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1.  Carbon nanotubes-based chemiresistive immunosensor for small molecules: Detection of nitroaromatic explosives 
Biosensors & bioelectronics  2010;26(4):1297-1301.
In recent years, there has been a growing focus on use of one-dimensional (1-D) nanostructures, such as carbon nanotubes and nanowires, as transducer elements for label-free chemiresistive/field-effect transistor biosensors as they provide label-free and high sensitivity detection. While research to-date has elucidated the power of carbon nanotubes- and other 1-D nanostructure- based field effect transistors immunosensors for large charged macromolecules such as proteins and viruses, their application to small uncharged or charged molecules has not been demonstrated. In this paper we report a single-walled carbon nanotubes (SWNTs)-based chemiresistive immunosensor for label-free, rapid, sensitive and selective detection of 2,4,6-trinitrotoluene (TNT), a small molecule. The newly developed immunosensor employed a displacement mode/format in which SWNTs network forming conduction channel of the sensor was first modified with trinitrophenyl (TNP), an analog of TNT, and then ligated with the anti-TNP single chain antibody. Upon exposure to TNT or its derivatives the bound antibodies were displaced producing a large change, several folds higher than the noise, in the resistance/conductance of SWNTs giving excellent limit of detection, sensitivity and selectivity. The sensor detected between 0.5 ppb and 5000 ppb TNT with good selectivity to other nitroaromatic explosives and demonstrated good accuracy for monitoring TNT in untreated environmental water matrix. We believe this new displacement format can be easily generalized to other one-dimensional nanostructure-based chemiresistive immuno/affinity-sensors for detecting small and/or uncharged molecules of interest in environmental monitoring and health care.
doi:10.1016/j.bios.2010.07.017
PMCID: PMC3108850  PMID: 20688506
Carbon nanotubes; chemiresistor; field-effect transistor; label-free; immunosensor; explosives
2.  Carbon Nanotubes in Biology and Medicine: In vitro and in vivo Detection, Imaging and Drug Delivery 
Nano research  2009;2(2):85-120.
Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications in the past few years. In this comprehensive review, we summarize the main results from our and other groups in this field and clarify that surface functionalization is critical to the behavior of carbon nanotubes in biological systems. Ultrasensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of biomolecules on the hydrophobic nanotube surface. Electrical nanosensors based on nanotubes provide a label-free approach to biological detection. Surface-enhanced Raman spectroscopy of carbon nanotubes opens up a method of protein microarray with detection sensitivity down to 1 fmol/L. In vitro and in vivo toxicity studies reveal that highly water soluble and serum stable nanotubes are biocompatible, nontoxic, and potentially useful for biomedical applications. In vivo biodistributions vary with the functionalization and possibly also size of nanotubes, with a tendency to accumulate in the reticuloendothelial system (RES), including the liver and spleen, after intravenous administration. If well functionalized, nanotubes may be excreted mainly through the biliary pathway in feces. Carbon nanotube-based drug delivery has shown promise in various In vitro and in vivo experiments including delivery of small interfering RNA (siRNA), paclitaxel and doxorubicin. Moreover, single-walled carbon nanotubes with various interesting intrinsic optical properties have been used as novel photoluminescence, Raman, and photoacoustic contrast agents for imaging of cells and animals. Further multidisciplinary explorations in this field may bring new opportunities in the realm of biomedicine.
doi:10.1007/s12274-009-9009-8
PMCID: PMC2824900  PMID: 20174481
Carbon nanotubes; biomedical applications; surface functionalization; biosensor; drug delivery; biomedical imaging
3.  Electronic Detection of Lectins Using Carbohydrate Functionalized Nanostructures: Graphene versus Carbon Nanotubes 
ACS Nano  2011;6(1):760-770.
