Restricting Conformational Space: A New Blueprint for Electrically Switchable Self-Assembled Monolayers.

Tunnel junctions comprising self-assembled monolayers (SAMs) from liquid crystal-inspired molecules show a pronounced hysteretic current-voltage response, due to electric field-driven dipole reorientation in the SAM. This renders these junctions attractive device candidates for emerging technologies such as in-memory and neuromorphic computing. Here, the novel molecular design, device fabrication, and characterization of such resistive switching devices with a largely improved performance, compared to the previously published work are reported. Those former devices suffer from a stochastic switching behavior limiting reliability, as well as from critically small read-out currents. The present progress is based on replacing Al/AlOx with TiN as a new electrode material and as a key point, on redesigning the active molecular material making up the SAM: a previously present, flexible aliphatic moiety has been replaced by a rigid aromatic linker, thereby introducing a molecular "ratchet". This restricts the possible molecular conformations to only two major states of opposite polarity. The above measures have resulted in an increase of the current density by five orders of magnitude as well as in an ON/OFF conductance ratio which is more than ten times higher than the individual scattering ranges of the high and low resistance states.

Near-Temperature-Independent Electron Transport Well beyond Expected Quantum Tunneling Range via Bacteriorhodopsin Multilayers.

A key conundrum of biomolecular electronics is efficient electron transport (ETp) through solid-state junctions up to 10 nm, often without temperature activation. Such behavior challenges known charge transport mechanisms, especially via nonconjugated molecules such as proteins. Single-step, coherent quantum-mechanical tunneling proposed for ETp across small protein, 2-3 nm wide junctions, but it is problematic for larger proteins. Here we exploit the ability of bacteriorhodopsin (bR), a well-studied, 4-5 nm long membrane protein, to assemble into well-defined single and multiple bilayers, from ∼9 to 60 nm thick, to investigate ETp limits as a function of junction width. To ensure sufficient signal/noise, we use large area (∼10-3 cm2) Au-protein-Si junctions. Photoemission spectra indicate a wide energy separation between electrode Fermi and the nearest protein-energy levels, as expected for a polymer of mostly saturated components. Junction currents decreased exponentially with increasing junction width, with uniquely low length-decay constants (0.05-0.5 nm-1). Remarkably, even for the widest junctions, currents are nearly temperature-independent, completely so below 160 K. While, among other things, the lack of temperature-dependence excludes, hopping as a plausible mechanism, coherent quantum-mechanical tunneling over 60 nm is physically implausible. The results may be understood if ETp is limited by injection into one of the contacts, followed by more efficient charge propagation across the protein. Still, the electrostatics of the protein films further limit the number of charge carriers injected into the protein film. How electron transport across dozens of nanometers of protein layers is more efficient than injection defines a riddle, requiring further study.

Conductance Switching in Liquid Crystal-Inspired Self-Assembled Monolayer Junctions.

We present the prototype of a ferroelectric tunnel junction (FTJ), which is based on a self-assembled monolayer (SAM) of small, functional molecules. These molecules have a structure similar to those of liquid crystals, and they are embedded between two solid-state electrodes. The SAM, which is deposited through a short sequence of simple fabrication steps, is extremely thin (3.4 ± 0.5 nm) and highly uniform. The functionality of the FTJ is ingrained in the chemical structure of the SAM components: a conformationally flexible dipole that can be reversibly reoriented in an electrical field. Thus, the SAM acts as an electrically switchable tunnel barrier. Fabricated stacks of Al/Al2O3/SAM/Pb/Ag with such a polar SAM show pronounced hysteretic, reversible conductance switching at voltages in the range of ±2-3 V, with a conductance ratio of the low and the high resistive states of up to 100. The switching mechanism is analyzed using a combination of quantum chemical, molecular dynamics, and tunneling resistance calculation methods. In contrast to more common, inorganic material-based FTJs, our approach using SAMs of small organic molecules allows for a high degree of functional complexity and diversity to be integrated by synthetic standard methods, while keeping the actual device fabrication process robust and simple. We expect that this technology can be further developed toward a level that would then allow its application in the field of information storage and processing, in particular for in-memory and neuromorphic computing architectures.

