The magnitude of surface enhancement from thin metal films is known to be critically dependent on film morphology. In order to establish the best methodology for generating reproducible vapor-deposited thin metal films, the influence of a wide range of experimental deposition variables on Ag film morphology and optical properties was investigated by use of a combination of optical absorption, atomic force microscopy, and surface-enhanced Raman spectroscopy (SERS). The specific variables examined include quality of glass substrate, glass pretreatment, deposition rate, deposition temperature, deposition geometry, and postdeposition annealing. The type of glass substrate ("white" glass vs "float" glass) was found to be an important factor for producing high-quality Ag films. However, glass pretreatment appeared to be relatively unimportant Deposition rate and geometry are critical parameters in generating reproducible films. In addition, mild elevation of substrate temperature (A20 °C) strongly affects film characteristics. A detailed analysis of SERS reproducibility, based on these variables, is reported.Thin metal films are employed as substrates in a broad range of fields due to their unique optical and electronic properties.Perhaps the most widespread application of thin metal films is as the active surface for surface-enhanced Raman scattering (SERS).Although other rough metal substrates provide surface enhancement, such as electrodes, colloids, and metal-coated nanospheres, vapor-deposited thin metal films are widely used because of their stability and the ease with which they are prepared and characterized.1-6 While the morphology and optical characteristics of vapor-deposited thin metal films have been studied as a function of deposition parameters, film reproducibility, especially in the context of SERS, remains an issue. SERS active metal films are prepared differently in every laboratory, resulting in a unique morphology and therefore unique optical properties. The goal of this work is to establish which of the many experimental variables of vapor deposition are most important in generating reproducible SERS active Ag films.
A queous solubility is one of the most critical physicochemical properties to be determined in the process of drug lead optimization. Particularly, an equilibrium solubility method is highly valuable to the study of structure property relationship (SPR), while meeting the needs of analytical sensitivity, reproducibility, and throughput. In this report, an automated solubility assay in a 96-well library format was designed and developed by means of robotic liquid handling, centrifugal separation, and HPLC-UV quantification. Requiring 1 mg of solid compound, this assay was used to determine the equilibrium solubility in three user-selected media, that is, 0.01 N HCl, phosphate buffer saline (PBS), and fasted state simulated intestinal fluid (SIF), with a throughput of up to 192 compounds a week. The assay parameters, including the equilibration time and the separation technique, were optimized to ensure that the thermodynamic solubility was measured at the presence of excess solid compound. A fast gradient HPLC method was developed with single-point on-plate calibration for each compound, followed by a customized 96-well chromatographic data analysis. The reporting solubility range was 1-200 mg/mL, appropriate for oral drug candidate selection at the stage of discovery lead optimization. Based on the test results obtained on the commercially available drugs and Amgen research compounds, this assay was considered to be equivalent to the conventional shake-flask methods. Examples were given to demonstrate that the thermodynamic solubility determined by this assay enabled the SPR study to support drug lead optimization. ( JALA 2005;10:364-73)
A novel approach to high-throughput logP measurement based on liquid chromatography/ultraviolet/mass spectrometry (LC/UV/MS) is proposed. The logP value is determined by correlation with the logk value, where k is the capacity factor k = (t(r)-t(0))/t(0), with the logP value using a defined set of standards. Since the analyte retention time (t(r)) is determined from the appropriate extracted ion chromatogram (EIC), there are no interferences from impurities and this allows the pooling of multiple compounds into one injection. To ensure the accuracy and instrument robustness in a routine high-throughput environment, a simple and MS-friendly mobile phase consisting of 20 mM ammonium carbonate (pH 8.0) for basic compounds or 20 mM ammonium formate (pH 1.0) for acidic compounds, both in combination with methanol at a ratio of 45:55, is used. This approach has been successfully used on single as well as parallel multi-channel LC/UV/MS systems to screen small to large sets of lead compounds and their analogs. A high-throughput capability to analyze over 1000 compounds per day has been achieved.
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