Abstract
Dilution is a common procedure in biological and chemical analyses to perform tests at different concentrations. In previously reported micro diluters, although they could provide a wide dilution range, only limited dilution ratios were demonstrated, i.e. low flexibility in dilution ratio. Here, a droplet-based micro diluter with high flexibility on dilution ratio is proposed, fabricated, and tested. Through combination of five different electrode sizes using electrowetting-on-dielectric (EWOD) technique, the proposed micro diluter can provide 49 dilution ratios at dilution range from 1/2 to 1/50. Experimental results verify that different dilution ratios can be successfully generated, even at the most difficult low concentration range. Comparing to the design with equal electrode size in conventional EWOD-based microfluidic chip, the proposed design with unequal electrode sizes can reduce the operation steps to achieve high flexibility on dilution ratios efficiently.
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References
Ainla A, Gozen I, Orwar O, Jesorka A (2009) A microfluidic diluter based on pulse width flow modulation. Anal Chem 81:5549–5556
Bhattacharjee B, Najjaran H (2012) Droplet sensing by measuring the capacitance between coplanar electrodes in a digital microfluidic system. Lab Chip 12:4416–4423
Brassard D, Malic L, Miville-Godin C, Normandin F, Veres T (2011) Advanced EWOD-based digital microfluidic system for multiplexed analysis of biomolecular interactions. IEEE 24th international conference on micro electro mechanical systems (MEMS), IEEE, 23–27 Jan 2011. doi:10.1109/MEMSYS.2011.5734384
Chang K, Wang F, Ding Y, Pan F, Li F, Jia S, Lu W, Deng S, Shi J, Chen M (2014) Development and validation of a novel leaky surface acoustic wave immunosensor array for label-free and high-sensitive detection of cyclosporin A in whole-blood samples. Biosens Bioelectron Biosens Bioelectron 54:151–157
Chikkaveeraiah BV, Mani V, Patel V, Gutkind JS, Rusling JF (2011) microfluidic electrochemical immunoarray for ultrasensitive detection of two cancer biomarker proteins in serum. Biosens Bioelectron 26:4477–4483
Cho SK, Moon H, Kim CJ (2003) Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits. J Microelectromech 12:70–80
Choi K, Ng AHC, Fobel R, Wheeler AR (2012) Digital microfluidics. Annu Rev Anal Chem 5:413–440
Dertinger SKW, Chiu DT, Jeon NL, Whitesides GM (2001) Generation of gradients having complex shapes using microfluidic networks. Anal Chem 73:1240–1246
Huang CY, Tsai PY, Lee IC, Hsu HY, Huang HY, Fan SK, Yao DJ, Liu CH, Hsu W (2016a) A highly efficient bead extraction technique with low dead number for digital microfluidic immunoassay. Biomicrofluidics 10:011901
Huang CY, Shih PH, Tsai PY, Lee IC, Hsu HY, Huang HY, Fan SK, Hsu W (2016b) AMPFLUID: aggregation magnified post-assay fluorescence for ultrasensitive immunodetection on digital microfluidics. Proc IEEE 103(2):225–235
Jang YH, Hancock MJ, Kim SB, Selimovic S, Sim WY, Bae H, Khademhosseini A (2011) An integrated microfluidic device for two-dimensional combinatorial dilution. Lab Chip 11:3277–3286
Jebrail MJ, Yang H, Mudrik JM, Lafreniere NM, McRoberts C, Al-Dirbashi OY, Fisher L, Chakrabortybc P, Wheeler AR (2011) Lab Chip 11:3218–3224
Jebrail MJ, Bartsch MS, Patel KD (2012) Digital microfluidics: a versatile tool for applications in chemistry, biology and medicine. Lab Chip 12:2452–2463
Jiang H, Weng X, Li D (2011) Microfluidic whole-blood immunoassays. Microfluid Nanofluid 10:941–964
