Polymeric fully inertial lab-on-a-chip with enhanced-throughput sorting capabilities

  • Annalisa VolpeEmail author
  • Petra Paiè
  • Antonio Ancona
  • Roberto Osellame
Research Paper


In biology and medicine, the application of microfluidics filtration technologies to the separation of rare particles requires processing large amounts of liquid in a short time to achieve an effective separation yield. In this direction, the parallelization of the sorting process is desirable, but not so easy to implement in a lab on a chip (LoC) device, especially if it is fully inertial. In this work, we report on femtosecond laser microfabrication (FLM) of a poly(methyl methacrylate) (PMMA) inertial microfluidic sorter, separating particles based on their size and providing an enhanced-throughput capability. The LoC device consists of a microchannel with expansion chambers provided with siphoning outlets, for a continuous sorting process. Different from soft lithography, which is the most used technique for LoC prototyping, FLM allows developing 3D microfluidic networks connecting both sides of the chip. Exploiting this capability, we are able to parallelize the circuit while keeping a single output for the sorted particles and one for the remaining sample, thus increasing the number of processed particles per unit time without compromising the simplicity of the chip connections. We investigated several device layouts (at different flow rates) to define a configuration that maximizes the selectivity and the throughput.


Lab on a chip Fs-Laser micromachining Inertial sorting Microfabrication PMMA 



The authors gratefully acknowledge the Apulian Region and the Italian Ministry of Education, University and Research (MIUR) for having supported this research activity within the projects MICROTRONIC (Lab Network cod. 71). In addition, the authors gratefully thank Francesco Bellifemine for helping during the experiments. The authors would also like to thank Professor Dino Di Carlo for the useful discussions on this topic.


