An Alternative Direct Compound Dispensing Method Using the HP D300 Digital Dispenser

Jones, R. L.; Zheng, Wei; McKew, John C.; Chen, Catherine Z.

doi:10.1177/2211068213491094

Cited by 25 publications

(18 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Jones et al (2013) [23] observed differences in EC 50 using the BioPrinter vs. delivery via 1536 pin tool. They found that 7 of the 9 compounds tested in their study had comparable EC 50s , while the other two were less active (Cortisol and Tamoxifen) when delivered via pin tool.…”

Section: Resultsmentioning

confidence: 99%

Optimizing multi-dimensional high throughput screening using zebrafish

Truong

Bugel

Chlebowski

et al. 2016

Reproductive Toxicology

View full text Add to dashboard Cite

The use of zebrafish for high throughput screening (HTS) for chemical bioactivity assessments is becoming routine in the fields of drug discovery and toxicology. Here we report current recommendations from our experiences in zebrafish HTS. We compared the effects of different high throughput chemical delivery methods on nominal water concentration, chemical sorption to multi-well polystyrene plates, transcription responses, and resulting whole animal responses. We demonstrate that digital dispensing consistently yields higher data quality and reproducibility compared to standard plastic tip-based liquid handling. Additionally, we illustrate the challenges in using this sensitive model for chemical assessment when test chemicals have trace impurities. Adaptation of these better practices for zebrafish HTS should increase reproducibility across laboratories.

show abstract

Section: Resultsmentioning

confidence: 99%

Optimizing multi-dimensional high throughput screening using zebrafish

Truong

Bugel

Chlebowski

et al. 2016

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…Since the model is quantitative, adjusting the parameters in the assay protocol could allow the experimentalist to optimize the protocol to make sure the data is appropriate to the question at hand. For example, in our own laboratory, it has informed the decision to use only direct dispensing technologies—in particular the HP D300 [42]—for fluorescent ligand-binding assays that require preparation of a range of compound concentrations.…”

Section: Discussionmentioning

confidence: 99%

Modeling error in experimental assays using the bootstrap principle: understanding discrepancies between assays using different dispensing technologies

Hanson

Ekins

Chodera

2015

J Comput Aided Mol Des

View full text Add to dashboard Cite

All experimental assay data contains error, but the magnitude, type, and primary origin of this error is often not obvious. Here, we describe a simple set of assay modeling techniques based on the bootstrap principle that allow sources of error and bias to be simulated and propagated into assay results. We demonstrate how deceptively simple operations—such as the creation of a dilution series with a robotic liquid handler—can significantly amplify imprecision and even contribute substantially to bias. To illustrate these techniques, we review an example of how the choice of dispensing technology can impact assay measurements, and show how large contributions to discrepancies between assays can be easily understood and potentially corrected for. These simple modeling techniques—illustrated with an accompanying IPython notebook—can allow modelers to understand the expected error and bias in experimental datasets, and even help experimentalists design assays to more effectively reach accuracy and imprecision goals.

show abstract

“…For dose-response virus inhibition experiments, A549 cells were washed with phosphate-buffered saline (PBS) twice and replaced with serum-free DMEM supplied with 1 mg/mL TPCK-trypsin (Worthington Biochemical) and 0.3% BSA before titration of drugs using the Hewlett-Packard (HP) D300 Digital Dispenser (Tecan). 39 For all wells, the final DMSO concentration was normalized to 1%. Two hours posttreatment, cells were infected with influenza virus strains at the indicated MOI without removal of drug.…”

Section: Antiviral Efficacy Assaysmentioning

confidence: 99%

Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication

PerwitasariOlivia

YanXiuzhen

O'DonnellJason

et al. 2015

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

Influenza A virus (IAV) infection causes seasonal epidemics of contagious respiratory illness that causes substantial morbidity and some mortality. Regular vaccination is the principal strategy for controlling influenza virus, although vaccine efficacy is variable. IAV antiviral drugs are available; however, substantial drug resistance has developed to two of the four currently FDAapproved antiviral drugs. Thus, new therapeutic approaches are being sought to reduce the burden of influenza-related disease. A high-throughput screen using a human kinase inhibitor library was performed targeting an emerging IAV strain (H7N9) in A549 cells. The inhibitor library contained 273 structurally diverse, active cell permeable kinase inhibitors with known bioactivity and safety profiles, many of which are at advanced stages of clinical development. The current study shows that treatment of human A549 cells with kinase inhibitors dinaciclib, flavopiridol, or PIK-75 exhibits potent antiviral activity against H7N9 IAV as well as other IAV strains. Thus, targeting host kinases can provide a broad-spectrum therapeutic approach against IAV. These findings provide a path forward for repurposing existing kinase inhibitors safely as potential antivirals, particularly those that can be tested in vivo and ultimately for clinical use.

show abstract

An Alternative Direct Compound Dispensing Method Using the HP D300 Digital Dispenser

Cited by 25 publications

References 9 publications

Optimizing multi-dimensional high throughput screening using zebrafish

Optimizing multi-dimensional high throughput screening using zebrafish

Modeling error in experimental assays using the bootstrap principle: understanding discrepancies between assays using different dispensing technologies

Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication

Contact Info

Product

Resources

About