Abstract
Microfluidics is modifying the way modern biology is performed. Microfluidic (MF) devices are being used for everything from accelerating molecular biology reactions to platforms for cell growth and analysis. The beauty lies in the precise control of quantities and rate of flow of samples and reagents that enables the separation and detection of analytes with high accuracy and sensitivity. This chapter will explore the practical applications of MF in different fields of biology. Further, lab on chip technologies employed for mutiple and single cell analysis, drug delivery systems, synthetic biology, stem cell research and various other areas will be discussed. The present scenario of commercialization of MF devices and new opportunities in the respective field will also be mentioned.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Mark D, Haeberle S, Roth G, von Stetten F, Zengerle R (2010) Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications. Chem Soc Rev 39(3):1153–1182
Valones MAA, Guimarães RL, Brandão LAC, de Souza PRE, de Albuquerque Tavares Carvalho A, Crovela S (2009) Principles and applications of polymerase chain reaction in medical diagnostic fields: a review. Braz J Microbiol 40(1):1–11
Barbulovic-Nad I, Yang H, Park PS, Wheeler AR (2008) Digital microfluidics for cell-based assays. Lab Chip 8(4):519–526
Manz A, Miyahara Y, Miura J, Watanabe Y, Miyagi H, Sato K (1990) Design of an open-tubular column liquid chromatograph using silicon chip technology. Sens Actuators B Chem 1(1):249–255
Aa M, Graber N, Widmer HÃM (1990) Miniaturized total chemical analysis systems: a novel concept for chemical sensing. Sens Actuators B Chem 1(1):244–248
Mehling M, Tay S (2014) Microfluidic cell culture. Curr Opin Biotechnol 25:95–102
Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32(8):760–772
Fernandes TG, Diogo MM, Clark DS, Dordick JS, Cabral JMS (2009) High-throughput cellular microarray platforms: applications in drug discovery, toxicology and stem cell research. Trends Biotechnol 27(6):342–349
Griffith LG, Naughton G (2002) Tissue engineering—current challenges and expanding opportunities. Science 295(5557):1009–1014
Gupta K, Kim D-H, Ellison D, Smith C, Kundu A, Tuan J, Suh K-Y, Levchenko A (2010) Lab-on-a-chip devices as an emerging platform for stem cell biology. Lab Chip 10(16):2019–2031
Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW (2015) Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161(5):1187–1201
Jung H, Chun M-S, Chang M-S (2015) Sorting of human mesenchymal stem cells by applying optimally designed microfluidic chip filtration. Analyst 140(4):1265–1274
Kang W, Giraldo-Vela JP, Nathamgari SSP, McGuire T, McNaughton RL, Kessler JA, Espinosa HD (2014) Microfluidic device for stem cell differentiation and localized electroporation of postmitotic neurons. Lab Chip 14(23):4486–4495
Reitinger S, Jr W, Kapferer W, Heer R, Gn L (2012) Electric impedance sensing in cell-substrates for rapid and selective multipotential differentiation capacity monitoring of human mesenchymal stem cells. Biosens Bioelectron 34(1):63–69
Gross PG, Kartalov EP, Scherer A, Weiner LP (2007) Applications of microfluidics for neuronal studies. J Neurol Sci 252(2):135–143
Farinas J, Chow AW, Wada HG (2001) A microfluidic device for measuring cellular membrane potential. Anal Biochem 295(2):138–142
Grant SC, Aiken NR, Plant HD, Gibbs S, Mareci TH, Webb AG, Blackband SJ (2000) NMR spectroscopy of single neurons. Magn Reson Med 44(1):19–22
Massin C, Vincent F, Homsy A, Ehrmann K, Boero G, Besse PA, Daridon A, Verpoorte E, De Rooij NF, Popovic RS (2003) Planar microcoil-based microfluidic NMR probes. J Magn Reson 164(2):242–255
Huang Y, Williams JC, Johnson SM (2012) Brain slice on a chip: opportunities and challenges of applying microfluidic technology to intact tissues. Lab Chip 12(12):2103–2117
