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1.  Morphological and chemical stability of silicon nanostructures and their molecular overlayers under physiological conditions: towards long-term implantable nanoelectronic biosensors 
The detection of biological and chemical species is of key importance to numerous areas of medical and life sciences. Therefore, a great interest exists in developing new, rapid, miniature, biocompatible and highly sensitive sensors, capable to operate under physiological conditions and displaying long-term stabilities (e.g. in-body implantable sensors). Silicon nanostructures, nanowires and nanotubes, have been extensively explored as building blocks for the creation of improved electrical biosensing devices, by virtue of their remarkably high surface-to-volume ratios, and have shown exceptional sensitivity for the real time label-free detection of molecular species adsorbed on their surfaces, down to the sensitivity of single molecules.
Yet, till this date, almost no rigorous studies have been performed on the temporal morphological stability of these nanostructures, and their resulting electrical devices, under physiological conditions (e.g. serum, blood), as well as on the chemical stability of the molecular recognition over-layers covering these structures.
Here, we present systematic time-resolved results on the morphological stability of bare Si nanowire building blocks, as well on the chemical stability of siloxane-based molecular over-layers, under physiological conditions. Furthermore, in order to overcome the observed short-term morpho-chemical instabilities, we present on the chemical passivation of the Si nanostructures by thin metal oxide nanoshells, in the range of 3–10 nm. The thickness of the metal oxide layer influences on the resulting electrical sensitivity of the fabricated FETs (field effect transistors), with an optimum thickness of 3–4 nm.
The core-shell structures display remarkable long-term morphological stability, preventing both, the chemical hydrolytic dissolution of the silicon under-structure and the concomitant loss of the siloxane-based chemical over-layers, for periods of at least several months. Electrical devices constructed from these nanostructures display excellent electrical characteristics and detection sensitivities, with exceptionally high morphological and functional stabilities. These results pave the road for the creation of long-term implantable biosensing devices in general, and nanodevices in particular.
PMCID: PMC3975481  PMID: 24606762
Nanowire; Field effect transistors; Chemical stability; Silicon; Dissolution; Biosensors
2.  Metal Oxide Nanosensors Using Polymeric Membranes, Enzymes and Antibody Receptors as Ion and Molecular Recognition Elements 
Sensors (Basel, Switzerland)  2014;14(5):8605-8632.
The concept of recognition and biofunctionality has attracted increasing interest in the fields of chemistry and material sciences. Advances in the field of nanotechnology for the synthesis of desired metal oxide nanostructures have provided a solid platform for the integration of nanoelectronic devices. These nanoelectronics-based devices have the ability to recognize molecular species of living organisms, and they have created the possibility for advanced chemical sensing functionalities with low limits of detection in the nanomolar range. In this review, various metal oxides, such as ZnO-, CuO-, and NiO-based nanosensors, are described using different methods (receptors) of functionalization for molecular and ion recognition. These functionalized metal oxide surfaces with a specific receptor involve either a complex formation between the receptor and the analyte or an electrostatic interaction during the chemical sensing of analytes. Metal oxide nanostructures are considered revolutionary nanomaterials that have a specific surface for the immobilization of biomolecules with much needed orientation, good conformation and enhanced biological activity which further improve the sensing properties of nanosensors. Metal oxide nanostructures are associated with certain unique optical, electrical and molecular characteristics in addition to unique functionalities and surface charge features which shows attractive platforms for interfacing biorecognition elements with effective transducing properties for signal amplification. There is a great opportunity in the near future for metal oxide nanostructure-based miniaturization and the development of engineering sensor devices.
PMCID: PMC4063009  PMID: 24841244
ZnO nanostructures; CuO nanostructures; NiO nanostructures; potentiometric nanosensors; biosensors; chemical sensors
3.  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.
PMCID: PMC3108850  PMID: 20688506
Carbon nanotubes; chemiresistor; field-effect transistor; label-free; immunosensor; explosives
4.  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.
PMCID: PMC3190593  PMID: 21203849
Nanowire; Biosensor; pH sensing; Sensitivity; Biasing; Width; Dielectric
5.  Analytical Calculation of Sensing Parameters on Carbon Nanotube Based Gas Sensors 
Sensors (Basel, Switzerland)  2014;14(3):5502-5515.
