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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

The manuscript presents a miniature implantable pH sensor with ASK modulated wireless output together with a fully passive receiver circuit based on zero-bias Schottky diodes. This solution can be used as a basis in the development of in vivo calibrated electrostimulation therapy devices and for ambulatory pH monitoring.

Abstract

Ambulatory pH monitoring of pathological reflux is an opportunity to observe the relationship between symptoms and exposure of the esophagus to acidic or non-acidic refluxate. This paper describes a method for the development, manufacturing, and implantation of a miniature wireless-enabled pH sensor. The sensor is designed to be implanted endoscopically with a single hemostatic clip. A fully passive rectenna-based receiver based on a zero-bias Schottky diode is also constructed and tested. To construct the device, a two-layer printed circuit board and off-the-shelf components were used. A miniature microcontroller with integrated analog peripherals is used as an analog front end for the ion-sensitive field-effect transistor (ISFET) sensor and to generate a digital signal which is transmitted with an amplitude shift keying transmitter chip. The device is powered by two primary alkaline cells. The implantable device has a total volume of 0.6 cm3 and a weight of 1.2 grams, and its performance was verified in an ex vivo model (porcine esophagus and stomach). Next, a small footprint passive rectenna-based receiver which can be easily integrated either into an external receiver or the implantable neurostimulator, was constructed and proven to receive the RF signal from the implant when in proximity (20 cm) to it. The small size of the sensor provides continuous pH monitoring with minimal obstruction of the esophagus. The sensor could be used in routine clinical practice for 24/96 h esophageal pH monitoring without the need to insert a nasal catheter. The "zero-power" nature of the receiver also enables the use of the sensor for automatic in-vivo calibration of miniature lower esophageal sphincter neurostimulation devices. An active sensor-based control enables the development of advanced algorithms to minimize the used energy to achieve a desirable clinical outcome. One of the examples of such an algorithm would be a closed-loop system for on-demand neurostimulation therapy of gastroesophageal reflux disease (GERD).

Introduction

The Montreal Consensus defines gastroesophageal reflux disease (GERD) as "a condition that develops when refluxing the contents of the stomach causes unpleasant symptoms and/or complications". It may be associated with other specific complications such as esophageal strictures, Barrett's esophagus, or esophageal adenocarcinoma. GERD affects approximately 20% of the adult population, mainly in countries with high economic status1.

Ambulatory pH monitoring of pathological reflux (acid exposure time of more than 6%) allows us to distinguish the relationship between symptoms and acidic or non-acidic gastroeso....

Protocol

No living animals were involved in this study. The experiment was performed on an ex vivo model consisting of a porcine esophagus and stomach. The stomach and esophagus were purchased from a local butchery as their standard product. This procedure is in accordance with Czech laws, and we prefer it because of the "3R" principle (Replacement, Reduction, and Refinement).

1. Fabrication of the pH sensor assembly

NOTE: Observe precautions for handling elec.......

Representative Results

A device capable of autonomous pH sensing and wireless transmitting of the pH value was successfully constructed, as shown in Figure 8. The constructed device is a miniature model; it weighs 1.2 g and has a volume of 0.6 cm3. The approximate dimensions are 18 mm x 8.5 mm x 4.5 mm. As shown in Figure 15, Figure 16, and Figure 17, it can be implanted to the proxi.......

Discussion

This method is suitable for researchers who work on the development of novel active implantable medical devices. It requires a level of proficiency in the manufacturing of electronic prototypes with surface mount components. The critical steps in the protocol are related to the manufacturing of the electronics, especially populating the PCBs, which is prone to operator error in placement and soldering of small components. Then, correct encapsulation is crucial to prolong the lifetime of the device when exposed to moistur.......

Acknowledgements

The authors gratefully acknowledge Charles University (project GA UK No 176119) for supporting this study. This work was supported by the Charles University research program PROGRES Q 28 (Oncology).

....

