Abstract
Biological assays around “lab-on-a-chip (LoC)” are required in multiple concentration (or dilution) factors, satisfying specific sample concentrations. Unfortunately, most of them suffer from non-locality and are non-protectable, requiring a large footprint and high purchase cost. A digital geometric technique can generate arbitrary gradient profiles for digital microfluidic biochips (DMFBs). A next- generation DMFB has been proposed based on the microelectrode-dot-array (MEDA) architectures are shown to produce and disperse droplets by channel dispensing and lamination mixing. Prior work in this area must address the problem of reactant and waste minimization and concurrent sample preparation for multiple target concentrations. This paper proposes the first splitting-droplet sharing algorithm for reactant and waste minimization of multiple target concentrations on MEDAs. The proposed algorithm not only minimizes the consumption of reagents but also reduces the number of waste droplets by preparing the target concentrations concurrently. Experimental results on a sequence of exponential gradients are presented in support of the proposed method and demonstrate its effectiveness and efficiency. Compared to prior work, the proposed algorithm can achieve up to a 24.8% reduction in sample usage and reach an average of 50% reduction in waste droplets.
Similar content being viewed by others
Data Availibility
The datasets generated and analyzed during The current study is available from the corresponding author upon reasonable request.
References
Bhattacharjee S, Banerjee A, Ho TY et al (2013) On producing linear dilution gradient of a sample with a digital microfluidic biochip. IEEE Comput Soc USA 5:77–81. https://doi.org/10.1109/ISED.2013.22
Bhattacharjee S, Banerjee A, Ho TY et al (2019) Efficient generation of dilution gradients with digital microfluidic biochips. IEEE Trans Comput Aided Des Integr Circuits Syst 38(5):874–887. https://doi.org/10.1109/TCAD.2018.2834413
Bhattacharjee S, Poddar S, Roy S et al (2016) Dilution and mixing algorithms for flow-based microfluidic biochips. IEEE Trans Comput Aided Des Integr Circuits Syst 36(4):614–627. https://doi.org/10.1109/TCAD.2016.2597225
Dong C, Liu L, Liu H et al (2020) A survey of dmfbs security: State-of-the-art attack and defense. In: 2020 21st International Symposium on Quality Electronic Design (ISQED), p 14–20. https://doi.org/10.1109/ISQED48828.2020.9137016
Friedrich D, Please CP, Melvin T (2012) Design of novel microfluidic concentration gradient generators suitable for linear and exponential concentration ranges. Chem Eng J 193–194:296–303. https://doi.org/10.1016/j.cej.2012.04.041
Guo W, Lian S, Dong C et al (2022) A survey on security of digital microfluidic biochips: Technology, attack, and defense. ACM Trans Des Autom Electron Syst 27(4):33. https://doi.org/10.1145/3494697
Huang X, Liang CC, Li J et al (2019) Open-source incubation ecosystem for digital microfluidics – status and roadmap: Invited paper. In: 2019 IEEE/ACM International Conference on Computer-Aided Design (ICCAD), p 1–6. https://doi.org/10.1109/ICCAD45719.2019.8942172
Huang HC, Liang CC, Wang Q et al (2022) Nr-router: Non-regular electrode routing with optimal pin selection for electrowetting-on-dielectric chips. In: 2022 27th Asia and South Pacific Design Automation Conference (ASP-DAC), p 56–61. https://doi.org/10.1109/ASP-DAC52403.2022.9712567
Huang JD, Liu CH, Chiang TW (2012) Reactant minimization during sample preparation on digital microfluidic biochips using skewed mixing trees. In: Proceedings of the International Conference on Computer-Aided Design. Association for Computing Machinery, New York, NY, USA, 7, p 377–383. https://doi.org/10.1145/2429384.2429464
Huang JD, Liu CH, Lin HS (2013) Reactant and waste minimization in multitarget sample preparation on digital microfluidic biochips. IEEE Trans Comput Aided Des Integr Circuits Syst 32(10):1484–1494. https://doi.org/10.1109/TCAD.2013.2263035
Huang, Juinn-Dar, Liu et al (2015) Reactant minimization in sample preparation on digital microfluidic biochips. p 1429–1440. https://doi.org/10.1109/TCAD.2015.2418286
Hsieh YL, Ho TY, Chakrabarty K (2014) Biochip synthesis and dynamic error recovery for sample preparation using digital microfluidics. IEEE Trans Comput Aided Des Integr Circuits Syst 33(2):183–196. https://doi.org/10.1109/TCAD.2013.2284010
Jebrail MJ, Wheeler AR (2009) Digital microfluidic method for protein extraction by precipitation. Anal Chem 81(1):330–335. https://doi.org/10.1021/ac8021554
Lee CY, Chang CL, Wang YN et al (2011) Microfluidic mixing: A review. Int J Mol Sci 12(5):3263–3287. https://doi.org/10.3390/ijms12053263
Li Z, Chakrabarty K, Ho TY et al (2019) Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Design Automation, Optimization, and Test Techniques. Design Automation, Optimization, and Test Techniques, Micro-Electrode-Dot-Array Digital Microfluidic Biochips
