Label‐Free Electrical Detection of DNA Hybridization on Graphene using Hall Effect Measurements: Revisiting the Sensing Mechanism

Abstract

There is broad interest in using graphene or graphene oxide sheets as a transducer for label-free and selective electrical detection of biomolecules such as DNA. However, it is still not well explored how the DNA molecules interact with and infl uence the properties of graphene during the detection. Here, Hall effect measurements based on the Van der Pauw method are used to perform single-base sequence selective detection of DNA on graphene sheets, which are prepared by chemical vapor deposition. The sheet resistance increases and the mobility decreases with the addition of either complementary or one-base mismatched DNA to the graphene device. The hole carrier concentration of the graphene devices increases signifi cantly with the addition of complementary DNA but it is less affected by the one-base mismatched DNA. It is concluded that the increase in hole carrier density, indicating p-doping to graphene, is better correlated with the DNA hybridization compared to the commonly used parameters such as conductivity change. The different electrical observations of p-doping from Hall effect measurements and n-doping from electrolyte-gated transistors can be explained by the characteristic morphology of partially hybridized DNA on graphene and the mismatch between DNA chain length and Debye length in electrolytes.

Sensing at the Surface of Graphene Field‐Effect Transistors

“…[12] The broad sensing potential of graphene can only be unlocked by the introduction of sensitizer (bio)molecules and structures, e.g. various inorganic groups, [23][24][25][81][82][83][84][85][86][87][88][89][90] organic or organometallic molecules, [37,[91][92][93][94][95][96] DNAs, [97][98][99][100][101] proteins, [102] peptides, [30,31,103,104] nanoparticles, [105,106,107] and 2D heterostructure. [51,52,61,108] These molecules are able to respond chemically or physically to their nearby environment, whose responses could then be transduced into an appreciable change in the conductivity of the carbon-based honeycomb scaffold.…”

Nanomaterials for Diagnosis: Challenges and Applications in Smart Devices Based on Molecular Recognition

“…153 The first DNA biosensor was published in 1993 using a reversible electroactive cobalt complex for voltammetric detection of covalently immobilized DNA. 154 Since then, other principles of detection have been used, including optical, 155 piezoelectric, 156 electrical, 157 and electrochemical measurements. 158,159 DNA biosensors have been obtained with several methods of immobilization 160,161 and in conjunction with other nanomaterials.…”

Simplified detection of the hybridized DNA using a graphene field effect transistor

“…The interaction between rGO and DNA can also be affected by the defects present in rGO sheets. Device performance reported by Lin et al [22] revealed a shift of the transfer curve (V Dirac point) to the left (negative), clearly describing the n-doping of nucleobase DNA on the graphene and sometimes revealed shifts to the right (positive), referring to p-doping (hole carrier concentration).…”

“…DNA hybridization, the formation of double-stranded DNA by hydrogen bonds between nucleotide bases of single-stranded DNA and its complementary DNA, is used to detect specific DNA expression. In a DNA sensing experiment, phosphate groups play a vital role, which creates van der Waals dispersion forces [30–32] and electronic interactions such as induced dipole [33] and doping [22] between the DNA nucleobases and graphene. Optical detection is generally used for detecting DNA hybridization.…”

“…[13] Among these approaches, label-free electrical detection has been studied extensively, as it does not require fluorescent tags. [22,23] Thus, the GFET has been developed as a label-free sensing device for DNA detection. Detection of label-free target DNA using GFET is based on the change in Fermi level [18,34,35] upon hybridization of the target DNA with the probe DNA on graphene.…”