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Nano Res

1

Oxide-on-graphene field effect bio-ready sensors

Bei Wang1†

, Kristi L. Liddell2†

, Junjie Wang1, Brandon Koger

1, Christine D. Keating

2, and Jun Zhu

1,3 ()

Nano Res., Just Accepted Manuscript • DOI: 10.1007/s12274-014-0489-9

http://www.thenanoresearch.com on May 3, 2014

© Tsinghua University Press 2014

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Nano Research

DOI 10.1007/s12274-014-0489-9

1

TABLE OF CONTENTS (TOC)


Bei Wang, Kristi L. Liddell, Junjie Wang, Brandon

Koger, Christine D. Keating, and Jun Zhu*

The Pennsylvania State University, USA

This work reports on the fabrication, functionalization and operation of

a novel oxide-on-graphene field effect bio-ready sensor. pH sensing is

demonstrated.

Provide the authors’ website if possible.

Jun Zhu, http://www.personal.psu.edu/jxz26/zhulab/

2


Bei Wang1†, Kristi L. Liddell2†, Junjie Wang1, Brandon Koger1, Christine D. Keating2, and Jun Zhu1,3 (*) 1 Department of Physics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA 2 Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA 3 Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, USA † These authors contributed equally to this work. Received: day month year / Revised: day month year / Accepted: day month year (automatically inserted by the publisher) © Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2011

ABSTRACT

Electrical detection schemes using nanoscale devices offer fast and label-‐‑free alternatives to biosensing

techniques based on chemical and optical interactions. Here we report on the design, fabrication, and

operation of oxide-‐‑on-‐‑graphene ion-‐‑sensitive field effect sensor arrays using large-‐‑area graphene sheets

synthesized by chemical vapor deposition. In this scheme, HfO2 and SiO2 thin films are deposited atop the

graphene sheet and play the dual role of the sensing interface, as well as the passivation layer protecting the

channel and electrodes underneath from direct contact with the electrolyte. We further demonstrate the

functionalization of the SiO2 surface with 3-‐‑aminopropyltrimethoxysilane (APTMS). The oxide-‐‑on-‐‑graphene

sensors operate in solution with high stability and a high average mobility of 5000 cm2/Vs. As a proof of

principle, we demonstrate pH sensing using the bare or the APTMS-‐‑functionalized SiO2 as the sensing

surface. The measured sensitivities, 46 mV/pH and 43 mV/pH respectively, agree well with existing studies.

We further show that by applying the solution gate voltage in pulse, the hysteresis in the transfer curve of

the graphene transducer can be eliminated, greatly improving the ionic potential resolution of the sensor.

Nano Res DOI (automatically inserted by the publisher) Research Article

Jun � 2/16/14 4:07 PM

Deleted: bio

Jun � 2/16/14 4:13 PM

Deleted: The latter enables further attachment ofto protein and nucleic acid

molecules

Jun � 2/16/14 4:13 PM

Deleted: . This design utilizes both the excellent transport characteristics of the

graphene transducer and the

well-‐‑established linker chemistry of the

SiO2 surface to achieve specific binding

and detection of biomolecules.

Jun � 2/16/14 4:12 PM

Deleted: 3-‐‑aminopropyltrimethoxysilane

(

3

These experiments demonstrate the potential of oxide-‐‑on-‐‑graphene ion-‐‑sensitive field effect sensors in

on-‐‑chip, label-‐‑free and real-‐‑time biosensing applications.

KEYWORDS graphene, biosensor, pH sensor, ISFET, APTMS, label-‐‑free

1. Introduction

Sensors are essential to biomedical diagnosis. Compared to traditional methods such as fluorescence,

surface plasmon resonance, and bioassays, sensors based on electrical detection schemes can potentially be

faster, more cost effective, and require less specialized equipment. Ion-‐‑sensitive field effect transistors

(ISFETs), for example, work by converting charge accumulation caused by the binding of biomolecules on a

sensing surface into a potential signal, which is then detected by the conductance change of the FET

transducer [1]. Such sensors can be readily integrated into a multiplexing system to deliver low-‐‑cost, on-‐‑chip

biomedical diagnosis [2-‐‑4], or used to study the hybridization and binding kinetics of DNA and proteins

[5-‐‑10].