Kalsi S, Valiadi M, Tsaloglou MN, Lesley PJ, Jacobs A, Watson R, Turner C (2015) A digital microfluidic method for dried blood spot analysis. Lab Chip 15:3065–3075
Kim C, Lee K, Kim JH, Shin KS, Lee KJ, Kim TS, Kang JY (2008) A serial dilution microfluidic device using a ladder network generating logarithmic or linear concentrations. Lab Chip 8:473–479
Laiwattanapaisal W, Songjaroen T, Maturos T, Lomas T, Sappat A, Tuantranont A (2009) On-Chip immunoassay for Determination of urinary Albumin. Sensors 9:10066–10079
Lee K, Kim C, Ahn B, Panchapakesan R, Full AR, Nordee L, Kangb JY, Oh KW (2009) Generalized serial dilution module for monotonic and arbitrary microfluidic gradient generators. Lab Chip 9:709–717
Lee BS, Lee YU, Kim HS, Kim TH, Park J, Lee JG, Kim J, Kim H, Lee WG, Cho YK (2011) Fully integrated lab-on-a-disc for simultaneous analysis of biochemistry and immunoassay from whole blood. Lab Chip 11:70–78
Lin TH, Yao DJ (2012) Applications of EWOD systems for DNA reaction and analysis. J Adhes Sci Technol 12:1789–1804
Lin YH, Chen YJ, Lai CS, Chen YT, Chen CL, Chang Y-S (2013) A negative-pressure-driven microfluidic chip for the rapid detection of a bladder cancer biomarker in urine using bead-based enzyme-linked immunosorbent assay. Biomicrofluidics 7(2):024103
Lu W, Qian C, Bi L, Tao L, Ge J, Dong J, Qian W (2014) Biomolecule-based formaldehyde resin microspheres loaded with Au nanoparticles: a novel immunoassay for detection of tumor markers in human serum. Biosens Bioelectron 53:346–354
Manage DP, Lauzon J, Atrazhev A, Pang X, Pilarski LM (2013) A novel methods for sample delivery and testing of whole blood: gel strip PCR for point of care (POC) molecular diagnostics. Lab Chip 13:4011–4014
Paik P, Pamula VK, Fair RB (2003a) Electrowetting-based droplet mixers for microfluidic systems. Lab Chip 13:253–529
Paik P, Pamula VK, Pollack MG, Fair RB (2003b) Electrowetting-based droplet mixers for microfluidic systems. Lab Chip 3:28–33
Park S, Wijethunga PAL, Moon H, Han B (2011) On-chip characterization of cryoprotective agent mixtures using an EWOD-based digital microfluidic device. Lab Chip 11:2212–2221
Schertzer MJ, Ben-Mrad R, Sullivan PE (2010) Using capacitance measurements in EWOD devices to identify fluid composition and control droplet mixing. Sens Actuators, B 145:340–347
Shen HH, Fan SK, Kim CJ, Yao DJ (2014) EWOD microfluidic systems for biomedical applications. Microfluid Nanofluid 16:965–987
Walker GM, Monteiro-Riviere N, Rouse J, O’Neill AT (2007) A linear dilution microfluidic device for cytotoxicity assays. Lab Chip 2:226–232
Wang S, Ji N, Wang W, Li Z (2010) Effects of non-ideal fabrication on the dilution performance of serially functioned microfluidic concentration gradient generator. In: IEEE International Conference on Nano/Micro Engineered and Molecular Systems (NEMS) 169–172
Yen CY, Hou MF, Yang ZW, Tang JY, Li KT, Huang HW, Huang YH, Lee SY, Hsieh CY, Chen B-U, Chang H-W (2015) Concentrations effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. BMC Complement Altern Med 15:94
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This work was partially supported by the Panasonic Corporation of Japan. The facilities and technical support from Nano Facility Center of National Chiao Tung University are also appreciated.
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Wang, YB., Huang, JH., Lee, MS. et al. An EWOD-based micro diluter with high flexibility on dilution ratio. Microsyst Technol 23, 3645–3651 (2017). https://doi.org/10.1007/s00542-016-3146-2
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DOI: https://doi.org/10.1007/s00542-016-3146-2