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Tiffany's daring experiments in glass technologies and materials beginning in the 1870s resulted in entirely new products that revolutionized the glass industry in the Western world. His opalescent glass, patented by 1881 and utilized in the Ayer Mansion, for example, "proved to be among the most important advances in decorative windows since the Middle Ages." The mosaics of the apse-like stair opening are composed of semitransparent glass backed by metallic foil to reflect light. The iridescent effects created by Tiffany in a similar commission proved to a contemporary critic that "a Yankee brain can outdo nature." The three-dimensional effect of the tromp l'oeil pavilion on the stair landing was created through Tiffany's characteristic use of "plating" or layering clear and opaque glasses to add depth of color and three dimensionality. The adjoining marble engaged columns, raised on a slightly projecting plane, further adds to the optical illusion.

Two contemporary sources link Louis Comfort Tiffany to the design of the Ayer Mansion at 395 Commonwealth Avenue in Boston. The American Architect and Building News illustrated the newly-completed house in December 21, 1901, and described Tiffany's involvement. "In carrying out his design, the architect had the benefit of association with Mr. Louis Comfort Tiffany, who designed the exterior mosaic-work, which makes the house so notable on a Boston street, as well as decorated the interesting main staircase…" Secondly, a sketch titled "Smoking Room at the Ayer Mansion, Boston," and owned by Ayer descendents is attributed to Rene de Qualin, Tiffany's head designer. The Turkish Smoking Room is reminiscent of Tiffany's own studio, now destroyed. It is not known whether it was ever executed.

The New York architect of the Ayer Mansion to which the American Architect and Building News and the building permit refer was A.J. Manning, about whom little is known. Manning worked for New York architect Robert H. Robertson beginning in 1884, and became his partner, head draftsman and office manager in 1887. In about 1900, when the Ayer Mansion was designed, he broke from Robertson and practiced independently in New York until 1914. His association with Tiffany may have begun while in the office with his mentor. During the 1870s, Robertson had worked in the firms of George B. Post, Edward T. Potter, and William A. Potter. Post and the Potters were frequent collaborators with L.C. Tiffany.