Figure 1. (a) Top view of the microfluidic-magnetophoretic device, (b) Schematic representation of the channel cross-sections studied in this work, and (c) the magnet position relative to the channel location (Sepy and Sepz are the magnet separation distances in y and z, respectively).

Continuous-Flow Separation of Magnetic Particles from Biofluids: How Does the Microdevice Geometry Determine the Separation Performance?

1Department of Chemical and Biomolecular Engineering, ETSIIT, University of Cantabria, Avda. Los Castros s/n, 39005 Santander, Spain
2William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 W. Woodruff Ave., Columbus, OH 43210, USA
*Author to whom correspondence should be addressed.
Sensors 202020(11), 3030; https://doi.org/10.3390/s20113030
Received: 16 April 2020 / Revised: 21 May 2020 / Accepted: 25 May 2020 / Published: 27 May 2020
(This article belongs to the Special Issue Lab-on-a-Chip and Microfluidic Sensors)

Abstract

The use of functionalized magnetic particles for the detection or separation of multiple chemicals and biomolecules from biofluids continues to attract significant attention. After their incubation with the targeted substances, the beads can be magnetically recovered to perform analysis or diagnostic tests. Particle recovery with permanent magnets in continuous-flow microdevices has gathered great attention in the last decade due to the multiple advantages of microfluidics. As such, great efforts have been made to determine the magnetic and fluidic conditions for achieving complete particle capture; however, less attention has been paid to the effect of the channel geometry on the system performance, although it is key for designing systems that simultaneously provide high particle recovery and flow rates. Herein, we address the optimization of Y-Y-shaped microchannels, where magnetic beads are separated from blood and collected into a buffer stream by applying an external magnetic field. The influence of several geometrical features (namely cross section shape, thickness, length, and volume) on both bead recovery and system throughput is studied. For that purpose, we employ an experimentally validated Computational Fluid Dynamics (CFD) numerical model that considers the dominant forces acting on the beads during separation. Our results indicate that rectangular, long devices display the best performance as they deliver high particle recovery and high throughput. Thus, this methodology could be applied to the rational design of lab-on-a-chip devices for any magnetically driven purification, enrichment or isolation.

Keywords: particle magnetophoresisCFDcross sectionchip fabrication

Korea Abstract

생체 유체에서 여러 화학 물질과 생체 분자의 검출 또는 분리를위한 기능화 된 자성 입자의 사용은 계속해서 상당한 관심을 받고 있습니다. 표적 물질과 함께 배양 한 후 비드를 자기 적으로 회수하여 분석 또는 진단 테스트를 수행 할 수 있습니다. 연속 흐름 마이크로 장치에서 영구 자석을 사용한 입자 회수는 마이크로 유체의 여러 장점으로 인해 지난 10 년 동안 큰 관심을 모았습니다. 

따라서 완전한 입자 포획을 달성하기 위한 자기 및 유체 조건을 결정하기 위해 많은 노력을 기울였습니다. 그러나 높은 입자 회수율과 유속을 동시에 제공하는 시스템을 설계하는 데있어 핵심이기는 하지만 시스템 성능에 대한 채널 형상의 영향에 대해서는 덜주의를 기울였습니다. 

여기에서 우리는 자기 비드가 혈액에서 분리되고 외부 자기장을 적용하여 버퍼 스트림으로 수집되는 YY 모양의 마이크로 채널의 최적화를 다룹니다. 비드 회수 및 시스템 처리량에 대한 여러 기하학적 특징 (즉, 단면 형상, 두께, 길이 및 부피)의 영향을 연구합니다. 

이를 위해 분리 중에 비드에 작용하는 지배적인 힘을 고려하는 실험적으로 검증 된 CFD (Computational Fluid Dynamics) 수치 모델을 사용합니다. 우리의 결과는 직사각형의 긴 장치가 높은 입자 회수율과 높은 처리량을 제공하기 때문에 최고의 성능을 보여줍니다. 

따라서 이 방법론은 자기 구동 정제, 농축 또는 분리를 위한 랩온어 칩 장치의 합리적인 설계에 적용될 수 있습니다.

Figure 1. (a) Top view of the microfluidic-magnetophoretic device, (b) Schematic representation of the channel cross-sections studied in this work, and (c) the magnet position relative to the channel location (Sepy and Sepz are the magnet separation distances in y and z, respectively).
Figure 1. (a) Top view of the microfluidic-magnetophoretic device, (b) Schematic representation of the channel cross-sections studied in this work, and (c) the magnet position relative to the channel location (Sepy and Sepz are the magnet separation distances in y and z, respectively).
Figure 2. (a) Channel-magnet configuration and (b–d) magnetic force distribution in the channel midplane for 2 mm, 5 mm and 10 mm long rectangular (left) and U-shaped (right) devices.
Figure 2. (a) Channel-magnet configuration and (b–d) magnetic force distribution in the channel midplane for 2 mm, 5 mm and 10 mm long rectangular (left) and U-shaped (right) devices.
Figure 3. (a) Velocity distribution in a section perpendicular to the flow for rectangular (left) and U-shaped (right) cross section channels, and (b) particle location in these cross sections.
Figure 3. (a) Velocity distribution in a section perpendicular to the flow for rectangular (left) and U-shaped (right) cross section channels, and (b) particle location in these cross sections.
Figure 4. Influence of fluid flow rate on particle recovery when the applied magnetic force is (a) different and (b) equal in U-shaped and rectangular cross section microdevices.
Figure 4. Influence of fluid flow rate on particle recovery when the applied magnetic force is (a) different and (b) equal in U-shaped and rectangular cross section microdevices.
Figure 5. Magnetic bead capture as a function of fluid flow rate for all of the studied geometries.
Figure 5. Magnetic bead capture as a function of fluid flow rate for all of the studied geometries.
Figure 6. Influence of (a) magnetic and fluidic forces (J parameter) and (b) channel geometry (θ parameter) on particle recovery. Note that U-2mm does not accurately fit a line.
Figure 6. Influence of (a) magnetic and fluidic forces (J parameter) and (b) channel geometry (θ parameter) on particle recovery. Note that U-2mm does not accurately fit a line.
Figure 7. Dependence of bead capture on the (a) functional channel volume and (b) particle residence time (tres). Note that in the curve fitting expressions V represents the functional channel volume and that U-2mm does not accurately fit a line.
Figure 7. Dependence of bead capture on the (a) functional channel volume and (b) particle residence time (tres). Note that in the curve fitting expressions V represents the functional channel volume and that U-2mm does not accurately fit a line.

