Abstract
Microfluidics as a field has a plethora of applications in several fields. From heat transfer to biomedical applications, microfluidic techniques are used to deliver solutions. In the present chapter, we look into the basics of microfluidic techniques used to manipulate tiny volumes of fluids. Further, a detailed discussion on acoustofluidics, lab/organ-on-chip, biosensing, and cell manipulation follows. Section 2.4 focuses on the use of bulk and surface acoustic waves to manipulate particles and cells. Section 2.5 sheds light on the use of microfluidic chips mimicking an organ or its basic process and how the same is used to study the effect of drugs on the organs. Section 2.6 focuses on using microfluidic techniques for disease detection and prognosis monitoring. The part on Cell manipulation cuts through various active and passive techniques for cell trapping, focusing, and sorting.
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References
Leibacher I, Reichert P, Dual J (2015) Microfluidic droplet handling by bulk acoustic wave (BAW) acoustophoresis. Lab Chip 15:2896–2905
McGrath J, Jimenez M, Bridle H (2014) Deterministic lateral displacement for particle separation: a review. Lab Chip 14:4139–4158
Bijarchi MA, Dizani M, Honarmand M, Shafii MB (2021) Splitting dynamics of ferrofluid droplets inside a microfluidic T-junction using a pulse-width modulated magnetic field in micro-magnetofluidics. Soft Matter 17:1317–1329
Majhy B, Singh VP, Sen AK (2020) Understanding wetting dynamics and stability of aqueous droplet over superhydrophilic spot surrounded by superhydrophobic surface. J Colloid Interface Sci. https://doi.org/10.1016/j.jcis.2020.01.056
Hazra S et al (2019) Non-inertial lift induced migration for label-free sorting of cells in a co-flowing aqueous two-phase system. Analyst 144:2574–2583
Sajeesh P, Sen AK (2014) Particle separation and sorting in microfluidic devices: a review. Microfluid Nanofluid 17:1–52
Zhou J, Papautsky I (2020) Viscoelastic microfluidics: progress and challenges. Microsyst Nanoeng 6:113
Convery N, Gadegaard N (2019) 30 Years of microfluidics. Micro Nano Eng 2:76–91
Cui P, Wang S (2019) Application of microfluidic chip technology in pharmaceutical analysis: a review. J Pharm Anal 9:238–247
Gabriel EFM, Lucca BG, Duarte GRM, Coltro WKT (2018) Recent advances in toner-based microfluidic devices for bioanalytical applications. Anal Methods 10:2952–2962
Nguyen NT, Hejazian M, Ooi CH, Kashaninejad N (2017) Recent advances and future perspectives on microfluidic liquid handling. Micromachines 8:186
Bai Y et al (2018) Applications of microfluidics in quantitative biology. Biotechnol J 13:e1700170
Oakey J, Allely J, Marr DWM (2002) Laminar-flow-based separations at the microscale. Biotechnol Prog 18:1439–1442
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 76:5465–5471
Berendsen JTW, Eijkel JCT, Wetzels AM, Segerink LI (2019) Separation of spermatozoa from erythrocytes using their tumbling mechanism in a pinch flow fractionation device. Microsyst Nanoeng 5:24
Park JS, Jung HI (2009) Multiorifice flow fractionation: continuous size-based separation of microspheres using a series of contraction/expansion microchannels. Anal Chem 81:8280–8288
Zeng L, Balachandar S, Fischer P (2005) Wall-induced forces on a rigid sphere at finite Reynolds number. J Fluid Mech 536:1–25
Alghalibi D, Rosti ME, Brandt L (2019) Inertial migration of a deformable particle in pipe flow. Phys Rev Fluids 4:104201
Yoon DH et al (2009) Size-selective separation of micro beads by utilizing secondary flow in a curved rectangular microchannel. Lab Chip 9:87–90
Russom A et al (2009) Differential inertial focusing of particles in curved low-aspect-ratio microchannels. New J Phys 11:75025
Duraiswamy S, Yung LYL (2021) Dean migration of unfocused micron sized particles in low aspect ratio spiral microchannels. Biomed Microdevices 23:1–16
Huang LR, Cox EC, Austin RH, Sturm JC (2016) Continuous particle separation through deterministic lateral displacement. Science 304:987–990
Zhang Z, Henry E, Gompper G, Fedosov DA (2015) Behavior of rigid and deformable particles in deterministic lateral displacement devices with different post shapes. J Chem Phys 143:243145
Davis JA et al (2006) Deterministic hydrodynamics: taking blood apart. Proc Natl Acad Sci U S A 103:14779–14784
Beech JP, Holm SH, Adolfsson K, Tegenfeldt JO (2012) Sorting cells by size, shape and deformability. Lab Chip 12:1048–1051
