Skip to main content
SpringerLink
Log in

Manipulation of bio-micro/nanoparticles in non-Newtonian microflows

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

A Correction to this article was published on 07 May 2019

This article has been updated

Abstract

Most bio-micro/nanoparticles, including cells, platelets, bacteria, and extracellular vesicles, are inherently suspended in biofluids (i.e., blood) with non-Newtonian fluid characteristics. Understanding migration behaviors of bioparticles in non-Newtonian microfluidics is of significance in label-free manipulation of bioparticles, playing important roles in cell analysis and disease diagnostics. This review presents recent advances in focusing and sorting of bio-micro/nanoparticles by non-Newtonian microfluidics. Principle and examples for passive and active manipulation of bioparticles in non-Newtonian and non-Newtonian/Newtonian hybrid microflows are highlighted. Limitations and perspectives of non-Newtonian microfluidics for clinical applications are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

(Reproduced with permission (Tian et al. 2017). Copyright 2017, Royal Society of Chemistry)

Fig. 4
Fig. 5

Similar content being viewed by others

Change history

  • 07 May 2019

    The correct author names are as below, Fei Tian, Qiang Feng, Qinghua Chen, Chao Liu, Tiejun Li, Jiashu Sun.

References

  • Abercrombie M, Ambrose EJ (1962) Surface properties of cancer cells—a review. Cancer Res 22:525–548

    Google Scholar 

  • Ahmed MG et al (2017) Isolation, detection, and antigen-based profiling of circulating tumor cells using a size-dictated immunocapture chip. Angew Chem Int Ed 56:10681–10685

    Google Scholar 

  • Amini H, Lee W, Di Carlo D (2014) Inertial microfluidic physics. Lab Chip 14:2739–2761

    Google Scholar 

  • Bhagat AAS, Hou HW, Li LD, Lim CT, Han J (2011) Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation. Lab Chip 11:1870–1878

    Google Scholar 

  • Campo-Deaño L, Dullens RPA, Aarts DGAL, Pinho FT, Oliveira MSN (2013) Viscoelasticity of blood and viscoelastic blood analogues for use in polydymethylsiloxane in vitro models of the circulatory system. Biomicrofluidics 7:034102

    Google Scholar 

  • Chen B et al (2016) Targeting negative surface charges of cancer cells by multifunctional nanoprobes. Theranostics 6:1887–1898

    Google Scholar 

  • Ciftlik AT, Ettori M, Gijs MAM (2013) High throughput-per-footprint inertial focusing. Small 9:2764–2773

    Google Scholar 

  • Colombo M, Raposo G, Théry C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289

    Google Scholar 

  • Contreras-Naranjo JC, Wu H-J, Ugaz VM (2017) Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. Lab Chip 17:3558–3577

    Google Scholar 

  • D’Avino G, Romeo G, Villone MM, Greco F, Netti PA, Maffettone PL (2012) Single line particle focusing induced by viscoelasticity of the suspending liquid: theory, experiments and simulations to design a micropipe flow-focuser. Lab Chip 12:1638–1645

    Google Scholar 

  • D’Avino G, Greco F, Maffettone PL (2017) Particle migration due to viscoelasticity of the suspending liquid and its relevance in microfluidic devices. Annu Rev Fluid Mech 49:341–360

    MathSciNet  MATH  Google Scholar 

  • De Santo I, D’Avino G, Romeo G, Greco F, Netti PA, Maffettone PL (2014) Microfluidic lagrangian trap for brownian particles: three-dimensional focusing down to the nanoscale. Phys Rev Applied 2:064001

    Google Scholar 

  • Del Giudice F, D’Avino G, Greco F, De Santo I, Netti PA, Maffettone PL (2015a) Rheometry-on-a-chip: measuring the relaxation time of a viscoelastic liquid through particle migration in microchannel flows. Lab Chip 15:783–792

    Google Scholar 

  • Del Giudice F et al (2015b) Magnetophoresis ‘meets’ viscoelasticity: deterministic separation of magnetic particles in a modular microfluidic device. Lab Chip 15:1912–1922

