Membrane-less microfiltration using inertial microfluidics
Abstract
Microfiltration is a ubiquitous and often crucial part of many industrial processes, including biopharmaceutical manufacturing. Yet, all existing filtration systems suffer from the issue of membrane clogging, which fundamentally limits the efficiency and reliability of the filtration process. Herein, we report the development of a membrane-less microfiltration system by massively parallelizing inertial microfluidics to achieve a macroscopic volume processing rates (~ 500 mL/min). We demonstrated the systems engineered for CHO (10–20 μm) and yeast (3–5 μm) cells filtration, which are two main cell types used for large-scale bioreactors. Our proposed system can replace existing filtration membrane and provide passive (no external force fields), continuous filtration, thus eliminating the need for membrane replacement. This platform has the desirable combinations of high throughput, low-cost, and scalability, making it compatible for a myriad of microfiltration applications and industrial purposes.
- Authors:
-
- Univ. of New South Wales, Sydney, NSW (Australia); Singapore-MIT Alliance for Research and Technology (SMART) Centre (Singapore)
- National Univ. of Singapore (Singapore); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
- Publication Date:
- Research Org.:
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
- Sponsoring Org.:
- USDOE Advanced Research Projects Agency - Energy (ARPA-E)
- OSTI Identifier:
- 1557435
- Grant/Contract Number:
- AR0000294
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 5; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 42 ENGINEERING
Citation Formats
Warkiani, Majid Ebrahimi, Tay, Andy Kah Ping, Guan, Guofeng, and Han, Jongyoon. Membrane-less microfiltration using inertial microfluidics. United States: N. p., 2015.
Web. doi:10.1038/srep11018.
Warkiani, Majid Ebrahimi, Tay, Andy Kah Ping, Guan, Guofeng, & Han, Jongyoon. Membrane-less microfiltration using inertial microfluidics. United States. https://doi.org/10.1038/srep11018
Warkiani, Majid Ebrahimi, Tay, Andy Kah Ping, Guan, Guofeng, and Han, Jongyoon. Wed .
"Membrane-less microfiltration using inertial microfluidics". United States. https://doi.org/10.1038/srep11018. https://www.osti.gov/servlets/purl/1557435.
@article{osti_1557435,
title = {Membrane-less microfiltration using inertial microfluidics},
author = {Warkiani, Majid Ebrahimi and Tay, Andy Kah Ping and Guan, Guofeng and Han, Jongyoon},
abstractNote = {Microfiltration is a ubiquitous and often crucial part of many industrial processes, including biopharmaceutical manufacturing. Yet, all existing filtration systems suffer from the issue of membrane clogging, which fundamentally limits the efficiency and reliability of the filtration process. Herein, we report the development of a membrane-less microfiltration system by massively parallelizing inertial microfluidics to achieve a macroscopic volume processing rates (~ 500 mL/min). We demonstrated the systems engineered for CHO (10–20 μm) and yeast (3–5 μm) cells filtration, which are two main cell types used for large-scale bioreactors. Our proposed system can replace existing filtration membrane and provide passive (no external force fields), continuous filtration, thus eliminating the need for membrane replacement. This platform has the desirable combinations of high throughput, low-cost, and scalability, making it compatible for a myriad of microfiltration applications and industrial purposes.},
doi = {10.1038/srep11018},
journal = {Scientific Reports},
number = 1,
volume = 5,
place = {United States},
year = {Wed Jul 08 00:00:00 EDT 2015},
month = {Wed Jul 08 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
The origins and the future of microfluidics
journal, July 2006
- Whitesides, George M.
- Nature, Vol. 442, Issue 7101, p. 368-373
Physics and Applications of Microfluidics in Biology
journal, August 2002
- Beebe, David J.; Mensing, Glennys A.; Walker, Glenn M.
