Silicon Nanowire Biosensor Research Articles

Fabrication of N-Type Silicon Nanowire Biosensor for Sub-10-Femtomolar Concentration of Immunoglobulin

A simple fabrication process of an n-type silicon nanowire (SiNW) biosensor for sub-10 femtomolar (fM) concentration immunoglobulin detection was presented in this work. The SiNWs with different widths of 80-190 nm were fabricated using electron beam lithography and reaction ion etching techniques. The electrical characteristics of SiNWs with various widths were measured. And it can be observed that thin SiNW has high resistance, which is in agreement with electrical resistance theory. Furthermore, the surface of the fabricated SiNW was functionalized by 3-aminopropyltriethoxysilane for making the biosensor device to detect the binding of immunoglobulin G (IgG) molecules. The responsivity of the biosensor was investigated by observing electrical performance in response due to IgG with various concentration from 6 fM to 600 nanomolar (nM). The resistance changing ratio based on the current voltage (I-V) characteristics was analyzed and it increased with increasing of the IgG concentration. As a result, it demonstrated that the n-type SiNW biosensor has the ability to detect the IgG molecules with low concentration of 6 fM.

The impact of the modified Poisson–Boltzmann model on protein bound to a lipid coated silicon nanowire field effect transistor biosensor in an electrolyte environment

ABSTRACTThe aim of this work was to analyse the electrostatic potential profile, various effects of electrolyte concentrations, and the influences of surface charge on a protein bound to a lipid coated Silicon nanowire field effect transistor (Si-NW FET) biosensor by implementing the modified Poisson–Boltzmann (MPB) model. In this work, we modelled a lipid monolayer-coated Si-NW FET for the sensing of proteins, which consisted of variable amounts of aspartic acid. The electrostatic potential profile, protein charge distributions, the response to various electrolyte concentration, and the impacts of various surface charge were studied by implementing the MPB model with the Si-NW FET biosensor. Additionally, a comparison between the use of the MPB and the Poisson–Boltzmann model in studying the effects of various surface charges was carried out. Taken together, it was found that the MPB model showed a higher resolution in studying the Si-NW FET biosensor model when higher concentrations and surface charges were administered.

Label-Free Direct Detection of MiRNAs with Poly-Silicon Nanowire Biosensors.

The diagnostic and prognostic value of microRNAs (miRNAs) in diseases becomes promising. Owing to fast response and high sensitivity, silicon nanowire (SiNW) biosensor has been considered a potential tool for miRNAs detection. Here, we describe a booming method to detect miRNAs with poly-silicon nanowire biosensors. Standard and real miRNA samples are applied in this study. The results show a limitation of 1 fM in the detection of standard miRNA sample with our poly-nanowire devices. Meanwhile, one-base mismatched sequence could be distinguished. Furthermore, these poly-SiNW arrays can detect snRNA U6 in total RNA samples extracted from HepG2 cells with a detection limitation of 0.2 μg/mL.

Recent Advances in Silicon Nanowire Biosensors: Synthesis Methods, Properties, and Applications.

The application of silicon nanowire (SiNW) biosensor as a subtle, label-free, and electrical tool has been extensively demonstrated by several researchers over the past few decades. Human ability to delicately fabricate and control its chemical configuration, morphology, and arrangement either separately or in combination with other materials as lead to the development of a nanomaterial with specific and efficient electronic and catalytic properties useful in the fields of biological sciences and renewable energy. This review illuminates on the various synthetic methods of SiNW, with its optical and electrical properties that make them one of the most applicable nanomaterials in the field of biomolecule sensing, photoelectrochemical conversion, and diseases diagnostics.

