Healthy Aims - secrets under the skin

TWI Bulletin, January - February 2007

Implantable microsystems-based medical devices in the spotlight

Sue Dunkerton joined TWI in 1979 after a degree in metallurgy at UMIST. She has held many roles whilst at TWI and is currently Business Manager for TWI's Process Technology Groups with particular emphasis on the medical, electronics, aerospace and automotive sectors. Sue is also Director of the UK's Health Technologies Knowledge Transfer Network, a DTI sponsored business support initiative to advance technology exploitation.

There are currently very few implanted, microsystems-based medical devices despite end user requirements being clearly present. As Colin McLean and Sue Dunkerton report there are a number of reasons for this, including the fact that most micro-structures, micro-sensors and micro-actuators have not been developed for medical applications, and there are only a few materials available for long-term implantation in the human body.

In December 2003, an EU collaborative project, 'Healthy Aims', was launched to address these and related issues. A consortium of 27 organisations from ten countries is participating in this ambitious and cross-disciplinary project which is in part supported by the Core Research Programme of TWI. The project proposes to develop a number of next generation, intelligent, microsystems-based medical implants, together with a range of underpinning technologies.

There has been considerable growth in microsystems technology in recent years, with good commercial examples found in the automotive, telecommunications and environmental sectors, but surprisingly little so far in the medical device area. Despite significant potential benefits, developments in this sector have been held back due to a number of factors, including:

Technical:

• Limited number of materials available suitable for implantation in the human body
• No rechargeable implantable batteries
• A lack of suitable packaging and interconnect technologies, particularly for flexible 3D micro-structures
• A lack of implantable micro-structures, micro-sensors and micro-actuators

Clinical:

• The system concepts conceived by clinicians often cannot be produced due to lack of access to the relevant technology providers.

Commercial:

• The perceived volumes for many applications are often low.
• The time to market is long, which dissuades large organisations and makes investment risky for small and medium size enterprises (SMEs).
• The risk is very high.

Considering the products available today, the focus appears to be on cardiovascular applications, for example pacemakers. This is because research activities, including clinical research, has been well funded in this area and the potential market is relatively large. As a result, the main players are large organisations. There are also a few other implants available including cochlear implants for the profoundly deaf, a bladder stimulator for incontinent people and, most recently, a simple two-channel functional electrical stimulator (FES) for 'dropped foot' sufferers. In Europe, some of these implants are produced by SMEs, demonstrating that such companies can successfully address smaller, high-risk, niche markets.

By examining the market potential, clinical needs and available technical resources, NEXUS, a European microsystems network, undertook a roadmapping excercise which led to the establishment of a major EU project to develop new implantable products using advanced generic technologies. This four-year project, named 'Healthy Aims', comprises 27 partners across ten countries and started on 1 December 2003. The project has a total budget of €25 million. TWI has been one of several RTOs in the consortium, leading the development of packaging and interconnect technologies. This work has been supported via a concurrent Core Research Programme project.

Programme structure

The work programme has been structured to enable generic technologies to be developed, targeted towards a specific range of end products, Fig.1. The core technologies are:

• RF communications suitable for implantation into the human body
• Implantable power sources
• Biocompatible materials
• Micro-electrodes for connection to nerves and muscles
• Micro-assembly and packaging techniques for 3D, flexible structures
• Sensors and actuators to fit inside or on the body

The initial target products include:

• Cochlear implants
  
• FES systems for upper and lower limbs
  
• Sphincter pressure sensor
  
• Intracranial pressure sensor for long term implantation (>10 years)

Fig.1. Implantable devices targeted for development within the 'Healthy Aims' project

The consortium is addressing the entire project needs, from basic research through to clinical trials and subsequent regulatory approvals. Complementary skills in the core technologies were included to ensure that the products did not focus on using one technology but would use knowledge from a number of key technical research areas.

Technology development

The programme is addressing core technologies that will advance microsystems development, by targeting miniaturisation, higher reliability and alternative power systems necessary for small scale medical implants.

Communication

Some current medical devices require a level of communication with the outside world, but the data rates are relatively low and an external antenna is used to collect data from the implant. Within 'Healthy Aims' the system will be miniaturised such that an internal antenna is employed with low power RF electronics, all packaged in a sealed system for implantation, Fig.2. This device will communicate higher data rates (500 kbps) to base stations up to 3m away. A micro-controller, to manage an RF transceiver, together with an on-board antenna and associated electronics are all underdevelopment. Such a system could be used by many of the devices under development within the project, and thereby become a key component of a wireless Body Area Network system.

Fig.2. Implantable transceiver for a Body Area Network

Power sources

The requirement for a miniature, long life, secondary (rechargeable) power source is common to a range of microsystems, including those in 'Healthy Aims'. Implantable medical devices impose other challenges, namely: prevention of any form of failure mode over a 10-year life, high energy density, (in excess of 150mWh/cc), and non-standard forms.

Battery fuel cells and biofuel cells are being explored in this project, the first extending current (aerospace) state-of-the-art, the latter developing completely new systems using body chemistry as a means of generating power. The current power limit of implanted biofuel cells is 0.1µW/mm ² , a tenth of the power required. A concept study has compared the power capabilities of biofuel cells with alternative systems such as mechanical generators, thermal generators and galvanic cells. The biofuelcell appears superior in terms of continuous output, longevity (excluding enzymatic fuel cells), minimally-invasive implantation capability and biocompatibility. Within this category, there are three options:

• Direct fuel cells - long life, amenable to sterilisation and biocompatible
• Enzymatic fuel cells - high reactant specificity allowing a simple, one-compartment design
• Microbial fuel cells - superior longevity (self-regenerating), but need to consider the potential for infection of the body

Early work has focused on a direct glucose/oxygen fuel cell with improved power output, and an enzymatic fuel cell. On the more conventional route, lithium ion battery technology is being explored.

