WO2004073518A1

WO2004073518A1 - Oesophageal sphincter sensor

Info

Publication number: WO2004073518A1
Application number: PCT/GB2004/000638
Authority: WO
Inventors: Diana Hodgins; Joseph Mark Hatt
Original assignee: European Technology For Business Limited
Priority date: 2003-02-18
Filing date: 2004-02-17
Publication date: 2004-09-02
Also published as: GB0303693D0

Abstract

A sensor (13) for the remote monitoring of the closing action of a human sphincter muscle has a micro-fabricated electrode array (12) formed on a flexible substrate (11) and which is in use deformed by the action of a sphincter muscle. The substrate (11) encircles a core electrode (10) and the variations in capacitance with the electrodes is sensed to produce an electrical data output. A multiplexed RF link to an external module allows monitoring of the output of the sensor. I

Description

OESOPHAGEAL SPHINCTER SENSOR

This invention relates to a sensor for detecting correct closure of a sphincter associated with a body duct. In particular, but not exclusively, the invention is concerned with a sensor for closure of the lower oesophageal sphincter (LOS) of a human body. The invention further relates to a sphincter sensor system including a control module external of a body in which the sensor is located, at least to record data from the sensor.

An estimated 10% of the population in the US and UK are affected by 'heartburn' or gastro-oesophageal reflux disease (GORD), which totals around 30M people. This is where the lower oesophageal sphincter (LOS) relaxes, allowing the stomach fluid to reflux into the oesophagus. The initial symptoms are a burning sensation in the chest, and many people suffer this on an occasional basis, for example after eating a large meal. However, reflux is classified as a medical condition if it occurs on a regular basis, since this can lead to further longer-term complications, including ulceration and possibly cancer of the oesophagus due to acid damage.

Factors that are believed to cause GORD include: transient lower oesophageal sphincter relaxations, decreased LOS resting tone, delayed stomach emptying, and ineffective oesophageal clearance. One primary cause of gastro-oesophageal reflux disease is the lack of competency of the lower oesophageal sphincter. The lower oesophageal sphincter or valve is comprised of both smooth and skeletal muscle located at the gastro-oesophageal junction.

Tests can be carried out on patients to determine the competency of the

LOS. These are all diagnostic tests and the sensor is disposed of after use. It is believed that if the tests were easier to carry out and to give more reliable results than the systems currently available, then the number of tests performed would significantly increase. Were a sensor available to test sphincter competency in general, the sensor could be used to measure other sphincters in the body, for example the urethral sphincter. Current methods of diagnosing gastro-oesophageal reflux rely on the recording of pressure or pH within the LOS or oesophagus. This involves up to 24-hour intubation, with the associated patient discomfort. Natural movement of the LOS with respiration and physical activity affects the readings, since the pressure sensors become misaligned with the sphincter. The pressure sensors fall into 2 categories:

o Water perfused catheter systems. A multi-lumen catheter is introduced through the naso-gastric passage into the stomach. The lumens are closed at the lower end and each one has a pressure port on the side of the catheter. The individual lumen ports are arranged along the length and around the circumference of the catheter to allow the study of pressure variations in the oesophagus and lower oesophageal sphincter. The pressure at each port is determined by using a pneumo-hydraulic pump to perfuse water through the lumen, and measuring the pump pressure required. The water perfusion improves the fidelity of the readings compared to static water-filled lumen pressure measurement, since the effect of catheter elasticity is to incur a negligible time delay rather than to attenuate the pressure readings. Catheters vary in diameter from 2 to 5mm for oesophageal use, and number of ports from 1 to 8. • Solid state catheters. Solid-state catheters are arranged with a similar spread of radial and axial pressure reading positions as are found on water-perfused catheters. The pressure is read directly by solid-state strain gauge sensors deposited on metal diaphragms placed on the body of the catheter, and these can be either directional (radial) or circumferential. The sensors are not sensitive to inclination and movement, unlike water-perfused catheters, and require much less calibration. The electrical signals are carried by wires, routed through the naso-gastric passage, and can be continuously recorded away from the clinical environment. Solid-state catheters allow 24-hour ambulatory studies to be conducted. Patients are encouraged to follow a relatively normal routine, including meals, during the 24-hour study, so the shape and size of the solid-state catheters is important to avoid blockages of the oesophagus. The catheter is usually between 2 and 3mm diameter and smooth.

