Spring 2006
In This Issue:
Focus On BioMaterials
Fine-Tuning Sensors for Health, Security, and the Economy
Though we may not notice them, sensors are all around us, from the automatically opening doors at the supermarket to the bathroom scales. "People like to sense the things in their environment," says Joe Dougherty, a research associate for Penn State Electro-Optics Center and an expert on electronic sensing devices. "We use sensors of one kind or another for everything from barometers to measure air pressure to measuring the light that comes through the lens of your digital camera. Electronic sensors tell us how close we are standing to something, what chemicals are in our environment, and whether the vegetables in the supermarket are ripe." At Penn State, scientists are exploiting the remarkable properties of nano and biomaterials to diagnose diseases inside the human body, to detect chemicals in the environment, and to develop self-cleaning sensors of unmatched sensitivity.
Although some fields of nanotechnology have been slow to develop, sensor technology is on the cusp of a rapid expansion. According to a 2004 industry market analysis,* sensors designed and built using nanotechnology will generate revenues of $2.7 billion worldwide in the year 2008 and $17.2 billion in 2012. Sensors built by nanotechnology or containing nanomaterials will have the greatest impact in the areas of military and homeland defense - $3.9 billion by 2012; biomedical - $1.2 billion; automotive - $1.5 billion; and aerospace - $2.1 billion, all by 2012.The growth in nanosensors will come from unique features that surpass current technologies, the analysts tell us.
Penn State is a hotbed of sensor research. Penn State faculty and students are looking into biosensors that can monitor the physical state of soldiers in combat; hydrogen sensors that can detect minute levels of hydrogen in the body or in the environment; and nanomaterials that can be used as bioprobes and biosensors for identifying genes and proteins, and for drug discovery. Sensor platforms are being created for early detection of cancers, and, for defense and homeland security, insect/electrical hybrid biosensors are being developed to sense the odor plumes of biohazardous agents.
Chemical Sensors for Medical Applications
Michael Pishko, professor of chemical engineering, and materials science and engineering, has been working with sensors for the past 15 years. In that time he has garnered 19 patents for work done at the University of Texas, MIT, and Texas A&M. One of his earliest devices, an implanted glucose sensor for diabetes monitoring and management, is currently going through FDA trials, giving some indication of the long lag-time between invention and commercialization. "It takes a lot of work on the engineering side and a lot on the science side. Whether you work for the Army or the NHA, there are a lot of obstacles to getting devices out," Pishko says about the sensors that he and his collaborators across campus are developing.
Michael Pishko
* "Nanosensors: A Market Opportunity Analysis" NanoMarkets, LC
Pishko sees a significant need for the development of chemical sensor technology for medical applications. His biosensors are meant to monitor key metabolites during surgery, as well as in critical care units, neonatal monitoring, and for soldiers in the field. In a battlefield injury, for example, blood is cut off to a certain organ as a result of a clot or trauma. As a result, there is a rise in metabolites such as lactic acid and pyrobic acid which a sensor can detect.
The metabolites he measures include glucose, lactic acid, and pyrobic acid that are sensitive indicators of the metabolic state of the patient. "Measuring metabolites is a way of getting an idea of how somebody is doing that goes beyond the standard measures of heart rate and blood pressure," Pishko says. "We’re trying to create devices that give more information to a physician, EMT, or other medical personnel to help them make more intelligent decisions about what’s happening to somebody. To do that we are creating miniaturized devices to sense metabolites using many of the same techniques that are used to make computer microchips." Pishko"s group teamed with Charles Palmer, professor of pediatrics at Penn State College of Medicine, on the glucose sensor.
Pishko continues, "The way we do the sensing, and what my group is primarily involved with, is using something called biological molecular recognition. That means the body, and nature in general, has created a lot of different kinds of proteins that are able to recognize other chemicals. An example of this is that the AIDS antibody recognizes the AIDS virus, and it binds to it very selectively."
Enzymes in the body recognize the chemicals that they catalyze very specifically, he says. Pishko and his collaborators take advantage of that ability for recognition and use it as a way of creating a selective sensor. They take enzymes, antibodies, and receptors that come in nature and couple them with microelectronic devices to do chemical sensing.
