Abstract
Stem cell fate is directed by a complex chemical and mechanical microenvironment composed of secreted factors, extracellular matrix, and direct interactions with other cells. These signals ultimately control stem cell renewal and lineage fate in a developmental context. It may be possible to dissect the role of specific signaling pathways by precise control of microenvironment. However, traditional flask cell culture methods are unable to control microenvironment at microscale. Microfluidic platforms have the potential of mimicking the signals that direct stem cell fate by precise control of the chemical and mechanical milieu of cells at microscale. Furthermore, so called “lab-on-a-chip” technologies can increase research throughput by cost-effect automation of multiple parallel microscale cultures. This chapter will reveal how microfluidics and lab-on-a-chip technologies can be applied to the study of stem cell dynamics.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Csete M (2010) Q&A: what can microfluidics do for stem-cell research? J Biol 9(1):1
Schroeder T (2008) Imaging stem-cell-driven regeneration in mammals. Nature 453(7193):345–351. doi:10.1038/nature07043
Sia SK, Whitesides GM (2003) Microfluidic devices fabricated in poly(dimethylsiloxane) for biological studies. Electrophoresis 24(21):3563–3576. doi:10.1002/elps.200305584
Lin B, Basuray S (2011) Microfluidics: technologies and applications. Springer, Heidelberg
Lecault V, VanInsberghe M, Sekulovic S, Knapp D, Wohrer S, Bowden W, Viel F, McLaughlin T, Jarandehei A, Miller M, Falconnet D, White AK, Kent DG, Copley MR, Taghipour F, Eaves CJ, Humphries RK, Piret JM, Hansen CL (2011) High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays. Nat Methods 8(7):581–586. doi:10.1038/nmeth.1614
Kim L, Toh YC, Voldman J, Yu H (2007) A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab Chip 7(6):681–694. doi:10.1039/b704602b
Harrison DJ, Glavina PG, Manz A (1993) Towards miniaturized electrophoresis and chemical analysis systems on silicon: an alternative to chemical sensors. Sens Actuators B Chem 10(2):107–116. doi:10.1016/0925-4005(93)80033-8
Harrison DJ, Manz A, Fan Z, Luedi H, Widmer HM (1992) Capillary electrophoresis and sample injection systems integrated on a planar glass chip. Anal Chem 64(17):1926–1932. doi:10.1021/ac00041a030
Harrison DJ, Fluri K, Seiler K, Fan Z, Effenhauser CS, Manz A (1993) Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science 261(5123):895–897
Nguyen N-T (2006) Fundamentals and applications of microfluidics. Artech House, Boston
Effenhauser CS, Bruin GJM, Paulus A, Ehrat M (1997) Integrated capillary electrophoresis on flexible silicone microdevices: analysis of DNA restriction fragments and detection of single DNA molecules on microchips. Anal Chem 69(17):3451–3457. doi:10.1021/ac9703919
Duffy DC, McDonald JC, Schueller OJA, Whitesides GM (1998) Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal Chem 70(23):4974–4984
Goral VN, Hsieh YC, Petzold ON, Faris RA, Yuen PK (2011) Hot embossing of plastic microfluidic devices using poly(dimethylsiloxane) molds. J Micromech Microeng 21(1). doi:01700210.1088/0960-1317/21/1/017002
Young EWK, Berthier E, Guckenberger DJ, Sackmann E, Lamers C, Meyvantsson I, Huttenocher A, Beebe DJ (2011) Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays. Anal Chem 83(4):1408–1417. doi:10.1021/ac102897h
Chen CS, Breslauer DN, Luna JI, Grimes A, Chin WC, Leeb LP, Khine M (2008) Shrinky-dink microfluidics: 3D polystyrene chips. Lab Chip 8(4):622–624. doi:10.1039/b719029h
Zhang W, Lin S, Wang C, Hu J, Li C, Zhuang Z, Zhou Y, Mathies RA, Yang CJ (2009) PMMA/PDMS valves and pumps for disposable microfluidics. Lab Chip 9(21):3088–3094
Kuo JS, Ng L, Yen GS, Lorenz RM, Schiro PG, Edgar JS, Zhao Y, Lim DSW, Allen PB, Jeffries GDM, Chiu DT (2009) A new USP class VI-compliant substrate for manufacturing disposable microfluidic devices. Lab Chip 9(7):870–876
Kuo JS, Zhao Y, Ng L, Yen GS, Lorenz RM, Lim DSW, Chiu DT (2009) Microfabricating high-aspect-ratio structures in polyurethane-methacrylate (PUMA) disposable microfluidic devices. Lab Chip 9(13):1951–1956
Sikanen T, Aura S, Heikkilä L, Kotiaho T, Franssila S, Kostiainen R (2010) Hybrid ceramic polymers: new, nonbiofouling, and optically transparent materials for microfluidics. Anal Chem 82(9):3874–3882. doi:10.1021/ac1004053
Kuo JS, Chiu DT (2011) Disposable microfluidic substrates: transitioning from the research laboratory into the clinic. Lab Chip 11(16):2656–2665. doi:10.1039/c1lc20125e
Park J, Lee D, Kim W, Horiike S, Nishimoto T, Lee SH, Ahn CH (2007) Fully packed capillary electrochromatographic microchip with self-assembly colloidal silica beads. Anal Chem 79(8):3214–3219. doi:10.1021/ac061714g
Do J, Ahn CH (2008) A polymer lab-on-a-chip for magnetic immunoassay with on-chip sampling and detection capabilities. Lab Chip 8(4):542–549
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. doi:10.1021/ac9013989
Robert P (2009) Bioactive paper provides a low-cost platform for diagnostics. Trends Analyt Chem 28(8):925–942. doi:10.1016/j.trac.2009.05.005