Carbon Nanotubes (CNTs) are generally nano-scale tubes comprising a network of carbon atoms in a cylindrical setting that compared with silicon counterparts present outstanding characteristics such as high mechanical strength, high sensing capability and large surface-to-volume ratio. These characteristics, in addition to the fact that CNTs experience changes in their electrical conductance when exposed to different gases, make them appropriate candidates for use in sensing/measuring applications such as gas detection devices. In this research, a model for a Field Effect Transistor (FET)-based structure has been developed as a platform for a gas detection sensor in which the CNT conductance change resulting from the chemical reaction between NH3 and CNT has been employed to model the sensing mechanism with proposed sensing parameters. The research implements the same FET-based structure as in the work of Peng et al. on nanotube-based NH3 gas detection. With respect to this conductance change, the I–V characteristic of the CNT is investigated. Finally, a comparative study shows satisfactory agreement between the proposed model and the experimental data from the mentioned research.
PMCID: PMC4004004  PMID: 24658617
carbon nanotubes (CNTs); NH3 gas sensor; I–V characteristic; field effect transistor (FET)
6.  Analytical modeling of glucose biosensors based on carbon nanotubes 
In recent years, carbon nanotubes have received widespread attention as promising carbon-based nanoelectronic devices. Due to their exceptional physical, chemical, and electrical properties, namely a high surface-to-volume ratio, their enhanced electron transfer properties, and their high thermal conductivity, carbon nanotubes can be used effectively as electrochemical sensors. The integration of carbon nanotubes with a functional group provides a good and solid support for the immobilization of enzymes. The determination of glucose levels using biosensors, particularly in the medical diagnostics and food industries, is gaining mass appeal. Glucose biosensors detect the glucose molecule by catalyzing glucose to gluconic acid and hydrogen peroxide in the presence of oxygen. This action provides high accuracy and a quick detection rate. In this paper, a single-wall carbon nanotube field-effect transistor biosensor for glucose detection is analytically modeled. In the proposed model, the glucose concentration is presented as a function of gate voltage. Subsequently, the proposed model is compared with existing experimental data. A good consensus between the model and the experimental data is reported. The simulated data demonstrate that the analytical model can be employed with an electrochemical glucose sensor to predict the behavior of the sensing mechanism in biosensors.
PMCID: PMC3898395  PMID: 24428818
Carbon nanotube; SWCNT FET; Glucose detection; Biosensor; Analytical model; I-V characteristics; PBS; Glucose oxide
7.  Porphyrins-Functionalized Single-Walled Carbon Nanotubes Chemiresistive Sensor Arrays for VOCs 
Single-walled carbon nanotubes (SWNTs) have been used extensively for sensor fabrication due to its high surface to volume ratio, nanosized structure and interesting electronic property. Lack of selectivity is a major limitation for SWNTs-based sensors. However, surface modification of SWNTs with a suitable molecular recognition system can enhance the sensitivity. On the other hand, porphyrins have been widely investigated as functional materials for chemical sensor fabrication due to their several unique and interesting physico-chemical properties. Structural differences between free-base and metal substituted porphyrins make them suitable for improving selectivity of sensors. However, their poor conductivity is an impediment in fabrication of prophyrin-based chemiresistor sensors. The present attempt is to resolve these issues by combining freebase- and metallo-porphyrins with SWNTs to fabricate SWNTs-porphyrin hybrid chemiresistor sensor arrays for monitoring volatile organic carbons (VOCs) in air. Differences in sensing performance were noticed for porphyrin with different functional group and with different central metal atom. The mechanistic study for acetone sensing was done using field-effect transistor (FET) measurements and revealed that the sensing mechanism of ruthenium octaethyl porphyrin hybrid device was governed by electrostatic gating effect, whereas iron tetraphenyl porphyrin hybrid device was governed by electrostatic gating and Schottky barrier modulation in combination. Further, the recorded electronic responses for all hybrid sensors were analyzed using a pattern-recognition analysis tool. The pattern-recognition analysis confirmed a definite pattern in response for different hybrid material and could efficiently differentiate analytes from one another. This discriminating capability of the hybrid nanosensor devices open up the possibilities for further development of highly dense nanosensor array with suitable porphyrin for E-nose application.
