Arbitrarily Accessible 3D Microfluidic Device for Combinatorial High-Throughput Drug Screening.
Microfluidics-based drug-screening systems have enabled efficient and high-throughput drug screening, but their routine uses in ordinary labs are limited due to the complexity involved in device fabrication and system setup. In this work, we report an easy-to-use and low-cost arbitrarily accessible 3D microfluidic device that can be easily adopted by various labs to perform combinatorial assays for high-throughput drug screening. The device is capable of precisely performing automatic and simultaneous reagent loading and aliquoting tasks and performing multistep assays with arbitrary sequences. The device is not intended to compete with other microfluidic technologies regarding ultra-low reaction volume. Instead, its freedom from tubing or pumping systems and easy operation makes it an ideal platform for routine high-throughput drug screening outside traditional microfluidic labs. The functionality and quantitative reliability of the 3D microfluidic device were demonstrated with a histone acetyltransferase-based drug-screening assay using the recombinantPlasmodium falciparumGCN5 enzyme, benchmarked with a traditional microtiter plate-based method. This arbitrarily accessible, multistep capable, low-cost, and easy-to-use device can be widely adopted in various combinatorial assays beyond high-throughput drug screening.
Department of Electrical Engineering, Pennsylvania State University, University Park, PA 16802, USA. zjc5117@psu.edu.
Zhuofa
Z
Chen
Department of Entomology, Pennsylvania State University, University Park, PA 16802, USA. wxl23@psu.edu.
Weizhi
W
Li
Department of Electrical Engineering, Pennsylvania State University, University Park, PA 16802, USA. gmc5400@psu.edu.
Gihoon
G
Choi
Department of Electrical Engineering, Pennsylvania State University, University Park, PA 16802, USA. xuy113@psu.edu.
Xiaonan
X
Yang
Department of Entomology, Pennsylvania State University, University Park, PA 16802, USA. jum23@psu.edu.
Jun
J
Miao
Department of Entomology, Pennsylvania State University, University Park, PA 16802, USA. luc2@psu.edu.
Liwang
L
Cui
Department of Electrical Engineering, Pennsylvania State University, University Park, PA 16802, USA. w.guan@psu.edu.|Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, USA. w.guan@psu.edu.
Weihua
W
Guan
combinatorial; drug screening; high-throughput; microfluidic; multiplex
Lab Chip. 2010 Sep 21;10(18):2433-42
20717617
Eukaryot Cell. 2008 Jul;7(7):1200-10
18487348
J Cell Sci. 2010 Apr 1;123(Pt 7):1039-49
20197405
Science. 2000 Apr 7;288(5463):113-6
10753110
Environ Sci Technol. 2014 Jul 15;48(14):8003-11
24926900
Anal Chem. 2010 Oct 1;82(19):8278-82
20822164
Lab Chip. 2010 Mar 7;10(5):571-80
20162232
Nature. 2005 Nov 3;438(7064):103-7
16267556
Drug Discov Today. 2013 Aug;18(15-16):716-23
23732176
Lab Chip. 2012 Apr 24;12(10):1813-22
22456798
Science. 1976 Aug 20;193(4254):673-5
781840
Lab Chip. 2009 Aug 21;9(16):2286-92
19636458
Electrophoresis. 2005 Oct;26(19):3780-8
16152663
Lab Chip. 2007 Jun;7(6):740-5
17538716
J Biomol Screen. 1999;4(2):67-73
10838414
Anal Chim Acta. 2016 Jan 15;903:36-50
26709297
Essays Biochem. 2012;52:1-12
22708559
Lab Chip. 2012 Jun 21;12(12):2146-55
22318506
Lab Chip. 2015 Jun 21;15(12):2634-46
25987291
Lab Chip. 2011 Dec 7;11(23):4057-62
22012599
Chem Biol. 2008 May;15(5):427-37
18482695
Drug Discov Today. 2014 May;19(5):654-60
24269836
Lab Chip. 2010 Oct 7;10(19):2622-7
20689865
Lab Chip. 2014 Feb 7;14(3):471-81
24287736
Lab Chip. 2007 Dec;7(12):1696-704
18030389
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6
9380737
Biotechnol Prog. 2015 Nov-Dec;31(6):1526-35
26317582
Anal Biochem. 2016 Apr 1;498:53-8
26778528
Mol Microbiol. 2010 Nov;78(4):883-902
20807207
Anal Chem. 2004 Jan 15;76(2):458-63
14719897
Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14195-200
19617544
Lab Chip. 2015 Jun 7;15(11):2429-36
25904463
Lab Chip. 2011 Oct 7;11(19):3305-12
21842069
Nat Rev Drug Discov. 2012 Aug;11(8):620-32
22850786
J Med Chem. 2009 Jan 22;52(2):530-6
19099397
ALTEX. 2013;30(1):51-6
23338806
Bioorg Med Chem. 2014 Mar 1;22(5):1680-9
24513187
J Vis Exp. 2015 May 14;(99):e52755
26068617
Anal Chem. 2011 Mar 15;83(6):2020-8
21344866
Eukaryot Cell. 2010 Aug;9(8):1138-49
20453074
Anal Chem. 2006 Jul 1;78(13):4291-8
16808435
Langmuir. 2006 Jul 4;22(14):6234-7
16800680
Cell Mol Biol (Noisy-le-grand). 2012 Dec 22;58(1):182-6
23273210