scholarly journals Droplet-Based Microfluidics

2013 ◽  
Vol 19 (4) ◽  
pp. 483-496 ◽  
Author(s):  
Oliver J. Dressler ◽  
Richard M. Maceiczyk ◽  
Soo-Ik Chang ◽  
Andrew J. deMello
Keyword(s):  
Biological Sciences ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Efficiency ◽  
Small Sample ◽  
Operational Flexibility ◽  
High Throughput Experimentation ◽  
The Impact ◽  
Functional Components ◽  
Fabrication Costs

Over the past two decades, the application of microengineered systems in the chemical and biological sciences has transformed the way in which high-throughput experimentation is performed. The ability to fabricate complex microfluidic architectures has allowed scientists to create new experimental formats for processing ultra-small analytical volumes in short periods and with high efficiency. The development of such microfluidic systems has been driven by a range of fundamental features that accompany miniaturization. These include the ability to handle small sample volumes, ultra-low fabrication costs, reduced analysis times, enhanced operational flexibility, facile automation, and the ability to integrate functional components within complex analytical schemes. Herein we discuss the impact of microfluidics in the area of high-throughput screening and drug discovery and highlight some of the most pertinent studies in the recent literature.

scholarly journals Large-scale, high-throughput screening for coagulation and hematologic phenotypes in mice*

2002 ◽  
Vol 11 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Luanne L. Peters ◽  
Eleanor M. Cheever ◽  
Heather R. Ellis ◽  
Phyllis A. Magnani ◽  
Karen L. Svenson ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Sample Volume ◽  
Small Sample ◽  
Mouse Strains ◽  
Phenotypic Data ◽  
Multiple Tests

The Mouse Phenome Project is an international effort to systematically gather phenotypic data for a defined set of inbred mouse strains. For such large-scale projects the development of high-throughput screening protocols that allow multiple tests to be performed on a single mouse is essential. Here we report hematologic and coagulation data for more than 30 inbred strains. Complete blood counts were performed using an Advia 120 analyzer. For coagulation testing, we successfully adapted the Dade Behring BCS automated coagulation analyzer for use in mice by lowering sample and reagent volume requirements. Seven automated assay procedures were developed. Small sample volume requirements make it possible to perform multiple tests on a single animal without euthanasia, while reductions in reagent volume requirements reduce costs. The data show that considerable variation in many basic hematological and coagulation parameters exists among the inbred strains. These data, freely available on the World Wide Web, allow investigators to knowledgeably select the most appropriate strain(s) to meet their individual study designs and goals.

scholarly journals Stability of Screening Compounds in Wet DMSO

2008 ◽  
Vol 13 (10) ◽  
pp. 999-1006 ◽  
Author(s):  
Caroline Engeloch ◽  
Ulrich Schopfer ◽  
Ingo Muckenschnabel ◽  
Francois Le Goff ◽  
Hervé Mees ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Medicinal Chemistry ◽  
Storage Conditions ◽  
Pragmatic Approach ◽  
Analytical Quality ◽  
The Past ◽  
Effect Of Water ◽  
The Impact

The impact of storage conditions on compound stability and compound solubility has been debated intensely over the past 5 years. At Novartis, the authors decided to opt for a storage concept that can be considered controversial because they are using a DMSO/water (90/10) mixture as standard solvent. To assess the effect of water in DMSO stocks on compound stability, the authors monitored the purity of a subset of 1404 compounds from ongoing medicinal chemistry projects over several months. The study demonstrated that 85% of the compounds were stable in wet DMSO over a 2-year period at 4 °C. This result validates the storage concept developed at Novartis as a pragmatic approach that takes advantage of the benefits of DMSO/water mixtures while mediating the disadvantages. In addition, the authors describe how purity data collected over the course of the chemical validation of high-throughput screening actives are used to improve the analytical quality of the Novartis screening deck. ( Journal of Biomolecular Screening 2008:999-1006)

scholarly journals Development of a Novel Cell-Based Assay System for High-Throughput Screening of Compounds Acting on Background Two-Pore Domain K+ Channels

2019 ◽  
Vol 24 (6) ◽  
pp. 641-652
Author(s):  
Keisuke Kawasaki ◽  
Yoshiaki Suzuki ◽  
Hisao Yamamura ◽  
Yuji Imaizumi
Keyword(s):  
Cell Death ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Efficiency ◽  
Equilibrium Potential ◽  
Channel Blockers ◽  
Pore Domain ◽  
Druggable Targets ◽  
Relative Cell Viability ◽  
Or Task

