Micro-system platforms/new materials for biosensor applications
04/01/2004
Microelectronic-based biosensors consist of a physicochemical transducer in direct contact with a biological recognition element such as antibodies, DNA probes, cells, neurons, and so on. Surface chemistry is used to link both elements. Biosensors are expected to be relatively cheap, small, fast, and easy to use — all achievements of microelectronic fabrication technologies characterized by mass (batch) fabrication, system integration, and a continuous quest for miniaturization. More recently, the emergence of new materials in IC fabrication has opened new avenues for biosensor development. Materials such as gallium arsenide (GaAs), semiconducting polymers, and piezoelectric quartz have proven their capabilities in specific biosensor applications.
Gallium arsenide
GaAs shows a 6–7× higher electron mobility than silicon for normal doping levels. This results in a higher transconductance with values ranging from 200–300mS/.mm for GaAs MESFETs to 600–700mS/.mm for HEMT, HFET, and MODFET devices. These high transconductance values imply a much higher potential sensitivity for GaAs transducers compared to their silicon counterparts.
A second advantage of this III-V material is the controlled growth of the layers using molecular beam epitaxy, allowing exact control over the optoelectronic properties of the substrate and device that can further enhance the sensitivity of the transducer.
First considered a disadvantage, the absence of a stable native oxide is truly an advantage in biosensor applications because it allows direct contact between the biological layer and the semiconductor substrate. Because direct access to the surface states is enabled, electronic properties can be tuned, making possible ways of sensing over a distance other than the classical field-effect.
 Figure 2. A dual-gated MESFET was developed in a later stage of the project. |
At IMEC, researchers have developed a modified GaAs MESFET transducer in which the metallized gate is replaced by a molecular gate (Fig. 1a). The influence of the organic self-assembled monolayers that constitute this molecular gate on the electronic properties of the MESFET was evaluated by measuring the I-V curve after each assembly step (Fig. 1b). This proof-of-principle experiment is the first step toward a highly sensitive and selective GaAs-based sensor (Fig. 2). Future work will focus on the specific relationship between the physicochemical properties of the surface structure/composition and the semiconductor properties of the device.
Semiconducting polymers
Organic semiconductors offer a relatively low material cost and a simpler fabrication technique compared to silicon, and they are biocompatible, as well as compatible with plastic substrates. These attributes are very interesting for health-related and environmental applications where single-use, disposable biosensors are preferred.
 Figure 3. a) A photograph of a polymer-based ISFET prototype, encapsulated with silicon rubber, and b) its glucose response. |
A prototype of a polymer-based field-effect transistor was developed in which the polymer P3HT (poly(3-hexylthiophene)regioregular) is used as active layer material. Evaporated Ta2O5 is used as the H+-sensitive gate insulator. This ISFET is able to detect protons and glucose in aqueous media (demonstrated), as well as a variety of charged and uncharged chemical species if layers with a specific functionality are added to the transistor. For example, to detect glucose, an enzymatic layer consisting of glucose oxidase is anchored onto the gate insulator (Fig. 3). The hydrolysis of the glucose, catalyzed by the enzyme, increases the proton concentration at the Ta2O5 surface and consequently generates a current variation proportional to the glucose concentration.
AW devices with piezoelectric materials
Piezoelectric materials, such as quartz and lithium niobate, can generate and transmit acoustic waves in a frequency-dependent way. They are used in affinity-type biosensor transducers called acoustic-wave (AW) devices for the direct detection of analyte concentrations of biological species in solution. As opposed to existing optical techniques, such as fluorescence and surface plasmon resonance, AW technology is more compact and robust, and consumes less power because no optical components or moving parts are present. Because AW technology is very similar to the well-established production of quartz resonators and high-frequency SAW filters in the electronics industry, the possibility of obtaining large production quantities in a reliable way is another advantage.
IMEC researchers developed an AW device on 500µm-thick ST-cut quartz wafers. The prototype sensor was able to determine the presence and amount of prostate specific antigen (PSA) — a parameter important in the follow-up of prostate cancer. The key element of the biological recognition layer is a specially engineered camel antibody against PSA (developed at the Flemish Institute of Biotechnology). Directly binding PSA to the recognition layer results in a sensor response that is in the range of the noise level of the AW transducer. An indirect assay however, shows much higher sensitivity: it includes an extra step in which a conventional antibody is introduced after binding PSA to the surface. This binding event generates much larger sensor responses because the molecular weight of a conventional antibody (150,000 Da) is 5× larger than the molecular weight of the PSA (30,000 Da).
Conclusion
The unique combination of microelectronics and biology within biosensors allows information about a person's health, the quality of food, and the state of the environment to be collected. Advances in biosensor technology have been made possible in part by the emergence of new materials. Whereas silicon semiconductor devices were the first to be used in solid-state biosensor applications, today new materials enter this domain with additional benefits for specific applications. Research on transducer configuration (materials and processes) is only one key element for successful development of microelectronic-based biosensors. Surface chemistry, optimization of biochemical probes and packaging are equally important. Optimal microsystem platforms for biosensor applications can only be realized when surface chemistry (for the creation of biochemical or chemical functional surfaces) and engineering of materials and processes go hand in hand.
Els Parton received her engineering degree and PhD in applied biological sciences at the Catholic U. of Leuven, Belgium. She joined IMEC in 2001 as a scientific editor. E-mail [email protected].
Carmen Bartic received her PhD in physics from the Catholic U. of Leuven, Belgium. She is an R&D scientist within the Biosensors and Systems Group at IMEC.
Andrew Campitelli is group leader of the Biosensor Group at IMEC. He received his PhD in electronic engineering, specializing in sensor technology, from the RMIT, Melbourne, Australia.