Niklaus F, Stemme G, Lu JQ, Gutmann RJ (2006) Adhesive wafer bonding. J Appl Phys 99(3). doi:10.1063/1.2168512
Ko JS, Yoon HC, Yang HS, Pyo HB, Chung KH, Kim SJ, Kim YT (2003) A polymer-based microfluidic device for immunosensing biochips. Lab Chip 3(2):106–113. doi:10.1039/b301794j
McDonald JC, Whitesides GM (2002) Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc Chem Res 35(7):491–499. doi:10.1021/ar010110q
Khademhosseini A, Yeh J, Eng G, Karp J, Kaji H, Borenstein J, Farokhzad OC, Langer R (2005) Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays. Lab Chip 5(12):1380–1386. doi:10.1039/b508096g
McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu HK, Schueller OJA, Whitesides GM (2000) Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21(1):27–40
Eddings MA, Johnson MA, Gale BK (2008) Determining the optimal PDMS-PDMS bonding technique for microfluidic devices. J Micromech Microeng 18(6). doi:10.1088/0960-1317/18/6/067001
Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288(5463):113–116
Hillborg H, Gedde UW (1998) Hydrophobicity recovery of polydimethylsiloxane after exposure to corona discharges. Polymer 39(10):1991–1998. doi:10.1016/s0032-3861(97)00484-9
Hillborg H, Ankner JF, Gedde UW, Smith GD, Yasuda HK, Wikstrom K (2000) Crosslinked polydimethylsiloxane exposed to oxygen plasma studied by neutron reflectometry and other surface specific techniques. Polymer 41(18):6851–6863. doi:10.1016/s0032-3861(00)00039-2
Bodas D, Khan-Malek C (2007) Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment – an SEM investigation. Sens Actuator B Chem 123(1):368–373. doi:10.1016/j.snb.2006.08.037
Haubert K, Drier T, Beebe D (2006) PDMS bonding by means of a portable, low-cost corona system. Lab Chip 6(12):1548–1549. doi:10.1039/b610567j
Eddings MA, Gale BK (2006) A PDMS-based gas permeation pump for on-chip fluid handling in microfluidic devices. J Micromech Microeng 16(11):2396–2402. doi:10.1088/0960-1317/16/11/021
Go JS, Shoji S (2004) A disposable, dead volume-free and leak-free in-plane PDMS microvalve. Sens Actuator A Phys 114(2–3):438–444. doi:10.1016/j.sna.2003.12.028
Samel B, Chowdhury MK, Stemme G (2007) The fabrication of microfluidic structures by means of full-wafer adhesive bonding using a poly(dimethylsiloxane) catalyst. J Micromech Microeng 17(8):1710–1714. doi:10.1088/0960-1317/17/8/038
Im SG, Bong KW, Lee CH, Doyle PS, Gleason KK (2009) A conformal nano-adhesive via initiated chemical vapor deposition for microfluidic devices. Lab Chip 9(3):411–416. doi:10.1039/b812121d
Rezai P, Selvaganapathy PR, Rwohl G (2011) Plasma enhanced bonding of polydimethylsiloxane with parylene and its optimization. J Micromech Microeng 21(6). doi:10.1088/0960-1317/21/6/065024
Tsao CW, DeVoe DL (2009) Bonding of thermoplastic polymer microfluidics. Microfluid Nanofluid 6(1):1–16. doi:10.1007/s10404-008-0361-x
Thorsen T, Maerkl SJ, Quake SR (2002) Microfluidic large-scale integration. Science 298(5593):580–584. doi:10.1126/science.1076996
Melin J, Quake SR (2007) Microfluidic large-scale integration: the evolution of design rules for biological automation. Annu Rev Biophys Biomol Struct 36:213–231. doi:10.1146/annurev.biophys.36.040306.132646
Hansen CL, Classen S, Berger JM, Quake SR (2006) A microfluidic device for kinetic optimization of protein crystallization and in situ structure determination. J Am Chem Soc 128(10):3142–3143. doi:10.1021/ja0576637
Hansen CL, Skordalakes E, Berger JM, Quake SR (2002) A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion. Proc Natl Acad Sci USA 99(26):16531–16536
Hansen CL, Sommer MOA, Quake SR (2004) Systematic investigation of protein phase behavior with a microfluidic formulator. Proc Natl Acad Sci USA 101(40):14431–14436. doi:10.1073/pnas.0405847101
Liu J, Hansen C, Quake SR (2003) Solving the “world-to-chip” interface problem with a microfluidic matrix. Anal Chem 75(18):4718–4723. doi:10.1021/ac0346407
Skelley AM, Scherer JR, Aubrey AD, Grover WH, Ivester RHC, Ehrenfreund P, Grunthaner FJ, Bada JL, Mathies RA (2005) Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars. Proc Natl Acad Sci USA 102(4):1041–1046. doi:10.1073/pnas.0406798102
Gu W, Zhu XY, Futai N, Cho BS, Takayama S (2004) Computerized microfluidic cell culture using elastomeric channels and Braille displays. Proc Natl Acad Sci USA 101(45):15861–15866. doi:10.1073/pnas.0404353101
Marcus JS, Anderson WF, Quake SR (2006) Microfluidic single-cell mRNA isolation and analysis. Anal Chem 78(9):3084–3089. doi:10.1021/ac0519460
Ng JMK, Gitlin I, Stroock AD, Whitesides GM (2002) Components for integrated poly(dimethylsiloxane) microfluidic systems. Electrophoresis 23(20):3461–3473
Gomez-Sjoberg R, Leyrat AA, Pirone DM, Chen CS, Quake SR (2007) Versatile, fully automated, microfluidic cell culture system. Anal Chem 79(22):8557–8563. doi:10.1021/ac071311w
Yamahata C, Lacharme F, Gijs MAM (2005) Glass valveless micropump using electromagnetic actuation. Microelectron Eng 78–79:132–137. doi:10.1016/j.mee.2004.12.018
