High-content screening in microfluidic devices

Importance of the field: Miniaturization is the key to advancing the state of the art in high-content screening (HCS) in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review: This perspective highlights a real-world example from the authors' work of HCS assays implemented in a highly miniaturized microfluidic format. The advantages of this technology are discussed, including cost savings, high-throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration and scaling. What the reader will gain: The reader will understand the capabilities of a new microfluidics-based platform for HCS and the advantages it provides over conventional plate-based HCS. Take home message: Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery.

[1]  Robert Nadon,et al.  High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments , 2010, Expert opinion on drug discovery.

[2]  Rustem F Ismagilov,et al.  Microfluidic cartridges preloaded with nanoliter plugs of reagents: an alternative to 96-well plates for screening. , 2006, Current opinion in chemical biology.

[3]  E. Krausz,et al.  Cell-based high-content screening of small-molecule libraries. , 2007, Current opinion in chemical biology.

[4]  D. Beebe,et al.  High-throughput microfluidics: improved sample treatment and washing over standard wells. , 2007, Lab on a chip.

[5]  K. Yeow,et al.  Cellular imaging in drug discovery , 2006, Nature Reviews Drug Discovery.

[6]  Roland Zengerle,et al.  Microfluidic platforms for lab-on-a-chip applications. , 2007, Lab on a chip.

[7]  Andre Levchenko,et al.  High Content Cell Screening in a Microfluidic Device*S , 2009, Molecular & Cellular Proteomics.

[8]  Philip Denner,et al.  High-content analysis in preclinical drug discovery. , 2008, Combinatorial chemistry & high throughput screening.

[9]  Robert T Kennedy,et al.  Fully integrated microfluidic separations systems for biochemical analysis. , 2007, Journal of chromatography. A.

[10]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[11]  Ramesh Ramakrishnan,et al.  High Throughput Gene Expression Measurement with Real Time PCR in a Microfluidic Dynamic Array , 2008, PloS one.

[12]  S. Kain,et al.  Green fluorescent protein (GFP): applications in cell-based assays for drug discovery. , 1999, Drug discovery today.

[13]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[14]  Ursula Bilitewski,et al.  Biochemical analysis with microfluidic systems , 2003, Analytical and bioanalytical chemistry.

[15]  Christoph A. Merten,et al.  Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms. , 2008, Chemistry & biology.

[16]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.

[17]  James R. Johnson,et al.  Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression , 2004, Science.

[18]  D A. Dunn,et al.  Challenges and solutions to ultra-high-throughput screening assay miniaturization: submicroliter fluid handling. , 2000, Drug discovery today.

[19]  Dan Bratton,et al.  Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays. , 2009, Lab on a chip.

[20]  Jude Dunne,et al.  Comparison of on-chip and off-chip microfluidic kinase assay formats. , 2004, Assay and drug development technologies.

[21]  Qifeng Xue,et al.  Multiplexed enzyme assays in capillary electrophoretic single‐use microfluidic devices , 2001, Electrophoresis.

[22]  Andre Levchenko,et al.  Comment on "Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression" , 2005, Science.

[23]  Jing Zhang,et al.  High-content screening moves to the front of the line. , 2006, Drug discovery today.

[24]  G. Whitesides,et al.  Soft lithography in biology and biochemistry. , 2001, Annual review of biomedical engineering.

[25]  R. Cheong,et al.  Using a Microfluidic Device for High-Content Analysis of Cell Signaling , 2009, Science Signaling.