Silicon nanowire based biosensing platform for electrochemical sensing of Mebendazole drug activity on breast cancer cells

Electrochemical approaches have played crucial roles in bio sensing because of their Potential in achieving sensitive, specific and low-cost detection of biomolecules and other bio evidences. Engineering the electrochemical sensing interface with nanomaterials tends to new generations of label-free biosensors with improved performances in terms of sensitive area and response signals. Here we applied Silicon Nanowire (SiNW) array electrodes (in an integrated architecture of working, counter and reference electrodes) grown by low pressure chemical vapor deposition (LPCVD) system with VLS procedure to electrochemically diagnose the presence of breast cancer cells as well as their response to anticancer drugs. Mebendazole (MBZ), has been used as antitubulin drug. It perturbs the anodic/cathodic response of the cell covered biosensor by releasing Cytochrome C in cytoplasm. Reduction of cytochrome C would change the ionic state of the cells monitored by SiNW biosensor. By applying well direct bioelectrical contacts with cancer cells, SiNWs can detect minor signal transduction and bio recognition events, resulting in precise biosensing. Our device detected the trace of MBZ drugs (with the concentration of 2nM) on electrochemical activity MCF-7 cells. Also, experimented biological analysis such as confocal and Flowcytometry assays confirmed the electrochemical results.

Electrical detection of dengue virus (DENV) DNA oligomer using silicon nanowire biosensor with novel molecular gate control

In this paper, a silicon nanowire biosensor with novel molecular gate control has been demonstrated for Deoxyribonucleic acid (DNA) detection related to dengue virus (DENV). The silicon nanowire was fabricated using the top–down nanolithography approach, through nanostructuring of silicon-on-insulator (SOI) layers achieved by combination of the electron-beam lithography (EBL), plasma dry etching and size reduction processes. The surface of the fabricated silicon nanowire was functionalized by means of a three-step procedure involving surface modification, DNA immobilization and hybridization. This procedure acts as a molecular gate control to establish the electrical detection for 27-mers base targets DENV DNA oligomer. The electrical detection is based on the changes in current, resistance and conductance of the sensor due to accumulation of negative charges added by the immobilized probe DNA and hybridized target DNA. The sensitivity of the silicon nanowire biosensors attained was 45.0µAM−1, which shows a wide-range detection capability of the sensor with respect to DNA. The limit of detection (LOD) achieved was approximately 2.0fM. The demonstrated results show that the silicon nanowire has excellent properties for detection of DENV with outstanding repeatability and reproducibility performances.

Label-Free Direct Detection of miRNAs with Poly-Silicon Nanowire Biosensors.

BackgroundThe diagnostic and prognostic value of microRNAs (miRNAs) in a variety of diseases is promising. The novel silicon nanowire (SiNW) biosensors have advantages in molecular detection because of their high sensitivity and fast response. In this study, poly-crystalline silicon nanowire field-effect transistor (poly-SiNW FET) device was developed to achieve specific and ultrasensitive detection of miRNAs without labeling and amplification.MethodsThe poly-SiNW FET was fabricated by a top–down Complementary Metal Oxide Semiconductor (CMOS) wafer fabrication based technique. Single strand DNA (ssDNA) probe was bind to the surface of the poly-SiNW device which was silanated and aldehyde-modified. By comparing the difference of resistance value before and after ssDNA and miRNA hybridization, poly-SiNW device can be used to detect standard and real miRNA samples.ResultsPoly-SiNW device with different structures (different line width and different pitch) was applied to detect standard Let-7b sample with a detection limitation of 1 fM. One-base mismatched sequence could be distinguished meanwhile. Furthermore, these poly-SiNW arrays can detect snRNA U6 in total RNA samples extracted from HepG2 cells with a detection limitation of 0.2 μg/mL. In general, structures with pitch showed better results than those without pitch in detection of both Let-7b and snRNA U6. Moreover, structures with smaller pitch showed better detection efficacy.ConclusionOur findings suggest that poly-SiNW arrays could detect standard and real miRNA sample without labeling or amplification. Poly-SiNW biosensor device is promising for miRNA detection.