Until recently, ISFET technology primarily focused on silicon transistors [1, 7, 8, 11]. The sensitivity of

bulk devices is ultimately limited by its bulk carrier mobility of ~500 cm2/Vs. More recent efforts explore field

effect transistors (FETs) based on low-‐‑dimensional nanostructures, such as nanowires and carbon nanotubes,

because of their size, large surface-‐‑to-‐‑volume ratio, and potentially higher sensitivity. Although high

performances have been demonstrated [12-‐‑15], much work needs to be done to address practical issues such

as uniformity, stability and scalability before applications can be developed [16, 17]. Graphene FET may be a

———————————— Address correspondence to Jun Zhu, [email protected]

Jun � 2/16/14 4:14 PM

Deleted: romise

4

good candidate for biosensing because of its excellent carrier mobility and the availability of low-‐‑cost

large-‐‑scale synthetic methods [18-‐‑21]. Indeed, several recent studies report using graphene FETs as a pH

sensor [22-‐‑25] and for the detection of protein and DNA [23, 26, 27]. However, the underlying sensing

mechanism of a graphene FET is not clear. The reported pH sensitivities of as-‐‑grown graphene sheets vary

from 6—99 mV/pH [22-‐‑25, 28]. Fu et al. demonstrates that a pristine graphene sheet is insensitive to H+

concentration change in solution [28] and points to the role of uncontrolled extrinsic imperfections, such as

defects and contaminations, in the sensing process. These complications require further studies to clarify.

Furthermore, a pristine graphene surface precludes specific binding and detection. Functionalization,

however, severely reduces the carrier mobility in graphene. For example, the introduction of 1013/cm2 sp3

centers (e. g. C-‐‑NH2 to bind to protein and DNA) will reduce the mobility to less than 100 cm2/Vs,

compromising the advantage of graphene FETs [29-‐‑31]. In comparison, SiO2 has been widely used as the

dielectric layer and sensing surface in ISFETs made from bulk silicon to nanowires because of the

well-‐‑established silanization chemistry that enables the immobilization of specific bioprobes and targets [32].

The ion sensitivity of a SiO2 surface is well understood by the site dissociation model [33, 34].

In this work, we demonstrate the fabrication and operation of a novel oxide-‐‑on-‐‑graphene bio-‐‑ready

sensor. In this scheme, the graphene channel is passivated by a SiO2/HfO2 (25 nm/20 nm) double oxide layer,

which uses the top SiO2 layer as the sensing/immobilization surface and the high-‐‑quality HfO2 layer to

protect the channel from the solution. This design preserves the high carrier mobility of the graphene

transducer, which averages 5000 cm2/Vs in our devices. We demonstrate the functionalization of the SiO2

surface with 3-‐‑aminopropyltrimethoxysilane (APTMS), as a pathway to the immobilization of proteins and

DNA [35]. The devices operate stably and reproducibly in solution. Bare and APTMS-‐‑functionalized devices

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are sensitive to the pH value of phosphate buffer saline (PBS) solutions ranging from 4-‐‑9. The observed

sensitivity of 46 mV/pH and 34 mV/pH respectively are in good agreement with results obtained on similar

surfaces [1, 33, 34, 36]. Operating the solution gate in pulse mode eliminates the hysteresis in the transfer

curve of the graphene FET, which is a common issue in nanostructure-‐‑based biosensors. Our experiments

show the potential of this new graphene-‐‑based device design in on-‐‑chip sensing applications.

2. Experimental

The pH sensing study uses 0.010 M PBS (0.010 M potassium chloride and 0.001 M sodium phosphate, pH

4.1, 6.0, 6.9, or 8.8); chemicals are purchased from Sigma Aldrich. HPLC grade water for buffer preparation

is purchased from EMD Chemicals.

APTMS functionalization is carried out in 3% 3-‐‑aminopropyltrimethoxysilane (APTMS, TCI America) in

200 proof ethanol (Koptec) for 1 hour. Excess APTMS is removed with an ethanol rinse followed by a 10

minute cure at 110oC.

pH sensing measurements are performed by covering the device channel area in a droplet of PBS

solution of the desired pH, avoiding contact between the liquid and the electrodes. A silicone ring is

sometimes used to confine the droplet. Transfer curves are obtained at each pH value in the course of ~20

minutes. After each pH measurement, the chip is thoroughly rinsed in DI water followed by the PBS solution

of the next desired pH value before the next set of measurements is begun.

