Rapid Screen for Antiviral T-Cell Immunity with Nanowire Electrochemical Biosensors.

The ability to rapidly assess and monitor patient immune responses is critical for clinical diagnostics, vaccine design, and fundamental investigations into the presence or generation of protective immunity against infectious diseases. Recently, findings on the limits of antibody-based protection provided by B-cells have highlighted the importance of engaging pathogen-specific T-cells for long-lasting and broad protection against viruses and their emergent variants such as in SARS-CoV-2. However, low-cost and point-of-care tools for detecting engagement of T-cell immunity in patients are conspicuously lacking in ongoing efforts to assess and control population-wide disease risk. Currently available tools for human T-cell analysis are time and resource-intensive. Using multichannel silicon-nanowire field-effect transistors compatible with complementary metal-oxide-semiconductor, a device designed for rapid and label-free detection of human T-cell immune responses is developed. The generalizability of this approach is demonstrated by measuring T-cell responses against melanoma antigen MART1, common and seasonal viruses CMV, EBV, flu, as well as emergent pandemic coronavirus, SARS-CoV-2. Further, this device provides a modular and translational platform for optimizing vaccine formulations and combinations, offering quick and quantitative readouts for acquisition and persistence of T-cell immunity against variant-driven pathogens such as flu and pandemic SARS-CoV-2.

Impact of Porosity and Boundary Scattering on Thermal Transport in Diameter-Modulated Nanowires.

We study the thermal conductivity of diameter-modulated Si nanowires to understand the impact of different nanoscale transport mechanisms as a function of nanowire morphology. Our investigation couples transient suspended microbridge measurements of diameter-modulated Si nanowires synthesized via vapor-liquid-solid growth and dopant-selective etching with predictive Boltzmann transport modeling. We show that the presence of a low thermal conductivity phase (i.e., porosity) dominates the reduction in effective thermal conductivity and is supplemented by increased phonon-boundary scattering. The relative contributions of both mechanisms depend on the details of the nanoscale morphology. Our findings provide valuable insights into the factors that govern thermal conduction in complex nanoscale materials.

Silicon nanowires decorated with platinum nanoparticles were applied for photothermal-enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) can overcome pivotal limitations of photo-therapy owing to its high depth-penetration and low phototoxicity. However, there is still a need to develop more efficient sonosensitizes to enhance the therapy efficiency. Methods: In this study, Pt nanoparticles (Pt NPs) are reduced on silicon nanowires (SiNWs) by in situ reduction to prepare Si-Pt nanocomposites (Si-Pt NCs). Results: Si-Pt NCs can produce reactive oxygen radicals (ROS) under ultrasound (US) irradiation, which have sonodynamic therapy (SDT) effect. Meanwhile, Si-Pt NCs can convert excess hydrogen peroxide (H2O2) into ROS in the tumor microenvironment, which endow strong chemodynamic therapy (CDT) effect. Taking the advantages of the mesoporous structure of SiNWs, the SDT and CDT effects of Si-Pt NCs are stronger than those of the pure Pt NPs and SiNWs. Besides, the mild photothermal effect of Si-Pt NCs further improves the SDT&CDT activity and realizes the combined cancer therapy. Conclusion: The developed Si-Pt NCs with the ability of photothermal enhanced SDT/CDT combined therapy play a momentous role in the novel cancer treatment.

Complementary Photo-Synapses Based on Light-Stimulated Porphyrin-Coated Silicon Nanowires Field-Effect Transistors (LPSNFET).

