It is increasingly evident that direct dilution has a future role to play in doseresponse analysis and where acoustic droplet ejection is preferentially deployed additional benefits will be derived in terms of reduced waste stream generated, less source material used and no cross-contamination. Some groups are now reporting that IC50 values of compounds tend to be lower (more active) when the concentrations are made via direct dilutions. These investigations have been aided by the availability of low volume dispensing systems with good precision at low nL dispense volumes and a relatively wide dynamic range. This in turn adds to concern over the reliability of the results generated and the extent to which they are a true reflection of the potency of the compounds being evaluated.Īs part of the general drive to enhance the quality of screening data generated researchers are investigating strategies based on the direct dilution of micro-volumes of compound (ie on a volumetric basis). In addition, it is now suspected that hydrophobic compounds may be lost from solution during aqueous serial dilutions and absorbed to intermediate plastic surfaces. However, it is well recognised that inadequacies in the liquid handling or mixing technique will affect the dilution ratio and hence the compound concentration and any errors will be compounded during each successive serial dilution, mix and transfer.Ī recent poll of end users ranked better precision, particularly at lower drug concentrations, and the reduction in compound precipitation as the improvements in dose-response analysis they most desired. The serial dilution method is standard practice in the preparation of doseresponse series for IC50 determination.
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