Assay Explorer

Out-of-the-box HTS informatics software solutions with integrated functionality of all three operational components (HTS data, plate and sample tracking, chemical structures) include ActivityBase from IDBS, Assay Explorer from Symyx (former MDL), BioAssay Enterprise from CambridgeSoft, Accord Enterprise (Accelrys), Chemlnnovation (CBIS), and others. However, we recommend careful evaluation of functionality, usability, architecture, and availability of a published application programming interface (API) if the system is to be integrated with other informatics components. Because the commercial solutions have different strengths, one answer is to combine different components or build certain functionalities in-house. 

Oppenlander T (1988) A Comprehensive Photochemical and Photophysical Assay Exploring the Photoreactivity of Drugs, Chimia 42, No. 10 331-342. 

Oppenlander, T., 1988, A comprehensive photochemical and photophysical assay exploring the photoreactivity of drugs. CHIMIA, 42, 331-342. 

Iversen (1991) stresses the need for some in vivo testing for neurotoxicity and emphasizes the value of sensitive behavioral tests. Behavioral tests are described for mice and rats, which provide measures of mood, posture, CNS excitation, motor coordination, sedation, exploration, responsiveness, learning, and memory function. Such assays can function as primary screens for neurotoxicity before adopting a stepwise scheme of in vitro tests to discover more about the initial site of action of neurotoxic compounds. It is argued that the requirement for animal testing can be drastically reduced by adopting structured in vitro protocols such as these. 

Hill WE Jr. (1974) The use of analytical standards to control assaying projects in Geochemical Exploration 1974. In Elliott IL and Fletcher WK, eds. Proc 5th International Geochemical Exploration Symposium pp. 651-657. 

For example, use of 10 different isocyanides and amines, along with 40 different aldehydes and carboxylic acids has the potential to generate 160,000 different dipeptide analogs.65 This system was explored by synthesizing arbitrarily chosen sets of 20 compounds that were synthesized in parallel. The biological assay data from these 20 combinations were then used to select the next 20 combinations for synthesis. The synthesis-assay-selection process was repeated 20 times. At the end of this process the average inhibitory concentration of the set of 20 products had been decreased from 1 mM to less than 11xM. 

Validate routine methods, i.e., define the conditions under which the assay results are meaningful.115 To do that, one must select samples that are truly representative of the product stream. This may be a difficult task when the process is still under development and the product stream variable. The linearity of detector response should be defined over a range much broader than that expected to be encountered. Interference from the sample matrix and bias from analyte loss in preparation or separation often can be inferred from studies of linearity. Explicit detection or quantitation limits should be established. The precision (run-to-run repeatability) and accuracy (comparison with known standards) can be estimated with standards. Sample stability should be explored and storage conditions defined. 

Sugano et al. [561,562] explored the lipid model containing several different phospholipids, closely resembling the mixture found in reconstituted brush border lipids [433,566] and demonstrated dramatically improved property predictions. The best-performing lipid composition consisted of a 3% wt/vol lipid solution in 1,7-octadiene (lipid consisting of 33% wt/wt cholesterol, 27% PC, 27% PE, 7% PS, 7% PI). The donor and acceptor compartments were adjusted in the pH interval between 5.0 and 7.4 [562]. With such a mixture, membrane retention is expected to be extensive when lipophilic drugs are assayed. The use of 1,7-octadiene in the assay was noted to require special safety precautions. 

Four neutral lipid models were explored at pH 7.4 (1) 2% wt/vol DOPC in dode-cane, (2) olive oil, (3) octanol, and (4) dodecane. Table 7.5 lists the effective permeabilities Pe, standard deviations (SDs), and membrane retentions of the 32 probe molecules (Table 7.4). The units of Pe and SD are 10 6 cm/s. Retentions are expressed as mole percentages. Figure 7.22a is a plot of log Pe versus log Kd (octanol-water apparent partition coefficients, pH 7.4) for filters loaded with 2% wt/vol DOPC in dodecane (model 1.0, hlled-circle symbols) and with phospholipid-free dodecane (model 4.0, open-circle symbols). The dashed line in the plot was calculated assuming a UWL permeability (see Section 7.7.6) Pu, 16 x 10-6 cm/s (a typical value in an unstirred 96-well microtiter plate assay), and Pe of 0.8 x 10-6 cm/s... 

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