References

  1. Gómez-Pastora, J.; Xue, X.; Karampelas, I.H.; Bringas, E.; Furlani, E.P.; Ortiz, I. Analysis of separators for magnetic beads recovery: From large systems to multifunctional microdevices. Sep. Purif. Technol. 2017172, 16–31. [Google Scholar] [CrossRef]
  2. Wise, N.; Grob, T.; Morten, K.; Thompson, I.; Sheard, S. Magnetophoretic velocities of superparamagnetic particles, agglomerates and complexes. J. Magn. Magn. Mater. 2015384, 328–334. [Google Scholar] [CrossRef]
  3. Khashan, S.A.; Elnajjar, E.; Haik, Y. CFD simulation of the magnetophoretic separation in a microchannel. J. Magn. Magn. Mater. 2011323, 2960–2967. [Google Scholar] [CrossRef]
  4. Khashan, S.A.; Furlani, E.P. Scalability analysis of magnetic bead separation in a microchannel with an array of soft magnetic elements in a uniform magnetic field. Sep. Purif. Technol. 2014125, 311–318. [Google Scholar] [CrossRef]
  5. Furlani, E.P. Magnetic biotransport: Analysis and applications. Materials 20103, 2412–2446. [Google Scholar] [CrossRef]
  6. Gómez-Pastora, J.; Bringas, E.; Ortiz, I. Design of novel adsorption processes for the removal of arsenic from polluted groundwater employing functionalized magnetic nanoparticles. Chem. Eng. Trans. 201647, 241–246. [Google Scholar]
  7. Gómez-Pastora, J.; Bringas, E.; Lázaro-Díez, M.; Ramos-Vivas, J.; Ortiz, I. The reverse of controlled release: Controlled sequestration of species and biotoxins into nanoparticles (NPs). In Drug Delivery Systems; Stroeve, P., Mahmoudi, M., Eds.; World Scientific: Hackensack, NJ, USA, 2017; pp. 207–244. ISBN 9789813201057. [Google Scholar]
  8. Ruffert, C. Magnetic bead-magic bullet. Micromachines 20167, 21. [Google Scholar] [CrossRef]
  9. Yáñez-Sedeño, P.; Campuzano, S.; Pingarrón, J.M. Magnetic particles coupled to disposable screen printed transducers for electrochemical biosensing. Sensors 201616, 1585. [Google Scholar] [CrossRef]
  10. Schrittwieser, S.; Pelaz, B.; Parak, W.J.; Lentijo-Mozo, S.; Soulantica, K.; Dieckhoff, J.; Ludwig, F.; Guenther, A.; Tschöpe, A.; Schotter, J. Homogeneous biosensing based on magnetic particle labels. Sensors 201616, 828. [Google Scholar] [CrossRef]
  11. He, J.; Huang, M.; Wang, D.; Zhang, Z.; Li, G. Magnetic separation techniques in sample preparation for biological analysis: A review. J. Pharm. Biomed. Anal. 2014101, 84–101. [Google Scholar] [CrossRef]
  12. Ha, Y.; Ko, S.; Kim, I.; Huang, Y.; Mohanty, K.; Huh, C.; Maynard, J.A. Recent advances incorporating superparamagnetic nanoparticles into immunoassays. ACS Appl. Nano Mater. 20181, 512–521. [Google Scholar] [CrossRef]
  13. Gómez-Pastora, J.; González-Fernández, C.; Fallanza, M.; Bringas, E.; Ortiz, I. Flow patterns and mass transfer performance of miscible liquid-liquid flows in various microchannels: Numerical and experimental studies. Chem. Eng. J. 2018344, 487–497. [Google Scholar] [CrossRef]
  14. Gale, B.K.; Jafek, A.R.; Lambert, C.J.; Goenner, B.L.; Moghimifam, H.; Nze, U.C.; Kamarapu, S.K. A review of current methods in microfluidic device fabrication and future commercialization prospects. Inventions 20183, 60. [Google Scholar] [CrossRef]
  15. Nanobiotechnology; Concepts, Applications and Perspectives; Niemeyer, C.M.; Mirkin, C.A. (Eds.) Wiley-VCH: Weinheim, Germany, 2004; ISBN 3527305068. [Google Scholar]
  16. Khashan, S.A.; Dagher, S.; Alazzam, A.; Mathew, B.; Hilal-Alnaqbi, A. Microdevice for continuous flow magnetic separation for bioengineering applications. J. Micromech. Microeng. 201727, 055016. [Google Scholar] [CrossRef]
  17. Basauri, A.; Gomez-Pastora, J.; Fallanza, M.; Bringas, E.; Ortiz, I. Predictive model for the design of reactive micro-separations. Sep. Purif. Technol. 2019209, 900–907. [Google Scholar] [CrossRef]
  18. Abdollahi, P.; Karimi-Sabet, J.; Moosavian, M.A.; Amini, Y. Microfluidic solvent extraction of calcium: Modeling and optimization of the process variables. Sep. Purif. Technol. 2020231, 115875. [Google Scholar] [CrossRef]
  19. Khashan, S.A.; Alazzam, A.; Furlani, E. A novel design for a microfluidic magnetophoresis system: Computational study. In Proceedings of the 12th International Symposium on Fluid Control, Measurement and Visualization (FLUCOME2013), Nara, Japan, 18–23 November 2013. [Google Scholar]
  20. Pamme, N. Magnetism and microfluidics. Lab Chip 20066, 24–38. [Google Scholar] [CrossRef]
  21. Gómez-Pastora, J.; Amiri Roodan, V.; Karampelas, I.H.; Alorabi, A.Q.; Tarn, M.D.; Iles, A.; Bringas, E.; Paunov, V.N.; Pamme, N.; Furlani, E.P.; et al. Two-step numerical approach to predict ferrofluid droplet generation and manipulation inside multilaminar flow chambers. J. Phys. Chem. C 2019123, 10065–10080. [Google Scholar] [CrossRef]
  22. Gómez-Pastora, J.; Karampelas, I.H.; Bringas, E.; Furlani, E.P.; Ortiz, I. Numerical analysis of bead magnetophoresis from flowing blood in a continuous-flow microchannel: Implications to the bead-fluid interactions. Sci. Rep. 20199, 7265. [Google Scholar] [CrossRef]
  23. Tarn, M.D.; Pamme, N. On-Chip Magnetic Particle-Based Immunoassays Using Multilaminar Flow for Clinical Diagnostics. In Microchip Diagnostics Methods and Protocols; Taly, V., Viovy, J.L., Descroix, S., Eds.; Humana Press: New York, NY, USA, 2017; pp. 69–83. [Google Scholar]
  24. Phurimsak, C.; Tarn, M.D.; Peyman, S.A.; Greenman, J.; Pamme, N. On-chip determination of c-reactive protein using magnetic particles in continuous flow. Anal. Chem. 201486, 10552–10559. [Google Scholar] [CrossRef]
  25. Wu, X.; Wu, H.; Hu, Y. Enhancement of separation efficiency on continuous magnetophoresis by utilizing L/T-shaped microchannels. Microfluid. Nanofluid. 201111, 11–24. [Google Scholar] [CrossRef]
  26. Vojtíšek, M.; Tarn, M.D.; Hirota, N.; Pamme, N. Microfluidic devices in superconducting magnets: On-chip free-flow diamagnetophoresis of polymer particles and bubbles. Microfluid. Nanofluid. 201213, 625–635. [Google Scholar] [CrossRef]
  27. Gómez-Pastora, J.; González-Fernández, C.; Real, E.; Iles, A.; Bringas, E.; Furlani, E.P.; Ortiz, I. Computational modeling and fluorescence microscopy characterization of a two-phase magnetophoretic microsystem for continuous-flow blood detoxification. Lab Chip 201818, 1593–1606. [Google Scholar] [CrossRef] [PubMed]
  28. Forbes, T.P.; Forry, S.P. Microfluidic magnetophoretic separations of immunomagnetically labeled rare mammalian cells. Lab Chip 201212, 1471–1479. [Google Scholar] [CrossRef]
  29. Nandy, K.; Chaudhuri, S.; Ganguly, R.; Puri, I.K. Analytical model for the magnetophoretic capture of magnetic microspheres in microfluidic devices. J. Magn. Magn. Mater. 2008320, 1398–1405. [Google Scholar] [CrossRef]
  30. Plouffe, B.D.; Lewis, L.H.; Murthy, S.K. Computational design optimization for microfluidic magnetophoresis. Biomicrofluidics 20115, 013413. [Google Scholar] [CrossRef] [PubMed]
  31. Hale, C.; Darabi, J. Magnetophoretic-based microfluidic device for DNA isolation. Biomicrofluidics 20148, 044118. [Google Scholar] [CrossRef] [PubMed]
  32. Becker, H.; Gärtner, C. Polymer microfabrication methods for microfluidic analytical applications. Electrophoresis 200021, 12–26. [Google Scholar] [CrossRef]
  33. Pekas, N.; Zhang, Q.; Nannini, M.; Juncker, D. Wet-etching of structures with straight facets and adjustable taper into glass substrates. Lab Chip 201010, 494–498. [Google Scholar] [CrossRef]
  34. Wang, T.; Chen, J.; Zhou, T.; Song, L. Fabricating microstructures on glass for microfluidic chips by glass molding process. Micromachines 20189, 269. [Google Scholar] [CrossRef]
  35. Castaño-Álvarez, M.; Pozo Ayuso, D.F.; García Granda, M.; Fernández-Abedul, M.T.; Rodríguez García, J.; Costa-García, A. Critical points in the fabrication of microfluidic devices on glass substrates. Sens. Actuators B Chem. 2008130, 436–448. [Google Scholar] [CrossRef]
  36. Prakash, S.; Kumar, S. Fabrication of microchannels: A review. Proc. Inst. Mech. Eng. Part B J. Eng. Manuf. 2015229, 1273–1288. [Google Scholar] [CrossRef]
  37. Leester-Schädel, M.; Lorenz, T.; Jürgens, F.; Ritcher, C. Fabrication of Microfluidic Devices. In Microsystems for Pharmatechnology: Manipulation of Fluids, Particles, Droplets, and Cells; Dietzel, A., Ed.; Springer: Basel, Switzerland, 2016; pp. 23–57. ISBN 9783319269207. [Google Scholar]
  38. Bartlett, N.W.; Wood, R.J. Comparative analysis of fabrication methods for achieving rounded microchannels in PDMS. J. Micromech. Microeng. 201626, 115013. [Google Scholar] [CrossRef]
  39. Ng, P.F.; Lee, K.I.; Yang, M.; Fei, B. Fabrication of 3D PDMS microchannels of adjustable cross-sections via versatile gel templates. Polymers 201911, 64. [Google Scholar] [CrossRef] [PubMed]
  40. Furlani, E.P.; Sahoo, Y.; Ng, K.C.; Wortman, J.C.; Monk, T.E. A model for predicting magnetic particle capture in a microfluidic bioseparator. Biomed. Microdevices 20079, 451–463. [Google Scholar] [CrossRef]
  41. Tarn, M.D.; Peyman, S.A.; Robert, D.; Iles, A.; Wilhelm, C.; Pamme, N. The importance of particle type selection and temperature control for on-chip free-flow magnetophoresis. J. Magn. Magn. Mater. 2009321, 4115–4122. [Google Scholar] [CrossRef]
  42. Furlani, E.P. Permanent Magnet and Electromechanical Devices; Materials, Analysis and Applications; Academic Press: Waltham, MA, USA, 2001. [Google Scholar]
  43. White, F.M. Viscous Fluid Flow; McGraw-Hill: New York, NY, USA, 1974. [Google Scholar]
  44. Mathew, B.; Alazzam, A.; El-Khasawneh, B.; Maalouf, M.; Destgeer, G.; Sung, H.J. Model for tracing the path of microparticles in continuous flow microfluidic devices for 2D focusing via standing acoustic waves. Sep. Purif. Technol. 2015153, 99–107. [Google Scholar] [CrossRef]
  45. Furlani, E.J.; Furlani, E.P. A model for predicting magnetic targeting of multifunctional particles in the microvasculature. J. Magn. Magn. Mater. 2007312, 187–193. [Google Scholar] [CrossRef]
  46. Furlani, E.P.; Ng, K.C. Analytical model of magnetic nanoparticle transport and capture in the microvasculature. Phys. Rev. E 200673, 061919. [Google Scholar] [CrossRef]
  47. Eibl, R.; Eibl, D.; Pörtner, R.; Catapano, G.; Czermak, P. Cell and Tissue Reaction Engineering; Springer: Berlin/Heidelberg, Germany, 2009. [Google Scholar]
  48. Pamme, N.; Eijkel, J.C.T.; Manz, A. On-chip free-flow magnetophoresis: Separation and detection of mixtures of magnetic particles in continuous flow. J. Magn. Magn. Mater. 2006307, 237–244. [Google Scholar] [CrossRef]
  49. Alorabi, A.Q.; Tarn, M.D.; Gómez-Pastora, J.; Bringas, E.; Ortiz, I.; Paunov, V.N.; Pamme, N. On-chip polyelectrolyte coating onto magnetic droplets-Towards continuous flow assembly of drug delivery capsules. Lab Chip 201717, 3785–3795. [Google Scholar] [CrossRef]
  50. Zhang, H.; Guo, H.; Chen, Z.; Zhang, G.; Li, Z. Application of PECVD SiC in glass micromachining. J. Micromech. Microeng. 200717, 775–780. [Google Scholar] [CrossRef]
  51. Mourzina, Y.; Steffen, A.; Offenhäusser, A. The evaporated metal masks for chemical glass etching for BioMEMS. Microsyst. Technol. 200511, 135–140. [Google Scholar] [CrossRef]
  52. Mata, A.; Fleischman, A.J.; Roy, S. Fabrication of multi-layer SU-8 microstructures. J. Micromech. Microeng. 200616, 276–284. [Google Scholar] [CrossRef]
  53. Su, N. 8 2000 Negative Tone Photoresist Formulations 2002–2025; MicroChem Corporation: Newton, MA, USA, 2002. [Google Scholar]
  54. Su, N. 8 2000 Negative Tone Photoresist Formulations 2035–2100; MicroChem Corporation: Newton, MA, USA, 2002. [Google Scholar]
  55. Fu, C.; Hung, C.; Huang, H. A novel and simple fabrication method of embedded SU-8 micro channels by direct UV lithography. J. Phys. Conf. Ser. 200634, 330–335. [Google Scholar] [CrossRef]
  56. Kazoe, Y.; Yamashiro, I.; Mawatari, K.; Kitamori, T. High-pressure acceleration of nanoliter droplets in the gas phase in a microchannel. Micromachines 20167, 142. [Google Scholar] [CrossRef]
  57. Sharp, K.V.; Adrian, R.J.; Santiago, J.G.; Molho, J.I. Liquid flows in microchannels. In MEMS: Introduction and Fundamentals; Gad-el-Hak, M., Ed.; CRC Press: Boca Raton, FL, USA, 2006; pp. 10-1–10-46. ISBN 9781420036572. [Google Scholar]
  58. Oh, K.W.; Lee, K.; Ahn, B.; Furlani, E.P. Design of pressure-driven microfluidic networks using electric circuit analogy. Lab Chip 201212, 515–545. [Google Scholar] [CrossRef]
  59. Bruus, H. Theoretical Microfluidics; Oxford University Press: New York, NY, USA, 2008; ISBN 9788578110796. [Google Scholar]
  60. Beebe, D.J.; Mensing, G.A.; Walker, G.M. Physics and applications of microfluidics in biology. Annu. Rev. Biomed. Eng. 20024, 261–286. [Google Scholar] [CrossRef] [PubMed]
  61. Yalikun, Y.; Tanaka, Y. Large-scale integration of all-glass valves on a microfluidic device. Micromachines 20167, 83. [Google Scholar] [CrossRef] [PubMed]
  62. Van Heeren, H.; Verhoeven, D.; Atkins, T.; Tzannis, A.; Becker, H.; Beusink, W.; Chen, P. Design Guideline for Microfluidic Device and Component Interfaces (Part 2), Version 3; Available online: http://www.makefluidics.com/en/design-guideline?id=7 (accessed on 9 March 2020).
  63. Scheuble, N.; Iles, A.; Wootton, R.C.R.; Windhab, E.J.; Fischer, P.; Elvira, K.S. Microfluidic technique for the simultaneous quantification of emulsion instabilities and lipid digestion kinetics. Anal. Chem. 201789, 9116–9123. [Google Scholar] [CrossRef] [PubMed]
  64. Lynch, E.C. Red blood cell damage by shear stress. Biophys. J. 197212, 257–273. [Google Scholar]
  65. Paul, R.; Apel, J.; Klaus, S.; Schügner, F.; Schwindke, P.; Reul, H. Shear stress related blood damage in laminar Couette flow. Artif. Organs 200327, 517–529. [Google Scholar] [CrossRef] [PubMed]
  66. Gómez-Pastora, J.; Karampelas, I.H.; Xue, X.; Bringas, E.; Furlani, E.P.; Ortiz, I. Magnetic bead separation from flowing blood in a two-phase continuous-flow magnetophoretic microdevice: Theoretical analysis through computational fluid dynamics simulation. J. Phys. Chem. C 2017121, 7466–7477. [Google Scholar] [CrossRef]
  67. Lim, J.; Yeap, S.P.; Leow, C.H.; Toh, P.Y.; Low, S.C. Magnetophoresis of iron oxide nanoparticles at low field gradient: The role of shape anisotropy. J. Colloid Interface Sci. 2014421, 170–177. [Google Scholar] [CrossRef] [PubMed]
  68. Culbertson, C.T.; Sibbitts, J.; Sellens, K.; Jia, S. Fabrication of Glass Microfluidic Devices. In Microfluidic Electrophoresis: Methods and Protocols; Dutta, D., Ed.; Humana Press: New York, NY, USA, 2019; pp. 1–12. ISBN 978-1-4939-8963-8. [Google Scholar]
Figure 3. (a) Velocity distribution in a section perpendicular to the flow for rectangular (left) and Ushaped (right) cross section channels, and (b) particle location in these cross sections.

