Small Science. Better Diagnosis.
The researchers glance furtively at each other and shift in their seats when asked the question: “So, exactly how do these carbon nanotubes detect chemicals in the body?” They hesitate. They smile demurely. They want to accommodate, but, as one of them says in half jest, “the answer to that question might take up the rest of the day.”
Their boss is in an anteroom, his office, gathering materials, and the smiles widen when he returns because they know he will take a stab at it. It’s not the nanotubes and nanowires and other three-dimensional structures themselves — although they are the critical material — but how they are integrated with thin film transistors — special kinds of transistors that deposit thin film semiconductors on substrates — and electronic communications modules that allow the researchers to build many types of wireless biosensors that detect “biologically derived electronic signals.”
“To do this, the nanostructures are ‘functionalized’ with conductive linkers such as proteins and peptides that interface with soluble biological targets,” says Vijay Varadan, distinguished professor of electrical engineering and director of the Center for Wireless Nano-, Bio- and Info-Tech Sensors and Systems. “The use of vertically aligned nanowire bundles provides a large surface-area density and an excellent base for many sensor surfaces operating in parallel. This creates an increased electrochemically active area for high sensitivity and high signal intensity.”
With assistance from the Walton Family Charitable Support Foundation, the university lured Varadan to Arkansas in late 2004 to build a major research center focused on sensor technology with a health-care focus. While at Penn State University, Varadan had established a reputation as pioneer in the field of biosensors to treat neurological disorders, such as Parkinson’s disease, Alzheimer’s disease and epilepsy.
Today, with additional assistance from the National Science Foundation and the Arkansas Science & Technology Authority, Varadan’s biosensor work has expanded into four distinct laboratories that comprise the center. Each lab has it own mission or application, but all rely on the unique properties of nanotubes and nanowires, made of carbon, gold, titanium and conducting polymer, to develop products that will provide better information to health-care professionals, reduce the costs of health care and influence quality of human life.
All this is made possible by the unique characteristics of Varadan’s nanotubes and their packaging and interaction with various chemical agents. The nanotubes and wires are hollow, lightweight, chemically inert and mechanically strong. They grow on arrays combined to make chips not unlike those found in computers and other electronic devices. These chips are bio-compatible; the human body will not reject them as a foreign object.
The research started years ago with Varadan’s wireless, implantable biosensor that he continues to refine in the center’s Brain Wave Lab. Today, the device senses, monitors and actually manipulates chemicals, called neurotransmitters, in the brain. It accomplishes this by recording the loss of dopamine, a major neurotransmitter, and stimulating activity between neurons and neurites, which are immature, developing neurons.
The sensor also works in tandem with other types of sensors to control tremors, the primary physical symptom of Parkinson’s, and to direct movement of prosthetic limbs. Specifically, the device communicates with an organic, polymer-based sensor attached to an area of the body in which a tremor occurs. The signal from the sensor implanted in the brain controls and directs the motion of the area of the body on which the exterior sensor is attached.
“If neurites in the brain can be manipulated properly, we can control symptoms of Parkinson’s,” Varadan says. “We can stop tremors, and patients can live relatively normal lives.”
Another sensor, developed by Jining Xie, research assistant professor, detects and monitors blood-glucose levels in near real time.
Working with Varadan, Xie and researchers in the Nanomaterials and Nanotubes Research Laboratory test the sensor, which is made of carbon nanotubes coated with platinum particles between 1 and 5 nanometers in diameter.
The platinum-coated nanotubes exhibit a high sensitivity to detecting glucose, because the platinum nanoparticles create a larger electro-active surface area, Xie said. The larger surface area allows the nanotubes to act as a glucose-oxidase reservoir, which helps create uniform immobilization and high loading of glucose oxides for sensing.
The sensitivity value of the researchers’ device is among the best results reported for glucose biosensors. Xie says their goal is to further increase sensitivity. Equally important, the biosensor has a response time of 15 to 30 seconds, which renders it capable of providing glucose screenings close to real time.
“To manage and control diabetes, patients must continuously monitor blood-glucose levels,” Xie says. “So they understand the importance of a device that provides rapid response.”
