Microelectronics technology creates miracles in the medical industry

The long-term forecast for medical diagnosis, treatment and therapy looks like it will benefit healthier people than ever before, judging by the latest microelectronic sensors and sensory implants. These sensors and implants can give medical professionals a better understanding of a patient's discomfort and illness, while providing faster and more accurate diagnosis and treatment for specific symptoms. Many of the technologies behind these advances stem from advances in microelectromechanical systems (MEMS) devices.

The use of these MEMS components is expected to increase rapidly in the next few years. According to the BioMEMS 2010 report by Yole Développement, an iSuppli company, the MEMS technology market for medical applications will explode from $1.2 billion in 2009 to $4.5 billion in 2015, which is equivalent to more than 1 billion units shipped each year before 2015.

These devices are diverse and include pressure sensors, silicon microphones, accelerometers, gyroscopes, optical MEMS and image sensors, microfluidic chips, micro-dispenser drug delivery systems, flow meters, IR temperature sensors, and emerging MEMS devices such as RFID, strain sensors, and energy harvesters.

Some MEMS are already commercially available or are being marketed. The MEMS currently under development are expected to enter the market within a few years. At the same time, existing MEMS IC products continue to find their place in emerging applications in the medical field.

For example, the small inertial management unit (IMU) developed by Movea uses MEMS three-axis accelerometer, gyroscope and magnetometer sensors to help rehabilitation and fitness activities achieve high-precision, wireless nine-degree-of-freedom measurement. The company's existing 2.4GHz wireless transmission MotionPod uses a fully integrated printed circuit board (PCB) module with a size of 33×22×15mm3 and a weight of 14g.

The module is roughly the size of a small watch and can be easily attached to the body by clipping it to a strap or attaching it directly to the body. A network of multiple MotionPods can simultaneously collect information from different parts of the body, making it suitable for applications such as performance analysis and full-body motion capture.

“Nine-axis sensing provides precise, real-time angular information with a dynamic accuracy of one degree,” said Sam Guilaumé, CEO of Movea.

Another interesting MEMS sensor is the MPL115A digital MEMS barometer from Freescale Semiconductor. This patented device essentially saves oxygen and energy in ventilator systems by determining altitude (i.e., the higher the altitude, the more oxygen is needed, and vice versa). It uses differential pressure measurement and can be used as a smart bandage for negative pressure wound therapy (Figure 2).

Figure 2: MEMS digital barometers such as Freescale’s MPL115A can be used as smart bandages to heal injuries through negative differential pressure measurements.

Even traditional analog and mixed-signal ICs are being incorporated into medical sensing applications. TI's low-power, eight-channel, 24-bit ADS 1298R analog front end is designed specifically for biopotential measurements in medical instrumentation sensors for electrocardiograms (ECGs), electromyograms (EMGs) and electroencephalograms (EEGs). Essentially, it's an ECG solution on a chip.

Moving forward, researchers at the University of Michigan have developed a piezoelectric MEMS device that can generate 10 times more energy than conventional energy harvesters. This device could be important for powering medical implants in the human body and wireless sensor networks in cars.

This large-size micromechanical device is packaged together with other tiny circuit components to form a complete vibration energy harvester with a tiny 27mm3 package. It can use vibration energy between 14 and 155Hz, and a vibration of 1.5gs can generate about 200μW of power.

The device can charge a supercapacitor to 1.5 V. The supercapacitor then powers the wireless sensor instead of the capacitor. The researchers estimate that the energy harvester can repeat this cycle for 10 to 20 years without degradation.

The piezoelectric effect can also be used for ultrasonic pressure sensing echo detection using aluminum nitride film, which can achieve non-invasive measurement of living tissue. This technology was developed by the Japan Industrial Technology Association. The 40μm-thick film can directly measure contact pressure while having little effect on the transmission and reception of ultrasonic waves.

The sensor is mechanically strong and durable because a single inner electrode is placed between two thin-film outer electrodes with a piezoelectric layer on the inner side, and the inner electrode between the two outer electrodes is completely shielded from the outside (Figure 3).

Figure 3: This ultrasonic pressure measurement sensor probe uses the piezoelectric effect to achieve noninvasive measurement of human tissue. This probe was developed by the Japan Industrial Technology Association.

Stunning implantation

Tiny passive MEMS LC resonators are at the heart of CardioMEMS’ Champion implantable device, which is used to monitor and treat aneurysms, the leading cause of heart failure (Figure 4). The U.S. Food and Drug Administration (FDA) has cleared the device for monitoring purposes, with treatment approval expected in the near future.