Continuous-Flow Separation of Magnetic Particles from Biofluids: How Does the Microdevice Geometry Determine the Separation Performance?

Cristina González Fernández,1 Jenifer Gómez Pastora,2 Arantza Basauri,1 Marcos Fallanza,1 Eugenio Bringas,1 Jeffrey J. Chalmers,2 and Inmaculada Ortiz1,*
Author information Article notes Copyright and License information Disclaimer

생체 유체에서 자성 입자의 연속 흐름 분리 : 마이크로 장치 형상이 분리 성능을 어떻게 결정합니까?

Abstract

The use of functionalized magnetic particles for the detection or separation of multiple chemicals and biomolecules from biofluids continues to attract significant attention. After their incubation with the targeted substances, the beads can be magnetically recovered to perform analysis or diagnostic tests. Particle recovery with permanent magnets in continuous-flow microdevices has gathered great attention in the last decade due to the multiple advantages of microfluidics. As such, great efforts have been made to determine the magnetic and fluidic conditions for achieving complete particle capture; however, less attention has been paid to the effect of the channel geometry on the system performance, although it is key for designing systems that simultaneously provide high particle recovery and flow rates. Herein, we address the optimization of Y-Y-shaped microchannels, where magnetic beads are separated from blood and collected into a buffer stream by applying an external magnetic field. The influence of several geometrical features (namely cross section shape, thickness, length, and volume) on both bead recovery and system throughput is studied. For that purpose, we employ an experimentally validated Computational Fluid Dynamics (CFD) numerical model that considers the dominant forces acting on the beads during separation. Our results indicate that rectangular, long devices display the best performance as they deliver high particle recovery and high throughput. Thus, this methodology could be applied to the rational design of lab-on-a-chip devices for any magnetically driven purification, enrichment or isolation.

생체 유체에서 여러 화학 물질과 생체 분자의 검출 또는 분리를 위한 기능화된 자성 입자의 사용은 계속해서 상당한 관심을 받고 있습니다. 표적 물질과 함께 배양 한 후 비드는 자기적으로 회수되어 분석 또는 진단 테스트를 수행 할 수 있습니다.

연속 흐름 마이크로 장치에서 영구 자석을 사용한 입자 회수는 마이크로 유체의 여러 장점으로 인해 지난 10 년 동안 큰 관심을 모았습니다. 따라서 완전한 입자 포획을 달성하기 위한 자기 및 유체 조건을 결정하기 위해 많은 노력을 기울였습니다.

그러나 높은 입자 회수율과 유속을 동시에 제공하는 시스템을 설계하는데 있어 핵심이기는 하지만 시스템 성능에 대한 채널 형상의 영향에 대해서는 덜 주의를 기울였습니다.

여기에서 우리는 자기 비드가 혈액에서 분리되어 외부 자기장을 적용하여 버퍼 스트림으로 수집되는 Y-Y 모양의 마이크로 채널의 최적화를 다룹니다. 비드 회수 및 시스템 처리량에 대한 여러 기하학적 특징 (즉, 단면 형상, 두께, 길이 및 부피)의 영향을 연구합니다.

이를 위해 분리 중에 비드에 작용하는 지배적인 힘을 고려하는 실험적으로 검증된 CFD (Computational Fluid Dynamics) 수치 모델을 사용합니다.

우리의 결과는 직사각형의 긴 장치가 높은 입자 회수율과 높은 처리량을 제공하기 때문에 최고의 성능을 보여줍니다. 따라서 이 방법론은 자기 구동 정제, 농축 또는 분리를 위한 랩 온어 칩 장치의 합리적인 설계에 적용될 수 있습니다.

Keywords: particle magnetophoresis, CFD, cross section, chip fabrication

Figure 1 (a) Top view of the microfluidic-magnetophoretic device, (b) Schematic representation of the channel cross-sections studied in this work, and (c) the magnet position relative to the channel location (Sepy and Sepz are the magnet separation distances in y and z, respectively).
Figure 1 (a) Top view of the microfluidic-magnetophoretic device, (b) Schematic representation of the channel cross-sections studied in this work, and (c) the magnet position relative to the channel location (Sepy and Sepz are the magnet separation distances in y and z, respectively).
Figure 2. (a) Channel-magnet configuration and (b–d) magnetic force distribution in the channel midplane for 2 mm, 5 mm and 10 mm long rectangular (left) and U-shaped (right) devices.
Figure 2. (a) Channel-magnet configuration and (b–d) magnetic force distribution in the channel midplane for 2 mm, 5 mm and 10 mm long rectangular (left) and U-shaped (right) devices.
Figure 3. (a) Velocity distribution in a section perpendicular to the flow for rectangular (left) and Ushaped (right) cross section channels, and (b) particle location in these cross sections.
Figure 3. (a) Velocity distribution in a section perpendicular to the flow for rectangular (left) and Ushaped (right) cross section channels, and (b) particle location in these cross sections.
Figure 4. Influence of fluid flow rate on particle recovery when the applied magnetic force is (a) different and (b) equal in U-shaped and rectangular cross section microdevices.
Figure 4. Influence of fluid flow rate on particle recovery when the applied magnetic force is (a) different and (b) equal in U-shaped and rectangular cross section microdevices.
Figure 5. Magnetic bead capture as a function of fluid flow rate for all of the studied geometries.
Figure 5. Magnetic bead capture as a function of fluid flow rate for all of the studied geometries.
Figure 6. Influence of (a) magnetic and fluidic forces (J parameter) and (b) channel geometry (θ parameter) on particle recovery. Note that U-2mm does not accurately fit a line.
Figure 6. Influence of (a) magnetic and fluidic forces (J parameter) and (b) channel geometry (θ parameter) on particle recovery. Note that U-2mm does not accurately fit a line.
Figure 7. Dependence of bead capture on the (a) functional channel volume, and (b) particle residence time (tres). Note that in the curve fitting expressions V represents the functional channel volume and that U-2mm does not accurately fit a line.
Figure 7. Dependence of bead capture on the (a) functional channel volume, and (b) particle residence time (tres). Note that in the curve fitting expressions V represents the functional channel volume and that U-2mm does not accurately fit a line.

