Fabrication and Functionalisation of Nanocarbon-Based Field-Effect Transistor Biosensors

Abstract

Nanocarbon-based field-effect transistor (NC-FET) biosensors are at the forefront of future diagnostic technology. By integrating biological molecules with electrically conducting carbon-based platforms, high sensitivity real-time multiplexed sensing is possible. Combined with their small footprint, portability, ease of use, and label-free sensing mechanisms, NC-FETs are prime candidates for the rapidly expanding areas of point-of-care testing, environmental monitoring and biosensing as a whole. In this review we provide an overview of the basic operational mechanisms behind NC-FETs, synthesis and fabrication of FET devices, and developments in functionalisation strategies for biosensing applications.

Keywords: biosensors; carbon nanotubes; field-effect transistors; graphene; point-of-care diagnostics; surface functionalisation.

Figure 1

Overview of FET biosensor setups. Targets can range from large macromolecular systems such as viruses to complex biomolecules such as proteins and DNA to small molecules (e. g., hormones). The receptors for the targets include nucleic acid aptamers, binding proteins (e. g., antibodies) and peptides. Nanocarbon materials are placed between electrodes and the receptor attached. Signal transduction is then achieved though binding of the target (via the receptor) to generate a change in electrical signal.

Figure 2

Comparison of detection mechanisms used in an electrochemical biosensors and FET electrical biosensors.

Figure 3

Structures of different types of FET devices.

Figure 4

Mechanisms of detecting analyte binding through changes in FET transfer characteristics. I_DS is source‐drain current, V_LG is applied potential to liquid gate, and V_app is applied potential to gate with constant value for real‐time sensing. Insets represent the energy bands of the channels.

Figure 5

Signal modulation pathways for receptors immobilised on FET devices. Signals can be generated by: A. conformational changes of the charged receptors changing the charge within the Debye length; B. charged molecules from an enzymatic reaction; and C. changes in local charge upon analyte binding.

Figure 6

A. FET transfer characteristics with the band structures for majority of electron transfer at each regime. B. Changes in transfer characteristic by charged molecular gating via charged analyte.

Figure 7

Biocompatible nanocarbon functionalisation strategies. Covalent modification introduces functional groups directly into the carbon lattice, and these can conjugate biomolecules directly or indirectly (via attachment of linker molecule). Non‐covalent functionalisation utilises hydrophobic interactions and π–π stacking of biomolecules to directly decorate the surface of nanocarbon. Linker molecules can play an adaptor role; covalently or non‐covalently interfacing with nanocarbon, whilst providing reactive biochemical handles for biomolecule conjugation.

Figure 8

Biomolecule functionalisation strategies. Native biomolecules have a range of functional chemistries at their disposal. Proteins can utilise carboxyl, amine, thiol, and hydrophobic groups as prospective nanocarbon interfacing sites, whilst ssDNA and ssRNA can stack via π–π interactions. Tweaking of biomolecules via synthetic biology introduces new capabilities for proteins, such as azide functionalisation sites and novel N/C terminal mutations to incorporate carbon or gold binding peptides. Aptamers constructed from ssDNA and ssRNA represent its own field of biochemistry but offers huge potential in NC‐FET design.