Planar Junctionless Field-Effect Transistor for Detecting Biomolecular Interactions.

Label-free field-effect transistor-based immunosensors are promising candidates for proteomics and peptidomics-based diagnostics and therapeutics due to their high multiplexing capability, fast response time, and ability to increase the sensor sensitivity due to the short length of peptides. In this work, planar junctionless field-effect transistor sensors (FETs) were fabricated and characterized for pH sensing. The device with SiO2 gate oxide has shown voltage sensitivity of 41.8 ± 1.4, 39.9 ± 1.4, 39.0 ± 1.1, and 37.6 ± 1.0 mV/pH for constant drain currents of 5, 10, 20, and 50 nA, respectively, with a drain to source voltage of 0.05 V. The drift analysis shows a stability over time of -18 nA/h (pH 7.75), -3.5 nA/h (pH 6.84), -0.5 nA/h (pH 4.91), 0.5 nA/h (pH 3.43), corresponding to a pH drift of -0.45, -0.09, -0.01, and 0.01 per h. Theoretical modeling and simulation resulted in a mean value of the surface states of 3.8 × 1015/cm2 with a standard deviation of 3.6 × 1015/cm2. We have experimentally verified the number of surface sites due to APTES, peptide, and protein immobilization, which is in line with the theoretical calculations for FETs to be used for detecting peptide-protein interactions for future applications.

Photothermal Circular Dichroism of Single Nanoparticles Rejecting Linear Dichroism by Dual Modulation.

Circular dichroism (CD) is the property of chiral nanoobjects to absorb circularly polarized light of either handedness to different extents. Photothermal microscopy enables the detection of CD signals with high sensitivity and provides a direct absorptive response of the samples under study. To achieve CD measurements at the single-particle level, one must reduce such artifacts as leakage of linear dichroism (LD) and residual intensity modulation. We have simulated our setup with a simple model, which allows us to tune modulation parameters to obtain a CD signal virtually free from artifacts. We demonstrate the sensitivity of our setup by measuring the very weak inherent CD signals of single gold nanospheres. We furthermore demonstrate that our method can be extended to obtain spectra of the full absorptive properties of single nanoparticles, including isotropic absorption, linear dichroism, and circular dichroism. We then investigate nominally achiral gold nanoparticles immersed in a chiral liquid. Carefully taking into account the intrinsic chirality of the particles and its change due to heat-induced reshaping, we find that the chiral liquid carvone surrounding the particle has no measurable effect on the particles' chirality, down to g-factors of 3 × 10-4.

Circular Dichroism Measurement of Single Metal Nanoparticles Using Photothermal Imaging.

Circular dichroism (CD) spectroscopy is a powerful optical technique for the study of chiral materials and molecules. It gives access to an enantioselective signal based on the differential absorption of right and left circularly polarized light, usually obtained through polarization analysis of the light transmitted through a sample of interest. CD is routinely used to determine the secondary structure of proteins and their conformational state. However, CD signals are weak, limiting the use of this powerful technique to ensembles of many molecules. Here, we experimentally realize the concept of photothermal circular dichroism, a technique that combines the enantioselective signal from circular dichroism with the high sensitivity of photothermal microscopy, achieving a superior signal-to-noise ratio to detect chiral nano-objects. As a proof of principle, we studied the chiral response of single plasmonic nanostructures with CD in the visible range, demonstrating a signal-to-noise ratio better than 40 with only 30 ms integration time for these nanostructures. The high signal-to-noise ratio allows us to quantify the CD signal for individual nanoparticles. We show that we can distinguish relative absorption differences for right circularly and left circularly polarized light as small as gmin = 4 × 10-3 for a 30 ms integration time with our current experimental settings. The enhanced sensitivity of our technique extends CD studies to individual nano-objects and opens CD spectroscopy to numbers of molecules much lower than those in conventional experiments.

1/f noise in solid-state nanopores is governed by access and surface regions.

The performance of solid-state nanopores as promising biosensors is severely hampered by low-frequency 1/f noise in the through-pore ionic current recordings. Here, we develop a model for the 1/f noise in such nanopores, that, unlike previous reports, accounts for contributions from both the pore-cylinder, pore-surface, and access regions. To test our model, we present measurements of the open-pore current noise through solid-state nanopores of different diameters (1-50 nm). To describe the observed trends, it appears essential to include the access resistance in the modeling of the 1/f noise. We attribute a different Hooge constant for the charge carrier fluctuations occurring in the bulk electrolyte and at the pore surface. The model reported here can be used to accurately analyze different contributions to the nanopore low-frequency noise, rendering it a powerful tool for characterizing and comparing different membrane materials in terms of their 1/f noise properties.

Label-Free Optical Detection of DNA Translocations through Plasmonic Nanopores.

