Dr. Mansoor Nasir
“Medical device” is a catch-all term that can include anything and everything from prosthetics and diagnostic instruments to imaging and therapeutic devices. Sometimes, these are also referred to as “biosensors.” However, the term biosensor is more commonly used for specific devices or techniques that can qualitatively and quantitatively detect targets of interest. The targets include pathogens, DNA or some other specific protein, or a molecule. Examples of some of the most widely used medical devices that also qualify as biosensors are pregnancy tests, glucose sensors, and environmental sensors.
Of the aforementioned example, pregnancy tests and glucose sensors also qualify as Point-of-Care (POC) diagnostic devices. POCs are all the rage these days. To many, they espouse images of Tricorders and other instruments that might show up in an episode of Star Trek (Trekkie here) in the hands of Dr. McCoy. However, to a ‘serious’ BME student, they represent medical devices that can do the testing and analyze and present the data onsite were patient is located. This could be under supervision of a medical practitioner but certainly, one of the reasons for the success of pregnancy tests and glucose sensors is their ease of use and easy interpretation of results by layfolk.
In the research community, another term that is commonly used for a type of biosensor is a Lab-on-a-Chip (LOC) device (also called Micro Total Analysis System or mTAS). While similar in concept to POCs, LOCs are more sophisticated in their architecture and sensing capabilities. The might include fluidic conduits (sometimes referred to as microfluidics) and a variety of sensing modalities, such as optical, electrical, electrochemical, or acoustic, to name a few. Some may also include instrumentation and signal conditioning components. The holy grail in LOCs is a complete platform that can take a raw sample, filter and separate it into constituents, and then selectively identify and/or analyze the target, all on a device no bigger than a credit card.
Figure 1. (Left) First commercially available Glucose Biosensor (YSI 23A)*. (Right) A 3mm-long glucose sensor under development at Lawrence Technological University in Dr. Kandaswamy’s lab. Notice the drive toward miniaturization.
LOC devices are attractive in part because they can work with extremely small sample volumes and have very fast detection times. Integrating so many functionalities on a single platform is tremendously challenging and many such devices still require bulky pumps and instrumentation and the end result is almost never the size of a credit card.
This is nowhere truer than in the case of biosensors based on fluorescent tagging. While fluorescent sensors set the bar for high sensitivity for bio/molecular detection, they require bulky measurement setup. Perhaps more importantly, these sensors require the need to label the target with fluorescent molecules. This introduces a host of new issues, such as selectivity and non-specific binding, which can introduce error in measured signal. In many cases, the required reagents are also temperature or light sensitive. The result is that fluorescent biosensors are not cost effective and also not easily miniaturized. Here electrical biosensors have an advantage as they rely solely on the measurement of voltages or currents for detection. The main advantage for studying impedance biosensors is their ability to perform label-free detection. While there are many variations of electrical sensors, the mostly commonly used techniques measure change in impedance or conductivity in the presence of the target. Further information about the target can be elicited if the frequency is also varied while holding the amplitude of the electrical stimulus constant. This technique is called Electrical Impedance Spectroscopy (EIS).
Figure 2. The figure shows an example of an impedance-based sensor made by using a micromachined Plexiglas flow channel that interfaces with a glass slide with microfabricated gold electrodes. There are two inlets and one outlet. The flow-rate ratio between sheath (faster) and sample (slower) fluids controls the sensitivity of this sensor.
My research interests lie in the area of EIS but combine it with microfluidic sensor technology with the goal of rapid identification of chemical and biological threats. By using microchannels with different architectures as well as changing the flow rates of laminar fluid streams, impedance sensors with tunable sensitivity can be achieved. Working on such projects requires expertise from a multidisciplinary team with expertise in surface modification, microfabrication, and bioinstrumentation. Future research efforts will focus on extending the detection to a multielectrode system for impedance-based imaging systems.
There is considerable potential for incorporating such ideas in classroom teaching. A new BME course (BME4093), offered in Spring 2013, will focus on with various medical device technologies, including commercialized products such as the glucose sensor. EIS research includes elements of circuit design, electrochemical (EC) response of electrodes in electrolytic solutions, as well as bioinstrumentation for signal amplification and filtering. Students in the Bioelectrical Engineering Physics course (BME 4503) offered this semester learned about the theory behind EIS. In short, impedance biosensors have the potential for not only the development of simple, label-free detection of biosensors but can also be valuable tools in teaching students about some fundamental principles of biosensing platforms based on electrical measurements.