Nanoliter Quantitative High-Throughput Screening with Large-Scale Tunable Gradients Based on a Microfluidic Droplet Robot under Unilateral Dispersion Mode

Analytical Chemistry
Yan WeiQun Fang

Abstract

Performing quantitative high throughput screening (qHTS) is in urgent need in current chemical, biological, and medical research. In this work, we developed an automated microfluidic dilution and large-scale screening system in the nanoliter range, by combining the droplet-based microfluidic robot technique with a novel unilateral Taylor-Aris dispersion-based dilution approach. The unilateral dispersion approach utilizes multiphase microfluidic design to generate a concentration gradient with fast gradient generation time, low sample/reagent consumption, and high operation efficiency over the widely used bilateral Taylor-Aris dispersion approach adopted in previous dilution systems. The present system is capable of automatically generating a large and tunable range of concentration gradients covering ca. 6 orders of magnitude in droplet arrays and achieving qHTS of a large number of different samples. We applied the microfluidic droplet system in miniaturized enzyme kinetic assay in 8-nL droplets and high-throughput quantitative screening of enzyme inhibitors with a library of 102 compounds. Only 9.8 μL of enzyme solution was consumed in 2448 droplet assays containing 102 compounds and 24 concentrations, representing an approxi...Continue Reading

References

May 31, 2003·Nature Reviews. Drug Discovery·Terry Kenakin
Dec 17, 2003·Analytical Chemistry·Jian LiuStephen R Quake
May 24, 2005·Biochimica Et Biophysica Acta·Mikael Björklund, Erkki Koivunen
Jan 20, 2006·Nature Chemical Biology·Nils G Walter
Feb 9, 2006·Nature Biotechnology·Nathalie MaloRobert Nadon
Jul 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·James IngleseChristopher P Austin
Jul 28, 2006·Nature·George M Whitesides
Sep 15, 2006·Analytical Chemistry·Wen-Bin DuZhao-Lun Fang
Dec 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Liang LiRustem F Ismagilov
Jul 3, 2007·British Journal of Pharmacology·D A Pereira, J A Williams
Jan 31, 2008·Lab on a Chip·Shia-Yen TehAbraham P Lee
Mar 13, 2008·Environmental Health Perspectives·Menghang XiaChristopher P Austin
May 3, 2008·Cancer Research·Christina BendrikCharlotta Dabrosin
Jul 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Eric BrouzesMichael L Samuels
Feb 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jeremy J AgrestiDavid A Weitz
May 24, 2011·Nature Chemistry·Xize NiuAndrew J deMello
Jun 24, 2011·Analytical Chemistry·Jae Young YunJong Wook Hong
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Oliver J MillerAndrew D Griffiths
Jun 22, 2013·Analytical Chemistry·Guan-Sheng DuQun Fang
Mar 14, 2014·Nature·Eric K SackmannDavid J Beebe
Apr 19, 2017·Neurochemical Research·Wolfgang Walz, Francisco S Cayabyab
Aug 25, 2017·Nature Protocols·Alexandre BaccoucheAnthony J Genot

❮ Previous
Next ❯

Citations

Nov 22, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zhen LeiZhenxin Wang
Dec 20, 2019·Analytical and Bioanalytical Chemistry·David HessStavros Stavrakis
Aug 9, 2020·Chemical Society Reviews·Yuanyuan WeiKen-Tye Yong
Mar 12, 2021·Chemical Communications : Chem Comm·Hao-Yu DongZhi-Ling Zhang
May 25, 2021·Chemical Reviews·Yuxiao LiuYuanjin Zhao
Jun 8, 2021·Lab on a Chip·David Sinton, Shana O Kelley
Aug 1, 2021·Drug Discovery Today·Boqian WangXianting Ding

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.