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Quality Control Procedures for Dose-Response Curve Generation Using Nanoliter Dispense Technologies
Catherine Quintero
Merck & Co., Inc., Merck Research Laboratories, Boston
Craig Rosenstein
Merck & Co., Inc., Merck Research Laboratories, Boston
Bethany Hughes
Merck & Co., Inc., Merck Research Laboratories, Boston
Richard Middleton
Merck & Co., Inc., Merck Research Laboratories, Boston
Ilona Kariv
Merck & Co., Inc., Merck Research Laboratories, Boston, Ilona_Kariv{at}Merck.com
With the advancement of high-throughput biomolecular screening techniques to the lead optimization stage, there is a critical need to quality control (QC) dose-response curves generated by robotic liquid handlers to ensure accurate affinity determinations. One challenge in evaluating the performance of liquid handlers is identifying and validating a robust method for testing dispense volumes across different instruments. Although traditional automated liquid handlers are still considered the standard platform in many laboratories, nanoliter dispensers are becoming more common and pose new challenges for routine quality control procedures. For example, standard gravimetric measurements are unreliable for testing the accuracy of nanoliter liquid dispenses. However, nanoliter dispensing technology allows for the conservation of compound, reduces compound carryover from well to well through discrete dispenses, and eliminates the need for intermediate compound dilution steps to achieve a low final DMSO assay concentration. Moreover, an intermediate dilution step in aqueous solution might result in compound precipitation at high concentrations. This study compared representative automation procedures done on a variety of liquid dispensers, including manual, traditional, and nanodispense volumes. The data confirmed the importance of establishing robust QC procedures for dose-response generation in addition to accuracy and precision determinations for each instrument, and they validated the use of nanoliter pipettors for dose-response testing. The results of this study also support the requirement for thorough mixing during serial compound dilutions prepared for high-throughput lead optimization strategies using traditional liquid handlers. (Journal of Biomolecular Screening 2007:891-899)
Key Words: nanoliter liquid handlers • discrete dispense • serial dilution • dose-response curve • lead optimization
References
- Taylor PB, Ashman S., Baddeley SM, Bartram SL, Battle CD, Bond BC, et al: A standard operating procedure for assessing liquid handler performance in high-throughput screening. J Biomol Screen 2002;7:554-569.[Abstract/Free Full Text]
- Stevens ME, Bouchard PJ, Kariv I., Chung Tdy, Oldenburg KR: Comparison of automation equipment in high throughput screening. J Biomol Screen 1998;3:305-311.[Abstract]
- Berg M., Undisz K., Thiericke R., Zimmermann P., Moore T., Posten C.: Evaluation of liquid handling conditions in microplates. J Biomol Screen 2001;6:47-56.[Abstract/Free Full Text]
- Cleveland PH, Koutz PJ: Dispensing for uHTS using pin tools. Assay Drug Dev Technol 2005;3:213-225.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Knaide TR, Bradshaw JT, Rogers A., McNally C., Curtis RH, Spaulding B.: Rapid volume verification in high-density microtiter plates using dual-dye photometry. JALA 2006;11:319-322.
- Astle TW, Akowitz A.: Accuracy and tip carryover contamination in 96-well pipetting. J Biomol Screen 1996;1:211-216.[Abstract]
- Haber C., Boillat M., van der Schoot B.: Precise nanoliter fluid handling system with integrated high-speed flow sensor. Assay Drug Dev Technol 2005;3:203-212.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Niles WD, Coassin PJ: Piezo- and solenoid valve-based liquid dispensing for miniaturized assays. Assay Drug Dev Technol 2005;3:189-202.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Olechno J., Ellson R., Browning B., Stearns R., Mutz M., Travis M., et al: Acoustic auditing as a real-time, non-invasive quality control process for both source and assay plates. Assay Drug Dev Technol 2005;3:425-437.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Jäger S., Garbow N., Kirsch A., Preckel H., Gandenberger FU, Herrenknecht K., et al: A modular, fully integrated ultra-high-throughput screening system based on confocal fluorescence analysis techniques. J Biomol Screen 2003; 8:648-659.[Abstract/Free Full Text]
- Panchuk-Voloshina N., Haugland RP, Bishop-Stewart J., Bhalgat MK, Millard PJ, Mao F., et al: Alexa dyes, a series of new fluorescent dyes that yield exceptionally bright, photostable conjugates. J Histochem Cytochem 1999;47:1179-1188.[Abstract/Free Full Text]
- Rhode H., Schulze M., Renard S., Zimmerman P., Moore T., Cumme GA, et al: An improved method for checking HTS/uHTS liquid-handling systems. J Biomol Screen 2004;9:726-733.[Abstract/Free Full Text]
- Harris DL, Mutz M.: Debunking the myth: validation of fluorescein for testing the precision of nanoliter dispensing. JALA 2006;11:223-239.
- Richon V.: Cancer biology: mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor. Br J Cancer 2006;95:S2-S6.[CrossRef][Web of Science]
- Berlier JE, Rothe A., Buller G., Bradford J.,, Gray DR, Filanoski BJ, et al: Quantitative comparison of long-wavelength Alexa Fluor dyes to Cy dyes: fluorescence of the dyes and their bioconjugates. J Histochem Cytochem 2003;51:1699-1712.[Abstract/Free Full Text]
This version was published on September
1, 2007
Journal of Biomolecular Screening, Vol. 12, No. 6,
891-899 (2007)
DOI: 10.1177/1087057107302114
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