Here we investigated the interactions between lectins and carbohydrates using field-effect transistor (FET) devices comprised of chemically converted graphene (CCG) and single-walled carbon nanotubes (SWNTs). Pyrene- and porphyrin-based glycoconjugates were functionalized noncovalently on the surface of CCG-FET and SWNT-FET devices, which were then treated with 2 µM of nonspecific and specific lectins. In particular, three different lectins (PA-IL, PA-IIL and ConA) and three carbohydrate epitopes (galactose, fucose and mannose) were tested. The responses of 36 different devices were compared and rationalized using computer-aided models of carbon nanostructure/glycoconjugate interactions. Glycoconjugates surface coverage in addition to one-dimensional structures of SWNTs resulted in optimal lectin detection. Additionally, lectin titration data of SWNT- and CCG-based biosensors were used to calculate lectin dissociation constants (Kd) and compare them to the values obtained from the isothermal titration microcalorimetry (ITC) technique.
doi:10.1021/nn2042384
PMCID: PMC3265614  PMID: 22136380
carbon nanotubes; graphene; carbohydrate; lectin; sensors
4.  Ferroelectric memory based on nanostructures 
Nanoscale Research Letters  2012;7(1):285.
In the past decades, ferroelectric materials have attracted wide attention due to their applications in nonvolatile memory devices (NVMDs) rendered by the electrically switchable spontaneous polarizations. Furthermore, the combination of ferroelectric and nanomaterials opens a new route to fabricating a nanoscale memory device with ultrahigh memory integration, which greatly eases the ever increasing scaling and economic challenges encountered in the traditional semiconductor industry. In this review, we summarize the recent development of the nonvolatile ferroelectric field effect transistor (FeFET) memory devices based on nanostructures. The operating principles of FeFET are introduced first, followed by the discussion of the real FeFET memory nanodevices based on oxide nanowires, nanoparticles, semiconductor nanotetrapods, carbon nanotubes, and graphene. Finally, we present the opportunities and challenges in nanomemory devices and our views on the future prospects of NVMDs.
doi:10.1186/1556-276X-7-285
PMCID: PMC3506495  PMID: 22655750
5.  Toxicogenomics to Improve Comprehension of the Mechanisms Underlying Responses of In Vitro and In Vivo Systems to Nanomaterials: A Review  
Current Genomics  2008;9(8):571-585.
Engineered nanomaterials are commonly defined as materials with at least one dimension of 100 nanometers or less. Such materials typically possess nanostructure-dependent properties (e.g., chemical, mechanical, electrical, optical, magnetic, biological), which make them desiderable for commercial or medical application. However, these same properties may potentially lead to nanostructure-dependent biological activity that differs from and is not directly predicted by the bulk properties of the constitutive chemicals and compounds. Nanoparticles and nanomaterials can be on the same scale of living cells components, including proteins, nucleic acids, lipids and cellular organelles. When considering nanoparticles it must be asked how man-made nanostructures can interact with or influence biological systems. Carbon nanotubes (CNTs) are an example of carbon-based nanomaterial, which has won a huge spreading in nanotechnology. The incorporation of CNTs in living systems has raised many concerns because of their hydrophobicity and tendency to aggregate and accumulate into cells, organs, and tissues with dangerous effects.
Applications of toxicogenomics to both investigative and predictive toxicology will contribute to the in-depth investigation of molecular mechanisms or the mode of nanomaterials action that is achieved by using conventional toxicological approaches. Parallel toxicogenomic technologies will promote a valuable platform for the development of biomarkers, in order to predict possible nanomaterial’s toxicity. The potential of characteristic gene expression profiles (“fingerprint”) of exposure or toxicological response to nanoparticles will be discussed in the review to enhance comprehension of the molecular mechanism of in vivo and in vitro system exposed to nanomaterials.
doi:10.2174/138920208786847962
PMCID: PMC2694561  PMID: 19516964
Nanomaterials; toxicogenomics.
6.  Subthreshold Regime has the Optimal Sensitivity for Nanowire FET Biosensors 
Nano letters  2010;10(2):547.