  1. Amini H, Lee W, Di Carlo D (2014) Inertial microfluidic physics. Lab Chip 14:2739–2761CrossRefGoogle Scholar
  2. Bayat P, Rezai P (2018) Microfluidic curved-channel centrifuge for solution exchange of target microparticles and their simultaneous separation from bacteria. Soft Matter 14:5356–5363CrossRefGoogle Scholar
  3. Becker H, Gärtner C (2008) Polymer microfabrication technologies for microfluidic systems. Anal Bioanal Chem 390:89–111CrossRefGoogle Scholar
  4. Bhagat AAS, Kuntaegowdanahalli SS, Papautsky I (2008) Continuous particle separation in spiral microchannels using Dean flows and differential migration. Lab on a chip 8:1906–1914CrossRefGoogle Scholar
  5. Bhagat AAS, Kuntaegowdanahalli SS, Papautsky I (2009) Inertial microfluidics for continuous particle filtration and extraction. Microfluid Nanofluid 7:217–226CrossRefGoogle Scholar
  6. 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 11:1870–1878CrossRefGoogle Scholar
  7. Chan JY, Kayani ABA, Ali MAM, Kok CK, Majlis BY et al (2018) Dielectrophoresis-based microfluidic platforms for cancer diagnostics. Biomicrofluidics 12:011503–011521CrossRefGoogle Scholar
  8. Cheung P, Toda-Peters K, Shen A (2012) In situ pressure measurement within deformable rectangular polydimethylsiloxane microfluidic devices. Biomicrofluidics 6:026501–2650112CrossRefGoogle Scholar
  9. Cho H, Kim J, Song H, Sohn KY, Jeon MH, Han KH (2018) Microfluidic technologies for circulating tumor cell isolation. Analyst 143:2936–2970CrossRefGoogle Scholar
  10. Chun B, Ladd AJC (2006) Inertial migration of neutrally buoyant particles in a square duct: an investigation of multiple equilibrium positions. Phys Fluids 18:031704CrossRefGoogle Scholar
  11. Davis JA, Inglis DW, Morton KJ, Lawrence DA, Huang LR, Chou SY, Sturm JC, Austin RH (2006) Deterministic hydrodynamics: taking blood apart. Proc Natl Acad Sci USA PNAS 103:14779–14784CrossRefGoogle Scholar
  12. Farson DF, Choi HW, Zimmerman B, Steach JK, Chalmers JJ, Olesik SV, Lee LJ (2008) Femtosecond laser micromachining of dielectric materials for biomedical applications. J Micromech Microeng 18:035020–035028CrossRefGoogle Scholar
  13. Gänshirt D, Smeets FWM, Dohr A, Walde C, Steen I, Lapucci C, Falcinelli C, Sant R, Velasco M, Garritsen HSP (1998) Enrichment of fetal nucleated red blood cells from the maternal circulation for prenatal diagnosis: experiences with triple density gradient and MACS based on more than 600 cases. Fetal Diagn Ther 13:276–286CrossRefGoogle Scholar
  14. Gervais T, El-Ali J, Günther A, Jensen KF (2006) Flow-induced deformation of shallow microfluidic channels. Lab Chip 6:500–507CrossRefGoogle Scholar
  15. Guo MT, Rotem A, Heyman JA, Weitz DA (2012) Droplet microfluidics for high-throughput biological assays. Lab Chip 12:2146–2155CrossRefGoogle Scholar
  16. Hardy BS, Uechi K, Zhen J, Kavehpour HP (2009) The deformation of flexible PDMS microchannels under a pressure driven flow. Lab Chip 7:935–938CrossRefGoogle Scholar
  17. Heckele M, Schomburg WK (2004) Review on micro molding of thermoplastic polymers. J Micromech Microeng 14:R1–R14CrossRefGoogle Scholar
  18. Holm SH, Beech JP, Barrett MP, Tegenfeldt JO (2011) Separation of parasites from human blood using deterministic lateral displacement. Lab Chip 11:1326–1332CrossRefGoogle Scholar
  19. Karimi A, Yazdi S, Ardekani AM (2013) Hydrodynamic mechanisms of cell and particle trapping in microfluidics. Biomicrofluidics 7(2):021501–021522CrossRefGoogle Scholar
  20. Kim YW, Yoo JY (2008) The lateral migration of neutrally-buoyant spheres transported through square microchannels. J Micromech Microeng 18:065015CrossRefGoogle Scholar
  21. Kim P, Kwon KW, Park MC, Lee SH, Kim SM, Suh KY (2008) Soft lithography for microfluidics: a review. Biochip Journal 2:1–11Google Scholar
  22. Kononenko T, Konov V, Garnov S, Danielius R, Piskarskas A, Tamosauskas G, Dausinger F (1999) Comparative study of the ablation of materials by femtosecond and pico- or nanosecond laser pulses. Quantum Electron 29:724–728CrossRefGoogle Scholar
  23. Liu F, Jiang L, Tan HM, Yadav A, Biswas P, van der Maarel JRC, Nijhuis CA, van Kan JA (2016) Separation of superparamagnetic particles through ratcheted Brownian motion and periodically switching magnetic fields. Biomicrofluidics 10:064105CrossRefGoogle Scholar