Principles of Small-Molecule Transport through Synthetic Nanopores.

Synthetic nanopores made from DNA replicate the key biological processes of transporting molecular cargo across lipid bilayers. Understanding transport across the confined lumen of the nanopores is of fundamental interest and of relevance to their rational design for biotechnological applications. Here we reveal the transport principles of organic molecules through DNA nanopores by synergistically combining experiments and computer simulations. Using a highly parallel nanostructured platform, we synchronously measure the kinetic flux across hundreds of individual pores to obtain rate constants. The single-channel transport kinetics are close to the theoretical maximum, while selectivity is determined by the interplay of cargo charge and size, the pores' sterics and electrostatics, and the composition of the surrounding lipid bilayer. The narrow distribution of transport rates implies a high structural homogeneity of DNA nanopores. The molecular passageway through the nanopore is elucidated via coarse-grained constant-velocity steered molecular dynamics simulations. The ensemble simulations pinpoint with high resolution and statistical validity the selectivity filter within the channel lumen and determine the energetic factors governing transport. Our findings on these synthetic pores' structure-function relationship will serve to guide their rational engineering to tailor transport selectivity for cell biological research, sensing, and drug delivery.

Bipolar Resistive Switching in Junctions of Gallium Oxide and p-type Silicon.

In this work, native GaOx is positioned between bulk gallium and degenerately doped p-type silicon (p+-Si) to form Ga/GaOx/SiOx/p+-Si junctions. These junctions show memristive behavior, exhibiting large current-voltage hysteresis. When cycled between -2.5 and 2.5 V, an abrupt insulator-metal transition is observed that is reversible when the polarity is reversed. The ON/OFF ratio between the high and low resistive states in these junctions can reach values on the order of 108 and retain the ON and OFF resistive states for up to 105 s with an endurance exceeding 100 cycles. The presence of a nanoscale layer of gallium oxide is critical to achieving reversible resistive switching by formation and dissolution of the gallium filament across the switching layer.

Contact Architecture Controls Conductance in Monolayer Devices.

The architecture of electrically contacting the self-assembled monolayer (SAM) of an organophosphonate has a profound effect on a device where the SAM serves as an intermolecular conductive channel in the plane of the substrate. Nanotransfer printing (nTP) enabled the construction of top-contact and bottom-contact architectures; contacts were composed of 13 nm thin metal films that were separated by a ca. 20 nm gap. Top-contact devices were fabricated by assembling the SAM across the entire surface of an insulating substrate and then applying the patterned metallic electrodes by nTP; bottom-contact ones were fabricated by nTP of the electrode pattern onto the substrate before the SAM was grown in the patterned nanogaps. SAMs were prepared from (9,10-di(naphthalen-2-yl)anthracen-2-yl)phosphonate; here, the naphthyl groups extend laterally from the anthracenylphosphonate backbone. Significantly, top-contact devices supported current that was about 3 orders of magnitude greater than that for comparable bottom-contact devices and that was at least 100,000 times greater than for a control device devoid of a SAM (at 0.5 V bias). These large differences in conductance between top- and bottom-contact architectures are discussed in consideration of differential contact-to-SAM geometries and, hence, resistances.

Synthetic protein-conductive membrane nanopores built with DNA.

Nanopores are key in portable sequencing and research given their ability to transport elongated DNA or small bioactive molecules through narrow transmembrane channels. Transport of folded proteins could lead to similar scientific and technological benefits. Yet this has not been realised due to the shortage of wide and structurally defined natural pores. Here we report that a synthetic nanopore designed via DNA nanotechnology can accommodate folded proteins. Transport of fluorescent proteins through single pores is kinetically analysed using massively parallel optical readout with transparent silicon-on-insulator cavity chips vs. electrical recordings to reveal an at least 20-fold higher speed for the electrically driven movement. Pores nevertheless allow a high diffusive flux of more than 66 molecules per second that can also be directed beyond equillibria. The pores may be exploited to sense diagnostically relevant proteins with portable analysis technology, to create molecular gates for drug delivery, or to build synthetic cells.

Space charge-limited current transport in thin films of alkyl-functionalized silicon nanocrystals.