Nanowire field-effect transistors (NW-FETs) are emerging as powerful sensors for detection of chemical/biological species with various attractive features including high sensitivity and direct electrical readout. Yet to date there have been limited systematic studies addressing how the fundamental factors of devices affect their sensitivity. Here we demonstrate that the sensitivity of NW-FET sensors can be exponentially enhanced in the subthreshold regime where the gating effect of molecules bound on surface is the most effective due to the reduced screening of carriers in NWs. This principle is exemplified in both pH and protein sensing experiments where the operational mode of NW-FET biosensors was tuned by electrolyte gating. The lowest charge detectable by NW-FET sensors working under different operational modes is also estimated. Our work shows that optimization of NW-FET structure and operating conditions can provide significant enhancement and fundamental understanding for the sensitivity limits of NW-FET sensors.
doi:10.1021/nl9034219
PMCID: PMC2820132  PMID: 19908823
7.  High-k dielectric Al2O3 nanowire and nanoplate field effect sensors for improved pH sensing 
Biomedical microdevices  2011;13(2):335-344.
Over the last decade, field-effect transistors (FETs) with nanoscale dimensions have emerged as possible label-free biological and chemical sensors capable of highly sensitive detection of various entities and processes. While significant progress has been made towards improving their sensitivity, much is yet to be explored in the study of various critical parameters, such as the choice of a sensing dielectric, the choice of applied front and back gate biases, the design of the device dimensions, and many others. In this work, we present a process to fabricate nanowire and nanoplate FETs with Al2O3 gate dielectrics and we compare these devices with FETs with SiO2 gate dielectrics. The use of a high-k dielectric such as Al2O3 allows for the physical thickness of the gate dielectric to be thicker without losing sensitivity to charge, which then reduces leakage currents and results in devices that are highly robust in fluid. This optimized process results in devices stable for up to 8 h in fluidic environments. Using pH sensing as a benchmark, we show the importance of optimizing the device bias, particularly the back gate bias which modulates the effective channel thickness. We also demonstrate that devices with Al2O3 gate dielectrics exhibit superior sensitivity to pH when compared to devices with SiO2 gate dielectrics. Finally, we show that when the effective electrical silicon channel thickness is on the order of the Debye length, device response to pH is virtually independent of device width. These silicon FET sensors could become integral components of future silicon based Lab on Chip systems.
doi:10.1007/s10544-010-9497-z
PMCID: PMC3190593  PMID: 21203849
Nanowire; Biosensor; pH sensing; Sensitivity; Biasing; Width; Dielectric
8.  Label-free electrical detection of pyrophosphate generated from DNA polymerase reactions on field-effect devices† 
The Analyst  2012;137(6):1351-1362.
We introduce a label-free approach for sensing polymerase reactions on deoxyribonucleic acid (DNA) using a chelator-modified silicon-on-insulator field-effect transistor (SOI-FET) that exhibits selective and reversible electrical response to pyrophosphate anions. The chemical modification of the sensor surface was designed to include rolling-circle amplification (RCA) DNA colonies for locally enhanced pyrophosphate (PPi) signal generation and sensors with immobilized chelators for capture and surface-sensitive detection of diffusible reaction by-products. While detecting arrays of enzymatic base incorporation reactions is typically accomplished using optical fluorescence or chemiluminescence techniques, our results suggest that it is possible to develop scalable and portable PPi-specific sensors and platforms for broad biomedical applications such as DNA sequencing and microbe detection using surface-sensitive electrical readout techniques.
doi:10.1039/c2an15930a
PMCID: PMC3367324  PMID: 22262038
9.  High Sensitivity Gas Detection Using a Macroscopic Three-Dimensional Graphene Foam Network 
Scientific Reports  2011;1:166.
Nanostructures are known to be exquisitely sensitive to the chemical environment and offer ultra-high sensitivity for gas-sensing. However, the fabrication and operation of devices that use individual nanostructures for sensing is complex, expensive and suffers from poor reliability due to contamination and large variability from sample-to-sample. By contrast, conventional solid-state and conducting-polymer sensors offer excellent reliability but suffer from reduced sensitivity at room-temperature. Here we report a macro graphene foam-like three-dimensional network which combines the best of both worlds. The walls of the foam are comprised of few-layer graphene sheets resulting in high sensitivity; we demonstrate parts-per-million level detection of NH3 and NO2 in air at room-temperature. Further, the foam is a mechanically robust and flexible macro-scale network that is easy to contact (without Lithography) and can rival the durability and affordability of traditional sensors. Moreover, Joule-heating expels chemisorbed molecules from the foam's surface leading to fully-reversible and low-power operation.
doi:10.1038/srep00166
PMCID: PMC3240974  PMID: 22355681
10.  Protein Biosensors Based on Polymer Nanowires, Carbon Nanotubes and Zinc Oxide Nanorods 
Sensors (Basel, Switzerland)  2011;11(5):5087-5111.
