Fabrication and application of silicon nanowire transistor arrays for biomolecular detection

Đây là một bài báo khoa học về dây nano silic trong lĩnh vực nghiên cứu công nghệ nano dành cho những người nghiên cứu sâu về vật lý và khoa học vật liệu.Tài liệu có thể dùng tham khảo cho sinh viên các nghành vật lý và công nghệ có đam mê về khoa học

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Contents lists available at ScienceDirect

&

Fabrication and application of silicon nanowire transistor arrays for

biomolecular detection

X.T Vu, R GhoshMoulick, J.-F Eschermann, R Stockmann, A Offenhausser, S Ingebrandt*

Institute of Bio- and Nanosystems and CNI - Centre of Nanoelectronic Systems for Information Technology, Forschungszentrum Jiilich GmbH,

Leo-Brandt-Str., D-52428 fiilich, Germany

Article history:

Available online xxx

We present a novel approach for large-scale silicon nanowire (SiINW) array fabrication for bioelectronic applications Nanoimprint lithography was combined with standard CMOS processing on 4 in SOI wafers

in order to produce highly integrated arrays of silicon nanowire field-effect transistors (SINW-FET) Witha very smooth surface due to wet anisotropic etching, SINW-FET arrays show a good electronic performance with a subthreshold slope of about 85 mV/decade When applying a front-gate control of the wires via an electrochemical reference electrode, reliable electronic performance inside an electrolyte solution can be achieved Our SiNW-FET sensors exhibit almost no electronic hysteresis on forward and backward bias sweeps In this article the fabrication process, electronic and electrochemical characterizations and first biomolecular detection experiments are presented For biodetection experiments we used a differential readout between molecule-free wires and wires carrying covalently attached biomolecules such as short, single-stranded DNA or biotin With our SINW-FET arrays a reliable detection of biomolecular layers can

Keywords:

Biosensor

Silicon nanowire transistor arrays

Field-effect sensors

Nanoimprint lithography

be achieved

1 Introduction

Nano-scale bioelectronic devices have the potential to achieve

exquisite sensitivity for the direct detection of biomolecular inter-

actions at surfaces Because of their high surface-to-volume ratio,

fast response time and reliability of the electronic readout, sil-

icon nanowire field-effect transistor (SiINW-FET) arrays promise

ultra high sensitivity for various, label-free biosensing applications

These device types will have a high impact for analyses in biomed-

ical diagnosis and early warning of bioterrorism attacks In the past

few years, the number of reports about SiNW-biosensors, which

were either fabricated by “top-down” or “bottom-up” methods, is

steadily increasing The biosensors were used for glucose detec-

tion|[1], protein binding or DNA hybridization detection [2-4], virus

detection [5], and even for extracellular recording from electrogenic

cells [6]

For real biosensor applications, the reliability of the devices

and the reduction of the fabrication cost are the major issues

In our project, we developed a wafer-scale approach to fabri-

cate the SiNW-FET biosensors We employ a novel method in

* Corresponding author Present address: University of Applied Sciences Kaiser-

slautern - Campus Zweibrticken, Department of Informatics & Microsystem

Technology, Amerikastr.1, D-66482 Zweibriicken, Germany Tel.: +49 6332 914 413;

fax: +49 6332 914 313

E-mail address: sven.ingebrandt@fh-kl.de (S Ingebrandt)

doi:10.1016/j.snb.2008.11.048

nanofabrication, the nanoimprint lithography [7], in combination with anisotropic wet etching with tetramethylammonium hydroxide (TMAH) [8,9] In addition, our process includes standard CMOS processes like wet, dry etching and conventional photolithography techniques We improved the device performance by boron doping on the conducting lines to reduce the serial resistance, while retaining the high charge mobility inside the SiNW-FETs Chips were passivated by a layer of low pressure chemical vapor deposited (LPCVD) SiOz As gate oxide of the SINW-FETs, a thin thermal SiOz (6-8 nm) was chosen, which serves as input dielectric Main advantage of our process flow is that mass production with reproducible devices can be achieved

We developed a portable electronic readout system for the use

of the SiNW-FET arrays in biosensing experiments [10,11] With this system, the simultaneous readout of all 16-channels can be achieved

