Silicon Nanowire-based Biosensor Research Articles

Emulating Multimemristive Behavior of Silicon Nanowire-Based Biosensors by Using CMOS-Based Implementations

Emulating Multimemristive Behavior of Silicon Nanowire-Based Biosensors by Using CMOS-Based Implementations

Estimation of the Depletion Layer Thickness in Silicon Nanowire-Based Biosensors from Attomolar-Level Biomolecular Detection.

Silicon nanowire (SiNW) biosensors have attracted a lot of attention due to their superior sensitivity. Recently, the dependence of biomolecule detection sensitivity on the nanowire (NW) width, number, and doping density has been partially investigated. However, the primary reason for achieving ultrahigh sensitivity has not been elucidated thus far. In this study, we designed and fabricated SiNW biosensors with different widths (10.8-155 nm) by integrating a complementary metal-oxide-semiconductor process and electron beam lithography. We aimed to investigate the detection limit of SiNW biosensors and reveal the critical effect of the 10-nm-scaled SiNW width on the detection sensitivity. The sensing performance was evaluated by detecting antiovalbumin immunoglobulin G (IgG) with various concentrations (from 6 aM to 600 nM). The initial thickness of the depletion region of the SiNW and the changes in the depletion region due to biomolecule binding were calculated. The basis of this calculation are the resistance change ratios as functions of IgG concentrations using SiNWs with different widths. The calculation results reveal that the proportion of the depletion region over the entire SiNW channel is the essential reason for high-sensitivity detection. Therefore, this study is crucial for an indepth understanding on how to maximize the sensitivity of SiNW biosensors.

Rapid and quantitative detection of tear MMP-9 for dry eye patients using a novel silicon nanowire-based biosensor

Dry eye disease (DED) is the most common chronic eye disease characterized by ocular surface inflammation that affects hundreds of millions of people worldwide. The diagnosis and monitoring of DED require fast and reliable tools in the clinical setting. Matrix metalloproteinase 9 (MMP-9) has been proven to be a reliable indicator of DED owing to its close relationship with inflammation. A novel biosensor based on silicon nanowire-based field-effect transistor (SiNW FET) devices was fabricated for the quantitative measurement of MMP-9 in human tears. A modified controllable process was applied to improve the uniformity of the SiNWs in size and stabilize their performance with optical calibration at low salt concentrations for clinical application. With this protocol, correlation analysis proved the high agreement between the biosensor and enzyme-linked immunosorbent assay (correlation coefficient of 0.92 for DED patients and 0.90 for healthy controls). A diagnostic sensitivity of 86.96% and specificity of 90% were achieved in human tear samples from DED patients and healthy subjects in real-world clinical settings. Furthermore, the tear MMP-9 concentrations monitored using the device correlated with the therapeutic response of the patients with DED. Our enhanced SiNW biosensor device demonstrated its potential as an alternative tool for real-time diagnosis and monitoring for prognostic prediction toward point-of-care testing for DED.

Design and Fabrication of Silicon Nanowire-Based Biosensors with Integration of Critical Factors: Toward Ultrasensitive Specific Detection of Biomolecules.

As critical factors affecting the sensing performance of silicon nanowire (SiNW) biosensors, the structure, functional interface, and detection target were analyzed and designed to improve sensing performance. For an improved understanding of the dependence of sensor structure on sensitivity, a simple theoretical analysis was proposed to predict the sensitivity of biosensors with different SiNW types, widths, and doping concentrations. Based on the theoretical analysis, a biosensor integrating optimized critical factors was designed and fabricated. Optimizations focusing on the following aspects are considered: (1) employing n-type SiNW and controlling the impurity doping concentration of SiNW at approximately 2 × 1016-6 × 1016 atoms/cm3 to obtain a suitable charge density, (2) minimizing the SiNW width to 16.0 nm to increase the surface area-to-volume ratio, (3) using a native oxide layer on SiNW as a gate insulator to transport the captured charge molecules closer to the SiNW surface, (4) modifying the SiNW surface by 2-aminoethylphosphonic acid coupling to form a high-density self-assembled monolayer for enhancing the stability bound molecules, and (5) functionalizing the SiNW with ovalbumin molecules for specifically capturing the target immunoglobulin G (IgG) molecules. The sensing performance was evaluated by detecting IgG with concentrations ranging from 6 aM to 600 nM and control experiments. The SiNW biosensor revealed ultrahigh sensitivity and specific detection of target IgG with a measured limit of detection of 6 aM. The integration of the critical SiNW biosensor factors provides a significant possibility of a rapid and ultrasensitive diagnosis of diseases at their early stages.