PMCID: PMC3292351  PMID: 22393460
Single-Walled Carbon Nanotubes; Porphyrins; Chemiresistive; Nanosensor; Array; Volatile Organic Compounds
8.  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.
PMCID: PMC2824900  PMID: 20174481
Carbon nanotubes; biomedical applications; surface functionalization; biosensor; drug delivery; biomedical imaging
9.  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.
PMCID: PMC3303933  PMID: 22309132
nanosensor; nanoprobe; nano-bioelectronics; nanoelectronic device; diode
10.  Sequence-dependent electrical response of ssDNA-decorated carbon nanotube, field-effect transistors to dopamine 
Single-walled carbon nanotube (SWCNT)-based field-effect transistors (FETs) have been explored for use as biological/chemical sensors. Dopamine (DA) is a biomolecule with great clinical significance for disease diagnosis, however, SWCNT FETs lack responsivity and selectivity for its detection due to the presence of interfering compounds such as uric acid (UA). Surface modification of CNTs using single-stranded deoxyribonucleic acid (ssDNA) renders the surface responsive to DA and screens the interferent. Due to the presence of different bases in ssDNA, it is necessary to investigate the effect of sequence on the FET-based molecular recognition of DA. SWCNT FETs were decorated with homo- and repeated-base ssDNA sequences, and the electrical response induced by DA in the presence and absence of UA was gauged in terms of the variation in transistor electrical parameters including conductance, transconductance, threshold voltage and hysteresis gap. Our results showed that the response of ssDNA-decorated devices to DA, irrespective of the presence or absence of UA, was DNA sequence dependent and exhibited the trend: G > A > C and GA > GT > AC > CT, for homo- and repeated-base sequences, respectively. The different response of various SWCNT–ssDNA systems to DA underlines the sequence selectivity, whereas the detection of DA in the presence of UA highlights the molecular selectivity of the ssDNA-decorated devices.
PMCID: PMC4273222  PMID: 25551039
carbon nanotube; deoxyribonucleic acid; dopamine; field-effect transistor; uric acid
11.  Advances in NO2 sensing with individual single-walled carbon nanotube transistors 
The charge carrier transport in carbon nanotubes is highly sensitive to certain molecules attached to their surface. This property has generated interest for their application in sensing gases, chemicals and biomolecules. With over a decade of research, a clearer picture of the interactions between the carbon nanotube and its surroundings has been achieved. In this review, we intend to summarize the current knowledge on this topic, focusing not only on the effect of adsorbates but also the effect of dielectric charge traps on the electrical transport in single-walled carbon nanotube transistors that are to be used in sensing applications. Recently, contact-passivated, open-channel individual single-walled carbon nanotube field-effect transistors have been shown to be operational at room temperature with ultra-low power consumption. Sensor recovery within minutes through UV illumination or self-heating has been shown. Improvements in fabrication processes aimed at reducing the impact of charge traps have reduced the hysteresis, drift and low-frequency noise in carbon nanotube transistors. While open challenges such as large-scale fabrication, selectivity tuning and noise reduction still remain, these results demonstrate considerable progress in transforming the promise of carbon nanotube properties into functional ultra-low power, highly sensitive gas sensors.
PMCID: PMC4273237  PMID: 25551046
carbon nanotube field-effect transistors (CNFETs); cross-sensitivity; functionalization; gas sensors; hysteresis; low power; selectivity; self-heating; single walled carbon nanotubes
12.  Chemo-sensors development based on low-dimensional codoped Mn2O3-ZnO nanoparticles using flat-silver electrodes 
Semiconductor doped nanostructure materials have attained considerable attention owing to their electronic, opto-electronic, para-magnetic, photo-catalysis, electro-chemical, mechanical behaviors and their potential applications in different research areas. Doped nanomaterials might be a promising owing to their high-specific surface-area, low-resistances, high-catalytic activity, attractive electro-chemical and optical properties. Nanomaterials are also scientifically significant transition metal-doped nanostructure materials owing to their extraordinary mechanical, optical, electrical, electronic, thermal, and magnetic characteristics. Recently, it has gained significant interest in manganese oxide doped-semiconductor materials in order to develop their physico-chemical behaviors and extend their efficient applications. It has not only investigated the basic of magnetism, but also has huge potential in scientific features such as magnetic materials, bio- & chemi-sensors, photo-catalysts, and absorbent nanomaterials.
