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The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response relationships...
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Quality control procedures for dose-response curve generation using nanoliter dispense technologies.

Catherine Quintero1, Craig Rosenstein, Bethany Hughes

  • 1Merck & Co., Inc., Merck Research Laboratories, Boston, MA 02115, USA.

Journal of Biomolecular Screening
|May 23, 2007
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Summary

Quality control (QC) of robotic liquid handlers is crucial for accurate drug discovery. This study validates nanoliter dispensers for dose-response testing, highlighting the need for robust QC procedures in high-throughput screening.

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Area of Science:

  • Biomolecular screening
  • Drug discovery automation
  • Assay development

Background:

  • High-throughput screening (HTS) requires precise liquid handling for accurate dose-response curves.
  • Traditional automated liquid handlers face challenges with nanoliter volumes and QC.
  • Nanoliter dispensers offer compound conservation and reduced carryover but require validated QC methods.

Purpose of the Study:

  • To compare automated liquid dispensing procedures across different instruments.
  • To validate quality control (QC) methods for dose-response curve generation.
  • To assess the suitability of nanoliter dispensers for lead optimization.

Main Methods:

  • Comparison of manual, traditional automated, and nanoliter liquid dispensers.
  • Evaluation of dispense volume accuracy and precision.
  • Assessment of dose-response curve generation using various liquid handling platforms.

Main Results:

  • Established the critical need for robust QC procedures for all liquid handlers.
  • Validated nanoliter pipettors as reliable tools for dose-response testing.
  • Confirmed the importance of thorough mixing in serial dilutions with traditional liquid handlers.

Conclusions:

  • Robust QC procedures are essential for accurate affinity determinations in lead optimization.
  • Nanoliter dispensing technology is validated for dose-response curve generation in HTS.
  • Optimized mixing protocols are necessary for serial dilutions using traditional liquid handlers.