Summary

自主和可充电 Microneurostimulator 内窥镜植入黏膜下层

Published: September 27, 2018
doi:

Summary

高频低能量刺激的应用可以缓解胃动力障碍的症状。在这项研究中, 提出了一个微型, 内窥镜植入和无线可充电装置, 植入到黏膜下口袋里。成功的双向沟通和刺激控制是在生猪实验中取得的。

Abstract

胃动力障碍可能是常见疾病的标志, 如长期糖尿病。应用高频低能量刺激可有效缓解胃动力障碍的症状, 提高其效果。研究的目的是开发一个微型的, 内窥镜植入装置的黏膜下口袋。植入装置是一种完全定制的电子封装, 专门为黏膜下层的实验目的而设计。该装置装有锂离子电池, 可通过接收来自充电/发射线圈的入射磁场来无线充电。上行通信以 432 MHz 的 MedRadio 波段实现。该装置被内窥镜插入到一个活体猪的黏膜下袋中, 用作体内模型, 特别是胃窦。实验证实, 所设计的装置可植入黏膜下层, 具有双向通信能力。该装置可对肌肉组织进行双极刺激。

Introduction

胃动力障碍可以是一些比较常见的疾病, 如胃轻瘫的迹象, 这通常是慢性进展的特点, 并对患者的社会、工作和身体状况施加相当严重的后果。大多数的胃轻瘫病例通常是糖尿病或特发性的起源, 通常对现有药物有抗药性1。患者患有这种情况最常见的是恶心和反复呕吐。在前人研究的基础上, 应用高频低能量电刺激可以有效缓解和减轻胃动力障碍12的症状。

在前人研究的基础上, 证明高频胃电刺激可显著改善胃排空障碍3。结果表明, 下食管括约肌神经刺激器治疗胃食管反流病 (食管逆流), 减少酸暴露, 消除每日质子泵抑制剂 (PPI) 的使用是安全有效的, 无需刺激相关不良反应4。在人类试验之前, 第一项研究是在动物模型 (犬模型5) 上进行的。根据这些研究, 电刺激下食管括约肌 (les, 20 赫兹, 脉宽3毫秒) 造成了长期收缩的 LES5。研究了胃食管反流病患者高 (20 赫兹、脉宽200微秒) 和低 (6 转/分、脉宽375毫秒) 电刺激对 LES 的相似效应。高、低频刺激均有效6。然而, 目前, 只有两个神经刺激设备的胃或食道刺激可利用的市场7,8。在这些设备中, 电极可以植入手术, 腹腔或机器人。该设备本身被植入皮下。这需要全身麻醉, 并有一个笨重的设备安装, 使用肌肉导管, 可以刺激胃或食管肌肉组织。因此, 选择使用无线通讯设备植入胃黏膜下层将是一个明确的优势和改善患者的舒适性。如前一项研究910所述, 事实证明, 将微型神经刺激器植入黏膜下层是可能的。在内镜下黏膜下植入术中, 我们使用一种称为内镜下黏膜下扒窃 (ESP) 的技术, 基于内镜下黏膜下隧道解剖10。本研究的目的是进一步改进这种植入式神经刺激器的概念, 主要是在电源管理 (特别是无线充电能力) 的范围内, 符合各自的无线通信法规医学植入装置中的通信链路和双极神经刺激的可能性。其次, 提出的 microneurostimulator 是双向通信的, 即使在植入设备的同时, 也可以实时改变激励参数。

该技术适用于有治疗 endoscopist 经验的内镜扒窃或隧道解剖的团队。接下来, 我们需要一个硬件和嵌入式软件设计师, 有经验的硬件原型与微控制器和射频电路使用表面贴装技术。为了构建硬件原型, 需要一个装有回流焊站的实验室和电气测量的基本设备 (至少有数字万用表、示波器、频谱分析仪和 PICkit3 程序员)。

Protocol

所有内镜手术, 包括动物实验都已在捷克共和国 PIGMOD 动物生理学和遗传学研究所 (生物医学中心, Libechov, 捷克共和国) 批准 (在植入的项目实验无电池和电池设备进入黏膜下层的食管和胃实验研究)。所有的实验都是遵照捷克法律246/1992 某人 “关于保护动物免受虐待, 经修订”。发射机设备不需要被灭菌, 因为它是一个外部设备, 是不与动物直接接触。 1. 植入装置设计 使用?…

