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The life of neurological prostheses
THE LIFE OF NEUROLOGICAL P.E.K.
PROSTHESES
Donaldson
ABSTRACT Reliable and long-lived certain
neurotogical
technical
prostheses
conditions
for the amelioration
can probably,
point of view, be made widely
of
from o
available.
Their
achievement seems to be not so much a matter microelectronics’ high technology as of materials particularly a proper understanding of adhesion, possibly
of new
materials
of science, and
technology.
INTRODUCTION
Neurological prostheses have found a number of useful clinical applications1J~3*4*5. For the few people who have received them in the UK, they can be of great help. If the fitting of these devices is to emerge from the research stage and become general, a number of conditions must be fulfilled. Amongst these are, (1) that the devices themselves must be reasonably easy and cheap to manufacture, (2) they must be reliable, and (3) they must offer an expectation of life which is both adequate and predictable. Price, reliability and life are matters for the engineer and in this paper attention is focused on the life of neurological prostheses, in particular the microelectronic part which is implanted. Failure of external equipment can be overcome by resorting to a spare ,set; failure in an implant means reoperation. Sometimes this is a relatively trivial matter; sometimes not. Implants can fail prematurely through inexperience on the part of the designers. For example, there may be a simple mechanical failure, such as a broken wire, because the implant is not strong enough to withstand the forces imparted to it during movements of the body. Alternatively, a straightforward electronic failure might result from attempts to squeeze an excessive output from a radio-cotipled implanted stimulator, which would not have happened had a suitable voltage-limiting device been included. When elementary mistakes such as these are no longer made, when ‘infant mortality’ has been practically eliminated, how long can a patient expect his implant to last - 2 years, 10 years or 25 years?
Figure
MRC Neurological Prostheses Unit, 1 Windsor Walk, London SE5 8RB
294
J. Biomed.
Engng.
1981,
Vol. 3, October
Electrical
skeleton
of imaginary
implant.
Stratagems to prevent implants waterlogging include the use of osmotic pumping, the use of hermetic sealing, and the use of heat. None of these is ideal. Osmotic pumping is not very effective6, and hermetic sealing solves only part of the problem, as will be explained. Internal heating is effective, but requires a supply of energy which the system designer may be unwilling to provide. Figure 1 represents the skeleton of an imaginary implant. The irregular shape in the middle is a collection of electronic components, which can be supported on a thick- or thin-film substrate, or perhaps just soldered together to make a ‘better birdsnest’. Four bare flexible wires are connected from the electronic components to four platinum electrodes. To turn this into an implant we ideally need an encapsulating material (Figure 2) which: (a) is flexible, so that the wires can be repeatedly bent, (b)
adheres to the electrodes, or to the wires, so that body fluid cannot seep in along the surface of the wires,
(c)
is impermeable, so that water vapour cannot diffuse through it to the electronic components,
THE PRORLkM.
Modem microelectronic components are reliable and have almost indefinite life, provided they are not subjected to excessive voltage and temperature, and provided the ambient humidity fluctuates within the normal range. Thus, a plastic-encapsulated transistor will work reliably in 95% RH, or even 100% RH (when it absorbs moisture) provided there are counterbalancing periods of, say, 40% RH (when it loses moisture again). The trouble about the interior of the body, for a microelectronic implant, is not so much that it is wet, but that it is always wet. There is a tendency for implants to become waterlogged, with consequent short circuiting, electrolysis, corrosion and eventual failure.
1
/
Figure 2 Ideal but unpracticable for implant.
encapsulation
0141-5426/81/040294-03 $02.00 @ 1981 IPC Business Press
The
(b)
life of neurological
3
One practicable
encapsulation
scheme.
Unfortunately, no such encapsulating material exists. Ignoring adhesion for the moment, the sequence of autodavable, stable materials: silicone rubber, epoxy resin, polymerized fluorocarbon, glass, metal, in ascending order of impermeability, is almost in descending order of flexibility. An alternative approach is to split the provision of flexibility, adhesion and impermeability among up to three separate materials. The components are encased in a ceramic or metal box, with hermeticallysealed lead-throughs, which provides the impermeability. The wires are insulated with a flexible silicone rubber or fluorocarbon sleeve. An encapsulant, which adheres to ceramic or metal in the presence of water, is used to insulate the joints between the wires and the lead-throughs (Figure 3). Thus, body fluid is allowed to seep along the outside of the wires but is stopped at the point where the lead-throughs meet the box. Hermetically sealed boxes and PTFE-coated platinum wires are already commercially available and may be regarded as fully developed. So also are silicone-rubber-coated 5-conductor cables, developed especially for implantation by Mr J.D. Cooper of the MRC Neurological Prostheses Unit. These have helically disposed, platinumiridium conductors which enable the cables to stretch, bend and twist. The boxes are sealed sufficiently hermetically to allow them a possible lifetime of decades, and in vitro accelerated fatigue tests on the cables indicate an expected lifetime in uiuo of the same order. Further research into encapsulants is required urgently. Non-toxic materials are needed whose adhesion is maintained despite the environment within the body. Knowledge of the best adherend surfaces to form the outside of the box is also required, as is an understanding of the preparatory treatment such surfaces should be given before the encapsulant is poured. Finally, it is necessary to know how long the adhesive-adherend system can be expected to last in use.