The development of biosensors using electrochemical methods is a promising application in the field of biotechnology. High sensitivity sensors for the bio-detection of proteins have been developed using several kinds of nanomaterials. The performance of the sensors depends on the type of nanostructures with which the biomaterials interact. One dimensional (1-D) structures such as nanowires, nanotubes and nanorods are proven to have high potential for bio-applications. In this paper we review these three different kinds of nanostructures that have attracted much attention at recent times with their great performance as biosensors. Materials such as polymers, carbon and zinc oxide have been widely used for the fabrication of nanostructures because of their enhanced performance in terms of sensitivity, biocompatibility, and ease of preparation. Thus we consider polymer nanowires, carbon nanotubes and zinc oxide nanorods for discussion in this paper. We consider three stages in the development of biosensors: (a) fabrication of biomaterials into nanostructures, (b) alignment of the nanostructures and (c) immobilization of proteins. Two different methods by which the biosensors can be developed at each stage for all the three nanostructures are examined. Finally, we conclude by mentioning some of the major challenges faced by many researchers who seek to fabricate biosensors for real time applications.
doi:10.3390/s110505087
PMCID: PMC3231366  PMID: 22163892
biosensor; nanostructures; electrochemical; immobilization
11.  Carbon Nanotube Thin Film Biosensors for Sensitive and Reproducible Whole Virus Detection 
Theranostics  2012;2(3):251-257.
Here, we report the label-free, sensitive, and real-time electrical detection of whole viruses using carbon nanotube thin film (CNT-TF) field effect devices. Selective detection of approximately 550 model viruses, M13-bacteriophage, is demonstrated using a simple two-terminal (no gate electrode) configuration. Chemical gating through specific antibody-virus binding on CNT surface is proposed to be the sensing mechanism. Compared to electrical impedance sensors with identical microelectrode dimensions (no CNT), the CNT-TF sensors exhibit sensitivity 5 orders higher. We believe the reported approach could lead to a reproducible and cost-effective solution for rapid viral identification.
doi:10.7150/thno.3726
PMCID: PMC3311235  PMID: 22448194
carbon nanotube; thin film; virus detection; electrochemical impedance sensor; microelectrodes; M13-pIII antibody; M13 bacteriophage; ELISA.
12.  Top-gated CVD Graphene Transistors with Current Saturation 
Nano letters  2011;11(6):2555-2559.
Graphene transistors are of considerable interest for radio frequency (RF) applications. In general, transistors with large transconductance and drain current saturation is desirable for RF performance, which is however nontrivial to achieve in graphene transistors. Here we report high performance top-gated graphene transistors based on chemical vapor deposition (CVD) grown graphene with large transconductance and drain current saturation. The graphene transistors were fabricated with evaporated high dielectric constant material (HfO2) as the top-gate dielectrics. Length scaling studies of the transistors with channel length from 5.6 µm to 100 nm shows that complete current saturation can be achieved in 5.6 µm devices and the saturation characteristics degrade as the channel length shrinks down to 100–300 nm regime. The drain current saturation was primarily attributed to drain bias induced shift of the Dirac points. With the selective deposition of HfO2 gate dielectrics, we have further demonstrated a simple scheme to realize a 300 nm channel length graphene transistors with self-aligned source-drain electrodes to achieve the highest transconductance of 250 µS/µm reported in CVD graphene to date.
doi:10.1021/nl201331x
PMCID: PMC3236244  PMID: 21548551
Graphene; transistors; dielectrics; current saturation; self-alignment
13.  A Critical Review of Glucose Biosensors Based on Carbon Nanomaterials: Carbon Nanotubes and Graphene 
Sensors (Basel, Switzerland)  2012;12(5):5996-6022.
