Abstract
This paper describes microfluidic systems containing immobilized hydrogel-encapsulated mammalian cells that can be used as cell-based biosensors. Mammalian cells were encapsulated in three-dimensional poly(ethylene glycol)(PEG) hydrogel microstructures which were photolithographically polymerized in microfluidic devices and grown under static culture conditions. The encapsulated cells remained viable for a week and were able to carry out enzymatic reactions inside the microfluidic devices. Cytotoxicity assays proved that small molecular weight toxins such as sodium azide could easily diffuse into the hydrogel microstructures and kill the encapsulated cells, which resulted in decreased viability. Furthermore, heterogeneous hydrogel microstructures encapsulating two different phenotypes in discrete spatial locations were also successfully fabricated inside microchannels.
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Sundberg CJ (2000) Curr Opin Biotechnol 11:47–53
Khandurina J, Guttman A (2002) Curr Opin Chem Biol 6:359–366
Bousse L (1996) Sens Actuators B 34:270–275
O’Connor SM, Andreadis JD, Shaffer KM, Ma W, Pancrazio JJ, Stenger DA (2000) Biosens Bioelectron 14:871–881
Park TH, Shuler ML (2003) Biotechnol Prog 19:243–253
Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE (1998) Biotechnol Prog 14:356–363
Folch A, Toner M (2000) Annu Rev Biomed Eng 2:227–256
Ito Y (1999) Biomaterials 20:2333–2342
Jung DR, Kapur R, Adams T, Giuliano KA, Mrksich M, Craighead HG, Taylor DL (2001) Crit Rev Biotechnol 21:111–154
Kane RS, Takayama S, Ostuni E, Ingber DE, Whitesides GM (1999) Biomaterials 20:2363–2376
Matsuda T, Sugawara T (1995) J Biomed Mater Res 29:749–756
Singhvi R, Kumer A, Lopez GP, Stephanopoulos GN, Daniel IC, Wang DIC, Whitesides GM, Ingber DE (1994) Science 264:696–698
Whitesides GM, Ostuni E, Takayama S, Jiang X, Ingber DE (2001) Annu Rev Biomed Eng 3:335–373
Koh W, Revzin A, Simonian A, Reeves T, Pishko MV (2003) Biomed Microdev 5:11–19
Amirpour ML, Ghosh P, Lackowski WM, Crooks RM, Pishko MV (2001) Anal Chem 73:1560–1566
Koh W, Revzin A, Pishko MV (2002) Langmuir 18:2459–2462
Koh W, Itle LJ, Pishko MV (2003) Anal Chem 75:5783–5789
Revzin A, Russell RJ, Yadavalli VK, Koh W, Deister C, Hile DD, Mellott MB, Pishko MV (2001) Langmuir 17:5440–5447
Russell RJ, Simonian A, Wild J, Pishko MV (1999) Anal Chem 71:4909–4912
Heo J, Thomas KJ, Seong GH, Crooks RM (2003) Anal Chem 75:22–26
Koh W, Pishko MV (2003) Langmuir 19:10310–10316
Sirkar K, Pishko MV (1998) Anal Chem 70:2888–2894
Zhan W, Seong GH, Crooks RM (2002) Anal Chem 74:4647–4652
Seong GH, Zhan W, Crooks RM (2002) Anal Chem 74:3372–3377
Olsen KG, Ross DJ, Tarlov MJ (2002) Anal Chem 74:1436–1441
Liu VA, Bhatia SN (2002) Biomed Microdev 4:257–256
Beebe DJ, Moore JS, Bauer JM, Yu Q, Liu RH, Devadoss C, Jo B (2000) Nature 404:588–590
Li PCH, Harrison DJ (1997) Anal Chem 69:1564–1568
Leclerc E, Sakai Y, Fujii T (2003) Biomed Microdev 5:109–114
Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH, Farrell K, Manger ID, Daridon A (2003) Anal Chem 75:3581–3586
Griffith LG, Naughton G (2002) Science 295:1009–1014
Strain AJ, Neuberger JM (2002) Science 295:1005–1009
Walker GM, Ozers MS, Beebe DJ (2002) Biomed Microdev 4:161–166
Takayama S, McDonald JC, Ostuni E, Liang MN, Kenis PJA, Ismagilov RF, Whitesides GM (1999) Proc Natl Acad Sci USA 96:5545–5548
Hediger S, Fontannaz J, Sayah A, Hunziker W, Gijs MAM (2000) Sens Actuators B 63:63–73
Krishnan M, Namasivayam V, Lin RS, Pal R, Burns MA (2001) Curr Opin Biotechnol 12:92–98
Sanders GHW, Manz A (2000) Trends Anal Chem 19:364–378
Figeys D, Pinto D (2000) Anal Chem 72:330A–335A
Koch M, Evans A, Brunnschweiler A (2000) Microfluidic technology and applications. Research Studies Press Ltd., Baldock, UK
McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Schueller OJA, Whitesides GM (2000) Electrophoresis 21:27–40
Mata A, Fleischman AJ, Roy S (2005) Biomed Microdev 7:281–293
Anderson JR, Chiu DT, Jackman RJ, Cherniavskaya O, McDonald JC, Wu HK, Whitesides SH, Whitesides GM (2000) Anal Chem 72:3158–3164
Charati SG, Stern SA (1998) Macromolecules 31:5529–5535
Ertel S, Ratner B, Kaul A, Schway M, Horbett T (1994) J Biomed Mater Res 28:667–675
Mellott MB, Searcy K, Pishko MV (2001) Biomaterials 22:929–941
Cruise GM, Scharp DS, Hubbell JA (1998) Biomaterials 19:1287–1294
Peppas NA, Bar-Howel BD (1986) Hydrogels in medicine and pharmacy. CRC Press, Boca Raton, FL, pp 27–56
Canal T, Peppas NA (1989) J Biomed Mater Res 23:1183–1193
Bhatia SN, Yarmush ML, Toner M (1997) J Biomed Mater Res 34:189–199
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The work described in this paper was supported by a grant from the National Aeronautics and Space Administration (NASA, NAG 91277).
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Koh, WG., Pishko, M.V. Fabrication of cell-containing hydrogel microstructures inside microfluidic devices that can be used as cell-based biosensors. Anal Bioanal Chem 385, 1389–1397 (2006). https://doi.org/10.1007/s00216-006-0571-6
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DOI: https://doi.org/10.1007/s00216-006-0571-6