Medical Device Link.

DESIGN

Extending the benefits of sensors

Figure 1. (click to enlarge) Schematic of an implantable telemetric pressure measurement system. (Source: Campus Micro Technologies GmbH)

Microsensors are the core components for realising and supporting partly and fully autonomous therapeutic feedback (closed-loop) control systems. Implantable pressure monitoring systems (Figure 1) seek to provide long-term monitoring inside the human body, that is, for at least 10 years or even the patient’s full lifetime. This requires systems that function with minimal power that is supplied from outside the body rather than incorporating a battery, which limits the lifetime of the implant. Requirements regarding biocompatibility and the long-term functioning put high demands on the packaging and assembly of the implant. The complete system has to be hermetically sealed to isolate the electronic components and ensure drift-free and reliable performance of the implant over the full lifetime in a toxic biological environment. Work on developing these systems for several application areas is described below.

Wireless monitoring of brain pressure

Hydrocephalus is a congenital or acquired dysfunction of the circulation of the cerebrospinal fluid. It leads to an increase in intracranial pressure, which can cause severe damage to the brain. State-of-the-art therapy uses implantable shunt systems to drain excessive liquor, which are controlled by a mechanical valve to maintain the physiological brain pressure. Despite progress in shunt therapy a large number of shunt systems require revision within the first year after implantation. Therefore, continuous monitoring of hydrocephalus therapy is required so that the doctor can evaluate the performance of the shunt system over its entire lifetime and intervene immediately if there are complications. Currently, it is not possible to measure the success of the therapy under everyday conditions.

Figure 2. Prototype of an implantable telemetric pressure measurement system for intracranial pressure measurement. (Source: Campus Micro Technologies GmbH)

A wireless implant for measuring intracranial pressure (ICP) (Figure 2) has been developed under the Healthy Aims project, which is funded by the European Commission (www.healthyaims.org).

Technical description

The ICP monitor consists of measurement and telemetry units connected by a lead. The measurement tip comprises a capacitive absolute pressure sensor, a reference capacitor and a signal-processing chip mounted on a 65-mm flexible printed circuit board (PCB). Micromechanical sensors based on a capacitive measurement principle are well suited for use in electronic implants, because there is no electrical current flowing through the sensor itself. A capacitive pressure sensor consists of a silicon diaphragm as a movable electrode and a second underlying fixed electrode. The pressure to be measured is applied across the diaphragm, bending it towards the fixed electrode. The reduction in the distance between the two electrodes results in an increased capacitance of the system. The sensor output is a direct result of geometric parameters only, which leads to an extremely stable sensor. In contrast to piezoresistive pressure sensors
capacitive sensors, therefore, show a negligible temperature dependence of the sensor output in the relevant temperature range (35– 42 °C).

Power consumption can be as low as a few 100s of microwatts for the whole system if it is combined with suitable low-power electronic components. The lead is connected to a flat flange PCB containing the electronic circuitry for telemetric function. The planar antenna coil is integrated into the PCB and allows wireless data and power transmission by receiving the power inductively from an external electromagnetic field supplied by an external transmitter integrated into a reader device. At the same time measurement data can be transmitted to the reader device.

The electronics are covered by a passivation layer of parylene C. This material is characterised by low permeability, chemical inertness, high electrical insulation and the ability to form a conformal and adhesive surface film. It has been widely used as a protective barrier for implantable medical devices such as vascular stents. The passivation layer isolates the electronics from biological fluids and prevents potentially harmful substrates from leaking out.

The complete implant is moulded into a medical-grade silicone rubber housing, except for the measurement tip. A bag, fabricated from the same silicone rubber, is formed and slipped over the (free) pressure sensor tip. The bag is filled with medical-grade silicone gel. This high purity, optically clear gel is a two-component system of low-viscosity liquids that is ideal for coupling external pressure to the pressure sensor. The silicone bag is linked to the silicone bulk with medical-grade silicone glue. The sensing tip is 3 mm in diameter, comparable with conventional ICP monitoring catheters. Silicone rubber was selected as the coating material in view of its chemical stability and its biocompatibility with reference to breast implants, pacemakers and vagus nerve stimulators. Additional nanocoating layers are deposited on top of this dual-layer barrier and provide modified surfaces for biofunctional behaviour of the implant. Typically, those coatings are deposited using wet chemistry or gas-plasma treatment. Innovative three-dimensional packaging technologies such as chip-on-flex, chip stacking and chip-on-board, allow the manufacture of highly flexible products that meet the demands of minimal size and hand-ling required in minimally invasive surgical procedures (bending of the implant in small radii).