- Annual Review of Biomedical Engineering, Vol. 4, Issue 1
Microfluidics for cell separation
journal, April 2010
- Bhagat, Ali Asgar S.; Bow, Hansen; Hou, Han Wei
- Medical & Biological Engineering & Computing, Vol. 48, Issue 10
Membrane-free microfiltration by asymmetric inertial migration
journal, July 2007
- Seo, Jeonggi; Lean, Meng H.; Kole, Ashutosh
- Applied Physics Letters, Vol. 91, Issue 3
Enhanced particle filtration in straight microchannels using shear-modulated inertial migration
journal, October 2008
- Bhagat, Ali Asgar S.; Kuntaegowdanahalli, Sathyakumar S.; Papautsky, Ian
- Physics of Fluids, Vol. 20, Issue 10
Continuous inertial focusing, ordering, and separation of particles in microchannels
journal, November 2007
- Di Carlo, D.; Irimia, D.; Tompkins, R. G.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 48, p. 18892-18897
Fundamentals of inertial focusing in microchannels
journal, January 2013
- Zhou, Jian; Papautsky, Ian
- Lab on a Chip, Vol. 13, Issue 6
Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells
journal, July 2014
- Khoo, Bee Luan; Warkiani, Majid Ebrahimi; Tan, Daniel Shao-Weng
- PLoS ONE, Vol. 9, Issue 7
An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells
journal, January 2014
- Warkiani, Majid Ebrahimi; Khoo, Bee Luan; Tan, Daniel Shao-Weng
- The Analyst, Vol. 139, Issue 13
Spiral microchannel with rectangular and trapezoidal cross-sections for size based particle separation
journal, March 2013
- Guan, Guofeng; Wu, Lidan; Bhagat, Ali Asgar
- Scientific Reports, Vol. 3, Issue 1
Recombinant expression systems in the pharmaceutical industry
journal, July 2004
- Schmidt, F. R.
- Applied Microbiology and Biotechnology, Vol. 65, Issue 4
A new method for yeast recovery in batch ethanol fermentations: Filter aid filtration followed by separation of yeast from filter aid using hydrocyclones
journal, January 2000
- Martins da Matta, Virgínia; Andrade Medronho, Ricardo de
- Bioseparation, Vol. 9, Issue 1, p. 43-53
Recent advances in mammalian protein production
journal, December 2013
- Bandaranayake, Ashok D.; Almo, Steven C.
- FEBS Letters, Vol. 588, Issue 2
Acoustic Cell Filter for High Density Perfusion Culture of Hybridoma Cells
journal, March 1994
- Trampler, Felix; Sonderhoff, Stefan A.; Pui, Phylis W. S.
- Bio/Technology, Vol. 12, Issue 3
Continuous hybridoma growth and monoclonal antibody production in hollow fiber reactors-separators
journal, May 1986
- Altshuler, Gordon L.; Dziewulski, David M.; Sowek, Judith A.
- Biotechnology and Bioengineering, Vol. 28, Issue 5
Cell Retention Devices for Suspended-Cell Perfusion Cultures
book, January 2002
- Castilho, Leda R.; Medronho, Ricardo A.
- Tools and Applications of Biochemical Engineering Science
Direct visual observation of yeast deposition and removal during microfiltration
journal, August 2001
- Mores, W.
- Journal of Membrane Science, Vol. 189, Issue 2
Fuel ethanol production from lignocellulose: a challenge for metabolic engineering and process integration
journal, July 2001
- Zaldivar, J.; Nielsen, J.; Olsson, L.
- Applied Microbiology and Biotechnology, Vol. 56, Issue 1-2
Isoporous Micro/Nanoengineered Membranes
journal, March 2013
- Warkiani, Majid Ebrahimi; Bhagat, Ali Asgar S.; Khoo, Bee Luan
- ACS Nano, Vol. 7, Issue 3
Multivariate biophysical markers predictive of mesenchymal stromal cell multipotency
journal, October 2014
- Lee, Wong Cheng; Shi, Hui; Poon, Zhiyong
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 42
Fluid shear stress induction of the transcriptional activator c-fos in human and bovine endothelial cells, HeLa, and Chinese hamster ovary cells
journal, February 1996
- Ranjan, Vibhu; Waterbury, Raymond; Xiao, Zeshuai
- Biotechnology and Bioengineering, Vol. 49, Issue 4
Microfluidic sorting of mammalian cells by optical force switching
journal, December 2004
- Wang, Mark M.; Tu, Eugene; Raymond, Daniel E.
