Skip to main content
Book cover

Applications of Microfluidic Systems in Biology and Medicine pp 1–25Cite as

Acoustofluidic Blood Component Sample Preparation and Processing in Medical Applications

Part of the Bioanalysis book series (BIOANALYSIS,volume 7)

Abstract

Recent developments of bulk acoustofluidic technology (BAW – bulk acoustic wave) in biomedical applications is described in this chapter. The basic principles for setting up an acoustic standing wave in a microchannel in 1 or 2 dimensions in the transversal direction to flow is outlined. BAW acoustofluidics is a preferred solution as compared to SAW based acoustofluidics due to the relatively higher acoustic energies that can be accomplished in BAW systems. This in turn lends BAW technology to perform cell manipulation based handling in a sufficiently high flow through format that can fulfill many biomedical and bioanalytical applications. Several unit operations for BAW based cell handling have today reached a level of maturity where these are being integral components in cytometry and cell processing instrumentation. Most of these applications are still realized at an analytical level and have not yet reached process scale or therapeutic scale throughput. However, intense developments are in progress to also reach into this domain of larger scale processing since the performance and label free operation offered from BAW systems would significantly impact current bioprocess industry and clinical practice. The importance of having full control of the buffer systems used is discussed since poorly matched buffers/fluids, with respect to the acoustic properties (acoustic impedance), may significantly impact the processing outcome as a consequence of acoustically driven fluid relocation. Also, the challenge of manipulating smaller bioparticles, e.g. bacteria, is discussed and strategies to tackle the fact that the inherent acoustic streaming in acoustic standing wave based microfluidics may be counteracting the desired alignment of cell/particles defined by the acoustic standing wave. A focus is put on applications in blood component processing, where unit operations such as cell separation (WBC, RBC, WBC subpopulations, CTC and platelets), buffer exchange and concentrating cell samples have become important modalities in cell based microfluidics. The current state of diagnostic BAW applications such as blood plasma separation, circulating tumor cell (CTC) isolation, rapid hematocrit determination and bacteria enrichment/purification in sepsis are discussed.

Keywords

  • Acoustofluidics
  • Acoustophoresis
  • Cell separation plasmapheresis
  • CTC
  • Sepsis
  • Hematocrit

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-981-13-6229-3_1
  • Chapter length: 25 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   129.00
Price excludes VAT (USA)
  • ISBN: 978-981-13-6229-3
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   169.99
Price excludes VAT (USA)
Hardcover Book
USD   169.99
Price excludes VAT (USA)
Learn about institutional subscriptions
Fig. 1.1
Fig. 1.2
Fig. 1.3
Fig. 1.4
Fig. 1.5
Fig. 1.6
Fig. 1.7
Fig. 1.8
Fig. 1.9
Fig. 1.10
Fig. 1.11
Fig. 1.12
Fig. 1.13
Fig. 1.14

References

  1. Lenshof A, Magnusson C, Laurell T (2012) Acoustofluidics 8: applications of acoustophoresis in continuous flow microsystems. Lab Chip 12:1210–1223. https://doi.org/10.1039/c2lc21256k

    CrossRef  CAS  Google Scholar 

  2. Jakobsson OJE, Grenvall C, Nordin M et al (2014) Acoustic actuated fluorescence activated sorting of microparticles. Lab Chip 14:1943–1950. https://doi.org/10.1039/c3lc51408k

    CrossRef  CAS  Google Scholar 

  3. Jakobsson O, Antfolk M, Laurell T (2014) Continuous flow two-dimensional acoustic orientation of non-spherical cells. Anal Chem 86:6111–6114

    CrossRef  CAS  Google Scholar 

  4. Gedge M, Hill M (2012) Acoustofluidics 17: theory and applications of surface acoustic wave devices for particle manipulation. Lab Chip 12:2998. https://doi.org/10.1039/c2lc40565b

    CrossRef  CAS  Google Scholar 

  5. 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. https://doi.org/10.1039/b601326k

    CrossRef  CAS  Google Scholar 

  6. Li S, Ding X, Mao Z et al (2015) Standing surface acoustic wave (SSAW)-based cell washing. Lab Chip 15:331–338. https://doi.org/10.1039/c4lc00903g

    CrossRef  CAS  Google Scholar 

  7. King LV (1934) On the acoustic radiation pressure on spheres. Proc R Soc Lond Ser A-Math Phys Sci 147:212–240

    Google Scholar 

  8. Yoshioka K, Kawashima Y (1955) Acoustic radiation pressure on a compressible sphere. Acustica 5:167–173

    Google Scholar 

  9. Gor’kov LP (1962) On the forces acting on a small particle in an acoustical field in an ideal fluid. Sov Phys Dokl 6:773–775