Quek R, Le DV, Chiam KH (2011) Separation of deformable particles in deterministic lateral displacement devices. Phys Rev E Stat Nonlinear Soft Matter Phys 83:1–7
Loutherback K et al (2010) Improved performance of deterministic lateral displacement arrays with triangular posts. Microfluid Nanofluid 9:1143–1149
Gascoyne PRC, Vykoukal J (2002) Particle separation by dielectrophoresis. Electrophoresis 23:1973–1983
Pesch GR, Du F (2021) A review of dielectrophoretic separation and classification of non-biological particles. Electrophoresis 42:134–152
Yaman S, Anil-Inevi M, Ozcivici E, Tekin HC (2018) Magnetic force-based microfluidic techniques for cellular and tissue bioengineering. Front Bioeng Biotechnol 6:192
Kersaudy-Kerhoas M, Dhariwal R, Desmulliez MPY, Jouvet L (2010) Hydrodynamic blood plasma separation in microfluidic channels. Microfluid Nanofluid 8:105–114
Kim J, Massoudi M, Antaki JF, Gandini A (2012) Removal of malaria-infected red blood cells using magnetic cell separators: a computational study. Appl Math Comput 218:6841–6850
Adams JD, Kim U, Soh HT (2008) Multitarget magnetic activated cell sorter. Proc Natl Acad Sci U S A 105:18165–18170
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
McGloin D (2006) Optical tweezers: 20 years on. Philos Trans R Soc A Math Phys Eng Sci 364:3521–3537
Dao M, Lim CT, Suresh S (2003) Mechanics of the human red blood cell deformed by optical tweezers. J Mech Phys Solids 51:2259–2280
Bruus H (2012) Acoustofluidics 7: The acoustic radiation force on small particles. Lab Chip 12:1014–1021
Hoque SZ, Sen AK (2020) Interparticle acoustic radiation force between a pair of spherical particles in a liquid exposed to a standing bulk acoustic wave. Phys Fluids 32:072004
Hoque SZ, Nath A, Sen AK (2021) Dynamical motion of a pair of microparticles at the acoustic pressure nodal plane under the combined effect of axial primary radiation and interparticle forces. J Acoust Soc Am 150:307–320
Sohrabi S, Kassir N, Keshavarz Moraveji M (2020) Droplet microfluidics: fundamentals and its advanced applications. RSC Adv 10:27560–27574
Link DR, Anna SL, Weitz DA, Stone HA (2004) Geometrically mediated breakup of drops in microfluidic devices. Phys Rev Lett 92:4
Surya HPN, Parayil S, Banerjee U, Chander S, Sen AK (2015) Alternating and merged droplets in a double T-junction microchannel. Biochip J 9:16–26
Hatch AC, Patel A, Beer NR, Lee AP (2013) Passive droplet sorting using viscoelastic flow focusing. Lab Chip 13:1308–1315
Umbanhowar PB, Prasad V, Weitz DA (2000) Monodisperse emulsion generation via drop break off in a coflowing stream. Langmuir 16:347–351
Utada AS et al (2005) Monodisperse double emulsions generated from a microcapillary device. Science 308:537–541
Jayaprakash KS, Sen AK (2019) Droplet encapsulation of particles in different regimes and sorting of particle-encapsulating-droplets from empty droplets. Biomicrofluidics 13:034108
Zhu P, Wang L (2017) Passive and active droplet generation with microfluidics: a review. Lab Chip 17:34–75
Ménétrier-Deremble L, Tabeling P (2006) Droplet breakup in microfluidic junctions of arbitrary angles. Phys Rev E Stat Nonlinear Soft Matter Phys 74:1–4
Tan YC, Fisher JS, Lee AI, Cristini V, Lee AP (2004) Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting. Lab Chip 4:292–298
Cho SK, Moon H, Kim CJ (2003) Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits. J Microelectromech Syst 12:70–80
Jung JH, Destgeer G, Ha B, Park J, Sung HJ (2016) On-demand droplet splitting using surface acoustic waves. Lab Chip 16:3235–3243
Christopher GF et al (2009) Coalescence and splitting of confined droplets at microfluidic junctions. Lab Chip 9:1102–1109
Xu B, Nguyen N-T, Neng Wong T (2012) Droplet coalescence in microfluidic systems. Micro Nanosyst 3:131–136
Niu X, Gulati S, Edel JB, Demello AJ (2008) Pillar-induced droplet merging in microfluidic circuits. Lab Chip 8:1837–1841
Bremond N, Thiam AR, Bibette J (2008) Decompressing emulsion droplets favors coalescence. Phys Rev Lett 100:1–4
Hemachandran E, Laurell T, Sen AK (2019) Continuous droplet coalescence in a microchannel coflow using bulk acoustic waves. Phys Rev Appl 12:1
Sesen M, Fakhfouri A, Neild A (2019) Coalescence of surfactant-stabilized adjacent droplets using surface acoustic waves. Anal Chem 91:7538–7545
Sudeepthi A, Nath A, Yeo LY, Sen AK (2021) Coalescence of droplets in a microwell driven by surface acoustic waves. Langmuir. https://doi.org/10.1021/acs.langmuir.0c03292