Scott A, Weir K, Easton C, Huynh W, Moody WJ, Folch A (2013) A microfluidic microelectrode array for simultaneous electrophysiology, chemical stimulation, and imaging of brain slices. Lab Chip 13(4):527–535
Mauleon G, Fall CP, Eddington DT (2012) Precise spatial and temporal control of oxygen within in vitro brain slices via microfluidic Gas channels. PLoS One 7(8):e43309
Kang L, Chung BG, Langer R, Khademhosseini A (2008) Microfluidics for drug discovery and development: from target selection to product lifecycle management. Drug Discov Today 13(1):1–13
Psaltis D, Quake SR, Yang C (2006) Developing optofluidic technology through the fusion of microfluidics and optics. Nature 442(7101):381–386
Caviglia C, Zór K, Montini L, Tilli V, Canepa S, Melander F, Muhammad HB, Carminati M, Ferrari G, Raiteri R (2015) Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs. Anal Chem 87(4):2204–2212
Sung JH, Kam C, Shuler ML (2010) A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 10(4):446–455
Sakolish CM, Esch MB, Hickman JJ, Shuler ML, Mahler GJ (2016) Modeling barrier tissues in vitro: methods, achievements, and challenges. EBioMedicine 5:30–39
Huh D, Hamilton GA, Ingber DE (2011) From three-dimensional cell culture to organs-on-chips. Trends Cell Biol 21(12):745–754
Huh D, Kim HJ, Fraser JP, Shea DE, Khan M, Bahinski A, Hamilton GA, Ingber DE (2013) Microfabrication of human organs-on-chips. Nat Protoc 8(11):2135–2157
Jang K-J, Suh K-Y (2010) A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip 10(1):36–42
Douville NJ, Zamankhan P, Tung Y-C, Li R, Vaughan BL, Tai C-F, White J, Christensen PJ, Grotberg JB, Takayama S (2011) Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model. Lab Chip 11(4):609–619
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328(5986):1662–1668
Booth R, Kim H (2012) Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB). Lab Chip 12(10):1784–1792
Nakao Y, Kimura H, Sakai Y, Fujii T (2011) Bile canaliculi formation by aligning rat primary hepatocytes in a microfluidic device. Biomicrofluidics 5(2):022212
Kim HJ, Huh D, Hamilton G, Ingber DE (2012) Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12(12):2165–2174
Lee PJ, Hung PJ, Lee LP (2007) An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng 97(5):1340–1346
Jiang B, Zheng W, Zhang W, Jiang X (2013) Organs on microfluidic chips: a mini review. Sci China Chem 57(3):356–364
Maschmeyer I, Lorenz AK, Schimek K, Hasenberg T, Ramme AP, Hübner J, Lindner M, Drewell C, Bauer S, Thomas A (2015) A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15(12):2688–2699
Huh D, Y-s T, Hamilton GA, Kim HJ, Ingber DE (2012) Microengineered physiological biomimicry: organs-on-chips. Lab Chip 12(12):2156–2164
Esch MB, King TL, Shuler ML (2011) The role of body-on-a-chip devices in drug and toxicity studies. Annu Rev Biomed Eng 13:55–72
Sung JH, Srinivasan B, Esch MB, McLamb WT, Bernabini C, Shuler ML, Hickman JJ (2014) Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure. Exp Biol Med 239(9):1225–1239
Esch MB, Mahler GJ, Stokol T, Shuler ML (2014) Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip 14(16):3081–3092
Prot JM, Maciel L, Bricks T, Merlier F, Cotton J, Paullier P, Bois FY, Leclerc E (2014) First pass intestinal and liver metabolism of paracetamol in a microfluidic platform coupled with a mathematical modeling as a means of evaluating ADME processes in humans. Biotechnol Bioeng 111(10):2027–2040
Kim J-Y, Fluri DA, Kelm JM, Hierlemann A, Frey O (2015) 96-well format-based microfluidic platform for parallel interconnection of multiple multicellular spheroids. J Lab Autom 20(3):274–282
Kim J-Y, Fluri DA, Marchan R, Boonen K, Mohanty S, Singh P, Hammad S, Landuyt B, Hengstler JG, Kelm JM, Hierlemann A, Frey O (2015) 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis. J Biotechnol 205:24–35
