Attenuated total reflectance-based biosensor for conformation and secondary structure analysis

Inventors

GERWERT, KlausWiltfang, JensOLLESCH, JulianNabers, AndreasSCHARTNER, JonasKÖTTING, Carsten

Assignees

Betasense GmbH

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Publication Number

US-11073470-B2

Patent

Publication Date

2021-07-27

Expiration Date


Abstract

Provided herein is a biosensor for conformation and secondary structure analysis, notably for the direct non-invasive qualitative secondary structure analysis of a single selected protein within a complex mixture, as e.g. a body fluid, by vibrational spectroscopic methods. For the analysis it is not required that the selected substance be isolated, concentrated, or pretreated by a special preparative procedure.

Core Innovation

The patent discloses an infrared sensor element adapted for detection of different conformations of a secondary structure of a biomarker protein that undergoes conformational transitions associated with disease progression. The sensor element comprises a germanium internal reflection element of a trapezoid or parallelogram shape that is transparent in an infrared spectrum and is configured to provide for at least five internal reflections at a functionalized surface.

The sensor element further comprises an antibody directly grafted to the functionalized surface. The antibody specifically binds amyloid-beta or alpha-synuclein and binds independently of the conformation of the secondary structure of the biomarker protein.

For amyloid-beta, the antibody specifically binds amino acid residues 13-28, and for alpha-synuclein, the antibody specifically binds amino acid residues 103-108. The infrared sensor element is configured to detect different conformations of the secondary structure of the amyloid-beta or alpha-synuclein in a body fluid from a patient.

Claims Coverage

Two independent claims are present. Both independent claims cover the same overall concept of an infrared sensor element using a transparent germanium internal reflection element with at least five internal reflections and an antibody directly grafted to a functionalized surface, configured to detect different secondary-structure conformations of amyloid-beta or alpha-synuclein in patient body fluid.

Infrared sensor element for conformational secondary-structure detection using a germanium internal reflection element with direct antibody grafting

An infrared sensor element adapted for detection of different conformations of a secondary structure of a biomarker protein, wherein the infrared sensor element comprises a germanium internal reflection element of a trapezoid or parallelogram shape that is transparent in an infrared spectrum and configured to provide for at least five internal reflections at the functionalized surface, and an antibody directly grafted to the functionalized surface that specifically binds amino acid residues 13-28 of amyloid-beta or amino acid residues 103-108 of alpha-synuclein, the antibody binding independent of the conformation of the secondary structure, and the infrared sensor element is configured to detect different conformations of the secondary structure of the amyloid-beta or alpha-synuclein in a body fluid from a patient.

Germanium internal reflection infrared sensor element with at least five internal reflections and conformation-independent antibody binding

An infrared sensor element comprising a germanium internal reflection element of a trapezoid or parallelogram shape that is transparent in the infrared spectrum and configured to provide for at least five internal reflections at the functionalized surface, and an antibody directly grafted to the functionalized surface that specifically binds amino acid residues 13-28 of amyloid-beta or amino acid residues 103-108 of alpha-synuclein, wherein the antibody binds independent of the conformation of the secondary structure of amyloid-beta or alpha-synuclein, and the infrared sensor element is configured to detect different conformations of a secondary structure of the amyloid-beta or alpha-synuclein in a body fluid from a patient.

The independent claims focus on a germanium trapezoid/parallelogram infrared internal reflection element providing at least five internal reflections at a functionalized surface, with an antibody directly grafted to that surface and selected epitope specificity for amyloid-beta or alpha-synuclein that binds independently of secondary-structure conformation, enabling detection of different secondary-structure conformations in patient body fluid.

Stated Advantages

Documented Applications

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