    Google Scholar 

  • Einarsson J, Mehlig B (2017) Spherical particle sedimenting in weakly viscoelastic shear flow. Phys Rev Fluids 2:063301

    Google Scholar 

  • Gay LJ, Felding-Habermann B (2011) Contribution of platelets to tumour metastasis. Nat Rev Cancer 11:123

    Google Scholar 

  • Ha B, Park J, Destgeer G, Jung JH, Sung HJ (2016) Transfer of microparticles across laminar streams from non-Newtonian to Newtonian fluid. Anal Chem 88:4205–4210

    Google Scholar 

  • Hejazian M, Li W, Nguyen N-T (2015) Lab on a chip for continuous-flow magnetic cell separation. Lab Chip 15:959–970

    Google Scholar 

  • Ho BP, Leal LG (1976) Migration of rigid spheres in a 2-dimensional unidirectional shear-flow of a 2nd-order fluid. J Fluid Mech 76:783–799

    MATH  Google Scholar 

  • Huang PY, Feng J, Hu HH, Joseph DD (1997) Direct simulation of the motion of solid particles in Couette and Poiseuille flows of viscoelastic fluids. J Fluid Mech 343:73–94

    MathSciNet  MATH  Google Scholar 

  • Kale A, Song L, Lu X, Yu L, Hu G, Xuan X (2018) Electrothermal enrichment of submicron particles in an insulator-based dielectrophoretic microdevice. Electrophoresis 39:887–896

    Google Scholar 

  • Kang K, Lee SS, Hyun K, Lee SJ, Kim JM (2013) DNA-based highly tunable particle focuser. Nat Commun 4:2567

    Google Scholar 

  • Karlsen JT, Qiu W, Augustsson P, Bruus H (2018) Acoustic streaming and its suppression in inhomogeneous fluids. Phys Rev Lett 120:054501

    Google Scholar 

  • Kim JY, Ahn SW, Lee SS, Kim JM (2012) Lateral migration and focusing of colloidal particles and DNA molecules under viscoelastic Flow. Lab Chip 12:2807–2814

    Google Scholar 

  • Ko C-H, Li D, Malekanfard A, Wang Y-N, Fu L-M, Xuan X (2018) Electroosmotic flow of non-Newtonian fluids in a constriction microchannel. Electrophoresis. https://doi.org/10.1002/elps.201800315

    Article  Google Scholar 

  • Lamparski HG, Metha-Damani A, Yao J-Y, Patel S, Hsu D-H, Ruegg C, Le Pecq J-B (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 270:211–226

    Google Scholar 

  • Laurell T, Petersson F, Nilsson A (2007) Chip integrated strategies for acoustic separation and manipulation of cells and particles. Chem Soc Rev 36:492–506

    Google Scholar 

  • Lee DJ, Brenner H, Youn JR, Song YS (2013) Multiplex particle focusing via hydrodynamic force in viscoelastic fluids. Sci Rep 3:3258

    Google Scholar 

  • Lee K et al (2018) Multiplexed profiling of single extracellular vesicles. ACS Nano 12:494–503

    Google Scholar 

  • Leshansky AM, Bransky A, Korin N, Dinnar U (2007) Tunable nonlinear viscoelastic “focusing” in a microfluidic device. Phys Rev Lett 98:234501

    Google Scholar 

  • Li D, Xuan X (2018) Electrophoretic slip-tuned particle migration in microchannel viscoelastic fluid flows. Phys Rev Fluids 3:074202

    Google Scholar 

  • Li M, Li WH, Zhang J, Alici G, Wen W (2014) A review of microfabrication techniques and dielectrophoretic microdevices for particle manipulation and separation. J Phys D Appl Phys 47:063001

    Google Scholar 

  • Li D, Lu X, Xuan X (2016) Viscoelastic separation of particles by size in straight rectangular microchannels: a parametric study for a refined understanding. Anal Chem 88:12303–12309

