Top TechnologiesMedical devices involve multiple technologies, from metallurgy to microprocessors. This article, based on interviews with experts in the field, takes a look at several that will have a significant impact in the years to come: smart implants and wireless communication, smart materials, MRI compatibility, and nanotechnology.
On the cover: AcryMed scientists take a close look at the surface of catheters coated with nanoparticles of antimicrobial silver.
By Peter Cleaveland, West Coast Editor
At A Glance:
- Monitoring applications
- Bioabsorbable materials
- Resolving electronics concerns
- Promoting natural healing
Smart materials, smart implants, nanotechnology, wireless devices, and MRI compatibility are on the leading edge of medical device technology. This article will examine each of these important sectors.
Smart Implants and Wireless CommunicationsWireless technology is finding increasing use in medicine, much of it in monitoring: sensors for heart rate, BP, and other functions can feed a small transmitter that communicates with a nearby receiver. The communication can also be two-way, so medical devices can be adjusted in real time from a distance, either on command or automatically. An example is Guidant Corp.’s Latitude Communicator and secure data storage system, which received FDA approval in September of 2005. This is the final components of the company’s Latitude Patient Management system, which makes it possible to conduct wireless, automatic device data uploads from the patient’s home. The communicator transmits the data to an Internet server where it can be accessed by the physician.
AAA pressure sensor
is implanted to measure
pressure in an aneurism
being treated by a stent graft.
(Photo: Pat Cahill, CardioMEMS)
Communicating over much shorter distances is a new device from CardioMEMS, which has created a sensor called the EndoSure that can monitor for pressure buildup in the aneurism sac following endovascular repair of an aortic aneurism, eliminating the need for CT scans (with their attendant radiation dose and need for injection of contrast agents) to monitor the stents. To read the sensor, the physician waves a wand over the patient’s abdomen; the wand simultaneously powers up the sensor and reads its output. “It’s essentially an electromagnetic coupling between an external antenna and our implanted sensor,” says David Stern, president and CEO of CardioMEMS. The device can detect pressure changes of as little as 1.0 mm Hg. The system received FDA approval in November, Stern continues, and has been used in several hundred procedures.
MicroCHIPS is developing an intelligent drug-delivery implant that can be controlled internally or by wireless command. The device contains a microchip with a set of individual reservoirs that can be filled with therapeutic agents, each capped with a 380 nm electrically-erodable membrane made of platinum and titanium. The contents of each reservoir can be released either on schedule or by external command via a wireless link. First human demonstrations are about five years away, says MicroCHIPS president Dr. John Santini.
It’s also possible to put sensors in the reservoirs, adds Santini, exposing them as needed. Right now there are no implantable continuous glucose sensors, he says, because the sensors degrade rapidly in the body, “but if I have 24 of those in sealed reservoirs, then I open the first one and use it for two weeks and when that starts to degrade or fail, open the second one, which has never seen the body, and then do that again and again and again, I have a one-year implant.”
This intelligent drug-delivery implant contains a microchip with a set of individual reservoirs that can be filled with therapeutic agents, each capped with an electrically-erodable membrane. The contents of each reservoir can be released either on schedule or by external command via a wireless link. (Photo: MicroCHIPS)
Biophan Technologies is working on another wirelessly controlled drug delivery system. The company’s Nanolution division is working on a coating of ferromagnetic nanoparticles, each linked to drug molecules. The nanoparticles resonate electrically at certain frequencies, so by applying an RF field, they can be vibrated to release their drug molecules. Implants like artificial hips, for example, could be coated with a mixture of particles that would release successive doses of anti-inflammatory drugs as needed.
Smart MaterialsA recent report, “RGB-154N Smart Materials: A Technology and Market Assessment,” from Business Communications Co. Inc., estimates the worldwide smart materials market at $8.1 billion in 2005 and expects it to rise at an average annual growth rate of 8.6% to $12.3 billion in 2010. Smart materials studied in the report include piezoelectric, magnetostrictive, electrochromic, thermoresponsive, and electrostrictive materials.
One hard-to-ignore trend in materials is the increasing popularity of bioabsorbable polymers. While absorbable polymers have been available for some time, the methods of making them have begun to change. A good example is a pair of related companies: Metabolix and Tepha. Both produce polyhydroxyalkanoate biopolymers, and Metabolix is also developing production from plant sources, although currently most of what they do is also from fermentation. Tepha’s lead biomaterial—TephaFLEX polymer—says Dr. Ajay Ahuja, Tepha’s director of business development, displays “increased strength and strength retention, increased softness, and flexibility, as well as excellent tissue biocompatibility.” Bioabsorbable materials, says Dr. Ahuja, are part of a larger move towards regenerative medicine. “As medical devices have advanced to the point where implantable devices have quite good safety and efficacy . . . the medical community would be looking for . . . devices that take advantage of the body’s own regenerative mechanisms from absorbable devices that allow the body’s own tissue regeneration to wound healing [where] there’s no implantable material left, to full-blown tissue engineering devices.” The company hopes to have its first product, an absorbable suture, on the market shortly.
MRI CompatibilityInteraction between implanted devices and MRI equipment has been a challenge. The physician must balance the usefulness of an implant with the fact that it may make it impossible to do an MRI.