References

  1. Gómez-Pastora J., Xue X., Karampelas I.H., Bringas E., Furlani E.P., Ortiz I. Analysis of separators for magnetic beads recovery: From large systems to multifunctional microdevices. Sep. Purif. Technol. 2017;172:16–31. doi: 10.1016/j.seppur.2016.07.050. [CrossRef] [Google Scholar]
  2. Wise N., Grob T., Morten K., Thompson I., Sheard S. Magnetophoretic velocities of superparamagnetic particles, agglomerates and complexes. J. Magn. Magn. Mater. 2015;384:328–334. doi: 10.1016/j.jmmm.2015.02.031. [CrossRef] [Google Scholar]
  3. Khashan S.A., Elnajjar E., Haik Y. CFD simulation of the magnetophoretic separation in a microchannel. J. Magn. Magn. Mater. 2011;323:2960–2967. doi: 10.1016/j.jmmm.2011.06.001. [CrossRef] [Google Scholar]
  4. Khashan S.A., Furlani E.P. Scalability analysis of magnetic bead separation in a microchannel with an array of soft magnetic elements in a uniform magnetic field. Sep. Purif. Technol. 2014;125:311–318. doi: 10.1016/j.seppur.2014.02.007. [CrossRef] [Google Scholar]
  5. Furlani E.P. Magnetic biotransport: Analysis and applications. Materials. 2010;3:2412–2446. doi: 10.3390/ma3042412. [CrossRef] [Google Scholar]
  6. Gómez-Pastora J., Bringas E., Ortiz I. Design of novel adsorption processes for the removal of arsenic from polluted groundwater employing functionalized magnetic nanoparticles. Chem. Eng. Trans. 2016;47:241–246. [Google Scholar]
  7. Gómez-Pastora J., Bringas E., Lázaro-Díez M., Ramos-Vivas J., Ortiz I. The reverse of controlled release: Controlled sequestration of species and biotoxins into nanoparticles (NPs) In: Stroeve P., Mahmoudi M., editors. Drug Delivery Systems. World Scientific; Hackensack, NJ, USA: 2017. pp. 207–244. [Google Scholar]
  8. Ruffert C. Magnetic bead-magic bullet. Micromachines. 2016;7:21. doi: 10.3390/mi7020021. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  9. Yáñez-Sedeño P., Campuzano S., Pingarrón J.M. Magnetic particles coupled to disposable screen printed transducers for electrochemical biosensing. Sensors. 2016;16:1585. doi: 10.3390/s16101585. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  10. Schrittwieser S., Pelaz B., Parak W.J., Lentijo-Mozo S., Soulantica K., Dieckhoff J., Ludwig F., Guenther A., Tschöpe A., Schotter J. Homogeneous biosensing based on magnetic particle labels. Sensors. 2016;16:828. doi: 10.3390/s16060828. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  11. He J., Huang M., Wang D., Zhang Z., Li G. Magnetic separation techniques in sample preparation for biological analysis: A review. J. Pharm. Biomed. Anal. 2014;101:84–101. doi: 10.1016/j.jpba.2014.04.017. [PubMed] [CrossRef] [Google Scholar]
  12. Ha Y., Ko S., Kim I., Huang Y., Mohanty K., Huh C., Maynard J.A. Recent advances incorporating superparamagnetic nanoparticles into immunoassays. ACS Appl. Nano Mater. 2018;1:512–521. doi: 10.1021/acsanm.7b00025. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  13. Gómez-Pastora J., González-Fernández C., Fallanza M., Bringas E., Ortiz I. Flow patterns and mass transfer performance of miscible liquid-liquid flows in various microchannels: Numerical and experimental studies. Chem. Eng. J. 2018;344:487–497. doi: 10.1016/j.cej.2018.03.110. [CrossRef] [Google Scholar]
  14. Gale B.K., Jafek A.R., Lambert C.J., Goenner B.L., Moghimifam H., Nze U.C., Kamarapu S.K. A review of current methods in microfluidic device fabrication and future commercialization prospects. Inventions. 2018;3:60. doi: 10.3390/inventions3030060. [CrossRef] [Google Scholar]
  15. Niemeyer C.M., Mirkin C.A., editors. Nanobiotechnology; Concepts, Applications and Perspectives. Wiley-VCH; Weinheim, Germany: 2004. [Google Scholar]
  16. Khashan S.A., Dagher S., Alazzam A., Mathew B., Hilal-Alnaqbi A. Microdevice for continuous flow magnetic separation for bioengineering applications. J. Micromech. Microeng. 2017;27:055016. doi: 10.1088/1361-6439/aa666d. [CrossRef] [Google Scholar]
  17. Basauri A., Gomez-Pastora J., Fallanza M., Bringas E., Ortiz I. Predictive model for the design of reactive micro-separations. Sep. Purif. Technol. 2019;209:900–907. doi: 10.1016/j.seppur.2018.09.028. [CrossRef] [Google Scholar]
  18. Abdollahi P., Karimi-Sabet J., Moosavian M.A., Amini Y. Microfluidic solvent extraction of calcium: Modeling and optimization of the process variables. Sep. Purif. Technol. 2020;231:115875. doi: 10.1016/j.seppur.2019.115875. [CrossRef] [Google Scholar]
  19. Khashan S.A., Alazzam A., Furlani E. A novel design for a microfluidic magnetophoresis system: Computational study; Proceedings of the 12th International Symposium on Fluid Control, Measurement and Visualization (FLUCOME2013); Nara, Japan. 18–23 November 2013. [Google Scholar]
  20. Pamme N. Magnetism and microfluidics. Lab Chip. 2006;6:24–38. doi: 10.1039/B513005K. [PubMed] [CrossRef] [Google Scholar]
  21. Gómez-Pastora J., Amiri Roodan V., Karampelas I.H., Alorabi A.Q., Tarn M.D., Iles A., Bringas E., Paunov V.N., Pamme N., Furlani E.P., et al. Two-step numerical approach to predict ferrofluid droplet generation and manipulation inside multilaminar flow chambers. J. Phys. Chem. C. 2019;123:10065–10080. doi: 10.1021/acs.jpcc.9b01393. [CrossRef] [Google Scholar]
  22. Gómez-Pastora J., Karampelas I.H., Bringas E., Furlani E.P., Ortiz I. Numerical analysis of bead magnetophoresis from flowing blood in a continuous-flow microchannel: Implications to the bead-fluid interactions. Sci. Rep. 2019;9:7265. doi: 10.1038/s41598-019-43827-x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  23. Tarn M.D., Pamme N. On-Chip Magnetic Particle-Based Immunoassays Using Multilaminar Flow for Clinical Diagnostics. In: Taly V., Viovy J.L., Descroix S., editors. Microchip Diagnostics Methods and Protocols. Humana Press; New York, NY, USA: 2017. pp. 69–83. [Google Scholar]
  24. Phurimsak C., Tarn M.D., Peyman S.A., Greenman J., Pamme N. On-chip determination of c-reactive protein using magnetic particles in continuous flow. Anal. Chem. 2014;86:10552–10559. doi: 10.1021/ac5023265. [PubMed] [CrossRef] [Google Scholar]
  25. Wu X., Wu H., Hu Y. Enhancement of separation efficiency on continuous magnetophoresis by utilizing L/T-shaped microchannels. Microfluid. Nanofluid. 2011;11:11–24. doi: 10.1007/s10404-011-0768-7. [CrossRef] [Google Scholar]
  26. Vojtíšek M., Tarn M.D., Hirota N., Pamme N. Microfluidic devices in superconducting magnets: On-chip free-flow diamagnetophoresis of polymer particles and bubbles. Microfluid. Nanofluid. 2012;13:625–635. doi: 10.1007/s10404-012-0979-6. [CrossRef] [Google Scholar]
  27. Gómez-Pastora J., González-Fernández C., Real E., Iles A., Bringas E., Furlani E.P., Ortiz I. Computational modeling and fluorescence microscopy characterization of a two-phase magnetophoretic microsystem for continuous-flow blood detoxification. Lab Chip. 2018;18:1593–1606. doi: 10.1039/C8LC00396C. [PubMed] [CrossRef] [Google Scholar]
  28. Forbes T.P., Forry S.P. Microfluidic magnetophoretic separations of immunomagnetically labeled rare mammalian cells. Lab Chip. 2012;12:1471–1479. doi: 10.1039/c2lc40113d. [PubMed] [CrossRef] [Google Scholar]
  29. Nandy K., Chaudhuri S., Ganguly R., Puri I.K. Analytical model for the magnetophoretic capture of magnetic microspheres in microfluidic devices. J. Magn. Magn. Mater. 2008;320:1398–1405. doi: 10.1016/j.jmmm.2007.11.024. [CrossRef] [Google Scholar]
  30. Plouffe B.D., Lewis L.H., Murthy S.K. Computational design optimization for microfluidic magnetophoresis. Biomicrofluidics. 2011;5:013413. doi: 10.1063/1.3553239. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  31. Hale C., Darabi J. Magnetophoretic-based microfluidic device for DNA isolation. Biomicrofluidics. 2014;8:044118. doi: 10.1063/1.4893772. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  32. Becker H., Gärtner C. Polymer microfabrication methods for microfluidic analytical applications. Electrophoresis. 2000;21:12–26. doi: 10.1002/(SICI)1522-2683(20000101)21:1<12::AID-ELPS12>3.0.CO;2-7. [PubMed] [CrossRef] [Google Scholar]
  33. Pekas N., Zhang Q., Nannini M., Juncker D. Wet-etching of structures with straight facets and adjustable taper into glass substrates. Lab Chip. 2010;10:494–498. doi: 10.1039/B912770D. [PubMed] [CrossRef] [Google Scholar]
  34. Wang T., Chen J., Zhou T., Song L. Fabricating microstructures on glass for microfluidic chips by glass molding process. Micromachines. 2018;9:269. doi: 10.3390/mi9060269. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  35. Castaño-Álvarez M., Pozo Ayuso D.F., García Granda M., Fernández-Abedul M.T., Rodríguez García J., Costa-García A. Critical points in the fabrication of microfluidic devices on glass substrates. Sens. Actuators B Chem. 2008;130:436–448. doi: 10.1016/j.snb.2007.09.043. [CrossRef] [Google Scholar]
  36. Prakash S., Kumar S. Fabrication of microchannels: A review. Proc. Inst. Mech. Eng. Part B J. Eng. Manuf. 2015;229:1273–1288. doi: 10.1177/0954405414535581. [CrossRef] [Google Scholar]
  37. Leester-Schädel M., Lorenz T., Jürgens F., Ritcher C. Fabrication of Microfluidic Devices. In: Dietzel A., editor. Microsystems for Pharmatechnology: Manipulation of Fluids, Particles, Droplets, and Cells. Springer; Basel, Switzerland: 2016. pp. 23–57. [Google Scholar]
  38. Bartlett N.W., Wood R.J. Comparative analysis of fabrication methods for achieving rounded microchannels in PDMS. J. Micromech. Microeng. 2016;26:115013. doi: 10.1088/0960-1317/26/11/115013. [CrossRef] [Google Scholar]
  39. Ng P.F., Lee K.I., Yang M., Fei B. Fabrication of 3D PDMS microchannels of adjustable cross-sections via versatile gel templates. Polymers. 2019;11:64. doi: 10.3390/polym11010064. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  40. Furlani E.P., Sahoo Y., Ng K.C., Wortman J.C., Monk T.E. A model for predicting magnetic particle capture in a microfluidic bioseparator. Biomed. Microdevices. 2007;9:451–463. doi: 10.1007/s10544-007-9050-x. [PubMed] [CrossRef] [Google Scholar]
  41. Tarn M.D., Peyman S.A., Robert D., Iles A., Wilhelm C., Pamme N. The importance of particle type selection and temperature control for on-chip free-flow magnetophoresis. J. Magn. Magn. Mater. 2009;321:4115–4122. doi: 10.1016/j.jmmm.2009.08.016. [CrossRef] [Google Scholar]
  42. Furlani E.P. Permanent Magnet and Electromechanical Devices; Materials, Analysis and Applications. Academic Press; Waltham, MA, USA: 2001. [Google Scholar]
  43. White F.M. Viscous Fluid Flow. McGraw-Hill; New York, NY, USA: 1974. [Google Scholar]
  44. Mathew B., Alazzam A., El-Khasawneh B., Maalouf M., Destgeer G., Sung H.J. Model for tracing the path of microparticles in continuous flow microfluidic devices for 2D focusing via standing acoustic waves. Sep. Purif. Technol. 2015;153:99–107. doi: 10.1016/j.seppur.2015.08.026. [CrossRef] [Google Scholar]
  45. Furlani E.J., Furlani E.P. A model for predicting magnetic targeting of multifunctional particles in the microvasculature. J. Magn. Magn. Mater. 2007;312:187–193. doi: 10.1016/j.jmmm.2006.09.026. [CrossRef] [Google Scholar]
  46. Furlani E.P., Ng K.C. Analytical model of magnetic nanoparticle transport and capture in the microvasculature. Phys. Rev. E. 2006;73:061919. doi: 10.1103/PhysRevE.73.061919. [PubMed] [CrossRef] [Google Scholar]
  47. Eibl R., Eibl D., Pörtner R., Catapano G., Czermak P. Cell and Tissue Reaction Engineering. Springer; Berlin/Heidelberg, Germany: 2009. [Google Scholar]
  48. Pamme N., Eijkel J.C.T., Manz A. On-chip free-flow magnetophoresis: Separation and detection of mixtures of magnetic particles in continuous flow. J. Magn. Magn. Mater. 2006;307:237–244. doi: 10.1016/j.jmmm.2006.04.008. [CrossRef] [Google Scholar]
  49. Alorabi A.Q., Tarn M.D., Gómez-Pastora J., Bringas E., Ortiz I., Paunov V.N., Pamme N. On-chip polyelectrolyte coating onto magnetic droplets-Towards continuous flow assembly of drug delivery capsules. Lab Chip. 2017;17:3785–3795. doi: 10.1039/C7LC00918F. [PubMed] [CrossRef] [Google Scholar]
  50. Zhang H., Guo H., Chen Z., Zhang G., Li Z. Application of PECVD SiC in glass micromachining. J. Micromech. Microeng. 2007;17:775–780. doi: 10.1088/0960-1317/17/4/014. [CrossRef] [Google Scholar]
  51. Mourzina Y., Steffen A., Offenhäusser A. The evaporated metal masks for chemical glass etching for BioMEMS. Microsyst. Technol. 2005;11:135–140. doi: 10.1007/s00542-004-0430-3. [CrossRef] [Google Scholar]
  52. Mata A., Fleischman A.J., Roy S. Fabrication of multi-layer SU-8 microstructures. J. Micromech. Microeng. 2006;16:276–284. doi: 10.1088/0960-1317/16/2/012. [CrossRef] [Google Scholar]
  53. Su N. 8 2000 Negative Tone Photoresist Formulations 2002–2025. MicroChem Corporation; Newton, MA, USA: 2002. [Google Scholar]
  54. Su N. 8 2000 Negative Tone Photoresist Formulations 2035–2100. MicroChem Corporation; Newton, MA, USA: 2002. [Google Scholar]
  55. Fu C., Hung C., Huang H. A novel and simple fabrication method of embedded SU-8 micro channels by direct UV lithography. J. Phys. Conf. Ser. 2006;34:330–335. doi: 10.1088/1742-6596/34/1/054. [CrossRef] [Google Scholar]
  56. Kazoe Y., Yamashiro I., Mawatari K., Kitamori T. High-pressure acceleration of nanoliter droplets in the gas phase in a microchannel. Micromachines. 2016;7:142. doi: 10.3390/mi7080142. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  57. Sharp K.V., Adrian R.J., Santiago J.G., Molho J.I. Liquid flows in microchannels. In: Gad-el-Hak M., editor. MEMS: Introduction and Fundamentals. CRC Press; Boca Raton, FL, USA: 2006. pp. 10-1–10-46. [Google Scholar]
  58. Oh K.W., Lee K., Ahn B., Furlani E.P. Design of pressure-driven microfluidic networks using electric circuit analogy. Lab Chip. 2012;12:515–545. doi: 10.1039/C2LC20799K. [PubMed] [CrossRef] [Google Scholar]
  59. Bruus H. Theoretical Microfluidics. Oxford University Press; New York, NY, USA: 2008. [Google Scholar]
  60. Beebe D.J., Mensing G.A., Walker G.M. Physics and applications of microfluidics in biology. Annu. Rev. Biomed. Eng. 2002;4:261–286. doi: 10.1146/annurev.bioeng.4.112601.125916. [PubMed] [CrossRef] [Google Scholar]
  61. Yalikun Y., Tanaka Y. Large-scale integration of all-glass valves on a microfluidic device. Micromachines. 2016;7:83. doi: 10.3390/mi7050083. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  62. Van Heeren H., Verhoeven D., Atkins T., Tzannis A., Becker H., Beusink W., Chen P. [(accessed on 9 March 2020)];Design Guideline for Microfluidic Device and Component Interfaces (Part 2) Version 3. Available online: http://www.makefluidics.com/en/design-guideline?id=7.
  63. Scheuble N., Iles A., Wootton R.C.R., Windhab E.J., Fischer P., Elvira K.S. Microfluidic technique for the simultaneous quantification of emulsion instabilities and lipid digestion kinetics. Anal. Chem. 2017;89:9116–9123. doi: 10.1021/acs.analchem.7b01853. [PubMed] [CrossRef] [Google Scholar]
  64. Lynch E.C. Red blood cell damage by shear stress. Biophys. J. 1972;12:257–273. [PMC free article] [PubMed] [Google Scholar]
  65. Paul R., Apel J., Klaus S., Schügner F., Schwindke P., Reul H. Shear stress related blood damage in laminar Couette flow. Artif. Organs. 2003;27:517–529. doi: 10.1046/j.1525-1594.2003.07103.x. [PubMed] [CrossRef] [Google Scholar]
  66. Gómez-Pastora J., Karampelas I.H., Xue X., Bringas E., Furlani E.P., Ortiz I. Magnetic bead separation from flowing blood in a two-phase continuous-flow magnetophoretic microdevice: Theoretical analysis through computational fluid dynamics simulation. J. Phys. Chem. C. 2017;121:7466–7477. doi: 10.1021/acs.jpcc.6b12835. [CrossRef] [Google Scholar]
  67. Lim J., Yeap S.P., Leow C.H., Toh P.Y., Low S.C. Magnetophoresis of iron oxide nanoparticles at low field gradient: The role of shape anisotropy. J. Colloid Interface Sci. 2014;421:170–177. doi: 10.1016/j.jcis.2014.01.044. [PubMed] [CrossRef] [Google Scholar]
  68. Culbertson C.T., Sibbitts J., Sellens K., Jia S. Fabrication of Glass Microfluidic Devices. In: Dutta D., editor. Microfluidic Electrophoresis: Methods and Protocols. Humana Press; New York, NY, USA: 2019. pp. 1–12. [Google Scholar]

