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A novel low temperature fabrication approach of multichannel zinc oxide nanowire field effect transistors for biosensing applications
Abstract
p class="MsoNormal">Sensing of bacteria, viruses and biomolecules is increasingly important for environmental monitoring and healthcare applications. Electronic devices as transducer elements, that are scaled down to nanometre dimensions offer a sensitive electrical detection of bioanalytes. In this work, nanowire field effect transistors (NWFET) made from zinc oxide (ZnO) offer high sensitivity and low thermal budget fabrication compared to silicon nanowire sensors.
The novelty of this work is a new low temperature top-down fabrication process, which makes it possible to define ZnO NWFET arrays with different numbers of nanowires simultaneously and systematically compare their electrical performance. The main feature of this process is a developed bilayer photoresist pattern with a retrograde profile, which enables the modification of the nanowire in width, length, height and the number of transistor channels. The approach is compatible with low cost manufacture without electron beam lithography and benefits from process temperatures below 150ºC. Process reliability has been investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD) and atomic force microscopy (AFM). The nanowires exhibit a cross section dimension of 30.9 nm height and 257.4 nm width and varying lengths from 5 µm to 45 µm and show a very smooth top surface with a root mean squared (rms) roughness of only 1.2 nm. Electrical measurements demonstrate enhancement mode transistors, which show a scalable correlation between the number of nanowires and the electrical characteristics. Thereby, devices with 100 nanowires exhibit the best performance with a high field effect mobility of 11.0 cm<sup>2</sup>/Vs, on/off current ratio of 4 × 10<sup>7</sup> and subthreshold swing of 660 mV/dec.
The fabricated multichannel ZnO NWFET have been investigated for their potential bio-sensing capabilities. The ZnO NWFET passivated with Al<sub>2</sub>O<sub>3</sub> is able to operate 16 hours continuously in phosphate buffered saline (PBS) solution with a very small current drift of 1.3 % per hour. It was found, that an Al<sub>2</sub>O<sub>3</sub> passivation layer of 30 nm gives the best electrical performance of the ZnO NWFETs. Hereby, the ZnO NWFET shows a very good recovery behaviour up to 81.8 % of its original signal output current. The output current of the ZnO NWFET shifts to different ionic strengths in aqueous solutions and changes during exposure with 10x, 100x and 1000x diluted PBS of up to 23.7%. Investigations on the sensing capabilities on proteins show that the ZnO NWFET responds at a very low drain voltage of 5 mV to varying charges within liquid solutions containing lysozyme and bovines serum albumin (BSA). An output current signal change between these two proteins of 295.5 % was measured, indicating a very good sensitivity of the ZnO nanowire channel to the presence of surrounding charges.
After evidence was provided that the fabricated ZnO NWFET are capable for bio-sensing experiments, a mask design was developed, which allows to package the ZnO NWFET with gold wire bonding onto a polychlorinated biphenyl (PCB) board to enable statistical bio-sensing experiments. Hereby individual ZnO NWFETs can be addressed and measured by flushing laser cut poly(methyl methacrylate) (PMMA) micro fluidic channels with analytes solutions.</p
... 1: A schematic of the structure of a biosensor[34]. ...
... IBE was used instead of a plasma etching technique because IBE prevents unwanted uncontrollable side effects such as charging. IBE was also preferred to etching with CHF3 and Cl2 prevent the reaction of the ZnO with the photoresist which would leave difficult to remove residues such as zinc fluoride (ZnF 2 ) and zinc chloride (ZnCl 2 )[34]. Using a two step etch process with a beam current of 300 mA, beam voltage of 500 V, 400 V beam accelerator, 550 mA neutralizer, 500 W RF, 5 o C platen temperature, the exposed ZnO layer was etched at a rate of 17 nm/min. ...
