More than five million Americans suffer from congestive heart failure, and one out of five die within the first year of contracting the disease. The most common way to treat heart disease is through medication, but the particular drugs and specific doses vary based on the patient. Each patient's condition changes with time, and doctors have limited information about what is happening inside the heart, so they are forced to adjust dosages or regimens based on the patient's behavior, exercise regimen, weight changes, and other factors. "They're trying to manage this complicated system of medications and disease in a rudimentary way," says electrical engineer Nader Najafi, founder of Integrated Sensing Systems Inc.
Najafi's company is developing the Titan implantable hemodynamic sensor (IHM), a device the size of a pencil eraser that can be implanted in the heart of a patient to measure critical variables such as temperature, and then wirelessly transmit this data to a secure database. The Titan device could give caregivers the detailed information they need to adjust medication regimens precisely and improve patient health.
The Titan is one of just two such IHM devices that have completed clinical trials, but a wide range of wireless implantable sensors are in development inside and outside academia. Researchers are designing and testing devices that could be embedded in different parts of the body to measure pressure, temperature, acidity, and even electrical activity. A group at the University of California, Berkeley, recently reported results in animal models demonstrating the effectiveness of its neural dust, millimeter-scale devices that reside on nerves, measuring and relaying their electrical signals.
These tiny devices may be the first in a wave of new implantable sensors that change the way doctors and scientists gather information about the human body. "We are starting to bring to reality some of these more science-fiction ideas about how you can build electronic systems that interface with the body in fundamentally different ways than were possible in the past," says John Rogers, an electrical engineer at the University of Illinois at Urbana-Champaign.
The need for wireless implantable sensors is not just about data scarcity; it also stems in part from the flaws of their wired predecessors. In cases such as deep brain stimulation, in which an implanted electrode is wired to a device on the skull, the wires themselves can present an infection risk; often, they need to be surgically removed, too. This increases both the expense of the procedure and the risk of complications. Existing sensors are not always biocompatible, either, so they can trigger a foreign-body response, effectively inducing the host's immune system to attack them.
The human body simply is not a hospitable environment for electronics. "We are basically giant bags of salt water," explains electrical engineer Michel Maharbiz, one of the leaders of the neural dust project at the University of California, Berkeley. "If I were to say I'm going to take a chip and throw it into the ocean and that it has to operate under the ocean for 25 years, most people would realize that's pretty hard."
An effective, long-term implantable sensor therefore has to be strong enough to resist the corrosive effects of the environment. It also has to be small and biocompatible, so it will avoid interfering with the body's normal functioning or provoking an immune response. These requirements put strong constraints on the design of the sensors, the materials used, and more.
At the University of Illinois at Urbana-Champaign, Rogers has led a multidisciplinary and institutional team focused on building biocompatible sensors for the brain. The idea stemmed in part from neurosurgeons working with patients who suffered from severe traumatic brain injury (TBI). "One of the first things the neuro-surgeon will do is insert sensors for pressure and temperature because those two parameters are critically important," he says. "If the values fall outside a narrow, healthy range, there can be brain damage."
Current wired sensors capture the necessary data, but they need to be surgically removed, so Rogers and his group designed a device that can be left in place and absorbed into the body. The millimeter-scale device is flexible rather than rigid to be more biocompatible, and can be adapted to sense a number of variables, including fluid flow, temperature, and pressure. In the most recent study in animals, the miniature sensor is attached to degradable wires, but the group also demonstrated that the sensors would work when combined with an implanted, wireless data transmitter, eliminating the need for wires entirely.
The neural dust group has adopted a different approach to data transmission. Their package consists of a small electronic mote, which is surgically implanted near a nerve or muscle, and an external, handheld ultrasound transducer. The mote is roughly two millimeters long and one-half millimeter wide, and packs a piezoelectric crystal, a transistor, and two electrodes. There is no onboard power source. To activate the mote, the researchers press a transducer against the skin, which sends out six quick bursts of ultrasound. The transducer then switches modes to receive signals, effectively listening for the pulses to rebound. When these sound waves strike the mote, the piezoelectric crystal captures some of the energy, while some of it bounces back toward the transducer.
In the absence of neuronal activity, those rebounded signals will look roughly the same each time. But if the nerve being monitored fires during this process, the two electrodes pick up that electrical signal. The attached transistor captures this jolt, which modulates the current already flowing through the piezoelectric crystal from the ultra-sound. Once this current changes, the amount of energy reflected back to the handheld transducer changes as well. After some computation to filter the received ultrasound pulses, the external devices tease out the strength of the neuronal signal. "Because you're listening, you can back out what's happening at the neurons," Maharbiz says.
Although this version is coated with epoxy, Maharbiz and the group are now developing one coated with a biocompatible thin film that could function in the body for 10 years without degrading.
Yet another key consideration is to avoid disrupting function at the site of the sensorto protect the body's systems, as well as the electronic ones. Najafi and the team behind the Titan sensor say this is a major factor, since they have been testing their device in a crucial region, the left side of the heart. Their goal is to measure filling pressure as an indicator of cardiovascular health, or how well the heart is pumping. In this setting, though, building something that is biocompatible is more challenging. "One element of biocompatibility is the material you use, but the element that is much more important is whether your device is disturbing the blood flow or not."
"If I think forward I think the amount of integration between what we today consider synthetic and what we consider organismal or biological is going to be extremely high."
The Titan, a cylindrical device with a pressure-sensing module at one end, must be surgically implanted, but in a small human trial of 20 patients, the device was inserted so that only the pressure-sensing tip of the cylinder was exposed to blood flow. The rest of the device was buried in surrounding tissue, and they went through a number of design iterations to minimize possible spots where bacteria could accumulate.
Once implanted, the Titan could wirelessly trigger alerts through a wand-like telemetry device that transmits information to a patient database. A rapid rise in filling pressure, for example, could be a warning sign for an arrhythmia, but if a healthcare professional were alerted in real time, he or she could proactively adjust the patient's medicine or schedule an appointment. "If patients have to be monitored by a specialist every day, that's not practical," Najafi says. "This way, you can look at the data over the last two weeks, and based on that, you can adjust the medications."
The timeline for when these sensors become a regular part of patient care is unclear, but the researchers paint a fascinating picture of their potential. Najafi hopes he and his group will be able to build devices that could be safely implanted in children with severe heart problems and last 30 to 50 years. Other scientists are designing wireless implants that will be application-agnostic. A multidisciplinary group at Brown University, for example, is building a high-throughput device that could potentially work with any type of sensor.
The neural dust group has taken a similar approach, but Maharbiz says it is also moving closer to its original goal of building devices that continually read neuronal activity in key parts of the brain, and allow subjects to control their prosthetics as if they are their own limbs. Indeed, the group has published a proof-of-concept study showing the motes could be shrunk to half the width of an average human hair, which would open up a whole new realm of possibilities.
"If I think forward and dream a little bit," says Maharbiz, "I really do think the amount of integration between what we today consider synthetic and what we consider organismal or biological is going to be extremely high."
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