Solid-state nanopores are single-molecule sensors that hold great potential for rapid protein and nucleic-acid analysis. Despite their many opportunities, the conventional ionic current detection scheme that is at the heart of the sensor suffers inherent limitations. This scheme intrinsically couples signal strength to the driving voltage, requires the use of high-concentration electrolytes, suffers from capacitive noise, and impairs high-density sensor integration. Here, we propose a fundamentally different detection scheme based on the enhanced light transmission through a plasmonic nanopore. We demonstrate that translocations of single DNA molecules can be optically detected, without the need of any labeling, in the transmitted light intensity through an inverted-bowtie plasmonic nanopore. Characterization and the cross-correlation of the optical signals with their electrical counterparts verify the plasmonic basis of the optical signal. We demonstrate DNA translocation event detection in a regime of driving voltages and buffer conditions where traditional ionic current sensing fails. This label-free optical detection scheme offers opportunities to probe native DNA-protein interactions at physiological conditions.

Double Barrel Nanopores as a New Tool for Controlling Single-Molecule Transport.

The ability to control the motion of single biomolecules is key to improving a wide range of biophysical and diagnostic applications. Solid-state nanopores are a promising tool capable of solving this task. However, molecular control and the possibility of slow readouts of long polymer molecules are still limited due to fast analyte transport and low signal-to-noise ratios. Here, we report on a novel approach of actively controlling analyte transport by using a double-nanopore architecture where two nanopores are separated by only a ∼ 20 nm gap. The nanopores can be addressed individually, allowing for two unique modes of operation: (i) pore-to-pore transfer, which can be controlled at near 100% efficiency, and (ii) DNA molecules bridging between the two nanopores, which enables detection with an enhanced temporal resolution (e.g., an increase of more than 2 orders of magnitude in the dwell time) without compromising the signal quality. The simplicity of fabrication and operation of the double-barrel architecture opens a wide range of applications for high-resolution readout of biological molecules.

Probing DNA Translocations with Inplane Current Signals in a Graphene Nanoribbon with a Nanopore.

Many theoretical studies predict that DNA sequencing should be feasible by monitoring the transverse current through a graphene nanoribbon while a DNA molecule translocates through a nanopore in that ribbon. Such a readout would benefit from the special transport properties of graphene, provide ultimate spatial resolution because of the single-atom layer thickness of graphene, and facilitate high-bandwidth measurements. Previous experimental attempts to measure such transverse inplane signals were however dominated by a trivial capacitive response. Here, we explore the feasibility of the approach using a custom-made differential current amplifier that discriminates between the capacitive current signal and the resistive response in the graphene. We fabricate well-defined short and narrow (30 nm × 30 nm) nanoribbons with a 5 nm nanopore in graphene with a high-temperature scanning transmission electron microscope to retain the crystallinity and sensitivity of the graphene. We show that, indeed, resistive modulations can be observed in the graphene current due to DNA translocation through the nanopore, thus demonstrating that DNA sensing with inplane currents in graphene nanostructures is possible. The approach is however exceedingly challenging due to low yields in device fabrication connected to the complex multistep device layout.

Effect of Gamma Irradiation on Dynamics of Charge Exchange Processes between Single Trap and Nanowire Channel.

In the present study, transport properties and single trap phenomena in silicon nanowire (NW) field-effect transistors (FETs) are reported. The dynamic behavior of drain current in NW FETs studied before and after gamma radiation treatment deviates from the predictions of the Shockley-Read-Hall model and is explained by the concept taking into account an additional energy barrier in the accumulation regime. It is revealed that dynamics of charge exchange processes between single trap and nanowire channel strongly depend on gamma radiation treatment. The results represent potential for utilizing single trap phenomena in a number of advanced devices.

Integrating Sub-3 nm Plasmonic Gaps into Solid-State Nanopores.

Plasmonic nanopores combine the advantages of nanopore sensing and surface plasmon resonances by introducing confined electromagnetic fields to a solid-state nanopore. Ultrasmall nanogaps between metallic nanoantennas can generate the extremely enhanced localized electromagnetic fields necessary for single-molecule optical sensing and manipulation. Challenges in fabrication, however, hamper the integration of such nanogaps into nanopores. Here, a top-down approach for integrating a plasmonic antenna with an ultrasmall nanogap into a solid-state nanopore is reported. Employing a two-step e-beam lithography process, the reproducible fabrication of nanogaps down to a sub-1 nm scale is demonstrated. Subsequently, nanopores are drilled through the 20 nm SiN membrane at the center of the nanogap using focused-electron-beam sculpting with a transmission electron microscope, at the expense of a slight gap expansion for the smallest gaps. Using this approach, sub-3 nm nanogaps can be readily fabricated on solid-state nanopores. The functionality of these plasmonic nanopores for single-molecule detection is shown by performing DNA translocations. These integrated devices can generate intense electromagnetic fields at the entrance of the nanopore and can be expected to find applications in nanopore-based single-molecule trapping and optical sensing.

Mechanical Trapping of DNA in a Double-Nanopore System.