Two-pore domain K+ (K2P) channels are thought to be druggable targets. However, only a few agents specific for K2P channels have been identified, presumably due to the lack of an efficient screening system. To develop a new high-throughput screening (HTS) system targeting these channels, we have established a HEK293-based “test cell” expressing a mutated Na+ channel (Nav1.5) with markedly slowed inactivation, as well as a K+ channel (Kir2.1) that sets the membrane potential quite negative, close to K+ equilibrium potential. We found in this system that Kir2.1 block by 100 μM Ba2+ application consistently elicited a large depolarization like a long-lasting action potential. This maneuver resulted in cell death, presumably due to the sustained Na+ influx. When either the TWIK-related acid-sensitive K+ (TASK)-1 or TASK-3 channel was expressed in the test cells, Ba2+-induced cell death was markedly weakened. Stronger activation of TASK-1 by extracellular acidification further decreased the cell death. In contrast, the presence of K2P channel blockers enhanced cell death. IC50 values for TASK-1 and/or TASK-3 blockers acquired by measurements of relative cell viability were comparable to those obtained using patch-clamp recordings. Both blockers and openers of K2P channels can be accurately assessed with high efficiency and throughput by this novel HTS system.

Abstracts

2008 ◽  
Vol 27 (6) ◽  
pp. 405-405
Author(s):  
David J. Dix
Keyword(s):  
Risk Assessment ◽  
High Throughput ◽  
Environmental Protection Agency ◽  
High Throughput Screening ◽  
Human Health Risk ◽  
Environmental Chemicals ◽  
In Vitro Assays ◽  
The Impact ◽  
Toxicity Pathways

The U.S. Environmental Protection Agency (EPA), National Toxicology Program (NTP), and National Institutes of Health (NIH) Chemical Genomics Center (NCGC) have complementary research programs designed to improve chemical toxicity evaluations by developing high throughput screening (HTS) methods that evaluate the impact of environmental chemicals on key toxicity pathways. These federal partners are coordinating an extension of the EPA’s ToxCast program, the NTP’s HTS initiative, and the NCGC’s Molecular Libraries Initiative into a collaborative research program focused on identifying toxicity pathways and developing in vitro assays to characterize the ability of chemicals to perturb those pathways. The goal is to develop new paradigm for high throughput toxicity testing that collects mechanistic and quantitative data from in vitro assays measuring chemical modulation of biological processes involved in the progression to toxicity. As toxicity pathways are identified, the in vitro assays can be optimized for comparison to in vivo animal studies, and for predicting effects in humans. Subsequent computational modeling of toxicity pathway responses and appropriate chemical dosimetry will need to be developed to make these predictions relevant for human health risk assessment. This work was reviewed by EPA and approved for publication but does not necessarily reflect official Agency policy. Index Terms: Toxicogenomics, High Throughput Screening/Testing, EPA ToxCast, Chemical Risk Assessment

scholarly journals Electroporation Knows No Boundaries

2015 ◽  
Vol 20 (8) ◽  
pp. 932-942 ◽  
Author(s):  
Christin Luft ◽  
Robin Ketteler
Keyword(s):  
Cell Lines ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Efficiency ◽  
Target Identification ◽  
Cell Types ◽  
Rnai Technology ◽  
Drug Target Identification ◽  
Interfering Rna ◽  
Calcium Phosphate Precipitation

The discovery of RNA interference (RNAi) has enabled several breakthrough discoveries in the area of functional genomics. The RNAi technology has emerged as one of the major tools for drug target identification and has been steadily improved to allow gene manipulation in cell lines, tissues, and whole organisms. One of the major hurdles for the use of RNAi in high-throughput screening has been delivery to cells and tissues. Some cell types are refractory to high-efficiency transfection with standard methods such as lipofection or calcium phosphate precipitation and require different means. Electroporation is a powerful and versatile method for delivery of RNA, DNA, peptides, and small molecules into cell lines and primary cells, as well as whole tissues and organisms. Of particular interest is the use of electroporation for delivery of small interfering RNA oligonucleotides and clustered regularly interspaced short palindromic repeats/Cas9 plasmid vectors in high-throughput screening and for therapeutic applications. Here, we will review the use of electroporation in high-throughput screening in cell lines and tissues.