- Nature Biotechnology, Vol. 23, Issue 1
Promotion of microtubule assembly in vitro by taxol
journal, February 1979
- Schiff, Peter B.; Fant, Jane; Horwitz, Susan B.
- Nature, Vol. 277, Issue 5698
Production of recombinant protein therapeutics in cultivated mammalian cells
journal, November 2004
- Wurm, Florian M.
- Nature Biotechnology, Vol. 22, Issue 11
Mechanisms of regulating tubulin synthesis in cultured mammalian cells
journal, June 1979
- Ben-Ze'ev, Avri; Farmer, Stephen R.; Penman, Sheldon
- Cell, Vol. 17, Issue 2
A Restriction Point for Control of Normal Animal Cell Proliferation
journal, April 1974
- Pardee, A. B.
- Proceedings of the National Academy of Sciences, Vol. 71, Issue 4
Principle of a Counter-streaming Centrifuge for the Separation of Particles of Different Sizes
journal, April 1948
- Lindahl, Per Eric
- Nature, Vol. 161, Issue 4095
Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis
journal, December 2007
- Kim, U.; Shu, C. -W.; Dane, K. Y.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 52
High-throughput cell cycle synchronization using inertial forces in spiral microchannels
journal, January 2011
- Lee, Wong Cheng; Bhagat, Ali Asgar S.; Huang, Sha
- Lab on a Chip, Vol. 11, Issue 7
Inertial microfluidics for continuous particle filtration and extraction
journal, December 2008
- Bhagat, Ali Asgar S.; Kuntaegowdanahalli, Sathyakumar S.; Papautsky, Ian
- Microfluidics and Nanofluidics, Vol. 7, Issue 2
Polymeric micro-filter manufactured by a dissolving mold technique
journal, May 2010
- Chen, Longqing; Warkiani, Majid Ebrahimi; Liu, Hao-Bing
- Journal of Micromechanics and Microengineering, Vol. 20, Issue 7
Differential immediate-early gene responses to shear stress and intraluminal pressure in intact human conduit vessels
journal, July 2000
- Gan, Li-ming; Doroudi, Roya; Hägg, Ulrika
- FEBS Letters, Vol. 477, Issue 1-2
Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly
journal, May 1990
- Beckmann, R.; Mizzen, L.; Welch, W.
- Science, Vol. 248, Issue 4957
Continuous hybridoma growth and monoclonal antibody production in hollow fiber reactors-separators
journal, May 1986
- Altshuler, Gordon L.; Dziewulski, David M.; Sowek, Judith A.
- Biotechnology and Bioengineering, Vol. 28, Issue 5
Recombinant expression systems in the pharmaceutical industry
journal, July 2004
- Schmidt, F. R.
- Applied Microbiology and Biotechnology, Vol. 65, Issue 4
Fuel ethanol production from lignocellulose: a challenge for metabolic engineering and process integration
journal, July 2001
- Zaldivar, J.; Nielsen, J.; Olsson, L.
- Applied Microbiology and Biotechnology, Vol. 56, Issue 1-2
Microfluidics for cell separation
journal, April 2010
- Bhagat, Ali Asgar S.; Bow, Hansen; Hou, Han Wei
- Medical & Biological Engineering & Computing, Vol. 48, Issue 10
Mechanisms of regulating tubulin synthesis in cultured mammalian cells
journal, June 1979
- Ben-Ze'ev, Avri; Farmer, Stephen R.; Penman, Sheldon
- Cell, Vol. 17, Issue 2
Recent advances in mammalian protein production
journal, December 2013
- Bandaranayake, Ashok D.; Almo, Steven C.