Representative Results

图 17显示, 内镜下放置胃神经刺激器到黏膜下层的口袋里, 以及正确放置电极到肌肉层是成功的。设备的尺寸 (图 10) 为 35 x 15 x 5 毫米3 , 而重量为 2.15 g.图 17显示了设备的电路图, 表明该设备包括6个不同模块, 它们连接在一起。图 3显示了设备中的 PCB 布局和组件放置。<strong…

Discussion

植入装置的设计应主要关注设备的整体尺寸、可实现的刺激外形 (最大电压、最大可交付电流、脉冲长度和脉冲频率)。从硬件角度来看, 主要的限制是适当组件的大小和可用性。为了最小化整体尺寸, 表面贴装组件是首选, 因为其紧凑的包装。最好的解决方案是将裸芯片模具集成到基板上。然而, 这是有限的可用的裸模具包装选项的组件和可访问性的电线粘合技术。第二个重要参数是电池。锂电池?…

Disclosures

The authors have nothing to disclose.

Acknowledgements

作者声明他们没有竞争的财政利益。

Materials

EIA 0402 ceramic capacitor 1.8 pF AVX 04025U1R8BAT2A 1 pc
EIA 0402 ceramic capacitor 100 nF TDK CGA2B3X7R1H104K050BB 7 pcs
EIA 0402 ceramic capacitor 100 pF Murata Electronics GRM1555C1H101JA01D 1 pc
EIA 0402 thick film resistor 10 kΩ Vishay CRCW040210K7FKED 1 pc
EIA 0402 ceramic capacitor 10 nF Murata Electronics GRM155R71C103KA01D 3 pcs
EIA 0402 ceramic capacitor 10 pF Murata Electronics GJM1555C1H100JB01D 3 pc
EIA 0402 ceramic capacitor 12 pF Murata Electronics GJM1555C1H120JB01D 2 pcs
EIA 0402 ceramic capacitor 18 pF KEMET C0402C180J3GACAUTO 2 pcs
EIA 0402 resistor 1 mΩ Vishay MCS04020C1004FE000 2 pcs
EIA 0402 resistor 1 kΩ Yageo RC0402FR-071KL 1 pc
EIA 0402 ceramic capacitor 1 nF Murata Electronics GRM1555C1H102JA01D 3 pcs
EIA 0603 ceramic capacitor 2.2 uF Murata Electronics GCM188R70J225KE22D 2 pcs
EIA 0402 resistor 220 kΩ Vishay CRCW0402220KJNED 5 pcs
0805 22 uH inductor TDK MLZ2012N220LT000 1 pc
EIA 0402 resistor 330 kΩ Vishay CRCW0402330KFKED 1 pc
EIA 0603 ceramic capacitor 4.7 uF TDK C1608X6S1C475K080AC 1 pc
EIA 0402 resistor 470 Ω Vishay RCG0402470RJNED 1 pc
EIA 0402 resistor 470 kΩ Vishay CRCW0402470KJNED 1 pc
EIA 0603 inductor 470 nH Murata Electronics LQW18ANR47G00D 1 pc
EIA 0402 resistor 47 kΩ Murata Electronics CRCW040247K0JNED 2 pcs
27.0000 MHz crystal 5032 AVX / Kyocera KC5032A27.0000CMGE00 1 pc
EIA 0402 capacitor 6.8 pF Murata Electronics GJM1555C1H6R8CB01D 1 pc
EIA 0402 inductor 82 nH EPCOS / TDK B82498F3471J 1 pc
ABS05 32.768 kHz crystal ABRACON ABS05-32.768KHZ-T 1 pc
CDBU00340-HF schottky diode COMCHIP technology CDBU00340-HF 2 pcs
CG-320S Li-Ion pinpoint battery Panasonic CG-320S 1 pc
HSMS282P schottky diode rectifier Broadcom / Avago HSMS-282P-TR1G 1 pc
MAX8570 step-up converter Maxim Integrated MAX8570EUT+T 1 pc
MICRF113 RF transmitter Microchip Technology MICRF113YM6-TR 1 pc
4.3 V Zener diode ON Semiconductor MM3Z4V3ST1G 1 pc
OPA237 operational amplifier Texas Instruments OPA237N 1 pc
PIC16LF1783 8-bit microcontroller Microchip Technology PIC16LF1783-I/ML 1 pc
TPS70628 low-drop regulator Texas Instruments TPS70628DBVT 1 pc
EIA 1206 thick film resistor 0 Ω Yageo RC1206JR-070RL 2 pcs
EIA 0603 thick film resistor 0 Ω Yageo RC0603JR-070RL 1 pc
EIA 0402 thick film resistor 100 kΩ Yageo RC0402FR-07100KL 1 pc
EIA 0603 thick film resistor 100 kΩ Yageo RC0603FR-07100KL 1 pc
EIA 0805 ceramic capacitor 100 nF KEMET C0805C104K5RAC7210 2 pcs
EIA 0402 thick film resistor 10 kΩ Yageo RC0402JR-0710KL 1 pc