P.E.K.
Donaldson
characterize the adhesive-adherend systems we already use, allotting a figure or figures of merit to each, in order to provide a basis of comparison with each other and with new, as yet untried, systems.
Conditions
Figure
prostheses:
at adhesive-adherond
interface
Consider Figure 4, which shows part of the wall of the box, dry inside, with two lead-outs passing through, some neighbouring encapsulant and some body fluid in contact with it. Suppose that there is a failure of adhesion leading to the formation of a small void. The water vapour which saturates the encapsulant will condense in the void and N,, O2 and CO, will dissolve in the water: Depending on the permeability of the encapsulants, Na’, Cl-, HCO~ and other ions may also be present in the water. A complete analysis of the equilibrium solution eventually achieved, if any, is not worth seeking, but the pH and the electrical conductivity are of interest. The former is likely to affect whether the region of failed adhesion grows and, if it does, the latter determines how the implant is affected when the region spans the two lead-out wires. We are currently trying to measure these quantities, for silicone rubber encapsulation. Characterization systems
of adhesive-adherend
This is achieved by measuring the time-to-failure of lap shear pull-test specimens (Figure 5) submerged under water at various temperatures in the range 50-100°C, and at various pH values. The results, when presented as Arrhenius plots (log time against the reciprocal of absolute temperature) appear to be linear and can be defined by an intercept and a slope. The intercept indicates the
Body of box
SOME SOLUTIONS
To advance in this direction we need to do two things : (a)
characterize the conditions at the adhesiveadherend interface, in Go, so that the right in vitro studies on proposed new materials and processes are performed;
Figure 4 Incipient adhesion failure at the surface of the hermetic box.
J. Biomed.
Engng.
1981, Vol. 3, October
295
The life of neurological
prostheses:
P.E.K. Donaldson
faith, but which shows no useful underwater adhesion whatever. ADHEREND
TEST
/
\
FORCE
F&m-e 5
Lap shear adhesion test piece.
life at some suitable elevated temperature, say 80°C. The slope is of the nature of an activation energy which should enable the life of the joint at 37OC to be predicted. For example, an adherend-adhesive system having an activation energy of 0.8 eV which pulls apart after 40 days at 80°C should last for 5 years at 37’C. Tests on alumina, frittedgoldrthick film conductor, gold, ‘Kovar’ (Fe-Ni-Co alloy which seals to glass) and tin-lead solder as adherends, and one of 3 silicone rubber adhesives, all at neutral pH, are in progress. The most promising adherend material is alumina which, even with the least satisfactory of the adhesives, lasts for an average of 200 days at 80°C and shows an activation energy of -1.0 eV, suggesting a life at 37°C of some 30 years. The least promising is gold, a material in which microelectronic engineers generally have a good deal of
296
J. Biomed.
Engng.
1981, Vol. 3, October
CONCLUSIONS
Implants removed from patients, in order that they may be replaced by something functionally more advanced, show little or no signs of degradation 2-3 years after implantation. It is not known how long these implants would have lasted had they been left in position. It looks as if it may eventually be possible to make implants with a definite life expectancy. Just how satisfactory are the materials presently used should become clearer in the next few months. Should better performance then seem desirable, the way seems clear to identifying better materials quickly, once the search for them has begun. REFERENCES
Donaldson, P.E.K. and Davies, J.G., Microelectronic Devices for Surgical Implantation, Radio Electron. Eng. 1973,43, 125-132. Hambrecht, F.T. and Reswick, J.B., in Functional Electrical Stimulation, Marcel Dekker, New York, 1977. Donaldson, P.E.K., In Search of the Reliable Microelectronic Implant, T.Z.N.S. 1978, August, 49-50. Hambrecht, F.T., Neural Prostheses, Annu. Rev. Biophys. Bioeng. 1979,8,239-267. Donaldson, P.E.K., in The Use of Technology in the care of the Elderly and the Disabled, (Eds. Jean Bray and Sheila Wright) Francis Pinta, London, 1980, pp 100-104. Donaldson, P.E.K. and; Sayer, E., Osmotic pumping of non-hermetic neuroprorthetic implants. Med. Biol. Eng. Comput. 1981, In press.