Improved Hydrolytic Stability and Repeatability: pH sensing with APTES-coated silicon nanowire bio-FETs

This article addresses the hydrolytic instability issue of surface chemistry and the repeatability issue of silicon (Si) nanowire (NW) biosensors. Si multi-NWs or nanograting (NG) field-effect transistors (FETs) were fabricated using semiconductor lithographic processing techniques. Then, the NG surfaces were coated with 3-aminopropyltriethoxysilane (APTES) via the vapor- and solution-phase methods. Their performance, including drift, stability, sensitivity, accuracy, and linearity of pH sensing, was evaluated. Sensors treated with both APTES deposition methods exhibit linear pH response with good sensitivity. Devices treated with vapor APTES show better linearity and sensitivity, and APTES-solution-coated devices are more stable with smaller drift. A hydrolysis process was developed to significantly improve the hydrolytic stability of the APTES-coated sensor surface. As a result, an accuracy of ?0.008 pH was achieved, which is comparable to or better than commercially available ion-sensitive FETs (ISFETs), whereas the sensor drift was significantly reduced for both sensors treated with vapor and solution APTES. This hydrolysis process has greatly improved the stability and repeatability of charge sensing of our Si NG bio-FETs.

Facile fabrication of a silicon nanowire sensor by two size reduction steps for detection of alpha-fetoprotein biomarker of liver cancer

We present a facile technique that only uses conventional micro-techniques and two size-reduction steps to fabricate wafer-scale silicon nanowire (SiNW) with widths of 200 nm. Initially, conventional lithography was used to pattern SiNW with 2 μm width. Then the nanowire width was decreased to 200 nm by two size-reduction steps with isotropic wet etching. The fabricated SiNW was further investigated when used with nanowire field-effect sensors. The electrical characteristics of the fabricated SiNW devices were characterized and pH sensitivity was investigated. Then a simple and effective surface modification process was carried out to modify SiNW for subsequent binding of a desired receptor. The complete SiNW-based biosensor was then used to detect alpha-fetoprotein (AFP), one of the medically approved biomarkers for liver cancer diagnosis. Electrical measurements showed that the developed SiNW biosensor could detect AFP with concentrations of about 100 ng mL−1. This concentration is lower than the necessary AFP concentration for liver cancer diagnosis.

Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a silicon nanowire biosensor

Alpha-fetoprotein (AFP) is a tumor-associated fetal protein that can be expressed in large amounts in adult tumor cells, serving as a useful clinical tumor-marker. Silicon nanowire (SiNW) biosensors have emerged as a powerful tool in detecting protein biomarkers, due to their ultrahigh sensitivity, real-time response and label-free detection. We fabricated a SiNW-based field-effect transistor (FET) according to “top-down” methodology. First, anti-AFP antibodies were immobilized onto the surface of the SiNW-FET. A polydimethylsiloxane (PDMS) microchannel was then integrated to the modified SiNW-FET. Various concentrations of AFP were then pumped through the sensing area. We observed a current change that corresponded to binding of AFP onto the surface of our anti-AFP functionalized SiNW-FET biosensor. Concentrations of AFP as low as 0.1 ng/mL were detected. The results implicate our SiNW biosensor as an effective AFP biomarker detector with promising potential in clinical applications.

An enhancement of high-k/oxide stacked dielectric structure for silicon-based multi-nanowire biosensor in cardiac troponin I detection

In this study, we demonstrate a series of multi-channel silicon nanowire (Si-NW) biosensors coated with different high-k dielectric materials for sensing property improvements. To enhance the compatibility to 3-Aminopropyltriethoxysilane (APTES) without any harsh surface treatment, a stacked structure of high-k dielectrics with ultrathin SiO2 is developed. Fluorescent experiments are employed to verify the enhancement. To experimentally examine the improvement of implemented devices, in addition, an acute myocradial infarction biomarker, cardiac troponin I (cTnI), with different concentrations is used. Based on the experimental results of ultrathin SiO2 sensing membrane structures stacked with 14nm Al2O3 and 10nm HfO2, compared with only high-k dielectric devices, the sensing property can be enhanced by 3.8 and 1.4 times, respectively. For the detection of lowest concentration, i.e. 320fM, the signal enhancement is 20%. Based on this work, the proposed SiO2/high-k structure for Si-NW biosensor can be experimentally demonstrates a good potential for future applications in cTnI detections.