There has been an explosion of research into the physical and chemical properties of carbon-based nanomaterials, since the discovery of carbon nanotubes (CNTs) by Iijima in 1991. Carbon nanomaterials offer unique advantages in several areas, like high surface-volume ratio, high electrical conductivity, chemical stability and strong mechanical strength, and are thus frequently being incorporated into sensing elements. Carbon nanomaterial-based sensors generally have higher sensitivities and a lower detection limit than conventional ones. In this review, a brief history of glucose biosensors is firstly presented. The carbon nanotube and grapheme-based biosensors, are introduced in Sections 3 and 4, respectively, which cover synthesis methods, up-to-date sensing approaches and nonenzymatic hybrid sensors. Finally, we briefly outline the current status and future direction for carbon nanomaterials to be used in the sensing area.
doi:10.3390/s120505996
PMCID: PMC3386727  PMID: 22778628
glucose biosensor; carbon nanotube; graphene; non-enzymatic sensor; nanotechnology
14.  A pH sensor based on electric properties of nanotubes on a glass substrate 
Nanoscale Research Letters  2007;2(4):207-212.
We fabricated a pH-sensitive device on a glass substrate based on properties of carbon nanotubes. Nanotubes were immobilized specifically on chemically modified areas on a substrate followed by deposition of metallic source and drain electrodes on the area. Some nanotubes connected the source and drain electrodes. A top gate electrode was fabricated on an insulating layer of silane coupling agent on the nanotube. The device showed properties of ann-type field effect transistor when a potential was applied to the nanotube from the top gate electrode. Before fabrication of the insulating layer, the device showed that thep-type field effect transistor and the current through the source and drain electrodes depend on the buffer pH. The current increases with decreasing pH of the CNT solution. This device, which can detect pH, is applicable for use as a biosensor through modification of the CNT surface.
doi:10.1007/s11671-007-9053-9
PMCID: PMC3246224  PMID: 21806848
Carbon nanotube; Field effect transistor; pH; Glass; Immobilization
15.  One-Dimensional Oxide Nanostructures as Gas-Sensing Materials: Review and Issues 
Sensors (Basel, Switzerland)  2010;10(4):4083-4099.
In this article, we review gas sensor application of one-dimensional (1D) metal-oxide nanostructures with major emphases on the types of device structure and issues for realizing practical sensors. One of the most important steps in fabricating 1D-nanostructure devices is manipulation and making electrical contacts of the nanostructures. Gas sensors based on individual 1D nanostructure, which were usually fabricated using electron-beam lithography, have been a platform technology for fundamental research. Recently, gas sensors with practical applicability were proposed, which were fabricated with an array of 1D nanostructures using scalable micro-fabrication tools. In the second part of the paper, some critical issues are pointed out including long-term stability, gas selectivity, and room-temperature operation of 1D-nanostructure-based metal-oxide gas sensors.
doi:10.3390/s100404083
PMCID: PMC3274262  PMID: 22319343
1-dimensional nanostructures; gas sensors; long-term stability; gas selectivity; electronic-nose; room-temperature operation
16.  Electrophoretic deposition of biomaterials 
Journal of the Royal Society Interface  2010;7(Suppl_5):S581-S613.
Electrophoretic deposition (EPD) is attracting increasing attention as an effective technique for the processing of biomaterials, specifically bioactive coatings and biomedical nanostructures. The well-known advantages of EPD for the production of a wide range of microstructures and nanostructures as well as unique and complex material combinations are being exploited, starting from well-dispersed suspensions of biomaterials in particulate form (microsized and nanoscale particles, nanotubes, nanoplatelets). EPD of biological entities such as enzymes, bacteria and cells is also being investigated. The review presents a comprehensive summary and discussion of relevant recent work on EPD describing the specific application of the technique in the processing of several biomaterials, focusing on (i) conventional bioactive (inorganic) coatings, e.g. hydroxyapatite or bioactive glass coatings on orthopaedic implants, and (ii) biomedical nanostructures, including biopolymer–ceramic nanocomposites, carbon nanotube coatings, tissue engineering scaffolds, deposition of proteins and other biological entities for sensors and advanced functional coatings. It is the intention to inform the reader on how EPD has become an important tool in advanced biomaterials processing, as a convenient alternative to conventional methods, and to present the potential of the technique to manipulate and control the deposition of a range of nanomaterials of interest in the biomedical and biotechnology fields.