The chemical sensor also displays the higher-sensitivity, reproducibility, long-term stability, and enhanced electrochemical responses. The calibration plot is linear (r2 = 0.977) over the 0.1 nM to 50.0 μM 4-nitrophenol concentration ranges. The sensitivity and detection limit is ~4.6667 μA cm-2 μM-1 and ~0.83 ± 0.2 nM (at a Signal-to-Noise-Ratio, SNR of 3) respectively. To best of our knowledge, this is the first report for detection of 4-nitrophenol chemical with doped Mn2O3-ZnO NPs using easy and reliable I-V technique in short response time.
As for the doped nanostructures, NPs are introduced a route to a new generation of toxic chemo-sensors, but a premeditate effort has to be applied for doped Mn2O3-ZnO NPs to be taken comprehensively for large-scale applications, and to achieve higher-potential density with accessible to individual chemo-sensors. In this report, it is also discussed the prospective utilization of Mn2O3-ZnO NPs on the basis of carcinogenic chemical sensing, which could also be applied for the detection of hazardous chemicals in ecological, environmental, and health care fields.
PMCID: PMC3630067  PMID: 23537000
Doped Mn2O3-ZnO nanoparticles; Wet-chemical method; Powder X-ray diffraction; 4-nitrophenol; I-V technique; X-ray photoelectron spectroscopy; Sensitivity
13.  Electrochemical Sensors for the Detection of Lead and Other Toxic Heavy Metals: The Next Generation of Personal Exposure Biomonitors 
Environmental Health Perspectives  2007;115(12):1683-1690.
To support the development and implementation of biological monitoring programs, we need quantitative technologies for measuring xenobiotic exposure. Microanalytical based sensors that work with complex biomatrices such as blood, urine, or saliva are being developed and validated and will improve our ability to make definitive associations between chemical exposures and disease. Among toxic metals, lead continues to be one of the most problematic. Despite considerable efforts to identify and eliminate Pb exposure sources, this metal remains a significant health concern, particularly for young children. Ongoing research focuses on the development of portable metal analyzers that have many advantages over current available technologies, thus potentially representing the next generation of toxic metal analyzers. In this article, we highlight the development and validation of two classes of metal analyzers for the voltammetric detection of Pb, including: a) an analyzer based on flow injection analysis and anodic stripping voltammetry at a mercury-film electrode, and b) Hg-free metal analyzers employing adsorptive stripping voltammetry and novel nanostructure materials that include the self-assembled monolayers on mesoporous supports and carbon nanotubes. These sensors have been optimized to detect Pb in urine, blood, and saliva as accurately as the state-of-the-art inductively coupled plasma-mass spectrometry with high reproducibility, and sensitivity allows. These improved and portable analytical sensor platforms will facilitate our ability to conduct biological monitoring programs to understand the relationship between chemical exposure assessment and disease outcomes.
PMCID: PMC2137133  PMID: 18087583
biomonitoring; dosimetry technology; electrochemical sensors; exposure assessment; lead (Pb)
14.  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.
PMCID: PMC3265614  PMID: 22136380
carbon nanotubes; graphene; carbohydrate; lectin; sensors
15.  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.
PMCID: PMC3506495  PMID: 22655750
16.  An analytical approach to evaluate the performance of graphene and carbon nanotubes for NH3 gas sensor applications 
Carbon, in its variety of allotropes, especially graphene and carbon nanotubes (CNTs), holds great potential for applications in variety of sensors because of dangling π-bonds that can react with chemical elements. In spite of their excellent features, carbon nanotubes (CNTs) and graphene have not been fully exploited in the development of the nanoelectronic industry mainly because of poor understanding of the band structure of these allotropes. A mathematical model is proposed with a clear purpose to acquire an analytical understanding of the field-effect-transistor (FET) based gas detection mechanism. The conductance change in the CNT/graphene channel resulting from the chemical reaction between the gas and channel surface molecules is emphasized. NH3 has been used as the prototype gas to be detected by the nanosensor and the corresponding current–voltage (I–V) characteristics of the FET-based sensor are studied. A graphene-based gas sensor model is also developed. The results from graphene and CNT models are compared with the experimental data. A satisfactory agreement, within the uncertainties of the experiments, is obtained. Graphene-based gas sensor exhibits higher conductivity compared to that of CNT-based counterpart for similar ambient conditions.
