Could implantable electronics revolutionise the healthcare industry?

Despite the challenges of designing for environments that are typically inhospitable to conventional electronics, research teams from around the world are developing novel methods for the continuous, real time monitoring and sensing of a range of chronic diseases. These advances, according to Dr Timothy Constandinou, deputy director of the Centre for Bio-Inspired Technology at Imperial College London, are providing patients with a more portable, precise and personal way of managing their illness than ever before. "We've come a long way since the days of the humble pacemaker," he noted. "Advances in biomedicine and information and communications technologies have enabled the healthcare industry to move towards a smarter, more decentralised approach centred not on the physician, but the patient. "Our research involves a strong combination of integrated miniature sensing with intelligent processing, leveraging on state of the art semiconductor technology. We aim to make electronics work with biological processes, while still remaining small and consuming tiny amounts of energy." Perhaps most significant of all about Imperial's research is that it relies heavily on a biologically inspired approach. Dr Constandinou explains: "This means that, rather than take a problem and engineer a mathematical solution, we say to ourselves 'how does the body do it?' and then model some electronics around that." Dr Constandinou and his fellow biomedical engineers recently completed work on an artificial pancreas, which they believe has the potential to 'close the loop' on Type 1 diabetes. The bionic system comprises an electrochemical sensor that monitors blood sugar levels continuously; a chip that mimics the unique electrical characteristics of alpha and beta cells in the human pancreas; and two small pumps worn on the body. "In a patient with Type 1 ¬diabetes, the body's immune system attacks and kills the insulin, secreting beta cells and causing an increase in blood glucose," explained Dr Constandinou. "Over time, the glucagon secreting alpha cells also tend to fail, so people with Type 1 diabetes become prone to episodes of extremely low blood sugar. "As such, we designed the chip's control algorithms to mimic the very different behaviours of the two cell populations. An alpha cell tends to react to rapid electrical events (spikes), while the beta cell tends to react in bursts of voltage spikes, punctuated by low voltage silent periods that last for seconds or even minutes. When glucose concentrations rise, the beta cells remain in the high voltage burst state longer, secreting more insulin as a result." Imperial's bionic pancreas mimics this biological process by detecting the user's glucose level via a sensor every five minutes. If it reports a high level of glucose, the silicon beta cell generates a signal that drives a motor. This motor pushes a syringe, dispensing insulin into the tissue beneath the skin until the glucose reading at the sensor drops. If the sensor reports a low glucose value, the silicon alpha cell activates the second pump to administer glucagon instead. "This biomimetic approach diverges from today's dominant method of delivering only insulin using a relatively simple control system," commented Dr Pantelis Georgiou, who led the project. "The great thing about our system is that it lets people with diabetes do away with multiple insulin injections and administer the insulin in a more biologically faithful way. This reduces any secondary complications and means patients no longer have to worry about what they eat and drink." Transmitting raw data through the skin barrier In 2009, the Imperial engineers embarked on a different project to develop a brain-machine interface for patients with spinal cord injury and neurological disorders. The ultra low power cortical implant – still under development as part of a collaborative effort between Imperial and the Universities of Newcastle and Leicester – is designed to interface between the central nervous system and low power, custom built digital microelectronics. The system works by converting analogue signals recorded from microelectrodes implanted in the brain, into a stream of digital spike events. The significance of this project over other research efforts, claims Dr Constandinou, is that it overcomes the bottleneck of transmitting raw data through the skin barrier. "Early implementations of brain-machine interfaces connected intracortical electrodes to external amplifiers via wires passing through the skin," he explained. "This breaches the body's natural barrier to bacterial infections, compromising the implant and presenting a serious danger to patients. "Several groups have begun developing wireless neural links, but these generally transmit all the raw data that is recorded. The problem with that is it requires a relatively high data rate. For example, for a 2Mbit/s wireless link, if the data is sampled at 20ksample/s requiring 10bit/s, you can only look at 10 channels. That's nothing when you think that the brain has about 100billion neurons." By putting what Dr Constandinou describes as 'local intelligence' on the array, the Imperial researchers were able to overcome this issue and sort the data before it was transmitted out of the body. "This resulted in a huge data reduction, as only the timestamp and neuron identifier