  24. McGrath J, Jimenez M, Bridle H (2014) Deterministic lateral displacement for particle separation: a review. Lab Chip 14:4139–4158CrossRefGoogle Scholar
  25. Nivedita N, Garg N, Lee AP, Papautsky I (2017) A high throughput microfluidic platform for size-selective enrichment of cell populations in tissue and blood samples. Analyst 142:2558–2569CrossRefGoogle Scholar
  26. Paiè P, Bragheri F, Di Carlo D, Osellame R (2017a) Particle focusing by 3D inertial microfluidics. Microsyst Nanoeng 3:17027–17034CrossRefGoogle Scholar
  27. Paiè P, Che J, Di Carlo D (2017b) Effect of reservoir geometry on vortex trapping of cancer cells. Microfluid Nanofluid 21:104CrossRefGoogle Scholar
  28. Rana A, Zhang Y, Esfandiari L (2018) Advancements in microfluidic technologies for isolation and early detection of circulating cancer-related biomarkers. Analyst 143:2971–2991CrossRefGoogle Scholar
  29. Segre G, Silberberg A (1961) Radial particle displacements in poiseuille flow of suspensions. Nature 189:209–210CrossRefGoogle Scholar
  30. Sima F, Sugioka K, Vázquez RM, Osellame R, Kelemen L, Ormos P (2018) Three-dimensional femtosecond laser processing for lab-on-a-chip applications. Nanophotonics 7:613–634CrossRefGoogle Scholar
  31. Simon G, Andrade MAB, Reboud J, Marques-Hueso J, Desmulliez MPY, Cooper JM, Riehle MO, Bernassau AL (2017) Particle separation by phase modulated surface acoustic waves. Biomicrofluidics 11:054115CrossRefGoogle Scholar
  32. Sollier E, Go D, Che J, Gossett DR, O’Byrne S, Weaver WM, Kummer N, Rettig M, Goldman J, Nickols N, McCloskey S, Kulkarni RP, Di Carlo D (2014) Size-selective collection of circulating tumor cells using vortex technology. Lab Chip 14:63–77CrossRefGoogle Scholar
  33. Trotta G, Vázquez RM, Volpe A, Modica F, Ancona A, Fassi I, Osellame R (2018) Disposable optical stretcher fabricated by microinjection moulding. Micromachines 9:388–400CrossRefGoogle Scholar
  34. Vázquez RM, Trotta G, Volpe A, Bernava G, Basile V, Paturzo M, Ferraro P, Ancona A, Fassi I, Osellame R (2017) Rapid prototyping of plastic lab-on-a-chip by femtosecond laser micromachining and removable insert microinjection molding. Micromachines 8:328–336CrossRefGoogle Scholar
  35. Volpe A, Paiè P, Ancona A, Osellame R, Lugarà PM, Pascazio G (2017) A computational approach to the characterization of a microfluidic device for continuous size-based inertial sorting. J Phys D Appl Phys 50:255601CrossRefGoogle Scholar
  36. Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schütze K, Capron F, Franco D, Pazzagli M, Vekemans M et al (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol 156:57–63CrossRefGoogle Scholar
  37. Wang X, Papautsky I (2015) Size-based microfluidic multimodal microparticle sorter. Lab Chip 15:1350–1359CrossRefGoogle Scholar
  38. Wang X, Zandi M, Ho CC, Kaval N, Papautsky I (2015) Single stream inertial focusing in a straight microchannel. Lab Chip 15:1812–1821CrossRefGoogle Scholar
  39. Wu Z, Chen Y, Wang M, Chung AJ (2016) Continuous inertial microparticle and blood cell separation in straight channels with local microstructures. Lab Chip 16:532–542CrossRefGoogle Scholar
  40. Yamada M, Nakashima M, Seki M (2004) Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. Anal Chem 76:5465–5471CrossRefGoogle Scholar
  41. Zhang J, Li W, Li M, Alici G, Nguyen N (2014a) Particle inertial focusing and its mechanism in a serpentine microchannel. Microfluid Nanofluid 17:305–316CrossRefGoogle Scholar
  42. Zhang J, Yan S, Sluyter R, Li W, Alici G, Nguyen NT (2014b) Inertial particle separation by differential equilibrium positions in a symmetrical serpentine micro-channel. Sci Rep 4:4527–4535CrossRefGoogle Scholar
  43. Zhang J, Yan S, Yuan D, Alici G, Nguyen N, Warkianic ME, Li W (2016) Fundamentals and applications of inertial microfluidics: a review. Lab Chip 16:10–34CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Institute for Photonics and Nanotechnologies (IFN)-CNRBariItaly
  2. 2.Institute for Photonics and Nanotechnologies (IFN)-CNRMilanItaly
  3. 3.Department of PhysicsPolitecnico di MilanoMilanItaly

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