scholarly journals Discovery of temperature-induced stability reversal in perovskites using high-throughput robotic learning

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yicheng Zhao ◽  
Jiyun Zhang ◽  
Zhengwei Xu ◽  
Shijing Sun ◽  
Stefan Langner ◽  
...  
Keyword(s):  
High Throughput ◽  
Perovskite Solar Cells ◽  
Temperature Stability ◽  
Underlying Mechanism ◽  
Accelerated Ageing ◽  
Inorganic Cation ◽  
High Throughput Experimentation ◽  
Robotic Learning ◽  
The Impact ◽  
Detrimental Impact

AbstractStability of perovskite-based photovoltaics remains a topic requiring further attention. Cation engineering influences perovskite stability, with the present-day understanding of the impact of cations based on accelerated ageing tests at higher-than-operating temperatures (e.g. 140°C). By coupling high-throughput experimentation with machine learning, we discover a weak correlation between high/low-temperature stability with a stability-reversal behavior. At high ageing temperatures, increasing organic cation (e.g. methylammonium) or decreasing inorganic cation (e.g. cesium) in multi-cation perovskites has detrimental impact on photo/thermal-stability; but below 100°C, the impact is reversed. The underlying mechanism is revealed by calculating the kinetic activation energy in perovskite decomposition. We further identify that incorporating at least 10 mol.% MA and up to 5 mol.% Cs/Rb to maximize the device stability at device-operating temperature (<100°C). We close by demonstrating the methylammonium-containing perovskite solar cells showing negligible efficiency loss compared to its initial efficiency after 1800 hours of working under illumination at 30°C.

scholarly journals DDRE-30. HIGH-THROUGHPUT DRUG SCREENING OF FDA-APPROVED ANTINEOPLASTIC DRUGS FOR THE TREATMENT OF AGGRESSIVE MENINGIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii68-ii68
Author(s):  
Gerhard Jungwirth ◽  
Tao Yu ◽  
Fang Liu ◽  
Rolf Warta ◽  
Andreas Unterberg ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Screening ◽  
Surgical Removal ◽  
Antineoplastic Drugs ◽  
Recurrence Rates ◽  
High Throughput Drug Screening ◽  
The Impact ◽  
Grade Iii

Abstract The management of aggressive meningiomas remains challenging due to limited treatment options besides surgical removal and radiotherapy. High recurrence rates and lack of effective chemotherapies may be reasons for the unfavorable prognosis of these patients. Consequently, there is an urgent need to identify effective therapeutic agents. For this purpose, we performed a high-throughput screening utilizing a drug library consisting of 147 FDA-approved antineoplastic drugs on the anaplastic meningioma cell line NCH93 using CellTiter-Glo (Promega). Based on the lowest IC50, the top 5 drugs were selected including Bortezomib, Carfilzomib, Omacetaxine, Ixabepilone, and Romidepsin. Validation of candidate compounds was performed in Ben-Men-1 (grade I), NCH93 (grade III), and IOMM-Lee cells (grade III) using crystal violet assay. Dose-curve analysis revealed IC50 values in the lower nanomolar range for all compounds and all cell lines (0.2 – 16.2 nM). To further substantiate our findings, cell proliferation assessed by manual counting was significantly reduced by up to 90% by each candidate drug at 10xIC50 after 48 h (P &lt; 0.001). Furthermore, cell migration was inhibited up to 60% by all candidate drugs at the respective IC50 (P &lt; 0.05). However, colony formation was only significantly reduced by Bortezomib and Carfilzomib (P &lt; 0.001). The impact of the drugs on cell cycle and apoptosis was analyzed by flow cytometry using Annexin V/PI staining. All candidate drugs induced cell cycle arrest at G0/G1 or G2/M phase (P &lt; 0.001) and subsequently induced apoptosis. Among them, Bortezomib exhibited the most pronounced effect by up to 80% of apoptotic cells (P &lt; 0.001). In summary, by utilizing a high-throughput drug screening we were able to identify Bortezomib, Carfilzomib, Omacetaxine, Ixabepilone, and Romidepsin as potent antineoplastic agents for the treatment of aggressive meningiomas.

Sign in / Sign up

Export Citation Format

Share Document