- FEBS Letters, Vol. 588, Issue 2
Industrial choices for protein production by large-scale cell culture
journal, April 2001
- Chu, Lily; Robinson, David K.
- Current Opinion in Biotechnology, Vol. 12, Issue 2
Isoporous Micro/Nanoengineered Membranes
journal, March 2013
- Warkiani, Majid Ebrahimi; Bhagat, Ali Asgar S.; Khoo, Bee Luan
- ACS Nano, Vol. 7, Issue 3
Promotion of microtubule assembly in vitro by taxol
journal, February 1979
- Schiff, Peter B.; Fant, Jane; Horwitz, Susan B.
- Nature, Vol. 277, Issue 5698
The origins and the future of microfluidics
journal, July 2006
- Whitesides, George M.
- Nature, Vol. 442, Issue 7101, p. 368-373
Microfluidic sorting of mammalian cells by optical force switching
journal, December 2004
- Wang, Mark M.; Tu, Eugene; Raymond, Daniel E.
- Nature Biotechnology, Vol. 23, Issue 1
Spiral microchannel with rectangular and trapezoidal cross-sections for size based particle separation
journal, March 2013
- Guan, Guofeng; Wu, Lidan; Bhagat, Ali Asgar
- Scientific Reports, Vol. 3, Issue 1
High-throughput cell cycle synchronization using inertial forces in spiral microchannels
journal, January 2011
- Lee, Wong Cheng; Bhagat, Ali Asgar S.; Huang, Sha
- Lab on a Chip, Vol. 11, Issue 7
Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells
journal, January 2014
- Warkiani, Majid Ebrahimi; Guan, Guofeng; Luan, Khoo Bee
- Lab Chip, Vol. 14, Issue 1
Continuous inertial focusing, ordering, and separation of particles in microchannels
journal, November 2007
- Di Carlo, D.; Irimia, D.; Tompkins, R. G.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 48, p. 18892-18897
Multivariate biophysical markers predictive of mesenchymal stromal cell multipotency
journal, October 2014
- Lee, Wong Cheng; Shi, Hui; Poon, Zhiyong
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 42
A Restriction Point for Control of Normal Animal Cell Proliferation
journal, April 1974
- Pardee, A. B.
- Proceedings of the National Academy of Sciences, Vol. 71, Issue 4
Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly
journal, May 1990
- Beckmann, R.; Mizzen, L.; Welch, W.
- Science, Vol. 248, Issue 4957
Physics and Applications of Microfluidics in Biology
journal, August 2002
- Beebe, David J.; Mensing, Glennys A.; Walker, Glenn M.