Cancer is a complex disease characterised by genes which encode oncogenic and tumour-suppressor proteins. microRNAs (miRNA), a group of small noncoding RNAs that regulate gene expression, have been shown to participate in a number of essential biological process including cell proliferation control, hematopoietic B-cell lineage fate, B-cell survival, brain patterning, pancreatic cell insulin secretion and adipocyte development [1]. Abnormal expression, that is, the loss, amplification and mutations of miRNA genes has been identified in a wide variety of cancers including B-Cell Chronic Lymphocytic Leukemia (B-CLL) [2], breast carcinoma [3], primary glioblastoma [4], hepatocellular carcinoma [5], papillary thyroid carcinoma [6], lung cancer [7], colon carcinoma [8], and pancreatic tumours [9]. Presently, medical diagnostic tests, by and large, are performed in laboratories equipped with benchtop analyzers and operated by trained lab technicians. Although these systems have a high throughput, in most cases patients wait a number of days to receive their test results [10]. Being able to perform diagnostic tests at or near the site where patients encounter the health care system; and receiving the results within the time frame of a consultation with a healthcare professional (approximately 15 minutes [11]), would be extremely beneficial. It would provide actionable information that can lead to several changes in patient management. With respect to cancer diagnostics and treatment, this would reduce the need for multiple patient visits; enabling the prompt treatment of the illness in a more targeted fashion. Point of Care (PoC) devices are diagnostic devices which rapidly provide actionable information for patient care at the time and location of an encounter with the health care system. They are becoming more prevalent. The most commonly found type of PoC device is the Lateral Flow Immunoassays (LFIA) [12] [13]. However, LFIA conventionally provide qualitative results (i.e., yes or no) which are of little use when trying to gauge changes in concentration as would be needed in detecting the loss or amplification miRNA strands. Furthermore, LFIA suffers from difficulties due to varying consistency of the flow rate and from non-uniform dispersion of the sample to label [10]. Field Effect Transistor (FET) biosensors, a promising class of PoC devices, have been shown to able to distinguish between iv different concentrations of molecular analyte [14]. This function would be vital in cancer diagnosis revolving around detection of the abnormal expression of miRNA. This is because cancerous cells typically manifest a deviation in miRNA concentration from the normal range. These FETs are made with established semiconductor techniques and technologies meaning that, they can be readily integrated with other electronic systems. This would enable on chip signal processing and the instantaneous electronic transmission of results from remote areas to a centralised hub. The goal is to leverage the advantages in semiconductor technologies to develop a PoC device for cancer diagnostics. This is to enable cancers to be caught and treated earlier thus reducing the need for invasive or debilitating treatments like surgery or chemotherapy. In pursuit of this goal, the preliminary step was to fabricate FETs capable of detecting changes in miRNA concentration. The FETs fabricated for this purpose were Zinc Oxide Nanowire Field Effect Transistors (NWFETs) arrays. ZnO is an ideal material with which to fabricate these NWFETs because it is naturally a n-type semiconductor [15], thus eliminating the need for a high temperature doping process steps. ZnO has a large and direct band-gap (3.37 eV [16]) which enables it to sustain large electric fields; withstand higher breakdown voltages; generate lower levels of noise; and operate at high temperatures and levels of power [17]. The ZnO NWFETs were passivated with stack high-κ dielectrics. The stack layer consists of a layer of Hafnium dioxide sandwiched between two Aluminium oxide layers which has been shown to diminish threshold voltage drift effectively [18]. Once fabricated, the ZnO NWFETs were first tested to observe how well they functioned as transducers of ionic charge. The ZnO NWFETs were seen to be excellent transducers of ionic charge with a shift in gate voltage per pH of 117 mV/pH. This shift in gate voltage per pH is comparable to largest known value of 220 mV/pH recorded by Knopfmacher’s single Silicon NWFET with a Dual Gate [19]. It is also twice as large as the Nernst limit (59 mV/pH). Following the pH-sensing experiment, a microDNA(miDNA) detection investigation was conducted. miDNA are the stable biological equivalent of miRNA and thus can serve as proxy of miRNA detection. The result of the investigation was compelling. The ZnO NWFETs were found to have a 43.88% Sensitivity to one order of magnitude changes in miDNA concentration (10 nM, 100 nM and 1 µM). Subsequently, the same investigation was carried out with miRNA as the analyte. In this instance the ZnO NWFETs were found to have a 5.07% Sensitivity to one order of magnitude changes in miRNA concentration of (10 nM, 100 nM and 1 µM). These results irrevocably demonstrate that ZnO NWFETs are capable of detecting changes in miRNA concentration. Thus, making ZnO NWFETs a suitable candidate for the development of a PoC device with which to conduct cancer diagnostics.
An ion sensitive field effect transistor can outperform conventional ion-selective electrodes. Thus, a zinc oxide (ZnO) nanowire field effect transistor (NWFET) pH sensor was fabricated and measured. The sensor contained a channel with 1.7×1018 cm-3 donor concentration and 100 ZnO nanowires in parallel, each with the following dimensions: 10 μm×120 nm×20 nm. The active channel is passivated with an 18 nm Al2O3 layer. The device was measured under a controlled environment with and without pH solutions. The pH range was 3–9 with a sensitivity of 2.48 mV to 10.3 mV. The voltage sensitivity translates to a percentage value of 15%. The measurements obtained before and after the pH solution treatment demonstrate the possibility of re-use of the device by rinsing and brushing the sensing layer.