PROSTHESES
Donaldson
ABSTRACT Reliable and long-lived certain
neurotogical
technical
prostheses
conditions
for the amelioration
can probably,
point of view, be made widely
of
from o
available.
Their
achievement seems to be not so much a matter microelectronics’ high technology as of materials particularly a proper understanding of adhesion, possibly
of new
materials
of science, and
technology.
INTRODUCTION
Neurological prostheses have found a number of useful clinical applications1J~3*4*5. For the few people who have received them in the UK, they can be of great help. If the fitting of these devices is to emerge from the research stage and become general, a number of conditions must be fulfilled. Amongst these are, (1) that the devices themselves must be reasonably easy and cheap to manufacture, (2) they must be reliable, and (3) they must offer an expectation of life which is both adequate and predictable. Price, reliability and life are matters for the engineer and in this paper attention is focused on the life of neurological prostheses, in particular the microelectronic part which is implanted. Failure of external equipment can be overcome by resorting to a spare ,set; failure in an implant means reoperation. Sometimes this is a relatively trivial matter; sometimes not. Implants can fail prematurely through inexperience on the part of the designers. For example, there may be a simple mechanical failure, such as a broken wire, because the implant is not strong enough to withstand the forces imparted to it during movements of the body. Alternatively, a straightforward electronic failure might result from attempts to squeeze an excessive output from a radio-cotipled implanted stimulator, which would not have happened had a suitable voltage-limiting device been included. When elementary mistakes such as these are no longer made, when ‘infant mortality’ has been practically eliminated, how long can a patient expect his implant to last - 2 years, 10 years or 25 years?
Figure
MRC Neurological Prostheses Unit, 1 Windsor Walk, London SE5 8RB
294
J. Biomed.
Engng.
1981,
Vol. 3, October
Electrical
skeleton
of imaginary
implant.
Stratagems to prevent implants waterlogging include the use of osmotic pumping, the use of hermetic sealing, and the use of heat. None of these is ideal. Osmotic pumping is not very effective6, and hermetic sealing solves only part of the problem, as will be explained. Internal heating is effective, but requires a supply of energy which the system designer may be unwilling to provide. Figure 1 represents the skeleton of an imaginary implant. The irregular shape in the middle is a collection of electronic components, which can be supported on a thick- or thin-film substrate, or perhaps just soldered together to make a ‘better birdsnest’. Four bare flexible wires are connected from the electronic components to four platinum electrodes. To turn this into an implant we ideally need an encapsulating material (Figure 2) which: (a) is flexible, so that the wires can be repeatedly bent, (b)
adheres to the electrodes, or to the wires, so that body fluid cannot seep in along the surface of the wires,
(c)
is impermeable, so that water vapour cannot diffuse through it to the electronic components,
THE PRORLkM.
Modem microelectronic components are reliable and have almost indefinite life, provided they are not subjected to excessive voltage and temperature, and provided the ambient humidity fluctuates within the normal range. Thus, a plastic-encapsulated transistor will work reliably in 95% RH, or even 100% RH (when it absorbs moisture) provided there are counterbalancing periods of, say, 40% RH (when it loses moisture again). The trouble about the interior of the body, for a microelectronic implant, is not so much that it is wet, but that it is always wet. There is a tendency for implants to become waterlogged, with consequent short circuiting, electrolysis, corrosion and eventual failure.
1
/
Figure 2 Ideal but unpracticable for implant.
encapsulation
0141-5426/81/040294-03 $02.00 @ 1981 IPC Business Press
The
(b)
life of neurological
3
One practicable
encapsulation
scheme.
Unfortunately, no such encapsulating material exists. Ignoring adhesion for the moment, the sequence of autodavable, stable materials: silicone rubber, epoxy resin, polymerized fluorocarbon, glass, metal, in ascending order of impermeability, is almost in descending order of flexibility. An alternative approach is to split the provision of flexibility, adhesion and impermeability among up to three separate materials. The components are encased in a ceramic or metal box, with hermeticallysealed lead-throughs, which provides the impermeability. The wires are insulated with a flexible silicone rubber or fluorocarbon sleeve. An encapsulant, which adheres to ceramic or metal in the presence of water, is used to insulate the joints between the wires and the lead-throughs (Figure 3). Thus, body fluid is allowed to seep along the outside of the wires but is stopped at the point where the lead-throughs meet the box. Hermetically sealed boxes and PTFE-coated platinum wires are already commercially available and may be regarded as fully developed. So also are silicone-rubber-coated 5-conductor cables, developed especially for implantation by Mr J.D. Cooper of the MRC Neurological Prostheses Unit. These have helically disposed, platinumiridium conductors which enable the cables to stretch, bend and twist. The boxes are sealed sufficiently hermetically to allow them a possible lifetime of decades, and in vitro accelerated fatigue tests on the cables indicate an expected lifetime in uiuo of the same order. Further research into encapsulants is required urgently. Non-toxic materials are needed whose adhesion is maintained despite the environment within the body. Knowledge of the best adherend surfaces to form the outside of the box is also required, as is an understanding of the preparatory treatment such surfaces should be given before the encapsulant is poured. Finally, it is necessary to know how long the adhesive-adherend system can be expected to last in use.
