Letter pubs.acs.org/NanoLett
Enhanced Sensing of Nucleic Acids with Silicon Nanowire Field Effect Transistor Biosensors Anran Gao,†,∥ Na Lu,†,§,∥ Yuchen Wang,‡ Pengfei Dai,† Tie Li,*,† Xiuli Gao,† Yuelin Wang,*,† and Chunhai Fan*,§ †
State Key Laboratories of Transducer Technology and Science and Technology on Micro-system Laboratory, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China ‡ Department of Microelectronics, Peking University, Beijing 100871, China § Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China S Supporting Information *
ABSTRACT: Silicon nanowire (SiNW) field effect transistors (FETs) have emerged as powerful sensors for ultrasensitive, direct electrical readout, and label-free biological/chemical detection. The sensing mechanism of SiNW-FET can be understood in terms of the change in charge density at the SiNW surface after hybridization. So far, there have been limited systematic studies on fundamental factors related to device sensitivity to further make clear the overall effect on sensing sensitivity. Here, we present an analytical result for our triangle cross-section wire for predicting the sensitivity of nanowire surface-charge sensors. It was confirmed through sensing experiments that the back-gated SiNW-FET sensor had the highest percentage current response in the subthreshold regime and the sensor performance could be optimized in low buffer ionic strength and at moderate probe concentration. The optimized SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of target DNA with a detection limit of 0.1 fM and high specificity for single-nucleotide polymorphism discrimination. In our work, enhanced sensing of biological species by optimization of operating parameters and fundamental understanding for SiNW FET detection limit was obtained. KEYWORDS: SiNW-FETs, biosensor, ultrasensitive, detection limit
U
concluded that detection in the subthreshold regime of NW FET sensor has much improved the conductance response and better detection limit. However, yet to date there have been limited systematic studies and experimental data on factors related to the sensing sensitivity of field effect based device. In order to further make clear the overall effect on detection sensitivity, obtain a sensitivity enhancement, and the fundamental understanding on detection limit, we present a theoretical analysis to estimate the change in signal, that is, device sensitivity of a nano-FET sensor upon binding its target molecules. Various parameters including the gate voltage, probe concentration, and buffer ionic strength, which are critical considerations for designing optimal protocols for label-free sensing using SiNW-FETs, were studied. The high quality nanowires with high aspect ratio and good tunable electrical properties fabricated by a novel complementary metal oxide semiconductor (CMOS) compatible approach were used. By employing the optimal factors, the SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of
ltrasensitive detection of biological and chemical species is critical to many areas, including the disease diagnosis,1 drugs discovery,2 and biomolecular analysis.3,4 Semiconducting nanowire field effect transistor (FET),1,5,6 one of the most promising platforms for unlabeled sensing, is emerging as powerful sensors for recognizing a wide range of biological and chemical species7 with many attractive properties including low cost, ultrahigh sensitivity, direct electrical readout, and multiplexed detection.8−10 The sensing mechanism for a silicon nanowire (SiNW) biosensor operated as an FET is charged molecule-induced field effect on the carrier conduction inside the nanowires.10,11 The enhanced sensitivity of nanodevices capable of sensing the presence of even a small quantity of charged species by their intrinsic charge is mainly due to their comparable size to molecules and larger surface/volume ratio.12 Therefore it is natural to expect that the highest sensitivity should be achieved when the whole volume of the nanodevice is gated by the charged species. This charge sensitivity is affected by many factors such as SiNW size,12 Debye screening,13 surface chemistry,10 charge layer distance from SiNW surface,14 and so on. Gao et al.11 have given a pioneering and creative study addressing how the fundamental factors of the device affect their sensitivity and © 2012 American Chemical Society
Received: July 4, 2012 Revised: September 12, 2012 Published: September 17, 2012 5262