Mazutis L et al (2013) Single-cell analysis and sorting using droplet-based microfluidics. Nat Protoc 8:870–891
Huh D et al (2007) Gravity-driven microfluidic particle sorting device with hydrodynamic separation amplification. Anal Chem 79:1369–1376
Xi HD et al (2017) Active droplet sorting in microfluidics: a review. Lab Chip 17:751–771
Shang L, Cheng Y, Zhao Y (2017) Emerging droplet microfluidics. Chem Rev 117:7964–8040
Nooranidoost M, Haghshenas M, Muradoglu M, Kumar R (2019) Cell encapsulation modes in a flow-focusing microchannel: effects of shell fluid viscosity. Microfluid Nanofluid 23:1–10
Di Carlo D, Irimia D, Tompkins RG, Toner M (2007) Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc Natl Acad Sci U S A 104:18892–18897
He M et al (2005) Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets. Anal Chem 77:1539–1544
Zeng J et al (2012) Three-dimensional magnetic focusing of particles and cells in ferrofluid flow through a straight microchannel. J Micromech Microeng 22:105018
Kemna EWM et al (2012) High-yield cell ordering and deterministic cell-in-droplet encapsulation using Dean flow in a curved microchannel. Lab Chip 12:2881–2887
Kamalakshakurup G, Lee AP (2017) High-efficiency single cell encapsulation and size selective capture of cells in picoliter droplets based on hydrodynamic micro-vortices. Lab Chip 17:4324–4333
Gaikwad R, Sen AK (2021) An optomicrofluidic device for the detection and isolation of drop-encapsulated target cells in single-cell format. Analyst 146:95–108
Hemachandran E, Hoque SZ, Laurell T, Sen AK (2021) Reversible stream drop transition in a microfluidic coflow system via on demand exposure to acoustic standing waves. Phys Rev Lett 127:134501
Banerjee U, Jain SK, Sen AK (2021) Particle encapsulation in aqueous ferrofluid drops and sorting of particle-encapsulating drops from empty drops using a magnetic field. Soft Matter 17:6020–6028
Niculescu AG, Chircov C, Bîrcă AC, Grumezescu AM (2021) Fabrication and applications of microfluidic devices: a review. Int J Mol Sci 22:1–26
Choi K, Ng AHC, Fobel R, Wheeler AR (2012) Digital microfluidics. Annu Rev Anal Chem 5:413–440
Friend J, Yeo LY (2011) Microscale acoustofluidics: microfluidics driven via acoustics and ultrasonics. Rev Mod Phys. https://doi.org/10.1103/RevModPhys.83.647
Wenzel RN (1936) Resistance of solid surfaces to wetting by water. Ind Eng Chem 28:988–994
Brittain ST, Paul KE, Zhao X-M, Whitesides GM (1998) Soft lithography and microfabrication. Phys World 11:31–36
Luz GM, Leite ÁJ, Neto AI, Song W, Mano JF (2011) Wettable arrays onto superhydrophobic surfaces for bioactivity testing of inorganic nanoparticles. Mater Lett 65:296–299
Rahmawan Y, Xu L, Yang S (2013) Self-assembly of nanostructures towards transparent, superhydrophobic surfaces. J Mater Chem A 1:2955–2969
Xu T, Xu L-P, Zhang X, Wang S (2019) Bioinspired superwettable micropatterns for biosensing. Chem Soc Rev 48:3153–3165
Li J-F, Zhang Y-J, Ding S-Y, Panneerselvam R, Tian Z-Q (2017) Core–shell nanoparticle-enhanced Raman spectroscopy. Chem Rev 117:5002–5069
Song Y, Xu T, Xu L-P, Zhang X (2018) Superwettable nanodendritic gold substrates for direct miRNA SERS detection. Nanoscale 10:20990–20994
Hou J et al (2015) Hydrophilic–hydrophobic patterned molecularly imprinted photonic crystal sensors for high-sensitive colorimetric detection of tetracycline. Small 11:2738–2742
Connacher W, Orosco J, Friend J (2020) Droplet ejection at controlled angles via acoustofluidic jetting. Phys Rev Lett 125:184504
Sudeepthi A, Sen AK, Yeo L (2019) Aggregation of a dense suspension of particles in a microwell using surface acoustic wave microcentrifugation. Microfluid Nanofluid 23:76
Wiklund M, Green R, Ohlin M (2012) Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices. Lab Chip. https://doi.org/10.1039/c2lc40203c
Aijian AP, Garrell RL (2015) Digital microfluidics for automated hanging drop cell spheroid culture. J Lab Autom 20:283–295
Nelson WC, Kim CJC (2012) Droplet actuation by electrowetting-on-dielectric (EWOD): a review. J Adhes Sci Technol 26:1747–1771
Mugele F, Baret J-C (2005) Electrowetting: from basics to applications. J Phys Condens Matter 17:R705–R774
Jones TB (2001) Liquid dielectrophoresis on the microscale. J Electrost 51–52:290–299
Kaler KVIS, Prakash R, Chugh D (2010) Liquid dielectrophoresis and surface microfluidics. Biomicrofluidics 4:022805