    Google Scholar 

  • Li D, Zielinski J, Kozubowski L, Xuan X (2018) Continuous sheath-free separation of drug-treated human fungal pathogen Cryptococcus neoformans by morphology in biocompatible polymer solutions. Electrophoresis 39:2362–2369

    Google Scholar 

  • Lim EJ et al (2014) Inertio-elastic focusing of bioparticles in microchannels at high throughput. Nat Commun 5:4120

    Google Scholar 

  • Liu C, Hu G, Jiang X, Sun J (2015a) Inertial focusing of spherical particles in rectangular microchannels over a wide range of Reynolds numbers. Lab Chip 15:1168–1177

    Google Scholar 

  • Liu C, Xue C, Chen X, Shan L, Tian Y, Hu G (2015b) Size-based separation of particles and cells utilizing viscoelastic effects in straight microchannels. Anal Chem 87:6041–6048

    Google Scholar 

  • Liu C, Ding B, Xue C, Tian Y, Hu G, Sun J (2016a) Sheathless focusing and separation of diverse nanoparticles in viscoelastic solutions with minimized shear thinning. Anal Chem 88:12547–12553

    Google Scholar 

  • Liu C, Xue C, Sun J, Hu G (2016b) A generalized formula for inertial lift on a sphere in microchannels. Lab Chip 16:884–892

    Google Scholar 

  • Liu C et al (2017) Field-free isolation of exosomes from extracellular vesicles by microfluidic viscoelastic flows. ACS Nano 11:6968–6976

    Google Scholar 

  • Liu C, Feng Q, Sun J (2019a) Lipid nanovesicles by microfluidics: manipulation, synthesis, and drug delivery. Adv Mater. https://doi.org/10.1002/adma.201804788

    Article  Google Scholar 

  • Liu C et al (2019b) Low-cost thermophoretic profiling of extracellular vesicle surface proteins for the early detection and classification of cancers. Nat Biomed Eng 3:183–193

    Google Scholar 

  • Lu X, Xuan X (2015) Inertia-enhanced pinched flow fractionation. Anal Chem 87:4560–4565

    Google Scholar 

  • Lu X, Zhu L, R-m Hua, Xuan X (2015) Continuous sheath-free separation of particles by shape in viscoelastic fluids. Appl Phys Lett 107:264102

    Google Scholar 

  • Lu X, Liu C, Hu G, Xuan X (2017) Particle manipulations in non-Newtonian microfluidics: a review. J Colloid Interface Sci 500:182–201

    Google Scholar 

  • Nam J, Lim H, Kim D, Jung H, Shin S (2012) Continuous separation of microparticles in a microfluidic channel via the elasto-inertial effect of non-Newtonian fluid. Lab Chip 12:1347–1354

    Google Scholar 

  • Nam J, Namgung B, Lim CT, Bae J-E, Leo HL, Cho KS, Kim S (2015) Microfluidic device for sheathless particle focusing and separation using a viscoelastic fluid. J Chromatogr A 1406:244–250

    Google Scholar 

  • Nam J, Shin Y, Tan JKS, Lim YB, Lim CT, Kim S (2016) High-throughput malaria parasite separation using a viscoelastic fluid for ultrasensitive PCR detection. Lab Chip 16:2086–2092

    Google Scholar 

  • Peinado H et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891

    Google Scholar 

  • Plaks V, Koopman CD, Werb Z (2013) Circulating tumor cells. Science 341:1186–1188

    Google Scholar 

  • Poudineh M, Sargent EH, Pantel K, Kelley SO (2018) Profiling circulating tumour cells and other biomarkers of invasive cancers. Nat Biomed Eng 2:72–84

    Google Scholar 

  • Shao H, Im H, Castro CM, Breakefield X, Weissleder R, Lee H (2018) New technologies for analysis of extracellular vesicles. Chem Rev 118:1917–1950

    Google Scholar 

  • Shurtleff MJ, Temoche-Diaz MM, Schekman R (2018) Extracellular vesicles and cancer: caveat lector. Annu Rev Cancer Biol 2:395–411

    Google Scholar 

  • Stickel JJ, Powell RL (2005) Fluid mechanics and rheology of dense suspensions. Annu Rev Fluid Mech 37:129–149