Both of the above devices measure pressure at discrete points around the sphincter. However, the requirement is to determine whether the sphincter has closed all the way around, and not what the pressure is at discrete points. This proposed new system of this invention monitors the movement of the sphincter around its inner circumference, thus more readily matching the need of clinicians. Whilst eight measuring points around the circumference are proposed initially, perhaps arranged in three rows each of eight measuring points, this could be increased if an increased resolution is required. The proposed sensor should be sized to allow insertion through a standard endoscope. This proposed solution is only achievable by combining a range of microstructure technology (MST) fabrication processes with micro-electronics, and a flexible RF coil to allow remote telemetry, if the device is not to be hardwired to a monitor external to the body. Having regard to the above, a principal aim of this invention is the provision of a micro-fabricated sensor that can detect whether a sphincter (human valve) is closing correctly.

Accordingly, one aspect of this invention provides sphincter closure sensor for the remote monitoring of the closing action of a human sphincter muscle, comprising a micro-fabricated electrode array formed on a flexible substrate which is in use deformed by the action of a sphincter muscle with which the sensor is associated, a control circuit connected lo the electrodes to produce an electrical data output, and a data link to permit the transfer of electrical signals to and from the circuit with respect to a location remote from the substrate.

A sensor of this invention includes a micro-fabricated electrode array on a flexible substrate, micro-connections to a control circuit which might include a multiplexer, and a data link for signals from the sensor, which data link typically may have a micro-fabricated RF coil or may comprise a hard-wired data cable. The assembly may be coated in a suitable inert biomaterial for insertion in the human body, and be activated externally.

The complete micro-system may be used for diagnosis in hospital clinics, and could be linked to a local body area network (BAN). A prime specific medical application for the device is to determine whether the lower oesophageal sphincter (LOS) is closing properly. For this, the sensor would be located within the body to extend through the LOS, an external data recorder being connected to a BAN. The sensor may be a disposable device and work for up to 24 hours in the body, without any maintenance during this period. It should also be of low cost, in order that it can be widely utilised.

The sensor must be compliant in order to fit through the nose or throat passage, before being located in the sphincter region. It must also be coated with a biocompatible material to stop bacterial growth and prevent malfunction or injury to the patient. When the LOS is open, the sensor must allow the passage of food and liquid into the stomach without damage to the sensor. The sensor should thus be very small (02mm or less) in order not to affect the flow of food and liquid, nor the closure of the sphincter. Ideally, it may be inserted by a nurse or doctor at an outpatient clinic, and may also be sufficiently small to pass through a standard endoscope. A typical specification for a sensor of this invention might be:

Measurement requirements of the closure sensor

Determine when the LOS is open or closed, and how effectively closure is achieved

Allow sphincter to close 2mm diameter or less

Sense radial asymmetry of closure within 30°

Sense axial position of sphincter within 10mm

Frequency of recording 8Hz

Positioning of the closure sensor in the Oesophagus

Insertion and positioning using a naso-gastric catheter

Swallowed, and retained by a tether from the mouth (e.g. tooth)

Insertion using a catheter or endoscope, with an oesophageal clip to retain the sensor Note: The sensor is likely to be too long to pass through the patient after the recording period, so must be retrieved by the tether.

Data transfer system options

Direct connection to an external data-recorder via a cable through the naso- gastric passage

Data storage, then retrieval and down-load

Data transmission to an external data-recorder by radio link

MST will be combined with biomaterials, low power electronics, a miniature power source and RF communications in order to achieve this overall objective. There are a number of innovative features in the sensor of this invention.

At the system level, the aim is to provide a micro-fabricated displacement sensor system that can function within the body and monitor radial displacement down to micron levels, data of this displacement being transmitted to an external unit without any human intervention. In order lo achieve this, an embodiment of the invention has:

• A sensor mechanism - micro-electrodes are micro-fabricated on to a cylindrical structure. This will be of a highly compliant material including foamed elastomers or a compliant structure in the form of an elongate balloon. The balloon would be internally pressurised during use to increase the compliance of the sensor above that of the parent materials.

• A biomaterial coating - the sensor assembly is coated with a biomaterial that allows the passage of food and liquids, without being damaged or harming the patient.

• A miniature multiplexer - in order to reduce the number of data transfer channels the electrode outputs will be multiplexed, within an electronics/RF enclosure. • An RF receiver unit.

• Assembly and packaging - the sensor will be a true 3D structure with electrical connections made between rigid structures mounted on to compliant materials. So far, packaging methods address 2D or 2¹/£D structures, and are focussed on connecting to silicon.