"The hard part of this," says Pishko, "is that these proteins were not designed to be coupled to devices. So we spend a lot of time looking at how we can stabilize the proteins, and how we can couple them to microelectronics devices in ways that will allow these devices to be manufactured. We’ve adapted microprocessing techniques like photolithography in such a way that we can use that technique to incorporate enzymes, antibodies, even whole cells on the surface of microelectronic devices. That’s a difficult challenge, because these proteins tend to be very sensitive to their environment. So we have to spend a lot of time looking at the material science to stabilize these proteins so that they will last for a sufficient amount of time and perform their biological function to the same degree they would in their native environment."
Another difficulty with implanted sensors is that the body is not a welcoming environment for foreign objects. The body has very active and effective mechanisms for trying to destroy implanted devices. If the body can’t destroy the foreign object, it will try to wall it off and isolate it. "That’s been a major obstacle to the success of implanted sensors, the whole response of the patient’s body to the implanted device. It’s possible to find ways around it in the short term, for periods of up to 72 hours, and we’ve been effective at doing that. But for longer periods of time, different biological mechanisms come into play. It becomes more a challenge to make a device that is going to be relatively immune to the body’s defenses. That’s another major research effort in my group, to understand how the body’s host of defenses influence the functions of the sensor, and then how can we modify sensor design to minimize that response."
Highly sensitive hydrogen sensors
Another difficulty with sensors, both inside and outside the body, is that they are easily contaminated. Once a sensor is placed into its working environment, it may come into contact with chemicals, pollutants, soot or dust that distort its readings and make it unusable. Craig Grimes, professor of electrical engineering, has developed self-cleaning titania nanotubes arrays that have the ability to break down contaminants when exposed to ultraviolet light.
Craig Grimes (photo provided)
"Titania nanotubes make a great hydrogen sensor in and of themselves," Grimes says. "In addition, they are a phenomenal photocatalytic material, great for degrading contaminants. One of the unspoken problems with sensors is that, basically, the more sensitive you make a sensor, the more rapidly it gets contaminated. People don’t talk about it because there is no benefit to saying that now you have a sensor but it can’t be used. Sensors get dirty, and the better they are the quicker they get dirty. It is so difficult to clean them that what you would like to do is just throw them away."
Titania, however, absorbs ultraviolet photons, creating what is called an electron-hole pair – the energy of the photon knocks the electron out of its orbit – stimulating chemical activity that breaks down organic contaminants into water and carbon dioxide.
A sensor to measure transcutaneous hydrogen levels
The Grimes group coated titania nano-array sensors with a thin layer of 10W-30 motor oil that completely eliminated the sensors’ ability to react to hydrogen. With exposure to ultraviolet light, the sensors were able to recover their hydrogen sensing ability to their original value. Experiments were also performed on stearic acid - a long-chain fatty acid found in some foods - and cigarette smoke, with similar results. The sensors were able to recover 100 percent of their hydrogen sensing capabilities.
The titania nanotube array makes a remarkable hydrogen sensor and with its self-cleaning has potential for a much longer useful lifetime. In medical applications, titania nanotubes can sense low levels of hydrogen from bacterial infection and can be used to detect a devastating form of infant colitis in an early stage, as well as infections of the digestive system in adults. The Grimes group teamed with James Kendig and Charles Palmer, both professors of pediatrics at Penn State Children’s Hospital, on the infant colitis sensor.
With the development of hydrogen fueling stations and hydrogen-powered vehicles, the titania nanotube array has wide potential application as a low-cost leak detector and could be a valuable tool in monitoring hydrogen levels in spaceflight.
Genomic DNA detection using single wall nanotubes
A rising star in chemical engineering, Jong-in Hahm’s biosensor work relies on the unique properties of low-dimensional nanomaterials for fabricating highly sensitive biosensors and bioprobes. "We’ve had excellent results creating nanowires with biological materials," says Hahm, an assistant professor of chemical engineering who arrived at Penn State in the fall of 2003 after a postdoctoral stint at Harvard University.
Her ultimate goal is to show that nanomaterials can be of real help in investigating biomolecules, such as DNA, proteins, and cells. "Current techniques that are used in medicine and biology for screening and biomedical research face many problems," she says. "I want to show that nanomaterials have unique qualities that can overcome these problems."
Jong-in Hahm
Using single wall carbon nanotubes as the tip for scanning probe microscopy, her group is able to probe the topology of biomolecules to a resolution that is currently down to 10 nucleotides. Nucleotides are the molecules that form the double helix of DNA. In her biosensor work, Hahm and her group use arrays of nanomaterials, such as carbon nanotubes, silicon nanowires, and zinc oxide nanorods, that are linked to biomolecules. A target molecule is introduced to the biosensor in a liquid or other form, the molecule interacts with the complementary biomolecule, and an optical or electrical signal is triggered.
