In Vivo Dynamic Monitoring Of Blood Glucose With Implantable Fluorescent Polymer-dot Transducer

Diabetes mellitus is defined as a group of metabolic disorders characterized by high blood glucose levels.Diabetes severely threatens human health because it can cause numerous complications in heart,kidney,retina,and neural system.Tight glycemic control along with regular moderate exercise,strict diet management,and hypoglycemic drug treatments is crucial for reducing pernicious morbidity and preventing diabetic complications.Therefore,reliable and continuous detection of blood glucose level is essential to manage diabetes progression and treatment.Over the past decades,various glucose monitoring technologies have been developed,which detect glucose levels in the blood or interstitial fluid.Electrochemical sensors are used in most current monitoring systems in clinical practice.Electrochemical sensors are used in most current monitoring systems in clinical practice.Optical methods for glucose sensing have the potential to overcome the limitations of electrochemical sensors.Despite many efforts,the clinical application of optical glucose sensors is severely limited by their inability to meet the required sensitivity and accuracy for transdermal detection.Another important aspect for practical application is the availability of inexpensive and portable devices for glucose measurement.However,the optical approache typically require bulky and expensive instruments,which are obstacles in their wide spread applications.Advances in nanotechnology,molecular imaging,and biomedical tools are creating new opportunities for early diagnosis,staging and monitoring of disease progression in diabetic patients.The new technologies offer solutions to overcome the problems with current glucose monitoring devices.As promising fluorescent materials,semiconducting polymer dots(Pdots)have attracted considerable interest for their applications in biological imaging and biosensors because of their high brightness,excellent stability,and biocompatibility.Based on Pdots,we developed an optical glucose transducer with high brightness,high selectivity,high sensitivity,nontoxicity,implantable.In particular,instrument miniaturization is an important consideration in the design and development of glucose monitoring devices.The miniaturisation of the optical monitoring platform can promot the clinical application of biosensor,and provide information support for diagnosis of diabetes.The results of e research ere shown as follows:1.We demonstrate sensitive detection and real-time dynamic monitoring of glucose by an implantable Pdot oxygen transducer.Upon the formation of the enzyme corona via surface conjugation,the Pdot-enzyme platforms behaved as a nanoreactor that depleted its internal oxygen reservoir in the presence of glucose substrates.We exemplify this detection strategy by using glucose-oxidase-functionalized polymer dots,yielding extraordinary brightness,excellent sensitivity,high selectivity,large dynamic range,reversible glucose detection,and good biocompatibility in cell and tissue environments.After subcutaneous implantation,the transducer-enzyme assembly continuously responsive to blood glucose fluctuations for up to 30 days.In view of a large library of oxygen-consuming enzymes,this strategy is promising for in vivo detection and quantitative determination of a variety of small molecules.2.We show that an ultrasensitive optical transducer can be used for wireless glucose monitoring via a smartphone.The optical transducer combines oxygen?sensitive polymer dots(Pdots)with glucose oxidase that sensitively detect glucose when oxygen is consumed in the glucose oxidation reaction.Because palladium porphyrin complexes have a longer lifetimes,the resulting Pdot transducer exhibits a significantly higher sensitivity in both in vitro and in vivo glucose detection.As a result,the optical images of subcutaneous glucose level obtained with the smartphone camera could be utilised to clearly distinguish between euglycemia and hyperglycemia.We further developed an image processing algorithm and a software application that was installed on a smartphone.We demonstrated real?time,dynamic glucose monitoring of blood glucose level in live mice with the smartphone and the implanted Pdot transducer.3.We developed a noninvasive method for in vivo fluorescence imaging glucose uptake by using an implantable NIR Pdot transducer.This method differs from existing molecular imaging methods that rely on radiolabeled glucose analogs.Instead,we use optical imaging technololy with high sensitivity,high selectivity,and non-invasive for in vivo glucose monitoring.After implantation,the NIR Pdot transducer can continuously responsive to blood glucose in the tumor of hyperglycemic model mice.The NIR Pdot transducer is promising clinical method for monitoring the glucose uptake and metabolism in tissue4.We developed an implantable hydrogel Pdot transducer for in vivo dynamic glucose monitoring.Due to the nature of low temperature hydrogel material,the implant process is non-invasive that looks like solution.The hydrogel Pdot transducer after subcutaneous implantation can monitor the change of blood glucose concentrations.The sensitivity obtained by hydrogel Pdot transducer was lower than the liquid Pdot transducer in the in vivo glucose monitoring results.However,these results indicated that the hydrogel Pdots transducer provieds a viable approach for the oncoming experimental study.