Teymoori MM, Abbaspour-Sani E (2005) Design and simulation of a novel electrostatic peristaltic micromachined pump for drug delivery applications. Sens Actuators A Phys 117(2):222–229. doi:10.1016/j.sna.2004.06.025
Kim J-H, Kang CJ, Kim Y-S (2004) A disposable polydimethylsiloxane-based diffuser micropump actuated by piezoelectric-disc. Microelectron Eng 71(2):119–124. doi:10.1016/j.mee.2003.10.005
Yoo JC, Moon MC, Choi YJ, Kang CJ, Kim YS (2006) A high performance microfluidic system integrated with the micropump and microvalve on the same substrate. Microelectron Eng 83(4–9):1684–1687. doi:10.1016/j.mee.2006.01.202
Xu D, Wang L, Ding G, Zhou Y, Yu A, Cai B (2001) Characteristics and fabrication of NiTi/Si diaphragm micropump. Sens Actuators A Phys 93(1):87–92. doi:10.1016/s0924-4247(01)00628-8
Goedecke N, Eijkel J, Manz A (2002) Evaporation driven pumping for chromatography application. Lab Chip 2(4):219–223
Hosokawa K, Sato K, Ichikawa N, Maeda M (2004) Power-free poly(dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis. Lab Chip 4(3):181–185. doi:10.1039/b403930k
Zhang T, Cui T (2011) High-performance surface-tension-driven capillary pumping based on layer-by-layer self assembly of TiO2 nanoparticles. International Conference on Solid State Sensors and Actuators - TRANSDUCERS. Beijing. 5–9 June 2011. doi:10.1109/TRANSDUCERS.2011.5969775
Kamei KI, Guo SL, Yu ZTF, Takahashi H, Gschweng E, Suh C, Wang XP, Tang JG, McLaughlin J, Witte ON, Lee KB, Tseng HR (2009) An integrated microfluidic culture device for quantitative analysis of human embryonic stem cells. Lab Chip 9(4):555–563. doi:10.1039/b809105f
Liu WM, Li L, Wang XM, Ren L, Wang XQ, Wang JC, Tu Q, Huang XW, Wang JY (2010) An integrated microfluidic system for studying cell-microenvironmental interactions versatilely and dynamically. Lab Chip 10(13):1717–1724. doi:10.1039/c001049a
Falconnet D, Niemisto A, Taylor RJ, Ricicova M, Galitski T, Shmulevich I, Hansen CL (2011) High-throughput tracking of single yeast cells in a microfluidic imaging matrix. Lab Chip 11(3):466–473. doi:10.1039/c0lc00228c
Grover WH, Ivester RHC, Jensen EC, Mathies RA (2006) Development and multiplexed control of latching pneumatic valves using microfluidic logical structures. Lab Chip 6(5):623–631. doi:10.1039/b518362f
Hulme SE, Shevkoplyas SS, Whitesides GM (2009) Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices. Lab Chip 9(1):79–86. doi:10.1039/b809673b
Park W, Han S, Kwon S (2010) Fabrication of membrane-type microvalves in rectangular microfluidic channels via seal photopolymerization. Lab Chip 10(20):2814–2817. doi:10.1039/c005173j
Lai HY, Folch A (2011) Design and dynamic characterization of “single-stroke” peristaltic PDMS micropumps. Lab Chip 11(2):336–342. doi:10.1039/c0lc00023j
Huang CW, Huang SB, Lee GB (2006) Pneumatic micropumps with serially connected actuation chambers. J Micromech Microeng 16(11):2265–2272. doi:10.1088/0960-1317/16/11/003
Skelley AM, Voldman J (2008) An active bubble trap and debubbler for microfluidic systems. Lab Chip 8(10):1733–1737. doi:10.1039/b807037g
Johnson M, Liddiard G, Eddings M, Gale B (2009) Bubble inclusion and removal using PDMS membrane-based gas permeation for applications in pumping, valving and mixing in microfluidic devices. J Micromech Microeng 19(9). doi:09501110.1088/0960-1317/19/9/095011
Zheng WF, Wang Z, Zhang W, Jiang XY (2010) A simple PDMS-based microfluidic channel design that removes bubbles for long-term on-chip culture of mammalian cells. Lab Chip 10(21):2906–2910. doi:10.1039/c005274d
Kang JH, Kim YC, Park JK (2008) Analysis of pressure-driven air bubble elimination in a microfluidic device. Lab Chip 8(1):176–178. doi:10.1039/b712672g
Freeman BD, Pinnau I (1999) Polymeric materials for gas separations. In: Polymer membranes for gas and vapor separation, vol 733, ACS symposium series. American Chemical Society, Washington, pp 1–27. doi:10.1021/bk-1999-0733.ch001
Cheng DM, Jiang HR (2009) A debubbler for microfluidics utilizing air-liquid interfaces. Appl Phys Lett 95(21). doi:21410310.1063/1.3263944
Sung JH, Shuler ML (2009) Prevention of air bubble formation in a microfluidic perfusion cell culture system using a microscale bubble trap. Biomed Microdevices 11(4):731–738. doi:10.1007/s10544-009-9286-8
Kang E, Lee DH, Kim CB, Yoo SJ, Lee SH (2010) A hemispherical microfluidic channel for the trapping and passive dissipation of microbubbles. J Micromech Microeng 20(4). doi:045009 10.1088/0960-1317/20/4/045009
Liu CC, Thompson JA, Bau HH (2011) A membrane-based, high-efficiency, microfluidic debubbler. Lab Chip 11(9):1688–1693. doi:10.1039/c1lc20089e
Raser JM, O’Shea EK (2005) Noise in gene expression: origins, consequences, and control. Science 309(5743):2010–2013. doi:10.1126/science.1105891
Rao CV, Wolf DM, Arkin AP (2002) Control, exploitation and tolerance of intracellular noise. Nature 420(6912):231–237. doi:10.1038/nature01258
Lindstrom S, Andersson-Svahn H (2010) Overview of single-cell analyses: microdevices and applications. Lab Chip 10(24):3363–3372. doi:10.1039/c0lc00150c
Gallego-Perez D, Higuita-Castro N, Sharma S, Reen RK, Palmer AF, Gooch KJ, Lee LJ, Lannutti JJ, Hansford DJ (2010) High throughput assembly of spatially controlled 3D cell clusters on a micro/nanoplatform. Lab Chip 10(6):775–782. doi:10.1039/b919475d
