Silicon Nanowire Biosensor Research Articles

Electrical shielding for silicon nanowire biosensor in microchannels

When integrating silicon nanowire biosensors with a microfluidic sample delivery system, additional challenges are introduced. Noise and erroneous signal generation induced by sample fluidic handling such as flow rate fluctuations during sample switching reduce the quality and reliability of the measurement system. In this paper, we propose an effective electrical shielding method to improve the stability and reliability of the setup by placing double electrodes instead of a single electrode that is traditionally used for nanowire sensors. Experimental results show that with proper shielding electrical measurements are not influenced by flow speed variations or during sample switching.

Highly sensitive covalently functionalised integrated silicon nanowire biosensor devices for detection of cancer risk biomarker

In this article we present ultra-sensitive, silicon nanowire (SiNW)-based biosensor devices for the detection of disease biomarkers. An electrochemically induced functionalisation method has been employed to graft antibodies targeted against the prostate cancer risk biomarker 8-hydroxydeoxyguanosine (8-OHdG) to SiNW surfaces. The antibody-functionalised SiNW sensor has been used to detect binding of the 8-OHdG biomarker to the SiNW surface within seconds of exposure. Detection of 8-OHdG concentrations as low as 1ng/ml (3.5nM) has been demonstrated. The active device has been bonded to a disposable printed circuit which can be inserted into an electronic readout system as part of an integrated Point of Care (POC) diagnostic. The speed, sensitivity and ease of detection of biomarkers using SiNW sensors render them ideal for eventual POC diagnostics.

Serotype-Specific Identification of Dengue Virus by Silicon Nanowire Array Biosensor

In this work, we demonstrated a silicon nanowire (SiNW) biosensing platform capable of simultaneously identifying different Dengue serotypes on a single sensing chip. Four peptide nucleic acids (PNAs), specific to each Dengue serotypes (DENV-1 to DENV-4), were spotted on different areas of the SiNW array surface, and the covalently immobilized PNA probes were then interacted with different Dengue serotypes target to establish the specificity of detection. Detection scheme is based on the changes in resistances due to accumulation of negative charges contributed by the hybridized DNA target. The results show that resistance changes only occur in regions where the Dengue target hybridizes with its complementary probe. What is more, a mixture of two different Dengue serotypes obtained from a one-step duplex RT-PCR was applied to the multiplex SiNW surface to validate SiNW capability to identify multiple Dengue serotypes on a single sensing platform. Through this study, we have established the multiplex SiNW biosensor as a promising device to detect multiple Dengue infections with high specificity.

Label-Free Detection of Carbohydrate–Protein Interactions Using Nanoscale Field-Effect Transistor Biosensors

Carbohydrate-protein interactions play a significant role in cell communication, cell adhesion, cell trafficking, and immune responses. Many efforts have been made to demonstrate detection of carbohydrate-protein interactions. However, the existing methods are still tedious and expensive. Therefore, the detection of carbohydrate-protein interactions is of great significance, and new, efficient methods are required for fast and sensitive recognition testing. In this report, we, for the first time, developed the silicon nanowire (SiNW)-based biosensor capable of label-free electrical detection of carbohydrate-protein interactions with high selectivity and sensitivity by covalently immobilizing unmodified carbohydrates on the sensor surface. We fabricated new SiNW sensor chips with more SiNW arrays for potential detection of multiple analytes. In order to realize the immobilization of the unmodified carbohydrates on the SiNW surface, we used X-ray photoelectron spectra and fluorescence microscopy to verify the successful surface functionalization on the silicon surface. Furthermore, we demonstrated real-time detection of carbohydrate-protein interactions using the carbohydrate-modified SiNW sensor chips. The results show good specificity between galactose-lectin EC and mannose-Con A, which is in good agreement with that reported previously. Finally, the results also show that we are able to use the galactose-modified SiNW biosensor to detect lectin EC as low as 100 fg/mL, which is 4 orders of magnitude lower than that reported by other technologies. We believe that the developed SiNW biosensor paves a novel way for studying carbohydrate-protein interactions.