Sudeepthi A, Yeo L, Sen AK (2020) Cassie-Wenzel wetting transition on nanostructured superhydrophobic surfaces induced by surface acoustic waves. Appl Phys Lett 116:1–6
Zhang Y, Nguyen NT (2017) Magnetic digital microfluidics - a review. Lab Chip 17:994–1008
Mandal C, Banerjee U, Sen AK (2019) Transport of a sessile aqueous droplet over spikes of oil based ferrofluid in the presence of a magnetic field. Langmuir. https://doi.org/10.1021/acs.langmuir.9b00631
Sen P, Kim CJ (2009) Capillary spreading dynamics of electrowetted sessile droplets in air. Langmuir 25:4302–4305
Jones TB, Wang KL, Yao DJ (2004) Frequency-dependent electromechanics of aqueous liquids: electrowetting and dielectrophoresis. Langmuir 20:2813–2818
Li J, Kim CJ (2020) Current commercialization status of electrowetting-on-dielectric (EWOD) digital microfluidics. Lab Chip 20:1705–1712
Cho HM, Kim C-J (2003) Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits. J Microelectromech Syst 12:70–80
Pang L, Ding J, Liu X-X, Fan S-K (2019) Digital microfluidics for cell manipulation. TrAC Trends Anal Chem. https://doi.org/10.1016/j.trac.2019.06.008
Zhuang J, Yin J, Lv S, Wang B, Mu Y (2020) Advanced “lab-on-a-chip” to detect viruses – current challenges and future perspectives. Biosens Bioelectron 163:112291
Nasseri B et al (2018) Point-of-care microfluidic devices for pathogen detection. Biosens Bioelectron 117:112–128
Bansal S, Subramanian S (2021) A microfluidic acoustic metamaterial using electrowetting: enabling active broadband tunability. Adv Mater Technol 6:2100491
Pohl HA (1958) Some effects of nonuniform fields on dielectrics. J Appl Phys 29:1182–1188
Khoshmanesh K, Nahavandi S, Baratchi S, Mitchell A, Kalantar-zadeh K (2011) Dielectrophoretic platforms for bio-microfluidic systems. Biosens Bioelectron 26:1800–1814
Piao Y, Yu K, Jones TB, Wang W (2021) Electrical actuation of dielectric droplets by negative liquid dielectrophoresis. Electrophoresis 42(23):2490–2497. https://doi.org/10.1002/elps.202100093
Nampoothiri KN, Sen P (2021) Motion of generated dumbbell-shaped satellite droplets during liquid dielectrophoresis. J Micromech Microeng 31
Nampoothiri KN, Bobji MS, Sen P (2019) Generation of micron-sized droplet streams by high frequency electric fields. Int J Heat Mass Transf 145:118709
Nampoothiri KN, Srinivasan V, Bobji MS, Sen P (2017) A novel sub-picoliter monodispersed droplet generation device based on liquid dielectrophoresis. Proc IEEE Int Conf Micro Electro Mech Syst 2017:87–90. https://doi.org/10.1109/MEMSYS.2017.7863346
Nampoothiri KN, Seshasayee MS, Srinivasan V, Bobji MS, Sen P (2018) Direct heating of aqueous droplets using high frequency voltage signals on an EWOD platform. Sensors Actuators B Chem 273:862–872
Nampoothiri KN, Bobji MS, Sen P (2020) De-icing device with self-adjusting power consumption and ice sensing capabilities. J Microelectromech Syst 29:562–570
Frozanpoor I et al (2021) Programmable droplet actuating platform using liquid dielectrophoresis. J Micromech Microeng 31:055014
Settnes M, Bruus H (2012) Forces acting on a small particle in an acoustical field in a viscous fluid. Phys Rev E Stat Nonlinear Soft Matter Phys 85:1–12
Bruus H et al (2011) Forthcoming lab on a chip tutorial series on acoustofluidics: acoustofluidics - exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation. Lab Chip 11:3579–3580
Ding X et al (2013) Surface acoustic wave microfluidics. Lab Chip 13:3626
Rasouli R, Tabrizian M (2021) Rapid formation of multicellular spheroids in boundary-driven acoustic microstreams. Small 17:1–12
Dolatmoradi A, Mirtaheri E, El-Zahab B (2017) Thermo-acoustofluidic separation of vesicles based on cholesterol content. Lab Chip 17:1332–1339
Dow P, Kotz K, Gruszka S, Holder J, Fiering J (2018) Acoustic separation in plastic microfluidics for rapid detection of bacteria in blood using engineered bacteriophage. Lab Chip 18:923–932
Ohlsson P, Petersson K, Augustsson P, Laurell T (2018) Acoustic impedance matched buffers enable separation of bacteria from blood cells at high cell concentrations. Sci Rep 8:1–11
Lenshof A, Magnusson C, Laurell T (2012) Acoustofluidics 8: Applications of acoustophoresis in continuous flow microsystems. Lab Chip 12:1210–1223
Antfolk M, Magnusson C, Augustsson P, Lilja H, Laurell T (2015) Acoustofluidic, label-free separation and simultaneous concentration of rare tumor cells from white blood cells. Anal Chem 87:9322–9328