Park JY, Morgan M, Sachs AN, Samorezov J, Teller R, Shen Y, Pienta KJ, Takayama S (2010) Single cell trapping in larger microwells capable of supporting cell spreading and proliferation. Microfluid Nanofluid 8(2):263–268. doi:10.1007/s10404-009-0503-9
Tokilmitsu Y, Kishi H, Kondo S, Honda R, Tajiri K, Motoki K, Ozawa T, Kadowaki S, Obata T, Fujiki S, Tateno C, Takaishi H, Chayama K, Yoshizato K, Tamiya E, Sugiyama T, Muraguchi A (2007) Single lymphocyte analysis with a microwell array chip. Cytometry A 71A(12):1003–1010. doi:10.1002/cyto.a.20478
Deutsch M, Deutsch A, Shirihai O, Hurevich I, Afrimzon E, Shafran Y, Zurgil N (2006) A novel miniature cell retainer for correlative high-content analysis of individual untethered non-adherent cells. Lab Chip 6(8):995–1000. doi:10.1039/b603961h
Liu CS, Liu JJ, Gao D, Ding MY, Lin JM (2010) Fabrication of microwell arrays based on two-dimensional ordered polystyrene microspheres for high-throughput single-cell analysis. Anal Chem 82(22):9418–9424. doi:10.1021/ac102094r
Rosenbluth MJ, Lam WA, Fletcher DA (2006) Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. Biophys J 90(8):2994–3003. doi:10.1529/biophysj.105.067496
Park MC, Hur JY, Cho HS, Park SH, Suh KY (2011) High-throughput single-cell quantification using simple microwell-based cell docking and programmable time-course live-cell imaging. Lab Chip 11(1):79–86. doi:10.1039/c0lc00114g
Lindstrom S, Andersson-Svahn H (2011) Miniaturization of biological assays – overview on microwell devices for single-cell analyses. Biochim Biophys Acta 1810(3):308–316. doi:10.1016/j.bbagen.2010.04.009
Charnley M, Textor M, Khademhosseini A, Lutolf MP (2009) Integration column: microwell arrays for mammalian cell culture. Integr Biol 1(11–12):625–634. doi:10.1039/b918172p
Khademhosseini A, Ferreira L, Blumling J, Yeh J, Karp JM, Fukuda J, Langer R (2006) Co-culture of human embryonic stem cells with murine embryonic fibroblasts on microwell-patterned substrates. Biomaterials 27(36):5968–5977. doi:10.1016/j.biomaterials.2006.06.035
Rettig JR, Folch A (2005) Large-scale single-cell trapping and imaging using microwell arrays. Anal Chem 77(17):5628–5634. doi:10.1021/ac0505977
Chen H, Rosengarten G, Li M, Nordon RE (2012) Design of microdevices for long-term live cell imaging. J Micromech Microeng (in press)
Cioffi M, Moretti M, Manbachi A, Chung BG, Khademhosseini A, Dubini G (2010) A computational and experimental study inside microfluidic systems: the role of shear stress and flow recirculation in cell docking. Biomed Microdevices 12(4):619–626. doi:10.1007/s10544-010-9414-5
Çengel YA, Cimbala JM (2010) Fluid mechanics: fundamentals and applications. McGraw-Hill Higher Education, Boston
Glatzel T, Litterst C, Cupelli C, Lindemann T, Moosmann C, Niekrawletz R, Streule W, Zengerle R, Koltay P (2008) Computational fluid dynamics (CFD) software tools for microfluidic applications – a case study. Comput Fluids 37(3):218–235. doi:10.1016/j.compfluid.2007.07.014
Erickson D (2005) Towards numerical prototyping of labs-on-chip: modeling for integrated microfluidic devices. Microfluid Nanofluid 1(4):301–318. doi:10.1007/s10404-005-0041-z
Wang ZH, Kim MC, Marquez M, Thorsen T (2007) High-density microfluidic arrays for cell cytotoxicity analysis. Lab Chip 7(6):740–745. doi:10.1039/b618734j
Zhang BY, Kim MC, Thorsen T, Wang ZH (2009) A self-contained microfluidic cell culture system. Biomed Microdevices 11(6):1233–1237. doi:10.1007/s10544-009-9342-4
Manbachi A, Shrivastava S, Cioffi M, Chung BG, Moretti M, Demirci U, Yliperttula M, Khademhosseini A (2008) Microcirculation within grooved substrates regulates cell positioning and cell docking inside microfluidic channels. Lab Chip 8(5):747–754. doi:10.1039/b718212k
Khabiry M, Chung BG, Hancock MJ, Soundararajan HC, Du YN, Cropek D, Lee WG, Khademhosseini A (2009) Cell docking in double grooves in a microfluidic channel. Small 5(10):1186–1194. doi:10.1002/smll.200801644
Han C, Zhang QF, Ma R, Xie L, Qiu TA, Wang L, Mitchelson K, Wang JD, Huang GL, Qiao J, Cheng J (2010) Integration of single oocyte trapping, in vitro fertilization and embryo culture in a microwell-structured microfluidic device. Lab Chip 10(21):2848–2854. doi:10.1039/c005296e
Kim MC, Wang ZH, Lam RHW, Thorsen T (2008) Building a better cell trap: applying Lagrangian modeling to the design of microfluidic devices for cell biology. J Appl Phys 103(4). doi:04470110.1063/1.2840059
Jang YH, Kwon CH, Kim SB, Selimovic S, Sim WY, Bae H, Khademhosseini A (2011) Deep wells integrated with microfluidic valves for stable docking and storage of cells. Biotechnol J 6(2):156–164. doi:10.1002/biot.201000394
Yang J, Li CW, Yang MS (2004) Hydrodynamic simulation of cell docking in microfluidic channels with different dam structures. Lab Chip 4(1):53–59. doi:10.1039/b309940g
Hufnagel H, Huebner A, Gulch C, Guse K, Abell C, Hollfelder F (2009) An integrated cell culture lab on a chip: modular microdevices for cultivation of mammalian cells and delivery into microfluidic microdroplets. Lab Chip 9(11):1576–1582. doi:10.1039/b821695a