Huh D, Hamilton GA, Ingber DE (2011) From 3D cell culture to organs-on-chips. Tren Cell Biol 21(12):745–754
Agarwal A, Goss JA, Cho A, McCain ML, Parker KK (2013) Microfluidic heart on a chip for higher throughput pharmacological studies. Lab Chip 13(18):3599–3608
Lee SA, da No Y, Kang E, Ju J, Kim DS, Lee SH (2013) Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects. Lab Chip 13(18):3529–3537
Jang K-J, Mehr AP, Hamilton GA, McPartlin LA, Chung S, Suh K-Y, Ingber DE (2013) Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol 5(9):1119–1129
Griep LM, Wolbers F, De Wagenaar B, Ter Braak PM, Weksler BB, Romero IA, Couraud PO, Vermes I, Van Der Meer AD, Van den Berg A (2013) BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed Microdevices 15(1):145–150
Shen F, Li X, Li PCH (2014) Study of flow behaviors on single-cell manipulation and shear stress reduction in microfluidic chips using computational fluid dynamics simulations. Biomicrofluidics 8(1):014109. doi:10.1063/1.4866358
Raj A, van Oudenaarden A (2008) Stochastic gene expression and its consequences. Cell 135(2):216–226
Singh A (2014) Transient changes in intercellular protein variability identify sources of noise in gene expression. Biophys J 107(9):2214–2220
Yin H, Marshall D (2012) Microfluidics for single cell analysis. Curr Opin Biotechnol 23(1):110–119
Poulsen CR, Culbertson CT, Jacobson SC, Ramsey JM (2005) Static and dynamic acute cytotoxicity assays on microfluidic devices. Anal Chem 77(2):667–672
Balagaddé FK, You L, Hansen CL, Arnold FH, Quake SR (2005) Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 309(5731):137–140
He M, Edgar JS, Jeffries GDM, Lorenz RM, Shelby JP, Chiu DT (2005) Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets. Anal Chem 77(6):1539–1544
Chiou PY, Ohta AT, Wu MC (2005) Massively parallel manipulation of single cells and microparticles using optical images. Nature 436(7049):370–372
Taff BM, Voldman J (2005) A scalable addressable positive-dielectrophoretic cell-sorting array. Anal Chem 77(24):7976–7983
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(14):4925–4930
Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH, Farrell K, Manger ID, Daridon A (2003) Microfluidic device for single-cell analysis. Anal Chem 75(14):3581–3586
Peng XY (2011) A micro surface tension pump (MISPU) in a glass microchip. Lab Chip 11(1):132–138
Roman GT, Chen Y, Viberg P, Culbertson AH, Culbertson CT (2006) Single-cell manipulation and analysis using microfluidic devices. Anal Bioanal Chem 387(1):9–12
Riordon J, Nash M, Jing W, Godin M (2014) Quantifying the volume of single cells continuously using a microfluidic pressure-driven trap with media exchange. Biomicrofluidics 8(1):011101
McClain MA, Culbertson CT, Jacobson SC, Allbritton NL, Sims CE, Ramsey JM (2003) Microfluidic devices for the high-throughput chemical analysis of cells. Anal Chem 75(21):5646–5655
Clausell-Tormos J, Lieber D, Baret J-C, El-Harrak A, Miller OJ, Frenz L, Blouwolff J, Humphry KJ, Köster S, Duan H, Holtze C, Weitz DA, Griffiths AD, Merten CA (2008) Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms. Chem Biol 15(5):427–437
Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Wang X, Bodeau J, Tuch BB, Siddiqui A (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 6(5):377–382
Wu J, Kodzius R, Cao W, Wen W (2014) Extraction, amplification and detection of DNA in microfluidic chip-based assays. Microchim Acta 181(13–14):1611–1631
Yager P, Edwards T, Fu E, Helton K, Nelson K, Tam MR, Weigl BH (2006) Microfluidic diagnostic technologies for global public health. Nature 442(7101):412–418
Hu S, Loo JA, Wong DT (2006) Human body fluid proteome analysis. Proteomics 6(23):6326–6353
Martinez AW, Phillips ST, Whitesides GM, Carrilho E (2009) Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal Chem 82(1):3–10