[FLOW-3D 물리모델]Droplet Source Model / (물)방울소스모델

Droplet Source Model ()방울소스모델

droplet 소스 모델은 지정된 위치와 양에 따라 계산영역 내로 방울이나 기포를 유입시키는 방법을 제공한다. 기포는 유체, 자유표면 시뮬레이션에서도 유입될 수 있다. 다르게 정의되지 않는 한 “droplet” 은 유체방울 또는 기포를 뜻할 수 있다. droplet 소스모델을 위한 변수들은 텍스트편집으로 prepin.* 파일에서 직접 입력해야 한다. 변수들의 자세한 설명은 Input Variable Summary and Units 장의 Fluid Droplet/Bubble Sources 섹션에서 볼 수 있다.

droplet source 모델을 활성화하기 위해 input 변수 NDROP 를 사용하여 소스의 숫자를 정의한다. 소스는 현재 30개까지 정의될 수 있다. 소스는 변수 IFDROP(n) 의 값에 따라 유체#1 또는 유체#2가 될 수 있다:  IFDROP(n) = 1 은 유체#1 의 droplets 그리고 2 의 값은 유체#2의 droplets 를 생성한다. one-fluid 자유표면의 경우 IFDROP(n) = 2 는 기포를 생성하는데 이는 단열 버블 모델과 함께 사용되어야 한다. 각 소스에서의 droplets 는 XDROP(n), YDROP(n) 그리고 ZDROP(n)에 의해 정의된 X, Y 그리고 Z의 각 지정 위치에서 생성된다. 반경은 변수 RDROP(n)에 의해 정의된다. droplet 이 유체가 이미 존재하는 지역으로 유입될 때 그 유체는 일정 압력 PDROP(n), 온도 TDROP(n), 밀도 RHODROP(n) 를 갖는 droplet 에 의해 대체되고, 유체일 경우에만 속도 UDROP(n), VDROP(n) 그리고WDROP(n) 를 갖는다.

droplet 생성의 시작과 종료 시간은 변수 SDROP(n) 와 EDROP(n)에 의해 정해진다. 그리고 이는 디폴트로 시뮬레이션 전체 시간에 해당한다. 변수 TIMDROP(n)(이는 연속적인 droplets 사이의 간격) 에 의해 정의된 일정한 비율로 방출된다.

초기압력 PDROP(n) 의 디폴트 값은 공간압력 PVOID 와 같은 초기값을 사용하는 기포소스에 대해서만 제외하고 초기압력 PRESI 와같게 지정된다. 밀도 RHODROP(n) 의 디폴트 값은 유체#1의 유체 방울 소스에 대해서는 유체#1의 밀도로 지정되고 유체 2의 유체방울 소스에 대해서는 유체#2의 밀도로 지정된다. 변수 RHODROP(n) 는 단지 밀도 전달 모델(1차또는2차)이 활성화될 때만 사용되며 기포소스에 대해서는 초기 속도와 밀도지정은 사용되지 않는다.

 

Microfluidics Bibliography

Microfluidics Bibliography

다음은 Microfluidics Bibliography의 기술 문서 모음입니다.
이 모든 논문은 FLOW-3D  결과를 특징으로  합니다. 미세 유체 공정 및 장치 를 성공적으로 시뮬레이션하기 위해 FLOW-3D 를 사용 하는 방법에 대해 자세히 알아보십시오  .

2022년 5월 23일 Update

42-22   Islam Hassan, P. Ravi Selvaganapathy, Microfluidic printheads for highly switchable multimaterial 3D printing of soft materials, Advanced Materials Technologies, 2101709, 2022. doi.org/10.1002/admt.202101709

138-21   Enver Guler, Mine Eti, Aydin Cihanoglu, Esra Altiok, Kadriye Ozlem Hamaloglu, Burcu Gokcal, Ali Tuncel, Nalan Kabay, Ion exchange membranes with enhanced antifouling properties to produce energy from renewable sources, Proceedings of the 6th International Symposium on Green and Smart Technologies for a Sustainable Society, Santander, Cantabria, Spain, December 9-10, 2021.

45-21   Navid Tonekaboni, Mahdi Feizbahr, Nima Tonekaboni, Guang-Jun Jiang, Hong-Xia Chen, Optimization of solar CCHP systems with collector enhanced by porous media and nanofluid, Mathematical Problems in Engineering, 2021; 9984940, 2021. doi.org/10.1155/2021/9984840

40-21   B. Hayes, G.L. Whiting, R. MacCurdy, Modeling of contactless bubble–bubble interactions in microchannels with integrated inertial pumps, Physics of Fluids, 33.4; 042002, 2021. doi.org/10.1063/5.0041924

Below is a collection of technical papers in our Microfluidics Bibliography. All of these papers feature FLOW-3D results. Learn more about how FLOW-3D can be used to successfully simulate microfluidic processes and devices.

14-21   Jian-Chiun Liou, Chih-Wei Peng, Philippe Basset, Zhen-Xi Chen, DNA printing integrated multiplexer driver microelectronic mechanical system head (IDMH) and microfluidic flow estimation, Micromachines, 12.1; 25, 2021. doi.org/10.3390/mi12010025

08-20   Li Yong-Qiang, Dong Jun-Yan and Rui Wei, Numerical simulation for capillary driven flow in capsule-type vane tank with clearances under microgravity, Microgravity Science and Technology, 2020. doi.org/10.1007/s12217-019-09773-z

89-19   Tim Dreckmann, Julien Boeuf, Imke-Sonja Ludwig, Jorg Lumkemann, and Jorg Huwyler, Low volume aseptic filling: impact of pump systems on shear stress, European Journal of Pharmeceutics and Biopharmeceutics, in press, 2019. doi:10.1016/j.ejpb.2019.12.006

88-19   V. Amiri Roodan, J. Gomez-Pastora, C. Gonzalez-Fernandez, I.H. Karampelas, E. Bringas, E.P. Furlani, and I. Ortiz, CFD analysis of the generation and manipulation of ferrofluid droplets, TechConnect Briefs, pp. 182-185, 2019. TechConnect World Innovation Conference & Expo, Boston, Massachussetts, USA, June 17-19, 2019.

55-19     Julio Aleman, Sunil K. George, Samuel Herberg, Mahesh Devarasetty, Christopher D. Porada, Aleksander Skardal, and Graça Almeida‐Porada, Deconstructed microfluidic bone marrow on‐a‐chip to study normal and malignant hemopoietic cell–niche interactions, Small, 2019. doi: 10.1002/smll.201902971

37-19     Feng Lin Ng, Miniaturized 3D fibrous scaffold on stereolithography-printed microfluidic perfusion culture, Doctoral Thesis, Nanyang Technological University, Singapore, 2019.