3. Results and discussion

The graphene sheets used in this study are synthesized by a low-‐‑pressure chemical vapor deposition

Kristi Liddell� 3/25/14 2:19 PM

Deleted: romise

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(CVD) technique on copper foil [18]. Figure 1(a) shows a scanning electron microscope (SEM) image of

as-‐‑grown graphene, showing a full monolayer coverage with ~5% multi-‐‑layer islands. The sheets are

transferred to 290 nm SiO2/highly doped Si substrates using a polymer-‐‑assisted wet transfer method [18]. A

typical Raman spectrum of transferred graphene is given in Fig. 1(b), where a small ID/IG ratio of less than 0.1

indicates high-‐‑quality growth [18]. The transferred sheet is annealed in Ar/H2 at 450°C for 2 hours. After

annealing, the graphene surface appears flat, continuous and mostly free of polymer residue, with small

amount remaining at the wrinkles and folds of the sheet.

Two-‐‑terminal graphene FETs of dimensions 2 µμm (width) × 4 µμm (length) are fabricated using optical

lithography, reactive ion etching and metal deposition. We then deposit 20 nm of HfO2 on the whole wafer

using atomic layer deposition and recipes previously established by our group [37], followed by the electron

beam evaporation of 25 nm of SiO2. An optical micrograph of a sensor array and an SEM image of a channel

are shown in Fig. 2.

Figure 3(a) shows a schematic of the oxide-‐‑on-‐‑graphene sensor operating in solution, using both the

doped silicon back gate and the solution top gate. A small droplet of deionized water or PBS solution forms

the solution gate above the channel area (see Fig. 2). Care is taken to ensure that the droplet does not cover

the contact pads of the device being measured. A tungsten electrode and an Ag/AgCl reference electrode are

inserted into the droplet to apply Vapp and read Vsg, the potential of the solution, respectively. The use of the

reference electrode is necessary to eliminate spurious changes in the characteristics of the sensor due to the

variation of the potential drop at the tungsten/solution interface. Because of the conformal growth of the

HfO2 film, the channel is well protected from the solution and the solution gate operates with a small leakage

current of less than 100 pA.

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Figure 3(b) plots the conductance of a graphene channel as a function of the back gate voltage Vbg (top

axis) and the solution gate voltage Vsg (bottom axis) using different symbols. The two axes are scaled and

offset with respect to one another so that the two measured traces overlap. The device is ambipolar with a

small amount of unintentional doping. The back gate sweeps are typically hysteretic with a separation of

ΔVbg ~7 V between the two charge neutrality points. Only one sweep direction is shown here. The solution

gate hysteresis ΔVsg is generally less than 100 mV. The scaling ratio γ between the two gate voltages Vsg and

Vbg in Fig. 3(b) gives the ratio between the capacitance of the solution gate, Csg and that of the back gate Cbg,

i.e., Csg = γ Cbg. Measurements on 11 devices yield γ = 11.3 ± 1.1, from which we determine Csg= (127 ± 12)

nF/cm2 using a back gate capacitance Cbg= 11.2 nF/cm2. This result can be understood by noting that Csg

consists of the capacitance of the solution CDL, and the capacitance of the double oxide layer (20 nm HfO2 and

25 nm SiO2) Cox in series:

.

In our experiment, CDL, which scales with the ionic concentration of the solution M as CDL~M1/2[5], is

much larger than Cox such that Csg≈ Cox. We determine Cox to be ~120 nF/cm2 through direct capacitance

measurement, which agrees very well with Csg obtained here.

We determine the field-‐‑effect mobility µFE of the graphene FETs by fitting the G(Vbg) curve to the

charged-‐‑impurity scattering model, following Eq. (2) of Hong et al [38]. The fit describes data very well, as

shown in Fig. 3(b). The field effect mobility µFE averages approximately 5000 cm2/Vs for both electrons and

holes, indicating the high quality of our devices among CVD-‐‑grown graphene [21]. The high µFE and Csg

together lead to a high normalized transconductance of gm= µFE·∙ Csg = 0.6 mS/V. In devices measured here, gm

€

Csg =CDLCox

CDL +Cox

8

is reduced by a factor of a few due to the contact resistance, which is around 5 kΩ in our devices. The contact

resistance can potentially be reduced by a few orders of magnitude by using gentle oxygen plasma etching

and annealing [39] to further increase gm.

In field effect devices made from nanomaterials such as nanotubes, nanowires, and graphene, hysteretic

transfer curves caused by interfacial changes and adsorbates are a common problem [13, 23, 40]. Adopting

pulsed gate sweep techniques (Fig. 4(b)) applied to carbon nanotube FETs [41, 42], we can suppress the

hysteresis in our graphene FETs completely. Examples of hysteretic and hysteresis-‐‑free G(Vsg) traces of the

same device are shown in Fig. 4(a). The elimination of hysteresis eliminates a source of uncertainty in the

operation of nanostructured sensors and greatly improves their long-‐‑term stability.