Liu LY, Loutherback K, Liao D, Yeater D, Lambert G, Estevez-Torres A, Sturm JC, Getzenberg RH, Austin RH (2010) A microfluidic device for continuous cancer cell culture and passage with hydrodynamic forces. Lab Chip 10(14):1807–1813. doi:10.1039/c003509b
Yu ZTF, Kamei KI, Takahashi H, Shu CJ, Wang XP, He GW, Silverman R, Radu CG, Witte ON, Lee KB, Tseng HR (2009) Integrated microfluidic devices for combinatorial cell-based assays. Biomed Microdevices 11(3):547–555. doi:10.1007/s10544-008-9260-x
Leclerc E, Sakai Y, Fujii T (2004) Microfluidic PDMS (polydimethylsiloxane) bioreactor for large-scale culture of hepatocytes. Biotechnol Prog 20(3):750–755. doi:10.1021/bp0300568
Wang L, Ni XF, Luo CX, Zhang ZL, Pang DW, Chen Y (2009) Self-loading and cell culture in one layer microfluidic devices. Biomed Microdevices 11(3):679–684. doi:10.1007/s10544-008-9278-0
Hung PJ, Lee PJ, Sabounchi P, Lin R, Lee LP (2005) Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnol Bioeng 89(1):1–8. doi:10.1002/bit.20289
Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A, Upadhyaya A, Kurzawski P, Wack KE, Stolz DB, Kamm R, Griffith LG (2002) A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 78(3):257–269. doi:10.1002/bit.10143
Chin VI, Taupin P, Sanga S, Scheel J, Gage FH, Bhatia SN (2004) Microfabricated platform for studying stem cell fates. Biotechnol Bioeng 88(3):399–415
Wu MH, Huang SB, Cui ZF, Cui Z, Lee GB (2008) A high throughput perfusion-based microbioreactor platform integrated with pneumatic micropumps for three-dimensional cell culture. Biomed Microdevices 10(2):309–319. doi:10.1007/s10544-007-9138-3
Shah P, Vedarethinam I, Kwasny D, Andresen L, Dimaki M, Skov S, Svendsen WE (2011) Microfluidic bioreactors for culture of non-adherent cells. Sens Actuator B Chem 156(2):1002–1008. doi:10.1016/j.snb.2011.02.021
Rodrigues CAV, Fernandes TG, Diogo MM, da Silva CL, Cabral JMS (2011) Stem cell cultivation in bioreactors. Biotechnol Adv 29(6):815–829. doi:10.1016/j.biotechadv.2011.06.009
Wu HW, Lin CC, Lee GB (2011) Stem cells in microfluidics. Biomicrofluidics 5(1). doi:10.1063/1.3528299
Zervantonakis IK, Kothapalli CR, Chung S, Sudo R, Kamm RD (2011) Microfluidic devices for studying heterotypic cell-cell interactions and tissue specimen cultures under controlled microenvironments. Biomicrofluidics 5(1). doi:01340610.1063/1.3553237
Paguirigan AL, Beebe DJ (2009) From the cellular perspective: exploring differences in the cellular baseline in macroscale and microfluidic cultures. Integr Biol 1(2):182–195. doi:10.1039/b814565b
Lee JN, Park C, Whitesides GM (2003) Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. Anal Chem 75(23):6544–6554. doi:10.1021/ac0346712
Eddington DT, Puccinelli JP, Beebe DJ (2006) Thermal aging and reduced hydrophobic recovery of polydimethylsiloxane. Sens Actuator B Chem 114(1):170–172. doi:10.1016/j.snb.2005.04.037
Hillborg H, Gedde UW (1999) Hydrophobicity changes in silicone rubbers. IEEE Trans Dielectr Electr Insul 6(5):703–717. doi:10.1109/94.798127
Regehr KJ, Domenech M, Koepsel JT, Carver KC, Ellison-Zelski SJ, Murphy WL, Schuler LA, Alarid ET, Beebe DJ (2009) Biological implications of polydimethylsiloxane-based microfluidic cell culture. Lab Chip 9(15):2132–2139. doi:10.1039/b903043c
Wlodkowic D, Faley S, Skommer J, McGuinness D, Cooper JM (2009) Biological implications of polymeric microdevices for live cell assays. Anal Chem 81(23):9828–9833. doi:10.1021/ac902010s
Chen H, Li J, Zhang H, Li M, Rosengarten G, Nordon RE (2011) Microwell perfusion array for high-throughput, long-term imaging of clonal growth. Biomicrofluidics 5(4):044117–044113
Ostuni E, Chen CS, Ingber DE, Whitesides GM (2001) Selective deposition of proteins and cells in arrays of microwells. Langmuir 17(9):2828–2834. doi:10.1021/la001372o
Abate AR, Lee D, Do T, Holtze C, Weitz DA (2008) Glass coating for PDMS microfluidic channels by sol–gel methods. Lab Chip 8(4):516–518
Roman GT, Hlaus T, Bass KJ, Seelhammer TG, Culbertson CT (2005) Sol–gel modified poly(dimethylsiloxane) microfluidic devices with high electroosmotic mobilities and hydrophilic channel wall characteristics. Anal Chem 77(5):1414–1422. doi:10.1021/ac048811z
Hu S, Ren X, Bachman M, Sims CE, Li GP, Allbritton NL (2004) Surface-directed, graft polymerization within microfluidic channels. Anal Chem 76(7):1865–1870. doi:10.1021/ac049937z
Sasaki H, Onoe H, Osaki T, Kawano R, Takeuchi S (2010) Parylene-coating in PDMS microfluidic channels prevents the absorption of fluorescent dyes. Sens Actuators B Chem 150(1):478–482
Wang Y, Balowski J, Phillips C, Phillips R, Sims CE, Allbritton NL (2011) Benchtop micromolding of polystyrene by soft lithography. Lab Chip 11(18):3089–3097
Price NM, Harrison PJ, Landry MR, Azam F, Hall KJF (1986) Toxic effects of latex and tygon tubing on marine-phytoplankton, zooplankton and bacteria. Mar Ecol Prog Ser 34(1–2):41–49. doi:10.3354/meps034041
Park H, Berzin I, De Luis J, Vunjak-Novakovic G (2005) Evaluation of silicone tubing toxicity using tobacco BY2 culture. Vitro Cell Dev Biol Plant 41(4):555–560. doi:10.1079/ivp2005670
