All cells release low molecular weight organic compounds that possess finite vapor pressures at body and/or ambient temperatures. These volatile organic compounds (VOCs) may possess an odor and can be found emanating from all body fluids. As cells turn malignant, analysis of changes in these VOCs can provide insight into cancer onset and diagnosis. Previous studies have demonstrated that dogs can be trained to distinguish ovarian cancer tissues of various stages and grades from normal ovarian tissue and other gynecological malignancies with sensitivity and specificity over 95%. When trained on biopsied tissue, dogs were able to detect the VOC disturbances in peripheral blood samples with the same accuracy. Building on these earlier studies, we examined the VOCs emanating from plasma samples from primary ovarian cancer patients, patients with benign reproductive tract growths, and healthy controls. We used a three-pronged sensor approach to analyze the VOCs from plasma: canines trained on tissue and plasma samples, analysis using solid phase microextraction gas chromatography–mass spectrometry, and novel single stranded DNA-coated carbon nanotube sensor field effect transistors. Each of the three experimental approaches used in this study provided preliminary evidence that plasma from ovarian cancer patients emits a volatile odor signature that can be distinguished from the VOCs of patients with benign ovarian tumors and controls. Our results provide optimism that a diagnostic approach based on the analysis of the VOC odor signature of ovarian cancer is achievable.

e17524 Background: All cells release volatile organic compounds (VOCs) which emanate from all body fluids. We hypothesize that as cells become malignant, the VOCs are altered and analysis of these changes in VOCs can provide a substrate for cancer diagnosis. We are working to develop a sensitive and specific, high-throughput screening test for ovarian cancer based on the analysis of VOCs. Our exploratory research is using a combination of trained detection dogs, analytical chemistry techniques, and DNA coated carbon nanotube vapor sensors. Methods: VOCs from ovarian cell cultures and pooled plasma samples were studied. The VOCs from ovarian cell cultures were analyzed with gas chromatography/mass spectrometry (GC/MS) and novel single-stranded DNA-Decorated Single-Walled Carbon Nanotubes (ssDNACNT). Plasma samples were pooled for 10 subjects each with ovarian cancer, benign ovarian disease and age-matched controls. VOCs from these samples were analyzed with GC/MS and SSDNACNT and trained detection dogs. Results: Many VOCs from the OVCAR3 cells are present in significantly greater relative amounts than from normal (ISOE) cells, while only 2 substances, acetic acid and isovaleric acid were present in lower amounts on the cancer cell line. Reproducibility was > .95 for most compounds. The ssDNACNT sensor was clearly able to discriminate cancer cell VOCs from normal cells and media with excellent reproducibility (correlation of .97 for duplicate analyses). When pooled blood samples were analyzed, detection dogs were able to correctly identify the cancer specimen with proportion of success between .9-1.0. GC/MS detected differences between the groups, most notably higher amount of 3,4 dimethylbenzaldehyde in patients with benign and cancerous ovarian disease. Preliminary SSDNACNT testing found significant differential responses based on the specific DNA sensor used. Conclusions: Using trained dogs, analytical organic chemistry and nano-enabled DNA coated vapor sensors, we provide strong evidence that ovarian cancer alters the VOC pattern emanating from plasma. Our results provide optimism that a diagnostic approach based on analysis of the odor signature of ovarian cancer is achievable.

This paper describes Intel's 10nm highperformance logic technology interconnect stack featuring 13 metal layers comprising two self-aligned quad patterned and four self-aligned double patterned layers. Quad patterned interconnect layers are introduced to continue Moore's Law, i.e. sub-40nm interconnect pitches to enable 10nm node cells that include 34nm fin pitch and Contact-over-active-gate (COAG) layout. Cobalt metallization is introduced in the pitch quartered interconnect layers in order to meet electromigration and gapfill-resistance requirements.