Next we demonstrate the proof-‐‑of-‐‑principle operation of the oxide-‐‑on-‐‑graphene sensor by measuring its

response to the pH of PBS solutions. Both bare SiO2 and APTMS-‐‑functionalized devices are tested and their

sensing performance evaluated in Figs. 5 and 6. The test protocol is described in the experimental. Briefly, we

measure the G(Vsg) curve of the graphene FET while it is immersed in a PBS solution droplet of a fixed pH

value. The device is thoroughly rinsed with de-‐‑ionized water prior to exposure to another droplet of a

different pH. Measurements of the same pH value are repeated at different times to check the stability of the

sensor. The same test is done on many graphene FETs.

Figure 5 shows the pH response of a bare FET. As the pH value of the PBS solution increases, the G(Vsg)

curve retains its shape but shifts toward positive Vsg. The inset of Fig. 5 plots the position of the Dirac point

VD vs pH. The error bars represent the spread of VD from repeated measurements in the course of 6 hours.

Measurements are reproducible after weeks, demonstrating excellent stability of the sensors. In the range of

pH = 4.1 to 8.8, VD (pH) is well described by a linear fit, with a slope of 43 mV/pH. Averaging many devices,

we obtain a voltage sensitivity of (46 ± 8) mV/pH. These results are in good agreement with literature results

9

and can be well understood by the site-‐‑dissociation model developed for oxide surfaces [1, 33, 34]. Briefly,

the pH of the solution affects the protonation and deprotonation of the oxide surface, leading to a change in

the potential drop ψ0 at the solution/oxide interface, which causes the G(Vsg) curve to shift in Vsg. In the case

of SiO2, increasing pH increases the presence of negative charges on the SiO2 surface, which results in a

larger ψ0, and a shift in G(Vsg) towards positive Vsg. This is exactly what we observed. In the linear regime of

G(Vsg) in Fig. 5, the conductance changes by 4.2 µS/pH. This is a large conductance change among

nanostructured sensors [4, 12] and can be further increased by reducing the oxide thickness (presently 45 nm)

and increasing carrier mobility (presently 5000 cm2/Vs).

In Table I, we compare the voltage sensitivity of our oxide-‐‑on-‐‑graphene sensor with other graphene FET

pH sensors reported in the literature. Existing studies show a large variation ranging from 6 to 99 mV/pH using

as-‐‑grown graphene obtained from different methods. This large variation makes graphene pH sensors ill suited

for applications. The underlying sensing mechanisms are not well understood at the present, but the presence

of defects, contaminations and unintentional chemical functionalizations has been suggested to play key

role[22, 28]. In contrast, the sensitivity of our oxide-‐‑on-‐‑graphene sensor is given by the well-‐‑characterized oxide

surface and is well understood. Indeed, ISFET based pH sensors are commercially available and used in

applications requiring continuous readings such as environmental monitoring[43]. They are also a crucial

component of a CMOS integrated non-‐‑optical genome sequence scheme demonstrated recently[8]. The

oxide-‐‑on-‐‑grahpene design can potentially take advantage of the CMOS architecture already developed for

silicon ISFETs while using higher mobility graphene as the FET transducer.

We next show that oxide-‐‑on-‐‑graphene FETs can be readily functionalized with amine groups, which are

commonly used to immobilize and recognize biomolecular probes and targets [7]. The top SiO2 surface of the

graphene FETs are functionalized with APTMS following procedures described in the experimental section.

Figure 6(a) shows the high-‐‑resolution X-‐‑ray photoelectron spectroscopy (XPS) spectra of the N-‐‑1s state on

bare and APTMS-‐‑functionalized SiO2 surfaces, respectively. The spectrum on functionalized surface exhibits

two prominent peaks at 399.9 and 401.9 eV whereas no such signal is detected on the bare SiO2 surface. These

peaks correspond to NH2 and NH3+ groups, respectively, with the latter due to the presence of water [44].