32-19     Jenifer Gómez-Pastora, Ioannis H. Karampelas, Eugenio Bringas, Edward P. Furlani, and Inmaculada Ortiz, Numerical analysis of bead magnetophoresis from flowing blood in a continuous-flow microchannel: Implications to the bead-fluid interactions, Nature: Scientific Reports, Vol. 9, No. 7265, 2019. doi: 10.1038/s41598-019-43827-x

01-19  Jelena Dinic and Vivek Sharma, Computational analysis of self-similar capillary-driven thinning and pinch-off dynamics during dripping using the volume-of-fluid method, Physics of Fluids, Vol. 31, 2019. doi: 10.1063/1.5061715

75-18   Tobias Ladner, Sebastian Odenwald, Kevin Kerls, Gerald Zieres, Adeline Boillon and Julien Bœuf, CFD supported investigation of shear induced by bottom-mounted magnetic stirrer in monoclonal antibody formulation, Pharmaceutical Research, Vol. 35, 2018. doi: 10.1007/s11095-018-2492-4

53-18   Venoos Amiri Roodan, Jenifer Gómez-Pastora, Aditi Verma, Eugenio Bringas, Inmaculada Ortiz and Edward P. Furlani, Computational analysis of magnetic droplet generation and manipulation in microfluidic devices, Proceedings of the 5th International Conference of Fluid Flow, Heat and Mass Transfer, Niagara Falls, Canada, June 7 – 9, 2018; Paper no. 154, 2018.  doi: 10.11159/ffhmt18.154

35-18   Jenifer Gómez-Pastora, Cristina González Fernández, Marcos Fallanza, Eugenio Bringas and Inmaculada Ortiz, Flow patterns and mass transfer performance of miscible liquid-liquid flows in various microchannels: Numerical and experimental studies, Chemical Engineering Journal, vol. 344, pp. 487-497, 2018. doi: 10.1016/j.cej.2018.03.110

16-18   P. Schneider, V. Sukhotskiy, T. Siskar, L. Christie and I.H. Karampelas, Additive Manufacturing of Microfluidic Components via Wax Extrusion, Biotech, Biomaterials and Biomedical TechConnect Briefs, vol. 3, pp. 162 – 165, 2018.

15-18   J. Gómez-Pastora, I.H. Karampelas, A.Q. Alorabi, M.D. Tarn, E. Bringas, A. Iles, V.N. Paunov, N. Pamme, E.P. Furlani, I. Ortiz, CFD analysis and experimental validation of magnetic droplet generation and deflection across multilaminar flow streams, Biotech, Biomaterials and Biomedical TechConnect Briefs, vol. 3, pp. 182-185, 2018.

14-18   J. Gómez-Pastora, C. González-Fernández, I.H. Karampelas, E. Bringas, E.P. Furlani, and I. Ortiz, Design of Magnetic Blood Cleansing Microdevices through Experimentally Validated CFD Modeling, Biotech, Biomaterials and Biomedical TechConnect Briefs, vol. 3, pp. 170-173, 2018.

10-18   A. Gupta, I.H. Karampelas, J. Kitting, Numerical modeling of the formation of dynamically configurable L2 lens in a microchannel, Biotech, Biomaterials and Biomedical TechConnect Briefs, Vol. 3, pp. 186 – 189, 2018.

17-17   I.H. Karampelas, J. Gómez-Pastora, M.J. Cowan, E. Bringas, I. Ortiz and E.P. Furlani, Numerical Analysis of Acoustophoretic Discrete Particle Focusing in Microchannels, Biotech, Biomaterials and Biomedical TechConnect Briefs 2017, Vol. 3

16-17   J. Gómez-Pastora, I.H. Karampelas, E. Bringas, E.P. Furlani and I. Ortiz, CFD analysis of particle magnetophoresis in multiphase continuous-flow bioseparators, Biotech, Biomaterials and Biomedical TechConnect Briefs 2017, Vol. 3

15-17   I.H. Karampelas, S. Vader, Z. Vader, V. Sukhotskiy, A. Verma, G. Garg, M. Tong and E.P. Furlani, Drop-on-Demand 3D Metal Printing, Informatics, Electronics and Microsystems TechConnect Briefs 2017, Vol. 4

102-16   J. Brindha, RA.G. Privita Edwina, P.K. Rajesh and P.Rani, “Influence of rheological properties of protein bio-inks on printability: A simulation and validation study,” Materials Today: Proceedings, vol. 3, no.10, pp. 3285-3295, 2016. doi: 10.1016/j.matpr.2016.10.010

99-16   Ioannis H. Karampelas, Kai Liu, Fatema Alali, and Edward P. Furlani, Plasmonic Nanoframes for Photothermal Energy Conversion, J. Phys. Chem. C, 2016, 120 (13), pp 7256–7264

98-16   Jelena Dinic and Vivek Sharma, Drop formation, pinch-off dynamics and liquid transfer of simple and complex fluidshttp://meetings.aps.org/link/BAPS.2016.MAR.B53.12, APS March Meeting 2016, Volume 61, Number 2, March 14–18, 2016, Baltimore, Maryland

67-16  Vahid Bazargan and Boris Stoeber, Effect of substrate conductivity on the evaporation of small sessile droplets, PHYSICAL REVIEW E 94, 033103 (2016), doi: 10.1103/PhysRevE.94.033103

57-16   Ioannis Karampelas, Computational analysis of pulsed-laser plasmon-enhanced photothermal energy conversion and nanobubble generation in the nanoscale, PhD Dissertation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, July 2016

44-16   Takeshi Sawada et al., Prognostic impact of circulating tumor cell detected using a novel fluidic cell microarray chip system in patients with breast cancer, EBioMedicine, Available online 27 July 2016, doi: 10.1016/j.ebiom.2016.07.027.

39-16   Chien-Hsun Wang, Ho-Lin Tsai, Yu-Che Wu and Weng-Sing Hwang, Investigation of molten metal droplet deposition and solidification for 3D printing techniques, IOP Publishing, J. Micromech. Microeng. 26 (2016) 095012 (14pp), doi: 10.1088/0960-1317/26/9/095012, July 8, 2016

30-16   Ioannis H. Karampelas, Kai Liu and Edward P. Furlani, Plasmonic Nanocages as Photothermal Transducers for Nanobubble Cancer Therapy, Nanotech 2016 Conference & Expo, May 22-25, Washington, DC.

29-16   Scott Vader, Zachary Vader, Ioannis H. Karampelas and Edward P. Furlani, Advances in Magnetohydrodynamic Liquid Metal Jet Printing, Nanotech 2016 Conference & Expo, May 22-25, Washington, DC.

02-16  Stephen D. Hoath (Editor), Fundamentals of Inkjet Printing: The Science of Inkjet and Droplets, ISBN: 978-3-527-33785-9, 472 pages, February 2016 (see chapters 2 and 3 for FLOW-3D results)

125-15   J. Berthier, K.A. Brakke, E.P. Furlani, I.H. Karampelas, V. Poher, D. Gosselin, M. Cubinzolles and P. Pouteau, Whole blood spontaneous capillary flow in narrow V-groove microchannels, Sensors and Actuators B: Chemical, 206, pp. 258-267, 2015.

86-15   Yousub Lee and Dave F. Farson, Simulation of transport phenomena and melt pool shape for multiple layer additive manufacturing, J. Laser Appl. 28, 012006 (2016). doi: 10.2351/1.4935711, published online 2015.

77-15   Ho-Lin Tsai, Weng-Sing Hwang, Jhih-Kai Wang, Wen-Chih Peng and Shin-Hau Chen, Fabrication of Microdots Using Piezoelectric Dispensing Technique for Viscous Fluids, Materials 2015, 8(10), 7006-7016. doi: 10.3390/ma8105355

63-15   Scott Vader, Zachary Vader, Ioannis H. Karampelas and Edward P. Furlani, Magnetohydrodynamic Liquid Metal Jet Printing, TechConnect World Innovation Conference & Expo, Washington, D.C., June 14-17, 2015

46-15   Adwaith Gupta, 3D Printing Multi-Material, Single Printhead Simulation, Advanced Qualification of Additive Manufacturing Materials Workshop, July 20 – 21, 2015, Santa Fe, NM

28-15   Yongqiang Li, Mingzhu Hu, Ling Liu, Yin-Yin Su, Li Duan, and Qi Kang, Study of Capillary Driven Flow in an Interior Corner of Rounded Wall Under MicrogravityMicrogravity Science and Technology, June 2015

20-15   Pamela J. Waterman, Diversity in Medical Simulation Applications, Desktop Engineering, May 2015, pp 22-26,

16-15   Saurabh Singh, Ann Junghans, Erik Watkins, Yash Kapoor, Ryan Toomey, and Jaroslaw Majewski, Effects of Fluid Shear Stress on Polyelectrolyte Multilayers by Neutron Scattering Studies, © 2015 American Chemical Society, DOI: 10.1021/acs.langmuir.5b00037, Langmuir 2015, 31, 2870−2878, February 17, 2015

11-15   Cheng-Han Wu and Weng-Sing Hwang, The effect of process condition of the ink-jet printing process on the molten metallic droplet formation through the analysis of fluid propagation direction, Canadian Journal of Physics, 2015. doi: 10.1139/cjp-2014-0259

03-15 Hanchul Cho, Sivasubramanian Somu, Jin Young Lee, Hobin Jeong and Ahmed Busnaina, High-Rate Nanoscale Offset Printing Process Using Directed Assembly and Transfer of Nanomaterials, Adv. Materials, doi: 10.1002/adma.201404769, February 2015

122-14  Albert Chi, Sebastian Curi, Kevin Clayton, David Luciano, Kameron Klauber, Alfredo Alexander-Katz, Sebastián D’hers and Noel M Elman, Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics, Research Gate, doi: 10.1007/s13346-014-0198-7, July 2014

113-14 Cihan Yilmaz, Arif E. Cetin, Georgia Goutzamanidis, Jun Huang, Sivasubramanian Somu, Hatice Altug, Dongguang Wei and Ahmed Busnaina, Three-Dimensional Crystalline and Homogeneous Metallic Nanostructures Using Directed Assembly of Nanoparticles, 10.1021/nn500084g, © 2014 American Chemical Society, April 2014

110-14 Koushik Ponnuru, Jincheng Wu, Preeti Ashok, Emmanuel S. Tzanakakis and Edward P. Furlani, Analysis of Stem Cell Culture Performance in a Microcarrier Bioreactor System, Nanotech, Washington, D.C., June 15-18, 2014

109-14   Ioannis H. Karampelas, Young Hwa Kim and Edward P. Furlani, Numerical Analysis of Laser Induced Photothermal Effects using Colloidal Plasmonic Nanostructures, Nanotech, Washington, D.C., June 15-18, 2014

108-14   Chenxu Liu, Xiaozheng Xue and Edward P. Furlani, Numerical Analysis of Fully-Coupled Particle-Fluid Transport and Free-Flow Magnetophoretic Sorting in Microfluidic Systems, Nanotech, Washington, D.C., June 15-18, 2014

95-14   Cheng-Han Wu, Weng-Sing Hwang, The effect of the echo-time of a bipolar pulse waveform on molten metallic droplet formation by squeeze mode piezoelectric inkjet printing, Accepted November 2014, Microelectronics Reliability (2014) , © 2014 Elsevier Ltd. All rights reserved.

85-14   Sudhir Srivastava, Lattice Boltzmann method for contact line dynamics, ISBN: 978-90-386-3608-5, Copyright © 2014 S. Srivastava

61-14   Chenxu Liu, A Computational Model for Predicting Fully-Coupled Particle-Fluid Dynamics and Self-Assembly for Magnetic Particle Applications, Master’s Thesis: State University of New York at Buffalo, 2014, 75 pages; 1561583, http://gradworks.umi.com/15/61/1561583.html

41-14 Albert Chi, Sebastian Curi, Kevin Clayton, David Luciano, Kameron Klauber, Alfredo Alexander-Katz, Sebastian D’hers, and Noel M. Elman, Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics, Drug Deliv. and Transl. Res., DOI 10.1007/s13346-014-0198-7, # Controlled Release Society 2014. Available for purchase online at SpringerLink.