Imagine a bed sheet that automatically takes a patient’s body temperature and sends the information to a computer at a nursing station, or a shirt that continuously monitors a marathon runner’s respiratory rate.
Collaborating with Varadan, researchers in the Organic Electronics and Devices Laboratory have developed two types of sensors — temperature and strain — that can be integrated with so-called “smart fabrics,” clothing and even bedding fitted with wireless technology. Such garments monitor vital signs and collect and send data to an information hub in real time. The information can provide immediate detection of physiological abnormalities, which will allow physicians to begin treatment or prevent illness before problems reach an acute stage.
Taeksoo Ji, assistant professor of electrical engineering, and research assistant professor Soyoun Jung work with pentacene, a hydrocarbon molecule, and carbon nanotubes to fabricate the two biosensors. Similar to Xie’s experience with platinum, Ji and Jung found that combining pentacene with carbon nanotubes increases sensor sensitivity. An additional benefit is that pentacene, as an organic semiconductor, is efficient and easy to control.
The strain sensor, which monitors respiratory rate, consists of an instrument that measures unknown electrical resistance, and a thin pentacene film that acts as a sensing layer. The system works when physiological strain, such as breathing, creates a mechanical deformation of the sensor, which then affects the electrical current’s resistance. The researchers found that the smaller the sensor, the more sensitive it is to current variations.
For the temperature sensor, Ji and Jung use a thin-film transistor, which allows them to observe electrical current in response to temperature change. Most importantly, in low voltage areas, the current displays the highest sensitivity to temperature changes.
“A sensor that can monitor a patient’s respiratory rate and body temperature in real time and thus provide point-of-care diagnostics to health-care professionals and greater freedom to patients is huge,” Ji says. “We’re trying to move diagnostic testing out of the lab and directly to the patient and health-care worker.”
Related to this work, a technology company, Shri Lakshmi Nano Technologies, has established a research and development facility in Fayetteville to incorporate an array of flexible nanosensors on bed sheets and pillow cases for physiological monitoring of patients. The company will work closely with Varadan and the other researchers.
Stimulating Nerves & Muscles
Researchers in the Innovative Nano- and Bio-Devices and Systems Laboratory are developing a better neural probe, one that has already demonstrated a greater charge-injection and storage capacity — meaning the probe can stimulate nerves and tissues with less damage and sense neural signals with better sensitivity — than all other neural prosthetic devices.
Needle probes are used as neural prostheses to help improve quality of life for patients with severe impairments, such as Parkinson’s disease and Tourette syndrome. Other clinical applications include cardiac pacing and defibrillation, restoration of bladder function, electrical stimulation in paralyzed individuals and deep brain stimulation.
“Our goal is to develop functional systems that can simultaneously stimulate nerves or muscle cells and record physiological changes in the human body,” says Hargsoon Yoon, research assistant professor of electrical engineering.
Yoon collaborates with Varadan to develop systems that include nanowire electrodes, wireless communication and a power source for bio-packaging. The wireless network facilitates dynamic adjustments of the system and continuous monitoring of patients during stimulation.
But it is the probe alone that will improve the function and reliability of neural prosthetic devices. Made of a gold core and iridium oxide outer layer nanowires grown vertically on polymer or titanium substrates,
Yoon’s probe has repeatedly demonstrated charge-storage capacity of more than twice the capacity of probes developed by other major academic research groups. The Arkansas probe has also displayed superior biocompatibility and mechanical strength compared to similar silicon structures.
Because charge-injection capacity is directly related to density of electrical current needed to stimulate nerves and muscle cells, the probe can transfer charge into biological cells and tissues using less voltage – and less battery power — and thus can operate longer with less tissue and cell damage.
“We work at the boundaries of physical, chemical, biological and medical sciences,” says Varadan. “Nanomedicine — the application of nanoscience and nanotechnology to medicine — provides revolutionary approaches for the diagnosis, prevention and treatment of fatal diseases. We are happy to be a part of this revolution. There is great excitement in our labs and the hallways that connect them.”