We describe the fabrication and electrical characterization of all-silicon electrode devices to study the electronic properties of thin films of silicon nanocrystals (SiNCs). Planar, highly doped Si electrodes with contact separation of 200 nm were fabricated from silicon-on-insulator substrates, by combination of electron beam lithography and reactive ion etching. The gaps between the electrodes of height 110 nm were filled with thin-films of hexyl functionalized SiNCs (diameter 3 nm) from colloidal dispersions, via a pressure-transducing PDMS (polydimethylsiloxane) membrane. This novel approach allowed the formation of homogeneous SiNC films with precise control of their thickness in the range of 15-90 nm, practically without any voids or cracks. The measured conductance of the highly resistive SiNC films at high bias voltages up to 60 V scaled approximately linearly with gap width (5-50 µm) and gap filling height, with little device-to-device variance. We attribute the observed, pronounced hysteretic current-voltage (I-V) characteristics to space-charge-limited current transport, which-after about twenty cycles-eventually blocks the current almost completely. We propose our all-silicon device scheme and gap filling methodology as a platform to investigate charge transport in novel hybrid materials at the nanoscale, in particular in the high resistivity regime.

Role of Different Receptor-Surface Binding Modes in the Morphological and Electrochemical Properties of Peptide-Nucleic-Acid-Based Sensing Platforms.

Label-free detection of charged biomolecules, such as DNA, has experienced an increase in research activity in recent years, mainly to obviate the need for elaborate and expensive pretreatments for labeling target biomolecules. A promising label-free approach is based on the detection of changes in the electrical surface potential on biofunctionalized silicon field-effect devices. These devices require a reliable and selective immobilization of charged biomolecules on the device surface. In this work, self-assembled monolayers of phosphonic acids are used to prepare organic interfaces with a high density of peptide nucleic acid (PNA) bioreceptors, which are a synthetic analogue to DNA, covalently bound either in a multidentate (∥PNA) or monodentate (⊥PNA) fashion to the underlying silicon native oxide surface. The impact of the PNA bioreceptor orientation on the sensing platform's surface properties is characterized in detail by water contact angle measurements, atomic force microscopy, X-ray photoelectron spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. Our results suggest that the multidentate binding of the bioreceptor via attachment groups at the γ-points along the PNA backbone leads to the formation of an extended, protruding, and netlike three-dimensional metastructure. Typical "mesh" sizes are on the order of 8 ± 2.5 nm in diameter, with no preferential spatial orientation relative to the underlying surface. Contrarily, the monodentate binding provides a spatially more oriented metastructure comprising cylindrical features, of a typical size of 62 ± 23 × 12 ± 2 nm2. Additional cyclic voltammetry measurements in a redox buffer solution containing a small and highly mobile Ru-based complex reveal strikingly different insulating properties (ion diffusion kinetics) of these two PNA systems. Investigation by electrochemical impedance spectroscopy confirms that the binding mode has a significant impact on the electrochemical properties of the functional PNA layers represented by detectable changes of the conductance and capacitance of the underlying silicon substrate in the range of 30-50% depending on the surface organization of the bioreceptors in different bias potential regimes.

Transparent Nanopore Cavity Arrays Enable Highly Parallelized Optical Studies of Single Membrane Proteins on Chip.

Membrane proteins involved in transport processes are key targets for pharmaceutical research and industry. Despite continuous improvements and new developments in the field of electrical readouts for the analysis of transport kinetics, a well-suited methodology for high-throughput characterization of single transporters with nonionic substrates and slow turnover rates is still lacking. Here, we report on a novel architecture of silicon chips with embedded nanopore microcavities, based on a silicon-on-insulator technology for high-throughput optical readouts. Arrays containing more than 14 000 inverted-pyramidal cavities of 50 femtoliter volumes and 80 nm circular pore openings were constructed via high-resolution electron-beam lithography in combination with reactive ion etching and anisotropic wet etching. These cavities feature both, an optically transparent bottom and top cap. Atomic force microscopy analysis reveals an overall extremely smooth chip surface, particularly in the vicinity of the nanopores, which exhibits well-defined edges. Our unprecedented transparent chip design provides parallel and independent fluorescent readout of both cavities and buffer reservoir for unbiased single-transporter recordings. Spreading of large unilamellar vesicles with efficiencies up to 96% created nanopore-supported lipid bilayers, which are stable for more than 1 day. A high lipid mobility in the supported membrane was determined by fluorescent recovery after photobleaching. Flux kinetics of α-hemolysin were characterized at single-pore resolution with a rate constant of 0.96 ± 0.06 × 10-3 s-1. Here, we deliver an ideal chip platform for pharmaceutical research, which features high parallelism and throughput, synergistically combined with single-transporter resolution.