doi:10.1098/rsif.2010.0156.focus
PMCID: PMC2952181  PMID: 20504802
electrophoretic deposition; carbon nanotubes; hydroxyapatite; bioactive glass; scaffolds; tissue engineering
17.  Kinked p-n Junction Nanowire Probes for High Spatial Resolution Sensing and Intracellular Recording 
Nano Letters  2012;12(3):1711-1716.
Semiconductor nanowires and other semiconducting nanoscale materials configured as field-effect transistors have been studied extensively as biological/chemical (bio/chem.) sensors. These nanomaterials have demonstrated high-sensitivity from one- and two-dimensional sensors, although the realization of the ultimate point-like detector has not been achieved. In this regard, nanoscale p-n diodes are attractive since the device element is naturally localized near the junction, and while nanowire p-n diodes have been widely studied as photovoltaic devices, their applications as bio/chem. sensors have not been explored. Here we demonstrate that p-n diode devices can serve as a new and powerful family of highly localized biosensor probes. Designed nanoscale axial p-n junctions were synthetically introduced at the joints of kinked silicon nanowires. Scanning electron microscopy images showed that the kinked nanowire structures were achieved, and electrical transport measurements exhibited rectifying behavior with well-defined turn-on in forward bias as expected for a p-n diode. In addition, scanning gate microscopy demonstrated that the most sensitive region of these nanowires was localized near the kinked region at the p-n junction. High spatial resolution sensing using these p-n diode probes was carried out in aqueous solution using fluorescent charged polystyrene nanobeads. Multiplexed electrical measurements show well-defined single-nanoparticle detection, and experiments with simultaneous confocal imaging correlate directly the motion of the nanobeads with the electrical signals recorded from the p-n devices. In addition, kinked p-n junction nanowires configured as three-dimensional probes demonstrate the capability of intracellular recording of action potentials from electrogenic cells. These p-n junction kinked nanowire devices, which represent a new way of constructing nanoscale probes with highly-localized sensing regions, provide substantial opportunity in areas ranging from bio/chem. sensing and nanoscale photon detection to three-dimensional recording from within living cells and tissue.
doi:10.1021/nl300256r
PMCID: PMC3303933  PMID: 22309132
nanosensor; nanoprobe; nano-bioelectronics; nanoelectronic device; diode
18.  Electronic sensitivity of single-walled carbon nanotube to internal electrolyte composition 
Nanotechnology  2012;23(8):085203.
Carbon nanotubes (CNTs) are well-known as materials for nanoelectronics and show great potential to be used as the sensing element in chemical and biological sensors. Recently, CNTs have been shown to be effective nanofluidic channels and the transport of substances through small diameter CNTs is intrinsically fast, selective, and operates at the single molecule level. It has been shown that the transport characteristics of semiconducting single-walled CNT (SWCNT) field effect transistor (FET) are sensitive to internal water wetting. We report here that the characteristics of semiconducting SWCNT FETs are also sensitive to the concentration, pH and ion type of ionic solution when the electrolytes are inside the CNT. Such sensitivity is not observed at the outside surface of a semiconducting SWCNT. This opens a new avenue for building new types of CNT sensor devices in which the SWCNT concurrently functions as a nanochannel and an electronic detector.
doi:10.1088/0957-4484/23/8/085203
PMCID: PMC3343206  PMID: 22293518
nanofluidics; nanopore; nanochannel; carbon nanotube; CNT FET; chemical and biosensor
19.  Electric Field Guided Assembly of One-Dimensional Nanostructures for High Performance Sensors 
Sensors (Basel, Switzerland)  2012;12(5):5725-5751.