    MathSciNet  MATH  Google Scholar 

  • Sun J et al (2018) Control over the emerging chirality in supramolecular gels and solutions by chiral micro vortices in milliseconds. Nat Commun 9:2599

    Google Scholar 

  • Tan SJ, Yobas L, Lee GYH, Ong CN, Lim CT (2009) Microdevice for the isolation and enumeration of cancer cells from blood. Biomed Microdevices 11:883–892

    Google Scholar 

  • Tan JKS, Park S, Leo HL, Kim S (2017) Continuous separation of white blood cells from whole blood using viscoelastic effects. IEEE Trans Biomed Circuits Syst 11:1431–1437

    Google Scholar 

  • Tang W, Tang D, Ni Z, Xiang N, Yi H (2017) Microfluidic impedance cytometer with inertial focusing and liquid electrodes for high-throughput cell counting and discrimination. Anal Chem 89:3154–3161

    Google Scholar 

  • Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    Google Scholar 

  • Tian F et al (2017) Microfluidic co-flow of Newtonian and viscoelastic fluids for high-resolution separation of microparticles. Lab Chip 17:3078–3085

    Google Scholar 

  • Tian F, Cai L, Chang J, Li S, Liu C, Li T, Sun J (2018) Label-free isolation of rare tumor cells from untreated whole blood by interfacial viscoelastic microfluidics. Lab Chip 18:3436–3445

    Google Scholar 

  • van Niel G, D’Angelo G, Raposo G (2018) Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 19:213–228

    Google Scholar 

  • Wang J et al (2015) Label-free isolation and mrna detection of circulating tumor cells from patients with metastatic lung cancer for disease diagnosis and monitoring therapeutic efficacy. Anal Chem 87:11893–11900

    Google Scholar 

  • Witwer KW et al (2013) Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2:20360

    Google Scholar 

  • Wu M et al (2017) Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci USA 114:10584–10589

    Google Scholar 

  • Wunsch BH et al (2016) Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm. Nat Nanotechnol 11:936–940

    Google Scholar 

  • Xiang N, Chen K, Dai Q, Jiang D, Sun D, Ni Z (2014) Inertia-induced focusing dynamics of microparticles throughout a curved microfluidic channel. Microfluid Nanofluid 18:29–39

    Google Scholar 

  • Xiang N, Zhang X, Dai Q, Cheng J, Chen K, Ni Z (2016) Fundamentals of elasto-inertial particle focusing in curved microfluidic channels. Lab Chip 16:2626–2635

    Google Scholar 

  • Xiang N, Ni Z, Yi H (2018) Concentration-controlled particle focusing in spiral elasto-inertial microfluidic devices. Electrophoresis 39:417–424

    Google Scholar 

  • Xue P, Wu Y, Guo J, Kang Y (2015) Highly efficient capture and harvest of circulating tumor cells on a microfluidic chip integrated with herringbone and micropost arrays. Biomed Microdevices 17:39

    Google Scholar 

  • Yan S et al (2015) A hybrid dielectrophoretic and hydrophoretic microchip for particle sorting using integrated prefocusing and sorting steps. Electrophoresis 36:284–291

    Google Scholar 

  • Yan S, Zhang J, Yuan D, Li W (2017) Hybrid microfluidics combined with active and passive approaches for continuous cell separation. Electrophoresis 38:238–249

    Google Scholar 

  • Yang S, Kim JY, Lee SJ, Lee SS, Kim JM (2011) Sheathless elasto-inertial particle focusing and continuous separation in a straight rectangular microchannel. Lab Chip 11:266–273

    Google Scholar 

  • Yang S et al (2012) Deformability-selective particle entrainment and separation in a rectangular microchannel using medium viscoelasticity. Soft Matter 8:5011–5019

    Google Scholar 

  • Yuan D, Pan C, Zhang J, Yan S, Zhao Q, Alici G, Li W (2016a) Tunable particle focusing in a straight channel with symmetric semicircle obstacle arrays using electrophoresis-modified inertial effects. Micromachines 7:195

