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Implantable Pulse Generators “Stimulate” Medical Device Industry

In recent years, there has been great excitement about the use of neuromodulation to treat a wide array of medical conditions and diseases. The technology uses electrical signals to stimulate or block different nerve impulses in the body and is adapted from technology used in cardiac rhythm management. It holds promise for reducing or eliminating back pain, curing obesity, lowering high blood pressure and controlling diabetes without daily injections of Insulin, as well as addressing many other conditions.

Advanced ceramic materials are playing an important role in the technology and are poised to play an even greater one as these medical devices flood onto the market to treat an increasing number of ailments. They make innovative treatment methods possible that traditional materials would not allow. Ceramic-to-metal brazed assemblies for hermetically sealed electrical feedthroughs, Piezocomposite materials that facilitate ultrasonic device communication, and biocompatible ceramics as an alternative to Titanium device casings, are just a few of the ways that advanced ceramics are playing a part in enhancing this technology.

Research and development on new ceramic composite materials and assemblies, as well as high pin density feedthrough assemblies, is being pursued to enable the next generation of neuromodulation devices. This new generation will provide better treatment, communicate with other devices and be even safer and more convenient for patients.

Implantable Pulse Generators – Key to the New Technology
Central to the technology is a neurostimulator, usually referred to as an Implantable Pulse Generator (IPG). The IPG is a battery-powered micro-electronic device, implanted in the body, which delivers electrical stimulation to the nervous system. An essential part of surgically implanted systems designed to treat a wide array of conditions, the IPG delivers very small pulses of electricity to block or stimulate nerve signals (or impulses), depending upon the condition. Figure 1 shows just some of the approved and future uses for this groundbreaking technology.

Figure 1
 
Figure 2 shows a typical IPG implanted in the body. Out of the IPG come a series of wires which control the device and transmit and receive electrical signals. The wires are attached to the nerve being stimulated or blocked.

Figure 2
 

In some cases, the devices are applied to conditions for which medicines either haven’t been completely effective, or have unpleasant side effects. In other cases, nerve stimulation is looked at as a way to control the condition more conveniently for the patient, either alone, or in combination with medicine. The payoff would be tremendous if a device could be implanted in the body laparoscopically, with only a very small incision. Imagine a twenty minute outpatient surgery, followed by years of 100 percent patient compliance, with no possibility of forgetting to take medication. The thought has doctors, patients and insurance companies very excited.

The Feedthrough – Hermetic Structure Key to Success
One key component of the IPG devices is the feedthrough, the mechanical structure that provides the electrical connection for the leads to get in and out of the device housing.

This tiny component, typically no more than one-half inch long by one-quarter inch wide, performs several key functions. First, the feedthrough provides the conduit for communication of signals between the IPG and the body. Second, the feedthrough’s hermetic seal keeps body fluids out of the inside of the IPG device and prevents electricity and battery materials from leaking out into the body. It must be completely and totally leak-free. It also has to be robust enough to withstand radio frequency and eliminate interference from MRI equipment and anti-theft scanners. This tiny piece of device real estate can contain as few as two leads, to around 30.

Figure 3 shows a feedthrough used in the Eon Mini™ Rechargeable IPG System, a device developed for chronic pain management by St. Jude Medical, Inc. The feedthrough, manufactured by Morgan Technical Ceramics’ Alberox business (MTC-Alberox), serves as the bridge between the outside and the inside of the case, and carries the signal from inside the Titanium package to the wires. It is a ceramic-to-metal assembly, made of weldable Titanium flanges, with Platinum or Platinum/Iridium pins, Polycrystalline Alumina and 99.99 percent gold braze. The ceramic serves as an insulator for the feedthrough. Alberox uses a die pressing process to make its own Alumina ceramic components and performs a brazing process to seal the electrical wires into the ceramic components to make the electrical feedthroughs.

Figure 3

MTC-Alberox specializes in customization of feedthroughs, providing design assistance and often working through design iterations with the device designer, before arriving at the feedthrough size and shape that works in a device.

“The feedthrough technology is changing rapidly, as next generation devices get smaller and more compact and device designers seek to add more leads to improve the therapeutic value of the devices,” says John Antalek, MTC-Alberox’s Medical Unit Business Manager.