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target DNA with a detection limit of 0.1 fM and high specificity for single-nucleotide polymorphism discrimination. Results and Discussion. In nanoelectronics, semiconducting nanowires can be fabricated either by “bottom-up”15 or “top-down”16,17 methods. Compared with bottom-up approach, which suffers from a complicated integration issue, the topdown nanowires have attracted great interest due to their mass manufacturing ability and high controllability.9,18,19 In this work, the semiconducting nanowires were top-down fabricated by applying a novel CMOS compatible anisotropic wet etching approach. Conventional optical lithography20 was combined with anisotropic wet etching by tetramethylammonium hydroxide (TMAH), which etches Si (111) planes 100 times slower than other planes, instead of using expensive electron beam lithography. This approach allows retention of pattern definition and smooth edge imperfections not aligned to the (111) plane,9 an effect that overcomes the limitations of traditional manufacturing methods.21 The homogeneous arrays of SiNW with triangular cross-section and large surface-tovolume-ratios were finally fabricated with low cost, high controllability, and reproducibility.22 The fabricated triangular SiNWs are smooth and well-ordered with small size (shown in Figure S1, Supporting Information), as well as have dominant Si(111) exposed planes, which is the preferred surface for surface functionalization.23 Following Gao’s11 work, we would like to present a more systematic study on device sensitivity of a nano-FET sensor upon binding its target molecules to further make clear the overall effect of various specific parameters on detection sensitivity and obtain a sensitivity enhancement. For a theoretical study on device sensitivity, the theory used before11,24 assumes a cylindrical nanowire of radius R by a cylindrical sheet of charge at distance l from the nanowire surface. In our case, the nanowires with triangle cross-section are used. Thus, we model the nanowire FET as a triangular prism with one side on top of the substrate and the other two sides for charged molecule gating effect (Figure 1). The
ΔID 2 4h2 + w 2 =− Ns ID,0 qwhn0
(1)
where w, h, and L are the nanowire width, thickness, and length, respectively; n0 is the initial carrier concentration; q is the elementary charge; and Ns is surface density of bound species. Noe that h = 0.706w due to the etching defined angle ∼54.7°. Following Sørensen et al.,24 the current change of a nanowire is due to a surface charge density directly on (σs) and at a distance l from (σb), the nanowire surface. We modified the sensitivity expression as ΔID 2 4h2 + w 2 =− Γ(Γlσb + σs) ID,0 qwhn0
(2)
Here Γ is a dimensionless function quantifying the actual sensitivity of the nanowire, which scales with the electron 24 density n0 as n1/3 0 in the dilute limit. And Γl is a dimensionless function quantifying the effect of σb. When the nanowire diameter is much larger than the distance from nanowire surface to surface charge density, it is given by25 −1 ⎡ ⎛ l ⎞⎤ Γl ≈ 2⎢1 + exp⎜ ⎟⎥ ⎢⎣ ⎝ λD ⎠⎥⎦
(3)
where λD is the solution Debye screening length. Consequently, these equations yield ⎫ ⎡ ⎛ l ⎞⎤ ⎪ ⎪ ΔID 2 4h2 + w 2 ⎧ ⎢ ⎥ ⎬ ⎨ σ σ = + + 2 1 exp ⎜ ⎟ b s⎪ 2/3 ⎪ ID,0 ⎝ λD ⎠⎥⎦ qwhn0 ⎭ ⎩ ⎢⎣
(4)
Equation 4 clearly demonstrates the tunability of the device sensitivity using nanowire size, initial carrier concentration, that is, gate voltage, Debye length, and surface charge density. Compared with the expression of highest sensitivity of a nanosensor obtained in ref 11, this result is more meaningful to characterize the sensitivity of a NW-FET sensor. It makes the overall effect of specific parameters on detection sensitivity more clear and gives critical considerations for better detection limit. The n-type, phosphorus-doped SiNW FETs were employed in this work. The transfer curve of our SiNW device yielded typical gate modulation of n-type devices, demonstrating excellent field effect property (Figure S2a, Supporting Information). The nanowire device allows field-effect control of surface charges on the nanowires sensing by controlling the accumulation and depletion of charge carrier with back-gate. In the IDS/VGS plot, where IDS depends exponentially on the back gate voltage VGS is known as the “subthreshold regime” in semiconductor device physics terminology.26 Column plot of subthreshold regime of a batch of SiNWs is shown in Figure S2b (Supporting Information), demonstrating the high reproducibility. Thirty-three nanowires were used for the measurement in total with smaller gate voltage step ∼0.5 V by sweeping VGS from −20 to 20 V. The back-gate controlled field effect on device sensitivity was first studied through pH sensing experiment. A conventional SiNW can act as a pH sensor with naturally occurring silanol (Si−OH) groups on nanowire surface, which undergo protonation/deprotonation reactions. In this process, surface charges change on SiNW surface, which in turn changes device current. Plots of SiNW current change versus time for real-time pH sensing show that the pH sensor is stable and reliable
Figure 1. Schematic of backgated triangle cross-sectional SiNW of width w, thickness h, and length L. The nanowire is yellow, the oxide is blue, and the backgate is gray.