    Google Scholar 

  • Yuan D, Zhang J, Sluyter R, Zhao Q, Yan S, Alici G, Li W (2016b) Continuous plasma extraction under viscoelastic fluid in a straight channel with asymmetrical expansion-contraction cavity arrays. Lab Chip 16:3919–3928

    Google Scholar 

  • Yuan D et al (2016c) Investigation of particle lateral migration in sample-sheath flow of viscoelastic fluid and Newtonian fluid. Electrophoresis 37:2147–2155

    Google Scholar 

  • Yuan D et al (2017) On-chip microparticle and cell washing using co-flow of viscoelastic fluid and Newtonian fluid. Anal Chem 89:9574–9582

    Google Scholar 

  • Yuan D, Zhao Q, Yan S, Tang S-Y, Alici G, Zhang J, Li W (2018) Recent progress of particle migration in viscoelastic fluids. Lab Chip 18:551–567

    Google Scholar 

  • Zhang J, Yan S, Sluyter R, Li W, Alici G, Nguyen N-T (2014) Inertial particle separation by differential equilibrium positions in a symmetrical serpentine micro-channel. Sci Rep 4:4527

    Google Scholar 

  • Zhang J, Yan S, Yuan D, Alici G, Nguyen N-T, Ebrahimi Warkiani M, Li W (2016a) Fundamentals and applications of inertial microfluidics: a review. Lab Chip 16:10–34

    Google Scholar 

  • Zhang J, Yan S, Yuan D, Zhao Q, Tan SH, Nguyen N-T, Li W (2016b) A novel viscoelastic-based ferrofluid for continuous sheathless microfluidic separation of nonmagnetic microparticles. Lab Chip 16:3947–3956

    Google Scholar 

  • Zhang J et al (2018a) Tunable particle separation in a hybrid dielectrophoresis (DEP)-inertial microfluidic device. Sens Actuators B Chem 267:14–25

    Google Scholar 

  • Zhang L, Xu Z, Kang Y, Xue P (2018b) Three-dimensional microfluidic chip with twin-layer herringbone structure for high efficient tumor cell capture and release via antibody-conjugated magnetic microbeads. Electrophoresis 39:1452–1459

    Google Scholar 

  • Zhao W, Cheng R, Miller JR, Mao L (2016) Label-free microfluidic manipulation of particles and cells in magnetic liquids. Adv Funct Mater 26:3916–3932

    Google Scholar 

  • Zhu Z, Yang CJ (2017) hydrogel droplet microfluidics for high-throughput single molecule/cell analysis. Accounts Chem Res 50:22–31

    Google Scholar 

Download references

Acknowledgements

This work was supported financially by NSFC (21622503), Youth Innovation Promotion Association CAS (2016035), and the open research fund of Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University (KF201804).

Author information

Authors and Affiliations

  1. School of Mechanical Engineering, Hebei University of Technology, Tianjin, 300401, China

    Fei Tian & Tiejun Li

  2. CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China

    Fei Tian, Qiang Feng, Qinghua Chen, Chao Liu & Jiashu Sun

  3. School of Mechanical Engineering, and Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing, 211189, China

    Chao Liu

  4. University of Chinese Academy of Sciences, Beijing, 100049, China

    Jiashu Sun

Authors
  1. Fei Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiang Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qinghua Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tiejun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiashu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chao Liu, Tiejun Li or Jiashu Sun.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the topical collection “Particle motion in non-Newtonian microfluidics” guest edited by Xiangchun Xuan and Gaetano D’Avino.

The original version of this article was revised: In the original publication, names of three authors were incorrect. The correct author names are as below,

Fei Tian, Qiang Feng, Qinghua Chen, Chao Liu, Tiejun Li, Jiashu Sun

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tian, F., Feng, Q., Chen, Q. et al. Manipulation of bio-micro/nanoparticles in non-Newtonian microflows. Microfluid Nanofluid 23, 68 (2019). https://doi.org/10.1007/s10404-019-2232-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10404-019-2232-z

Search

Navigation