An efficient J-aggregate based fluorescence turn-on and ratiometric sensor for heparin

Abstract

Heparin is the second most widely used natural drug and an extensively employed blood anticoagulant worldwide. Construction of fluorescent sensors for Heparin has remained heavily dependent on the complex and time-consuming laborious synthetic efforts. However, reports on the direct usage of in-expensive commercially available probe molecule, for sensitive and selective fluorimetric sensing of Heparin, which can greatly simplify the synthetic efforts, has been limited and remains highly desirable. Herein, we report a very sensitive and selective fluorescence turn-on sensor for Heparin, which utilizes a commercially available organic dye molecule, Pseudoisocyanine. The supramolecular interaction between the Pseudoisocyanine and Heparin leads to the J-aggregate formation of Pseudoisocyanine on the surface of Heparin, with an exceptional fluorescence enhancement of ∼400 fold. The J-aggregates of Pseudoisocyanine also display remarkable changes in the absorption features, in the presence of Heparin, which provides a unique advantageous feature of dual sensing of Heparin, by colorimetry and fluorimetry. Pseudoisocyanine also displays high selectivity towards Heparin over its structurally related analogs Chondroitin sulphate and Hyaluronic acid, and other analytes, with a detection limit of 2 nM. More importantly, our sensor system shows good performance in the serum samples, a complex biological media. We further demonstrate that, the interaction of Heparin with its only medically approved antidote, Protamine can also be monitored using Pseudoisocyanine J-aggregates. Thus, our assay is sensitive and selective, rapid, simple, and inexpensive, which can promote the Heparin related biochemical and biomedical research.