The RF wireless pressure sensor does not require a battery as it is powered by an external inductive coupling. Changes in pressure deflect the sensor's membrane and change the resonant frequency of the LC circuit, which can be monitored externally.

The pressure sensor and its wireless antenna are inserted near the heart via a catheter, a procedure that takes only a few minutes. Blood pressure readings are sent to a wireless scanner. If the blood pressure readings taken over the past few days are outside the expected range, the doctor will receive a phone call to further treat the condition.

CardioMEMS (a spin-off of Georgia Tech) makes electronic readers, signal processing circuits, and transmission circuits. MEMSCAP supplies sensors, antennas, and packaging for these devices. So far, the results have been very impressive.

“Patients monitored with the Champion device had a 38% lower hospitalization rate than the current gold standard of care,” said Mark Allen, professor at Georgia Tech and co-founder of CardioMEMS.

Many surgeries, such as endoscopy and robotic surgery, are becoming simpler and easier to perform, thanks to the continuous development of new equipment. Awaiba Lda, a Portuguese company, has developed a wafer-level digital CMOS image sensor that can be customized to the low-power requirements of medical applications. The Nan Eye camera measures only 0.5 × 0.5 mm2, roughly the size of a match head, and has a resolution of 140 × 140 pixels at a frame rate of 40 frames/s (Figure 5).

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The lens of this camera is designed with high borosilicate float glass, which makes the surface facing the object flat, thus minimizing the impact of the presence of intermediate objects between the lens and the object. Therefore, when the system works in an environment with contact with body fluids, only the opening angle of the lens is reduced.

The camera uses a Bayer pattern filter and a 3μm pitch 250×250 pixel rolling shutter to provide clear color images. A low-power version powered by a 1.8V battery is also available, and the camera consumes only 600μA of current.

Ophthalmic Implants

Ophthalmic implants are gaining more and more attention lately, as a promising new technology that could soon be a solution for patients with conditions such as glaucoma, retinitis pigmentosa, and age-related macular degeneration.

For example, STMicroelectronics (ST) and Swiss company Sensimed AG have jointly developed a smart contact lens called Triggerfish. This contact lens can measure, monitor and control the patient's intraocular pressure level, so as to detect the early symptoms of glaucoma in time. It can measure intraocular pressure 24 hours a day and then provide records to the attending physician. This pressure sensor is a MEMS strain gauge developed by STMicroelectronics and is manufactured on a flexible substrate (Figure 6).

Figure 6: Triggerfish’s ophthalmic implant can measure, monitor and control a patient’s intraocular pressure level 24 hours a day to detect early symptoms of glaucoma. The implant was jointly developed by Sensimed and STMicroelectronics.

The measurement is the circumferential fluctuation of the corneoscleral junction which directly correlates to the intraocular pressure reading. This information is then transmitted from the recorder via wireless communication.

The need to visit an ophthalmologist for cumbersome glaucoma testing could soon become a thing of the past with a simple, more accurate test that can detect the disease. An easy-to-use self-test probe designed by University of Alabama professor of aerospace and mechanical engineering Eniko Enokov would allow patients to detect glaucoma by gently rubbing their eyelids in their own home.

"The system detects the hardness and from that infers the intraocular pressure," Enokov said.

The concept of the probe looks simple, but the technology behind it is quite complex. It involves micro force sensors, specially designed microchips, and math-based programs programmed into the probe.

“It took us several years of refinement and modification to reach the current design,” Enokov said. “The innovation of our device is that it is non-invasive, simple to use and can be used in a variety of conditions that are difficult or impossible to test using current surgery.”

Great strides have been made in the use of artificial retinas that can be switched on by light. This non-invasive retina, developed by Imperial College London, enables neurons to be controlled by light, paving the way for more powerful brain-computer interfaces. An array of gallium nitride LEDs on a sapphire substrate can be used to trigger pulses of 1mW/mm2 to activate neurons.

This development could allow biomedical engineers to activate selected groups of neurons, rather than just cells near the site of stimulation, as current stimulating probes do. Light could also be used to inhibit neurons from firing, while the probes could only stimulate them. Perhaps most interesting is the engineering of light-triggered brain cells, which could pave the way for hybrid computers that use optical links to connect biological tissue and silicon components.

Hot technologies in the neuroscience field

How does the brain work? It’s a question that continues to drive researchers to find answers. And with some of the latest developments, researchers are digging deeper into solutions to a host of complex problems.