Atomic force microscopy shows that most areas of the functionalized surface are covered by a thin film of

average thickness 0.7 nm (Fig. 6(b)), which is consistent with the height of one APTMS molecule [36]. In

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some areas, partial coverage as well as local aggregation of APTMS molecules is also observed. Similar to the

bare oxide-‐‑on-‐‑graphene devices, G(Vsg) of APTMS-‐‑functionalized devices shift towards positive Vsg with

increasing pH, an example of which is shown in Fig. 6(c). The inset of Fig. 6(c) plots the pH-‐‑dependent Dirac

point VD of this device, from which we extract a slope of 28 mV/pH. Averaging many devices, we find the

pH sensitivity of APTMS-‐‑functionalized graphene FETs to be (34 ± 8) mV/pH. These results agree well with

previous studies [36]. The reduced pH sensitivity is expected, as the amine group is less amphoteric than the

Si-‐‑OH group and the coverage of the APTMS layer is also probably less dense than that of the SiO2. The

functionalization of the oxide-‐‑on-‐‑graphene sensor with APTMS paves the path to the immobilization and

detection of specific binding events of molecules, such as the hybridization of DNAs.

4. Conclusions

In summary, we have designed, fabricated and demonstrated the operation of a novel high-‐‑quality,

oxide-‐‑on-‐‑graphene field effect bio-‐‑ready sensor in solution. The use of thin oxide film as the sensing layer

preserves the high mobility of the graphene transducer and enables sensing specificity. The

oxide-‐‑on-‐‑graphene FETs function stably and reproducibly. As a proof of principle, we show that bare and

APTMS-‐‑functionalized SiO2 surfaces response to the pH of PBS solutions, with the sensitivity of 46 mV/pH

and 34 mV/pH respectively. Our studies open the door to using graphene-‐‑based electrical devices to

selectively detect the presence and binding events of molecules of interest.

Acknowledgements

We thank Xiahua Zhong and Wenchong Hu for helpful discussions on experimental setup. The synthesis

of graphene, device preparation and electrical measurements are supported by NSF NIRT grant No.

ECS-‐‑0609243, MRSEC grant No. DMR-‐‑0820404 and CAREER grant No. DMR-‐‑0748604. Wet chemistry and

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chemical functionalization work was supported by the MSD Focus Center, one of six research centers funded

under the Focus Center Research Program (FCRP), a Semiconductor Research Corporation entity. The authors

acknowledge use of facilities at the PSU site of NSF NNIN.

References [1] Bergveld, P. Thirty years of ISFETOLOGY: What happened in the past 30 years and what may happen in the

next 30 years. Sensor. Actuat. B-Chem. 2003, 88, 1-20. [2] Johannessen, E. A.; Wang, L.; Cui, L.; Tang, T. B.; Ahmadian, M.; Astaras, A.; Reid, S. W. J.; Murray, A. F.;

Flynn, B. W.; Beaumont, S. P. et al. Implementation of multichannel sensors for remote biomedical measurements in a microsystems format. IEEE T. Bio.-Med. Eng. 2004, 51, 525-535.

[3] Zhang, G. J.; Ning, Y. Silicon nanowire biosensor and its applications in disease diagnostics: A review. Anal. Chim. Acta. 2012, 749, 1-15.

[4] Patolsky, F.; Zheng, G.; Lieber, C. Nanowire-based biosensors. Anal. Chem. 2006, 78, 4260-4269. [5] Poghossian, A.; Cherstvy, A.; Ingebrandt, S.; Offenhausser, A.; Schoning, M. J. Possibilities and limitations of

label-free detection of DNA hybridization with field-effect-based devices. Sensor. Actuat. B-Chem. 2005, 111, 470-480.

[6] Bunimovich, Y. L.; Shin, Y. S.; Yeo, W. S.; Amori, M.; Kwong, G.; Heath, J. R. Quantitative real-time measurements of DNA hybridization with alkylated nonoxidized silicon nanowires in electrolyte solution. J. Amer. Chem. Soc. 2006, 128, 16323-16331.

[7] Gonçalves, D.; Prazeres, D.; Chu, V.; Conde, J. Detection of DNA and proteins using amorphous silicon ion-sensitive thin-film field effect transistors. Biosen. Bioelectron. 2008, 24, 545-551.

[8] Rothberg, J. M.; Hinz, W.; Rearick, T. M.; Schultz, J.; Mileski, W.; Davey, M.; Leamon, J. H.; Johnson, K.; Milgrew, M. J.; Edwards, M. et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011, 475, 348-352.

[9] Sorgenfrei, S.; Chiu, C.; Gonzalez Jr, R. L.; Yu, Y. J.; Kim, P.; Nuckolls, C.; Shepard, K. L. Label-free single-molecule detection of DNA-hybridization kinetics with a carbon nanotube field-effect transistor. Nat. Nanotechnol. 2011, 6, 126-132.

