Early history of Eastman Kodak Ektachem slides and instrumentation.

The Ektachem story starts in 1970 at the Eastman Kodak Co. in Rochester, NY. For some time, Eastman Organic Chemicals had supplied reagents to the clinical laboratory. Al Baitsholts, product manager for a thin-layer chromatographic system of impressive analyte sensitivity, became convinced that some kind of thin-layer format might form the basis for a new approach to routine clinical chemistry analysis. His timing was excellent because Kodak was interested in new products that could be made by using proprietary coating technology. Al visited his former boss and friend, Edwin Przybylowicz, a senior manager in the Kodak Research Laboratories. They discussed various configurations of thin-layer chemistry that would require no more than 10 mL of a biological fluid (serum, plasma, whole blood, and even cerebrospinal fluid) and that would yield a quantitative result. Przybylowicz was strongly taken with some of the suggestions. He formed a team consisting of Charles Warburton, Leo Kunzelsauer, and William Fellows to explore some possibilities. The goal that emerged from these early experiments was to create dry, thin films containing all of the reagents necessary for clinical analysis by colorimetry. Reagents in a matrix of hydrophilic polymer would be coated on top of a transparent plastic base and dried. Upon applying the test sample to the film, water and the analytes would diffuse into the reagent layers, initiating the reaction sequence(s). The extent of reaction would be determined by colorimetry. Spreading the test sample over the film proved to be a considerable challenge: The fluid tended to form a bead on the surface of the film. The exploratory group initially used filter paper, plastic filters, or woven fabric to spread the fluid over the reagent layer. A better solution was to coat the spreading layer as a slurry of solid particles along with a binding material over the reagent layer(s); this would become a porous solid formed in place during the drying of the coated slurry. A preferred composition, developed by Al Goffe, was based on cellulose acetate pigmented with titanium dioxide coated out of a solvent– nonsolvent mixture. When dried, this mixture yielded a highly porous structure. A schematic cross-section of an analysis slide with such a spreading layer coated over the reagent layer is shown in Fig. 1; Fig. 2 is a photomicrograph of the TiO2–cellulose acetate layer. When a drop of test fluid, such as serum, is touched to the spreading layer, it spreads rapidly until the capillary pores are filled. Applying twice the volume of fluid covers about twice the area (this was shown to be true for volumes of 5 to 15 mL). The spreading layer thus provides a coverage of fluid per unit area that is nearly independent of the volume of the applied drop. A 10-mL drop spreads to an area of ;1 cm. Because a spreading layer of TiO2–cellulose acetate is almost opaque, the colored reaction products must be quantified by reflection densitometry. Using instruments designed by the Kodak Research Laboratories, light of appropriate wavelength is directed through the film base into the reagent layers at an angle of 45° and the backreflected light is detected at 90°, thus minimizing specular reflection. Readings are made through a window in a small confined volume. The film is held at a controlled temperature as the reaction proceeds. A schematic of this setup is provided in Fig. 3. By the end of 1971, the exploratory group demonstrated that promising results could be obtained by use of common clinical chemical reaction schemes. Indeed, they produced a glucose analysis film based on the glucose