We demonstrate arrays of opioid biosensors based on chemical vapor deposition grown molybdenum disulfide (MoS2) field effect transistors (FETs) coupled to a computationally redesigned, water-soluble variant of the μ-opioid receptor (MOR). By transferring dense films of monolayer MoS2 crystals onto prefabricated electrode arrays, we obtain high-quality FETs with clean surfaces that allow for reproducible protein attachment. The fabrication yield of MoS2 FETs and biosensors exceeds 95%, with an average mobility of 2.0 cm(2) V(-1) s(-1) (36 cm(2) V(-1) s(-1)) at room temperature under ambient (in vacuo). An atomic length nickel-mediated linker chemistry enables target binding events that occur very close to the MoS2 surface to maximize sensitivity. The biosensor response calibration curve for a synthetic opioid peptide known to bind to the wild-type MOR indicates binding affinity that matches values determined using traditional techniques and a limit of detection ∼3 nM (1.5 ng/mL). The combination of scalable array fabrication and rapid, precise binding readout enabled by the MoS2 transistor offers the prospect of a solid-state drug testing platform for rapid readout of the interactions between novel drugs and their intended protein targets.

Monolayer transition metal dichalcogenides are materials with an atomic structure complementary to graphene but diverse properties, including direct energy bandgaps, which makes them intriguing candidates for optoelectronic devices. Various approaches have been demonstrated for the growth of molybdenum disulphide (MoS2) on insulating substrates, but to date, growth of isolated crystalline flakes has been demonstrated at random locations only. Here we use patterned seeds of molybdenum source material to grow flakes of MoS2 at predetermined locations with micrometre-scale resolution. MoS2 flakes are predominantly monolayers with high material quality, as confirmed by atomic force microscopy, transmission electron microscopy and Raman and photoluminescence spectroscopy. As the monolayer flakes are isolated at predetermined locations, transistor fabrication requires only a single lithographic step. Device measurements exhibit carrier mobility and on/off ratio that exceed 10 cm(2)V(-1)s(-1) and 10(6), respectively. The technique provides a path for in-depth physical analysis of monolayer MoS2 and fabrication of MoS2-based integrated circuits.

Chemical vapor deposition grown MoS2 single crystals were transferred onto the edge of a p-Si/SiO2 wafer, forming an abrupt heterogeneous junction diode at the MoS2/p-Si interface. When electrically characterized as a field effect transistor, MoS2 exhibits an n-type response and can be doped in the presence of ultraviolet (UV) light. As a diode, it operates satisfactorily in air, but has higher currents in vacuum with a turn on voltage of ∼1.3 V and an on/off ratio of 20 at ±2 V. UV irradiation increases the diode on state current, decreases the turn-on voltage, and reduces the ideality parameter below 2. These changes are reversible after annealing in air as desorption of electron trapping species like O2− and H2O− are believed responsible for this effect. A circuit integrating this diode was used to rectify a 1 kHz signal with an efficiency of 12%. Its simple design, coupled with the ability to clip AC signals, sense UV light, and reversibly tune these diodes, makes them inexpensive, multifunctional, and usable as active or passive circuit components in complex electronics.

Arrays of chemical vapor sensors based on graphene field effect transistors functionalized with single-stranded DNA have been demonstrated. Standard photolithographic processing was adapted for use on large-area graphene by including a metal protection layer, which protected the graphene from contamination and enabled fabrication of high quality field-effect transistors (GFETs). Processed graphene devices had hole mobilities of 1,640 ± 250 cm2·V−1·s−1 and Dirac voltages of 15 ± 10 V under ambient conditions. Atomic force microscopy was used to verify that the graphene surface remained uncontaminated and therefore suitable for controlled chemical functionalization. Single-stranded DNA was chosen as the functionalization layer due to its affinity to a wide range of target molecules and π-π stacking interaction with graphene, which led to minimal degradation of device characteristics. The resulting sensor arrays showed analyte- and DNA sequence-dependent responses down to parts-per-billion concentrations. DNA/GFET sensors were able to differentiate among chemically similar analytes, including a series of carboxylic acids, and structural isomers of carboxylic acids and pinene. Evidence for the important role of electrostatic chemical gating was provided by the observation of understandable differences in the sensor response to two compounds that differed only by the replacement of a (deprotonating) hydroxyl group by a neutral methyl group. Finally, target analytes were detected without loss of sensitivity in a large background of a chemically similar, volatile compound. These results motivate further development of the DNA/graphene sensor family for use in an electronic olfaction system.