EIA 1206 ceramic capacitor 10 nF Samsung CL31B103KHFSW6E 2 pcs
EIA 0402 thick film resistor 1 kΩ Yageo RC0402JR-071KL 2 pcs
EIA 0402 thick film resistor 220 Ω Yageo RC0402JR-07220RL 2 pcs
EIA 0402 ceramic capacitor 220 nF TDK C1005X5R1C224K050BB 1 pc
EIA 1206 ceramic capacitor 22 nF TDK C3216X7R2J223K130AA 2 pcs
SMC B tantalum capacitor 22 uF AVX TPSB226K010T0700  1 pc
EIA 0402 thick film resistor 27 Ω Yageo RC0402FR-0727RL 2 pcs
EIA 1206 thick film resistor 3.3 Ω Yageo RC1206JR-073K3L 3 pcs
SOT23 3.3V zener diode ON Semiconductor BZX84C3V3LT1G 1 pc
SMC A tantalum capacitor 4.7uF KEMET T491A475M016AT 2 pcs
EIA 0603 thick film resistor 470 Ω Yageo RC0603JR-07470RL 2 pcs
EIA 1206 ceramic capacitor 470 nF KEMET C1206C471J5GACTU 3 pcs
Electrolytic capacitor 470 uF Panasonic EEE-1CA471UP 3 pcs
EIA 0402 ceramic capacitor 47 pF AVX 04025A470JAT2A 2 pcs
0603 GREEN LED Lite-On Inc. LTST-C191KGKT 1 pc
0603 RED LED Lite-On Inc. LTST-C191KRKT 1 pc
16 MHz CX3225 crystal EPSON FA-238 16.0000MB-C3 1 pc
0805 ferrite bead Wurth Electronics Inc. 742792040 1 pc
IR2110SO FET driver Infineon Technologies IR2110SPBF 1 pc
FT230XS USB to seriál converter FTDI Ltd. FT230XS-R 1 pc
Mini USB connector EDAC Inc. 690-005-299-043 1 pc
PIC16F1783 8-bit microcontroller Microchip Technology PIC16F1783-I/ML 1 pc
REG1117 3.3 V regulator SOT223 Texas Instruments REG1117-3.3/2K5 1 pc
Schottky SMB diode rectifier STMicroelectronics STPS3H100UF 1 pc
SMB package TVS diode Littelfuse Inc. 1KSMBJ6V8 1 pc
IRLZ44NPBF N-channel MOSFET Infineon Technologies IRLZ44NPBF 2 pcs
RTL2832U receiver dongle EVOLVEO Mars 1 pc
PICkit 3 Microchip Technology PICkit 3 1 pc
Mini USB to USB A cable OEM Mini USB to USB-A 1 pc
Printed circuit board, implantable device Manufacture with the provided supplementary file 1 pc
Printed circuit board, transmitter/receiver device Manufacture with the provided supplementary file 1 pc
Printed circuit board, implantable device Manufacture with the provided supplementary file 1 pc
AWG18 wire Alpha Wire 3055 BK001 2 m
AWG42 wire Daburn Electronics 2420/42 BK-100 1 m
Olympus GIFQ-160 Olympus N/A (part is obsoleted) 1 pc
Single-use electrosurgical knife with knob-shaped tip and integrated jet function Olympus KD-655L 1 pc
Single-use oval electrosurgical snare Olympus SD-210U-15 1 pc
15.5 mm lens hood FujiFilm DH-28GR 1 pc
Injection therapy needle catheter Boston Scientific 25G 1 pc
Alligator law grasping forceps Olympus FG-6L-1 1 pc
Instant Mix 5 min epoxy Loctite N/A 1 pc
Heat shrinkable tubing, inside diameter 9.5 mm TE Connectivity RNF-100-3/8-X-STK 1 pc
ChipQuik solder paste Chip Quik SMD4300AX10 1 pc

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Cite This Article
Hajer, J., Novák, M. Autonomous and Rechargeable Microneurostimulator Endoscopically Implantable into the Submucosa. J. Vis. Exp. (139), e57268, doi:10.3791/57268 (2018).

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