sensitivity of the nano-FET sensor upon binding its target molecule is estimated. A surface charge density Ns will perturb the initial carrier concentration n0 in the nanowire by Δn, thus changing the initial current ID,0 by ΔID.The device sensitivity is derived as the following expression (see Supporting Information) 5263
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Figure 2. (a) Plots of normalized current change for real-time pH sensing for VDS = 1 V and VGS = −1 (subthreshold regime), 7, and 12 V. (b) Current of nanosensor as a function of pH value at V GS = −1, 7, and 12 V.
(Figure S3, Supporting Information). Figure 2a shows the normalized current versus time data as 10 mM phosphate buffer solutions with pH 5, 7, and 9 were sequentially delivered onto the SiNW sensor surface at different gate voltage. At higher pH, deprotonation of silanol groups at SiO2 surface makes the SiNW surface more negatively charged, inducing a negative surface potential at SiNW surface and thus decreasing the current of a n-type nanowire. Three sets of gate voltages are −1, 7, and 12 V. It is drawn out from the transfer characteristic curve that the device is at subthreshold regime when VGS = −1 V at which the most distinct current change was observed. We further studied the nanowire pH-sensor by plotting ΔIDS/I0 versus pH value curve in Figure 2b. We can see that the device is more negatively charged at higher pH and the relative current change is most obvious at subthreshold regime. The experimental result that the SiNW-FET sensor has the highest percentage conductance response in subthreshold regime is in good accordance with results reported before.11 In addition to this reported principle, the effect of surface chemistry, probe concentration, and buffer ionic strength, which are critical considerations for designing optimal protocols for label-free sensing using SiNW-FETs ,was also studied in this work. The SiNW surface underwent the same functionalization process as described before22 to employ the nanodevice for DNA detection. The transfer characteristic of a device was characterized before and after surface functionalization to study the effect of surface chemistry on device properties. The dependence of IDS on VDS for varying VGS for a representative device before and after surface functionalization is shown in Figure S4a,b (Supporting Information). The IDS/VDS curves show clear accumulation-mode of n-type device. We can obtain from the two figures that device functionalization with 3aminopropyltriethoxysilane (APTES), which converts silanol (Si−OH) groups to free amines, does have some effect on device performance. A small increase in IDS for the n-type device suggests the presence of a small parallel current path through the surface. A comparation of IDS/VGS curves for the same device before and after functionalization (Figure S4c, Supporting Informantion) indicates the surface chemistry effect more clearly. A larger subthreshold slope for modified nanowire sensor indicates more sensitive performance in subthreshold regime. We then employed the n-type SiNW-FET device to electrically detect DNA hybridization. The sequences of the capture probe DNA and the target DNAs are listed in Table 1. Capture probe DNA with the terminal carboxyl group was