We describe in this article the electrical and electrochemical characterization of the SiNW transistors The devices can be operated by applying a back gate voltage through the buried oxide (BOX) layer as well as to the front-gate through an electrolyte solution con- tacted by a liquid-junction Ag/AgCl reference electrode The wires showed good pH sensitivity with little hysteresis As a first proof- of-principle experiments for biomolecular detection we covalently immobilized short DNA molecules or biotin molecules at the wire surfaces The biomolecules were site-selectively attached at the array surface using a micro-spotter system A reliable detection

of the biomolecules can be done by using a differential read-

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out between molecule-free wires and wires having biomolecules

attached

2 Experimental methods

The fabrication process for our SiNW-FET arrays was recently

described in detail [12] Here we summarize the process and men-

tion the main steps

2.1 Imprint-mold fabrication

We used the electron-beam writer of the IBN clean room facil-

ities to fabricate the imprint-mold for the thermal nanoimprint

process in house The mold was etched ona 4 in silicon wafer froma

200 nm thick, thermal oxide Structures included templates for wet

etching of nanowires and feed lines to the individual sensor spots

Fabrication of the structures was done by direct electron-beam

lithography with a poly(methyl methacrylate) (PMMA) e-beam

resist Structures were transferred into the SiOz layer by reactive

ion etching (RIE) with CHF3 gas To improve release of the mold

after imprinting and to increase the aspect ratio of the small struc-

tures (down to 100nm), we used a monolayer of fluorsilane as

anti-adhesion layer on the mold surface

2.2 Si-nanowire process

For fabrication of the devices we used 4 in silicon-on-insulator

(SOI) wafers (SOITEC, France) with a BOX thickness of 400 nm

and a top Si layer of 360nm thickness (Si < 1002, boron doped

14-22 (22cm) The wafer carried three different layouts of nanowire

arrays (4 x 4-common source, 16 x 16 and 32 x 32-cross contacts)

The length of the wires was 3 wm in all three designs For investi-

gation of possible size effects we varied the widths of the starting

structures for wet etching by 100nm, 200nm, 500nm, and 1 wm

(mask measures), respectively In Fig 1a the layout of the 32 x 32

SiINW array and a scanning electron micrograph of a sensor spot

including six wires are shown (Fig 1b)

A schematic of the process flow is shown in Fig 2 Firstly the

top silicon layer of the SOI wafer was thinned out down to about

60 nm (Fig 2, steps 1 and 2) Then the starting structures were trans-

ferred from the mold to the 4 in SOI wafers by thermal nanoimprint

(Nanonex NX-2000, USA) (Fig 2, step 3) After imprinting, RIE was

used to etch the residual resist layer and to etch off the SiO» layer

between the contact lines (Fig 2, step 4) Then the device struc-

tures were transferred to the top Si layer by anisotropic wet etching

with TMAH (25%, 90°C) [8,9] Due to the large etch rate difference

between Si and SiOz, the Si was etched off in the regions which were

not covered by the oxide The etch rate ratio between the Si< 100>

and the Si< 11 1> directions was about 12:1 in our process Under

the oxide mask, when the wet etching process reached the < 1 1 1È

surface of the Si layer, the etching process was slowed down Fur-

ther etching slowly reduced the width of the wires under the oxide

mask (Fig 2, step 5) To maintain the surface quality of the SINWs

after TMAH etching, wire structures were protected by a 100nm

LPCVD silicon oxide This layer was further structured by optical

lithography to act as protection mask for the feed line implanta-

tion Boron ions (1 x 10'4 cm~2) were implanted on the conducting

lines with an energy of 7 keV and subsequently annealed at 900°C

for 30 min ina nitrogen atmosphere (Fig 2, step 6) After annealing,

270nm of LPCVD silicon oxide was deposited for passivation of the

contact lines against the electrolyte solution (Fig 2, step 7) The gate

areas and the bond pads were re-opened and a contact to the bulk

Si was realized as back gate contact A high quality thermal silicon

gate oxide (8 nm thickness) was grown on the wires surfaces At this

Stage the 16-channel devices were finalized by deposition of a metal

stack consisting of Al 150nm, Ti 10nm and Au 150 nm at the bond

(a)

<100>

<111

_—

Fig 1 (a) Differential interference contrast microscopy of the 32 x 32 silicon nanowire array (b) SEM image of one sensor spot with six nanowires The open- ing of the passivation layers on top of the nanowire area can be seen (c) Scanning

electron micrograph of a single silicon wire (<100 nm) One can see the Si <100È and Si 11 1È surfaces of the trapezoid wire structure

pads (Fig 2, step 8) For the 16 x 16 and 32 x 32 arrays this metal layer served as second contact line inside the grid array (Fig 1a)

To enable operation of these devices in an electrolyte solution, a nitride-oxide stack was deposited by plasma enhanced chemical vapor deposition (PECVD) (at the clean room facilities of the Uni- versity of Applied Sciences Kaiserslautern - Campus Zweibrticken, Germany) and the bond pads were re-opened

2.3 Electronic readout and detection methods For measurements in a liquid environment, devices were wire bonded on 68-pin LCC carriers (LCCO850, Spectrum, USA) and encapsulated using glass rings and a biocompatible epoxy glue

Actuators B: Chem (2009), doi:10.1016/j.snb.2008.11.048

Please cite this article in press as: X.T Vu, et al., Fabrication and application of silicon nanowire transistor arrays for biomolecular detection, Sens