Grenvall C, Magnusson C, Lilja H, Laurell T (2015) Concurrent isolation of lymphocytes and granulocytes using prefocused free flow acoustophoresis. Anal Chem 87:5596–5604
Johnson DA, Feke DL (1995) Methodology for fractionating suspended particles using ultrasonic standing wave and divided flow fields. Sep Technol 5:251–258
Chen Y et al (2016) High-throughput acoustic separation of platelets from whole blood. Lab Chip 16:3466–3472
Antfolk M, Laurell T (2017) Continuous flow microfluidic separation and processing of rare cells and bioparticles found in blood – a review. Anal Chim Acta 965:9–35
Petersson F, Åberg L, Swärd-Nilsson AM, Laurell T (2007) Free flow acoustophoresis: microfluidic-based mode of particle and cell separation. Anal Chem 79:5117–5123
Karthick S, Sen AK (2018) Improved understanding of acoustophoresis and development of an acoustofluidic device for blood plasma separation. Phys Rev Appl 10:1
Karthick S, Pradeep PN, Kanchana P, Sen AK (2018) Acoustic impedance-based size-independent isolation of circulating tumour cells from blood using acoustophoresis. Lab Chip 18:3802–3813
Piyasena ME et al (2012) Multinode acoustic focusing for parallel flow cytometry. Anal Chem 84:1831–1839
Goddard G, Martin JC, Graves SW, Kaduchak G (2006) Ultrasonic particle-concentration for sheathless focusing of particles for analysis in a flow cytometer. Cytometry A. https://doi.org/10.1002/cyto.a.20205
Kalb DM et al (2017) Line-focused optical excitation of parallel acoustic focused sample streams for high volumetric and analytical rate flow cytometry. Anal Chem. https://doi.org/10.1021/acs.analchem.7b02319
Jakobsson O, Grenvall C, Nordin M, Evander M, Laurell T (2014) Acoustic actuated fluorescence activated sorting of microparticles. Lab Chip 14:1943–1950
Jakobsson O et al (2015) Thousand-fold volumetric concentration of live cells with a recirculating acoustofluidic device. Anal Chem 87:8497–8502
Wiklund M, Radel S, Hawkes JJ (2013) Acoustofluidics 21: Ultrasound-enhanced immunoassays and particle sensors. Lab Chip 13:25–39
Reboud J et al (2012) Shaping acoustic fields as a toolset for microfluidic manipulations in diagnostic technologies. Proc Natl Acad Sci U S A 109:15162–15167
Gracioso Martins AM et al (2014) Toward complete miniaturisation of flow injection analysis systems: microfluidic enhancement of chemiluminescent detection. Anal Chem 86:10812–10819
Destgeer G et al (2014) Adjustable, rapidly switching microfluidic gradient generation using focused travelling surface acoustic waves. Appl Phys Lett 104:10–15
Cecchini M, Girardo S, Pisignano D, Cingolani R, Beltram F (2008) Acoustic-counterflow microfluidics by surface acoustic waves. Appl Phys Lett 92:2006–2009
Zhang SP et al (2018) Digital acoustofluidics enables contactless and programmable liquid handling. Nat Commun 9:1–11
Bourquin Y, Reboud J, Wilson R, Zhang Y, Cooper JM (2011) Integrated immunoassay using tuneable surface acoustic waves and lensfree detection. Lab Chip 11:2725–2730
Collins DJ, Ma Z, Ai Y (2016) Highly localized acoustic streaming and size-selective submicrometer particle concentration using high frequency microscale focused acoustic fields. Anal Chem 88:5513–5522
Bourquin Y et al (2014) Rare-cell enrichment by a rapid, label-free, ultrasonic isopycnic technique for medical diagnostics. Angew Chem Int Ed 53:5587–5590
Destgeer G et al (2016) Acoustofluidic particle manipulation inside a sessile droplet: four distinct regimes of particle concentration. Lab Chip 16:660–667
Lee K, Shao H, Weissleder R, Lee H, Al LEEET (2015) Acoustic purification of extracellular microvesicles. ACS Nano 9(3):2321–2327
Ding X et al (2012) Standing surface acoustic wave (SSAW) based multichannel cell sorting. Lab Chip 12:4228–4231
Chen Y et al (2014) Continuous enrichment of low-abundance cell samples using standing surface acoustic waves (SSAW). Lab Chip 14:924–930
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
Shi J, Mao X, Ahmed D, Colletti A, Huang TJ (2008) Focusing microparticles in a microfluidic channel with standing surface acoustic waves (SSAW). Lab Chip 8:221–223
Ren L et al (2015) A high-throughput acoustic cell sorter. Lab Chip 15:3870–3879
Shi J, Huang H, Stratton Z, Huang Y, Huang TJ (2009) Continuous particle separation in a microfluidic channel via standing surface acoustic waves (SSAW). Lab Chip 9:3354–3359