A Verilog-A model for silicon nanowire biosensors: From theory to verification

Silicon nanowires offer great potential as highly sensitive biosensors. Since the signals they produce are quite weak and noisy, the use of integrated circuits is preferable to read out and digitize these signals as quickly as possible following the sensing event to take full advantage of the properties of the nanowires. In order to design optimized and tailored circuits, simulations involving the sensor itself in the design phase are needed.We propose here a Verilog-A model for silicon nanowire-based biosensors. The model can easily be applied using commercially available electronic design automation (EDA) tools that are commonly used for integrated circuit design and simulations. The model is quite general and comprehensive; it can be used to simulate different types of sensing events, while still being quite simple and undemanding in terms of computational power.The model is described in detail and verified with measurements from two different nanowire sensors featuring aluminum-oxide and hafnium-oxide coatings. Good agreement has been achieved in all cases, with errors never exceeding 21%.The complete Verilog-A code is made available in the Appendix.

Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors

Monitoring the binding affinities and kinetics of protein interactions is important in clinical diagnostics and drug development because such information is used to identify new therapeutic candidates. Surface plasmon resonance is at present the standard method used for such analysis, but this is limited by low sensitivity and low-throughput analysis. Here, we show that silicon nanowire field-effect transistors can be used as biosensors to measure protein-ligand binding affinities and kinetics with sensitivities down to femtomolar concentrations. Based on this sensing mechanism, we develop an analytical model to calibrate the sensor response and quantify the molecular binding affinities of two representative protein-ligand binding pairs. The rate constant of the association and dissociation of the protein-ligand pair is determined by monitoring the reaction kinetics, demonstrating that silicon nanowire field-effect transistors can be readily used as high-throughput biosensors to quantify protein interactions.

Analysis of hysteresis characteristics of silicon nanowire biosensors in aqueous environment

The hysteresis phenomenon has been widely observed in transfer characteristics of silicon nanowire (SiNW) biosensor devices in aqueous environment. Considering the experimental observation in the change of the liquid potential due to the charge flow through the oxide layer, we build up an electrical model for the biosensor system with the solution, SiNW, dielectric oxide, and the back-gated substrate, and investigate the hysteresis behavior based on the model.

Silicon Nanowire as Virus Sensor in a Total Analysis System

Silicon nanowires are very promising candidates for the sensitive detection of viruses or even early detection of cancer. Due to their small dimensions the attachment of even one particle on their surface leads to detectable changes in their conductivity. In this paper we describe the development (fabrication and testing) of a silicon nanowire biosensor equipped with microfludic channels and automatized data aquisition for the detection of antibodies against a small virus (Aleutian Disease Virus) causing plasmacytosis on mink and ferrets.

Self-assembled monolayer-assisted silicon nanowire biosensor for detection of protein–DNA interactions in nuclear extracts from breast cancer cell

The large number of estrogen receptor (ER) binding sites of various sequence patterns requires a sensitive detection to differentiate between subtle differences in ER–DNA binding affinities. A self-assembled monolayer (SAM)-assisted silicon nanowire (SiNW) biosensor for specific and highly sensitive detection of protein–DNA interactions, remarkably in nuclear extracts prepared from breast cancer cells, is presented. As a typical model, estrogen receptor element (ERE, dsDNA) and estrogen receptor alpha (ERα, protein) binding was adopted in the work. The SiNW surface was coated with a vinyl-terminated SAM, and the termination of the surface was changed to carboxylic acid via oxidation. DNA modified with amine group was subsequently immobilized on the SiNW surface. Protein–DNA binding was finally investigated by the functionalized SiNW biosensor. X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were employed to characterize the stepwise functionalization of the SAM and DNA on bare silicon surface, and to visualize protein–DNA binding on the SiNW surface, respectively. We observed that ERα had high sequence specificity to the SiNW biosensor which was functionalized with three different EREs including wild-type, mutant and scrambled DNA sequences. We also demonstrate that the specific DNA-functionalized SiNW biosensor was capable of detecting ERα as low as 10 fM. Impressively, the developed SiNW biosensor was able to detect ERα–DNA interactions in nuclear extracts from breast cancer cells. The SAM-assisted SiNW biosensor, as a label-free and highly sensitive tool, shows a potential in studying protein–DNA interactions.

