System Design And Experimental Research Of Lower Esophageal Sphincter Stimulator For Treatment Of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease(GERD)is defined as"a condition which occurs when the reflux of stomach contents causes troublesome symptoms and/or complications".There are about 250 million GERD patients in the world.The prevalence of GERD is increasing in recent years.The diagnosis and treatment of GERD is of great significance to improve the patients' wellbeing and reduce the healthcare cost.The primary treatment option for GERD is acid suppressive therapy,which has been shown to be effective in releasing GERD symptoms.The most potent drugs are the proton pump inhibitors(PPIs),which blocks acid secretion.However,medical therapies don't "cure" reflux disease.Rather,it treats GERD in an indirect fashion.The medical therapy with acid suppression fails to deal with the bothersome symptoms which are related to weakly acidic or nonacidic reflux or nocturnal GERD.Laparoscopic fundoplication is currently the mainstay of surgical GERD therapy and is primarily offered to those for whom medical therapies fail.However,due to the concerns about long-term failure and side effects associated with anti-reflux surgery,only a small group of GERD patients are referred for surgery,leaving a significant number of patients without an effective treatment option.The electrical stimulation therapy of lower esophageal sphincters(LES)is a relatively new technique for the treatment of GERD that may address the need of GERD patients,who are unsatisfied with medical therapy and concerned with the potential risks of laparoscopic fndoplication.The EndoStim LES stimulation system(EndoStim BV,the Hague,Netherlands)is an implantable electrical stimulator that delivers long-term electrical stimulation therapy to the LES.A large number of clinical trials have been conducted using EndoStim system abroad.However,there are few domestic researches on the electrical stimulation therapy of LES.In order to avoid the monopoly of foreign products and to fill domestic technology gaps,a programmable and implantable LES stimulator with wireless power transmission is proposed for the treatment of GERD in this paper.The LES stimulator is composed of an external controller,a wireless power transmission module,and an implantable pulse generator(IPG).The problem of limited battery life in traditional implantable devices has been solved by the wireless power transmission.The specific works of this paper is presented as follows:1)System design.After analyzing the design requirements of the proposed implantable LES stimulator,system design is determined and a block diagram is presented in this paper.System integration and biocompatible materials packaging are also discussed in this paper.2)External controller.The external controller consists of 4 main parts including an MCU with a Bluetooth Low Energy(BLE)communication function(CC2541),a USB to UART interface circuit(CH340G),a Li-ion battery charge circuit(LTC4054-4.2)and a power management circuit(RT9013-33GB).The external controller allows for wireless data communication and programming of the IPG via the BLE module.CH340G is used for the communication with PC.The Li-Ion battery charger chip LTC4054-4.2 with thermal regulation is used to charge the battery with the charging current programmed as 500 mA.The protocol stack BLE-CC254x-1.3.2 is used for software development and a C#program is developed for BLE connection,stimulation parameters programming and communication with the IPG.3)Wireless power transmission module.It uses the method of electromagnetic induction,which utilizes the principle of magnetic induction between 2 coils.The module is composed of 2 parts including a wireless power transmitter and a power receiver.The power transmitter is based on a class-E power amplifier while the receiver is based on a capacitor-filtered bridge rectifier circuit and LTC3245 Buck-Boost charge pump.The wireless power transmission module works at the frequency of 4 MHz,which guarantees the power transmission efficiency.4)Implantable pulse generator.The implantable pulse generator(IPG)consists of an MCU with the BLE communication function(CC2541),a digital to analog converter(DAC,MAX5705),an LDO regulator(RT9013-33GB),2 charge pump regulators(MAX1595EUA50+ and MAX865EUA)and a voltage-regulated constant-current stimulation circuit(OPA4192).The IPG is capable of delivering electrical stimulations with a current ranging between 0 and 8 mA.5)Experimental Research.Silicon rubber(Sylgard 184)is used to enclosure the IPG and the lead in order to meet the biocompatibility requirements while the external controller is packaged by an ABS plastic shell.After that,system tests,which mainly foucus on the wireless power transmission,are carried out.The position tolerance values under 3 medium conditions are obtained.In order to evaluate the safety and efficacy of the proposed LES stimulator,experiments including GERD model establishing,esophageal manometry and LES stimulation are performed.The results show that the electrical stimulation delivered by the LES stimulator can safely and effectively increase resting LES pressure in acute animal models,suggesting that the stimulator is a perspective approach for treating GERD in clinics.