Advertisement

Active pumping and control of flows in centrifugal microfluidics

  • Liviu ClimeEmail author
  • Jamal Daoud
  • Daniel Brassard
  • Lidija Malic
  • Matthias Geissler
  • Teodor Veres
Review
  • 87 Downloads

Abstract

This review is an account of centrifugal microfluidic systems that use various actuation strategies in addition to intrinsic centrifugal forces to accurately regulate the motion of fluids during rotation. Platforms that integrate active methods of pumping and flow control render centrifugal microfluidics more versatile as they facilitate integration and process automation by enabling (or improving the reliability of) important fluidic functions, such as metering, aliquoting, valving, flow switching, mixing, and inward pumping. Principles and working mechanisms underlying these strategies are described in the context of recent trends in instrument design and development where centrifugal platforms have been equipped with pneumatic, magnetic or electromechanical actuators serving as pumping and valving elements. The potential of these platforms to perform complex bioanalytical assays in an automated fashion is illustrated by several examples, which include on-chip preparation of aliquot libraries, nucleic acid purification, amplification and analysis as well as blood separation.

Keywords

Active pumping Automation Centrifugal microfluidics Integration Valving Sample preparation 

Notes

Acknowledgements

This work was supported in part by the GRDI-funded program “Strengthening Food and Water Safety in Canada through an Integrated Federal Genomics Initiative”. We thank Burton W. Blais (Canadian Food Inspection Agency, Ottawa, ON), Nathalie Corneau (Health Canada, Ottawa, ON) as well as Denis Charlebois (Canadian Space Agency, St-Hubert, QC) for support and useful discussions.

