A Versatile Microarray Immobilization Strategy Based on a Biorthogonal Reaction Between Tetrazine and Trans-Cyclooctene.

Given its increasing importance in transforming biomedical research in recent years, microarray technology has become highly popular as a powerful screening platform in detecting biomolecule interactions, discovering new inhibitors, and identifying biomarkers as well as diagnosing disease. The success of microarray technology in various biological applications is highly dependent on the accessibility, the functionality, and the density of the surface bound biomolecules. Therefore, compound immobilization represents a critical step for the successful implementation of microarray screening. Herein we describe a fast and site-specific microarray immobilization approach by using trans-cyclooctene-tetrazine ligation. This approach not only ensures fast immobilization and uniform display of biomolecules, but also allows the optimum orientation of biomolecules after immobilization. All these excellent properties facilitate subsequent interactions of the biomolecules and their interacting partners during the screening process. We envision that the immobilization strategy described here can find useful applications in many other microarray related studies.