P.E.K.
Donaldson
characterize the adhesive-adherend systems we already use, allotting a figure or figures of merit to each, in order to provide a basis of comparison with each other and with new, as yet untried, systems.
Conditions
Figure
prostheses:
at adhesive-adherond
interface
Consider Figure 4, which shows part of the wall of the box, dry inside, with two lead-outs passing through, some neighbouring encapsulant and some body fluid in contact with it. Suppose that there is a failure of adhesion leading to the formation of a small void. The water vapour which saturates the encapsulant will condense in the void and N,, O2 and CO, will dissolve in the water: Depending on the permeability of the encapsulants, Na’, Cl-, HCO~ and other ions may also be present in the water. A complete analysis of the equilibrium solution eventually achieved, if any, is not worth seeking, but the pH and the electrical conductivity are of interest. The former is likely to affect whether the region of failed adhesion grows and, if it does, the latter determines how the implant is affected when the region spans the two lead-out wires. We are currently trying to measure these quantities, for silicone rubber encapsulation. Characterization systems
of adhesive-adherend
This is achieved by measuring the time-to-failure of lap shear pull-test specimens (Figure 5) submerged under water at various temperatures in the range 50-100°C, and at various pH values. The results, when presented as Arrhenius plots (log time against the reciprocal of absolute temperature) appear to be linear and can be defined by an intercept and a slope. The intercept indicates the
Body of box
SOME SOLUTIONS
To advance in this direction we need to do two things : (a)
characterize the conditions at the adhesiveadherend interface, in Go, so that the right in vitro studies on proposed new materials and processes are performed;
Figure 4 Incipient adhesion failure at the surface of the hermetic box.
J. Biomed.
Engng.
1981, Vol. 3, October
295
The life of neurological
prostheses:
P.E.K. Donaldson
faith, but which shows no useful underwater adhesion whatever. ADHEREND
TEST
/
\
FORCE
F&m-e 5
Lap shear adhesion test piece.
life at some suitable elevated temperature, say 80°C. The slope is of the nature of an activation energy which should enable the life of the joint at 37OC to be predicted. For example, an adherend-adhesive system having an activation energy of 0.8 eV which pulls apart after 40 days at 80°C should last for 5 years at 37’C. Tests on alumina, frittedgoldrthick film conductor, gold, ‘Kovar’ (Fe-Ni-Co alloy which seals to glass) and tin-lead solder as adherends, and one of 3 silicone rubber adhesives, all at neutral pH, are in progress. The most promising adherend material is alumina which, even with the least satisfactory of the adhesives, lasts for an average of 200 days at 80°C and shows an activation energy of -1.0 eV, suggesting a life at 37°C of some 30 years. The least promising is gold, a material in which microelectronic engineers generally have a good deal of
296
J. Biomed.
Engng.
1981, Vol. 3, October
CONCLUSIONS
Implants removed from patients, in order that they may be replaced by something functionally more advanced, show little or no signs of degradation 2-3 years after implantation. It is not known how long these implants would have lasted had they been left in position. It looks as if it may eventually be possible to make implants with a definite life expectancy. Just how satisfactory are the materials presently used should become clearer in the next few months. Should better performance then seem desirable, the way seems clear to identifying better materials quickly, once the search for them has begun. REFERENCES
Donaldson, P.E.K. and Davies, J.G., Microelectronic Devices for Surgical Implantation, Radio Electron. Eng. 1973,43, 125-132. Hambrecht, F.T. and Reswick, J.B., in Functional Electrical Stimulation, Marcel Dekker, New York, 1977. Donaldson, P.E.K., In Search of the Reliable Microelectronic Implant, T.Z.N.S. 1978, August, 49-50. Hambrecht, F.T., Neural Prostheses, Annu. Rev. Biophys. Bioeng. 1979,8,239-267. Donaldson, P.E.K., in The Use of Technology in the care of the Elderly and the Disabled, (Eds. Jean Bray and Sheila Wright) Francis Pinta, London, 1980, pp 100-104. Donaldson, P.E.K. and; Sayer, E., Osmotic pumping of non-hermetic neuroprorthetic implants. Med. Biol. Eng. Comput. 1981, In press.