This paper describes a new low cost top-down fabrication process, which makes
it possible to define nanowire field effect transistor (NWFET) arrays with different
numbers of nanowires simultaneously and systematically compare their electrical
performance. The main feature of this process is a developed bilayer photoresist
pattern with a retrograde profile, which enables the modification of the nanowire
in width, length, height and the number of transistor channels. The approach is
compatible with low cost manufacture without electron beam lithography and benefits from process temperatures below 190 deg C. Process reliability has been investigated by SEM, TEM and AFM. Electrical measurements demonstrate enhancement mode transistors, which show a scalable correlation between the number of nanowires and the electrical characteristics. Devices with 100 nanowires exhibit the best performance with a high field effect mobility of 11.0 cm2/Vs, on/off current ratio of 3.97e7 and subthreshold swing of 0.66 V/dec.
ZnO based nanowire FETs have been fabricated by implementing a top-down approach, which uses optical photolithography, atomic layer deposition (ALD) of ZnO thin film, and anisotropic plasma etching. The effects of Phosphate Buffered Saline (PBS) solution on the surface of ZnO nanowire were investigated by measuring the FET characteristics at different PBS dilutions. The drain current, ION , exhibited an increase of 39 times in the highest PBS solution concentration compared to measurement in air. From the measured transfer characteristics and output characteristics in various PBS dilutions, the device was found to maintain n-type behaviour. These results indicate that the device can be effectively used for biomolecules sensing.
Field-Effect Transistor sensors (FET-sensors) have been receiving increasing attention for biomolecular sensing over the last two decades due to their potential for ultra-high sensitivity sensing, label-free operation, cost reduction and miniaturisation. Whilst the commercial application of FET-sensors in pH sensing has been realised, their commercial application in biomolecular sensing (termed BioFETs) is hindered by poor understanding of how to optimise device design for highly reproducible operation and high sensitivity. In part, these problems stem from the highly interdisciplinary nature of the problems encountered in this field, in which knowledge of biomolecular-binding kinetics, surface chemistry, electrical double layer physics and electrical engineering is required. In this work, a quantitative analysis and critical review has been performed comparing literature FET-sensor data for pH-sensing with data for sensing of biomolecular streptavidin binding to surface-bound biotin systems. The aim is to provide the first systematic, quantitative comparison of BioFET results for a single biomolecular analyte, specifically Streptavidin, which is the most commonly used model protein in biosensing experiments, and often used as an initial proof-of-concept for new biosensor designs. This novel quantitative and comparative analysis of the surface potential behaviour of a range of devices demonstrated a strong contrast between the trends observed in pH-sensing and those in biomolecule-sensing. Potential explanations are discussed in detail and surface-chemistry optimisation is shown to be a vital component in sensitivity-enhancement. Factors which can influence the response, yet which have not always been fully appreciated, are explored and practical suggestions are provided on how to improve experimental design.
A novel supercycled atomic layer deposition (ALD) process which combines thermal ALD process with in situ O2 plasma treatment is presented in this work to deposit ZnO thin films with highly tunable electrical properties. Both O2 plasma time and the number of thermal ALD cycles in a supercycle can be adjusted to achieve fine tuning of film resistivity and carrier concentration up to six orders of magnitude without extrinsic doping. The concentration of hydrogen defects are believed to play a major role in adjusting the electrical properties of ZnO films. Kelvin probe force microscopy results evidently show the shift of Fermi level in different ZnO films and are well associated with the changing of carrier concentration. This reliable and robust technique reported here clearly points towards the capability of using this method to produce ZnO films with controlled properties in different applications.
Electronic supplementary material
The online version of this article (10.1186/s11671-017-2308-1) contains supplementary material, which is available to authorized users.
Aluminum-doped ZnO (AZO) has huge prospects in the field of conductive electrodes, due to its low price, high transparency, and pro-environment. However, enhancing the conductivity of AZO and realizing ohmic contact between the semiconductor and AZO source/drain (S/D) electrodes without thermal annealing remains a challenge. Here, an approach called pulsed laser deposition (PLD) is reported to improve the comprehensive quality of AZO films due to the high energy of the laser and non-existence of the ion damage. The 80-nm-thick AZO S/D electrodes show remarkable optical properties (transparency: 90.43%, optical band gap: 3.42 eV), good electrical properties (resistivity: 16 × 10−4 Ω·cm, hall mobility: 3.47 cm2/V·s, carrier concentration: 9.77 × 1020 cm−3), and superior surface roughness (Rq = 1.15 nm with scanning area of 5 × 5 μm2). More significantly, their corresponding thin film transistor (TFT) with low contact resistance (RSD = 0.3 MΩ) exhibits excellent performance with a saturation mobility (µsat) of 8.59 cm2/V·s, an Ion/Ioff ratio of 4.13 × 106, a subthreshold swing (SS) of 0.435 V/decade, as well as good stability under PBS/NBS. Furthermore, the average transparency of the unpatterned multi-films composing this transparent TFT can reach 78.5%. The fabrication of this TFT can be suitably transferred to transparent arrays or flexible substrates, which is in line with the trend of display development.