21-14  Suk-Hee Park, Ung Hyun Koh, Mina Kim, Dong-Yol Yang, Kahp-Yang Suh and Jennifer Hyunjong Shin, Hierarchical multilayer assembly of an ordered nanofibrous scaffold via thermal fusion bonding, Biofabrication 6 (2014) 024107 (10pp), doi:10.1088/1758-5082/6/2/024107, IOP Publishing, 2014. Available for purchase online at IOP.

17-14   Vahid Bazargan, Effect of substrate cooling and droplet shape and composition on the droplet evaporation and the deposition of particles, Ph.D. Thesis: Department of Mechanical Engineering, The University of British Columbia, March 2014, © Vahid Bazargan, 2014

73-13  Oliver G. Harlen, J. Rafael Castrejón-Pita, and Arturo Castrejon-Pita, Asymmetric Detachment from Angled Nozzles Plates in Drop-on Demand Inkjet Printing, NIP & Digital Fabrication Conference, 2013 International Conference on Digital Printing Technologies. Pages 253-549, pp. 277-280(4)

63-13  Fatema Alali, Ioannis H. Karampelas, Young Hwa Kim, and Edward P. Furlani, Photonic and Thermofluidic Analysis of Colloidal Plasmonic Nanorings and Nanotori for Pulsed-Laser Photothermal ApplicationsJ. Phys. Chem. C, Article ASAP, DOI: 10.1021/jp406986y, Copyright © 2013 American Chemical Society, September 2013.

25-13  Sudhir Srivastava, Theo Driessen, Roger Jeurissen, Herma Wijshoff, and Federico Toschi, Lattice Boltzmann Method to Study the Contraction of a Viscous Ligament, International Journal of Modern Physics © World Scientific Publishing Company, May 2013.

11-13  Li-Chieh Hsu, Yong-Jhih Chen, Jia-Huang Liou, Numerical Investigation in the Factors on the Pool Boiling, Applied Mechanics and Materials Vol. 311 (2013) pp 456-461, © (2013) Trans Tech Publications, Switzerland, doi:10.4028/www.scientific.net/AMM.311.456. Available for purchase online at Scientific.Net.

10-13 Pamela J. Waterman, CFD: Shaping the Medical World, Desktop Engineering, April 2013. Full article available online at Desktop Engineering.

90-12 Charles R. Ortloff and Martin Vogel, Spray Cooling Heat Transfer- Test and CFD Analysis, Electronics Cooling, June 2012. Available online at Electronics Cooling.

79-12    Daniel Parsaoran Siregar, Numerical simulation of evaporation and absorption of inkjet printed droplets, Ph.D. Thesis: Technische Universiteit Eindhoven, September 18, 2012, Copyright 2012 by D.P. Siregar, ISBN: 978-90-386-3190-5.

71-12   Jong-hyeon Chang, Kyu-Dong Jung, Eunsung Lee, Minseog Choi, Seungwan Lee, and Woonbae Kim, Varifocal liquid lens based on microelectrofluidic technology, Optics Letters, Vol. 37, Issue 21, pp. 4377-4379 (2012) http://dx.doi.org/10.1364/OL.37.004377

70-12   Jong-hyeon Chang, Kyu-Dong Jung, Eunsung Lee, Minseog Choi, and Seunwan Lee, Microelectrofluidic Iris for Variable ApertureProc. SPIE 8252, MOEMS and Miniaturized Systems XI, 82520O (February 9, 2012); doi:10.1117/12.906587

69-12   Jong-hyeon Chang, Eunsung Lee, Kyu-Dong Jung, Seungwan Lee, Minseog Choi, and  Woonbae Kim, Microelectrofluidic Lens for Variable CurvatureProc. SPIE 8486, Current Developments in Lens Design and Optical Engineering XIII, 84860X (October 11, 2012); doi:10.1117/12.925852.

61-12  Biddut Bhattacharjee, Study of Droplet Splitting in an Electrowetting Based Digital Microfluidic System, Thesis: Doctor of Philosophy in the College of Graduate Studies (Applied Sciences), The University of British Columbia, September 2012, © Biddut Bhattacharjee.

55-12 Hejun Li, Pengyun Wang, Lehua Qi, Hansong Zuo, Songyi Zhong, Xianghui Hou, 3D numerical simulation of successive deposition of uniform molten Al droplets on a moving substrate and experimental validation, Computational Materials Science, Volume 65, December 2012, Pages 291–301. Available for purchase online at SciVerse.

54-12   Edward P. Furlani, Anthony Nunez, Gianmarco Vizzeri, Modeling Fluid Structure-Interactions for Biomechanical Analysis of the Human Eye, Nanotech Conference & Expo, June 18-21, 2012, Santa Clara, CA.

53-12   Xinyun Wu, Richard D. Oleschuk and Natalie M. Cann, Characterization of microstructured fibre emitters in pursuit of improved nano electrospray ionization performance, The Royal Society of Chemistry 2012, http://pubs.rsc.org, DOI: 10.1039/c2an35249d, May 2012

25-12    Edward P. Furlani, Ioannis H. Karampelas and Qian Xie, Analysis of Pulsed Laser Plasmon-assisted Photothermal Heating and Bubble Generation at the Nanoscale, Lab on a Chip, 10.1039/C2LC40495H, Received 01 May 2012, Accepted 07 Jun 2012. First published on the web 13 Jun 2012.

22-12  R.A. Sultanov, D. Guster, Numerical Modeling and Simulations of Pulsatile Human Blood Flow in Different 3D-Geometries, Book chapter #21 in Fluid Dynamics, Computational Modeling and Applications (2012), ISBN: 978-953-51-0052-2, p. 475 [18 pages]. Available online at INTECH.

21-12  Guo-Wei Huang, Tzu-Yi Hung, and Chin-Tai Chen, Design, Simulation, and Verification of Fluidic Light-Guide Chips with Various Geometries of Micro Polymer Channels, NEMS 2012, Kyoto, Japan, March 5-8, 2012. Available for purchase online at IEEE.

103-11   Suk-Hee Park, Development of Three-Dimensional Scaffolds containing Electrospun Nanofibers and their Applications to Tissue Regeneration, Ph.D. Thesis: School of Mechanical, Aersospace and Systems Engineering, Division of Mechanical Engineering, KAIST, 2011.

81-11   Xinyun Wu, Modeling and Characterization of Microfabricated Emitters-In Pursuit of Improved ESI-MS Performance, thesis: Department of Chemistry, Queen’s University, December 2011, Copyright © Xinyun Wu, 2011

79-11  Cong Lu, A Cell Preparation Stage for Automatic Cell Injection, thesis: Graduate Department of Mechanical and Industrial Engineering, University of Toronto, Copyright © Cong Lu, 2011

77-11 Ge Bai, W. Thomas Leach, Computational fluid dynamics (CFD) insights into agitation stress methods in biopharmaceutical development, International Journal of Pharmaceutics, Available online 8 December 2011, ISSN 0378-5173, 10.1016/j.ijpharm.2011.11.044. Available online at SciVerse.

72-11  M.R. Barkhudarov, C.W. Hirt, D. Milano, and G. Wei, Comments on a Comparison of CFD Software for Microfluidic Applications, Flow Science Technical Note #93, FSI-11-TN93, December 2011

45-11  Chang-Wei Kang, Jiak Kwang Tan, Lunsheng Pan, Cheng Yee Low and Ahmed Jaffar, Numerical and experimental investigations of splat geometric characteristics during oblique impact of plasma spraying, Applied Surface Science, In Press, Corrected Proof, Available online 20 July 2011, ISSN 0169-4332, DOI: 10.1016/j.apsusc.2011.06.081. Available to purchase online at SciVers

33-11  Edward P. Furlani, Mark T. Swihart, Natalia Litchinitser, Christopher N. Delametter and Melissa Carter, Modeling Nanoscale Plasmon-assisted Bubble Nucleation and Applications, Nanotech Conference and Expo 2011, Boston, MA, June 13-16, 2011

32-11  Lu, Cong and Mills, James K., Three cell separation design for realizing automatic cell injection, Complex Medical Engineering (CME), 2011 IEEE/ICME, pp: 599 – 603, Harbin, China, 10.1109/ICCME.2011.5876811, June 2011. Available online at IEEEXplore.

25-11 Issam M. Bahadur, James K. Mills, Fluidic vacuum-based biological cell holding device with piezoelectrically induced vibration, Complex Medical Engineering (CME), 2011 IEEE/ICME International Conference on, 22-25 May 2011, pp: 85 – 90, Harbin, China. Available online at: IEEE Xplore.

14-11  Edward P. Furlani, Roshni Biswas, Alexander N. Cartwright and Natalia M. Litchinitser, Antiresonant guiding optofluidic biosensor, doi:10.1016/j.optcom.2011.04.014, Optics Communication, April 2011

05-11 Hyeju Eom and Keun Park, Integrated numerical analysis to evaluate replication characteristics of micro channels in a locally heated mold by selective induction, International Journal of Precision Engineering and Manufacturing, Volume 12, Number 1, 53-60, DOI: 10.1007/s12541-011-0007-x, 2011. Available online at: SpringerLink.

70-10  I.N. Volnov, V.S. Nagornyi, Modeling Processes for Generation of Streams of Monodispersed Fluid Droplets in Electro-inkjet Applications, Science and Technology News, St. Petersburg State Polytechnic University, 4, pp 294-300, 2010. In Russian.

62-10  F. Mobadersani, M. Eskandarzade, S. Azizi and S. Abbasnezhad, Effect of Ambient Pressure on Bubble Growth in Micro-Channel and Its Pumping Effect, ESDA2010-24436, pp. 577-584, doi:10.1115/ESDA2010-24436, ASME 2010 10th Biennial Conference on Engineering Systems Design and Analysis (ESDA2010), Istanbul, Turkey, July 12–14, 2010. Available online at the ASME Digital Library.

58-10 Tsung-Yi Ho, Jun Zeng, and Chakrabarty, K, Digital microfluidic biochips: A vision for functional diversity and more than moore, Computer-Aided Design (ICCAD), 2010 IEEE/ACM International Conference on, DOI: 10.1109/ICCAD.2010.5654199, © IEEE, November 2010. Available online at IEEE Explore.

51-10  Regina Bleul, Marion Ritzi-Lehnert, Julian Höth, Nico Scharpfenecker, Ines Frese, Dominik Düchs, Sabine Brunklaus, Thomas E. Hansen-Hagge, Franz-Josef Meyer-Almes, Klaus S. Drese, Compact, cost-efficient microfluidics-based stopped-flow device, Anal Bioanal Chem, DOI 10.1007/s00216-010-4446-5, Available online at Springer, November 2010

22-10    Krishendu Chakrabarty, Richard B. Fair and Jun Zeng, Design Tools for Digital Microfluidic Biochips Toward Functional Diversification and More than Moore, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, Vol. 29, No. 7, July 2010

14-10 E. P. Furlani and M. S. Hanchak, Nonlinear analysis of the deformation and breakup of viscous microjets using the method of lines, International Journal for Numerical Methods in Fluids (2010), © 2010 John Wiley & Sons, Ltd., Published online in Wiley InterScience. DOI: 10.1002/fld.2205

55-09 R.A. Sultanov, and D. Guster, Computer simulations of  pulsatile human blood flow through 3D models of the human aortic arch, vessels of simple geometry and a bifurcated artery, Proceedings of the 31st Annual International Conference of the IEEE EMBS (Engineering in Medicine and Biology Society), Minneapolis, September 2-6, 2009, p.p. 4704-4710.