Neuromorphic computing has emerged as the high-energy-efficiency and intelligent solution for processing sensory data. As a potential alternative to neuromorphic computing, photo-excited synaptic systems can integrate the functions of optoelectronic sensing and synaptic computing to realize the low-power and high-performance visual perception. However, one major challenge in high-efficient photo-excited synaptic system is to realize the complementarily enhanced and inhibited synaptic behaviors with small hardware cost as possible. Another challenge is to fabricate the photo-synapse devices with complementary metal oxide semiconductor (CMOS)-compatible process to achieve high enough integration density for practical application. Here, a CMOS-compatible Light-stimulated Porphyrin-coated Silicon Nanowire Field Effect Transistor (LPSNFET) technology is proposed and developed to form the complementary photo-synapses with only two CMOS-like transistors. LPSNFET exhibits fivefold improvement in photo-sensitivity compared to the bare silicon nanowire (SiNW) devices, and can still show obvious responses when incident illumination power is as low as 0.1 mW cm-2 . Moreover, it enables tunable dynamic synaptic plasticity and versatile synaptic functions. Especially, the complementarily enhanced and inhibited behaviors can be realized by modulating SiNW/porphyrin interface via simply changing the MOS type of LPSNFET, which acts like the photonic counterpart of CMOS technology to provide the basic brick for building complex neuromorphic circuits efficiently and economically. Finally, the CMOS process compatibility of LPSNFET provides potential application in future large scale in-sensor computing.

Turning Low-Nanoscale Intrinsic Silicon Highly Electron-Conductive by SiO2 Coating.

Impurity doping in silicon (Si) ultra-large-scale integration is one of the key challenges which prevent further device miniaturization. Using ultraviolet photoelectron spectroscopy and X-ray absorption spectroscopy in the total fluorescence yield mode, we show that the lowest unoccupied and highest occupied electronic states of ≤3 nm thick SiO2-coated Si nanowells shift by up to 0.2 eV below the conduction band and ca. 0.7 eV below the valence band edge of bulk silicon, respectively. This nanoscale electronic structure shift induced by anions at surfaces (NESSIAS) provides the means for low-nanoscale intrinsic Si (i-Si) to be flooded by electrons from an external (bigger, metallic) reservoir, thereby getting highly electron- (n-) conductive. While our findings deviate from the behavior commonly believed to govern the properties of silicon nanowells, they are further confirmed by the fundamental energy gap as per nanowell thickness when compared against published experimental data. Supporting our findings further with hybrid density functional theory calculations, we show that other group IV semiconductors (diamond, Ge) do respond to the NESSIAS effect in accord with Si. We predict adequate nanowire cross-sections (X-sections) from experimental nanowell data with a recently established crystallographic analysis, paving the way to undoped ultrasmall silicon electronic devices with significantly reduced gate lengths, using complementary metal-oxide-semiconductor-compatible materials.

Optimization of GOPS-Based Functionalization Process and Impact of Aptamer Grafting on the Si Nanonet FET Electrical Properties as First Steps towards Thrombin Electrical Detection.

Field effect transistors (FETs) based on networks of randomly oriented Si nanowires (Si nanonets or Si NNs) were biomodified using Thrombin Binding Aptamer (TBA-15) probe with the final objective to sense thrombin by electrical detection. In this work, the impact of the biomodification on the electrical properties of the Si NN-FETs was studied. First, the results that were obtained for the optimization of the (3-Glycidyloxypropyl)trimethoxysilane (GOPS)-based biofunctionalization process by using UV radiation are reported. The biofunctionalized devices were analyzed by atomic force microscopy (AFM) and scanning transmission electron microscopy (STEM), proving that TBA-15 probes were properly grafted on the surface of the devices, and by means of epifluorescence microscopy it was possible to demonstrate that the UV-assisted GOPS-based functionalization notably improves the homogeneity of the surface DNA distribution. Later, the electrical characteristics of 80 devices were analyzed before and after the biofunctionalization process, indicating that the results are highly dependent on the experimental protocol. We found that the TBA-15 hybridization capacity with its complementary strand is time dependent and that the transfer characteristics of the Si NN-FETs obtained after the TBA-15 probe grafting are also time dependent. These results help to elucidate and define the experimental precautions that must be taken into account to fabricate reproducible devices.

CMOS-Compatible and Low-Cost Thin Film MACE Approach for Light-Emitting Si NWs Fabrication.