Nanocylindrical confinement imparts highest structural order in molecular self-assembly of organophosphonates on aluminum oxide.

We report the impact of geometrical constraint on intramolecular interactions in self-assembled monolayers (SAMs) of alkylphosphonates grown on anodically oxidized aluminum (AAO). Molecular order in these films was determined by sum frequency generation (SFG) spectroscopy, a more sensitive measure of order than infrared absorption spectroscopy. Using SFG we show that films grown on AAO are, within detection limits, nearly perfectly ordered in an all-trans alkyl chain configuration. In marked contrast, films formed on planar, plasma-oxidized aluminum oxide or α-Al2O3 (0001) are replete with gauche defects. We attribute these differences to the nanocylindrical structure of AAO, which enforces molecular confinement.

Towards nanometer-spaced silicon contacts to proteins.

A vertical nanogap device (VND) structure comprising all-silicon contacts as electrodes for the investigation of electronic transport processes in bioelectronic systems is reported. Devices were fabricated from silicon-on-insulator substrates whose buried oxide (SiO2) layer of a few nanometers in thickness is embedded within two highly doped single crystalline silicon layers. Individual VNDs were fabricated by standard photolithography and a combination of anisotropic and selective wet etching techniques, resulting in p(+) silicon contacts, vertically separated by 4 or 8 nm, depending on the chosen buried oxide thickness. The buried oxide was selectively recess-etched with buffered hydrofluoric acid, exposing a nanogap. For verification of the devices' electrical functionality, gold nanoparticles were successfully trapped onto the nanogap electrodes' edges using AC dielectrophoresis. Subsequently, the suitability of the VND structures for transport measurements on proteins was investigated by functionalizing the devices with cytochrome c protein from solution, thereby providing non-destructive, permanent semiconducting contacts to the proteins. Current-voltage measurements performed after protein deposition exhibited an increase in the junctions' conductance of up to several orders of magnitude relative to that measured prior to cytochrome c immobilization. This increase in conductance was lost upon heating the functionalized device to above the protein's denaturation temperature (80 °C). Thus, the VND junctions allow conductance measurements which reflect the averaged electronic transport through a large number of protein molecules, contacted in parallel with permanent contacts and, for the first time, in a symmetrical Si-protein-Si configuration.

Disorder-derived, strong tunneling attenuation in bis-phosphonate monolayers.

Monolayers of alkyl bisphosphonic acids (bisPAs) of various carbon chain lengths (C4, C8, C10, C12) were grown on aluminum oxide (AlO(x)) surfaces from solution. The structural and electrical properties of these self-assembled monolayers (SAMs) were compared with those of alkyl monophosphonic acids (monoPAs). Through contact angle (CA) and Kelvin-probe (KP) measurements, ellipsometry, and infrared (IR) and x-ray photoelectron (XPS) spectroscopies, it was found that bisPAs form monolayers that are relatively disordered compared to their monoPA analogs. Current-voltage (J-V) measurements made with a hanging Hg drop top contact show tunneling to be the prevailing transport mechanism. However, while the monoPAs have an observed decay constant within the typical range for dense monolayers, ß(mono) = 0.85 ± 0.03 per carbon atom, a surprisingly high value, ß(bis) = 1.40 ± 0.05 per carbon atom, was measured for the bisPAs. We attribute this to a strong contribution of 'through-space' tunneling, which derives from conformational disorder in the monolayer due to strong interactions of the distal phosphonic acid groups; they likely form a hydrogen-bonding network that largely determines the molecular layer structure. Since bisPA SAMs attenuate tunnel currents more effectively than do the corresponding monoPA SAMs, they may find future application as gate dielectric modification in organic thin film devices.

