James Norman Cawse

The development of combinatorial chemistry methods for coating development: I. Overview of the experimental factory

Abstract Combinatorial chemistry has proven to be a valuable tool for the development of new compounds. The combinatorial methodology is well suited to the development of complex, multicomponent materials that, typically, require extensive experimentation for their development. As a result, coating development appeared to be a good candidate for the application of the combinatorial methodology. A “combinatorial factory” capable of preparing and testing over 100 coatings per day has been developed. The components of the factory consist of: (1) an automated system to prepare liquid coating formulations; (2) a novel coating application process capable of making high density arrays of coatings of controlled thickness; (3) curing of the coating arrays either thermally or with UV light; (4) testing of the coatings using newly developed high throughput screening methods; and (5) a data handling process to quickly identify the most promising coatings produced. Various aspects of the application of the combinatorial methodology to coating development are described.

Combinatorial discovery of metal co-catalysts for the carbonylation of phenol

Abstract The palladium-catalyzed carbonylation of phenol to form diphenyl carbonate (DPC) requires the presence of a metal co-catalyst to catalyze the reoxidation of palladium from Pd 0 to Pd 2+ in the presence of oxygen. In this study, we utilize a high throughput screening (HTS) methodology to rapidly study the nature of the co-catalyst with an emphasis on combinations of metal co-catalysts that appear to work in a synergistic manner to increase palladium usage. Critical new developments were made in using a small-scale reactor in diffusion controlled systems. The HTS system is described along with the optimized catalyst packages that were determined. Additionally, the results from HTS were used to better elucidate the mechanism of this potentially important commercial reaction.

Combinatorial chemistry methods for coating development: III. Development of a high throughput screening method for abrasion resistance: correlation with conventional methods and the effects of abrasion mechanism

Combinatorial chemistry has proven to be a valuable tool for the development of new compounds. In the pharmaceutical industry, where combinatorial chemistry began, the approach has been instrumental in the high-speed development of new drugs. Due to the overwhelming success of the combinatorial methodology in the pharmaceutical industry, it has been recently applied to materials development. We have developed a combinatorial factory capable of preparing and evaluating of the order of 100 organic clear coatings per day. One of the most challenging aspects of the creation of the combinatorial factory was the development of the high throughput screening (HTS) methods for determining the primary properties of interest such as optical clarity, abrasion resistance, adhesion, and weatherability. For each property, an entirely new method was developed that allowed for rapid measurement on very small samples. This paper describes, in detail, some of the results obtained during the development of an HTS method for abrasion resistance. In particular, this document illustrates the importance of understanding the mechanism of abrasion and its influence on the measurement of abrasion resistance.

Combinatorial chemistry methods for coating development: V. The importance of understanding process capability

A combinatorial method for the development of organic clear coatings for plastic substrates has been developed. The combinatorial process possesses all the aspects of a conventional combinatorial process such as automated sample preparation, miniaturized samples configured in an array format, high throughput screening (HTS) of the properties of interest, and computer software developed for data management, storage, and analysis. The combinatorial factory has greatly enhanced the rate of organic clear coat development. A very important activity involved in the development of the combinatorial factory was the determination of process capability for each component of the factory. A good understanding of process capability and sources of variability was required to obtain high quality, reliable data.

Doubly stochastic Poisson distribution of platelet adhesion on material surfaces and its implication on fluorescence image analysis

An image based assay has been developed to quantify platelet adhesion on material surfaces. Briefly, citrated platelet rich plasma (PRP) is incubated with materials for 2 h to allow platelet adhesion on the surface, followed by fluorescence labeling of platelets with Celltracker Green. Multiple images are acquired by an automatic fluorescence microscope, IN Cell Analyzer 1000. Platelets are identified and counted by an automatic image analysis algorithm. We have observed that the variance of the counts is considerably greater than expected from simple distribution laws. Statistical analysis of that difference shows that these measurements will often follow a doubly stochastic Poisson process in which the variance is inherently very large. To overcome this, multiple images (n > or = 8 images/well, about 3% of total area) are necessary to achieve accurate counting. This method has been compared to the commonly used enzyme based platelet adhesion assay, lactate dehydrogenase (LDH) assay. It is concluded that the present method is only effective in quantifying adherent platelets when a large number of samples are used. However, this method does provide additional information on platelet morphology and spatial distribution, which is lacking in the LDH assay.

High-Throughput Adhesion Evaluation and Scale-up of Combinatorial Leads of Organic Protective Coatings

Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. This approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 × 6 arrays of coating elements that are discretely deposited on a single 9 × 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss. This parameter is one primary consideration in end-use automotive applications. Coating leads identified from the HT screening have been validated on the traditional scale. Details of these validation studies are discussed.

Application of Combinatorial Chemistry Methods to The Development of Organic Coatings

A combinatorial method for the development of organic clear coatings for plastic substrates has been developed. The combinatorial process or combinatorial factory has a throughput on the order of 100–200 coatings per day and possesses all of the aspects of a conventional combinatorial process such as automated sample preparation, miniaturized samples configured in an array format, high throughput screening of the properties of interest, and computer software developed for data management, storage, and analysis. The combinatorial factory greatly enhanced the rate of organic clear coat development.