Nanopores have become ubiquitous components of systems for single-molecule manipulation and detection, in particular DNA sequencing where electric field driven translocation of DNA through a nanopore is used to read out the DNA molecule. Here, we present a double-pore system where two nanopores are drilled in parallel through the same solid-state membrane, which offers new opportunities for DNA manipulation. Our experiments and molecular dynamics simulations show that simultaneous electrophoretic capture of a DNA molecule by the two nanopores mechanically traps the molecule, increasing its residence time within the nanopores by orders of magnitude. Remarkably, by using two unequal-sized nanopores, the pore of DNA entry and exit can be discerned from the ionic current blockades, and the translocation direction can be precisely controlled by small differences in the effective force applied to DNA. The mechanical arrest of DNA translocation using a double-pore system can be straightforwardly integrated into any solid-state nanopore platform, including those using optical or transverse-current readouts.

Direct observation of DNA knots using a solid-state nanopore.

Long DNA molecules can self-entangle into knots. Experimental techniques for observing such DNA knots (primarily gel electrophoresis) are limited to bulk methods and circular molecules below 10 kilobase pairs in length. Here, we show that solid-state nanopores can be used to directly observe individual knots in both linear and circular single DNA molecules of arbitrary length. The DNA knots are observed as short spikes in the nanopore current traces of the traversing DNA molecules and their detection is dependent on a sufficiently high measurement resolution, which can be achieved using high-concentration LiCl buffers. We study the percentage of molecules with knots for DNA molecules of up to 166 kilobase pairs in length and find that the knotting occurrence rises with the length of the DNA molecule, consistent with a constant knotting probability per unit length. Our experimental data compare favourably with previous simulation-based predictions for long polymers. From the translocation time of the knot through the nanopore, we estimate that the majority of the DNA knots are tight, with remarkably small sizes below 100 nm. In the case of linear molecules, we also observe that knots are able to slide out on application of high driving forces (voltage).

Self-Aligned Plasmonic Nanopores by Optically Controlled Dielectric Breakdown.

We present a novel cost-efficient method for the fabrication of high-quality self-aligned plasmonic nanopores by means of an optically controlled dielectric breakdown. Excitation of a plasmonic bowtie nanoantenna on a dielectric membrane localizes the high-voltage-driven breakdown of the membrane to the hotspot of the enhanced optical field, creating a nanopore that is automatically self-aligned to the plasmonic hotspot of the bowtie. We show that the approach provides precise control over the nanopore size and that these plasmonic nanopores can be used as single molecule DNA sensors with a performance matching that of TEM-drilled nanopores. The principle of optically controlled breakdown can also be used to fabricate nonplasmonic nanopores at a controlled position. Our novel fabrication process guarantees alignment of the nanopore with the optical hotspot of the nanoantenna, thus ensuring that pore-translocating biomolecules interact with the concentrated optical field that can be used for detection and manipulation of analytes.

Sensitivity enhancement of Si nanowire field effect transistor biosensors using single trap phenomena.

Trapping-detrapping processes in nanostructures are generally considered to be destabilizing factors. However, we discovered a positive role for a single trap in the registration and transformation of useful signal. We use switching kinetics of current fluctuations generated by a single trap in the dielectric of liquid-gated nanowire field effect transistors (FETs) as a basic principle for a novel highly sensitive approach to monitor the gate surface potential. An increase in Si nanowire FET sensitivity of 400% was demonstrated.

Liquid and back gate coupling effect: toward biosensing with lowest detection limit.

We employ noise spectroscopy and transconductance measurements to establish the optimal regimes of operation for our fabricated silicon nanowire field-effect transistors (Si NW FETs) sensors. A strong coupling between the liquid gate and back gate (the substrate) has been revealed and used for optimization of signal-to-noise ratio in subthreshold as well as above-threshold regimes. Increasing the sensitivity of Si NW FET sensors above the detection limit has been predicted and proven by direct experimental measurements.

Features of transport in ultrathin gold nanowire structures.

The origin of the interface formation appearing due to the realization of contacts to ultrathin gold nanowire devices is revealed. Such interfaces play an important role in transport mechanisms in nanowire structures and can determine the electrical and operating parameters of a nanodevice. Based on experimental results, the specific electrical properties of bundles of ultrathin gold nanowires fabricated by wet chemical synthesis and subsequently assembled and contacted with gold electrodes are reported. It is demonstrated that these properties are strongly affected by the monolayers of organic molecules inevitably present on the surface of the nanowires due to synthetic conditions. In particular, such layers form a potential barrier to tunneling of the electrons from contacts to the nanowires. The electric transport behavior of the investigated nanowire structures in the temperature range from 500 mK to 300 K obeys the model of thermal fluctuation-induced tunneling conduction through the nanowire-metal electrode molecular junction. Application of this model allows calculation of the parameters of the molecular potential barrier. The formation of such a molecular barrier is verified by scanning tunneling microscope (STM) and transmission electron microscope (TEM) measurements performed using a supporting graphene layer. These findings are important for designing novel nanodevices for molecular electronics on the basis of ultrathin nanowires.