[10] Stern, E.; Klemic, J. F.; Routenberg, D. A.; Wyrembak, P. N.; Turner-Evans, D. B.; Hamilton, A. D.; LaVan, D. A.; Fahmy, T. M.; Reed, M. A. Label-free immunodetection with CMOS-compatible semiconducting nanowires. Nature 2007, 445, 519-522.

[11] Bausells, J.; Carrabina, J.; Errachid, A.; Merlos, A. Ion-sensitive field-effect transistors fabricated in a commercial CMOS technology. Sensor. Actuat. B-Chem. 1999, 57, 56-62.

[12] Cui, Y.; Wei, Q.; Park, H.; Lieber, C. M. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 2001, 293, 1289-1292.

[13] Allen, B. L.; Kichambare, P. D.; Star, A. Carbon nanotube field-effect-transistor-based biosensors. Adv. Mater. 2007, 19, 1439-1451.

[14] He, B.; Morrow, T.; Keating, C. Nanowire sensors for multiplexed detection of biomolecules. Curr. Opin. Chem. Bio. 2008, 12, 522-528.

12

[15] Roy, S.; Gao, Z. Q. Nanostructure-based electrical biosensors. Nano Today 2009, 4, 318-334. [16] Regonda, S.; Tian, R. H.; Gao, J. M.; Greene, S.; Ding, J. H.; Hu, W. Silicon multi-nanochannel FETs to

improve device uniformity/stability and femtomolar detection of insulin in serum. Biosen. Bioelectron. 2013, 45, 245-251.

[17] Tian, R. H.; Regonda, S.; Gao, J. M.; Liu, Y. L.; Hu, W. Ultrasensitive protein detection using lithographically defined Si multi-nanowire field effect transistors. Lab. Chip. 2011, 11, 1952-1961.

[18] Li, X. S.; Cai, W. W.; An, J. H.; Kim, S.; Nah, J.; Yang, D. X.; Piner, R.; Velamakanni, A.; Jung, I.; Tutuc, E. et al. Large-area synthesis of high-quality and uniform graphene films on copper foils. Science 2009, 324, 1312-1314.

[19] Shao, Y. Y.; Wang, J.; Wu, H.; Liu, J.; Aksay, I. A.; Lin, Y. H. Graphene based electrochemical sensors and biosensors: A review. Electroanal. 2010, 22, 1027-1036.

[20] Pumera, M.; Ambrosi, A.; Bonanni, A.; Chng, E. L. K.; Poh, H. L. Graphene for electrochemical sensing and biosensing. Trac-Trend. Anal. Chem. 2010, 29, 954-965.

[21] Mattevi, C.; Kim, H.; Chhowalla, M. A review of chemical vapour deposition of graphene on copper. J. Mater. Chem. 2011, 21, 3324-3334.

[22] Ang, P. K.; Chen, W.; Wee, A. T. S.; Loh, K. P. Solution-gated epitaxial graphene as pH sensor. J. Amer. Chem. Soc. 2008, 130, 14392-14393.

[23] Ohno, Y.; Maehashi, K.; Yamashiro, Y.; Matsumoto, K. Electrolyte-gated graphene field-effect transistors for detecting pH protein adsorption. Nano Lett. 2009, 9, 3318-3322.

[24] Cheng, Z. G.; Li, Q.; Li, Z. J.; Zhou, Q. Y.; Fang, Y. Suspended graphene sensors with improved signal and reduced noise. Nano Lett. 2010, 10, 1864-1868.

[25] Giacchetti, B. M.; Hsu, A.; Wang, H.; Kim, K. K.; Kong, J.; Palacios, T. CVD-grown graphene solution-gated field effect transistors for pH sensing. MRS Proc. 2011, 1283, DOI: 10.1557/opl.2011.583.

[26] Dong, X. C.; Shi, Y. M.; Huang, W.; Chen, P.; Li, L. J. Electrical detection of DNA hybridization with single-base specificity using transistors based on CVD-grown graphene sheets. Adv. Mater. 2010, 22, 1649-1653.

[27] Ang, P. K.; Jaiswal, M.; Lim, C.; Wang, Y.; Sankaran, J.; Li, A.; Lim, C. T.; Wohland, T.; Ozyilmaz, B.; Loh, K. P. A bioelectronic platform using a graphene-lipid bilayer interface. ACS Nano 2010, 4, 7387-7394.