The pressure-capacitance characteristics of the uncoated devices were evaluated at weekly intervals over a three-week period. Measurements during this time were identical confirming that there is zero drift during this period. Silicone gel encapsulation loads the sensor with a degree of prepressurisation, which shifts the pressure-capacitance curve. These changes are predictable from the mechanical properties of the materials and encapsulation does not introduce any unexpected error factor in the performance of the sensor. The stability of the sensor in a water medium has been confirmed in bench testing; the silicone bag forms a package around the sensor and is impervious to water. Protective packaging of implants has been a difficult problem throughout the development of ICP telemetry. The flange containing the electronic components, as well as the lead to the sensor, are coated with parylene C and an outer layer of silicone; this is cheaper to manufacture and bond than inert metallic seal, such as titanium, and is currently equally effective at preventing entry of moisture.

Benefits of the implant

The small size (3 mm) of its tip allows it to be inserted in the ventricular system or the brain parenchyma. This eliminates sources of inaccuracy, which are present in other systems. Principally, inaccuracies of those systems result from the variation of ICP with the depth of implantation and the difficulty in maintaining coplanarity between the device and the dura over the long lifetime of the implant. In addition, the sensor does not need to be inline with a fluid column; it is implanted independently of cerebro-spinal fluid diversion devices and is free from any error caused by progressive obstruction of a proximal catheter. Because the device automatically corrects for temperature and external barometric variation, it can be used reliably across a range of physiological and environmental conditions. The sampling frequency of 30 Hz enables a fast dynamic response and adequate ICP waveform definition. It has been shown that waveform scrutiny allows evaluation of several relevant parameters, including intracranial compliance. The sensor’s ability to measure negative pressures allows the investigation of shunt overdrainage and slit ventricle syndrome.

This device is currently undergoing in vivo animal trials. If its long-term stability is also confirmed in clinical practice, the possibility of networking the device to a programmable shunt could be considered. Data are transmitted to an external unit worn on the body, where they can be stored or transmitted to a base station, or via a mobile telephone directly to the clinician. All this will be done without requiring interaction with the patient. With this ICP implant, the clinician can evaluate the patient’s symptoms based on objective and continuous data and recognise a malfunctioning shunt at an early stage.

An implantable ICP implant is an alternative to tip transducers in the stationary treatment of severe head injuries. The capacitive sensor provides a stable and drift-free pressure measurement. Wireless communication and power supply mean the skin can be closed after implantation and the risk of infection kept to a minimum. Brain pressure is transmitted continuously to an external unit and then to a clinical monitor. Wireless operation means no permanent connection of the patient with the clinical monitor and more mobility for patient and clinician.

A second example of a wireless pressure monitoring implant follows, this time for glaucoma therapy.

Continuous measurement of intraocular pressure

Figure 3. Wireless microsystem for monitoring glaucoma integrated into an artificial lens. (Source: Campus Micro Technologies GmbH)

Glaucoma is a common eye disease. One form of it is characterised by obstruction of the outflow of aqueous humour from the eye and an increase of intraocular pressure. The increased pressure progressively damages the optic nerve and leads to blindness. With early detection, the progress of glaucoma can be stopped; medication or surgical intervention will prevent damage to the optical nerve and avoid blindness. Currently, there is no method available to continuously monitor intraocular pressure (IOP). IOP measurements are typically performed in six- to twelve-week intervals. Those measurements are not reliable because there are large variations in the IOP during the day. A prototype of a highly miniaturised pressure sensor system with wireless power supply and data transmission has been integrated into an artificial lens, which can be implanted minimally invasively (Figure 3). This would normally be done in cases, where the human lens has to be replaced anyway by an artificial lens as part of routine cataract surgery.

Another system developed by the EPFL group (Lausanne, Switzerland)¹ uses a flexible contact lens rather than an artificial lens. This allows access to a much larger group of patients, who do not have to undergo a surgical procedure. The different concepts address different groups of patients. In both cases pressure data are available continuously and transmitted via radio frequency technology to the reader. The reader can be integrated into special pair of glasses. Based on the data, the therapy can be monitored and optimised by adapting the medication to the actual condition of the patient.