As a proof of concept, Dr. Hahm chose well understood biomolecules that are frequently used in medical procedures, including human serum albumin and bovine serum albumen, to test the effectiveness of her nanomaterial biosensor. In one experiment, her team identified the DNA sequence of anthrax, singling out the lethal form from other closely related bacillus bacterial species that are less harmful.
In September 2005, Dr. Hahm and Philip Lazarus, professor of pharmacology and associate director of the Penn State Cancer Institute, were awarded a Woodward Grant, seed money for projects involving teams of medical doctors and engineers. Their work uses genomic DNA to identify susceptibility to cancer." This work has two roles," says Hahm. "The first is to develop screening that we can use as a warning to certain at-risk populations who are susceptible to environmentally caused cancers, such as smoking or aromatics in the air. The second is for the screening and treatment of cancers. Right now we have to try to deduce cancer risk from the history of parents and ancestors. There is currently no technology available to distinguish the genes that predict susceptibility to cancer. With our screening , it won’t be necessary to genotype an entire family tree."
An early detection sensor for cancer
Carcinomas shed cells into the vascular system before they metastasize. What if you could detect those malignant cancer cells in the blood before they had a chance to spread? That’s what professor of electrical engineering Theresa Mayer and her collaborators, which include Christine Keating, assistant professor of chemistry, and Gary Clawson, professor of pathology, and biochemistry and molecular biology at Penn State’s Hershey School of Medicine, are trying to achieve. They are developing highly specific and highly sensitive RNA sensors built on to a CMOS semiconductor chip that are expected to make the detection of early cancers easier and more effective.
Her group has incorporated functionalized single crystal silicon and metal nanowires that have been optimized to detect cancer cells onto lithographically patterned chips. In a process unique to the Penn State team, the nanowires are optimized chemically off the chip and then incorporated onto the chip through electrofluidic assembly, a process that can precisely control their placement.
Mayer’s group uses chemical vapor deposition techniques to make silicon nanowires. The single crystal structure results in high quality sensors. Arrays of silicon nanowires that have been optimized with various cancer-specific oligonucleotides will attach to circulating tumor cells from breast, prostate, and melanoma cancers. "If successful, this biosensing strategy will enable early diagnosis of these cancers and improve treatment success," Dr. Mayer says.
Hybrid biosensor sniffs out land mines
One of the most fascinating approaches to creating biosensors for defense and homeland security comes from Penn State professor of entomology Thomas Baker, whose research into hybrid insect antennal biosensors was sponsored by the Department of Defense through its Defense Advanced Projects Research Agency (DARPA). By using arrays of insect antennae, his olfactory biosensor can detect and locate the source of plumes of odor from toxic chemicals or unexploded land mines tens of meters up wind from the sensor. It can also detect odors in plumes that otherwise would have been masked by background odors or other strong odor plumes, such as from flowers.
Baker describes his software as tracking the source of chemical hazards in the way a hunting dog’s cold, wet nose points toward the source of an odor. Using a computer algorithm developed in conjunction with collaborators at the University of Illinois-Chicago, Baker’s sensor software can discriminate various drugs, toxins, and unexploded military ordinance in a real-time framework.
"Living moth antennae have only a short lifetime of an hour or so in the field," Baker says. "They need to be replaced with fresh antennae to keep the system sensitive." To overcome that obstacle, Professor Baker is now collaborating with David Allara, Penn State professor of polymer science and chemistry, and others in order to produce completely synthetic insect-antenna-inspired sensors.
Beyond biosensors
Along with nationally recognized research programs in acoustic and optical sensors, many informal faculty working groups are engaged in sensor and related technology research across the University Park campus. Sensors for agriculture and food; aqueous sensor networks to monitor water safety; nanowire sensors; heat sensors to monitor highway pavement conditions; remote MEMs vibration sensors; wireless biotoxin sensor networks that detect aerosolized biotoxins using magneto-elastic based sensors; and thin film sensors are all part of recent or ongoing work that is producing positive impacts on the health, safety, and economic well-being of both Pennsylvania and the nation.
Contacts:
Joe Dougherty, Validate to view address
Michael Pishko, Validate to view address
Craig Grimes, Validate to view address
Jong-in Hahm, Validate to view address
Theresa Mayer, Validate to view address
Thomas Baker, Validate to view address