PMCID: PMC4077376  PMID: 24991510
carbon nanotube (CNT); conductance; FET-based gas sensor; graphene
17.  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.
PMCID: PMC2820132  PMID: 19908823
18.  Direct Growth of Vertically-oriented Graphene for Field-Effect Transistor Biosensor 
Scientific Reports  2013;3:1696.
A sensitive and selective field-effect transistor (FET) biosensor is demonstrated using vertically-oriented graphene (VG) sheets labeled with gold nanoparticle (NP)-antibody conjugates. VG sheets are directly grown on the sensor electrode using a plasma-enhanced chemical vapor deposition (PECVD) method and function as the sensing channel. The protein detection is accomplished through measuring changes in the electrical signal from the FET sensor upon the antibody-antigen binding. The novel biosensor with unique graphene morphology shows high sensitivity (down to ~2 ng/ml or 13 pM) and selectivity towards specific proteins. The PECVD growth of VG presents a one-step and reliable approach to prepare graphene-based electronic biosensors.
PMCID: PMC3631944  PMID: 23603871
19.  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.
PMCID: PMC3367324  PMID: 22262038
20.  Highly sensitive glucose sensors based on enzyme-modified whole-graphene solution-gated transistors 
Scientific Reports  2015;5:8311.
Noninvasive glucose detections are convenient techniques for the diagnosis of diabetes mellitus, which require high performance glucose sensors. However, conventional electrochemical glucose sensors are not sensitive enough for these applications. Here, highly sensitive glucose sensors are successfully realized based on whole-graphene solution-gated transistors with the graphene gate electrodes modified with an enzyme glucose oxidase. The sensitivity of the devices is dramatically improved by co-modifying the graphene gates with Pt nanoparticles due to the enhanced electrocatalytic activity of the electrodes. The sensing mechanism is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate. The optimized glucose sensors show the detection limits down to 0.5 μM and good selectivity, which are sensitive enough for non-invasive glucose detections in body fluids. The devices show the transconductances two orders of magnitude higher than that of a conventional silicon field effect transistor, which is the main reason for their high sensitivity. Moreover, the devices can be conveniently fabricated with low cost. Therefore, the whole-graphene solution-gated transistors are a high-performance sensing platform for not only glucose detections but also many other types of biosensors that may find practical applications in the near future.
PMCID: PMC4319171  PMID: 25655666
21.  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.
PMCID: PMC2694561  PMID: 19516964
Nanomaterials; toxicogenomics.
22.  Solid-State, Dye-Labeled DNA Detects Volatile Compounds in the Vapor Phase 
PLoS Biology  2008;6(1):e9.
This paper demonstrates a previously unreported property of deoxyribonucleic acid—the ability of dye-labeled, solid-state DNA dried onto a surface to detect odors delivered in the vapor phase by changes in fluorescence. This property is useful for engineering systems to detect volatiles and provides a way for artificial sensors to emulate the way cross-reactive olfactory receptors respond to and encode single odorous compounds and mixtures. Recent studies show that the vertebrate olfactory receptor repertoire arises from an unusually large gene family and that the receptor types that have been tested so far show variable breadths of response. In designing biomimetic artificial noses, the challenge has been to generate a similarly large sensor repertoire that can be manufactured with exact chemical precision and reproducibility and that has the requisite combinatorial complexity to detect odors in the real world. Here we describe an approach for generating and screening large, diverse libraries of defined sensors using single-stranded, fluorescent dye–labeled DNA that has been dried onto a substrate and pulsed with brief exposures to different odors. These new solid-state DNA-based sensors are sensitive and show differential, sequence-dependent responses. Furthermore, we show that large DNA-based sensor libraries can be rapidly screened for odor response diversity using standard high-throughput microarray methods. These observations describe new properties of DNA and provide a generalized approach for producing explicitly tailored sensor arrays that can be rationally chosen for the detection of target volatiles with different chemical structures that include biologically derived odors, toxic chemicals, and explosives.