Table 1. Sequences of Capture Probe DNA and Target DNAs DNAs probe fully cDNA one-base mismatched target DNA two-base mismatched target DNA three-base mismatched target DNA
sequences 5′-HOOC-CAC GAC GTT GTA AAA CGA CGG CCA G-3′ 5′-CTG GCC GTC GTT TTA CAA CGT CGT G-3′ 5′-CTG GCC GTC GTT CTA CAA CGT CGT G-3′ 5′-CTG GCC GTC GTT CCA CAA CGT CGT G-3′ 5′-CTG GCC GTC GTG CCA CAA CGT CGT G-3′
conjugated to the amine of the APTES-modified SiNWs, with the help of N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3dimethylaminopropyl) carbodiimide (EDC). The change of SiNW characteristics after different treatment was studied and thus further elucidated the field-effect of the SiNWs. Upon exposure to different buffer solutions, the output IDS/VDS characteristic curves of the device are modified as shown in Figure 3a. The insets show electrostatic charge environment of SiNW with nothing in the presence of single-stranded DNA (ssDNA) and in the presence of double-stranded DNA (dsDNA). A clear representation of the process is demonstrated by plotting the effective resistance of the nanowire (Figure 3b). Compared to the blank SiNW, a significant increase in resistance was observed immediately upon the introduction of DNA capture probe on SiNW surface. Further hybridization of cDNA to the SiNW produced a substantial increase in SiNW resistance, implying that the build up of an electrical field after the hybridization of DNA at SiNW surface is indeed responsible for the observed resistance change.27 This effect is consistent with those previously noted on other semiconductor nanowire devices,28 including SiNW devices,5 and is essentially the mechanism of semiconductor nanowire biosensor. The probe surface density on which the hybridization efficiency between probe and target DNA depends is highly related to the change of surface charge density after the target molecule bounded. The probe surface density was optimized to obtain the maximum percentage change in SiNW current with hybridization for the development of an ultrasensitive DNA biosensor. The SiNWs used are n-type, phosphor-doped with length of 16 μm. In order to ensure that DNA charges are not significantly screened by counterions, we carefully chose 0.1× phosphate buffered saline (PBS, 137 mM NaCl, 2.7 mM KCl, 5264
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Figure 3. (a) The I−V characteristics of the same SiNW after different treatment. The insets show electrostatic charge environment of SiNW with nothing, in the presence of ssDNA and in the presence of dsDNA. (b) Resistance of SiNW after different treatment. (1) A blank SiNW, (2) SiNW with DNA capture probe, (3) SiNW with DNA capture probe after hybridized with 10 nm cDNA.
Figure 4. (a) Change of SiNW current upon hybridization to 10 nM target DNA as a function of concentration of probe DNA employed during sensor fabrication. The sensing measurement was operated in 0.1× PBS with nanowires of 16 μm. (b) Response of 2 μM probe DNA functionalized SiNW biosensor to 10 nM target DNA in varying buffer ionic strengths. The SiNW used was n-type with length of 65 μm.