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1 SOI substrate

2 Thin out of top Si |

3 Nanoimprint lithography

4 RIE etching of oxide mask

5 TMAH etching of Si

6 Contact line implantation

7 ONO passivation

8 RIE etching and lift-off

Si _ 1°

Ms sio, SN,

Mm Resist Metal

Fig 2 Main process steps for the fabrication of the SINW-FET arrays Our wafer-scale

process for SOI wafers is combining nanoimprint lithography with wet etching using

TMAH Contact lines are p-doped for reliable operation of the devices The finalized

structure in step 8 shows back gate contact, bond pad, contact line and open wire

(from left to right)

(U300 80Z, Epo-TEK, USA) (Fig 3b) Recording was done on a wafer

probe station or with our previously described 16-channel FET

amplifier system for dc and for ac readout [10-13] (Fig 3a) To record

the small currents of the SiNW-FETs in their respective working

points (about 1-10 pA), we used a 250 kQ2 feedback resistor in the

V

CL Ry, = 250 kOhm

Si-Backgate

Nanowire V,

L

Fig 3 (a) Portable, 16-channel amplifier system for SINW-FETs The electrochemical Ag/AgCl reference electrode is fixed on top of the encapsulated chip (b) Photograph

of a fully encapsulated, 16-channel SINW chip (c) Schematic principle of the readout circuit By applying a sinusoidal reference signal to the SINW-FET array, the transfer function of the system reference electrode/electrolyte solution/biomolecules/SINW- FET/first amplifier stage can be recorded using the lock-in electronics of the amplifier system

first amplifier stage (Fig 3c) For operation in a liquid environment, the gate voltage was applied via a small, liquid-junction Ag/AgCl electrode (Super Dry-Ref (SDR2), WPI, Germany) and the position

of this electrode with respect to the SiINW-FET array was fixed on top of the amplifier (see Fig 3a)

Generally, signals from biomolecular reactions at surfaces (such

as DNA hybridization or protein interaction) can be obtained either

by potentiometric dc [14-17] or impedimetric ac [10,18-21] readout It is generally accepted that for dc readout, the biomolecules are detected based on their intrinsic charge [14,15,22—26] or based

on a re-distribution of ions near the liquid-solid interface [27] When SiNW-FETs are functionalized with biomolecular receptors, specific binding of charged target molecules results in deple- tion or accumulation of charge carriers inside the SiNWs and hence in a change of the transistor’s drain-source current This

is because the resulting change in the surface charge density is shifting the flat band voltage of the transistor before and after the biomolecular adsorption process These effects were monitored in the present article by recording the transfer characteristics of the SiNW-FETs before and after biomolecule attachment and by a direct comparison of channels with biomolecules to channels without biomolecules

As a second effect, the biomolecular layer on the surface of the SiNWs is acting as an additional, passive RC element inside

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the readout circuit (resistance Rmem and capacitance Cmem of the

biomembrane in Fig 3c) The DNA hybridization reaction or the

protein binding is leading to a change of the input impedance of

the device This change can be accessed by using an impedimetric

readout method utilizing the transistor transfer function (TTF) prin-

ciple [10,11,18,20,21 ] For this detection method the combination of

sensor, its first amplification circuit with feedback resistor Rep, the

reference electrode resistance Rpr, the liquid solution resistance

Rcoj, the contact line capacitance Cc,, the gate oxide capacitance

Cox, and the resistance Rmem and capacitance Cmem of an attached

biomolecular membrane are regarded as an electronic circuit of

passive elements Such a circuit can be well described by a transfer

function H It is defined by the ratio of the output voy; to the input

voltage v;, of the amplifier H = voy /Vjn (Fig 3c) The parameter H is

dimensionless and simply describes the attenuation of the system

at a specific frequency

2.4 Covalent attachment of biomolecules on SiNW-FETs

For covalent immobilization of DNA molecules, the chips were

cleaned and activated in a protocol including both wet chemical and

plasma cleaning Firstly the chips were immersed for 20 min in 2%

Hellmanex (Hellma, Germany) followed by rinsing with ultra pure

water (Milli-Q, Gradient A10 18.2 MQ, Millipore Inc., Germany) and

drying with Argon The final activation of the silicon oxide surface

was done in oxygen plasma (100E Plasma System from Techniques

Plasma GmbH, 1.4 mbar, 200 W, and 1 min) For biofunctionaliza-

tion of the wire surfaces, we used a vapor phase silanization

protocol with 3-glycidoxypropyltrimethoxysilane (GPTES) [28,29]