    Google Scholar 

  10. Nyborg WL (1967) Radiation pressure on a small rigid sphere. J Acoust Soc Am 42:947–952

    CrossRef  Google Scholar 

  11. Bruus H (2012) Acoustofluidics 2: perturbation theory and ultrasound resonance modes. Lab Chip 12:20–28

    CrossRef  CAS  Google Scholar 

  12. Augustsson P, Karlsen JT, Su H-W et al (2016) Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping. Nat Commun 7:11556. https://doi.org/10.1038/ncomms11556

    CrossRef  CAS  Google Scholar 

  13. Cushing K, Garofalo F, Magnusson C et al (2017) Ultrasound characterization of microbead and cell suspensions by speed of sound measurements of neutrally buoyant samples. Anal Chem 89(17):8917–8923. https://doi.org/10.1021/acs.analchem.7b01388

    CrossRef  CAS  Google Scholar 

  14. Petersson F, Åberg LB, Swärd-Nilsson A-MK, Laurell T (2007) Free flow acoustophoresis: microfluidic-based mode of particle and cell separation. Anal Chem 79:5117–5123. https://doi.org/10.1021/ac070444e

    CrossRef  CAS  Google Scholar 

  15. Antfolk M, Magnusson C, Augustsson P et al (2015) Acoustofluidic, label-free separation and simultaneous concentration of rare tumor cells from white blood cells. Anal Chem 87:9322–9328. https://doi.org/10.1021/acs.analchem.5b02023

    CrossRef  CAS  Google Scholar 

  16. Antfolk M, Antfolk C, Lilja H et al (2015) A single inlet two-stage acoustophoresis chip enabling tumor cell enrichment from white blood cells. Lab Chip 15:2102–2109. https://doi.org/10.1039/C5LC00078E

    CrossRef  CAS  Google Scholar 

  17. Augustsson P, Magnusson C, Nordin M et al (2012) Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis. Anal Chem 84:7954–7962. https://doi.org/10.1021/ac301723s

    CrossRef  CAS  Google Scholar 

  18. Nordin M, Laurell T (2012) Two-hundredfold volume concentration of dilute cell and particle suspensions using chip integrated multistage acoustophoresis. Lab Chip 12:4610–4616. https://doi.org/10.1039/c2lc40629b

    CrossRef  CAS  Google Scholar 

  19. Wiklund M, Green R, Ohlin M (2012) Acoustofluidics 14: applications of acoustic streaming in microfluidic devices. Lab Chip 12:2438–2451. https://doi.org/10.1039/c2lc40203c

    CrossRef  CAS  Google Scholar 

  20. Rayleigh L (1884) On the circulation of air observed in Kundt’s tubes, and on some allied acoustical problems. Philos Trans R Soc Lond A 175:1–21. https://doi.org/10.1080/15265161.2011.596400

    CrossRef  Google Scholar 

  21. Schlichting H (1932) Berechnung obener periodischer Grenzschichtströmungen. Phys Z 33:327–335

    Google Scholar 

  22. Nyborg WL (1958) Acoustic streaming near a boundary. J Acoust Soc Am 30:329. https://doi.org/10.1121/1.1909587

    CrossRef  Google Scholar 

  23. Hamilton MF, Ilinskii YA, Zabolotskaya EA (2003) Acoustic streaming generated by standing waves in two-dimensional channels of arbitrary width. J Acoust Soc Am 113:153–160

    CrossRef  Google Scholar 

  24. Muller PB, Rossi M, Marín ÁG et al (2013) Ultrasound-induced acoustophoretic motion of microparticles in three dimensions. Phys Rev E 88:23006. https://doi.org/10.1103/PhysRevE.88.023006

    CrossRef  CAS  Google Scholar 

  25. Barnkob R, Augustsson P, Laurell T, Bruus H (2012) Acoustic radiation- and streaming-induced microparticle velocities determined by microparticle image velocimetry in an ultrasound symmetry plane. Phys Rev E 86:56307. https://doi.org/10.1103/PhysRevE.86.056307

    CrossRef  CAS  Google Scholar 

  26. Muller PB, Barnkob R, Jensen MJH, Bruus H (2012) A numerical study of microparticle acoustophoresis driven by acoustic radiation forces and streaming-induced drag forces. Lab Chip 12:4617–4627. https://doi.org/10.1039/c2lc40612h