Chau LT, Rolfe BE, Cooper-White JJ (2011) A microdevice for the creation of patent, three-dimensional endothelial cell-based microcirculatory networks. Biomicrofluidics 5(3). doi:10.1063/1.3609264
Tourovskaia A, Figueroa-Masot X, Folch A (2005) Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies. Lab Chip 5(1):14–19. doi:10.1039/b405719h
Villa M, Pope S, Conover J, Fan TH (2010) Growth of primary embryo cells in a microculture system. Biomed Microdevices 12(2):253–261. doi:10.1007/s10544-009-9380-y
Titmarsh D, Hidalgo A, Turner J, Wolvetang E, Cooper-White J (2011) Optimization of flowrate for expansion of human embryonic stem cells in perfusion microbioreactors. Biotechnol Bioeng 108(12):2894–2904. doi:10.1002/bit.23260
Moledina F, Clarke G, Oskooei A, Onishi K, Gunther A, Zandstra PW (2012) Predictive microfluidic control of regulatory ligand trajectories in individual pluripotent cells. Proc Natl Acad Sci USA 109(9):3264–3269. doi:10.1073/pnas.1111478109
Ellison D, Munden A, Levchenko A (2009) Computational model and microfluidic platform for the investigation of paracrine and autocrine signaling in mouse embryonic stem cells. Mol Biosyst 5(9):1004–1012
Chen H, Li J, Zhang H, Li M, Rosengarten G, Nordon RE (2011) Microwell perfusion array for high-throughput, long-term imaging of clonal growth. Biomicrofluidics 5. doi:10.1063/1.3669371
Young EWK, Beebe DJ (2010) Fundamentals of microfluidic cell culture in controlled microenvironments. Chem Soc Rev 39(3):1036–1048. doi:10.1039/b909900j
Masand SN, Mignone L, Zahn JD, Shreiber DI (2011) Nanoporous membrane-sealed microfluidic devices for improved cell viability. Biomed Microdevices 13(6):955–961. doi:10.1007/s10544-011-9565-z
Bose N, Das T, Chakraborty D, Maiti TK, Chakraborty S (2012) Enhancement of static incubation time in microfluidic cell culture platforms exploiting extended air-liquid interface. Lab Chip 12(1):69–73. doi:10.1039/c1lc20888h
Ziolkowska K, Kwapiszewski R, Brzozka Z (2011) Microfluidic devices as tools for mimicking the in vivo environment. New J Chem 35(5):979–990. doi:10.1039/c0nj00709a
Frampton JP, Lai D, Sriram H, Takayama S (2011) Precisely targeted delivery of cells and biomolecules within microchannels using aqueous two-phase systems. Biomed Microdevices 13(6):1043–1051. doi:10.1007/s10544-011-9574-y
Chung BG, Lin F, Jeon NL (2006) A microfluidic multi-injector for gradient generation. Lab Chip 6(6):764–768
Meyvantsson I, Beebe DJ (2008) Cell culture models in microfluidic systems. Annu Rev Anal Chem 1:423–449. doi:10.1146/annurev.anchem.1.031207.113042
Gupta K, Kim DH, Ellison D, Smith C, Kundu A, Tuan J, Suh KY, Levchenko A (2010) Lab-on-a-chip devices as an emerging platform for stem cell biology. Lab Chip 10(16):2019–2031. doi:10.1039/c004689b
Lii J, Hsu WJ, Parsa H, Das A, Rouse R, Sia SK (2008) Real-time microfluidic system for studying mammalian cells in 3D microenvironments. Anal Chem 80(10):3640–3647. doi:10.1021/ac8000034
Gunther A, Yasotharan S, Vagaon A, Lochovsky C, Pinto S, Yang JL, Lau C, Voigtlaender-Bolz J, Bolz SS (2010) A microfluidic platform for probing small artery structure and function. Lab Chip 10(18):2341–2349. doi:10.1039/C004675b
Blake AJ, Pearce TM, Rao NS, Johnson SM, Williams JC (2007) Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment. Lab Chip 7(7):842–849. doi:10.1039/b704754a
Kastrup CJ, Runyon MK, Lucchetta EM, Price JM, Ismagilov RF (2008) Using chemistry and microfluidics to understand the spatial dynamics of complex biological networks. Acc Chem Res 41(4):549–558. doi:10.1021/ar700174g
Lutolf MP, Gilbert PM, Blau HM (2009) Designing materials to direct stem-cell fate. Nature 462(7272):433–441. doi:10.1038/nature08602
Pek YS, Wan ACA, Ying JY (2010) The effect of matrix stiffness on mesenchymal stem cell differentiation in a 3D thixotropic gel. Biomaterials 31(3):385–391. doi:10.1016/j.biomaterials.2009.09.057
Park JY, Yoo SJ, Hwang CM, Lee SH (2009) Simultaneous generation of chemical concentration and mechanical shear stress gradients using microfluidic osmotic flow comparable to interstitial flow. Lab Chip 9(15):2194–2202. doi:10.1039/b822006a
Yamamoto K, Sokabe T, Watabe T, Miyazono K, Yamashita JK, Obi S, Ohura N, Matsushita A, Kamiya A, Ando J (2005) Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. Am J Physiol Heart Circ Physiol 288(4):H1915–H1924. doi:10.1152/ajpheart.00956.2004
Moraes C, Sun Y, Simmons CA (2011) (Micro)managing the mechanical microenvironment. Integr Biol 3(10):959–971. doi:10.1039/c1ib00056j
Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75(3):519–560
Gilbert PM, Havenstrite KL, Magnusson KEG, Sacco A, Leonardi NA, Kraft P, Nguyen NK, Thrun S, Lutolf MP, Blau HM (2010) Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science 329(5995):1078–1081. doi:10.1126/science.1191035
Park JY, Yoo SJ, Lee EJ, Lee DH, Kim JY, Lee SH (2010) Increased poly(dimethylsiloxane) stiffness improves viability and morphology of mouse fibroblast cells. BioChip J 4(3):230–236. doi:10.1007/s13206-010-4311-9