References

  1. Abi-Samra K, Clime L, Kong L, Gorkin R, Kim TH, Cho YK, Madou M (2011) Thermo-pneumatic pumping in centrifugal microfluidic platforms. Microfluid Nanofluid 11:643–652CrossRefGoogle Scholar
  2. Abi-Samra K, Kim TH, Park DK, Kim N, Kim J, Kim H, Cho YK, Madou M (2013) Electrochemical velocimetry on centrifugal microfluidic platforms. Lab Chip 13:3253–3260CrossRefGoogle Scholar
  3. Aeinehvand MM, Ibrahim F, Harun SW, Al-Faqheri W, Thio THG, Kazemzadeh A, Madou M (2014) Latex micro-balloon pumping in centrifugal microfluidic platforms. Lab Chip 14:988–997CrossRefGoogle Scholar
  4. Al-Faqheri W, Ibrahim F, Thio THG, Aeinehvand MM, Arof H, Madou M (2015) Sens Actuat A 222:245–254CrossRefGoogle Scholar
  5. Amasia M, Cozzens M, Madou MJ (2012) Centrifugal microfluidic platform for rapid PCR amplification using integrated thermoelectric heating and ice-valving. Sens Actuat B 161:1191–1197CrossRefGoogle Scholar
  6. Andreasen SZ, Kwasny D, Amato L, Brøgger AL, Bosco FG, Andersen KB, Svendsen WE, Boisen A (2015) Integrating electrochemical detection with centrifugal microfluidics for real-time and fully automated sample testing. RSC Adv 5:17187–17193CrossRefGoogle Scholar
  7. Bissonnette L, Bergeron MG (2016) The GenePOC platform, a rational solution for extreme point-of-care testing. Micromachines 7:94.1–94.14CrossRefGoogle Scholar
  8. Brassard D, Clime L, Mounier M, Veres T (2016) Programmable aliquots in passive microfluidic devices using a centrifugal platform with active pneumatic pumping. Proc 20th Int Conf Miniat Syst Chem Life Sci (MicroTAS 2016) pp. 31–32Google Scholar
  9. Burger S, Schulz M, von Stetten F, Zengerle R, Paust N (2016) Rigorous buoyancy driven bubble mixing for centrifugal microfluidics. Lab Chip 16:261–268CrossRefGoogle Scholar
  10. Cai Z, Xiang J, Chen H, Wang W (2016) Pneumatic siphon valving and switching in centrifugal microfluidics controlled by rotational frequency or rotational acceleration. Sens Actuat B 228:251–258CrossRefGoogle Scholar
  11. Cao X, deMello AJ, Elvira KS (2016) Enhanced versatility of fluid control in centrifugal microfluidic platforms using two degrees of freedom. Lab Chip 16:1197–1205CrossRefGoogle Scholar
  12. Choi K, Ng AHC, Fobel R, Wheeler AR (2012) Digital microfluidics. Annu Rev Anal Chem 5:413–440CrossRefGoogle Scholar
  13. Choi MS, Yoo JC (2015) Automated centrifugal-microfluidic platform for DNA purification using laser burst valve and Coriolis effect. Appl Biochem Biotechnol 175:3778–3787CrossRefGoogle Scholar
  14. Clime L, Brassard D, Geissler M, Veres T (2015) Active pneumatic control of centrifugal microfluidic flows for lab-on-a-chip applications. Lab Chip 15:2400–2411CrossRefGoogle Scholar
  15. Clime L, Brassard D, Daoud J, Miville-Godin C, Veres T (2016) Centrifugal microfluidic approach to human blood fractionation with density gradient medium and world-to-chip connectivity. Proc 20th Int Conf Miniat Syst Chem Life Sci (MicroTAS 2016) pp. 857–858Google Scholar
  16. Czilwik G, Messinger T, Strohmeier O, Wadle S, von Stetten F, Paust N, Roth G, Zengerle R, Saarinen P, Niittymäki J, McAllister K, Sheils O, O’Leary J, Mark D (2015) Rapid and fully automated bacterial pathogen detection on a centrifugal-microfluidic LabDisk using highly sensitive nested PCR with integrated sample preparation. Lab Chip 15:3749–3759CrossRefGoogle Scholar
  17. Deng Y, Fan J, Zhou S, Zhou T, Wu J, Li Y, Liu Z, Xuan M, Wua Y (2014) Euler force actuation mechanism for siphon valving in compact disk-like microfluidic chips. Biomicrofluidics 8:024101.1–024101.18Google Scholar
  18. Ducrée J, Haeberle S, Lutz S, Pausch S, von Stetten F, Zengerle R (2007) The centrifugal microfluidic Bio-Disk platform. J Micromech Microeng 17:S103–S115CrossRefGoogle Scholar
  19. Duncombe TA, Tentori AM, Herr AE (2015) Microfluidics: reframing biological enquiry. Nat Rev Mol Cell Biol 16:554–567CrossRefGoogle Scholar
  20. Eral HB,’t Mannetje DJCM, Oh JM (2013) Contact angle hysteresis: a review of fundamentals and applications. Colloid Polym Sci 291:247–260CrossRefGoogle Scholar