[28] Fu, W.; Nef, C.; Knopfmacher, O.; Tarasov, A.; Weiss, M.; Calame, M.; Schonenberger, C. Graphene transistors are insensitive to pH changes in solution. Nano Lett. 2012, 11, 3597-3600.

[29] Chen, J. H.; Cullen, W. G.; Jang, C.; Fuhrer, M. S.; Williams, E. D. Defect scattering in graphene. Phys. Rev. Lett. 2009, 102, 236805.

[30] Hong, X.; Cheng, S.-H.; Herding, C.; Zhu, J. Colossal negative magnetoresistance in dilute fluorinated graphene. Phys. Rev. B 2011, 83, 085410.

[31] Ni, Z. H.; Ponomarenko, L. A.; Nair, R. R.; Yang, R.; Anissimova, S.; Grigorieva, I. V.; Schedin, F.; Blake, P.; Shen, Z. X.; Hill, E. H. et al. On resonant scatterers as a factor limiting carrier mobility in graphene. Nano Lett. 2010, 10, 3868-3872.

[32] Pividori, M. I.; Merkoci, A.; Alegret, S. Electrochemical genosensor design: immobilisation of oligonucleotides onto transducer surfaces and detection methods. Biosen. Bioelectron. 2000, 15, 291-303.

[33] Akiyama, T.; Ujihira, Y.; Okabe, Y.; Sugano, T.; Niki, E. Ion-sensitive field-effect transistors with inorganic gate oxide for pH sensing. IEEE T. Electron Dev. 1982, 29, 1936-1941.

[34] Van Hal, R.; Eijkel, J.; Bergveld, P. A general model to describe the electrostatic potential at electrolyte oxide

13

interfaces. Adv. Colloid Interfac. 1996, 69, 31-62. [35] Zhang, F. X.; Srinivasan, M. P. Self-assembled molecular films of aminosilanes and their immobilization

capacities. Langmuir 2004, 20, 2309-2314. [36] Khamaisi, B.; Vaknin, O.; Shaya, O.; Ashkenasy, N. Electrical performance of silicon-on-insulator field-effect

transistors with multiple top-gate organic layers in electrolyte solution. ACS Nano 2010, 4, 4601-4608. [37] Zou, K.; Hong, X.; Keefer, D.; Zhu, J. Deposition of high-quality HfO2 on graphene and the effect of remote

oxide phonon scattering. Phys. Rev. Lett. 2010, 105, 126601. [38] Hong, X.; Zou, K.; Zhu, J. Quantum scattering time and its implications on scattering sources in graphene.

Phys. Rev. B 2009, 80, 241415. [39] Robinson, J. A.; LaBella, M.; Zhu, M.; Hollander, M.; Kasarda, R.; Hughes, Z.; Trumbull, K.; Cavalero, R.;

Snyder, D. Contacting graphene. Appl. Phys. Lett. 2011, 98, 053103. [40] Wang, H.; Wu, Y.; Cong, C.; Shang, J.; Yu, T. Hysteresis of electronic transport in graphene transistors. ACS

Nano 2012, 4, 7221-7228. [41] Mattmann, M.; Roman, C.; Helbling, T.; Bechstein, D.; Durrer, L.; Pohle, R.; Fleischer, M.; Hierold, C. Pulsed

gate sweep strategies for hysteresis reduction in carbon nanotube transistors for low concentration NO2 gas detection. Nanotechnology 2010, 21, 185501.

[42] Estrada, D.; Dutta, S.; Liao, A.; Pop, E. Reduction of hysteresis for carbon nanotube mobility measurements using pulsed characterization. Nanotechnology 2010, 21, 085702.

[43] Jimenez-Jorquera, C.; Orozco, J.; Baldi, A. ISFET based microsensors for environmental monitoring. Sensors 2009, 10, 61-83.

[44] Chauhan, A. K.; Aswal, D. K.; Koiry, S. P.; Gupta, S. K.; Yakhmi, J. V.; Surgers, C.; Guerin, D.; Lenfant, S.; Vuillaume, D. Self-assembly of the 3-aminopropyltrimethoxysilane multilayers on Si and hysteretic current-voltage characteristics. Appl. Phys A-Mater. 2008, 90, 581-589.

14

Figures

Figure 1. (a) SEM image of a continuous graphene film grown on copper substrate. Small, dark islands are multi-layers. (b) A typical

Raman spectrum of graphene transferred to SiO2/doped Si wafer showing a small ID/IG ratio of less than 0.1.

Figure 2. Optical image of one oxide-on-graphene field effect transistor array consisting of sixteen 2 µm × 4 µm two-terminal

graphene channels. The inset shows an SEM image of one such channel.