Ren L et al (2018) Standing surface acoustic wave (SSAW)-based fluorescence-activated cell sorter. Small 14:1–8
Chen Y et al (2014) Standing surface acoustic wave (SSAW)-based microfluidic cytometer. Lab Chip 14:916–923
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
Wang Z et al (2020) Erratum: Isolation of exosomes from whole blood by integrating acoustics and microfluidics (Proceedings of the National Academy of Sciences of the United States of America (2017) 114 (10584–10589) DOI: 10.1073/pnas.1709210114). Proc Natl Acad Sci U S A 117:28525
Ding X et al (2014) Cell separation using tilted-angle standing surface acoustic waves. Proc Natl Acad Sci U S A 111:12992–12997
Dao M et al (2015) Acoustic separation of circulating tumor cells. Proc Natl Acad Sci U S A 112:4970–4975
Wu M et al (2018) Circulating tumor cell phenotyping via high-throughput acoustic separation. Small 14:1–10
Franke T, Braunmüller S, Schmid L, Wixforth A, Weitz DA (2010) Surface acoustic wave actuated cell sorting (SAWACS). Lab Chip 10:789–794
Ma Z, Collins DJ, Ai Y (2016) Detachable acoustofluidic system for particle separation via a traveling surface acoustic wave. Anal Chem 88:5316–5323
Ung WL et al (2017) Enhanced surface acoustic wave cell sorting by 3D microfluidic-chip design. Lab Chip 17:4059–4069
Destgeer G, Ha BH, Jung JH, Sung HJ (2014) Submicron separation of microspheres via travelling surface acoustic waves. Lab Chip 14:4665–4672
Ahmed D et al (2016) Rotational manipulation of single cells and organisms using acoustic waves. Nat Commun 7:11085
Lee AP, Patel MV, Tovar AR, Okabe Y (2010) Microfluidic air-liquid cavity acoustic transducers for on-chip integration of sample preparation and sample detection. J Assoc Lab Autom 15:449–454
Rasouli MR, Tabrizian M (2019) An ultra-rapid acoustic micromixer for synthesis of organic nanoparticles. Lab Chip 19:3316–3325
Doinikov AA, Gerlt MS, Dual J (2020) Acoustic radiation forces produced by sharp-edge structures in microfluidic systems. Phys Rev Lett 124:154501
Huang PH et al (2014) A reliable and programmable acoustofluidic pump powered by oscillating sharp-edge structures. Lab Chip 14:4319–4323
Huang PH et al (2013) An acoustofluidic micromixer based on oscillating sidewall sharp-edges. Lab Chip 13:3847–3852
Huang PH et al (2015) An acoustofluidic sputum liquefier. Lab Chip 15:3125–3131
Wang Z et al (2019) Cell lysis: via acoustically oscillating sharp edges. Lab Chip 19:4021–4032
Leibacher I, Hahn P, Dual J (2015) Acoustophoretic cell and particle trapping on microfluidic sharp edges. Microfluid Nanofluid 19:923–933
Shanti A, Teo J, Stefanini C (2018) In vitro immune organs-on-chip for drug development: a review. Pharmaceutics 10:278
McKim J Jr (2010) Building a tiered approach to in vitro predictive toxicity screening: a focus on assays with in vivo relevance. Comb Chem High Throughput Screen 13:188–206
Prantil-Baun R et al (2018) Physiologically based pharmacokinetic and pharmacodynamic analysis enabled by microfluidically linked organs-on-chips. Annu Rev Pharmacol Toxicol 58:37–64
Sager JE, Yu J, Ragueneau-Majlessi I, Isoherranen N (2015) Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches: a systematic review of published models, applications, and model verification. Drug Metab Dispos 43:1823–1837
Rowland M, Peck C, Tucker G (2011) Physiologically-based pharmacokinetics in drug development and regulatory science. Annu Rev Pharmacol Toxicol 51:45–73
Kankala RK, Wang S-B, Chen A-Z (2019) Microengineered organ-on-a-chip platforms towards personalized medicine. Curr Pharm Des 24:5354–5366
Esch EW, Bahinski A, Huh D (2015) Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov 14:248–260
Huh D, Hamilton GA, Ingber DE (2011) From 3D cell culture to organs-on-chips. Trends Cell Biol 21:745–754
Huh D et al (2013) Microfabrication of human organs-on-chips. Nat Protoc 8:2135–2157
Yum K, Hong SG, Healy KE, Lee LP (2014) Physiologically relevant organs on chips. Biotechnol J 9:16–27
Zhang YS et al (2017) Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci U S A 114:E2293–E2302
Perestrelo AR, Águas ACP, Rainer A, Forte G (2015) Microfluidic organ/body-on-a-chip devices at the convergence of biology and microengineering. Sensors (Switzerland) 15:31142–31170
Huh D et al (2010) Reconstituting organ-level lung functions on a chip. Science 328:1662–1668
Inamdar NK, Borenstein JT (2011) Microfluidic cell culture models for tissue engineering. Curr Opin Biotechnol 22:681–689