Adamo L, Naveiras O, Wenzel PL, McKinney-Freeman S, Mack PJ, Gracia-Sancho J, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, Garcia-Cardena G, Daley GQ (2009) Biomechanical forces promote embryonic haematopoiesis. Nature 459(7250):1131–1135. doi:10.1038/nature08073
Kim S, Kim HJ, Jeon NL (2010) Biological applications of microfluidic gradient devices. Integr Biol 2(11–12):584–603. doi:10.1039/c0ib00055h
Boyden S (1962) Chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med 115(3):453. doi:10.1084/jem.115.3.453
Zigmond SH (1977) Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors. J Cell Biol 75(2):606–616. doi:10.1083/jcb.75.2.606
Zicha D, Dunn GA, Brown AF (1991) A new direct-viewing chemotaxis chamber. J Cell Sci 99:769–775
Gundersen RW, Barrett JN (1979) Neuronal chemotaxis – chick dorsal-root axons turn toward high-concentrations of nerve growth-factor. Science 206(4422):1079–1080. doi:10.1126/science.493992
Zheng JQ, Felder M, Connor JA, Poo MM (1994) Turning of nerve growth cones induced by neurotransmitters. Nature 368(6467):140–144. doi:10.1038/368140a0
Chung BG, Choo J (2010) Microfluidic gradient platforms for controlling cellular behavior. Electrophoresis 31(18):3014–3027. doi:10.1002/elps.201000137
Du Y, Hancock MJ, He J, Villa-Uribe JL, Wang B, Cropek DM, Khademhosseini A (2010) Convection-driven generation of long-range material gradients. Biomaterials 31(9):2686–2694. doi:10.1016/j.biomaterials.2009.12.012
Sundararaghavan HG, Monteiro GA, Firestein BL, Shreiber DI (2009) Neurite growth in 3D collagen gels with gradients of mechanical properties. Biotechnol Bioeng 102(2):632–643. doi:10.1002/bit.22074
Polinkovsky M, Gutierrez E, Levchenko A, Groisman A (2009) Fine temporal control of the medium gas content and acidity and on-chip generation of series of oxygen concentrations for cell cultures. Lab Chip 9(8):1073–1084
Sip CG, Bhattacharjee N, Folch A (2011) A modular cell culture device for generating arrays of gradients using stacked microfluidic flows. Biomicrofluidics 5(2). doi:10.1063/1.3576931
Sahai R, Cecchini M, Klingauf M, Ferrari A, Martino C, Castrataro P, Lionetti V, Menciassi A, Beltram F (2011) Microfluidic chip for spatially and temporally controlled biochemical gradient generation in standard cell-culture Petri dishes. Microfluid Nanofluid 11(6):763–771. doi:10.1007/s10404-011-0841-2
Chung BG, Park JW, Hu JS, Huang C, Monuki ES, Jeon NL (2007) A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods. BMC Biotechnol 7. doi:10.1186/1472-6750-7-60
Chung BG, Flanagan LA, Rhee SW, Schwartz PH, Lee AP, Monuki ES, Jeon NL (2005) Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. Lab Chip 5(4):401–406
Park JY, Hwang CM, Lee SH, Lee S-H (2007) Gradient generation by an osmotic pump and the behavior of human mesenchymal stem cells under the fetal bovine serum concentration gradient. Lab Chip 7(12):1673–1680
Park JY, Kim S-K, Woo D-H, Lee E-J, Kim J-H, Lee S-H (2009) Differentiation of neural progenitor cells in a microfluidic chip-generated cytokine gradient. Stem Cells 27(11):2646–2654. doi:10.1002/stem.202
Abhyankar VV, Beebe DJ (2007) Spatiotemporal micropatterning of cells on arbitrary substrates. Anal Chem 79(11):4066–4073. doi:10.1021/ac062371p
Schumacher K, Strehl R, de Vries U, Minuth WW (2002) Advanced technique for long term culture of epithelia in a continuous luminal–basal medium gradient. Biomaterials 23(3):805–815. doi:10.1016/s0142-9612(01)00186-7
Zanzotto A, Szita N, Boccazzi P, Lessard P, Sinskey AJ, Jensen KF (2004) Membrane-aerated microbioreactor for high-throughput bioprocessing. Biotechnol Bioeng 87(2):243–254. doi:10.1002/bit.20140
de Jong J, Lammertink RGH, Wessling M (2006) Membranes and microfluidics: a review. Lab Chip 6(9):1125–1139. doi:10.1039/b603275c
Evenou F, Hamon M, Fujii T, Takeuchi S, Sakai Y (2011) Gas-permeable membranes and co-culture with fibroblasts enable high-density hepatocyte culture as multilayered liver tissues. Biotechnol Prog 27(4):1146–1153. doi:10.1002/btpr.626
Evenou F, Fujii T, Sakai Y (2010) Spontaneous formation of stably-attached and 3D-organized hepatocyte aggregates on oxygen-permeable polydimethylsiloxane membranes having 3D microstructures. Biomed Microdevices 12(3):465–475. doi:10.1007/s10544-010-9403-8
Lo JF, Sinkala E, Eddington DT (2010) Oxygen gradients for open well cellular cultures via microfluidic substrates. Lab Chip 10(18):2394–2401. doi:10.1039/c004660d
Grist SM, Chrostowski L, Cheung KC (2010) Optical oxygen sensors for applications in microfluidic cell culture. Sensors 10(10):9286–9316. doi:10.3390/s101009286
Huang CW, Lee GB (2007) A microfluidic system for automatic cell culture. J Micromech Microeng 17(7):1266–1274. doi:10.1088/0960-1317/17/7/008
Adler M, Polinkovsky M, Gutierrez E, Groisman A (2010) Generation of oxygen gradients with arbitrary shapes in a microfluidic device. Lab Chip 10(3):388–391. doi:10.1039/b920401f
Thomas PC, Raghavan SR, Forry SP (2011) Regulating oxygen levels in a microfluidic device. Anal Chem 83(22):8821–8824. doi:10.1021/ac202300g
