:10.1016/j.bdq.2016.10.002]
33. Maleki MA, Soltani M, Kashaninejad N, Nguyen NT. Effects of magnetic nanoparticles on mixing in droplet-based microfluidics. Physics of Fluids. 2019;31(3):032001. [Link] [DOI:10.1063/1.5086867]
34. Doufène K, Tourné-Péteilh C, Etienne P, Aubert-Pouëssel A. Microfluidic systems for droplet generation in aqueous continuous phases: A focus review. Langmuir. 2019;35(39):12597-12612. [Link] [DOI:10.1021/acs.langmuir.9b02179]
35. Iqbal S, Bashir S, Ahsan M, Bashir M, Shoukat S. Effect of intersection angle and wettability on droplet generation in microfluidic flow-focusing device. Journal of Fluids Engineering. 2020;142(4):041404. [Link] [DOI:10.1115/1.4045366]
36. Do LQ, Vu QT, Nguyen NC, Nguyen TH, Tran TH, Bui TT, et al. Development of a flow focusing droplet generation microfluidic system based on rapidprototyping technique. Conference, 19 December 2019, Unknown location of conference?. Unknown Publisher city: Unknown Publisher; 2019. [Link]
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