  21. Garcia-Cordero JL, Kurzbuch D, Benito-Lopez F, Diamond D, Lee LP, Ricco AJ (2010a) Optically addressable single-use microfluidic valves by laser printer lithography. Lab Chip 10:2680–2687CrossRefGoogle Scholar
  22. Garcia-Cordero JL, Basabe-Desmonts L, Ducrée J, Ricco AJ (2010b) Liquid recirculation in microfluidic channels by the interplay of capillary and centrifugal forces. Microfluid Nanofluid 9:695–703CrossRefGoogle Scholar
  23. Gaughran J, Boyle D, Murphy J, Kelly R, Ducrée J (2016) Phase-selective graphene oxide membranes for advanced microfluidic flow control. Microsys Nanoeng 2:16008.1–16008.7CrossRefGoogle Scholar
  24. Geissler M, Clime L, Hoa XD, Morton KJ, Hébert H, Poncelet L, Mounier M, Deschênes M, Gauthier ME, Huszczynski G, Corneau N, Blais BW, Veres T (2015) Microfluidic integration of a cloth-based hybridization array system (CHAS) for rapid, colorimetric detection of enterohemorrhagic Escherichia coli (EHEC) using an articulated, centrifugal platform. Anal Chem 87:10565–10572CrossRefGoogle Scholar
  25. Glière A, Delattre C (2006) Modeling and fabrication of capillary stop valves for planar microfluidic systems. Sens Actuat A 130/131:601–608CrossRefGoogle Scholar
  26. Godino N, Gorkin R, Linares AV, Burger R, Ducrée J (2013) Comprehensive integration of homogeneous bioassays via centrifugo-pneumatic cascading. Lab Chip 13:685–694CrossRefGoogle Scholar
  27. Gorkin R, Park J, Siegrist J, Amasia M, Lee BS, Park J-M, Kim J, Kim H, Madou M, Cho Y-K (2010a) Centrifugal microfluidics for biomedical applications. Lab Chip 10:1758–1773CrossRefGoogle Scholar
  28. Gorkin R, Clime L, Madou M, Kido H (2010b) Pneumatic pumping in centrifugal microfluidic platforms. Microfluid Nanofluid 9:541–549CrossRefGoogle Scholar
  29. Gorkin R, Soroori S, Southard W, Clime L, Veres T, Kido H, Kulinsky L, Madou M (2012a) Suction-enhanced siphon valves for centrifugal microfluidic platforms. Microfluid Nanofluid 12:345–354CrossRefGoogle Scholar
  30. Gorkin R, Nwankire CE, Gaughran J, Zhang X, Donohoe GG, Rook M, O’Kennedy R, Ducrée J (2012b) Centrifugo-pneumatic valving utilizing dissolvable films. Lab Chip 12:2894–2902CrossRefGoogle Scholar
  31. Haeberle S, Schmitt N, Zengerle R, Ducrée J (2007) Centrifugo-magnetic pump for gas-to-liquid sampling. Sens Actuat A 135:28–33CrossRefGoogle Scholar
  32. Hitzbleck M, Avrain L, Smekens V, Lovchik RD, Mertens P, Delamarche E (2012) Capillary soft valves for microfluidics. Lab Chip 12:1972–1978CrossRefGoogle Scholar
  33. Huang LR, Cox EC, Austin RH, Sturm JC (2004) Continuous particle separation through deterministic lateral displacement. Science 304:987–990CrossRefGoogle Scholar
  34. Iverson BD, Garimella SV (2008) Recent advances in microscale pumping technologies: a review and evaluation. Microfluid Nanofluid 5:145–174CrossRefGoogle Scholar
  35. Kawai T, Naruishi N, Nagai H, Tanaka Y, Hagihara Y, Yoshida Y (2013) Rotatable reagent cartridge for high-performance microvalve system on a centrifugal microfluidic device. Anal Chem 85:6587–6592CrossRefGoogle Scholar
  36. Keller M, Wadle S, Paust N, Dreesen L, Nuese C, Strohmeier O, Zengerle R, von Stetten F (2015a) Centrifugo-thermopneumatic fluid control for valving and aliquoting applied to multiplex real-time PCR on off-the-shelf centrifugal thermocycler. RSC Adv 5:89603–89611CrossRefGoogle Scholar
  37. Keller M, Naue J, Zengerle R, von Stetten F, Schmidt U (2015b) Automated forensic animal family identification by nested PCR and melt curve analysis on an off-the-shelf thermocycler augmented with a centrifugal microfluidic disk segment. PLoS One 10:1–17Google Scholar
  38. Keller M, Czilwik G, Schott J, Schwarz I, Dormanns K, von Stetten F, Zengerle R, Paust N (2017) Robust temperature change rate actuated valving and switching for highly integrated centrifugal microfluidics. Lab Chip 17:864–875CrossRefGoogle Scholar
  39. Kim TH, Sunkara V, Park J, Kim CJ, Woo HK, Cho YK (2016) A lab-on-a-disc with reversible and thermally stable diaphragm valves. Lab Chip 16:3741–3749CrossRefGoogle Scholar