Chen Y-A, King AD, Shih H-C, Peng C-C, Wu C-Y, Liao W-H, Tung Y-C (2011) Generation of oxygen gradients in microfluidic devices for cell culture using spatially confined chemical reactions. Lab Chip 11(21):3626–3633. doi:10.1039/c1lc20325h
Liu K, Pitchimani R, Dang D, Bayer K, Harrington T, Pappas D (2008) Cell culture chip using low-shear mass transport. Langmuir 24(11):5955–5960. doi:10.1021/la8003917
Cooksey GA, Elliott JT, Plant AL (2011) Reproducibility and robustness of a real-time microfluidic cell toxicity assay. Anal Chem 83(10):3890–3896. doi:10.1021/ac200273f
Hsieh CC, Huang SB, Wu PC, Shieh DB, Lee GB (2009) A microfluidic cell culture platform for real-time cellular imaging. Biomed Microdevices 11(4):903–913. doi:10.1007/s10544-009-9307-7
Lin JL, Wang SS, Wu MH, Oh-Yang CC (2011) Development of an integrated microfluidic perfusion cell culture system for real-time microscopic observation of biological cells. Sensors 11(9):8395–8411. doi:10.3390/s110908395
Gaitan M, Locascio LE (2004) Embedded microheating elements in polymeric micro channels for temperature control and fluid flow sensing. J Res Nat Inst Stand Technol 109(3):335–344
Vigolo D, Rusconi R, Piazza R, Stone HA (2010) A portable device for temperature control along microchannels. Lab Chip 10(6):795–798. doi:10.1039/b919146a
Liu C-W, Gau C, Liu C-G, Yang C-S (2005) Design consideration and fabrication of a microchannel system containing a set of heaters and an array of temperature sensors. Sens Actuators A Phys 122(2):177–183. doi:10.1016/j.sna.2005.04.016
Wu JB, Cao WB, Wen WJ, Chang DC, Sheng P (2009) Polydimethylsiloxane microfluidic chip with integrated microheater and thermal sensor. Biomicrofluidics 3(1). doi:10.1063/1.3058587
Shen K, Chen X, Guo M, Cheng J (2005) A microchip-based PCR device using flexible printed circuit technology. Sens Actuators B Chem 105(2):251–258. doi:10.1016/j.snb.2004.05.069
King KR, Wang SH, Irimia D, Jayaraman A, Toner M, Yarmush ML (2007) A high-throughput microfluidic real-time gene expression living cell array. Lab Chip 7(1):77–85. doi:10.1039/b612516f
Lee PJ, Gaige TA, Hung PJ (2009) Dynamic cell culture: a microfluidic function generator for live cell microscopy. Lab Chip 9(1):164–166. doi:10.1039/b807682k
Albrecht DR, Underhill GH, Resnikoff J, Mendelson A, Bhatia SN, Shah JV (2010) Microfluidics-integrated time-lapse imaging for analysis of cellular dynamics. Integr Biol 2(5–6):278–287. doi:10.1039/b923699f
Rieger MA, Schroeder T (2009) Analyzing cell fate control by cytokines through continuous single cell biochemistry. J Cell Biochem 108(2):343–352. doi:10.1002/jcb.22273
Muzzey D, van Oudenaarden A (2009) Quantitative time-lapse fluorescence microscopy in single cells. In: Annual review of cell and developmental biology, vol 25. Annual Reviews Inc, Palo Alto, pp 301–327. doi:10.1146/annurev.cellbio.042308.113408
Vasdekis AE, Laporte GPJ (2011) Enhancing single molecule imaging in optofluidics and microfluidics. Int J Mol Sci 12(8):5135–5156. doi:10.3390/ijms12085135
Chirieleison SM, Bissell TA, Scelfo CC, Anderson JE, Li Y, Koebler DJ, Deasy BM (2011) Automated live cell imaging systems reveal dynamic cell behavior. Biotechnol Prog 27(4):913–924. doi:10.1002/btpr.629
Gerrits A, Dykstra B, Kalmykowa OJ, Klauke K, Verovskaya E, Broekhuis MJC, de Haan G, Bystrykh LV (2010) Cellular barcoding tool for clonal analysis in the hematopoietic system. Blood 115(13):2610–2618. doi:10.1182/blood-2009-06-229757
Perlingeiro RCR, Kyba M, Daley GQ (2001) Clonal analysis of differentiating embryonic stem cells reveals a hematopoietic progenitor with primitive erythroid and adult lymphoid-myeloid potential. Development 128(22):4597–4604
Stachura DL, Svoboda O, Lau RP, Balla KM, Zon LI, Bartunek P, Traver D (2011) Clonal analysis of hematopoietic progenitor cells in the zebrafish. Blood 118(5):1274–1282. doi:10.1182/blood-2011-01-331199
Hope K, Bhatia M (2011) Clonal interrogation of stem cells. Nat Methods 8(4):S36–S40
Eilken HM, Nishikawa SI, Schroeder T (2009) Continuous single-cell imaging of blood generation from haemogenic endothelium. Nature 457(7231):896–900. doi:10.1038/nature07760
Lindstrom S, Eriksson M, Vazin T, Sandberg J, Lundeberg J, Frisen J, Andersson-Svahn H (2009) High-density microwell chip for culture and analysis of stem cells. PLoS One 4(9). doi:e699710.1371/journal.pone.0006997
Huth J, Buchholz M, Kraus JM, Schmucker M, von Wichert G, Krndija D, Seufferlein T, Gress TM, Kestler HA (2010) Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system. BMC Cell Biol 11
Nordon RE, Ko KH, Odell R, Schroeder T (2011) Multi-type branching models to describe cell differentiation programs. J Theor Biol 277(1):7–18. doi:10.1016/j.jtbi.2011.02.006
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Chen, H., Nordon, R.E. (2013). Application of Microfluidics to Study Stem Cell Dynamics. In: Danquah, M., Mahato, R. (eds) Emerging Trends in Cell and Gene Therapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-417-3_19
Download citation
DOI: https://doi.org/10.1007/978-1-62703-417-3_19
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-416-6
Online ISBN: 978-1-62703-417-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)