Various nanowire or nanotube-based devices have been demonstrated to fulfill the anticipated future demands on sensors. To fabricate such devices, electric field-based methods have demonstrated a great potential to integrate one-dimensional nanostructures into various forms. This review paper discusses theoretical and experimental aspects of the working principles, the assembled structures, and the unique functions associated with electric field-based assembly. The challenges and opportunities of the assembly methods are addressed in conjunction with future directions toward high performance sensors.
doi:10.3390/s120505725
PMCID: PMC3386709  PMID: 22778610
review; electric field; nanowire; nanotubes; assembly; sensors
20.  Lipid bilayer coated Al2O3 nanopore sensors: towards a hybrid biological solid-state nanopore 
Biomedical microdevices  2011;13(4):671-682.
Solid-state nanopore sensors are highly versatile platforms for the rapid, label-free electrical detection and analysis of single molecules, applicable to next generation DNA sequencing. The versatility of this technology allows for both large scale device integration and interfacing with biological systems. Here we report on the development of a hybrid biological solid-state nanopore platform that incorporates a highly mobile lipid bilayer on a single solid-state Al2O3 nanopore sensor, for the potential reconstitution of ion channels and biological nanopores. Such a system seeks to combine the superior electrical, thermal, and mechanical stability of Al2O3 solid-state nanopores with the chemical specificity of biological nanopores. Bilayers on Al2O3 exhibit higher diffusivity than those formed on TiO2 and SiO2 substrates, attributed to the presence of a thick hydration layer on Al2O3, a key requirement to preserving the biological functionality of reconstituted membrane proteins. Molecular dynamics simulations demonstrate that the electrostatic repulsion between the dipole of the DOPC headgroup and the positively charged Al2O3 surface may be responsible for the enhanced thickness of this hydration layer. Lipid bilayer coated Al2O3 nanopore sensors exhibit excellent electrical properties and enhanced mechanical stability (GΩ seals for over 50 h), making this technology ideal for use in ion channel electrophysiology, the screening of ion channel active drugs and future integration with biological nanopores such as α-hemolysin and MspA for rapid single molecule DNA sequencing. This technology can find broad application in bio-nanotechnology.
doi:10.1007/s10544-011-9537-3
PMCID: PMC3175492  PMID: 21487665
Nanopore; Al2O3; Lipid bilayer; Hybrid biological solid-state Nanopore
21.  Nanostructured Substrates for Optical Sensing 
Sensors that change color have the advantages of versatility, ease of use, high sensitivity, and low cost. The recent development of optically based chemical sensing platforms has increasingly employed substrates manufactured with advanced processing or fabrication techniques to provide precise control over shape and morphology of the sensor micro- and nano-structure. New sensors have resulted with improved capabilities for a number of sensing applications, including the detection of biomolecules and environmental monitoring. This perspective focuses on recent optical sensor devices that utilize nanostructured substrates.
doi:10.1021/jz201147g
PMCID: PMC3235654  PMID: 22174955
Colorimetric Sensors; Diffraction Gratings; Photonics; Plasmonics; Nanostructures; Sensors
22.  Microfabricated Reference Electrodes and their Biosensing Applications 
Sensors (Basel, Switzerland)  2010;10(3):1679-1715.
Over the past two decades, there has been an increasing trend towards miniaturization of both biological and chemical sensors and their integration with miniaturized sample pre-processing and analysis systems. These miniaturized lab-on-chip devices have several functional advantages including low cost, their ability to analyze smaller samples, faster analysis time, suitability for automation, and increased reliability and repeatability. Electrical based sensing methods that transduce biological or chemical signals into the electrical domain are a dominant part of the lab-on-chip devices. A vital part of any electrochemical sensing system is the reference electrode, which is a probe that is capable of measuring the potential on the solution side of an electrochemical interface. Research on miniaturization of this crucial component and analysis of the parameters that affect its performance, stability and lifetime, is sparse. In this paper, we present the basic electrochemistry and thermodynamics of these reference electrodes and illustrate the uses of reference electrodes in electrochemical and biological measurements. Different electrochemical systems that are used as reference electrodes will be presented, and an overview of some contemporary advances in electrode miniaturization and their performance will be provided.
doi:10.3390/s100301679
PMCID: PMC3264446  PMID: 22294894
electrode; reference electrode; microfabrication; biosensor; electrochemical; lab-on-chip
23.  Wet-spinning assembly of continuous, neat, and macroscopic graphene fibers 
Scientific Reports  2012;2:613.