All-(111) Surface Silicon Nanowires: Selective Functionalization for Biosensing Applications

We demonstrate the utilization of selective functionalization of carbon-silicon (C-Si) alkyl and alkenyl monolayers covalently linked to all-(111) surface silicon nanowire (Si-NW) biosensors. Terminal amine groups on the functional monolayer surfaces were used for conjugation of biotin n-hydroxysuccinimide ester. The selective functionalization is demonstrated by contact angle, X-ray photoelectron spectroscopy (XPS), and high-resolution scanning electron microscopy (HRSEM) of 5 nm diameter thiolated Au nanoparticles linked with streptavidin and conjugated to the biotinylated all-(111) surface Si-NWs. Electrical measurements of monolayer passivated Si-NWs show improved device behavior and performance. Furthermore, an analytical model is presented to demonstrate the improvement in detection sensitivity of the alkyl and alkenyl passivated all-(111) Si-NW biosensors compared to conventional nanowire biosensor geometries and silicon dioxide passivation layers as well as interface design and electrical biasing guidelines for depletion-mode sensors.

Highly sensitive and reversible silicon nanowire biosensor to study nuclear hormone receptor protein and response element DNA interactions

To thoroughly understand the role that estrogen receptors partake in regulation of gene expression, characterization of estrogen receptors (ERs) and estrogen-response elements (EREs) interactions is essential. In the work, we present a highly sensitive and reusable silicon nanowire (SiNW) biosensor to study the interactions between human ER proteins (ER, α and β subtypes) and EREs (dsDNA). The proteins were covalently immobilized on the SiNW surface. Various EREs including wild-type, mutant and scrambled DNA sequences were then applied to the protein-functionalized SiNW surface. Due to negatively charged dsDNA, binding of the EREs to the ERs on the n-type SiNW biosensor leads to the accumulation of negative charges on the surface, thereby inducing increase in resistance. The results show that the specificity of the ERE–ERα binding is higher than that of the ERE–ERβ binding, what is more, the mutant ERE reduces the binding affinity for both ERα and ERβ. By applying various concentrations of wild-type ERE to the bound ERα, a very low concentration of 10 fM wild-type ERE was found to be able to bind to the ERα. The reversible association and dissociation between ERα and wt-ERE was achieved, pointing to a reusable biosensor for protein–DNA binding. Through the study, we have established the SiNW biosensor as a promising method in providing comprehensive study for hormone receptor–response element interactions.

Morpholino-functionalized silicon nanowire biosensor for sequence-specific label-free detection of DNA

We investigated Morpholino-functionalized silicon nanowires (SiNWs) as a novel gene chip platform for the sequence-specific label-free detection of DNA. Morpholino attachment and subsequent Morpholino–DNA hybridization on silicon surface was characterized by X-ray photoelectron spectroscopy and fluorescence microscopy. The resultant Morpholino-modified surfaces showed high specificity of recognition for DNA. Subsequently, by using the same protocol, the surface of the SiNW biosensor was functionalized with Morpholino, and this was used for label-free Morpholino-DNA hybridization detection. Real-time measurements of the Morpholino-functionalized SiNW biosensor exhibited a decrease in a time-dependent conductance when complementary and mutant DNA samples were added. Furthermore, identification of fully complementary versus mismatched DNA samples was carried out by the Morpholino-functionalized SiNW biosensor. We demonstrated that DNA detection using the Morpholino-functionalized SiNW biosensor could be carried out to the hundreds of femtomolar range. The Morpholino-functionalized SiNWs show a novel biosensor for label-free and direct detection of DNA with good selectivity, and a promising application in gene expression.