If the implant contains any ferromagnetic material, it can be subjected to forces or torques with serious or fatal consequences. But there are more subtle effects as well. An MRI machine produces a large static magnetic field, a gradient field that fluctuates at several hundred cycles per minute, and an RF field in the vicinity of 64 MHz. These fields can induce currents in the wire leads of a pacemaker, defibrillator, neurostimulator, or other pain device, says Michael Weiner, CEO, Biophan Technologies. “The tissue near the lead, the electrode in the myocardium, also next to the path of the lead, can get hot. And the heating can then result in subsequent post-MRI tissue scarring.” This scarring can impede electrical flow, he continues, “so you wind up with a situation where either the pacemaker or defibrillator can’t hear the heart signal; therefore, it can’t interpret it and respond, or the heart may not hear the pacing signal.” A patient can go home after an MRI procedure feeling fine and die that night when the defibrillator fails to fire. And the problem isn’t confined to cardiac devices. The leads to a neurostimulator in the brain can also cause tissue heating of as much as 30°C during an MRI scan.
Even if heating doesn’t occur, the gradient field can induce up to one half or one volt into the leads, which in some cases is enough to stimulate tissue and cause tachycardia.
|Making Electricity in the Body
A major drawback with electrically powered implants is the need to supply them with power. While lower-power circuits and better batteries have helped, there is still a need for repeated surgeries to replace failing batteries. There have been numerous attempts to find a better power source—even suggestions that piezoelectric materials could be included in orthopedic implants to create electrical power as the patient walks. Two companies have been working on a more widely applicable solution: using the body’s own heat to generate electricity. Thermoelectric generators have been known for a long time—they power interplanetary probes—but they generally require substantial temperature differences to work. These new devices can extract small amounts of power from the few degrees difference between the skin and the body core. Biophan Technologies’ Biothermal device uses a large number of thin-film bismuth telluride thermoelectric junctions placed electrically in series and thermally in parallel to produce about 50 µW at 3 V, which is enough to power a pacemaker. Another company, Thermo Life Energy Corp. is also working on small thermoelectric generators.
There are a number of ways to gain MRI compatibility. One is to eliminate all conductive materials in the implant, but that’s seldom practical. Biophan Technologies takes several approaches to the problem. One is to make sure the multiple fine conductors used in lead wires are insulated from each other. This tends, says Weiner, to make the electrical flow self-canceling. Another method is to place a small low-pass filter in the lead, with a cutoff frequency of about 30 kHz. The filter lets through the desired signals but blocks the 64 MHz RF, virtually eliminating heating. Another way is to use a resonant circuit. “If we put a small resonant circuit powered by the MRI energy itself near the electrode tip, like a 1.0 mm chip, it will eliminate the heating also.”
Induced voltage is more difficult to overcome, says Weiner, but it can be handled by creating a loop in the lead with the correct size, orientation, and number of turns to cancel the voltage induced in the lead. If the leads are not overly long, he adds, “it’s possible to put the canceling device inside the pacing device or whatever the device is itself, and even vary the length of those loops within the device to get the optimal self-canceling effect.”
Resonant circuit effects can have another benefit, Weiner adds. A metal stent creates a Faraday cage effect, shielding its interior from the MRI and making restenosis difficult to spot. Biophan is experimenting with coating the stent with a thin layer of nanomagnetic particles in a nonconducting matrix that allows the MRI to see inside it.
MRI compatibility standards are in a state of flux, says Weiner. The previously published ASTM standard, he says, used a phantom that simulates tissue, with the heating effect measured by optical probes. The problem, he says, is that the maximum heating does not occur at the tip, but several millimeters into the tissue. “We’ve seen 7° heating go up to 30 by moving the electrode.” What’s more, he adds, the two probes specified in the standard give differing readings. “There’s a lot underway right now between the FDA and the ASTM standards groups, the manufacturers of MRIs, the manufactures of pacemakers,” says Weiner. “We’re all on a regularly scheduled conference call trying to set a new level of standards, and I believe we’ll see the industry now move to make the devices safe.”
NanotechnologyOne application of nanotechnology has already been mentioned, but its main medical application is in antimicrobial coatings. Acrymed Inc. has developed a method for coating both the exterior and lumen of catheters and other devices with a uniform layer of
AcryMed founder Dr. Bruce Gibbins (right) and senior research scientist Balu Karandikar compare catheters before (white) and after treatment with new silver nanotechnology.
nanoparticulate silver. “Getting the antimicrobial both on the outside and the inside is really a goal of the industry,” says Dr. Bruce Gibbins, PhD, founder of AcryMed Inc. The nanoparticles, which measure between 5 and 15 nm, are applied with a dip process that can be used on almost anything: catheters, implants, contact lenses, wound dressings—even flesh. This could go a long way towards cutting back on nosocomial infections, which cause tens of thousands of deaths every year and can costs tens of thousand of dollars to treat. And the silver is released slowly enough that it doesn’t cause the unsightly staining that has limited acceptance of some silver-coated devices.
Researchers at Angstrom Medica have patented a nanostructured form of hydroxyapatite (HA) that could be used to create orthopedic devices that act as a scaffold by new bone growth and are eventually absorbed by the body. An alternative to this, suggests Gibbins, is to use nanostructured HA as a coating to encourage ingrowth into more conventional materials; it might also be possible, he adds, to combine nanoparticulate silver with HA to help prevent the formation of biofilms on implants.
ConclusionAdvances in medical device technology will become more and more sophisticated over the next few years, and those outlined in this article are opening the doors to medical devices that would have been unimaginable (or at least impossible) just a few years ago.
For additional information on the products and technologies discussed in this article, see the following websites: