PH Regulator on Digital Microfluidics with Pico-Dosing Technique

Overview

Journal Biosensors (Basel)

Specialty Biotechnology

Date 2023 Nov 24

PMID 37998126

Authors

Haoran Li

Tao Peng

Yunlong Zhong

Meiqing Liu

Pui-In Mak

Rui P Martins

Ping Wang

Yanwei Jia

Affiliations

Soon will be listed here.

Abstract

Real-time pH control on-chip is a crucial factor for cell-based experiments in microfluidics, yet difficult to realize. In this paper, we present a flexible pH regulator on a digital microfluidic (DMF) platform. The pico-dosing technology, which can generate and transfer satellite droplets, is presented to deliver alkali/acid into the sample solution to change the pH value of the sample. An image analysis method based on ImageJ is developed to calculate the delivered volume and an on-chip colorimetric method is proposed to determine the pH value of the sample solution containing the acid-base indicator. The calculated pH values show consistency with the measured ones. Our approach makes the real-time pH control of the on-chip biological experiment more easy to control and flexible.

References

Peng C, Zhang Z, Kim C, Ju Y . EWOD (electrowetting on dielectric) digital microfluidics powered by finger actuation. Lab Chip. 2014; 14(6):1117-22. DOI: 10.1039/c3lc51223a. View

Mehling M, Tay S . Microfluidic cell culture. Curr Opin Biotechnol. 2014; 25:95-102. DOI: 10.1016/j.copbio.2013.10.005. View

Welch D, Christen J . Real-time feedback control of pH within microfluidics using integrated sensing and actuation. Lab Chip. 2014; 14(6):1191-7. DOI: 10.1039/c3lc51205c. View

Gong J, Kim C . All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics. Lab Chip. 2008; 8(6):898-906. PMC: 2769494. DOI: 10.1039/b717417a. View

Cao H, Chen R, Wang L, Jiang L, Yang F, Zheng S . Soil pH, total phosphorus, climate and distance are the major factors influencing microbial activity at a regional spatial scale. Sci Rep. 2016; 6:25815. PMC: 4864422. DOI: 10.1038/srep25815. View

deMello A . Control and detection of chemical reactions in microfluidic systems. Nature. 2006; 442(7101):394-402. DOI: 10.1038/nature05062. View

Casey J, Grinstein S, Orlowski J . Sensors and regulators of intracellular pH. Nat Rev Mol Cell Biol. 2009; 11(1):50-61. DOI: 10.1038/nrm2820. View

Shamsi M, Choi K, Ng A, Wheeler A . A digital microfluidic electrochemical immunoassay. Lab Chip. 2013; 14(3):547-54. DOI: 10.1039/c3lc51063h. View

Webb B, Chimenti M, Jacobson M, Barber D . Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011; 11(9):671-7. DOI: 10.1038/nrc3110. View

10.

Wan L, Gao J, Chen T, Dong C, Li H, Wen Y . LampPort: a handheld digital microfluidic device for loop-mediated isothermal amplification (LAMP). Biomed Microdevices. 2019; 21(1):9. DOI: 10.1007/s10544-018-0354-9. View

11.

Keng P, Chen S, Ding H, Sadeghi S, Shah G, Dooraghi A . Micro-chemical synthesis of molecular probes on an electronic microfluidic device. Proc Natl Acad Sci U S A. 2012; 109(3):690-5. PMC: 3271918. DOI: 10.1073/pnas.1117566109. View

12.

Zhai J, Li H, Wong A, Dong C, Yi S, Jia Y . A digital microfluidic system with 3D microstructures for single-cell culture. Microsyst Nanoeng. 2021; 6:6. PMC: 8433300. DOI: 10.1038/s41378-019-0109-7. View

13.

Li H, Shen R, Dong C, Chen T, Jia Y, Mak P . Turning on/off satellite droplet ejection for flexible sample delivery on digital microfluidics. Lab Chip. 2020; 20(20):3709-3719. DOI: 10.1039/d0lc00701c. View

14.

Parks S, Chiche J, Pouyssegur J . pH control mechanisms of tumor survival and growth. J Cell Physiol. 2010; 226(2):299-308. DOI: 10.1002/jcp.22400. View

15.

Swietach P, Vaughan-Jones R, Harris A, Hulikova A . The chemistry, physiology and pathology of pH in cancer. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1638):20130099. PMC: 3917353. DOI: 10.1098/rstb.2013.0099. View

16.

Zhou H, Li G, Yao S . A droplet-based pH regulator in microfluidics. Lab Chip. 2014; 14(11):1917-22. DOI: 10.1039/c3lc51442k. View

17.

Ng A, Uddayasankar U, Wheeler A . Immunoassays in microfluidic systems. Anal Bioanal Chem. 2010; 397(3):991-1007. DOI: 10.1007/s00216-010-3678-8. View

18.

Contento N, Branagan S, Bohn P . Electrolysis in nanochannels for in situ reagent generation in confined geometries. Lab Chip. 2011; 11(21):3634-41. DOI: 10.1039/c1lc20570f. View

19.

Zhang C, Xu J, Ma W, Zheng W . PCR microfluidic devices for DNA amplification. Biotechnol Adv. 2005; 24(3):243-84. DOI: 10.1016/j.biotechadv.2005.10.002. View