increase of modification concentration. This plateau presumably arises due to the steric resistance and electrostatic repulsion between the negatively charged DNAs. The Debye screening length,13,25 the distance over which significant charge separation can take place, is an important parameter challenging device performance. A longer Debye length is expected to ensure fewer charges screened by using a dilute buffer solution with low electrolyte concentrations. Here, we demonstrate the effect of increasing buffer ionic strengths on device sensitivity for recognition by real time measurement of 10 nM DNA in 1× PBS, 0.1× PBS, and 0.01× PBS using a ntype device with length of 65 μm. A SiNW-FET device was functionalized with 1 μM DNA capture probe, and after establishing a baseline current in PBS 10 nM target DNA was added in the same buffer. As shown in Figure 4b, the addition of 10 nM DNA in 0.01× PBS resulted in a sharp decrease (60%) in current after establishing a baseline current in the same buffer solution, whereas addition of 10 nM DNA in 1× PBS just gave rise to a slight current drop (10%). A moderate current change was observed upon the injection of 10 nM target DNA in 0.1× PBS. When referencing the formula of the Debye screening length,13 the ionic strength of 0.01× PBS yields a Debye length of ∼7.3 nm, thus the majority of the DNA’s charge is unscreened at the SiNW-FET surface. A 10fold increase in the ionic strength of the buffer (0.1× PBS, ∼2.3 nm) partially screens DNA’s intrinsic charge, and a further 10fold increase in buffer ionic strength (1× PBS, ∼0.7 nm)
and 10 mM phosphate, pH 7.4) as buffer solution. Of note, the DNA surface density is controlled by varying the modification concentration of probe DNA within the same conditions including buffer solution, incubation time, temperature, and so on. In addition, the DNA surface density has been reported to be sequence and length dependent.29 The DNA with sequence of 5′-HOOC-CAC GAC GTT GTA AAA CGA CGG CCA G3′ was employed in this research. Figure 4a shows the result of SiNW current change upon hybridization with 10 nm 24-base fully cDNA in 0.1× PBS as a function of modification concentration. As illustrated in Figure 4a, the maximum current change was obtained at moderate probe density and the change in SiNW current decreased as the probe density increased at a certain range of probe density. At a certain density range, the efficiency of DNA hybridization is inversely proportional to its surface probe density because of the increased steric resistance of molecules, that is to say, the hybridization efficiency of DNA can be improved by reducing the surface density of the probe.30 However, even though highest hybridization efficiency occurred at a very low probe density (0.2 μM), large current change cannot be reached due to the reduction of total probe numbers. Therefore, as the surface probe density increases, the change in SiNW current will be a trade-off between increased probe number and decreasing hybridization efficiency. In addition, the maximum surface density was also achieved at a moderate fabrication concentration,31 beyond which no further increases would be observed. Our results also show the stable tendency as the 5265
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Figure 5. (a) Plots of normalized current change versus time with target DNA at a series of concentrations (0.1 fM, 1 fM, 10 fM, 1 pM, and 10 nM) for probe DNA modified SiNW device. Hybridization was demonstrated by 0.5 μM probe DNA functionalized SiNW biosensor in 0.01× PBS. The length of all SiNWs was 6 μm. (b) Normalized current change as a function of the logarithm of target DNA concentration. (c) Plot of current versus time for unmodified SiNW-FET, where region 1 stands for the presence of buffer solution and region 2 for the addition of 1 nM of fully complementary target DNA. The arrow marks the point when the solution was changed. (d) Hybridization specificity demonstrated by 1 μM probe DNA functionalized SiNW biosensor to (1) three-base mismatched (2) two-base mismatched, and (3) one-base mismatched 10 nM target DNAs. This experiment was carried out in 0.1× PBS. The length of SiNWs was 10 μm and sensors were n-type.
