Gradient, contact-free volume transfers minimize compound loss in dose-response experiments

Area of Science:

• Drug discovery and development
• Assay development
• Pharmacology

Background:

• Traditional aqueous serial dilutions introduce significant errors (up to 4 orders of magnitude) in dose-response values.
• Dimethyl sulfoxide (DMSO) as a diluent reduces but does not eliminate these errors.
• Compound handling in serial dilutions can lead to sample loss and contamination, particularly for less water-soluble compounds.

Purpose of the Study:

• To develop a more accurate method for constructing dose-response curves.
• To minimize errors and sample loss associated with compound handling in serial dilutions.
• To explore the utility of acoustic drop ejection (ADE) for creating concentration gradients.

Main Methods:

• Utilized acoustic drop ejection (ADE) technology to dispense varying volumes of model compounds.
• Directly created concentration gradient series in assay plates, bypassing traditional serial dilution steps.
• Focused on minimizing sample loss and contamination through precise liquid handling.

Main Results:

• ADE technology effectively eliminates errors associated with aqueous serial dilutions.
• Sample losses and contamination were minimized, particularly for compounds with low water solubility.
• Accurate dose-response curves were constructed without the need for traditional dilution methods.

Conclusions:

• Acoustic drop ejection (ADE) offers a superior alternative to traditional serial dilutions for constructing accurate dose-response curves.
• ADE is well-suited for assay miniaturization and improves the reliability of screening results.
• This method enhances the efficiency and accuracy of compound library screening in drug discovery.