1µm

a

1500 2000 2500 1500 2000 2500

Raman Shift (cm-1)

Inte

nsity

(Arb

. Uni

t) b

1 mm

4µm

15

Figure 3. (a) Schematic drawing of the oxide-on-graphene FET operating in solution. The solution gate voltage is applied

through a tungsten electrode and read by an Ag/AgCl reference electrode. (b) The conductance of a graphene channel vs the

solution gate voltage Vsg (magenta solid triangle, bottom axis) and the backgate voltage Vbg (blue hollow square, top axis). The

two traces overlap well after scaling the Vbg and Vsg axes. The black solid line is a fit to the charged impurity model,

1/G=Rc+2/(neuFE+σres) following Eq. (2) of Ref. [38]. Fits to electrons and holes separately yield µFEe = 3900 and µFE

h = 5300

cm2/Vs respectively and Rce = 4700 Ω and Rc

h = 6300 Ω. σres= 0.17 mS.

Figure 4. (a) The conductance of a graphene channel vs the solution gate voltage Vsg with Vsg changed continuously (solid

magenta traces) and in pulse (blue hollow circles). The arrows indicate the sweeping directions of the magenta traces. The

time-varying pattern of the applied pulse is shown in (b) thigh = 25 ms, tlow = 75 ms

resubmission*

Vapp Vsg

- - - - - - - - + + + + + + + + +

Vbg

V

~Vds

a

60.0

80.0

100.0

120.0

-12 -8 -4 0 4

-1.5 -1.0 -0.5 0.0 0.5

Vbg(V)

Vsg(V)

120

100

80

60

-12 -8 -4 0

-0.5 0 0.5

b

G(µ

S)

W Ag/AgCl

290nm SiO2

25nm SiO2 20nm HfO2

p++ Si

S D

Vsg(V)

-0.6 -0.4 -0.2 0 0.2

G(µ

S)

thigh!

tlow!

a b

0.4 120

140

160

180

200

16

Figure 5. G(Vsg) curves of a graphene sensor with bare SiO2 surface in PBS solutions of different pH values as indicated in the

plot. From left to right: pH = 4.1 (blue), 6.0 (magenta), 6.9 (black), 8.8 (red). Inset: The Dirac point voltage VD as a function

of the pH value. The solid line is a linear fit with the slope of 43 mV/pH and a correlation coefficient greater than 0.99.

-0.6 -0.5 -0.4 -0.3 -0.2 -0.1

80

90

100

110

120

130 pH4 1st pH5.25 1st pH6 1st pH7 1st pH8.75 1st pH10

G(µ

S)

Vref(V)

4.1 6.0 6.9 8.8

Vsg (V)

G(µ

S)

17

Figure 6. (a) High-resolution XPS spectra of the N-1s state on bare (blue trace) and APTMS-functionalized SiO2 surfaces

(magenta trace). (b) AFM micrograph showing a differential height of 0.7 nm between areas covered by APTMS and where

the molecules were removed by contact mode scanning prior to acquiring this image. (c) G(Vsg) traces of an APTMS

functionalized sensor in PBS solution of different pH values. From left to right: pH = 4.1 (blue), 5.0 (magenta), 6.9 (black),

8.9 (red). Inset: The Dirac point voltage VD as a function of the pH value. The solid line is a linear fit with the slope of 28

mV/pH and a correlation coefficient of 0.97.

405 400 395

CP

S (A

rb. u

nit)

Binding energy (eV)

10

8

6

4

2

0

µm

1086420µm

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

nm

a b NH3

+ NH2

0 2 4 6 8 10-0.50.00.51.01.52.02.53.03.5

Heigh

t (nm

)

X (µm)

-0.3 -0.2 -0.1 0.0 0.1 0.2 0.3

40.0

42.0

44.0

46.0

pH4 pH5 pH6 pH7 pH9

G (µ

S)

Vref (V)

4.1 5.0 6.9 8.9

z*

c

Vsg (V)

G(µ

S)

2 µm

18

Table I. Comparison of graphene pH sensors

Ang et al[22]

This work

Ohno et al[23]

Giacchetti et al[25]

Cheng et al[24]

Fu et al[28]

sensitivity (mV/pH)

99 46 27 24 18 6

graphene source epitaxial CVD exfoliation CVD exfoliation CVD

oxide-on-graphene field effect bio-ready sensors · oxide-on-graphene field effect bio-ready...

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