Antalek says that many device manufacturers often start with an off-the-shelf feedthrough to get their first generation device on the market. Their next generation devices are much smaller and more compact, which makes them more palatable to doctors and patients. “They also have a lot more bells and whistles and customers come to MTC-Alberox to get the custom size and shape of the feedthrough, so they can fit in these additional features. Since we make our ceramic components in house, we have developed numerous sizes and shapes of feedthroughs to match the device design needs.”

Stimulating from Head to Toe – Examples of IPG Applications
New medical uses for IPG devices are patented frequently. Among the conditions for which the devices show the most promise are chronic back pain, hypertension and diabetes. Examples of devices focused on these conditions (either available now or under investigation) are provided below.
 

Chronic back pain
IPG devices deliver mild electrical pulses to the spinal cord, which interrupt or mask the transmission of pain signals to the brain. For example, the Eon Mini™ treats chronic pain of the trunk or limbs and pain from failed back surgery. It is slightly larger than the circumference of a U.S. silver dollar, with only about a 10 mm profile and weighing about an ounce. Its small size allows for a smaller incision, which gives physicians increased flexibility in selecting the implant location and also makes the site less visible and more comfortable for patients.

In this application, the IPG is implanted in the back, in close proximity to the nerve that doctors are trying to block. This particular device is a 16-channel feedthrough, containing a ground wire and pins arranged on a long thin oval. The feedthrough can send sixteen different signals at a time, which doctors place in different locations. They then go through a process of elimination, stimulating one nerve at a time and in combination, working with the patient until they get a combination that effectively treats the pain.

Hypertension (high blood pressure)
Most patients with high blood pressure control the condition by using a regimen of anti-hypertensive drugs. However many studies have reported a persistence of refractive hypertension (elevated blood pressure despite using at least two anti-hypertensive drugs) in as many as 18 percent of the patient population. The IPG devices are being developed to provide a new and improved therapy for treating hypertension which is not only safe and effective, but avoids undesirable side effects of drug therapy.

The system includes an IPG, sensors and leads, external electronics for calibration, programming and periodic adjustment of parameters by the attending physician.

For example, one hypertension treatment clinical trial is investigating whether an implanted device can help control high blood pressure by stimulating pressure sensors called baroreceptors located on the carotid artery and in the carotid sinus. These sensors measure and report blood pressure to the brain, where it is compared to the needs of the body.

Another example is investigations on a device that stimulates the vagus nerve to control obesity; researchers testing the device have seen a dramatic drop in hypertension as an unexpected benefit of the therapy.

Diabetes
Several devices are being used or are under development, especially as an option for patients with diabetes that has proven unresponsive to drug therapy. An IPG is implanted and used to stimulate or inhibit the patient’s vagus nerve to modulate its electrical activity to increase or decrease secretion of natural insulin by the patient’s pancreas. The stimulator might be selectively activated in response to direct measurement of blood glucose or symptoms, or could be activated automatically for predetermined times or intervals. Alternatively, it could be automatically activated using an implanted sensor to detect the blood glucose concentrations.

For example, one implantable system, originally tested to control obesity and other gastrointestinal disorders, is showing some promise in controlling diabetes. The device is designed to precisely control nerve and organ function using the vagal nerves, which regulate much of the activity of the stomach and the pancreas. The device being studied delivers high frequency, low energy electrical signals through laparoscopically implanted leads to block vagal nerve transmission. The delivery of energy to the nerves is intermittent and the effects of the therapy on the nerves and end organs are intended to be reversible. The system is designed to be precisely programmed and non-invasively adjusted to meet individual needs.

Headaches, obesity, epilepsy, depression, Parkinson’s, syncope, sleep apnea and restless leg syndrome are a few of the many other conditions for which this treatment is being investigated.

Look to Even More Stimulation in the Future
Smaller but Better Devices with More Power and Features
The general trend in implantable devices is miniaturization. New devices tend to be smaller, but with a greater number of leads that get more signals into and out of a single device. It is clear that improving the feedthrough and expanding its capability is central to the next generation of IPGs. Future neurostimulator applications are currently looking at 100-200 leads, which will give device manufacturers opportunities to add further treatment to an implantable system.

“We know where the IPG device is headed and we want to proactively provide improved feedthrough capabilities to help the device manufacturers meet their needs,” says MTC-Alberox’s John Antalek. “Just look at how far we’ve come with cardiac rhythm management. Pacemakers were the size of a Blackberry just a few years ago and had just two leads. Now the typical pacemaker is only about the size of a lighter and can have as many as 10 leads, some of which allow better communication to the device, monitoring of other patient information and the ability to send information directly from the device to a doctor.”