Fabrication and application of a microfluidic‐embedded silicon nanowire biosensor chip

AbstractWe report the fabrication of a silicon nanowire (SiNW) transistor array realized in a top‐down process on 4′′ silicon‐on‐insulator (SOI) wafers. This process is a second, optimized version combining thermal nanoimprint lithography and wet chemical etching to define planar nanowires and contact lines out of the top silicon layer in one etching step. We used ion implantation to reduce series resistance of source and drain contact lines. In total 56 individually addressable SiNWs were aligned in two lines. Wires dimensions were down to 60 nm in width and 40 nm in height having lengths up to 40 µm. Due to an improved processing we obtained almost identical wire structures and electronic properties throughout the 4′′ wafer enabling direct comparison of signals from one chip. The wires were capped by a microfuidic structure, which was used to administer different analyte solutions. First pH characterization measurements and molecular detection experiments using charged polyelectrolytes (PEs) and poly(D)lysine were successful. In future these devices could be used to observe diffusion of analytes in a time‐dependent, spatially‐ and quantitatively‐resolved readout.

Multiscale Modeling of Planar and Nanowire Field-Effect Biosensors

Field-effect nanobiosensors (or Biofets, biologically sensitive field-effect transistors) have recently been demonstrated experimentally and have thus gained interest as a technology for direct, label-free, real-time, and highly sensitive detection of biomolecules. The experiments have not been accompanied by a quantitative understanding of the underlying detection mechanism. The modeling of field-effect biosensors poses a multiscale problem due to the different length scales in the sensors: the charge distribution and the electric potential of the biofunctionalized surface layer changes on the Ångström length scale, whereas the exposed sensor area is measured in micrometers squared. Here a multiscale model for the electrostatics of planar and nanowire field-effect sensors is developed by homogenization of the Poisson equation in the biofunctionalized boundary layer. The resulting interface conditions depend on the surface charge density and dipole moment density of the boundary layer. The multiscale model can be coupled to any charge transport model and hence makes the self-consistent quantitative investigation of the physics of field-effect sensors possible. Numerical verifications of the multiscale model are given. Furthermore a silicon nanowire biosensor is simulated to elucidate the influence of the surface charge density and the dipole moment density on the conductance of the semiconductor transducer. The numerical evidence shows that the conductance varies exponentially as a function of both charge and dipole moment. Therefore the dipole moment of the surface layer must be included in biosensor models. The conductance variations observed in experiments can be explained by the field effect, and they can be caused by a change in dipole moment alone.

Label-free direct detection of MiRNAs with silicon nanowire biosensors

MicroRNA (miRNA), an 18–24-nucleotide (nt) noncoding RNA molecule in the genes of humans, plants and animals, is emerging as a key player in gene regulation. As a result, label-free, rapid, and sensitive detection for miRNA is of great significance. In this work, a label-free and direct hybridization assay for ultrasensitive detection of miRNA using silicon nanowires (SiNWs) device has been developed. Peptide nucleic acids (PNAs), which serve as a receptor to recognize miRNA directly without labeling the target miRNA, are immobilized on the surface of the SiNW device. Resistance change measured before and after hybridization correlates directly to concentrations of the hybridized target miRNA. Concentration-dependent measurements indicate that a detection limit of 1fM was obtained using the optimized assay. The technique enables identification of fully matched versus mismatched miRNA sequences. Furthermore, the SiNW device is capable of detecting miRNA in total RNA extracted from Hela cells. This approach paves a way for label-free, early detection of miRNA as a biomarker in cancer diagnostics with very high sensitivity and good specificity.