Author Summary
Biological systems can provide engineering guidance on how evolution has solved particular problems. In the context of detecting chemicals in either the aqueous or vapor phase, two general biological approaches have emerged. The first relies on individual highly specific single receptors (sensors), each tuned to detect a single molecular species—examples include the receptors that mediate pheromone detection in insects or those that function in neurotransmission. Specificity is achieved by narrow band design. The second approach is implemented by arrays of receptors with relatively broad responses. In this case, specificity emerges from a constellation of receptor types that recognizes the molecule of interest—the canonical example here is the olfactory receptors in the main olfactory system of vertebrates. Specificity is achieved by a “one chemical–many broadly responsive detectors” paradigm. While trying to mimic the enormous odor coding ability of biological olfaction in an “artificial nose,” we searched for molecules with the requisite combinatorial capacity to serve as odor detectors. Here we show that single-stranded DNA molecules tagged with a fluorescent reporter and deposited onto solid surfaces can respond to vapor phase odor pulses in a sequence-selective manner. These findings demonstrate new properties of nucleotide molecules that can be exploited in engineered odor detection devices. In addition, this broadband responsivity to small molecules should be explored as a functional aspect of DNA (and RNA) as they exist in the normal cellular milieu.
Short sequences of solid-state DNA can selectively signal their interactions with small molecules in the vapor phase. These observations have been implemented in odor sensing in an electronic "nose" and further suggest that in vivo responses to small molecules may represent new, nongenetic attributes of DNA.
PMCID: PMC2211549  PMID: 18215112
23.  Carbon Nanotube Chemiresistor for Wireless pH Sensing 
Scientific Reports  2014;4:4468.
The ability to accurately measure real-time pH fluctuations in-vivo could be highly advantageous. Early detection and potential prevention of bacteria colonization of surgical implants can be accomplished by monitoring associated acidosis. However, conventional glass membrane or ion-selective field-effect transistor (ISFET) pH sensing technologies both require a reference electrode which may suffer from leakage of electrolytes and potential contamination. Herein, we describe a solid-state sensor based on oxidized single-walled carbon nanotubes (ox-SWNTs) functionalized with the conductive polymer poly(1-aminoanthracene) (PAA). This device had a Nernstian response over a wide pH range (2–12) and retained sensitivity over 120 days. The sensor was also attached to a passively-powered radio-frequency identification (RFID) tag which transmits pH data through simulated skin. This battery-less, reference electrode free, wirelessly transmitting sensor platform shows potential for biomedical applications as an implantable sensor, adjacent to surgical implants detecting for infection.
PMCID: PMC3966035  PMID: 24667793
24.  One-Dimensional Nanostructure Field-Effect Sensors for Gas Detection 
Sensors (Basel, Switzerland)  2014;14(8):13999-14020.
Recently; one-dimensional (1D) nanostructure field-effect transistors (FETs) have attracted much attention because of their potential application in gas sensing. Micro/nanoscaled field-effect sensors combine the advantages of 1D nanostructures and the characteristic of field modulation. 1D nanostructures provide a large surface area-volume ratio; which is an outstanding advantage for gas sensors with high sensitivity and fast response. In addition; the nature of the single crystals is favorable for the studies of the response mechanism. On the other hand; one main merit of the field-effect sensors is to provide an extra gate electrode to realize the current modulation; so that the sensitivity can be dramatically enhanced by changing the conductivity when operating the sensors in the subthreshold regime. This article reviews the recent developments in the field of 1D nanostructure FET for gas detection. The sensor configuration; the performance as well as their sensing mechanism are evaluated.
PMCID: PMC4179014  PMID: 25090418
gas sensors; one-dimensional nanostructures; semiconductor; field-effect transistor
25.  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.
PMCID: PMC2952181  PMID: 20504802
electrophoretic deposition; carbon nanotubes; hydroxyapatite; bioactive glass; scaffolds; tissue engineering

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