Biocompatible materials

Coatings already certified for in vivo use may not be suitable for the functionally more complex devices being developed within 'Healthy Aims'. This drive for higher levels of functionality in a package of minimal size is expected to lead to the development of new and improved coating materials and surface treatments to provide biocompatibility to such packages.

Encapsulation materials for electronic devices, together with surface modifications, need to be compatible with both the in-body environment and also the processing conditions used in the manufacture of the entire system. Strategiesto develop such materials will also include methods to reduce undesired tissue growth around the implant ('anti-fouling'). Other biomaterials are being developed specifically to enhance electrical conductivity at an electrode/nerveinterface.

Micro-assembly and packaging techniques

The objective of achieving enhanced functionality within reduced-size packages requires advanced assembly technologies based on 2D and 3D architectures. At the interconnect level, functional density is targeted to be twice that available today, with input/output (I/O) pitch on active devices reaching  40µm through modified wire bond and flip chip techniques, and interconnection on biocompatible rigid and flexible substrates increasing to 200 cm/cm ² . Existing methods are being adopted wherever possible, but adapted for these specialist applications to ease transfer to production. TWI has been one of several RTOs in the consortium, leading the development of packaging and interconnect technologies.

Micro-electrodes

For functional electrical stimulation (FES), micro-electrodes are needed that can interface effectively with targeted nerves and muscles and be integrated into a true microsystem. Although technology is available, it has so far been difficult to integrate effectively into medical microsystems because of the increased number and density of the electrodes required. Work is underway on a range of technologies, including thin flexible polymers containing micro-electrodes, and on thinning silicon electrodes to 25-30µm. In all cases, ways of maximising electrode surface area will be investigated, to improve contact with tissue.

For this new generation of active devices, it will be necessary to incorporate multiplexing electronics near the electrodes, which must be protected from ingress of moisture. Also, the tissue environment into which the device is to be implanted must be protected from leaching of any harmful species inherent in the electronic components. To date, work has focused on topographical changes to encourage/discourage cell adhesion, and the use of chemical and biomolecular cues to influence patterns of cell growth and differentiated function.

Sensors and actuators

Sensors and actuators are essential components of any microsystem. To date, the focus has been on silicon-based sensors for low cost, high volume automotive applications. However, the space envelope and power requirements of these are generally much too large for medical device applications. For instance, measurement of human limb motion requires six degrees of freedom, without restricting movement. A range of sensors and actuators is under investigation in this project, including:

• 3-axis gyro and 3-axis accelerometer combined in an inertial measurement unit for human body motion
• Pressure sensors for medical diagnostics

Complex algorithms and signal processing will also be developed during the project to enable the motion sensors to be used as a trigger for the FES application.

Product applications

Cochlear implant

The current generation of cochlear implants consists of a stimulator implanted into the temporal bone behind the ear, with a lead to 22 passive electrodes at the stimulation site in the cochlea, Fig.3. There is a drive to reduce the size of the implant to allow for faster, less traumatic implantation, and assist implantation in infants. Miniaturisation of the stimulator and delivery of improved hearing performance arekey targets.

 Fig.3. Cochlear implant, with silicone-encapsulated micro-fabricated tip
( Courtesy of Cochlear Technology Centre)

Functional Electrical Stimulation (FES)

FES can produce and control simple movements of otherwise paralysed limbs. Various devices already exist for this purpose but they are relatively unsophisticated in concept and design, giving limited scope to both clinicians and patients. An objective within 'Healthy Aims' is to develop an integrated, modular stimulator system with up to 12 stimulating channels and four recording channels. Ultimately these will be capable of stimulating both upper and lower limbs. Innovations required include miniaturisation, improved packaging, improved stimulation patterns/control algorithms, better sensors and wireless communication with an external controller.

Intra-cranial pressure sensor

For certain head trauma or diseases, conventional implants include shunts to allow pressure release on the brain, and stents to prevent arterial blockage. In both cases, it is not currently possible to continuously determine if these implants are operating successfully, and device failure, in the worst case, can be fatal. Monitoring performance, by measurement of local pressure, provides a means to identify on-set of failure, allowing time for treatment. This work package aims to develop a highly miniaturised ( 1mm ² ), capacitive, absolute pressure sensor chip. Critical features include electrical stability and low temperature dependency.

Summary and conclusions

The 'Healthy Aims' project has active involvement from academics, industrialists and clinicians to enable fundamental understanding, generic technology development, prototype application studies and early-stage clinical trials. It is ambitious, and one of the first of its kind supported in Europe. It is also unique in taking application design concepts into prototypes, and undertaking early clinical work. This is to demonstrate the benefits to clinicians and patients, as well as significantly extending state-of-the-art microsystem technology such that early exploitation in the medical sector becomes feasible. This has been achieved by having a truly multi-disciplinary approach.

The project will extend the use of microsystems in the medical sector, thus ultimately improving quality of life for citizens across Europe. Moreover, with a local body area network, medical devices can become 'intelligent systems' without the need for patient intervention. This project will help develop the concept of 'Ambient Intelligence' for people suffering with medical conditions that require implants in order to help them lead a near-normal life.