30-09 Anurag Chandorkar and Shayan Palit, Simulation of Droplet Dynamics and Mixing in Microfluidic Devices using a VOF-Based Method, Sensors & Transducers journal, ISSN 1726-5479 © 2009 by IFSA, Vol.7, Special Issue “MEMS: From Micro Devices to Wireless Systems,” October 2009, pp. 136-149.

13-09 E.P. Furlani, M.C. Carter, Analysis of an Electrostatically Actuated MEMS Drop Ejector, Presented at Nanotech Conference & Expo 2009, Houston, Texas, USA, May 3-7, 2009

12-09 A. Chandorkar, S. Palit, Simulation of Droplet-Based Microfluidics Devices Using a Volume-of-Fluid Approach, Presented at Nanotech Conference & Expo 2009, Houston, Texas, USA, May 3-7, 2009

3-09 Christopher N. Delametter, FLOW-3D Speeds MEMS Inkjet Development, Desktop Engineering, January 2009

42-08  Tien-Li Chang, Jung-Chang Wang, Chun-Chi Chen, Ya-Wei Lee, Ta-Hsin Chou, A non-fluorine mold release agent for Ni stamp in nanoimprint process, Microelectronic Engineering 85 (2008) 1608–1612

26-08 Pamela J. Waterman, First-Pass CFD Analyses – Part 2, Desktop Engineering, November 2008

09-08 M. Ren and H. Wijshoff, Thermal effect on the penetration of an ink droplet onto a porous medium, Proc. Eurotherm2008 MNH, 1 (2008)

04-08 Delametter, Christopher N., MEMS development in less than half the time, Small Times, Online Edition, May 2008

02-08 Renat A. Sultanov, Dennis Guster, Brent Engelbrekt and Richard Blankenbecler, 3D Computer Simulations of Pulsatile Human Blood Flows in Vessels and in the Aortic Arch – Investigation of Non-Newtonian Characteristics of Human Blood, The Journal of Computational Physics, arXiv:0802.2362v1 [physics.comp-ph], February 2008

01-08 Herman Wijshoff, thesis: University of Twente, Structure- and fluid dynamics in piezo inkjet printheads, ISBN 978-90-365-2582-4, Venlo, The Netherlands January 2008.

30-07 A. K. Sen, J. Darabi, and D. R. Knapp, Simulation and parametric study of a novel multi-spray emitter for ESI–MS applications, Microfluidics and Nanofluidics, Volume 3, Number 3, June 2007, pp. 283-298(16)

28-07 Dan Soltman and Vivek Subramanian, Inkjet-Printed Line Morphologies and Temperature Control of the Coffee Ring Effect, Langmuir; 2008; ASAP Web Release Date: 16-Jan-2008; (Research Article) DOI: 10.1021/la7026847

23-07 A K Sen and J Darabi, Droplet ejection performance of a monolithic thermal inkjet print head, Journal of Micromechanical and Microengineering,vol.17, pp.1420-1427 (2007) doi:10.1088/0960-1317/17/8/002; Abstract only.

18-07 Herman Wisjhoff, Better Printheads Via Simulation, Desktop Engineering, October 2007, Vol. 13, Issue 2

17-07 Jos de Jong, Ph.D. Thesis: University of Twente, Air entrapment in piezo inkjet printing, ISBN 978-90-365-2483-4, April 2007

15-07 Krishnendu Chakrabarty and Jun Zeng, (Ed.), Design Automation Methods and Tools for Microfluidics-Based Biochips, Springer, September 2006.

14-07 Fei Su and Jun Zeng, Computer-aided design and test for digital microfluidics, IEEE Design & Test of Computers, 24(1), 2007, 60-70.

13-07 Jun Zeng, Modeling and simulation of electrified droplets and its application to computer-aided design of digital microfluidics, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, 25(2), 2006, 224-233.

12-07 Krishnendu Chakrabarty and Jun Zeng, (2005), Automated top-down design for microfluidic biochips, ACM Journal on Emerging Technologies in Computing Systems, 1(3), 2005, 186–223.

01-07 Wijshoff, Herman, Drop formation mechanisms in piezo-acoustic inkjet, NSTI-Nanotech 2007, ISBN 1420061844 Vol. 3, 2007)

23-06 John J. Uebbing, Stephan Hengstler, Dale Schroeder, Shalini Venkatesh, and Rick Haven, Heat and Fluid Flow in an Optical Switch Bubble, Journal of Microelectromechanical Systems, Vol. 15, No. 6, December 2006

21-06 Wijshoff, Herman, Manipulating Drop Formation in Piezo Acoustic Inkjet, Proc. IS&T’s NIP22, 79 (2006)

20-06 J. de Jong, H. Reinten, M. van den Berg, H. Wijshoff, M. Versluis, G. de Bruin, A. Prosperetti and D. Lohse, Air entrapment in piezo-driven inkjet printheads, J. Acoust. Soc. Am. 120(3), 1257 (2006)

11-06 A. K. Sen, J. Darabi, D. R. Knapp and J. Liu, Modeling and Characterization of a Carbon Fiber Emitter for Electrospray Ionization, 1 MEMS and Microsystems Laboratory, Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208, USA, 2 Department of Pharmacology, Medical University of South Carolina, Charleston, SC

5-06 E. P. Furlani, B. G. Price, G. Hawkins, and A. G. Lopez, Thermally Induced Marangoni Instability of Liquid Microjets with Application to Continuous Inkjet Printing, Proceedings of NSTI Nanotech Conference 2006, Vol. 2, pp 534-537.

28-05 O B Fawehinmi, P H Gaskell, P K Jimack, N Kapur, and H M Thompson, A combined experimental and computational fluid dynamics analysis of the dynamics of drop formation, May 2005. DOI: 10.1243/095440605X31788

5-05 E. P. Furlani, Thermal Modulation and Instability of Newtonian Liquid Microjets, presented at Nanotech 2005, Anaheim, CA, May 8-12, 2005.

1-05 C.W. Hirt, Electro-Hydrodynamics of Semi-Conductive Fluids: With Application to Electro-Spraying, Flow Science Technical Note #70, FSI-05-TN70

19-04 G. F. Yao, Modeling of Electroosmosis Without Resolving Physics Inside a Electric Double Layer, Flow Science Technical Note (FSI-04-TN69)

12-04 Jun Zeng and Tom Korsmeyer, Principles of Droplet Electrohydrodynamics for Lab-on-a-Chip, Lab. Chip. Journal, 2004, 4(4), 265-277

9-04 Constantine N. Anagnostopoulos, James M. Chwalek, Christopher N. Delametter, Gilbert A. Hawkins, David L. Jeanmaire, John A. Lebens, Ali Lopez, and David P. Trauernicht, Micro-Jet Nozzle Array for Precise Droplet Metering and Steering Having Increased Droplet Deflection, Proceedings of the 12th International Conference on Solid State Sensors, Actuators and Microsystems, sponsored by IEEE, Boston, June 8-12, 2003, pp. 368-71

8-04 Christopher N. Delametter, David P. Trauernicht, James M. Chwalek, Novel Microfluidic Jet Deflection – Significant Modeling Challenge with Great Application Potential, Technical Proceedings of the 2002 International Conference on Modeling and Simulation of Microsystems sponsored by NSTI, San Juan, Puerto Rico, April 21-25, 2002, pp. 44-47

6-04 D. Vadillo*, G. Desie**, A Soucemarianadin*, Spreading Behavior of Single and Multiple Drops, *Laboratoire des Ecoulements Geophysiques et Industriels (LEGI), and **AGFA-Gevaert Group N.V., XXI ICTAM, 15-21 August 2004, Warsaw, Poland

2-04 Herman Wijshoff, Free Surface Flow and Acousto-Elastic Interaction in Piezo Inkjet, Nanotech 2004, sponsored by the Nano Science & Technology Institute, Boston, MA, March 2004

30-03 D Souders, I Khan and GF Yao, Alessandro Incognito, and Matteo Corrado, A Numerical Model for Simulation of Combined Electroosmotic and Pressure Driven Flow in Microdevices, 7th International Symposium on Fluid Control, Measurement and Visualization

27-03 Jun Zeng, Daniel Sobek and Tom Korsmeyer, Electro-Hydrodynamic Modeling of Electrospray Ionization – CAD for a µFluidic Device-Mass Spectrometer Interface, Agilent Technologies Inc, paper presented at Transducers 2003, June 03 Boston (note: Reference #10 is to FLOW-3D)

17-03 John Uebbing, Switching Fiber-optic Circuits with Microscopic Bubbles, Sensors Magazine, May 2003, Vol 20, No 5, p 36-42

16-03 CFD Speeds Development of MEMS-based Printing Technology, MicroNano Magazine, June 2003, Vol 8, No 6, p 16

3-03 Simulation Speeds Design of Microfluidic Medical Devices, R&D Magazine, March 2003, pp 18-19

1-03 Simulations Help Microscopic Bubbles Switch Fiber-Optic Circuits, Agilent Technologies, Fiberoptic Product News, January 2003, pp 22-23

27-02 Feng, James Q., A General Fluid Dynamic Analysis of Drop Ejection in Drop-on-Demand Ink Jet Devices, Journal of Imaging Science and Technology®, Volume 46, Number 5, September/October 2002

1-02 Feixia Pan, Joel Kubby, and Jingkuang Chen, Numerical Simulation of Fluid Structure Interaction in a MEMS Diaphragm Drop Ejector, Xerox Wilson Research Center, Institute of Physics Publishing, Journal of Micromechanics and Microengineering, 12 (2002), PII: SO960-1317(02)27439-2, pp. 70-76

48-01   Rainer Gruber, Radial Mass Transfer Enhancement in Bubble-Train Flow, PhD thesis in Engineering Sciences, Rheinisch- Westf alischen Technische Hochschule Aachen, December 2001.

34-01 Furlani, E.P., Delametter, C.N., Chwalek, J.M., and Trauernicht, D., Surface Tension Induced Instability of Viscous Liquid Jets, Fourth International Conference on Modeling and Simulation of Microsystems, April 2001

12-01 C. N. Delametter, Eastman Kodak Company, Micro Resolution, Mechanical Engineering, Col 123/No 7, July 2001, pp 70-72

11-01 C. N. Delametter, Eastman Kodak Company, Surface Tension Induced Instability of Viscous Liquid Jets, Technical Proceeding of the Fourth International Conference on Modeling and Simulation of Microsystems, April 2001

9-01 Aman Khan, Unipath Limited Research and Development, Effects of Reynolds Number on Surface Rolling in Small Drops, PVP-Col 431, Emerging Technologies for Fluids, Structures and Fluids, Structures and Fluid Structure Interaction — 2001

2-00 Narayan V. Deshpande, Significance of Inertance and Resistance in Fluidics of Thermal Ink-Jet Transducers, Journal of Imaging Science and Technology, Volume 40, Number 5, Sept./Oct. 1996, pp.457-461

4-98 D. Deitz, Connecting the Dots with CFD, Mechanical Engineering Magazine, pp. 90-91, March 1998

14-94 M. P. O’Hare, N. V. Deshpande, and D. J. Drake, Drop Generation Processes in TIJ Printheads, Xerox Corporation, Adv. Imaging Business Unit, IS&T’s Tenth International Congress on Advances in Non-Impact Printing, Tech. 1994

14-92 Asai, A.,Three-Dimensional Calculation of Bubble Growth and Drop Ejection in a Bubble Jet Printer, Journal of Fluids Engineering Vol. 114 December 1992:638-641