Multiphase Bioreaction Microsystem with Automated On-chip Droplet Operation

Overview

Journal Lab Chip

Publisher Royal Society of Chemistry

Specialties Biotechnology
Chemistry

Date 2010 May 7

PMID 20445885

Authors

Fang Wang

Mark A Burns

Affiliations

Soon will be listed here.

Abstract

A droplet-based bioreaction microsystem has been developed with automated droplet generation and confinement. On-chip electronic sensing is employed to track the position of the droplets by sensing the oil/aqueous interface in real time. The sensing signal is also used to control the pneumatic supply for moving as well as automatically generating four different nanolitre-sized droplets. The actual size of droplets is very close to the designed droplet size with a standard deviation less than 3% of the droplet size. The automated droplet generation can be completed in less than 2 s, which is 5 times faster than using manual operation that takes at least 10 s. Droplets can also be automatically confined in the reaction region with feedback pneumatic control and digital or analog sensing. As an example bioreaction, PCR has been successfully performed in the automated generated droplets. Although the amplification yield was slightly reduced with the droplet confinement, especially while using the analog sensing method, adding additional reagents effectively alleviated this inhibition.

References

Bringer M, Gerdts C, Song H, Tice J, Ismagilov R . Microfluidic systems for chemical kinetics that rely on chaotic mixing in droplets. Philos Trans A Math Phys Eng Sci. 2004; 362(1818):1087-104. PMC: 1769314. DOI: 10.1098/rsta.2003.1364. View

Kumaresan P, Yang C, Cronier S, Blazej R, Mathies R . High-throughput single copy DNA amplification and cell analysis in engineered nanoliter droplets. Anal Chem. 2008; 80(10):3522-9. DOI: 10.1021/ac800327d. View

Chen J, Darhuber A, Troian S, Wagner S . Capacitive sensing of droplets for microfluidic devices based on thermocapillary actuation. Lab Chip. 2004; 4(5):473-80. DOI: 10.1039/b315815b. View

Chabert M, Viovy J . Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells. Proc Natl Acad Sci U S A. 2008; 105(9):3191-6. PMC: 2265149. DOI: 10.1073/pnas.0708321105. View

Shestopalov I, Tice J, Ismagilov R . Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system. Lab Chip. 2004; 4(4):316-21. DOI: 10.1039/b403378g. View

Garstecki P, Fuerstman M, Stone H, Whitesides G . Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up. Lab Chip. 2006; 6(3):437-46. DOI: 10.1039/b510841a. View

Link D, Anna S, Weitz D, Stone H . Geometrically mediated breakup of drops in microfluidic devices. Phys Rev Lett. 2004; 92(5):054503. DOI: 10.1103/PhysRevLett.92.054503. View

Nisisako T, Torii T, Higuchi T . Droplet formation in a microchannel network. Lab Chip. 2004; 2(1):24-6. DOI: 10.1039/b108740c. View

Tan Y, Fisher J, Lee A, Cristini V, Lee A . Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting. Lab Chip. 2004; 4(4):292-8. DOI: 10.1039/b403280m. View

10.

Song H, Bringer M, Tice J, Gerdts C, Ismagilov R . Experimental test of scaling of mixing by chaotic advection in droplets moving through microfluidic channels. Appl Phys Lett. 2007; 83(12):4664-4666. PMC: 2025702. DOI: 10.1063/1.1630378. View

11.

Srivastava N, Burns M . Electronic drop sensing in microfluidic devices: automated operation of a nanoliter viscometer. Lab Chip. 2006; 6(6):744-51. PMC: 1987353. DOI: 10.1039/b516317j. View

12.

Thorsen T, Roberts R, Arnold F, Quake S . Dynamic pattern formation in a vesicle-generating microfluidic device. Phys Rev Lett. 2001; 86(18):4163-6. DOI: 10.1103/PhysRevLett.86.4163. View

13.

Huebner A, Srisa-Art M, Holt D, ABELL C, Hollfelder F, deMello A . Quantitative detection of protein expression in single cells using droplet microfluidics. Chem Commun (Camb). 2007; (12):1218-20. DOI: 10.1039/b618570c. View

14.

Pal R, Yang M, Lin R, Johnson B, Srivastava N, Razzacki S . An integrated microfluidic device for influenza and other genetic analyses. Lab Chip. 2005; 5(10):1024-32. DOI: 10.1039/b505994a. View

15.

Lehmann U, Vandevyver C, Parashar V, Gijs M . Droplet-based DNA purification in a magnetic lab-on-a-chip. Angew Chem Int Ed Engl. 2006; 45(19):3062-7. DOI: 10.1002/anie.200503624. View

16.

Collins J, Lee A . Microfluidic flow transducer based on the measurement of electrical admittance. Lab Chip. 2004; 4(1):7-10. DOI: 10.1039/b310282c. View

17.

Niu X, Zhang M, Peng S, Wen W, Sheng P . Real-time detection, control, and sorting of microfluidic droplets. Biomicrofluidics. 2009; 1(4):44101. PMC: 2717736. DOI: 10.1063/1.2795392. View

18.

Fang T, Ramalingam N, Xian-Dui D, Ngin T, Xianting Z, Lai Kuan A . Real-time PCR microfluidic devices with concurrent electrochemical detection. Biosens Bioelectron. 2009; 24(7):2131-6. DOI: 10.1016/j.bios.2008.11.009. View

19.

Wang F, Burns M . Performance of nanoliter-sized droplet-based microfluidic PCR. Biomed Microdevices. 2009; 11(5):1071-80. PMC: 2955802. DOI: 10.1007/s10544-009-9324-6. View

20.

Pollack M, Shenderov A, Fair R . Electrowetting-based actuation of droplets for integrated microfluidics. Lab Chip. 2004; 2(2):96-101. DOI: 10.1039/b110474h. View