According to a further aspect of this invention, there is provided a sphincter closure sensor system A sphincter closure sensor system for detecting closure of a body sphincter muscle, which system comprises:

- a sphincter closure sensor as claimed in any of the preceding claims and adapted for positioning within a body duct so as to be surrounded by a sphincter muscle; and

- a control unit adapted lo be remotely located from the sphincter closure sensor and operable to provide a drive signal to the sensor and to receive data signals therefrom. In order that this invention may be better understood, an example thereof will now be described with reference to the accompanying drawings. In the drawings:

Figure 1 conceptually shows a balloon and core of the sensor;

Figures 2A and 2B diagrammatically illustrate the micro-electrode structure for the balloon and core of Figure 1 ;

Figure 3 illustrates the use of the sensor within a lower oesophageal sphincter of a patient; and

Figures 4A and 4B show block diagrams of alternative arrangements for the oesophageal sensor and external control unit. Basic Principle

Referring to Figure 1 , the sensor comprises a conductive central core electrode 10, able to serve as a reference electrode for the sensor. This core electrode 10 is surrounded by a flexible sheet 11 having a plurality of micro- fabricated linear electrodes 12 formed thereon (Figures 2A and 2B), the flexible sheet 11 being carried on the inner surface of an outer highly compliant tubular balloon 13 or other tubular structure. The annular space 14 between the core electrode 10 and the tubular balloon 13 is closed at its ends and is filled with a fluid under pressure. Individual connections are made to the linear electrodes and the capacitance between each linear electrode and the core electrode 10 is determined. When the sensor is located in a sphincter (Figure 3) and the sphincter closes, the balloon will be squeezed as shown by arrow A, reducing the gap between sheet 11 and the core electrode 10 as shown at 15 and so altering the capacitances between the linear electrodes and the core electrode. The capacitances are determined and are multiplexed together, for supply to an external datalogger.

Core Electrode and Balloon

The balloon 13 is fabricated from a material that can be inflated by the fluid in the annular space 14 and has, in this embodiment, a wall thickness of approximately 100 microns. The balloon has sufficient strength to withstand the external forces from the sphincter and from food and liquid. The balloon typically might be of siiicone rubber and the core electrode 10 of a metal or other conductive material. Micro-Electrodes Structure

The electrodes 12 disposed within the balloon 13 are patterned on to polyamide strip, or on to a similar flexible circuit material as shown in Figures 2A and 2B. The electrodes 12 may be arranged in three rows along the axis of sensor, with interconnect electrodes 16 between the rows. Each electrode set is trimmed typically into twelve strips of electrodes, to allow expansion of the siiicone rubber balloon. The fabrication of the flexible circuits allows for the build-up of multiple layers, including a thin insulating dielectric layer to separate the electrodes from the central core of the sensor. Typical flexible electrode circuit designs are shown in Figures 2A and 2B.

Biomaterial

The coating of the sensor is critical in that it must not encourage bacterial growth whilst immersed in food or liquid which passes into the stomach, and must be compliant enough to be passed through the oesophagus to the LOS, and yet withstand the force from the sphincter. For example, the nano structure of certain materials may be modified to stop bacterial growth, either chemically or physically. The external form of the compliant biomaterial moulded over the exterior of the sensor must not cause damage to the sphincter when it closes on to the sensor. Control Circuit

A control circuit is formed as a part of the sensor. As best seen in Figure 3, the structure of the core electrode and the balloon 13 is elongate and of a relatively small diameter. At the upper end (when in use with the lower oesophageal sphincter 17) of that structure there is provided a housing 18 within which is disposed the control circuit, to which the individual linear electrodes 12 and the core electrode 10 are connected. That circuit includes a multiplexer in order to combine together the output of the linear electrodes. Typically, there may be seventy two such linear electrodes the outputs of which are to be combined by the multiplexer, to reduce the number of channels to be monitored. Actual embodiments of the sensor may have fewer or more than 72 linear electrodes, depending upon the design and the length of the core electrode and surrounding balloon.

The control circuit further comprises an RF coil, both for transmitting the output of the control circuit to an external monitor, and for receiving electrical energy from that external monitor to power the device. The joining of the electrodes to the control circuit including the multiplexer and also the RF coil may be achieved by true 3D micro-fabrications.

Overall Svstem Figure 4A shows one embodiment of a complete system which comprises the sensor balloon assembly, the control circuit including the multiplexer and RF coil, and an external module to record the sensor output.