Toward three-dimensional microelectronic systems: directed self-assembly of silicon microcubes via DNA surface functionalization.

The huge and intelligent processing power of three-dimensional (3D) biological "processors" like the human brain with clock speeds of only 0.1 kHz is an extremely fascinating property, which is based on a massively parallel interconnect strategy. Artificial silicon microprocessors are 7 orders of magnitude faster. Nevertheless, they do not show any indication of intelligent processing power, mostly due to their very limited interconnectivity. Massively parallel interconnectivity can only be realized in three dimensions. Three-dimensional artificial processors would therefore be at the root of fabricating artificially intelligent systems. A first step in this direction would be the self-assembly of silicon based building blocks into 3D structures. We report on the self-assembly of such building blocks by molecular recognition, and on the electrical characterization of the formed assemblies. First, planar silicon substrates were functionalized with self-assembling monolayers of 3-aminopropyltrimethoxysilane for coupling of oligonucleotides (single stranded DNA) with glutaric aldehyde. The oligonucleotide immobilization was confirmed and quantified by hybridization with fluorescence-labeled complementary oligonucleotides. After the individual processing steps, the samples were analyzed by contact angle measurements, ellipsometry, atomic force microscopy, and fluorescence microscopy. Patterned DNA-functionalized layers were fabricated by microcontact printing (µCP) and photolithography. Silicon microcubes of 3 µm edge length as model objects for first 3D self-assembly experiments were fabricated out of silicon-on-insulator (SOI) wafers by a combination of reactive ion etching (RIE) and selective wet etching. The microcubes were then surface-functionalized using the same protocol as on planar substrates, and their self-assembly was demonstrated both on patterned silicon surfaces (88% correctly placed cubes), and to cube aggregates by complementary DNA functionalization and hybridization. The yield of formed aggregates was found to be about 44%, with a relative fraction of dimers of some 30%. Finally, the electrical properties of the formed dimers were characterized using probe tips inside a scanning electron microscope.

Conductance enhancement of InAs/InP heterostructure nanowires by surface functionalization with oligo(phenylene vinylene)s.

We have investigated the electronic transport through 3 µm long, 45 nm diameter InAs nanowires comprising a 5 nm long InP segment as electronic barrier. After assembly of 12 nm long oligo(phenylene vinylene) derivative molecules onto these InAs/InP nanowires, we observed a pronounced, nonlinear I-V characteristic with significantly increased currents of up to 1 µA at 1 V bias, for a back-gate voltage of 3 V. As supported by our model calculations based on a nonequilibrium Green Function approach, we attribute this effect to charge transport through those surface-bound molecules, which electrically bridge both InAs regions across the embedded InP barrier.

Molecular architecture: construction of self-assembled organophosphonate duplexes and their electrochemical characterization.

Self-assembled monolayers of phosphonates (SAMPs) of 11-hydroxyundecylphosphonic acid, 2,6-diphosphonoanthracene, 9,10-diphenyl-2,6-diphosphonoanthracene, and 10,10'-diphosphono-9,9'-bianthracene and a novel self-assembled organophosphonate duplex ensemble were synthesized on nanometer-thick SiO(2)-coated, highly doped silicon electrodes. The duplex ensemble was synthesized by first treating the SAMP prepared from an aromatic diphosphonic acid to form a titanium complex-terminated one; this was followed by addition of a second equivalent of the aromatic diphosphonic acid. SAMP homogeneity, roughness, and thickness were evaluated by AFM; SAMP film thickness and the structural contributions of each unit in the duplex were measured by X-ray reflection (XRR). The duplex was compared with the aliphatic and aromatic monolayer SAMPs to determine the effect of stacking on electrochemical properties; these were measured by impedance spectroscopy using aqueous electrolytes in the frequency range 20 Hz to 100 kHz, and data were analyzed using resistance-capacitance network based equivalent circuits. For the 11-hydroxyundecylphosphonate SAMP, C(SAMP) = 2.6 ± 0.2 µF/cm(2), consistent with its measured layer thickness (ca. 1.1 nm). For the anthracene-based SAMPs, C(SAMP) = 6-10 µF/cm(2), which is attributed primarily to a higher effective dielectric constant for the aromatic moieties (ε = 5-10) compared to the aliphatic one; impedance spectroscopy measured the additional capacitance of the second aromatic monolayer in the duplex (2ndSAMP) to be C(Ti/2ndSAMP) = 6.8 ± 0.7 µF/cm(2), in series with the first.