Quality control of care

Figure 2. Intelligent microsystem for quality control during compression therapy. (Source: Campus Micro Technologies GmbH)

Sensor-based microsystems can contribute to quality control of therapeutic care. Objective data can help carers optimise their daily work. One application area is chronic vascular insufficiencies that cause ulcer or decubitus. The success of compression therapy is dependent on the pressure under the compress. In a recently developed prototype, a pressure sensor is integrated into an air-filled cushion, which is applied directly on the skin and covered by the compress (Figure 4).The air cushion couples the pressure at the area of interest to the sensor. The pressure readings can then be used to verify the performance of the compress and to indicate a change of compress when the measured pressure is outside the therapeutic window; this occurs frequently as a result of changes in the textile during wear.

Training of health-care professionals is another important application. Applying compresses with the exact pressure requires a large amount of training and experience. Using a pressure sensor as described above for direct feedback, the training of health-care personnel becomes more efficient. Feedback about the application of the compress is given immediately and is objective rather than being reliant on the outcome of therapy at a future time when the carer’s memory of it has faded. Wireless sensors are an essential part of this functionality; wire-based sensors would limit the usefulness of the system for the patient in everyday life.

Autonomous systems are the future

The realisation of truly autonomous sensor systems for therapy is closer than ever. Some of the remaining issues to resolve include the question of long-term stability over periods of several decades and further integration of currently available single modules into actual systems, where those individual modules closely interact. These require, for example, the use of multisensor networks, improved algorithms to combine the output of those sensors, extracting relevant information from pure data, and rule-based decisions controlled by the local intelligence.

Closed-loop control systems are in widespread use in the industry and are currently a focus of intense research. They are able to make their own decisions to try to reach and control a preset target. Examples include automated insulin delivery in response to regular blood–glucose measurement in diabetics and propofol-infusion coupled to electroencephalogram-derived parameters of unconsciousness in anaesthesia.

The integration of miniaturised, long-term stable pressure sensors such as those described in this article into devices such as implantable blood pumps, bladder stimulators and shunt systems is one of the preconditions for realising closed-loop control systems for these applications. Stand-alone monitoring devices (sensing devices allowed to measure pressure without further integration) and closed-loop systems (systems with integrated sensors and actuators) will be necessary in the future. They will be required for monitoring the success of therapy and its optimisation and for adapting therapy to the individual and actual conditions, rather than relying on past experience and averaged data from groups of patients.

As an intermediate step towards fully autonomous implants, therapy can be continuously monitored and parameters changed as necessary by the clinician via wireless communication with the implant. Therapy will be remotely monitored with the help of the implant and data will be sent on demand to the clinician for further evaluation. The clinician can then change the therapy based on the data provided by the implant. Those partly autonomous therapy systems will still rely on the expertise and intervention of the health-care professional. Visits of patients to hospitals or the doctor will be reduced to a necessary minimum, while increasing the quality of care that is provided.

It may seem that the major issues impeding closed-loop implant systems are technical ones. Another issue that has to be addressed is the acceptance of a closed-loop medical implant by clinicians and by patients. Clinicians maybe afraid of implants doing their work, particularly if patients can take the readings themselves at home rather than visiting the doctor. However, it is still the health-care professional who has the expertise to interpret the data and who must decide on which therapy is to be used. Future implants such as those described above will vastly improve the quality and availability of data. The doctor rather than having to collect the data him/herself with time-consuming procedures will be able to use that time for interpretation of data and improving therapy, thus providing more value to the patient and society.

Patients will have their own concerns. Initially, they may have limited trust in implants acting independently from a doctor based on rules programmed in the implant’s local “intelligence.” They will feel safer if a doctor still does all or at least part of the adjustments, even if the implant technically can do it by itself. However, with time, patients will develop trust in their implants and will take the next step and accept that the implant can do the job. When this is the case, the remaining technological issues will have been solved and the implants described here, will be available to benefit doctors and patients.

Acknowledgement

The development of the wireless ICP implant is taking place under the European Healthy Aims project. The author wishes to acknowledge funding by the European Commission under IST-2002-1-001837 of the Sixth Framework Programme.

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