ETTERS NATURE NANOTECHNOLOGY DOI: 10.1038/NNANO 2011.217 NW-NP FET -100nS 0.5 Distance to nanopore (um) Figure 1 I Nanowire-nanopore transistor a, Schematic of the nanowire-nanopore measurement set-up Inset: zoom-in view around the nanopore. NW-NP nanowire-nanopore. b, High-resolution TEM image of a silicon nanowire with the nanopore off-axis at the nanowire edge Scale bar, 10 nm. Inset: larger-scale EM image of a nanowire-nanopore FeT device showing the central silicon nanowire connected to darker NiSi contacts, which are indicated by the white ashed line. The region where the high-resolution TEM image was recorded is indicated by the yellow dashed square Scale bar (inset), 50 nm. c SGM image of a silicon nanowire-nanopore device recorded with the tip voltage at -10 V. Scale bar, 1 um Nanopore position is indicated by the black circle. Nickel contacts are indicated by white dashed lines and the nanowire between the two contacts is indicated by the black dashed line. Inset: AFM topographic image of the device, with the Sgm image area indicated by the white square. Colour scale(-100 to 200 nS) corresponds to the conductance change. d, scanning gate sensitivity profile of the same device before and after nanopore formation, with the profile taken along the black dashed line in c and averaged over an -100 nm width perpendicular to the dashed line. (nanowire-nanopore FET side) and cis(back side)chambers are FETs(Fig. 4b) and other silicon nanowire FET sensors2b2 filled with solutions of different ionic strength(for example, demonstrate that much lower noise(and correspondingly higher 10 mM in the trans chamber and 1 M in cis chamber), clear FEt signal-to-noise ratio)can be achieved in general for nanowire- conductance signals with perfect time correlation to ionic current nanopore FETs. In addition, the relatively large(30 nA)trans- events can be observed(Fig. 2b) for a voltage of x2 V. location signal from the FET suggests the potential for higher- alitatively, a larger voltage is expected given the lower solution bandwidth recording than with smaller ionic-current resistance and therefore lower electric field on the cis side. which detection schemes determines DNA entry into the nanopore. With a further increase To understand the nanowire-nanopore detection mechanism in the voltage to 2.4 V( Fig. 2c), the duration of translocation events we first consider basic experimental facts. First, and as discussed in both ionic current and FET channels decreased, while the fre- above, it is possible to exclude direct charge sensing by the quency increased. These changes in duration and frequency are con- nanowire-nanopore FET202, because the negative charge on the sistent with the previous results reported for ionic current events DNA backbone should produce an increase in conductance recorded in other nanopore experiments. 4. Importantly, the for the p-type device during translocation instead of the hange in the FET signal during translocation-a decrease in con- observed decrease. Second, the importance of the differential ductance-is opposite to that expected for charge-based sensing buffer salt concentration suggests that solution resistance plays of the DNA with a p-type semiconductor 2, therefore implying a an important role in the signal generation. Specifically, under new detection mechanism alanced buffer conditions (1 M/1 M), the nanopore dominates The amplitude of the nanowire-nanopore FET signal in a non- the solution resistance and the voltage drops primarily across balanced buffer salt concentration can be compared to the ionic the nanopore. The potential around the nanowire-nanopore urrent signal by converting the FET conductance to a current. sensor is very close to ground, regardless of the change in This conversion shows that the FET current change is 30 nA solution resistance during DNA translocation. However, when mpared with the 3 nA ionic current changes during DNA the buffer concentration in the trans chamber containing the translocation. Although the noise in this nanowire-nanopore nanowire-nanopore sensor is lower than that of the cis chamber, FET(Fig. 2)is relatively high, other nanowire-nanopore the nanopore and trans chamber solution resistances are NatureNanotEchnOlogYIVol7IFebRuaRy2012Iwww.nature.com/naturenanotechnology o 2012 Macmillan Publishers Limited. All rights reserved(nanowire–nanopore FET side) and cis (back side) chambers are filled with solutions of different ionic