- Annual Review of Biomedical Engineering, Vol. 4, Issue 1
Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells
journal, July 2014
- Khoo, Bee Luan; Warkiani, Majid Ebrahimi; Tan, Daniel Shao-Weng
- PLoS ONE, Vol. 9, Issue 7
Works referencing / citing this record:
Nano and Microtechnologies for the Study of Magnetotactic Bacteria
journal, July 2019
- Tay, Andy; McCausland, Hayley; Komeili, Arash
- Advanced Functional Materials, Vol. 29, Issue 38
Scaled‐Up Inertial Microfluidics: Retention System for Microcarrier‐Based Suspension Cultures
journal, April 2019
- Moloudi, Reza; Oh, Steve; Yang, Chun
- Biotechnology Journal, Vol. 14, Issue 5
Hybrid microfluidics combined with active and passive approaches for continuous cell separation: Microfluidics and Miniaturization
journal, October 2016
- Yan, Sheng; Zhang, Jun; Yuan, Dan
- ELECTROPHORESIS, Vol. 38, Issue 2
A smart and portable micropump for stable liquid delivery
journal, January 2019
- Zhang, Xinjie; Xia, Kang; Ji, Aimin
- ELECTROPHORESIS, Vol. 40, Issue 6
Low‐cost multi‐core inertial microfluidic centrifuge for high‐throughput cell concentration
journal, November 2019
- Xiang, Nan; Li, Qiao; Shi, Zhiguo
- ELECTROPHORESIS, Vol. 41, Issue 10-11
Particle/cell separation on microfluidic platforms based on centrifugation effect: a review
journal, May 2017
- Al-Faqheri, Wisam; Thio, Tzer Hwai Gilbert; Qasaimeh, Mohammad Ameen
- Microfluidics and Nanofluidics, Vol. 21, Issue 6
Enhanced particle self-ordering in a double-layer channel
journal, February 2018
- Yan, Sheng; Li, Yuxing; Zhao, Qianbin
- Biomedical Microdevices, Vol. 20, Issue 2
Microfluidic Mimic for Colloid Membrane Filtration: A Review
journal, May 2018
- Debnath, Nandini; Sadrzadeh, Mohtada
- Journal of the Indian Institute of Science, Vol. 98, Issue 2
Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture
journal, July 2017
- Kwon, Taehong; Prentice, Holly; Oliveira, Jonas De
- Scientific Reports, Vol. 7, Issue 1
Semi-Empirical Estimation of Dean Flow Velocity in Curved Microchannels
journal, October 2017
- Bayat, Pouriya; Rezai, Pouya
- Scientific Reports, Vol. 7, Issue 1
Microfluidic cell sorting: Towards improved biocompatibility of extracorporeal lung assist devices
journal, May 2018
- Bleilevens, Christian; Lölsberg, Jonas; Cinar, Arne
- Scientific Reports, Vol. 8, Issue 1
Inertial-Based Filtration Method for Removal of Microcarriers from Mesenchymal Stem Cell Suspensions
journal, August 2018
- Moloudi, Reza; Oh, Steve; Yang, Chun
- Scientific Reports, Vol. 8, Issue 1
Cascading and Parallelising Curvilinear Inertial Focusing Systems for High Volume, Wide Size Distribution, Separation and Concentration of Particles
journal, November 2016
- Miller, B.; Jimenez, M.; Bridle, H.
- Scientific Reports, Vol. 6, Issue 1
Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation
journal, January 2016
- Rafeie, Mehdi; Zhang, Jun; Asadnia, Mohsen
- Lab on a Chip, Vol. 16, Issue 15
Active bioparticle manipulation in microfluidic systems
journal, January 2016
- Md Ali, Mohd Anuar; Ostrikov, Kostya (Ken); Khalid, Fararishah Abdul
- RSC Advances, Vol. 6, Issue 114
Selective particle and cell capture in a continuous flow using micro-vortex acoustic streaming
journal, January 2017
- Collins, David J.; Khoo, Bee Luan; Ma, Zhichao
- Lab on a Chip, Vol. 17, Issue 10
Liquid metal-based amalgamation-assisted lithography for fabrication of complex channels with diverse structures and configurations
journal, January 2018
- Yan, Sheng; Li, Yuxing; Zhao, Qianbin
- Lab on a Chip, Vol. 18, Issue 5
Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
journal, January 2018
- Kwon, Taehong; Yao, Rujie; Hamel, Jean-François P.
- Lab on a Chip, Vol. 18, Issue 18
Enhanced inertial focusing of microparticles and cells by integrating trapezoidal microchambers in spiral microfluidic channels
journal, January 2019
- Al-Halhouli, Ala'aldeen; Albagdady, Ahmed; Al-Faqheri, Wisam
- RSC Advances, Vol. 9, Issue 33
Maximizing particle concentration in deterministic lateral displacement arrays
journal, March 2017
- Feng, Shilun; Skelley, Alison M.; Anwer, Ayad G.