Through their application in energy-efficient and environmentally friendly devices, zinc oxide (ZnO) and related classes of wide gap semiconductors, including GaN and SiC, are revolutionizing numerous areas, from lighting, energy conversion, photovoltaics, and communications to biotechnology, imaging, and medicine. With an emphasis on engineering and materials science, Handbook of Zinc Oxide and Related Materials provides a comprehensive, up-to-date review of various technological aspects of ZnO. Volume Two focuses on devices and nanostructures created from ZnO and similar materials. The book covers various nanostructures, synthesis/creation strategies, device behavior, and state-of-the-art applications in electronics and optoelectronics. It also provides useful information on the device and nanoscale process and examines the fabrication of LEDs, LDs, photodetectors, and nanodevices. Covering key properties and important technologies of ZnO-based devices and nanoengineering, the handbook highlights the potential of this wide gap semiconductor. It also illustrates the remaining challenging issues in nanomaterial preparation and device fabrication for R&D in the twenty-first century.
In 2006, the group of Dr C.M. Lieber pioneered the field of nanowire sensors by fabricating devices for the ultra-sensitive label-free detection of biological macromolecules. Since then, nanowire sensors have demonstrated their ability to detect cancer-associated analytes in peripheral blood, tumor tissue, and the exhaled breath of cancer patients. These innovative developments have marked a new era with unprecedented detection performance, capable of addressing crucial needs such as cancer diagnosis and monitoring disease progression and patient response to therapy. The ability of nanowire sensors to identify molecular features of patient tumor represents a first step toward precision medicine, and their integration into portable devices has the potential to revolutionize cancer diagnosis and patient monitoring.
p>Memristive biosensors have been proved as excellent candidates for ultrasensitive biosensing. In this work, a novel portable bio-detection system based on memristive biosensors is designed, developed and tested for providing a significantly fast, automatic and simultaneous sensing output of multiple memristive biosensors on a single chip. The suggested compact and independent bio-sensing prototype is achieved through the realization of an electronic board designed for addressing the specifications of the memristive biosensor signal acquisition. Memristive bio-sensing-chips are specially designed and fabricated as well. The system was tested for successfully sensing of Prostate Specific Antigen, one of the main biomarkers of prostate cancer, at fM concentrations. Overall, this novel scheme resembles to a memristive-biosensing-kit approach, paving the way for fast and ultrasensitive PoC (point-of-care) devices.</p
Available at: https://eprints.soton.ac.uk/id/eprint/419586
Field-Effect Transistor-sensors (FET-sensors) are a class of pH and biomolecule sensors that can be produced at a low cost and with high sensitivity, as a result having potential for commercialisation and widespread use. The response of a FET-sensor is generated when the electric field at the sensor surface changes, thereby inducing a measurable change in current through the device. The electric field can be modified by pH or by binding of an analyte to the surface. The solid state counterpart, the Metal Oxide Semiconductor FET, has been extensively studied as it is the basis of modern electronics. FET-sensors are less well understood, mainly due to the inherent complexity introduced by the aqueous media present at the sensor surface. The FET-sensor surface is usually an oxide such as silica and its interaction with aqueous solution introduces many complex effects, such as ion-dynamics and pH dependent ionisation, which make these systems non-trivial to understand and predict. To-date, most models of FET-sensor response have relied upon mean-field assumptions which neglect the multi-scale nature of the system and even qualitative predictions of FET-sensor response remain challenging.
In the work presented here, the interfacial physics of FET-sensors were modelled using a variety of simulation techniques at different time- and length-scales. Acid-base surface charging reactions at the oxide surface of the sensor are an important part of FET-sensor response. Density Functional Theory (DFT) simulations revealed a new mechanism of surface charging and also showed that these reactions have no well-defined transition state which can be used to model their kinetics. A Kinetic Monte Carlo (KMC) model was validated that can be used describe the dynamics of surface-charging reactions on a device scale.
As FET-sensors operate by detecting changes in the interfacial electric field, the mean net charge density of surface-bound biomolecules is an important parameter in most models of BioFET response. Semi-empirical calculations were performed to estimate the net charge of two different biomolecular systems relevant to biosensing studies. The ion dynamics in the electrical double layer at the silicawater-biomolecule interface were investigated using classical Molecular Dynamics (MD) simulations, which suggested that, in contrast to commonly used net-charge arguments for FET-sensor response, the importance of water polarisation for FET-sensor response has been hitherto underestimated.
A quantitative analysis of data extracted from the FET-sensor literature was performed, comparing experimental biosensing data with pH-sensing data. This revealed some frequent problems related to reproducibility and comparability of experimental data in this field, and highlighted that optimisation of surface chemistry is an underappreciated component of sensor optimisation. Despite these limitations, BioFET research is a rapidly advancing field in which novel device design and operation methodologies are constantly being developed which increase the viability of BioFET devices for commercial use.