strength (for example, 10 mM in the trans chamber and 1 M in cis chamber), clear FET conductance signals with perfect time correlation to ionic current events can be observed (Fig. 2b) for a voltage of 2 V. Qualitatively, a larger voltage is expected given the lower solution resistance and therefore lower electric field on the cis side, which determines DNA entry into the nanopore3 . With a further increase in the voltage to 2.4 V (Fig. 2c), the duration of translocation events in both ionic current and FET channels decreased, while the fre￾quency increased. These changes in duration and frequency are con￾sistent with the previous results reported for ionic current events recorded in other nanopore experiments10,24. Importantly, the change in the FET signal during translocation—a decrease in con￾ductance—is opposite to that expected for charge-based sensing of the DNA with a p-type semiconductor20, therefore implying a new detection mechanism. The amplitude of the nanowire–nanopore FET signal in a non￾balanced buffer salt concentration can be compared to the ionic current signal by converting the FET conductance to a current. This conversion shows that the FET current change is 30 nA compared with the 3 nA ionic current changes during DNA translocation. Although the noise in this nanowire–nanopore FET (Fig. 2) is relatively high, other nanowire–nanopore FETs (Fig. 4b) and other silicon nanowire FET sensors26,27 demonstrate that much lower noise (and correspondingly higher signal-to-noise ratio) can be achieved in general for nanowire– nanopore FETs. In addition, the relatively large (30 nA) trans￾location signal from the FET suggests the potential for higher￾bandwidth recording than with smaller ionic-current detection schemes. To understand the nanowire–nanopore detection mechanism we first consider basic experimental facts. First, and as discussed above, it is possible to exclude direct charge sensing by the nanowire–nanopore FET20,21, because the negative charge on the DNA backbone should produce an increase in conductance for the p-type device during translocation instead of the observed decrease. Second, the importance of the differential buffer salt concentration suggests that solution resistance plays an important role in the signal generation. Specifically, under balanced buffer conditions (1 M/1 M), the nanopore dominates the solution resistance and the voltage drops primarily across the nanopore. The potential around the nanowire–nanopore sensor is very close to ground, regardless of the change in solution resistance during DNA translocation. However, when the buffer concentration in the trans chamber containing the nanowire–nanopore sensor is lower than that of the cis chamber, the nanopore and trans chamber solution resistances are a c b SGM sensitivity (nS V−1) Distance to nanopore (μm) d Source Drain Cis Trans SiNx SiNx NW−NP FET Si chip Si Chip Nanowire Before nanopore After nanopore −1.0 −0.5 0.5 0 0 5 10 15 20 1.0 200nS −100nS NiSi NiSi Figure 1 | Nanowire–nanopore transistor. a, Schematic of the nanowire–nanopore measurement set-up. Inset: zoom-in view around the nanopore. NW–NP, nanowire–nanopore. b, High-resolution TEM image of a silicon nanowire with the nanopore off-axis at the nanowire edge. Scale bar, 10 nm. Inset: larger-scale TEM image of a nanowire–nanopore FET device showing the central silicon nanowire connected to darker NiSi contacts, which are indicated by the white dashed line. The region where the high-resolution TEM image was recorded is indicated by the yellow dashed square. Scale bar (inset), 50 nm. c, SGM image of a silicon nanowire–nanopore device recorded with the tip voltage at 210 V. Scale bar, 1 mm. Nanopore position is indicated by the black circle. Nickel contacts are indicated by white dashed lines and the nanowire between the two contacts is indicated by the black dashed line. Inset: AFM topographic image of the device, with the SGM image area indicated by the white square. Colour scale (2100 to 200 nS) corresponds to the conductance change. d, Scanning gate sensitivity profile of the same device before and after nanopore formation, with the profile taken along the black dashed line in c, and averaged over an 100 nm width perpendicular to the dashed line. LETTERS NATURE NANOTECHNOLOGY DOI: 10.1038/NNANO.2011.217 120 NATURE NANOTECHNOLOGY | VOL 7 | FEBRUARY 2012 | www.nature.com/naturenanotechnology © 2012 Macmillan Publishers Limited. All rights reserved.