Additional leads could also build in intentional redundancy, which would reduce the device downtime and eliminate the need to remove the device if any of the leads fail.

One of the most exciting avenues of research to increase the number of leads is the development of new high density feedthroughs that could contain ten times the amount of leads, while keeping the current size and spacing. Whereas today’s feedthroughs are constructed by assembling many different parts, stacking them into complicated arrays with braze materials and putting them in a furnace for joining, researchers are developing high density feedthroughs using cutting edge advanced ceramic materials and processing technologies focused on miniaturization that promise to be able to pack many more wires together in a much tighter space.

Body Communications
Another interesting development in the IPG arena is the development of “body communications” in which ultrasonic devices are placed into a medical device casing and used to remotely power and communicate with other devices in the body.

“This next level of improvement has great advantages, because it could mean that no wires would have to be implanted,” noted Mark Bartrum, Transducer Design Manager for the ElectroCeramics business of Morgan Technical Ceramics (MTC Electroceramics) in Bedford, Ohio. MTC Electroceramics uses its Piezo ceramic components (high density PZT and Single Crystal Piezo materials) in medical device manufacturing.

“Implanting wires in the body can be a challenge. They may eventually fail, and subsequent removal and replacement can be difficult. Also, using ultrasound means the communication stays within the body, unlike radio frequency. This means one person’s medical device is less likely to interfere with another person’s device and the device could be more readily hardened against interference from MRI equipment, scanners, or other large electrical devices.”

Using ultrasound to both power and interrogate remote sensors is probably on the cards for many implantable devices, but wiring would still be needed for neurostimulators, where leads are attached to the skull, brain, or spine. However, in the future, the main implant might be able to communicate with other devices implanted in the body or the external programmer via ultrasound, rather than radio frequency.

Extracting from technology used in cochlear implants and using Piezo ceramic components that enable increased resolution, the Bedford, Ohio plant has researched a custom assembly for an annunciator that could be inserted into a main IPG. The implant could use intelligible speech to warn the user that an event is occurring.
 

New Biocompatible Materials for IPGs
Most IPGs are currently made of Titanium, a strong and light metal that is lustrous and corrosion-resistant. However, along with efforts to improve the basic electrical feedthroughs so more leads can be added, research and development is being done on using Ceramic Injection Moulding (CIM) to develop a thin-walled ceramic case that could be smaller, simpler and provide more efficient communications to the electronics in the devices. CIM enables production of small components with very high precision and without a secondary grinding process.

For example, MTC’s Stourport UK CIM facility is currently in the early stages of developing an implantable housing made by Zirconia Injection Moulding for use in migraine and cluster headache treatment. The proposed use of ceramic in this device requires Zirconia rather than Alumina, because the component is very thin and Zirconia is much stronger than Alumina. The CIM ceramic would then be brazed and hermetically sealed to the feedthrough.
The Zirconia ceramic casing is stronger than Titanium, allowing for a mechanically robust structure in a smaller sized housing. An Alumina equivalent would be strong, but twice as thick. Both Zirconia and Alumina are transparent to radiofrequency energy, so signals could be passed through the wall for communication and possible charging. The hope is that developing a device casing out of Zirconia would mean that no feedthrough wires would be needed to connect to an antenna. Keeping the antenna within the device improves function for the patient. The Zirconia material is also inherently insulating, so electrical wires can be placed closer together than a metal flanged feedthrough brazed into a metal housing. Such a device would have no need for a battery, so it would not require replacement, as long as it retains its hermetic seal. Finally, the injection molded Zirconia is a biocompatible material that complies with ISO 13356 implants for surgery.
 

Next Steps
The market for neuromodulation is estimated at more than $2 billion, with a compound annual growth rate (CAGR) estimated at 18-22 percent and a seemingly never-ending supply of new applications for the basic technology. With an increasing acceptance by the Food and Drug Administration and insurance companies, preference over some drug therapies and increasing device complexity to deliver more features and tailored effect, it is clear that developing the next generation of IPGs is critical.

What is also clear is that advanced ceramics will be a major part of that quest. Morgan Technical Ceramics’ experience as a multi-national ceramic manufacturer gives them the ability to take technologies from other parts of the advanced ceramics business and use them in parts of the business where they haven’t been used before. The same robust biocompatible materials already being used to make implantable drug delivery devices may now be used to develop a feedthrough that will be used in next generation IPGs.