Nanoelectronic Heterodyne Sensor: A New Electronic Sensing Paradigm

Abstract

Nanoelectronic devices based on nanomaterials such as nanowires, carbon nanotubes, graphene, and other 2D nanomaterials offer extremely large surface-to-volume ratios, high carrier mobility, low power consumption, and high compatibility for integration with modern electronic technologies. These distinct advantages promise great potential for nanoelectronic devices as next generation chemical and biological sensors. Currently, majority of existing nanoelectronic sensors are direct current (DC) sensors, which rely ubiquitously on detection of conductance change associated with molecular adsorption. However, despite the simplicity of the conventional DC sensing technology, it also has severe limitations such as the Debye screening effect in ionic solutions, and the speed-sensitivity trade-off for the detection of charge-neutral molecules. Hence, the development of nanoelectronic sensors calls for new sensing platform technologies that can truly showcase the advantages of electronic sensors. In this Account, we will summarize recent efforts from our group on the development of a new electronic sensing paradigm, the nanoelectronic heterodyne sensors. Unlike conventional charge-detection based sensors, the heterodyne sensor explores the frequency mixing response between molecular dipoles and a nanoscale transistor. As an example, we first discuss the capability of heterodyne sensing in gas sensing applications by using graphene devices. Rapid (down to 0.1 s) and sensitive (down to 1 ppb) detection of a wide range of vapor analytes is achieved, representing orders of magnitude improvement over state-of-the-art nanoelectronic sensors. Furthermore, the heterodyne sensing technique enables electrical probing and tuning of the noncovalent physisorption of polar molecules on graphene surface for the first time. These results provide insight into small molecule-nanomaterial interaction dynamics and signify the ability to electrically tailor interactions, which can lead to rational designs of complex chemical processes for catalysis and drug discovery. Finally, we discuss the application of heterodyne sensing in solution for chemical and biological sensors by using carbon nanotube devices. The fundamental ionic screening effect can be mitigated by operating carbon nanotube field effect transistor as a heterodyne biosensor. Electrical detection of streptavidin binding to biotin in 100 mM buffer solution can be achieved at a frequency beyond 1 MHz. The results should promise a new biosensing platform for point-of-care detection, where biosensors functioning directly in physiologically relevant condition are desired.

Field-effect sensors – from pH sensing to biosensing: sensitivity enhancement using streptavidin–biotin as a model system

“…22,23,112 Another example for conventional FET-sensors is that the surface layer could be modified with a biomoleculepermeable polymer layer which is proposed to operate by extending the effective distance over which charges are screened within the layer. 113 A final example of particular interest is the use of frequency-mode detection, 15,46,[114][115][116][117] where the current response is measured in the frequency domain instead of the time-domain (details can be found in ESI 6 †). The lack of wide-spread adoption of alternative operating methods may be due to: complexity, with the additional required steps required making them less commercially appealing; a lack of awareness in a rapidly changing field; or lack of reproducibility.…”

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

“…Truncated antibody receptors (21) and small aptamers (22) also have been used to reduce the distance between target species and the FET surfaces, although the generality of such methods for real-time sensing in physiological conditions requires further study. In addition, recent work has shown that highfrequency mixing-based detection can be used to overcome Debye screening effects (23,24), although the device geometry may limit this approach in cellular and in vivo applications.Recently, we have developed a strategy to overcome the Debye screening limitation that involves modification of a FET sensor surface with a biomolecule-permeable polymer layer to increase the effective screening length in the region immediately adjacent to the device, and demonstrated this concept for nonspecific detection of PSA using silicon nanowire sensors in physiological solutions (25). To explore the generality of this approach for nanomaterials-based FET sensors and further extend the concept to selective analyte recognition and detection, we herein describe studies demonstrating controlled nonspecific and highly selective protein detection in physiological media using graphene FET sensors in which the device surfaces are modified only with a biomolecule-permeable polymer layer and comodified with DNA aptamer/biomolecule-permeable polymer layer, respectively.…”

“…Truncated antibody receptors (21) and small aptamers (22) also have been used to reduce the distance between target species and the FET surfaces, although the generality of such methods for real-time sensing in physiological conditions requires further study. In addition, recent work has shown that highfrequency mixing-based detection can be used to overcome Debye screening effects (23,24), although the device geometry may limit this approach in cellular and in vivo applications.…”

Bioelectronics and Interfaces Using Monolayer Graphene

“…Since the EDL plays a crucial role in the transduction principle in FETs, it has very often been claimed that Debye screening is a limiting factor for FET‐based detection ,,. At a total ionic strength of around 0.1 M, the EDL thickness is around 1 nm, and hence it is believed that it is not possible to detect larger biomolecules such as antibody or enzyme interactions. Despite this belief, numerous examples of sensitive detection of biomolecules have been reported not only using graphene, but also with nanowires, nanotubes and organic FETs ,,.…”