Khetani SR, Bhatia SN (2008) Microscale culture of human liver cells for drug development. Nat Biotechnol 26:120–126
Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32:760–772
Mittal R et al (2019) Organ-on-chip models: implications in drug discovery and clinical applications. J Cell Physiol 234:8352–8380
Arrigoni C, Gilardi M, Bersini S, Candrian C, Moretti M (2017) Bioprinting and organ-on-chip applications towards personalized medicine for bone diseases. Stem Cell Rev Rep 13:407–417
Skardal A et al (2017) Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep 7:1–16
Lee SH, Sung JH (2018) Organ-on-a-chip technology for reproducing multiorgan physiology. Adv Healthc Mater 7:1–17
Ronaldson-Bouchard K, Vunjak-Novakovic G (2018) Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell 22:310–324
Zamprogno P et al (2021) Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane. Commun Biol 4:1–10
Zhang M et al (2021) Biomimetic human disease model of SARS-CoV-2-induced lung injury and immune responses on organ chip system. Adv Sci 8:1–14
Singh AV et al (2021) Advances in smoking related in vitro inhalation toxicology: a perspective case of challenges and opportunities from progresses in lung-on-chip technologies. Chem Res Toxicol. https://doi.org/10.1021/acs.chemrestox.1c00219
Huang D et al (2021) Reversed-engineered human alveolar lung-on-a-chip model. Proc Natl Acad Sci U S A 118:1–10
Benam KH et al (2015) Engineered in vitro disease models. Annu Rev Pathol Mech Dis 10:195–262
Jin Y et al (2018) Three-dimensional brain-like microenvironments facilitate the direct reprogramming of fibroblasts into therapeutic neurons. Nat Biomed Eng 2:522–539
Estlack Z, Bennet D, Reid T, Kim J (2017) Microengineered biomimetic ocular models for ophthalmological drug development. Lab Chip 17:1539–1551
Ma C, Peng Y, Li H, Chen W (2021) Organ-on-a-chip: a new paradigm for drug development. Trends Pharmacol Sci 42:119–133
Wu Q et al (2020) Organ-on-a-chip: recent breakthroughs and future prospects. Biomed Eng Online 19:1–19
Yu F, Hunziker W, Choudhury D (2019) Engineering microfluidic organoid-on-a-chip platforms. Micromachines 10:1–12
Chinen AB et al (2017) Nanoparticle probes for the detection of cancer biomarkers. Cells Tissues Fluoresc 115:10530–10574
Shi W et al (2017) Magnetic particles assisted capture and release of rare circulating tumor cells using wavy-herringbone structured microfluidic devices. Lab Chip 17:3291–3299
Viganò P et al (2001) Development and characterization of microfluidic devices and systems for magnetic bead-based biochemical detection. Biomed Microdevices 3:191–200
Binkley MM, Cui M, Berezin MY, Meacham JM (2020) Antibody conjugate assembly on ultrasound-confined microcarrier particles. ACS Biomater Sci Eng 6:6108–6116
Nagrath S et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235–1239
Austin Suthanthiraraj PP, Sen AK (2019) Localized surface plasmon resonance (LSPR) biosensor based on thermally annealed silver nanostructures with on-chip blood-plasma separation for the detection of dengue non-structural protein NS1 antigen. Biosens Bioelectron 132:38–46
Khan NI, Song E (2020) Lab-on-a-chip systems for aptamer-based biosensing. Micromachines 11:220
Chen Y, Pulikkathodi K, Ma Y, Wang Y, Lee G (2019) Lab on a Chip transistors for enumeration of circulating tumor. Lab Chip. https://doi.org/10.1039/c8lc01072b
Song S, Wang L, Li J, Fan C, Zhao J (2008) Aptamer-based biosensors. Trends Anal Chem 27:108–117
Campaña AL et al (2019) Enzyme-based electrochemical biosensors for microfluidic platforms to detect pharmaceutical residues in wastewater. Biosensors 9:41
Hernández-Ibáñez N et al (2016) Electrochemical lactate biosensor based upon chitosan/carbon nanotubes modified screen-printed graphite electrodes for the determination of lactate in embryonic cell cultures. Biosens Bioelectron 77:1168–1174
Brahim S, Narinesingh D, Guiseppi-Elie A (2002) Polypyrrole-hydrogel composites for the construction of clinically important biosensors. Biosens Bioelectron 17:53–59
Maji SK, Sreejith S, Mandal AK, Ma X, Zhao Y (2014) Immobilizing gold nanoparticles in mesoporous silica covered reduced graphene oxide: a hybrid material for cancer cell detection through hydrogen peroxide sensing. ACS Appl Mater Interfaces 6:13648–13656
Jiang S et al (2013) Real-time electrical detection of nitric oxide in biological systems with sub-nanomolar sensitivity. Nat Commun 4:1–7
