Design of an integrated optics for transglutaminase conformational change

A detailed theoretical research on a novel integrated optics with surface plasmon resonance (SPR)-based waveguide is presented. An SPR multilayer section is designed by introducing intermediate layers to support fundamental mode and stronger electromagnetic field. Most current techniques excited with a single optical mode are "blind" to the conformational change of bound molecules. The greatest strength of such technique lies in monitoring protein conformational change. The Mach-Zehnder interferometry architecture is adopted to maximize sensor sensitivity and prevent unspecific binding from biological material and error from geometrical difference. A proof-of-concept is conducted on the integrated optics by detecting protein transglutaminase (tTG) specifically binding calcium ion (Ca²⁺) via the finite-element method. The minimum decrease of biolayer thickness (δ_a=0.5 nm) caused by tTG-Ca²⁺ interaction is much smaller than a single protein molecule (normally 1-100 nm). Associated with biolayer thickness and density, a thin dense layer is formed as Ca²⁺ binds to the tTG protein. Thus, the tTG protein undergoing conformational change on binding Ca²⁺ is traced and verified as molecular interaction occurs.