Graphene is now the most attractive carbon-based material. Integration of 2D graphene sheets into macroscopic architectures such as fibers illuminates the direction to translate the excellent properties of individual graphene into advanced hierarchical ensembles for promising applications in new graphene-based nanodevices. However, the lack of effective, low-cost and convenient assembly strategy has blocked its further development. Herein, we demonstrate that neat and macroscopic graphene fibers with high mechanical strength and electrical conductivity can be fluidly spun from the common graphene oxide (GO) suspensions in large scale followed with chemical reduction. The curliness-fold formation mechanism of GO fiber has been proposed. This wet-spinning technique presented here facilitates the multifunctionalization of macroscopic graphene-based fibers with various organic or inorganic components by an easy-handle in situ or post-synthesis approach, which builds the solid foundation to access a new family of advanced composite materials for the next practical applications.
doi:10.1038/srep00613
PMCID: PMC3430881  PMID: 22937222
24.  Label-free electrical detection of DNA hybridization using carbon nanotubes and graphene 
Nano Reviews  2010;1:10.3402/nano.v1i0.5354.
The interface between biosystems and nanomaterials is emerging for detection of various biomolecules and subtle cellular activities. In particular, the development of cost-effective and sequence-selective DNA detection is urgent for the diagnosis of genetic or pathogenic diseases. Graphene-based nanocarbon materials, such as carbon nanotubes and thin graphene layers, have been employed as biosensors because they are biocompatible, extraordinarily sensitive, and promising for large-area detection. Electrical and label-free detection of DNA can be achieved by monitoring the conductance change of devices fabricated from these carbon materials. Here, the recent advances in this research area are briefly reviewed. The key issues and perspectives of future development are also discussed.
doi:10.3402/nano.v1i0.5354
PMCID: PMC3215217  PMID: 22110861
carbon nanotubes; graphene; DNA hybridization; biosensors; label-free detection; transistors
25.  High speed graphene transistors with a self-aligned nanowire gate 
Nature  2010;467(7313):305-308.
Graphene has attracted considerable interest as a potential new electronic material1–11. With the highest carrier mobility exceeding 200,000 cm2/V·s, graphene is of particular interest for ultra-high speed radio frequency (RF) electronics12–18. However, the conventional dielectric integration and device fabrication processes cannot be readily applied to fabricate high speed graphene transistors because they can often introduce significant defects into the monolayer of carbon lattices and severely degrade the device performance19–21. Here we report a new approach to fabricate high-speed graphene transistors with a self-aligned nanowire gate to enable unprecedented performance. The graphene transistors are fabricated using a Co2Si/Al2O3 core/shell nanowire as the gate, with the source and drain electrodes defined through a self-alignment process and the channel length defined by the nanowire diameter. The physical assembly of nanowire gate preserves the high carrier mobility in graphene, and the self-aligned process ensures that the edges of the source, drain, and gate electrodes are automatically and precisely positioned so that no overlapping or significant gaps exist between these electrodes and thus minimizes access resistance. It therefore enables transistor performance not previously possible. Graphene transistors with channel length down to 140 nm have been fabricated with the highest scaled on-current (3.32 mA μm−1) and transconductance (1.27 mS μm−1) reported to date. Significantly, on-chip microwave measurements demonstrate that the self-aligned devices exhibit a record high intrinsic cutoff frequency (fT) in the range of 100–300 GHz, with the extrinsic fT in the range of a few gigahertz largely limited by parasitic pad capacitance. The reported intrinsic cutoff frequency of the graphene transistors is comparable to that of the very best high electron mobility transistors with similar gate lengths10. It therefore marks an important milestone in graphene RF devices and can enable exciting opportunities in high-speed electronics.
doi:10.1038/nature09405
PMCID: PMC2965636  PMID: 20811365

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