Improved specific biodetection with ion trap mobility spectrometry (ITMS): a 10-min, multiplexed, immunomagnetic ELISA.

Enabling trace chemical detection equipment utilized in the field to transduce a biodetection assay would be advantageous from a logistics, training, and maintenance standpoint. Described herein is an assay design that uses an unmodified, commercial off-the-shelf (COTS) ion trap mobility spectrometer to analyze an immunomagnetic enzyme-linked immunosorbant assay (ELISA). The assay, which uses undetectable enzymatic substrates and ELISA-generated detectable products, was optimized to quantitatively report the amount of target in the sample. Optimization of this ELISA design retained the assay specificity and detection limit (approximately 10(3) E. coli per assay) while decreasing the number of user steps and reducing the assay time to 10 min (>9-fold decrease as compared to past studies). Also discussed are previously undescribed, independent substrate/enzyme/product combinations used in the immunomagnetic ELISA. These discoveries allow for the possibility of a quantitative, multiplexed, 10-min assay that is analyzed by the ion trap mobility spectrometer trace chemical detector.

High-throughput determination of quantitative structure-property relationships using a resonant multisensor system: solvent resistance of bisphenol a polycarbonate copolymers.

Polymers are important materials for sensor, microfluidic, and other demanding applications. High-throughput screening methodology has been applied for the evaluation of the solvent resistance of a family of polycarbonate copolymers prepared from the reaction of bisphenol A (BPA), hydroquinone (HQ), and resorcinol (RS) in different solvents of practical importance, such as chloroform, tetrahydrofuran (THF), and methyl ethyl ketone (MEK). We employed a 24-channel acoustic-wave sensor system that provided previously unavailable capabilities for parallel evaluation of polymer solvent resistance. This high-throughput polymer evaluation approach assisted in construction of detailed solvent-resistance maps of polycarbonate copolymers and in determination of quantitative structure-property relationships. The best absolute solvent resistance of all studied copolymers was achieved in MEK, followed by chloroform and THF. A D-optimal mixture design was employed to explore the relationship between the copolymer compositions and their solvent resistance. The applied special cubic model for each solvent took into account the primary mixture terms such as BPA, HQ, and RS; binary interaction terms such as BPA-HQ, BPA-RS, and HQ-RS; and a ternary interaction term BPA-HQ-RS. A combination of the normal distribution of the model residuals and the very high values of adjusted R2 (0.97-0.99) demonstrated a good quality of the model. At a HQ concentration of 40 mol %, the solvent resistance was the highest for all tested solvents, and different concentrations of BPA (40 and 60 mol %) and RS (0 and 20 mol %) did not affect the solvent resistance. Without HQ, solvent resistance was decreasing with an increase of RS and decrease of BPA. Overall, with an increase of HQ concentration from 0 to 40 mol %, the solvent resistance of BPA-HQ-RS copolymers was improved by up to 3 times in THF, by 21 times in chloroform, and by 32 times in MEK.

Resonant multisensor system for high-throughput determinations of solvent/polymer interactions.

Solvent-resistant polymers are important in numerous research, engineering, and consumer applications. To address the limitations of existing methods of evaluation of polymer solubility and solvent resistance, we developed and built a 6 x 4 array of resonant acoustic-wave sensors operating in the thickness shear mode (TSM). The application of this system makes possible analysis of nanogram quantities of polymers in small amounts of solvent and permits the simultaneous analysis of multiple samples, such as those produced in combinatorial polymerization reactions. These parallel determinations of polymer/solvent interactions eliminate errors associated with serial determinations. During the periodic exposure of the TSM crystals to polymer/solvent combinations, the mass increase of the crystal is determined, which is proportional to the amount of polymer dissolved and deposited onto the sensor from a polymer solution. We demonstrate our sensor system for reliable quantification of solubility of several types of polymers in various solvents. The high mass sensitivity of our resonant TSM sensors (10 ng), use of only a minute volume of a solvent (< 2 mL), and parallel operation (matching a layout of available 24 well plates) make this system a good fit with available polymer combinatorial synthesis equipment.

Fluorescence spectroscopy and multivariate spectral descriptor analysis for high-throughput multiparameter optimization of polymerization conditions of combinatorial 96-microreactor arrays.

Selection of optimum process conditions in combinatorial microreactors is essential if the combinatorial synthesis process is to be correlated with the synthesis process on a more conventional scale and the materials are to have the desired chemical properties. We have developed a new methodology for the high-throughput multiparameter optimization of polymerization reaction conditions in arrays of microreactors. Our strategy is based on the application of nondestructive spectroscopic techniques to measure chemical properties of polymers directly in individual microreactors followed by the multivariate spectral descriptor analysis for rapid determination of the optimal process conditions. We have demonstrated our strategy in the high-throughput multiparameter optimization of process conditions in thin-film melt polymerization reactions performed in 96-microreactor arrays for combinatorial screening of new polymerization catalysts. The combinatorial polymerization system was optimized for the best processing parameters using a set of input variables that included reactant parameters (relative amounts of starting components and catalyst loading) and processing variables (reaction time, reaction temperature, and inert gas flow rate). The measured output parameters were the chemical properties of materials and reproducibility of the material formation in replicate polymerizations in microreactors. Spatially resolved nondestructive evaluation of polymer formation was performed directly in individual microreactors and provided information about the spatial homogeneity of polymers in microreactors. It showed to be another powerful indicator of the reproducible polymerization process on the combinatorial scale. Although the methodology described here was implemented for high-throughput optimization of polymerization conditions, it is more general and can be further implemented for a variety of applications in which optimization of process parameters can be studied in situ or off-line using spectroscopic and other tools.

Reaction of silicate minerals to form tetramethoxysilane.

Several silicon dioxide sources were used as reagents in the base-mediated reaction with dimethyl carbonate (DMC) to make tetramethoxysilane (Q'). Several commercially available diatomaceous earth materials were investigated. High throughput screening was employed to explore over 200 silicate rocks and minerals as alternative silicon dioxide sources for formation of Q' from DMC and base. Amorphous silicon dioxide materials are effective reagents for the Q' forming reaction. Effective silicon dioxide sources in addition to the diatomaceous earth materials include opal and various synthetic silicates (Li, Co, and Ca).