Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays

被引:179
作者
Khademhosseini, A
Yeh, J
Eng, G
Karp, J
Kaji, H
Borenstein, J
Farokhzad, OC
Langer, R [1 ]
机构
[1] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[3] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[4] Tohoku Univ, Grad Sch Engn, Dept Bioengn & Robot, Aoba Ku, Sendai, Miyagi 9808579, Japan
[5] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA
[6] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA
关键词
D O I
10.1039/b508096g
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We present a soft lithographic method to fabricate multiphenotype cell arrays by capturing cells within an array of reversibly sealed microfluidic channels. The technique uses reversible sealing of elastomeric polydimethylsiloxane (PDMS) molds on surfaces to sequentially deliver various fluids or cells onto specific locations on a substrate. Microwells on the substrate were used to capture and immobilize cells within low shear stress regions inside channels. By using an array of channels it was possible to deposit multiple cell types, such as hepatocytes, fibroblasts, and embryonic stem cells, on the substrates. Upon formation of the cell arrays on the substrate, the PDMS mold could be removed, generating a multiphenotype array of cells. In addition, the orthogonal alignment and subsequent attachment of a secondary array of channels on the patterned substrates could be used to deliver fluids to the patterned cells. The ability to position many cell types on particular regions within a two dimensional substrate could potentially lead to improved high-throughput methods applicable to drug screening and tissue engineering.
引用
收藏
页码:1380 / 1386
页数:7
相关论文
共 29 条
[1]   Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure [J].
Alaeddini, J ;
Uber, PA ;
Park, MH ;
Scott, RL ;
Ventura, HO ;
Mehra, MR .
AMERICAN JOURNAL OF CARDIOLOGY, 2004, 94 (11) :1475-1477
[2]   Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells [J].
Anderson, DG ;
Levenberg, S ;
Langer, R .
NATURE BIOTECHNOLOGY, 2004, 22 (07) :863-866
[3]  
BHATIA SN, 1994, ANN NY ACAD SCI, V745, P187
[4]   Probing heterotypic cell interactions: Hepatocyte function in microfabricated co-cultures [J].
Bhatia, SN ;
Balis, UJ ;
Yarmush, ML ;
Toner, M .
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 1998, 9 (11) :1137-1160
[5]   Microfabrication of hepatocyte/fibroblast co-cultures: Role of homotypic cell interactions [J].
Bhatia, SN ;
Balis, UJ ;
Yarmush, ML ;
Toner, M .
BIOTECHNOLOGY PROGRESS, 1998, 14 (03) :378-387
[6]  
Bhatia SN, 1997, J BIOMED MATER RES, V34, P189, DOI 10.1002/(SICI)1097-4636(199702)34:2<189::AID-JBM8>3.0.CO
[7]  
2-M
[8]   Fabrication of gradient hydrogels using a microfluidics/photopolymerization process [J].
Burdick, JA ;
Khademhosseini, A ;
Langer, R .
LANGMUIR, 2004, 20 (13) :5153-5156
[9]   Dedifferentiation of lineage-committed cells by a small molecule [J].
Chen, SB ;
Zhang, QS ;
Wu, X ;
Schultz, PG ;
Ding, S .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (02) :410-411
[10]  
Cheng, 1996, Mol Diagn, V1, P183, DOI 10.1016/S1084-8592(96)70004-8