  40. Kinahan DJ, Early PL, Vembadi A, MacNamara E, Kilcawley NA, Glennon T, Diamond D, Brabazon D, Ducrée J (2016) Xurography actuated valving for centrifugal flow control. Lab Chip 16:3454–3459CrossRefGoogle Scholar
  41. Kong MCR, Salin ED (2010) Pneumatically pumping fluids radially inward on centrifugal microfluidic platforms in motion. Anal Chem 82:8039–8041CrossRefGoogle Scholar
  42. Kong MCR, Salin ED (2011) Pneumatic flow switching on centrifugal microfluidic platforms in motion. Anal Chem 83:1148–1151CrossRefGoogle Scholar
  43. Kong MCR, Bouchard AP, Salin ED (2012) Displacement pumping of liquids radially inward on centrifugal microfluidic platforms in motion. Micromachines 3:1–9CrossRefGoogle Scholar
  44. Kong LX, Parate K, Abi-Samra K, Madou M (2015) Multifunctional wax valves for liquid handling and incubation on a microfluidic CD. Microfluid Nanofluid 18:1031–1037CrossRefGoogle Scholar
  45. Kong LX, Perebikovsky A, Moebius J, Kulinsky L, Madou M (2016) Lab-on-a-CD: a fully integrated molecular diagnostic system. J Lab Autom 21:323–355CrossRefGoogle Scholar
  46. Lin S, Lian W, Chen C, Yang C, Wo AM (2012) A multifunctional vent valve system in a centrifugal microfluidic platform. Proc 16th Int Conf Miniat Syst Chem Life Sci (MicroTAS 2012) pp. 884–886Google Scholar
  47. Mach AJ, Di Carlo D (2010) Continuous scalable blood filtration device using inertial microfluidics. Biotechnol Bioeng 107:302–311CrossRefGoogle Scholar
  48. Madou M, Zoval J, Jia G, Kido H, Kim J, Kim N (2006) Development of novel passive check valves for the microfluidic CD platform Lab on a CD. Annu Rev Biomed Eng 8:601–628CrossRefGoogle Scholar
  49. Mark D, Haeberle S, Roth G, von Stetten F, Zengerle R (2010) Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications. Chem Soc Rev 39:1153–1182CrossRefGoogle Scholar
  50. Miao B, Peng N, Li L, Li Z, Hu F, Zhang Z, Wang C (2015) Centrifugal microfluidic system for nucleic acid amplification and detection. Sensors 15:27954–27968CrossRefGoogle Scholar
  51. Michael IJ, Kim TH, Sunkara V, Cho YK (2016) Challenges and opportunities of centrifugal microfluidics for extreme point-of-care testing. Micromachines 7:32.1–32.14CrossRefGoogle Scholar
  52. Park JM, Cho YK, Lee BS, Lee JG, Ko C (2007) Multifunctional microvalves control by optical illumination on nanoheaters and its application in centrifugal microfluidic devices. Lab Chip 7:557–564CrossRefGoogle Scholar
  53. Pishbin E, Eghbal M, Fakhari S, Kazemzadeh A, Navidbakhsh M (2016) The effect of moment of inertia on the liquids in centrifugal microfluidics. Micromachines 7:215.1–215.12CrossRefGoogle Scholar
  54. Roy E, Stewart G, Mounier M, Malic L, Peytavi R, Clime L, Madou M, Bossinot M, Bergeron MG, Veres T (2015) From cellular lysis to microarray detection, an integrated thermoplastic elastomer (TPE) point of care Lab on a Disc. Lab Chip 15:406–416CrossRefGoogle Scholar
  55. Schwemmer F, Zehnle S, Mark D, von Stetten F, Zengerle R, Paust N (2015a) A microfluidic timer for timed valving and pumping in centrifugal microfluidics. Lab Chip 15:1545–1553CrossRefGoogle Scholar
  56. Schwemmer F, Hutzenlaub T, Buselmeier D, Paust N, von Stetten F, Mark D, Zengerle R, Kosse D (2015b) Centrifugo-pneumatic multi-liquid aliquoting—parallel aliquoting and combination of multiple liquids in centrifugal microfluidics. Lab Chip 15:3250–3258CrossRefGoogle Scholar
  57. Siegrist J, Gorkin R, Clime L, Roy E, Peytavi R, Kido H, Bergeron M, Veres T, Madou M (2010a) Serial siphon valving for centrifugal microfluidic platforms. Microfluid Nanofluid 9:55–63CrossRefGoogle Scholar
  58. Siegrist J, Gorkin R, Bastien M, Stewart G, Peytavi R, Kido H, Bergeron M, Madou M (2010b) Validation of a centrifugal microfluidic sample lysis and homogenization platform for nucleic acid extraction with clinical samples. Lab Chip 10:363–371CrossRefGoogle Scholar
  59. Smith S, Mager D, Perebikovsky A, Shamloo E, Kinahan D, Mishra R, Torres Delgado SM, Kido H, Saha S, Ducrée J, Madou M, Land K, Korvink JG (2016) CD-based microfluidics for primary care in extreme point-of-care settings. Micromachines 7:22.1–22.32CrossRefGoogle Scholar