Integration of microfluidic sample delivery system on silicon nanowire-based biosensor

Silicon nanowire-based (SiNW) biosensors have gained a lot of attention during recent years. However, studies often totally neglect, or only briefly describe, the incorporation of microfluidic channel into the sensor architecture, although it is a crucial step towards a real lab-on-chip device. This paper proposes a process that can be applied to integration of microfluidic sample delivery system onto different SiNW biosensors. The sample delivery system includes a hydrophilic channel that enables the use of capillary action in delivering sample directly onto the sensor array, which leads to reduced sample loss, faster detection process, and frees from the use of external pumps. In addition, the microfluidic channel system protects the fragile SiNWs from mechanical shocks, chemical spatters, and dust. The sample delivery system was fabricated of surface treated polydimethylsiloxane (PDMS), using a four-step approach, as follows: (1) master molds for soft lithography were etched onto Si. (2) PDMS replicas of the molds were fabricated and (3) bonded onto example sensor chips using oxygen plasma. (4) Oxygen plasma treatment also enabled the attachment of polyvinylpyrrolidone (PVP) to the sample channel surfaces to synthesize hydrophilic polymer coating. A contact angle for the PVP treated PDMS was 21 after 17 days, indicating the formation of a long-term hydrophilic PDMS surface. Finally, the example SiNW sensor is modified to allow direct real-time detection of thyroid-stimulating hormone (TSH). The sensor was able to detect as low TSH concentration values as 0.5 mIU/l, which indicates a successfully integrated sample delivery system.

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.

Detection of the Early Stage of Recombinational DNA Repair by Silicon Nanowire Transistors

A silicon nanowire-based biosensor has been designed and applied for label-free and ultrasensitive detection of the early stage of recombinational DNA repair by RecA protein. Silicon nanowires transistors were fabricated by atomic force microscopy nanolithography and integrated into a microfluidic environment. The sensor operates by measuring the changes in the resistance of the nanowire as the biomolecular reactions proceed. We show that the nanoelectronic sensor can detect and differentiate several steps in the binding of RecA to a single-stranded DNA filament taking place on the nanowire-aqueous interface. We report relative changes in the resistance of 3.5% which are related to the interaction of 250 RecA·single-stranded DNA complexes. Spectroscopy data confirm the presence of the protein-DNA complexes on the functionalized silicon surfaces.

CMOS-compatible fabrication of top-gated field-effect transistor silicon nanowire-based biosensors

Field-effect transistor (FET) nanowire-based biosensors are very promising tools for medical diagnosis. In this paper, we introduce a simple method to fabricate FET silicon nanowires using only standard microelectromechanical system (MEMS) processes. The key steps of our fabrication process were a local oxidation of silicon (LOCOS) and anisotropic KOH etchings that enabled us to reduce the width of the initial silicon structures from 10 µm to 170 nm. To turn the nanowires into a FET, a top-gate electrode was patterned in gold next to them in order to apply the gate voltage directly through the investigated liquid environment. An electrical characterization demonstrated the p-type behaviour of the nanowires. Preliminary chemical sensing tested the sensitivity to pH of our device. The effect of the binding of streptavidin on biotinylated nanowires was monitored in order to evaluate their biosensing ability. In this way, streptavidin was detected down to a 100 ng mL−1 concentration in phosphate buffered saline by applying a gate voltage less than 1.2 V. The use of a top-gate electrode enabled the detection of biological species with only very low voltages that were compatible with future handheld-requiring applications. We thus demonstrated the potential of our devices and their fabrication as a solution for the mass production of efficient and reliable FET nanowire-based biological sensors.