Dielectrophoretic trapping of DNA-coated gold nanoparticles on silicon based vertical nanogap devices.

We report on the successful dielectrophoretic trapping and electrical characterization of DNA-coated gold nanoparticles on vertical nanogap devices (VNDs). The nanogap devices with an electrode distance of 13 nm were fabricated from Silicon-on-Insulator (SOI) material using a combination of anisotropic reactive ion etching (RIE), selective wet chemical etching and metal thin-film deposition. Au nanoparticles (diameter 40 nm) coated with a monolayer of dithiolated 8 base pairs double stranded DNA were dielectrophoretically trapped into the nanogap from electrolyte buffer solution at MHz frequencies as verified by scanning and transmission electron microscopy (SEM/TEM) analysis. First electrical transport measurements through the formed DNA-Au-DNA junctions partially revealed an approximately linear current-voltage characteristic with resistance in the range of 2-4 GΩ when measured in solution. Our findings point to the importance of strong covalent bonding to the electrodes in order to observe DNA conductance, both in solution and in the dry state. We propose our setup for novel applications in biosensing, addressing the direct interaction of biomolecular species with DNA in aqueous electrolyte media.

Cleaved-edge-overgrowth nanogap electrodes.

We present a method to fabricate multiple metal nanogap electrodes of tailored width and distance in parallel, on the cleaved plane of a GaAs/AlGaAs heterostructure. The three-dimensional patterned structures are obtained by a combination of molecular-beam-epitaxial regrowth on a crystal facet, using the cleaved-edge-overgrowth (CEO) method, and subsequent wet selective etching and metallization steps. SEM and AFM studies reveal smooth and co-planar electrodes of width and distance of the order of 10 nm. Preliminary electrical characterization indicates electrical gap insulation in the 100 MΩ range with kΩ lead resistance. We propose our methodology to realize multiple electrode geometries that would allow investigation of the electrical conductivity of complex nanoscale objects such as branched organic molecules.

PNA-PEG modified silicon platforms as functional bio-interfaces for applications in DNA microarrays and biosensors.

The synthesis and characterization of two types of silicon-based biofunctional interfaces are reported; each interface bonds a dense layer of poly(ethylene glycol) (PEG(n)) and peptide nucleic acid (PNA) probes. Phosphonate self-assembled monolayers were derivatized with PNA using a maleimido-terminated PEG(45). Similarly, siloxane monolayers were functionalized with PNA using a maleimido-terminated PEG(45) spacer and were subsequently modified with a shorter methoxy-terminated PEG(12) ("back-filling"). The long PEG(45) spacer was used to distance the PNA probe from the surface and to minimize undesirable nonspecific adsorption of DNA analyte. The short PEG(12) "back-filler" was used to provide additional passivation of the surface against nonspecific DNA adsorption. X-ray photoelectron spectroscopic (XPS) analysis near the C 1s and N 1s ionization edges was done to characterize chemical groups formed in the near-surface region, which confirmed binding of PEG and PNA to the phosphonate and silane films. XPS also indicated that additional PEG chains were tethered to the surface during the back-filling process. Fluorescence hybridization experiments were carried out with complementary and noncDNA strands; both phosphonate and siloxane biofunctional surfaces were effective for hybridization of cDNA strands and significantly reduced nonspecific adsorption of the analyte. Spatial patterns were prepared by polydimethylsiloxane (PDMS) micromolding on the PNA-functionalized surfaces; selective hybridization of fluorescently labeled DNA was shown at the PNA functionalized regions, and physisorption at the probe-less PEG-functionalized regions was dramatically reduced. These results show that PNA-PEG derivatized phosphonate monolayers hold promise for the smooth integration of device surface chemistry with semiconductor technology for the fabrication of DNA biosensors. In addition, our results confirm that PNA-PEG derivatized self-assembled carboxyalkylsiloxane films are promising substrates for DNA microarray applications.