Detection Of Heparin Sodium Using Gold Nanorods And Cadmium Telluride Quantum Dots As Optical Probes

Heparin sodium is a strongly negatively charged linear sulfated glycosaminoglycan.In clinical practice,heparin sodium is widely used as an anticoagulant,antithrombotic and antitumor drug.The therapeutic dosing concentration range of heparin is 2–8 U m L^-1(10.8–43.2?g m L^-1)during cardiovascular surgery and0.2–1.2 U m L^-1(1.08–6.48?g m L^-1)in postoperative and long-term therapy.So it is necessary to detect sensitively and accurately for the concentration of heparin sodium.However,more simple,accurate and rapid assays for heparin sodium sensing with high sensitivity and selectivity are still highly desirable.Here,this thesis for the sensitive and accurate detection of heparin sodium includes the following two parts:1. Fluorescence quenching of quantum dot by aggregation for detecting heparin sodium.Quantum dots,a kind of semiconductor nanocrystal,have attracted great attention in chemical and biological fields owing to their unique optical properties,such as high quantum yield,low photobleaching,long fluorescence lifetime,broad absorption and tunable emission,depending on their size.Thioglycolic acid capped cadmium telluride quantum dots?TGA-Cd Te QDs?have been used because of its strong fluorescence emission and full of carboxylic acid.Heparin sodium including sulfonic acid group,amino and other functional groups,can form hydrogen bond with the carboxyl group from Cd Te QDs,resulting in quantum dot aggregation and selective quenching fluorescence.With the increase of heparin concentration,the aggregation of Cd Te QDs also deepened,so the fluorescence also decreased.Therefore,a fluorescence‘turn-on'analytical method for heparin sodium sensing could be established with a detection range of 0.2–5?g m L^-1 and the detection limit was 0.033?g m L^-1,which is applicable to determining heparin sodium in injection samples.2.Real-time dark-field light scattering imaging to monitor the coupling reaction with gold nanorods as an optical probe and detect heparin sodium.As a one-dimensional metal nanomaterial,gold nanorods?GNRs?are widely used in optical imaging,biochemical sensing and drug analysis with its specific morphology and unique optical properties.Recently,most of studies were established about biochemical analysis and photothermal treatment basing on absorption characteristics of GNRs.But it is also necessary to find out and take use of the scattering characteristics on the dark field.A slight shape or size change of GNRs can directly lead to its optical changes,so many application about GNRs are always based on a assemble and reshape.We report a chemical reshaping of GNRs induced by the coupling reaction among Au,ferric chloride and thiourea.In the coupling reaction,Fe³⁺oxidizes GNRs to yield Au?I?,which complexes with thiourea ligand,lowering the Gibbs free energy of gold species and promoting the reaction equilibrium to enable the chemically reshape of GNRs.This coupling reaction process was monitored by light-scattering dark-field microscopy?DFM?imaging technique and scanning electron microscopy?SEM?,undergoing the light scattering colour change from bright red to yellow and finally to green,and the morphological change from rod to fusiform and finally to sphere,which is somewhat different form other chemical etching of GNRs.Specific morphological changes of gold nanorods induced by coupling reaction can not only prepare the shuttle gold nanomaterials and monitor the coupling reaction process,but it also can analysis qualitatively and quantitatively the related substances in this coupling reaction with single gold nanorod as probe.Moreover,Au[CS?NH?₂]₂⁺can further form to be complexes with heparin sodium,so it can accelerately etch GNRs.Relationship between the concentration of heparin sodium and the etching time of GNRs from red to green under DFM was used to established a method for the analysis of heparin sodium with a detection range of0.1–10?g m L^-1.This time-dependent detecting assay for heparin sodium is relatively selective and is expected to be used for specific analysis of heparin in complex biological samples.In conclusion,we established assays for the determination of heparin sodium by heparin sodium-induced quantum dot aggregation with fluorescence quenching,and heparin sodium-promoted coupling reaction monitored by real-time dark-field light scattering imaging with gold nanorods as an optical probe to detect heparin sodium sensitively.