Silicon nanowire biosensor for highly sensitive and multiplexed detection of oral squamous cell carcinoma biomarkers in saliva.

Silicon nanowire (SiNW) field-effect transistor (FET) biosensors have already been used as powerful sensors for the direct detection of disease-related biomarkers. However, the multiplexed detection of biomarkers in real samples is still challenging. Interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) are two typical biomarkers of oral squamous cell carcinoma (OSCC). In this study, we developed a multiplexed detection methodology for IL-8 and TNF-α detection in saliva using SiNW FET biosensors. We fabricated the SiNW FET sensors using a top-down lithography fabrication technique. Subsequently, we achieved the multiplexed detection of two biomarkers in saliva by specific recognition of the two biomarkers with their corresponding antibodies, which were modified on the SiNW. The established method was found to have a limit of detection as low as 10 fg/mL in 1 × PBS as well as 100 fg/mL in artificial saliva. Because of its advantages, including label-free and multiplexed detection, non-invasive analysis, highly sensitive and specific determination, the proposed method is expected to be widely used for the early diagnosis of OSCC.

Selective-process-based silicon nanowires batch fabrication technique and its surface biomolecule assembly with the sensor applications

Aiming at the manufacturing demand of silicon nanowires in detection application in biological, medical, environmental and anti-terroristic area, silicon nanowire fabrication technique was developed using traditional lithography and etching process on silicon wafer. The well-aligned assemble method of multiple biological probes (including protein probe and gene probe) on silicon nanowire interface was studied carefully. The top-down batch manufacturing method of silicon nanowire with good consistency and precisely controlled technology of biological species recognization and acquisition were proposed, laying solid technical foundation for the production of high sensitive and high selective silicon nanowire biosensor and providing new principle and method for silicon nanowire and related biological assembly.

Sensitivity and detection limit analysis of silicon nanowire bio(chemical) sensors

This paper presents an analysis of the sensitivity and detection limit of silicon nanowire biosensors using an analytical model in combination with I–V and current noise measurements. The analysis shows that the limit of detection (LOD) and signal to noise ratio (SNR) can be optimized by determining an operating point in the depletion region with a large sensor transconductance, while maintaining a small system output noise amplitude. Both sensor and measurement configurations play equally important roles for optimal sensor performance. The analysis also shows that the LOD and SNR are minimally affected by the sensor cross-sectional geometry and size.

Detection of specific single-stranded DNA molecules through SiNW surface modulation

This paper demonstrate a silicon nanowire biosensor for the detection of specific ssDNA biomarker detection. The biosensor was fabricated using conventional photolithography coupled with an inductively coupled plasma dry etching process. The detection was performed with a semiconductor parameter analyzer which measured the changes in current and conductance of the nanowire electrodes upon target DNA hybridization. The sensor surface was silanized and directly aminated with (3-aminopropyl)triethoxysilane to create a molecular binding chemistry for bio-functionalization. The resulting Si---O---Si-components were functionalized with receptor ssDNA, which interacted with the targeted ssDNA to create a field across the silicon nanowire and increase the current. Hybridization detection discrimination among various concentration, the device response to the targets shows selectivity for the ssDNA in a linear range from ssDNA concentrations of 100 pM to 150 nM. Linearity of the device to molecular concentration, was confirm linear fit curve for the (0.1---0.5) nM concentration and (0---40) nM concentration.