Karunya R et al (2019) Rapid measurement of hydrogen sulphide in human blood plasma using a microfluidic method. Sci Rep 9:1–11
Gaikwad R, Thangaraj PR, Sen AK (2021) Direct and rapid measurement of hydrogen peroxide in human blood using a microfluidic device. Sci Rep 11:1–10
Del Ben F et al (2016) A method for detecting circulating tumor cells based on the measurement of single-cell metabolism in droplet-based microfluidics. Angew Chem Int Ed Engl. https://doi.org/10.1002/anie.201602328
Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? (vol 41, pg 211, 2016). Trends Biochem Sci 41:287
Balcells M et al (2002) Reactive polymer coatings: a platform for patterning proteins and mammalian cells onto a broad range of materials. Langmuir 9:3632–3638
Khademhosseini A, Yeh J, Jon S, Eng G, Suh KY (2004) Molded polyethylene glycol microstructures for capturing cells within microfluidic channels. Lab Chip 4:425–430
Vijayasai AP et al (2010) Haptic controlled three-axis MEMS gripper system. Rev Sci Instrum 81:105114
Tang Y et al (2014) Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells. Sci Rep. https://doi.org/10.1038/srep06052
Di Carlo D, Aghdam N, Lee LP (2006) Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays. Anal Chem 78:4925–4930
Kim H, Lee S, Lee JH, Kim J (2015) Integration of a microfluidic chip with a size-based cell bandpass filter for reliable isolation of single cells. Lab Chip 15:4128–4132
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 Engl 129:10821–10825
Teh SY, Lin R, Hung LH, Lee AP (2008) Droplet microfluidics. Lab Chip 8:198–220. https://doi.org/10.1039/B715524G
Fu AY, Spence C, Scherer A, Arnold FH, Quake SR (1999) A microfabricated fluorescence-activated cell sorter. Nat Biotechnol 17:1109–1111
Wyss HM, Blair DL, Morris JF, Stone HA, Weitz DA (2006) Mechanism for clogging of microchannels. Phys Rev E Stat Nonlinear Soft Matter Phys 74:1–4
Park J et al (2006) Asymmetric nozzle structure for particles converging into a highly confined region. Curr Appl Phys 6:992–995
Marella SV, Udaykumar HS (2004) Computational analysis of the deformability of leukocytes modeled with viscous and elastic structural components. Phys Fluids 16:244–264
Huh D et al (2002) Use of air-liquid two-phase flow in hydrophobic microfluidic channels for disposable flow cytometers. Biomed Microdevices 4:141–149
Choi S, Song S, Choi C, Park JK (2008) Sheathless focusing of microbeads and blood cells based on hydrophoresis. Small 4:634–641
Sajeesh P, Manasi S, Doble M, Sen AK (2015) A microfluidic device with focusing and spacing control for resistance-based sorting of droplets and cells. Lab Chip 15:3738–3748
Alazzam A, Mathew B, Alhammadi F (2017) Novel microfluidic device for the continuous separation of cancer cells using dielectrophoresis. J Sep Sci 40:1193–1200
Wang L et al (2009) Dual frequency dielectrophoresis with interdigitated sidewall electrodes for microfluidic flow-through separation of beads and cells. Electrophoresis 30:782–791
Wang X et al (2011) Enhanced cell sorting and manipulation with combined optical tweezer and microfluidic chip technologies. Lab Chip 11:3656–3662
Palmer RMJ, Ferrige AG, Moncada S (1987) Optical trapping and manipulation of single cells using infrared laser beam. Nature 327:524–526
Zhang Z, Kimkes TEP, Heinemann M (2019) Manipulating rod-shaped bacteria with optical tweezers. Sci Rep 9:1–9
Chiu TK et al (2016) Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis-cancer cell line model. Sci Rep 6:1–14
Robert D et al (2011) Cell sorting by endocytotic capacity in a microfluidic magnetophoresis device. Lab Chip 11:1902–1910
Shen F, Hwang H, Hahn YK, Park JK (2012) Label-free cell separation using a tunable magnetophoretic repulsion force. Anal Chem 84:3075–3081
Rodríguez-Villarreal AI et al (2011) Flow focussing of particles and cells based on their intrinsic properties using a simple diamagnetic repulsion setup. Lab Chip 11:1240–1248
Zeng J, Chen C, Vedantam P, Tzeng TR, Xuan X (2013) Magnetic concentration of particles and cells in ferrofluid flow through a straight microchannel using attracting magnets. Microfluid Nanofluid 15:49–55
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Satpathi, N.S. et al. (2022). Applications of Microfluidics. In: Mohanan, P.V. (eds) Microfluidics and Multi Organs on Chip . Springer, Singapore. https://doi.org/10.1007/978-981-19-1379-2_2
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