DNA concentration. The ability to detect 0.1 fM of target DNA is the lowest detection limit reported so far compared with DNA sensors using various methods,32−40 demonstrating the ultrahigh sensitivity of our nanosensor. The detection limit of 0.1 fM is not an absolute limit since it should be possible to further improve the electrical sensitivity of SiNWs through variation in effective dopant concentration, improvements in the contacts, and use of peptide nucleic acids (PNA) as receptors. As a control experiment, target DNA of the 1 nM was introduced onto an unmodified SiNW FET, which did not lead to significant current change (Figure 5c), suggesting the absence of nonspecific binding of target DNA to the SiNW surface. The specificity of the nanosensor was further evaluated by analyzing the one-, two-, and three-base mismatched target DNA (Figure 5d). Our device demonstrated great discrimination for unmatched DNAs. As illustrated before,22 the current change of the silicon nanosensor when it hybridized to the fully complementary 10 nM DNA in 0.1× PBS was about 40%. The introduction of one- and two-base mismatched target DNA only led to current change of ∼20 and ∼5%, which was significantly lower than that of fully complementary target DNA. It was indistinguishable from the background noise when three bases were mismatched. The sensing results readily allow selective detection of genes in a complex DNA mixture and
effectively screens most of the DNA’s charge, returning the current approximately to its baseline value. The study on these fundamental factors that affect device sensitivity offers a mechanism for enhancement of the device sensitivity. To develop a SiNW array chip able to detect ultralow concentrations of DNA in biological samples, detection and differentiation between various concentrations of DNA in optimized conditions were carried out. For the detection, we implemented the real-time DNA detection experiment by monitoring the current of SiNW sensor as a function of target DNA concentration. Hybridization was demonstrated by 0.5 μM probe DNA functionalized SiNW biosensor in 0.01× PBS. The data was normalized by computing IDS/I0, and plotted on the same axes for the effective comparison of relative change in SiNW current for different concentration of target DNA. An exploration of the detection limit of these sensors is shown in Figure 5a. Specifically, 0.01× PBS buffer was added on a device functionalized with 0.5 μM probe DNA to establish a baseline current. After the stable reading was obtained, known concentrations of target DNA were introduced to see current change relative to baseline current. We found that the nanosensor could reliably detect target DNA down to the concentration as low as 0.1 fM. Figure 5b shows a plot of SiNW sensor current versus target DNA concentration. The electrical current change increased monotonously with the logarithm of 5266
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(4) Bergveld, P. Development, Operation, and Application of the Ion-Sensitive Field-Effect Transistor as a Tool for Electrophysiology. IEEE Trans. Biomed. Eng. 1972, 19, 342−351. (5) Ramachandran, N.; Larson, D. N.; Stark, P. R. H.; Hainsworth, E.; LaBaer, J. Emerging tools for real-time label-free detection of interactions on functional protein microarrays. FEBS J. 2005, 272, 5412−5425. (6) Cheng, M. M.-C.; Cuda, G.; Bunimovich, Y. L.; Gaspari, M.; Heath, J. R.; Hill, H. D.; Mirkin, C. A.; Nijdam, A. J.; Terracciano, R.; Thundat, T.; Ferrari, M. Nanotechnologies for biomolecular detection and medical diagnostics. Curr. Opin. Chem. Biol. 2006, 10, 11−19. (7) Chen, K.-I; Li, B.-R.; Chen, Y.-T. Silicon nanowire field-effect transistor-based biosensors for biomedical diagnosis and cellular recording investigation. Nano Today 2011, 6, 131−154. (8) Patolsky, F.; Lieber, C. M. Nanowire nanosensors. Mater. Today 2005, 8, 20−28. (9) 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. (10) Bunimovitch, 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. Am. Chem. Soc. 2006, 128, 16323−16331. (11) Gao, X. P. A.; Zheng, G.; Lieber, C. M. Subthreshold Regime has the Optimal Sensitivity for Nanowire FET Biosensors. Nano Lett. 2010, 10, 547−552. (12) Elfström, N.; Juhasz, R.; Sychugov, I.; Engfeldt, T.; Karlström, A. E.; Linnros, J. Surface Charge Sensitivity of Silicon Nanowires: Size Dependence. Nano Lett. 2007, 7, 2608−2612. (13) Stern, E.; Wagner, R.; Sigworth, F. J.; Breaker, R.; Fahmy, T. M.; Reed, M. A. Importance of the Debye Screening Length on Nanowire Field Effect Transistor Sensors. Nano Lett. 2007, 7, 3405−3409. (14) Zhang, G.