The chips were placed in a desiccator containing a few drops of

Silane (300 wl) The desiccator was sealed, heated and the reac-

tion was allowed for 1h The complete silanization procedure was

performed inside a glove box containing a water- and oxygen-free

argon atmosphere The silanization procedure was finalized by rins-

ing several times with ultra pure water in order to remove unbound

silane molecules Finally all samples were dried with argon For

micro-spotting with our single-nozzle system with aiming option

[13], the amino-modified 20 base-pair (bp) DNA probes (MWG-

Biotech AG, Germany) were prepared in a concentration of 1 wM in

a 0.1 M phosphate buffer of pH 8.5 After micro-spotting, the immo-

bilization process was performed by overnight incubation at 37°C

in a humid atmosphere

For covalent immobilization of biotin to the SINW-FETs, the chip

surface was functionalized with 3-aminopropyl-triethoxysilane

(APTES) [30-32] Chips were wet-chemically cleaned in three steps

including ethanol for 2 min, HCl (2%, v/v) for 2 min, and piranha

solution for 2 min The chip surfaces were then activated by H2SO,

(20% (v/v), 80°C for 10 min) After each step, the chips were carefully

rinsed with ultra pure water and dried with argon For silaniza-

tion the chips were transferred to the glove box containing an

argon atmosphere Silanization with APTES was performed for 1h

inside a desiccator, too A drop of pure APTES (300 wl) was placed

inside the desiccator and the whole system was evacuated The

pressure of the desiccator was controlled at p=5 mbar residual

argon gas After silanization the chips were firstly rinsed with 1%

acetic acid and then rinsed with ultra pure water and dried with

argon [30] The EZ-Link Sulfo-NHS-LC-Biotin (sulfosuccinimidyl-

6-(biotinamido)hexanoate; Pierce Biotechnology, Inc., USA) with a

concentration of 1 ~M (1 mg/1.5 ml) was dissolved in sodium phos-

phate buffer (2.5 mM, pH 8.2) This biotin solution was spotted on

the SINW areas using our micro-spotter [13,33] Then the chips were

incubated for 1h at 37°C in a humid environment After that the

chips were rinsed with ultra pure water in order to remove unbound

biotin This protocol binds the biotin molecules covalently to the

silicon oxide surfaces

3 Results and discussion 3.1 Process characterization During the fabrication process of the SINW arrays imaging ellip- sometry, scanning electron microscopy, and optical microscopy were used for process control By the use of thermal nanoimprint in combination with the TMAH wet etching, the nanowire structures were reliably transferred to the full area of the 4in SOI wafers The imprint process was reproducible with a high aspect ratio of the structures The imprint-mold was very stable and was re-used many times However, due to the complexity of the structures, the residual resist layer after nanoimprint was not homogenous There- fore the RIE etching of this residual layer was strictly controlled to maintain the high aspect ratio of the structures

The anisotropic TMAH etching created a trapezoidal SINWSs

structure having Si < 111> sidewalls in an angle of 54.7° with <

1002 top and bottom surfaces (Fig 1c) By further etching, the size

of the top and bottom < 1 00> planes will be slowly reduced under

the top oxide mask The etching rate for the Si < 11 1> direction

was about 20nm/min for our process Using this process SiNWs with very smooth surfaces were achieved (Fig 1c) Since the contact lines of our chips were passivated by a high quality LPCVD oxide,

a reliable performance in electrolyte solution was achieved Addi- tionally, our chips can be re-used for many experiments by the use

of a standard cleaning protocol [30,31,33]

V = 0.5V

ls (HA)

|(A) 1 p ' T ' T ' T

Veo (V)

Fig 4 When the contact lines of the SINW-FET array are additionally implanted by boron, a reliable p-FET operation of the wires can be achieved (a) Transfer characteristics of a SINW-FET with p-doped contact lines (b) Subthreshold characteristics

of a SINW-FET

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4 DH nai pH, „ Vf

——— pH 10

24 pH 6

-pH 5

— pH 4

4-

V„(V)

p small -—> pH

Ved)

large

Fig 5 Characterization of the pH sensitivity of the SINW-FETs (six wires of 400 nm

width per sensor spot) (a) When the silicon contact lines of the wires are not

implanted by boron, an n-FET behavior is achieved The usage of different pH buffer

solutions is shifting the threshold voltage of the transistors as indicated in the graphs

(b) When we use an implantation of the contact lines, exclusively a p-FET behavior is

achieved With different pH buffer solutions the threshold voltage shifts are accord-

ingly Note that in the graphs both, forward and backward bias sweeps are shown

indication almost no electronic hysteresis

[NaCl],,,.,4—— small > [NaCl] large

Frequency (Hz)

Fig 6 Transfer function characteristics of the SINW-FETs with different NaCl con-

centrations of the electrolyte buffer The behavior is quite similar to what we usually

achieve with our standard, micro-sized FET arrays

3.2, Electrical and electrochemical characterization

We previously described that the performance of our SINW-FETs inside an electrolyte solution with front-gate operation is dependent on the implantation status of the silicon contact lines In Fig 4 the electronic performance of a SINW-FET with implanted contact lines is shown Fig 4a shows the transfer characteristics and Fig 4b the subthreshold characteristics of the device The wires can clearly be operated as p-type transistors and the subthreshold slope was as small as 85mV/decade for the best devices