Molecular layer deposition of APTES on silicon nanowire biosensors: Surface characterization, stability and pH response

We report the use of molecular layer deposition (MLD) for depositing 3-aminopropyltriethoxysilane (APTES) on a silicon dioxide surface. The APTES monolayer was characterized using spectroscopic ellipsometry, contact angle goniometry, and atomic force microscopy. Effects of reaction time of repeating pulses and simultaneous feeding of water vapor with APTES were tested. The results indicate that the synergistic effects of water vapor and reaction time are significant for the formation of a stable monolayer. Additionally, increasing the number of repeating pulses improved the APTES surface coverage but led to saturation after 10 pulses. In comparing MLD with solution-phase deposition, the APTES surface coverage and the surface quality were nearly equivalent. The hydrolytic stability of the resulting films was also studied. The results confirmed that the hydrolysis process was necessary for MLD to obtain stable surface chemistry. Furthermore, we compared the pH sensing results of Si nanowire field effect transistors (Si NWFETs) modified by both the MLD and solution methods. The highly repeatable pH sensing results reflected the stability of APTES monolayers. The results also showed an improved pH response of the sensor prepared by MLD compared to the one prepared by the solution treatment, which indicated higher surface coverage of APTES.

Highly sensitive silicon nanowire biosensor with novel liquid gate control for detection of specific single-stranded DNA molecules.

The study demonstrates the development of a liquid-based gate-control silicon nanowire biosensor for detection of specific single-stranded DNA (ssDNA) molecules. The sensor was fabricated using conventional photolithography coupled with an inductively coupled plasma dry etching process. Prior to the application of DNA to the device, its linear response to pH was confirmed by serial dilution from pH 2 to pH 14. Then, the sensor surface was silanized and directly aminated with (3-aminopropyl) triethoxysilane to create a molecular binding chemistry for biofunctionalization. The resulting Si‒O‒Si‒ components were functionalized with receptor ssDNA, which interacted with the targeted ssDNA to create a field across the silicon nanowire and increase the current. The sensor shows selectivity for the target ssDNA in a linear range from target ssDNA concentrations of 100 pM to 25 nM. With its excellent detection capabilities, this sensor platform is promising for detection of specific biomarkers and other targeted proteins.

Silicon nanowires integrated with CMOS circuits for biosensing application

We describe a silicon nanowire (SiNW) biosensor fabricated in a fully depleted SOI CMOS process. The sensor array consists of N by N pixel matrix (N2 pixels or test sites) and 8 input–output (I/O) pins. In each pixel a single crystalline SiNW with 75 by 20nm cross-section area is defined using sidewall transfer lithography in the SOI layer. The key advantage of the design is that each individual SiNWs can be read-out sequentially and used for real-time charge based detection of molecules in liquids or gases.

Models for the use of commercial TCAD in the analysis of silicon-based integrated biosensors

We present a simple approach to describe electrolytes in TCAD simulators for the modeling of nano-biosensors. The method exploits the similarity between the transport equations for electrons and holes in semiconductors and the ones for charged ions in a solution. We describe a few workarounds to improve the model accuracy in spite of the limitations of commercial TCAD. Applications to the simulations of silicon nanowire and nano-electrode biosensors are reported as relevant examples.

Silicon-based Multi-nanowire Biosensor with High-k Dielectric and Stacked Oxide Sensing Membrane for Cardiac Troponin I Detection

In order to diagnose acute myocardial infraction (AMI) quickly by detection of cTnI, silicon nanowire (Si-NW) transistor is chosen to be the bio-sensor. We demonstrate Si-NW biosensors coated with different dielectric materials to detect cTnI. Based on the experimental results of 14nm SiO2 and 28nm SiO2, it is found that high capacitance dielectrics contribute better sensitivity than that of low capacitance dielectrics. In addition, high-k material dielectrics stacked with ultrathin SiO2 sensing membrane structures are used for Al2O3 and HfO2 because SiO2 has better compatibility with 3-Aminopropyltriethoxysilane (APTES). The results show that high-k stacked structure improve the sensitivity. Based on this work, the proposed Si-NW biosensor structure is experimentally demonstrates a good potential for future applications in cTnI detections.