- Biomicrofluidics, Vol. 11, Issue 2
Experimental and numerical study of elasto-inertial focusing in straight channels
journal, May 2019
- Raoufi, Mohammad Amin; Mashhadian, Ali; Niazmand, Hamid
- Biomicrofluidics, Vol. 13, Issue 3
New insights into the physics of inertial microfluidics in curved microchannels. I. Relaxing the fixed inflection point assumption
journal, May 2019
- Rafeie, Mehdi; Hosseinzadeh, Shahin; Taylor, Robert A.
- Biomicrofluidics, Vol. 13, Issue 3
New insights into the physics of inertial microfluidics in curved microchannels. II. Adding an additive rule to understand complex cross-sections
journal, May 2019
- Rafeie, Mehdi; Hosseinzadeh, Shahin; Huang, Jingrui
- Biomicrofluidics, Vol. 13, Issue 3
Spiral microfluidic devices for cell separation and sorting in bioprocesses
journal, November 2019
- Herrmann, N.; Neubauer, P.; Birkholz, M.
- Biomicrofluidics, Vol. 13, Issue 6
Super-enhanced particle focusing in a novel microchannel geometry using inertial microfluidics
journal, April 2017
- Sonmez, U.; Jaber, S.; Trabzon, L.
- Journal of Micromechanics and Microengineering, Vol. 27, Issue 6
Investigation of Leukocyte Viability and Damage in Spiral Microchannel and Contraction-Expansion Array
journal, November 2019
- Suwannaphan, Thammawit; Srituravanich, Werayut; Sailasuta, Achariya
- Micromachines, Vol. 10, Issue 11
Spiral Microchannels with Trapezoidal Cross Section Fabricated by Femtosecond Laser Ablation in Glass for the Inertial Separation of Microparticles
journal, April 2018
- Al-Halhouli, Ala’aldeen; Al-Faqheri, Wisam; Alhamarneh, Baider
- Micromachines, Vol. 9, Issue 4
Spiral microfluidic devices for cell separation and sorting in bioprocesses
text, January 2019
- Herrmann, Niklas; Neubauer, Peter; Birkholz, Mario
- Technische Universität Berlin
Microfluidic cell sorting: Towards improved biocompatibility of extracorporeal lung assist devices
text, January 2018
- Bleilevens, Christian; Lölsberg, Jonas; Cinar, Arne
- RWTH Aachen University
Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture
journal, July 2017
- Kwon, Taehong; Prentice, Holly; Oliveira, Jonas De
- Scientific Reports, Vol. 7, Issue 1
Microfluidic cell sorting: Towards improved biocompatibility of extracorporeal lung assist devices
journal, May 2018
- Bleilevens, Christian; Lölsberg, Jonas; Cinar, Arne
- Scientific Reports, Vol. 8, Issue 1
Inertial-Based Filtration Method for Removal of Microcarriers from Mesenchymal Stem Cell Suspensions
journal, August 2018
- Moloudi, Reza; Oh, Steve; Yang, Chun
- Scientific Reports, Vol. 8, Issue 1
Cascading and Parallelising Curvilinear Inertial Focusing Systems for High Volume, Wide Size Distribution, Separation and Concentration of Particles
journal, November 2016
- Miller, B.; Jimenez, M.; Bridle, H.
- Scientific Reports, Vol. 6, Issue 1
Focusing and alignment of erythrocytes in a viscoelastic medium
journal, January 2017
- Go, Taesik; Byeon, Hyeokjun; Lee, Sang Joon
- Scientific Reports, Vol. 7, Issue 1
Microfluidic Passive Valve with Ultra-Low Threshold Pressure for High-Throughput Liquid Delivery
journal, November 2019
- Zhang, Xinjie; Oseyemi, Ayobami Elisha
- Micromachines, Vol. 10, Issue 12
Microfluidic Platform for Cell Isolation and Manipulation Based on Cell Properties
journal, January 2017
- Yousuff, Caffiyar; Ho, Eric; Hussain K., Ismail
- Micromachines, Vol. 8, Issue 1