Recording of the sensor output may be achieved by the external module including a timer circuit which supplies power to the sensor, to trigger a reading cycle to obtain data therefrom, typically at 8Hz. The power supply should be housed in an external module fitted to the patient. This module includes the transmitter unit, a datalogger, and a rechargeable power supply. The datalogger of the external module may link to a body area network (BAN). The internal sensor unit may then comprise the receiver and any passive components required to drive the sensor.

In an alternative embodiment (Figure 4B), a hard-wired link is provided between the sensor and the external module. By multiplexing the determined capacitances, the number of wires required to carry the data to the external module is greatly reduced, so minimising the size of the link and thus increasing patient comfort.

Claims

CLAI S

1. A sphincter closure sensor for the remote monitoring of the closing action of a human sphincter muscle, comprising a micro-fabricated electrode array formed on a flexible substrate which is in use deformed by the action of a sphincter muscle with which the sensor is associated, a control circuit connected to the electrodes to produce an electrical data output, and a data link to permit the transfer of electrical signals to and from the circuit with respect to a location remote from the substrate.

2. A sphincter closure sensor as claimed in claim 1 , wherein the sensor has an elongate core around which is arranged a compliant tubular substrate, the electrodes being provided on the substrate for movement towards and away from the core by the action of a sphincter muscle surrounding the sensor.

3. A sphincter closure sensor as claimed in claim 2, wherein each electrode is elongate and extends along the substrate.

4. A sphincter closure sensor as claimed in claim 3, wherein the electrodes are provided on the internal surface of the tubular substrate, to face the core.

5. A sphincter closure sensor as claimed in any of claims 2 to 4, wherein the electrodes are provided on a flexible film which is formed into a shell arranged within the bore of the tubular substrate.

6. A sphincter closure sensor as claimed in claim 4 or claim 5, wherein the surface of each electrode facing the core is coaled with an insulating dielectric material to insulate the electrode from the core.

7. A sphincter closure sensor as claimed in claim 2 to 6, wherein there is a generally annular space between the core and the inner surface of the tubular substrate, which space is closed and contains a dielectric liquid.

8. A sphincter closure sensor as claimed in any of claims 2 to 7, wherein the core is of a conducting material and serves as a reference electrode for the array of electrodes.

9. A sphincter closure sensor as claimed in any of claims 2 to 8, wherein the electrodes of the array are arranged as a plurality of capacitors, the control circuit determining the capacitances thereof to produce the data signal for transfer on the data link.

10. A sphincter closure sensor as claimed in claim 9, wherein the circuit is arranged to determine the capacitance of each electrode in the array with respect to the conductive core.

11. A sphincter closure sensor as claimed in any of the preceding claims, wherein the electrodes of the array are formed from one of piezo-electric material, piezo-resistive material and strain sensitive material.

12. A sphincter closure sensor as claimed in any of the preceding claims, wherein the data link comprises a data cable physically interconnecting the control circuit of the sensor with an external module whereby power for operating the sensor may be supplied to the sensor and data signals may be returned to the external module.

13. A sphincter closure sensor as claimed in any of claims 1 to 10, wherein the data link comprises an RF link, the sensor including an RF coil for receiving signals from an external module and for transmitting data back lo that module.

14. A sphincter closure sensor as claimed in any of the preceding claims, wherein the control circuit includes a multiplexer to combine the outputs from the individual electrodes of the array thereof into a data signal for transfer on the data link.

15. A sphincter closure sensor as claimed in any of the preceding claims, wherein the electrode array, control circuit and RF coil (if provided) are encapsulated in a biostable material.

16. A sphincter closure sensor system for detecting closure of a body sphincter muscle, which system comprises:

- a control unit adapted to be remotely located from the sphincter closure sensor and operable to provide a drive signal to the sensor and to receive data signals therefrom.

17. A sphincter closure sensor system as claimed in claim 16, wherein the control unit is adapted to be carried externally of the intended patient.

18. A sphincter closure sensor system as claimed in claim 16 or claim 17, wherein the control unit includes a timer to provide a repetitive drive signal to cause operation of the sensor actuator at regular time intervals, a receiver to receive data from the sensor and a datalogger to record such data.

19. A sphincter closure sensor system as claimed in any of claims 16 to 18, wherein power is supplied to the sensor and data is collected from the sensor by a data link comprising one of a bi-directional RF link or a data cable physically linking the control unit and the sensor.