A drug-screening assay method for determining the efficacy of a potential drug on a target protein undergoing secondary structural changes associated with a disease with misfolded target proteins in a complex body fluid, comprising the steps: (a) conducting, in an IR cell comprising an infrared sensor element having an internal reflection element with a core of an infrared transparent material and at least one receptor for the target protein directly grafted to at least one surface of said core, said at least one receptor for the target protein being antibodies capable of specific and conformationally independent binding to the target protein, a flux of a sample of the complex body fluid with soluble target protein; submitting an IR beam through said IR cell; and obtaining an infrared spectrum therefrom; (b) conducting, in the same IR cell of step (a), wherein the receptors for the target protein grafted to the surface of the core are loaded with the target protein, a flux of a solution with potential drug; submitting an IR beam through said IR cell; and obtaining an infrared spectrum therefrom; (c) subtracting a reference spectrum of the potential drug for detecting the shift of the amide I band of the target protein; and (d) analyzing the obtained infrared spectra to evaluate the effect of the potential drug by determining the secondary structure distribution of the soluble target protein in the sample and after application of the potential drug, wherein an upshift or disappearance of the amide I band characteristic for β-sheets in the spectrum of (b) relative to the corresponding amide I band in (a) is indicative for the efficacy of the potential drug; wherein the target protein undergoing conformational transitions is alpha-Synuclein. (a) conducting, in an IR cell comprising an infrared sensor element having an internal reflection element with a core of an infrared transparent material and at least one receptor for the target protein directly grafted to at least one surface of said core, said at least one receptor for the target protein being antibodies capable of specific and conformationally independent binding to the target protein, a flux of a sample of the complex body fluid with soluble target protein; submitting an IR beam through said IR cell; and obtaining an infrared spectrum therefrom; (b) conducting, in the same IR cell of step (a), wherein the receptors for the target protein grafted to the surface of the core are loaded with the target protein, a flux of a solution with potential drug; submitting an IR beam through said IR cell; and obtaining an infrared spectrum therefrom; (c) subtracting a reference spectrum of the potential drug for detecting the shift of the amide I band of the target protein; and (d) analyzing the obtained infrared spectra to evaluate the effect of the potential drug by determining the secondary structure distribution of the soluble target protein in the sample and after application of the potential drug, wherein an upshift or disappearance of the amide I band characteristic for β-sheets in the spectrum of (b) relative to the corresponding amide I band in (a) is indicative for the efficacy of the potential drug; <EOS>