  60. Squires TM, Quake SR (2005) Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys 77:977–1026CrossRefGoogle Scholar
  61. Strohmeier O, Emperle A, Roth G, Mark D, Zengerle R, von Stetten F (2013) Centrifugal gas-phase transition magnetophoresis (GTM)—a generic method for automation of magnetic bead based assays on the centrifugal microfluidic platform and application to DNA purification. Lab Chip 13:146–155CrossRefGoogle Scholar
  62. Strohmeier O, Keller M, Schwemmer F, Zehnle S, Mark D, von Stetten F, Zengerle R, Paust N (2015) Centrifugal microfluidic platforms: advanced unit operations and applications. Chem Soc Rev 44:6187–6229CrossRefGoogle Scholar
  63. Stumpf F, Schwemmer F, Hutzenlaub T, Baumann D, Strohmeier O, von Stetten F, Zengerle R, Mark D (2015) Automated sample-to-answer nucleic acid testing with frequency controlled reagent release from cartridge integrated stickpacks. Proc 18th Int Conf Solid-State Sens Actuat Microsys (Transducers 2015) pp. 743–746Google Scholar
  64. Stumpf F, Schwemmer F, Hutzenlaub T, Baumann D, Strohmeier O, Dingemanns G, Simons G, Sager C, Plobner L, von Stetten F, Zengerle R, Mark D (2016) LabDisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza A H3N2 virus. Lab Chip 16:199–207CrossRefGoogle Scholar
  65. Tang M, Wang G, Kong SK, Ho HP (2016) A Review of biomedical centrifugal microfluidic platforms. Micromachines 7:26.1–26.29CrossRefGoogle Scholar
  66. Thio THG, Ibrahim F, Al-Faqheri W, Soin N, Abdul Kahar MKB, Madou M (2013a) Multi-level 3D implementation of thermo-pneumatic pumping on centrifugal microfluidic CD platforms. Proc 35th Annu Int Conf IEEE EMBS pp. 5513–5516Google Scholar
  67. Thio THG, Ibrahim F, Al-Faqheri W, Moebius J, Khalid NS, Soin N, Kahar MKBA, Madou M (2013b) Push pull microfluidics on a multi-level 3D CD. Lab Chip 13:3199–3209CrossRefGoogle Scholar
  68. Thio THG, Ibrahim F, Al-Faqheri W, Soin N, Bador MK, Madou M (2015) Sequential push-pull pumping mechanism for washing and evacuation of an immunoassay reaction chamber on a microfluidic CD platform. PLoS One 10:1–17Google Scholar
  69. Ukita Y, Takamura Y, Utsumi Y (2015) Water-clock-based autonomous flow sequencing in steadily rotating centrifugal microfluidic device. Sens Actuat B 220:180–183CrossRefGoogle Scholar
  70. Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288:113–116CrossRefGoogle Scholar
  71. Urban PL (2015) Universal electronics for miniature and automated chemical assays. Analyst 140:963–975CrossRefGoogle Scholar
  72. van Oordt T, Barb Y, Smetana J, Zengerle R, von Stetten F (2013) Miniature stick-packaging—an industrial technology for pre-storage and release of reagents in lab-on-a-chip systems. Lab Chip 13:2888–2892CrossRefGoogle Scholar
  73. Vestad T, Marr DWM, Oakey J (2004) Flow control for capillary-pumped microfluidic systems. J Micromech Microeng 14:1503–1506CrossRefGoogle Scholar
  74. Wang GJ, Hsu WH, Chang YZ, Yang H (2004) Centrifugal and electric field forces dual-pumping CD-like microfluidic platform for biomedical separation. Biomed Microdev 6:47–53CrossRefGoogle Scholar
  75. Wang G, Ho HP, Chen Q, Yang AK-L, Kwok H-C, Wu S-Y, Kong S-K, Kwan Y-W, Zhang X (2013) A lab-in-a-droplet bioassay strategy for centrifugal microfluidics with density difference pumping, power to disc and bidirectional flow control. Lab Chip 13:3698–3706CrossRefGoogle Scholar
  76. Zehnle S, Schwemmer F, Roth G, von Stetten F, Zengerle R, Paust N (2012) Centrifugo-dynamic inward pumping of liquids on a centrifugal microfluidic platform. Lab Chip 12:5142–5145CrossRefGoogle Scholar
  77. Zehnle S, Schwemmer F, Bergmann R, von Stetten F, Zengerle R, Paust N (2015) Pneumatic siphon valving and switching in centrifugal microfluidics controlled by rotational frequency or rotational acceleration. Microfluid Nanofluid 19:1259–1269CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Life Sciences DivisionNational Research Council of CanadaBouchervilleCanada

Personalised recommendations