In Fig 5a comparison of a device with and without implanted contact lines is shown We characterized the pH sensitivity of both device types using titrisol buffer solutions between pH 2 and 10 The gate voltage was applied via the front-gate using the liquid-junction Ag/AgCl reference electrode In Fig 5a the n-FET characteristics

of a device with non-implanted contact lines is shown Note that

in both graphs of Fig 5 the data for forward and backward bias sweeps are shown Both device types show almost no electronic hysteresis indicating a small density of trapped charges inside the structure In previous version of these chips, when we used RIE etching in contrast to the TMAH etching, the wire surfaces were much rougher resulting in a strong electronic hysteresis (data not

(a)

no DNA

—: before DNA immoblization : after DNA immoblization

14 VINA _ -

Od xay cc==ntzee

immoblization

46 T T

Veg (VY)

Fig 7 Detection of immobilized DNA on the SiINW-FETs Transfer characteristics before (solid lines) and after DNA immobilization (dashed lines) are shown DNA was site-selectively immobilized on some channels out of the same array using a micro-spotter (a) One channel out of the same array having no DNA attached (b) Another channel out of the same array having 20-bp DNA attached with a high grafting density For the DNA-modified sensor a shift of 250 mV of the flat band voltage was recorded

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shown) For our current device types the transfer characteristics

was shifting to the left side for smaller pH values and to the

right side for larger pH values independent if p-type or n-type

devices were used The sensitivity in both cases was measured

to 38-41 mV/pH, which is a typical value for silicon oxide sur-

faces

With our lock-in based amplifier system the SiNW-FET devices

can also be used as impedimetric sensors like recently reported

with our standard, micro-sized FETs [10,11] In Fig 6 the trans-

fer characteristics of a SINW-FET in buffer solutions with different

concentrations of NaCl (pH 7) is shown Similar to what we previ-

ously reported for our micro-sized FETs, the transfer characteristics

is shifting, because the solution resistance R,,; in the electronic cir-

cuit is changing The time constant for this low pass is build out

of solution resistance R.9; plus reference electrode resistance RrE

in combination with the contact line capacitance Cc, (Fig 3c) In

future we will elaborate, if the previously described TTF method

for detection of DNA [10] and of cellular adhesion [11] can also be

used with our new SiNW-FET devices

3.3 Electronic detection of biomolecules

In Fig 7 the potentiometric detection of a covalently immo-

bilized DNA layer on top of the SiNWs is shown In Fig 7a an

exemplary molecule-free channel is shown, whereas the attach-

ment of the dense DNA layer was shifting the flat band voltage of

the SiNW-FET channel (six wires with 160 nm wire width in this

-1,2

AV=-33mV

Vic (V)

Fig 8 Detection of covalently immobilized biotin with the SINW-FET arrays Trans-

fer characteristics before (solid lines) and after biotin functionalization (dashed

lines) are shown Biotin was site-selectively immobilized on some channels out of the

same array using a micro-spotter (a) SINW-FET channel having no biotin attached

(b) SINW-FET channel of the same sensor array having biotin attached In this case

a flat band voltage shift of 33 mV was recorded

exemplary recording) by 250 mV This behavior was confirmed with several devices and many channels showed a similar shift The flat band voltage shift was very large compared to what we previously reported for the micro-sized FET devices [14,31,33] For this measurement a sodium phosphate buffer (5mM, pH 7) was used as electrolyte solution

In Fig 8a similar experiment for detection of biotin with the SiNW-FET arrays is shown In the biomolecular-free channels a minor shift was recorded, whereas in the channels spotted with biotin a shift of 33 mV was recorded (Fig 8b) For this measurement

a sodium phosphate buffer (2.5 mM, pH 8.2) was used as electrolyte solution Again with several chips containing many channels a similar, reliable behavior was observed

4 Conclusions

We present a robust, wafer-scale fabrication process for SINW transistor arrays With a combination of nanoimprint and TMAH wet anisotropic etching, we produced smooth surfaces for the SINW transistors We achieved a wire width down to 20nm on top and

