Multiplex label-free biosensor for detection of autoantibodies in human serum: Tool for new kinetics-based diagnostics of autoimmune diseases

• Published in: Biosensors & bioelectronics Vol. 159; p. 112187
• Main Authors: Orlov, A.V., Pushkarev, A.V., Znoyko, S.L., Novichikhin, D.O., Bragina, V.A., Gorshkov, B.G., Nikitin, P.I.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-07-2020
• Subjects: Autoantibodies - blood; Autoantibodies - immunology; Autoantibody activity; Autoimmune Diseases - blood; Autoimmune Diseases - diagnosis; Autoimmune Diseases - immunology; Biosensing Techniques; Diagnostics of autoimmune diseases; Human serum; Humans; Immunoassay - methods; Label-free biosensing; Microarray Analysis - methods; Surface-induced conformational changes; Human serum; Diagnostics of autoimmune diseases; Autoantibody activity; Label-free biosensing; Surface-induced conformational changes
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2020.112187

A multiplex label-free biosensor is developed for diagnostics of autoimmune diseases by highly sensitive measuring in human serum both critical characteristics of autoantibody: concentration and native kinetic parameters that reflect autoantibody aggressiveness to the organism's tissues. The biosensor is based on the spectral-correlation interferometry and image processing of a microarray glass biochip, affordable to be single-used in medical applications. Simultaneous 25-min detection and activity characterization of several autoantibodies in the same serum sample have been demonstrated for anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) as models. The biosensor offers extremely high sensitivity: limits of detection in serum are 1.7 IU/mL and 6 IU/mL for anti-TPO and anti-TG, respectively. The dynamic range covers the whole range of clinically relevant concentrations of the autoantibodies up to 1000 IU/mL. The developed method of characterization of autoantibody activity by recording the kinetics of their binding with free native antigens is based on autoantibody polyvalency. The measurements in clinical serum samples have shown that the native kinetic parameters are independent of concentration. The proposed biosensor and method of native kinetic registration can be used to develop new criteria for comprehensive diagnostics of autoimmune diseases, based not only on traditional measurements of concentration but also on quantitative evaluation of autoantibody aggressiveness. The developed method can be adapted to other label-free sensors such as those based on the surface plasmon resonance, optical waveguides, etc.
•Multiplex label-free biosensor for measuring both activity and concentration of autoantibodies.•Ultrasensitive rapid detection of anti-TPO and anti-TG in human serum.•Measuring kinetics of targeting free native antigens to quantify autoantibody aggressiveness.•Microarray glass biochips affordable to be single-used for medical diagnostics.•Tool for new kinetics-based criteria of comprehensive diagnostics of autoimmune diseases.