needed to be transmitted, instead of the entire recorded waveform," Dr Constandinou explained. "For the first time, we were able to measure thousands of neurons, not just tens. "Ultimately, this means we can manipulate multiple degrees of movement in the human body, opening up the possibility of helping people with neurological damage, amputees with prosthetic limbs and even the totally paralysed." While the technology is expected to take another five years to develop, Dr Constandinou believes it will form a key component of next generation brain-machine interfaces. Unblocking a bottleneck When designing devices for inside the human body, Dr Constandinou notes the importance of remaining miniature, whilst also consuming extremely small amounts of power. It is also imperative, he says, to ensure good biocompatibility and stability, to avoid patients having to undergo further invasive surgery. "Apart from the risks of infection and other surgical complications, electronic implants must withstand fluid leaks, mechanical stress and motion artefacts, while operating reliably on a low power battery supply," he said. "Moreover, it's a real challenge for designers to put everything together in a small enough package that works reliably." This bottleneck was also a major stumbling block for researchers in Germany developing a device that can monitor tumour growth in cancer patients. A team from the Technical University of Munich recently unveiled a biocompatible device, dubbed IntelliTuM (Intelligent Implant for Tumour Monitoring), that relies on a self calibrating sensor to measure oxygen levels in the blood; a key indicator of growth. According to Professor Bernhard Wolf, who led the research, the growth rate data measured by the sensor can be transmitted wirelessly to an external receiver carried by the patient and transferred to their doctor for remote monitoring and analysis. "We developed the device to monitor and treat slow growing tumours that are difficult to operate on, such as brain tumours and liver tumours, and for tumours in elderly patients for whom surgery might be dangerous," explained Wolf. "The main challenge for us was developing a sensor that functions entirely autonomously for long periods of time. The device had to continue to function and deliver correct values even in the presence of protein contamination or cell debris. It also had to be 'invisible' to the body so that it was not identified as a foreign object, attacked and encapsulated in tissue." Prof Wolf and his team are now planning to incorporate a miniature medication pump into the device to deliver chemotherapy directly into the tumour environment. However, even though it only measures 2cm, it still needs to be further miniaturised before it can be deployed. Prof Wolf believes the ultimate solution to this is for the device to employ energy harvesting; a technology which Constandinou and his team are also exploring at Imperial. "At present, our researchers are developing devices that can be powered simply by a person walking or moving their head," Constandinou said. "Although the technology is currently a way off, and a device measuring about 1cm3 can only give you a few microwatts, we believe it could be the main power source for devices in just a few years." Meanwhile, Dr Constandinou and his fellow engineers are working on several other projects, which he says in the next 10 years could help people with Parkinson's disease, Multiple Sclerosis, depression and even obesity. "The possibilities," he concluded, "are endless." Smart skin An ultra thin 'electronic tattoo' that self adheres to human skin to track muscle activity, heart rate and other vital signs was unveiled recently by researchers at the University of Illinois. The electronic patch, which bends, wrinkles and stretches with the mechanical properties of skin, has been demonstrated through an array of electronic components mounted on a thin, rubbery substrate, including sensors, leds, transistors, radio frequency capacitors, wireless antennas and solar cells. As well as offering advances in biomedical applications and wearable electronics, the researchers believe the technology could one day help patients with muscular or neurological disorders to communicate. The team has already used the electronic patch to control a video game, demonstrating the potential for human computer interfacing. They now plan to add Wi-Fi capability to the device. Going soft A new memory device that is soft, pliable and functions 'extremely well' in wet environments could open the door to a new generation of biocompatible electronic devices. According to Dr Michael Dickey, an assistant professor of chemical and biomolecular engineering at North Carolina State University, the memristor like device has the physical properties of gelatin and works in environments hostile to traditional electronics. The prototype module has two states: an on state in which it is conductive, and an off state in which it is resistive. These states can be controlled by the thickness of an oxide skin that forms on the liquid metal. "The device's ability to function in wet environments, and the biocompatibility of the gels, mean that this technology holds promise for interfacing electronics with biological systems such as cells, proteins, enzymes and even tissue," noted Prof Dickey. "These properties may allow it to be used for biological sensors or for medical monitoring."