Materials

NameCompanyCatalog NumberComments
AG1 batteryPanasonicSR621SWTwo batteries per one implant
Battery holderMYOUNGMY-521-01
Copper enamel wire for the antennapro-POWERQSE Wire - 0.15 mm diameter, 38 SWG
Epoxy for encapsulationLoctiteEA M-31 CLTwo-part medical-grade ISO10993 compliant epoxy
FEP cable for pH sensorMolex / Temp-Flex100057-0273
Flux cleanerShestoUTFLLU05Prepare 5% solution in deionized water for cleaning by sonication
Hemostatic clipBoston ScientificResolution
Hot air gun + soldering ironW.E.P.Model 706Any soldering iron capable of soldering with tin and hot-air gun capable of maintaining 260 °C can be used
Impedance matching softwareIowa Hills SoftwareSmith ChartCan be downloaded from http://www.iowahills.com/9SmithChartPage.html - alternatively, any RF design software supports calculation of impedance matching components
ISFET pH sensor on a PCBWinSenseWIPSOrder a model pre-mounted on a PCB with on-chip gold reference electrode
Laboratory pH meterHanna InstrumentsHI2210-02Used with HI1131B glass probe
Microcontorller programmerMicrochipPICkit 3Other PIC16 compatible programmers can be also used
Pig stomach with esophagusLocal pig farmObtained from approx. 40–50 kg pigIt is important that the stomach includes a full length of the esophagus.
Printed circuit board - receiverChoose preferred PCB supplierAccording to pcb2.zip dataOne layer, 0.8 mm thickness, FR4, no mask
Printed circuit board - sensorChoose preferred PCB supplierAccording to pcb1.zip dataTwo-layer with PTH, 0.6 mm thickness, FR4, 2x mask
Receiver - 0RVishayCRCW04020000Z0EDCSee Figure 12 and Figure 13 for placement
Receiver - 1.5 pFMurataGRM0225C1C1R5CA03LSee Figure 12 and Figure 13 for placement
Receiver - 100 pFMurataGRM0225C1E101JA02LSee Figure 12 and Figure 13 for placement
Receiver - 33 nHPulse ElectronicsPE-0402CL330JTTSee Figure 12 and Figure13 for placement
Receiver - RF schottky diodesMACOMMA4E2200B1-287TSee Figure 12 and Figure 13 for placement
Receiver - SMA antennaLPRSANT-433MS
Receiver - SMA connectorLinx TechnologiesCONSMA001See Figure 12 and Figure 13 for placement
Sensor - C1MurataGRM0225C1H8R0DA03L8 pF 0402 capacitor
Sensor - C2MurataGRM0225C1H8R0DA03L8 pF 0402 capacitor
Sensor - C3MurataGCM155R71H102KA37D1 nF 0402 capacitor
Sensor - C4MurataGRM0225C1H1R8BA03L1.8 pF
Sensor - C5VishayCRCW04020000Z0EDCPlace 0R 0402 resistor or use to match the antenna
Sensor - C6MurataGRM155C81C105KE11J1 uF 0402 capacitor
Sensor - C7MurataGRM155C81C105KE11J1 uF 0402 capacitor
Sensor - C8MurataGRM022R61A104ME01L100 nF 0402 capacitor
Sensor - IC1MicrochipMICRF113YM6-TRMICRF113 RF transmitter
Sensor - IC2MicrochipPIC16LF1704-I/MLPIC16LF1704 low-power microcontroller
Sensor - R1VishayCRCW040210K0FKEDC10 kOhm 0402 resistor
Sensor - R2VishayCRCW040233K0FKEDC33 kOhm 0402 resistor
Sensor - R3VishayCRCW04021K00FKEDC1 kOhm 0402 resistor
Sensor - R5VishayCRCW040210K0FKEDC10 kOhm 0402 resistor
Sensor - X1ABRACONABM8W-13.4916MHZ-8-J2Z-T33.2 x 2.5 mm 13.4916 MHz 8 pF crystal
Titanium wireSigma-AldrichGF368464340.125 mm titanium wire
Vector network analyzermini RADIO SOLUTIONSminiVNA TinyOther vector network analyzers can be used - the required operation frequency is 300–500 MHz, resolution bandwidth equal or lower than 1 MHz, output power of no more than 0 dBm and dynamic range preferably better than 60 dB for the receiving front-end

References

  1. El-Serag, H. B., Sweet, S., Winchester, C. C., Dent, J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 63 (6), 871-880 (2014).
  2. Gyawali, C. P., et al. Modern diagnosis of GERD: the....

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