    CrossRef  CAS  Google Scholar 

  27. Antfolk M, Muller PB, Augustsson P et al (2014) Focusing of sub-micrometer particles and bacteria enabled by two-dimensional acoustophoresis. Lab Chip 14:2791–2799

    CrossRef  CAS  Google Scholar 

  28. Grenvall C, Magnusson C, Lilja H, Laurell T (2015) Concurrent isolation of lymphocytes and granulocytes using prefocused free flow acoustophoresis. Anal Chem 87(11):5596–5604. https://doi.org/10.1021/acs.analchem.5b00370

    CrossRef  CAS  Google Scholar 

  29. Deshmukh S, Brzozka Z, Laurell T, Augustsson P (2014) Acoustic radiation forces at liquid interfaces impact the performance of acoustophoresis. Lab Chip 17:3394–3400. https://doi.org/10.1039/c4lc00572d

    CrossRef  Google Scholar 

  30. Burguillos MA, Magnusson C, Nordin M et al (2013) Microchannel acoustophoresis does not impact survival or function of microglia, leukocytes or tumor cells. PLoS One 8:e64233

    CrossRef  CAS  Google Scholar 

  31. Wiklund M (2012) Acoustofluidics 12: biocompatibility and cell viability in microfluidic acoustic resonators. Lab Chip 12:2018–2028. https://doi.org/10.1039/c2lc40201g

    CrossRef  CAS  Google Scholar 

  32. Dykes J, Lenshof A, Åstrand-Grundström I-B et al (2011) Efficient removal of platelets from peripheral blood progenitor cell products using a novel micro-chip based acoustophoretic platform. PLoS One 6:e23074. https://doi.org/10.1371/journal.pone.0023074

    CrossRef  CAS  Google Scholar 

  33. Urbansky A, Lenshof A, Dykes J et al (2016) Affinity-bead-mediated enrichment of CD8+ lymphocytes from peripheral blood progenitor cell products using acoustophoresis. Micromachines 7:101. https://doi.org/10.3390/mi7060101

    CrossRef  Google Scholar 

  34. Hultström J, Manneberg O, Dopf K et al (2007) Proliferation and viability of adherent cells manipulated by standing-wave ultrasound in a microfluidic chip. Ultrasound Med Biol 33:145–151. https://doi.org/10.1016/j.ultrasmedbio.2006.07.024

    CrossRef  Google Scholar 

  35. Nam J, Lim H, Kim D, Shin S (2011) Separation of platelets from whole blood using standing surface acoustic waves in a microchannel. Lab Chip 11:3361–3364. https://doi.org/10.1039/c1lc20346k

    CrossRef  CAS  Google Scholar 

  36. Chen Y, Wu M, Ren L et al (2016) High-throughput acoustic separation of platelets from whole blood. Lab Chip 16:3466–3472. https://doi.org/10.1039/C6LC00682E

    CrossRef  CAS  Google Scholar 

  37. Lenshof A, Jamal A, Dykes J et al (2014) Efficient purification of CD4+ lymphocytes from peripheral blood progenitor cell products using affinity bead acoustophoresis. Cytom Part A 85:933–941. https://doi.org/10.1002/cyto.a.22507

    CrossRef  CAS  Google Scholar 

  38. Urbansky A, Ohlsson P, Lenshof A et al (2017) Rapid and effective enrichment of mononuclear cells from blood using acoustophoresis. Sci Rep 7:17161. https://doi.org/10.1038/s41598-017-17200-9

    CrossRef  CAS  Google Scholar 

  39. 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 142:2558–2569. https://doi.org/10.1039/C7AN00290D

    CrossRef  CAS  Google Scholar 

  40. Lenshof A, Ahmad-Tajudin A, Järås K et al (2009) Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray diagnostics. Anal Chem 81:6030–6037. https://doi.org/10.1021/pr8007545.(27

    CrossRef  CAS  Google Scholar 

  41. Ahmad-Tajudin A, Petersson K, Lenshof A et al (2013) Integrated acoustic immunoaffinity-capture (IAI) platform for detection of PSA from whole blood samples. Lab Chip 13:1790–1796. https://doi.org/10.1039/c3lc41269e

    CrossRef  CAS  Google Scholar 

  42. Tenje M, Lundgren MN, Swärd-Nilsson A-M et al (2015) Acoustophoretic removal of proteins from blood components. Biomed Microdevices 17:95. https://doi.org/10.1007/s10544-015-0003-5

    CrossRef  CAS  Google Scholar 

  43. Adams JD, Ebbesen CL, Barnkob R et al (2012) High-throughput, temperature-controlled microchannel acoustophoresis device made with rapid prototyping. J Micromech Microeng 22:75017. https://doi.org/10.1088/0960-1317/22/7/075017