Li Z, Lai KYT, Chakrabarty K et al (2017) Droplet size-aware and error-correcting sample preparation using micro-electrode-dot-array digital microfluidic biochips. IEEE Trans Biomed Circuits Syst 11(6):1380–1391
Li Z, Lai YT, Chakrabarty K et al (2017) Droplet size-aware and error-correcting sample preparation using micro-electrode-dot-array digital microfluidic biochips. IEEE Trans Biomed Circuits Syst PP(99):1–12
Li Z, Lai KYT, Yu PH et al (2016) High-level synthesis for micro-electrode-dot-array digital microfluidic biochips. In: Proceedings of the 53rd Annual Design Automation Conference. Association for Computing Machinery, New York, NY, USA, 146, p 6. https://doi.org/10.1145/2897937.2898028
Liang TC, Chan YS, Ho TY et al (2019) Sample preparation for multiple-reactant bioassays on micro-electrode-dot-array biochips. In: Proceedings of the 24th Asia and South Pacific Design Automation Conference. Association for Computing Machinery, New York, NY, USA, 6, p 468–473. https://doi.org/10.1145/3287624.3287708
Liang TC, Chan YS, Ho TY et al (2020) Multitarget sample preparation using meda biochips. IEEE Trans Comput Aided Des Integr Circuits Syst 39(10):2682–2695. https://doi.org/10.1109/TCAD.2019.2942002
Mitra D, Roy S, Bhattacharjee S et al (2014) On-chip sample preparation for multiple targets using digital microfluidics. IEEE Trans Comput Aided Des Integr Circuits Syst 33(8):1131–1144. https://doi.org/10.1109/TCAD.2014.2323200
O’Neill AT, Monteiro-Riviere N, Walker GM (2006) A serial dilution microfluidic device for cytotoxicity assays. In: 2006 International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE, New York, NY, USA, p 2836–2839. https://doi.org/10.1109/IEMBS.2006.259270
Ottesen EA, Hong JW, Quake SR et al (2006) Microfluidic digital PCR enables multigene analysis of individual environmental bacteria. Lab on a Chip 314(5804):1464–1467. https://doi.org/10.1126/science.1131370
Poddar S, Bhattarcharjee S, Nandy SC et al (2018) Optimization of multi-target sample preparation on-demand with digital microfluidic biochips. IEEE Trans Comput Aided Des Integr Circuits Syst, p 1–1
Quan PL, Sauzade M, Brouzes E (2018) dpcr: a technology review. Sensors 18(4):1271. https://doi.org/10.3390/s18041271
Ren H, Srinivasan V, Fair RB (2003) Design and testing of an interpolating mixing architecture for electrowetting-based droplet-on-chip chemical dilution. In: TRANSDUCERS’03. 12th International Conference on Solid-State Sensors, Actuators and Microsystems. Digest of Technical Papers (Cat. No. 03TH8664), p 619–622. https://doi.org/10.1109/SENSOR.2003.1215549
Roy S, Bhattacharya BB, Chakrabarty K (2010) Optimization of dilution and mixing of biochemical samples using digital microfluidic biochips. IEEE Trans Comput Aided Des Integr Circuits Syst 29(11):1696–1708
Roy S, Bhattacharya BB, Chakrabarty K (2011) Waste-aware dilution and mixing of biochemical samples with digital microfluidic biochips. In: 2011 Design, Automation & Test in Europe. IEEE, Grenoble, France, p 1–6. https://doi.org/10.1109/DATE.2011.5763174
Saiki RK, Gelfand DH, Stoffel S et al (1988) Primer-directed enzymatic amplification of DNA with a thermostable. DNA polymerase 239(4839):487–491
Sun M, Bithi SS, Vanapalli SA (2011) Microfluidic static droplet arrays with tuneable gradients in material composition. Lab on a Chip 11(23):3949–3952. https://doi.org/10.1039/c1lc20709a
Thies W, Urbanski JP, Amarasinghe TS (2008) Abstraction layers for scalable microfluidic biocomputing. Nat Comput 7(2):255–275. https://doi.org/10.1007/s11047-006-9032-6
Walker GM, Monteiro-Riviere N, Rouse J et al (2007) A linear dilution microfluidic device for cytotoxicity assays. Lab on A Chip 7(2):226–232. https://doi.org/10.1039/B608990A
Wang J, Brisk P, Grover WH (2016) Random design of microfluidics. Lab on A Chip 16(21):4212–4219. https://doi.org/10.1039/C6LC00758A
Zhang L, Li Z, Huang X et al (2023) Enhanced built-in self-diagnosis and self-repair techniques for daisy-chain design in meda digital microfluidic biochips. IEEE Trans Comput Aided Des Integr Circuits Syst 42(10):3236–3249. https://doi.org/10.1109/TCAD.2023.3244524
Zhong Q, Bhattacharya S, Kotsopoulos S et al (2011) Multiplex digital PCR: breaking the one target per color barrier of quantitative. PCR 11(13):2167. https://doi.org/10.1039/c1lc20126c
Acknowledgements
This work was supported by the fund of Fujian Province Digital Economy Alliance, the National Natural Science Foundation of China (No. U1905211), and the Natural Science Foundation of Fujian Province (No.2020J01500).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Additional information
Responsible Editor: K. Chakrabarty
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Dong, C., Chen, X. & Chen, Z. Reactant and Waste Minimization during Sample Preparation on Micro-Electrode-Dot-Array Digital Microfluidic Biochips using Splitting Trees. J Electron Test 40, 87–99 (2024). https://doi.org/10.1007/s10836-024-06103-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10836-024-06103-z