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In this paper, we propose an evanescent wave-based infrared (IR) spectroscopic sensing method for the selective and sensitive detection of tyrosine in aqueous solution. In this approach, α-cyclodextrin (α-CTD) was chemically immobilized onto the surface of an IR-sensing element to attract tyrosine specifically to the surface of the sensing element. Theoretical equations were developed for the quantitative analysis of tyrosine. Based on its IR spectra, the synthesized α-CTD phase was stable in water. Optimal detection with this system occurred when the pH of the solution was ca. 10.5. Based on the absorption bands, we confirmed that α-CTD was most effective at attracting tyrosine under basic conditions. Using the unique absorption band of tyrosine at 1500
cm
−1, the α-CTD phase allowed the detection of tyrosine selectively from among a range of potentially interfering amino acids and other species commonly present in biological samples. For quantitative analysis, this CTD-modified phase was most suitable for sensing tyrosine at concentrations below 100
μM because of limits in the surface adsorption mechanism. The detection times were, in some instances, lower than 5
min. For a detection time of 10
min, the detection limit of tyrosine was ca. 0.4
μM.