100 nm at the bottom of the trapezoid nanowire structure having

a height of about 6Onm In future designs the width of the wire could be even reduced using longer etching times or a thinner start layer The devices were successfully operated in a liquid environment in different kinds of electrolyte solutions SINW-FETs with their silicon oxide surface had a linear pH response with a typical sensitivity of about 40 mV/pH The electronic performance was stable and forward and backward bias sweeps of the transfer characteristics revealed almost no hysteresis When applying the TTF method, we showed that the devices are sensitive to different ionic strengths of the buffer electrolyte similarly to what we previously reported for our micro-sized FET arrays For biomolecular experiments the devices were silanized with either APTES or GPTES using our standard protocols We present first biomolecular detection experiments with the SiNW-FET arrays, where we site-selectively and covalently attached single-stranded DNA molecules and biotin molecules at the wire surfaces In the case of DNA we recorded

a very large shift of the flat band voltage of 250 mV For biotin a smaller, but still large shift of 33 mV was measured

With this device platform and this protocol for biofunctionaliza- tion of the wire surfaces we are now ready for real bioassays such

as DNA hybridization or protein binding With our current amplifier system capable of simultaneous de and ac readout we want to unravel size scaling effects and mechanisms of biomolecular field- effect detection in future assays

Acknowledgments

We thank the German Research Foundation for the financial support through the project “Biointerface—GRK 1035” Main parts

of the funding came from the Helmholtz association of German research centers We like to thank K.H Deusen, W Michelsen and H.P Bochem for LPCVD deposition, ion implantation and SEM measurements, respectively We also thank N Wolters and D Lomparski for the electronic readout system and its operation software

References [1] X.H Wang, Y Chen, K.A Gibney, S Erramilli, P Mohanty, Silicon-based nanochannel glucose sensor, Appl Phys Lett 92 (1) (2008)

[2] E Stern, J.K Klemic, D.A Routenberg, P.N Wyrembak, D.B Turner-Evans, A.D Hamilton, D.A LaVan, T.M Fahmy, M.A Reed, Label-free immunodetection with CMOS-compatible semiconducting nanowires, Nature 445 (7127) (2007) 519-522

[3] Z.Q Gao, A Agarwal, A.D Trigg, N Singh, C Fang, C.H Tung, Y Fan, K.D Bud- dharaju, J.M Kong, Silicon nanowire arrays for label-free detection of DNA, Anal Chem 79 (9) (2007) 3291-3297

Trang 7

[4] Y Cui, QQ Wei, H.K Park, C.M Lieber, Nanowire nanosensors for highly sen-

sitive and selective detection of biological and chemical species, Science 293

(5533) (2001) 1289-1292

[5] F Patolsky, G.R Zheng, O Hayden, M Lakadamyali, X.W Zhuang, C.M Lieber,

Electrical detection of single viruses, Proc Natl Acad Sci U.S.A 101 (39) (2004)

14017-14022

[6] F Patolsky, B.P Timko, G.H Yu, Y Fang, A.B Greytak, G.F Zheng, C.M Lieber,

Detection, stimulation, and inhibition of neuronal signals with high-density

nanowire transistor arrays, Science 313 (5790) (2006) 1100-1104

[7] LJ Guo, P.R Krauss, S.Y Chou, Nanoscale silicon field effect transistors fabri-

cated using imprint lithography, Appl Phys Lett 71 (13) (1997) 1881-1883

[8] Y.X Liu, K Ishii, T Tsutsumi, M Masahara, E Suzuki, Ideal rectangu-

lar cross-section Si-Fin channel double-gate MOSFETs fabricated using

orientation-dependent wet etching, IEEE Electron Device Lett 24 (7) (2003)

484-486

K Sato, M Shikida, T Yamashiro, K Asaumi, Y Iriye, M Yamamoto, Anisotropic

etching rates of single-crystal silicon for TMAH water solution as a function of

crystallographic orientation, Sens Actuators A: Phys 73 (1-2) (1999) 131-137

[10] S Ingebrandt, Y Han, F Nakamura, A Poghossian, M.J Sch6ning, A Offen-

hdusser, Label-free detection of single nucleotide polymorphisms utilizing the

differential transfer function of field-effect transistors, Biosens Bioelectron 22

(12) (2007) 2834-2840

[11] S Schafer, S Eick, B Hofmann, T Dufaux, R Stockmann, G Wrobel, A

Offenhäusser, S Ingebrandt, Time-dependent observation of individual cel-

lular binding events to field-effect transistors Biosens Bioelectron., in press,

doi: 10.1016/J.bios.2008.1007.1003

[12] X.T Vu, J.F Eschermann, R Stockmann, R GhoshMoulick, A Offenhdusser, S

Ingebrandt, Top-down processed silicon nanowire transistor arrays for biosens-

ing Phys Status Solidi A: Appl Mater., in press

[13] S Ingebrandt, Y.H Han, M.R Sakkari, R Stockmann, O Belinskyy, A Offen-

hdusser, Electronic detection of nucleic acid molecules with a field-effect

transistor, in: Semiconductor Materials for Sensing, Warrendale, USA, 2005,

pp 307-312

[14] F Uslu, S Ingebrandt, D Mayer, S Bocker-Meffert, M Odenthal, A Offenhdusser,