Last year, NeuroPace applied to the FDA for approval of a brain implant to treat epilepsy. The company is expected to soon receive approval for its RNS system, an emerging research device that uses responsive brain neurostimulation to significantly reduce the frequency of seizures in people with common epilepsy, which is difficult to treat with medication.

“I think over the next decade, a variety of closed-loop and open-loop brain stimulation devices will replace invasive surgical procedures,” says Martha Morrell, chief medical officer at NeuroPace.

The device is one of many neurosurgical implants still under development to alleviate and treat conditions ranging from pain management and depression to Parkinson's and Alzheimer's. NeoStim and Trifectas Medical are just two of many companies working in this field.

The CSI (Central Nervous System Imaging) European project, launched last year, aims to improve the diagnosis and treatment of brain diseases while reducing the costs of related diagnosis and treatment. The project is expected to make great progress in the field of the latest 3D medical imaging platforms for sensing, computing and device platforms. The project members include leading European electronics companies, universities and research centers.

Researchers at the University of South Florida are using deep brain stimulation to treat essential tremor, which affects the hands, head and voice and is three times more common than Parkinson's disease. The largely genetic neurological disorder can cause uncontrollable shaking that can interfere with normal daily activities.

The researchers report that the technique enabled 77 percent of patients who underwent the stimulation procedure to stop needing follow-up medications a year after treatment. The treatment uses an implanted device similar to a pacemaker to stimulate targeted areas of the brain with electrical impulses, thereby blocking or correcting the abnormal nerve signals that cause tremors. The FDA approved the treatment in 1997.

Microfluidics

Microfluidics is gaining steady ground in the field of implantable devices and lab-on-a-chip technologies. Many lab-on-a-chip developments are focused on providing low-cost, high-precision and rapid blood diagnostics for detecting cancer. In fact, this is also the goal of the Miracle (Magnetic Isolation and Molecular Biological Analysis of Single Circulating and Disseminated Tumor Cells) project, which aims to detect cancer through blood and was launched last year by IMEC in Belgium and its partners.

In another area of ​​development, an emerging device developed at the University of Tokyo is based on this microfluidics technology and can simulate the process that food and oral medications undergo as they flow through the human body. Its developers believe that this device will be useful for applications such as drug screening and risk assessment of chemical drugs.

The developers designed a three-stop organ journey in which the micro-gut and micro-liver absorb the chemical, metabolize it, and then deliver it to breast cancer cells, the target tissue. They collected cells from the three organs onto a glass and plastic microfluidic chip measuring 7.5×2.5cm2. The sample enters the cells through an inlet and then enters the three organ chambers in sequence. The results are measured at the output (Figure 7).

Figure 7: Microfluidics can mimic the process that food and oral medications undergo as they flow through the human body to reach target breast cancer cells. Developers at the University of Tokyo believe that this device will be useful for applications such as drug screening and risk assessment of chemical drugs.

One of the more famous microfluidic drug delivery devices is the Jewel insulin pump, jointly developed by Debiotech and STMicroelectronics using Debiotech's microfluidic MEMS technology. (The device is awaiting FDA approval.) This insulin pump can be installed on a disposable skin patch to continuously infuse insulin. The emergence of this device indicates that the treatment efficiency and quality of life of diabetic patients will be significantly improved.

Smart infusion pumps are very complex devices that require careful consideration of all aspects of design. The FDA recently analyzed these infusion pumps and found that more than half of the 56,000 medical device reports it received related to the use of infusion pumps (over a five-year period) were caused by user errors, among which software errors were more common.

The FDA cited a lack of education for patients on proper setup and other issues, but it also praised the technology used in the pumps and said the problems were more likely due to user error than a defect in the device.

Researchers at the Imperial College London Biotechnology Center decided to use bionic technology to simplify insulin injections through a bionic pancreas. The bionic technology works just like the natural pancreas organ, relying on two populations of hormone-producing cells: beta cells that secrete insulin when blood sugar is high, and alpha cells that release a hormone called glucagon when blood sugar is low. Both of these cells were simulated in chip form.

The device designed by the researchers consists of an electrochemical glucose sensor that pierces the skin, a microchip, and two small pumps (one for each hormone) that are worn on the body. The sensor detects blood sugar levels every five minutes and drives a motor based on the blood sugar level, activating each corresponding pump. The motor pushes the dispensing syringe when needed.

Smell, breathe, touch, hear and see can all be monitored in detail using electronic device technology as a basic diagnostic and therapeutic construction platform. These research and development results are within reach, so their impact on improving human medical standards will inevitably be of historic significance.