    CrossRef  CAS  Google Scholar 

  44. Petersson K, Jakobsson O, Ohlsson P et al (2018) Acoustofluidic hematocrit determination. Anal Chim Acta 1000:199–204. https://doi.org/10.1016/J.ACA.2017.11.037

    CrossRef  CAS  Google Scholar 

  45. Cohen SJ, Punt CJA, Iannotti N et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26:3213–3221. https://doi.org/10.1200/JCO.2007.15.8923

    CrossRef  Google Scholar 

  46. Magnusson C, Augustsson P, Lenshof A et al (2017) Clinical-scale cell-surface-marker independent acoustic microfluidic enrichment of tumor cells from blood. Anal Chem 89:11954–11961. https://doi.org/10.1021/acs.analchem.7b01458

    CrossRef  CAS  Google Scholar 

  47. Iranmanesh I, Ramachandraiah H, Russom A, Wiklund M (2015) On-chip ultrasonic sample preparation for cell based assays. RSC Adv 5:74304–74311. https://doi.org/10.1039/C5RA16865A

    CrossRef  CAS  Google Scholar 

  48. Li P, Mao Z, Peng Z et al (2015) Acoustic separation of circulating tumor cells. Proc Natl Acad Sci U S A 112:4970–4975. https://doi.org/10.1073/pnas.1504484112

    CrossRef  CAS  Google Scholar 

  49. Faridi MA, Ramachandraiah H, Iranmanesh I et al (2017) Microbubble activated acoustic cell sorting. Biomed Microdevices 19:23. https://doi.org/10.1007/s10544-017-0157-4

    CrossRef  CAS  Google Scholar 

  50. Cushing K, Undvall E, Ceder Y et al (2018) Reducing WBC background in cancer cell separation products by negative acoustic contrast particle immuno-acoustophoresis. Anal Chim Acta 1000:256–264. https://doi.org/10.1016/J.ACA.2017.11.064

    CrossRef  CAS  Google Scholar 

  51. Jakobsson O, Oh SS, Antfolk M et al (2015) Thousand-fold volumetric concentration of live cells with a recirculating acoustofluidic device. Anal Chem 87:8497–8502. https://doi.org/10.1021/acs.analchem.5b01944

    CrossRef  CAS  Google Scholar 

  52. Kim SH, Antfolk M, Kobayashi M et al (2015) Highly efficient single cell arraying by integrating acoustophoretic cell pre-concentration and dielectrophoretic cell trapping. Lab Chip 15:4356–4363. https://doi.org/10.1039/C5LC01065A

    CrossRef  CAS  Google Scholar 

  53. Antfolk M, Kim SH, Koizumi S et al (2017) Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system. Sci Rep 7:46507. https://doi.org/10.1038/srep46507

    CrossRef  CAS  Google Scholar 

  54. Ai Y, Sanders CK, Marrone BL (2013) Separation of Escherichia coli bacteria from peripheral blood mononuclear cells using standing surface acoustic waves. Anal Chem 85:9126–9134. https://doi.org/10.1021/ac4017715

    CrossRef  CAS  Google Scholar 

  55. Ohlsson PD, Evander M, Petersson K et al (2016) Integrated acoustic separation, enrichment and microchip PCR detection of bacteria from blood for rapid sepsis diagnostics. Anal Chem 4:9403–9411. https://doi.org/10.1021/acs.analchem.6b00323

    CrossRef  CAS  Google Scholar 

  56. Ngamsom B, Lopez-Martinez MJ, Raymond J-C et al (2016) On-chip acoustophoretic isolation of microflora including S. typhimurium from raw chicken, beef and blood samples. J Microbiol Methods 123:79–86. https://doi.org/10.1016/J.MIMET.2016.01.016

    CrossRef  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Lund University, Lund, Sweden

    Maria Antfolk & Thomas Laurell

Authors
  1. Maria Antfolk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Laurell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Laurell .

Editor information

Editors and Affiliations

  1. Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Sapporo, Japan

    Dr. Manabu Tokeshi

Rights and permissions

Reprints and Permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Antfolk, M., Laurell, T. (2019). Acoustofluidic Blood Component Sample Preparation and Processing in Medical Applications. In: Tokeshi, M. (eds) Applications of Microfluidic Systems in Biology and Medicine . Bioanalysis, vol 7. Springer, Singapore. https://doi.org/10.1007/978-981-13-6229-3_1

Download citation