-J.; Zhang, G.; Chua, J. H.; Chee, R.-E.; Wong, E. H.; Agarwal, A.; Buddharaju, K. D.; Singh, N.; Gao, Z.; Balasubramanian, N. DNA Sensing by Silicon Nanowire: Charge Layer Distance Dependence. Nano Lett. 2008, 8, 1066−1070. (15) Huang, Y.; Duan, X.; Wei, Q.; Lieber, C. M. Directed Assembly of One-Dimensional Nanostructures into Functional Networks. Science 2001, 291, 630−633. (16) Kim, A.; Ah, C. S.; Yu, H. Y.; Yang, J.-H.; Baek, I.-B.; Ahn, C.-G.; Park, C. W.; Jun, M. S. Ultrasensitive, Label-Free, and Real-Time Immunodetection Using Silicon Field-Effect Transistors. Appl. Phys. Lett. 2007, 91, 103901. (17) Li, Z.; Chen, Y.; Li, X.; Kamins, T. I.; Nauka, K.; Williams, R. S. Sequence-Specific Label-Free DNA Sensors Based on Silicon Nanowires. Nano Lett. 2004, 4, 245−247. (18) Agarwal, A.; Buddharaju, K.; Lao, I. K.; Singh, N.; Balasubramanian, N.; Kwong, D. L. Silicon Nanowire Sensor Array Using Top-Down CMOS Technology. Sens. Actuators, A 2008, 145− 146, 207−213. (19) Pui, T.-S.; Agarwal, A.; Ye, F.; Balasubramanian, N.; Chen, P. CMOS-Compatible Nanowire Sensor Arrays for Detection of Cellular Bioelectricity. Small 2009, 5, 208−212. (20) Guo, L.; Krauss, P. R.; Chou, S. Y. Nanoscale Silicon Field Effect Transistors Fabricated Using Imprint Lithography. Appl. Phys. Lett. 1997, 71, 1881−1883. (21) Tabata, O.; Asahi, R.; Funabashi, H.; Shimaoka, K.; Sugiyama, S. Anisotropic Etching of Silicon in TMAH Solutions. Sens. Actuators, A 1992, 34, 51−57. (22) Gao, A.; Lu, N.; Dai, P.; Li, T.; Pei, P.; Gao, X.; Gong, Y.; Wang, Y.; Fan, C. Silicon-Nanowire-Based CMOS-Compatible Field-Effect Transistor Nanosensors. Nano Lett. 2011, 11, 3974−3978. (23) Bunimovich, Y. L.; Ge, G.; Beverly, K. C.; Ries, R. S.; Hood, L.; Heath, J. R. Electrochemically Programmed, Spatially Selective Biofunctionalization of Silicon Wires. Langmuir 2004, 20, 10630− 10638.
discrimination between the perfectly matched and mismatched sequences. Conclusions. In conclusion, the device sensitivity dependence from various parameters was explored for our representative nanowire device, and the operation of a nanoelectronic field-effect sensor for high-performance DNA detection by optimizing the gate voltage, buffer ionic strength, and probe concentration was demonstrated. The physically engineered silicon nanowire with back gate was fabricated by using CMOS compatible anisotropic wet etching approach with self-stop limitation. We demonstrated the back-gated SiNWFET sensor had the highest percentage current response in the subthreshold regime and experimentally confirmed in pH detection. Furthermore, we concluded that for DNA detection, the sensor performance could be optimized in low buffer ionic strength and at moderate probe concentration. The DNA detection limit could be improved to 0.1 fM by operating the sensor at the optimal conditions. Our results address the influence of fundamental factors on sensitivity of SiNW FET biosensors and offer the possibility of highly parallel detection with local back-gate control. Therefore, the method may have broad implications on the sensitivity limits of other FET sensors as well and the nanosensor may be used for the simultaneous detection of multiple chemical and biological species.
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ASSOCIATED CONTENT
S Supporting Information *
Fabricated SiNWs, theoretical analysis for device sensitivity, electrical measurement of subthreshold regime, pH sensing, and effect of surface modification on SiNW FETs transfer characteristic. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*(T.L.) E-mail:
[email protected]. Fax: (+) 86-21-6213-1744. (Y.W.)
[email protected]. Fax: (+) 86-21-6213-1744. (C.F.) E-mail:
[email protected]. Fax: (+) 86-21-3919-4702. Author Contributions ∥
The first two authors, A.G. and N.L., contributed equally to this work. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We appreciate financial support from National Basic Research Program of China (973 Program No. 2011CB309501, No. 2012CB933301, No. 2012CB932600), Creative Research of National Natural Science Foundation of China (No. 61021064), and the National Natural Science Foundation of China (No. 60936001, No. 91123037).
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REFERENCES
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