This diploma thesis deals with the fabrication of graphite/graphene layers and measurement of their transport properties as a function of relative humidity. Graphene flakes were deposited by mechanical exfoliation. For contacting the graphene flakes the electron beam lithography was used. Additional characterization was performed by optical microscopy, atomic force microscopy and scanning electron microscopy. The thesis describes the steps for the production, observation and characterization of the deposited graphene flakes. Kĺıčová slova grafen, AFM, EBL, SEM, grafit, litografie, čtyrbodová metoda, V−A meřeńı

CVD graphene devices on stacked CVD hexagonal boron nitride (hBN) are demonstrated using a novel low-contamination transfer method, and their electrical performance is systematically compared to devices on SiO(2). An order of magnitude improvement in mobility, sheet resistivity, current density, and sustained power is reported when the oxide substrate is covered with five-layer CVD hBN.

Singleand few-layer molybdenum disulfide (MoS2) thin films, which have recently been synthesized for the first time, are of great interest for potential applications due to their two-dimensional structure and electronic properties. With a bandgap of 1.8 eV, conduction through this material can be tuned between on and off states, a property that graphene, a more studied two dimensional material, does not possess. Furthermore MoS2 presents high thermal and chemical stability, which allows the creation of high-performance nano-electric devices such as field effect transistors (FETs), which could be used as ultrasensitive sensors for clinically-relevant proteins and other biomolecules. These kinds of sensors are currently fabricated with carbon based materials such as nanotubes and graphene and have detection limits at the pico-molar levels. However, the bandgap of MoS2 could allow for lower concentration detections. This study investigates the process of nickel chloride (NiCl2) mediated protein attachment to exfoliated MoS2 flakes using different methods of purification and different concentrations of NiCl2. Testing our mechanism is ongoing and will specify the most beneficial conditions of NiCl2 needed to attach the highest density of proteins to the MoS2. This is the first step towards building a biosensor based upon molybdenum disulfide.

The promise of graphene for use as a vapor sensor motivated exploration of the vapor responses of graphene nanomesh (GNM) functionalized with single stranded DNA. Devices detected different vapor types, including carboxylic acids, aldehydes, organophosphates, and explosives. As-fabricated GNM field effect transistors (FETs) had larger vapor responses than standard graphene FETs due to the effect of oxidized edges and lattice defects. DNA-GNM devices discriminated between homologous species with detection limits of a few parts per million, with fast response and recovery. Responses varied significantly when the base sequence of the DNA was changed, making the sensor class an intriguing candidate for use in an electronic nose system.

Graphene-boron nitride monolayer heterostructures contain adjacent electrically active and insulating regions in a continuous, single-atom thick layer. To date structures were grown at low pressure, resulting in irregular shapes and edge direction, so studies of the graphene-boron nitride interface were restricted to the microscopy of nanodomains. Here we report templated growth of single crystalline hexagonal boron nitride directly from the oriented edge of hexagonal graphene flakes by atmospheric pressure chemical vapor deposition, and physical property measurements that inform the design of in-plane hybrid electronics. Ribbons of boron nitride monolayer were grown from the edge of a graphene template and inherited its crystallographic orientation. The relative sharpness of the interface was tuned through control of growth conditions. Frequent tearing at the graphene-boron nitride interface was observed, so density functional theory was used to determine that the nitrogen-terminated interface was prone to instability during cool down. The electronic functionality of monolayer heterostructures was demonstrated through fabrication of field effect transistors with boron nitride as an in-plane gate dielectric.

The optical properties of GaNSb alloys with N contents of up to 2.5% have been investigated at room temperature using infrared absorption spectroscopy. The evolution of the absorption onsets with N content has been described using a three level band anticrossing model of the N localized states interactions with the GaSb conduction band. This approach includes the effect of N pair states, which is critical to reproduce the observed optical properties. This confirms theoretical predictions that N pair states have a more pronounced effect on the band dispersion in GaNSb than in GaNAs.

We developed a scalable, label-free all-electronic sensor for D-glucose based on a carbon nanotube transistor functionalized with pyrene-1-boronic acid. This sensor responds to glucose in the range 1 μM–100 mM, which includes typical glucose concentrations in human blood and saliva. Control experiments establish that functionalization with the boronic acid provides high sensitivity and selectivity for glucose. The devices show better sensitivity than commercial blood glucose meters and could represent a general strategy to bloodless glucose monitoring by detecting low concentrations of glucose in saliva.