Martinez AW, Phillips ST, Butte MJ, Whitesides GM (2007) Patterned paper as a platform for inexpensive, low volume, portable bioassays. Angew Chem Int Ed 46(8):1318–1320
Rosenfeld T, Bercovici M (2014) 1000-fold sample focusing on paper-based microfluidic devices. Lab Chip 14(23):4465–4474
Foudeh AM, Fatanat Didar T, Veres T, Tabrizian M (2012) Microfluidic designs and techniques using lab-on-a-chip devices for pathogen detection for point-of-care diagnostics. Lab Chip 12(18):3249–3266
Ghrera AS, Pandey CM, Ali MA, Malhotra BD (2015) Quantum dot-based microfluidic biosensor for cancer detection. Appl Phys Lett 106(19):193703
Dimov IK, Garcia-Cordero JL, O’Grady J, Poulsen CR, Viguier C, Kent L, Daly P, Lincoln B, Maher M, O’Kennedy R (2008) Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics. Lab Chip 8(12):2071–2078
Chang W-H, Wang C-H, Lin C-L, Wu J-J, Lee MS, Lee G-B (2015) Rapid detection and typing of live bacteria from human joint fluid samples by utilizing an integrated microfluidic system. Biosens Bioelectron 66:148–154
Lee W, Kwon D, Choi W, Jung GY, Jeon S (2015) 3D-printed microfluidic device for the detection of pathogenic bacteria using size-based separation in helical channel with trapezoid cross-section. Sci Rep 5:7717
Boehm DA, Gottlieb PA, Hua SZ (2007) On-chip microfluidic biosensor for bacterial detection and identification. Sens Actuators B Chem 126(2):508–514
Cho Y-K, Lee J-G, Park J-M, Lee B-S, Lee Y, Ko C (2007) One-step pathogen specific DNA extraction from whole blood on a centrifugal microfluidic device. Lab Chip 7(5):565–573
Manini TM, Vincent KR, Leeuwenburgh CL, Lees HA, Kavazis AN, Borst SE, Clark BC (2011) Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Acta Physiol (Oxf) 201(2):255–263
Chin CD, Linder V, Sia SK (2012) Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip 12(12):2118–2134
Gervais L, De Rooij N, Delamarche E (2011) Microfluidic chips for point-of-care immunodiagnostics. Adv Mater 23(24):H151–H176
Kim M, Choi J-C, Jung H-R, Katz JS, Kim M-G, Doh J (2010) Addressable micropatterning of multiple proteins and cells by microscope projection photolithography based on a protein friendly photoresist. Langmuir 26(14):12112–12118
B-H C, Huh D, Kyrtsos CR, Houssin T, Futai N, Takayama S (2007) Leakage-free bonding of porous membranes into layered microfluidic array systems. Anal Chem 79(9):3504–3508
Legendre LA, Morris CJ, Bienvenue JM, Barron A, McClure R, Landers JP (2008) Toward a simplified microfluidic device for ultra-fast genetic analysis with sample-in/answer-out capability: application to T-cell lymphoma diagnosis. J Lab Autom 13(6):351–360
Diercks AH, Ozinsky A, Hansen CL, Spotts JM, Rodriguez DJ, Aderem A (2009) A microfluidic device for multiplexed protein detection in nano-liter volumes. Anal Biochem 386(1):30–35
Global Point-of-Care Diagnostics Market Outlook (2018) http://www.rncos.com
Blow N (2007) Microfluidics: in search of a killer application. Nat Methods 4(8):665–672
Sia SK, Whitesides GM (2003) Microfluidic devices fabricated in poly (dimethylsiloxane) for biological studies. Electrophoresis 24(21):3563–3576
Acknowledgements
SS and CMP thank Prof. B. D. Malhotra (DTU, Delhi) and Dr. G. Sumana (NPL, New Delhi) for interesting discussions. Shipra Solanki is thankful to UGC, India, for the award of SRF. C. M. Pandey acknowledges the Department of Science & Technology, Govt of India for awarding the DST-INSPIRE Fellowship [DST/INSPIRE/04/2015/000932].
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Solanki, S., Pandey, C.M. (2016). Biological Applications of Microfluidics System. In: Dixit, C., Kaushik, A. (eds) Microfluidics for Biologists. Springer, Cham. https://doi.org/10.1007/978-3-319-40036-5_8
Download citation
DOI: https://doi.org/10.1007/978-3-319-40036-5_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-40035-8
Online ISBN: 978-3-319-40036-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)