Labelfree fully electronic nucleic acid detection system based on a field-effect

transistor device, Biosens Bioelectron 19 (12) (2004) 1723-1731

[15] J Fritz, E.B Cooper, S Gaudet, P.K Sorger, S.R Manalis, Electronic detection of

DNA by its intrinsic molecular charge, Proc Natl Acad Sci U.S.A 99 (22) (2002)

14142-14146

[16] E Souteyrand, J.P Cloarec, J.R Martin, C Wilson, I Lawrence, S Mikkelsen, M.F

Lawrence, Direct detection of the hybridization of synthetic homo-oligomer

DNA sequences by field effect, J Phys Chem B 101 (15) (1997) 2980-2985

[17] B.S Kang, S.J Pearton, J.J Chen, F Ren, J.W Johnson, R.J Therrien, P Rajagopal,

J.C Roberts, E.L Piner, K.J Linthicum, Electrical detection of deoxyribonucleic

acid hybridization with AlGaN/GaN high electron mobility transistors, Appl

Phys Lett 89 (12) (2006) 122102

[18] M.M.G Antonisse, B.H.M Snellink-Ruel, R.J.W Lugtenberg, J.FJ Engbersen, A

van den Berg, D.N Reinhoudt, Membrane characterization of anion-selective

CHEMFETs by impedance spectroscopy, Anal Chem 72 (2) (2000) 343-348

[19] E Katz, I Willner, Probing biomolecular interactions at conductive and semi-

conductive surfaces by impedance spectroscopy: routes to impedimetric

immunosensors, DNA-sensors, and enzyme biosensors, Electroanalysis 15 (11)

(2003) 913-947

[20] A.B Kharitonov, J Wasserman, E Katz, I Willner, The use of impedance spec-

troscopy for the characterization of protein-modified ISFET devices: application

of the method for the analysis of biorecognition processes, J Phys Chem B 105

(19) (2001) 4205-4213

[21] R.B.M Schasfoort, G.J Streekstra, P Bergveld, R.P.H Kooyman, J Greve, Influ-

ence of an immunological precipitate on Dc and Ac behavior of an Isfet, Sens

Actuators 18 (2) (1989) 119-129

[22] D Landheer, G Aers, W.R McKinnon, MJ Deen, J.C Ranuarez, Model for the

field effect from layers of biological macromolecules on the gates of metal-

oxide-semiconductor transistors, J Appl Phys 98 (4) (2005)

[23] D Landheer, W.R McKinnon, W.H Jiang, G Aers, Effect of screening on the

sensitivity of field-effect devices used to detect oligonucleotides, Appl Phys

Lett 92 (25) (2008)

[24] M.W Shinwari, MJ Deen, D Landheer, Study of the electrolyte-insulator-

semiconductor field-effect transistor (EISFET) with applications in biosensor

design, Microelectron Reliab 47 (12) (2007) 2025-2057

[25] D Landheer, W.R McKinnon, G Aers, W Jiang, M.J Deen, M.W Shinwari, Calcu-

lation of the response of field-effect transistors to charged biological molecules,

IEEE Sens J 7 (9-10) (2007) 1233-1242

[26] W.R McKinnon, D Landheer, Sensitivity of a field-effect transistor in detecting

DNA hybridization, calculated from the cylindrical Poisson-Boltzmann equa-

tion, J Appl Phys 100 (5) (2006)

[27] A Poghossian, A Cherstvy, S Ingebrandt, A Offenhdausser, MJ Schéning, Pos-

sibilities and limitations of label-free detection of DNA hybridization with

field-effect-based devices, Sens Actuators B: Chem 111 (2005) 470-480

[28] C.Consolandi, B Castiglioni, R Bordoni, E Busti, C Battaglia, LR Bernardi, G De

Bellis, Two efficient polymeric chemical platforms for oligonucleotide microar-

ray preparation, Nucleos Nucleot Nucleic Acids 21 (8-9) (2002) 561-580

[29] J Piehler, A Brecht, R Valiokas, B Liedberg, G Gauglitz, A high-density

poly(ethylene glycol) polymer brush for immobilization on glass-type surfaces,

Biosens Bioelectron 15 (9-10) (2000) 473-481

[9

[30] Y Han, D Mayer, A Offenhdusser, S Ingebrandt, Surface activation of thin silicon oxides by wet cleaning and silanization, Thin Solid Films 510 (1-2) (2006) 175-180

[31] Y.Han, A Offenhausser, S Ingebrandt, Detection of DNA hybridization by a field- effect transistor with covalently attached catcher molecules, Surf Interf Anal

38 (4) (2006) 176-181

[32] R GhoshMoulick, X.T Vu, S Gilles, D Mayer, A Offenhdusser, S Ingebrandt, Impedimetric detection of covalently attached biomolecules on field-effect transistors Phys Status Solidi A: Appl Mater., in press

