A hemicyanine based fluorescence turn-on sensor for amyloid fibril detection in the far-red region

Abstract

The designing or identification of extrinsic fluorescence probes for the sensitive and selective detection of amyloid fibrils, which can emit in the red to near infrared region, is an extremely important area of research. Long wavelength emission offers various crucial advantages such as preventing auto-fluorescence and photo-damage of specimen, reduced scattering, large penetration depth, etc. Herein, we have identified a hemicyanine based organic dye molecule, LDS722, which displays an impressive fluorescence turn-on emission (~200 fold increase), in the near infrared region of the spectrum, in presence of insulin fibrils. LDS722 also displays a very high selectivity to bind to the fibrillar form of insulin as opposed to its native conformation. Remarkably, the probe also registers a very large Stokes' shift of ~170 nm and a huge red shift of ~120 nm in the excitation spectra. The significant shift in the absorbance maximum of the fibril-bound probe, from its initial free form, results in the visual colour change facilitating naked eye detection of the fibril positive solution. LDS722 could also efficiently monitor the kinetic progression of the fibrillation process without any interference. Importantly, LDS722 also shows a good performance in the human serum matrix with a LOD of 55 nM.