Selective Biofunctionalization all-(111) Surface Silicon Nanowires

AbstractSelective biomolecular functionalization of our all-(111) surface silicon nanowire (SiNW) biosensors using covalently linked alkyl- monolayers is demonstrated. Monolayers were made using a commercially available six member carbon precursor N-(5-Hexynyl) phthalimide and UV based hydrosylilation reaction. Contact angle and x-ray photoelectron spectroscopy (XPS) measurements were used to characterize the monolayer at different stages on planar Si (111) samples. Terminal amine groups on the monolayer surface were used for further conjugation with (+)-Biotin N-hydroxysuccinimide ester after deprotection of the phthalimide group with a methylamine solution. Selective biofunctionalization was demonstrated by reacting the SiNW-monolayer-biotin surface with 5 nm gold nanoparticles conjugated with streptavidin and subsequent high resolution scanning electron microscopy imaging.

Highly sensitive measurements of PNA-DNA hybridization using oxide-etched silicon nanowire biosensors

The highly sensitive and sequence-specific detection of single-stranded oligonucleotides using nonoxidized silicon nanowires (SiNWs) is demonstrated. To maximize device sensitivity, the surface of the SiNWs was functionalized with a densely packed organic monolayer via hydrosilylation, subsequently immobilized with peptide nucleic acid (PNA) capable of recognizing the label-free complementary target DNA. Because of the selective functionalization of the SiNWs, binding competition between the nanowire and the underlying oxide is avoided. Transmission electron microscopy was conducted to clearly differentiate the SiNW surface before and after removal of SiO 2. Fluorescence microscopy was used to further realize the selectivity of the oxide-etched chemistry on the SiNWs and sequence specificity of PNA-DNA hybridization. The concentration-dependent resistance change measurements upon hybridization of PNA-DNA show that detection limit down to 10 fM can be obtained. The SiNW devices also reveal the capability of an obvious discrimination against mismatched sequences. Among several efforts being made to improve detection sensitivity, this work addresses one significant issue regarding surface functionalization which enables highly sensitive biomolecular sensing with SiNWs.

Fabrication and characterisation of CMOS compatible silicon nanowire biosensor

A silicon nanowire (SiNW) biosensor for label-free and real-time detection has been fabricated by complementary metal-oxide semiconductor (CMOS) technology. For the detection of prostate-specific antigen (PSA) used as a biomarker of prostate cancer the SiNW surface was modified to immobilise the antibody of PSA (anti-PSA). Real-time monitoring reveals the change in conductivity of the SiNW on specific binding of PSA to anti-PSA. For 355 nm SiNW, the response to 10 ng/ml of PSA was 7.3%.

Design Considerations of Silicon Nanowire Biosensors

Biosensors based on silicon nanowires (Si-NWs) promise highly sensitive dynamic label-free electrical detection of biomolecules. Despite the tremendous potential and promising experimental results, the fundamental mechanism of electrical sensing of biomolecules and the design considerations of NW sensors remain poorly understood. In this paper, we discuss the prospects and challenges of biomolecule detection using Si-NW biosensors as a function of device parameters, fluidic environment, charge polarity of biomolecules, etc., and refer to experimental results in literature to support the nonintuitive predictions wherever possible. Our results indicate that the design of Si nanobiosensor is nontrivial and as such, only careful optimization supported by numerical simulation would ensure optimal sensor performance.

Silicon nanowires for high-sensitivity glucose detection

Silicon nanowires (SiNWs) were investigated as supporting matrices for enzyme immobilization to construct glucose biosensors. Glucose oxidase was adsorbed onto SiNWs after different treatments, either as grown, HF etched, or carboxylic acid (COOH) functionalized. The amperometric biosensor with COOH-functionalized SiNWs performed the best with a detection limit of 0.01mM glucose (signal-to-noise ratio=3). For real-time detection of glucose, SiNW biosensor showed a linear response in the range of 0.1–15mM. This work demonstrates the utility of SiNWs as a biosensor component and provides a general method to modify the surface of semiconducting nanomaterials for potential biomedical applications.