Biosensing with a Graphene-Based FET

Introduction: A low-cost sensor that continuously and rapidly looks for a range of biomolecules is a longstanding goal for the biosensor community that remains unfulfilled. Such real-time sensors could lead to “more effective point of injury care for Sailors and Marines,” and “enhanced health and warfighter performance both afloat and ashore.”1 The arduous quest for such an “ultimate” biosensor, one that fully meets the Office of Naval Research (ONR) vision of enhancing warfighter health and survivability, has spanned nearly 50 years. One particular application of such a sensor, medical diagnostics, utilizes biosensor technologies based on nucleic acid and immunoassays. Most of these biosensor technologies currently use a label to facilitate detection. A label can be a fluorescent molecule or a magnetic bead or any component that helps signal the presence of the target biomolecule. In particular, fluorescence labels remain the predominant strategy because of their signal strength, availability of multiple emission wavelengths, and their compatibility with multiplexed, high-throughput, in situ and in vivo applications. The difficulty is that labels introduce complexity into the sensor system and, in the case of fluorescence labels, are consumed, whereby detection can only last a defined duration. In contrast, “label-free sensing” eliminates sample handling to attach the label to the target and alleviates steric hindrance, thus resulting in higher sensitivity, faster response, and ultimately lower costs. A popular approach for label-free sensing is based on the field effect transistor (FET), which consists of two terminals, the source and drain, and a gate that controls the resistance of the device (Fig. 1, top). For sensor applications, the gate terminal is replaced by a material that can sense biomolecules. Typically, it consists of covalently bound “probe” biomolecules that can capture the target biomolecule via biological interactions such as protein–ligand and DNA hybridization. We refer to these modified structures as biologically active field effect transistors, or BioFETs (Fig. 1, bottom). Several promising biosensing advances have used nanoscale one-dimensional materials such as carbon nanotubes as the gate.2 Recently, we demonstrated that an ideal gate material for BioFETs is chemically modified graphene (CMG).3 Because graphene is only one atom thick, the highly mobile electrons at or near its surface are extremely sensitive to local charge changes. Because most biomolecules are charged, their binding to a graphene-based gate will disrupt the flow of the electrons. Of course, this only works if the graphene is properly biofunctionalized such that protein–ligand interactions or nucleic acid hybridization can occur.