[33] S Ingebrandt, A Offenhdusser, Label-free detection of DNA using field-effect transistors, Phys Status Solidi A: Appl Mater 203 (14) (2006) 3399-3411

Biographies

Xuan Thang Vu was born in Thaibinh, Vietnam, in 1979 He graduated from the College of Science, Vietnam National University, Hanoi, in 2001 with a B.Sc degree

in Materials Science In 2003 he received a M.Sc degree in Materials Science at the International Training Institute for Materials Science (ITIMS), Hanoi University of Technology (HUT), Vietnam From 2003 to 2006 he was working as research assistant

at ITIMS Since 2006 he is working as Ph.D student at the RWTH-Aachen Univer- sity, Aachen, Germany and at the Institute of Bio- and Nanosystems (IBN), Institute 2: Bioelectronics, at the Forschungszentrum Jiilich, Germany His current research interests are SiNW transistor array design and fabrication for biosensor applications and for electronic detection of biomolecules

Ranjita Ghosh Moulick was born in India, near Kolkata, in 1976 She studied Chem- istry and Biochemistry for her Bachelor and Master Degree, respectively In 2007 she received her Ph.D in Biochemistry from the Calcutta University on the topic ‘Fold- ing and aggregation pattern of glycosylated hemoglobin’ Currently she is working

as a postdoctoral fellow in the Institute of Bio- and Nanosystems (IBN), Institute 2: Bioelectronics, at the Forschungszentrum Jiilich, Germany Her current research topics are covalent immobilization of biomolecules on oxidic sensor surfaces and electronic detection of biomolecules with field-effect devices

Jan Felix Eschermann was born in Friedrichshafen, Germany, in 1980 He graduated

in electrical engineering at the Technical University Munich, Germany in 2006 Dur- ing his master thesis he was working as a visiting scholar at the Beckman Institute in Urbana-Champaign, IL, USA Since 2006 he is working as Ph.D student at the RWTH- Aachen University, Aachen, Germany and at the Institute of Bio- and Nanosystems (IBN), Institute 2: Bioelectronics, at the Forschungszentrum Jiilich, Germany His current research interests are SiNW transistor array design, fabrication and simulation for bioelectronic applications and extracellular recording from electrogenic cells Regina Stockmann was born in Aachen, Germany, in 1969 She graduated in Applied Chemistry at the Aachen University of Applied Sciences in 1996 After years of experience in clean room processing she joined in 2002 the Institute of Bio- and Nanosystems (IBN), Institute 2: Bioelectronics, at the Forschungszentrum Jiilich, Germany From then on her main focus was on optimizing semiconductor chips

to achieve better sensors for bioelectronic measurements Her current interests are silicon nanowire design, fabrication and optimization for biosensor applications Andreas Offenhdausser was born in Heidenheim, Germany in 1959 He graduated

in physics (Diplom) from the University of Ulm in 1985 and completed a Ph.D at the University of Ulm in 1989 From 1990 to 1992 he worked as an engineer at Robert Bosch GmbH, Reutlingen From 1992 to 1994 he joined the Frontier Research Program, RIKEN, Japan From 1994 to 2001 he worked at the Max Planck Institute for Polymer Research, Mainz, as a group leader In 2000 he received his “habilitation” He moved to the Forschungszentrum Jiilich in 2001 where he is presently director of the Institute of Bio- and Nanosystems (IBN), Institute 2: Bioelectronics He is a professor for experimental physics at the RWTH-Aachen University, Germany The focus of his work is the functional coupling of sensory cells and neurons with microelectronic devices, signal processing in biological neuronal networks, electronic DNA-Chip, and biophysics of lipid bilayers and membrane receptors

Sven Ingebrandt was born in Alzey, Germany, in 1971 He graduated in physics (Diplom) in 1998 at the Johannes Gutenberg University Mainz, Germany From 1998

to 2001 he was working as Ph.D student at the Max Planck Institute for Polymer Research in Mainz, Germany He received his Ph.D degree in physical chemistry in

2001 from the Johannes Gutenberg University Mainz, Germany In 2001 and 2002

he was working as postdoctoral researcher at the Frontier Research Program, RIKEN, Japan From 2002 to 2008 he was working as group leader in the Institute of Bio- and Nanosystems (IBN), Institute 2: Bioelectronics, at the Forschungszentrum Jiilich, Germany Recently he moved to the Kaiserslautern University of Applied Sciences as

a professor of Biomedical Engineering Currently he is still leading a research group

in Julich elaborating topics such as cell-sensor coupling, whole-cell biosensors and electronic field-effect based sensors for biomolecular detection His main interests are micro- and nanochip design and fabrication for bioelectronic applications and bioelectronic signal recording and interpretation

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