Silicon nanowires (Si NWs) are emerging as an innovative building block in several fields, such as microelectronics, energetics, photonics, and sensing. The interest in Si NWs is related to the high surface to volume ratio and the simpler coupling with the industrial flat architecture. In particular, Si NWs emerge as a very promising material to couple the light to silicon. However, with the standard synthesis methods, the realization of quantum-confined Si NWs is very complex and often requires expensive equipment. Metal-Assisted Chemical Etching (MACE) is gaining more and more attention as a novel approach able to guarantee high-quality Si NWs and high density with a cost-effective approach. Our group has recently modified the traditional MACE approach through the use of thin metal films, obtaining a strong control on the optical and structural properties of the Si NWs as a function of the etching process. This method is Complementary Metal-Oxide-Semiconductors (CMOS)-technology compatible, low-cost, and permits us to obtain a high density, and room temperature light-emitting Si NWs due to the quantum confinement effect. A strong control on the Si NWs characteristics may pave the way to a real industrial transfer of this fabrication methodology for both microelectronics and optoelectronics applications.

Palladium-Decorated Silicon Nanomesh Fabricated by Nanosphere Lithography for High Performance, Room Temperature Hydrogen Sensing.

A hydrogen (H2 ) gas sensor based on a silicon (Si) nanomesh structure decorated with palladium (Pd) nanoparticles is fabricated via polystyrene nanosphere lithography and top-down fabrication processes. The gas sensor shows dramatically improved H2 gas sensitivity compared with an Si thin film sensor without nanopatterns. Furthermore, a buffered oxide etchant treatment of the Si nanomesh structure results in an additional performance improvement. The final sensor device shows fast H2 response and high selectivity to H2 gas among other gases. The sensing performance is stable and shows repeatable responses in both dry and high humidity ambient environments. The sensor also shows high stability without noticeable performance degradation after one month. This approach allows the facile fabrication of high performance H2 sensors via a cost-effective, complementary metal-oxide-semiconductor (CMOS) compatible, and scalable nanopatterning method.

Direct Measurement of Single-Molecule Adenosine Triphosphatase Hydrolysis Dynamics.

F1-ATPase (F1) is a bidirectional molecular motor that hydrolyzes nearly all ATPs to fuel the cellular processes. Optical observation of labeled F1 rotation against the α3ß3 hexamer ring revealed the sequential mechanical rotation steps corresponding to ATP binding/ADP release and ATP hydrolysis/Pi release. These substeps originate from the F1 rotation but with heavy load on the γ shaft due to fluorescent labeling and the photophysical limitation of an optical microscope, which hampers better understanding of the intrinsic kinetic behavior of ATP hydrolysis. In this work, we present a method capable of electrically monitoring ATP hydrolysis of a single label-free F1 in real time by using a high-gain silicon nanowire-based field-effect transistor circuit. We reproducibly observe the regular current signal fluctuations with two distinct levels, which are induced by the binding dwell and the catalytic dwell, respectively, in both concentration- and temperature-dependent experiments. In comparison with labeled F1, the hydrolysis rate of nonlabeled F1 used in this study is 1 order of magnitude faster (1.69 × 108 M-1 s-1 at 20 °C), and the differences between two sequential catalytic rates are clearer, demonstrating the ability of nanowire nanocircuits to directly probe the intrinsic dynamic processes of the biological activities with single-molecule/single-event sensitivity. This approach is complementary to traditional optical methods, offering endless opportunities to unravel molecular mechanisms of a variety of dynamic biosystems under realistic physiological conditions.

Single Nucleotide Polymorphism Genotyping in Single-Molecule Electronic Circuits.

Establishing low-cost, high-throughput, simple, and accurate single nucleotide polymorphism (SNP) genotyping techniques is beneficial for understanding the intrinsic relationship between individual genetic variations and their biological functions on a genomic scale. Here, a straightforward and reliable single-molecule approach is demonstrated for precise SNP authentication by directly measuring the fluctuations in electrical signals in an electronic circuit, which is fabricated from a high-gain field-effect silicon nanowire decorated with a single hairpin DNA, in the presence of different target DNAs. By simply comparing the proportion difference of a probe-target duplex structure throughout the process, this study implements allele-specific and accurate SNP detection. These results are supported by the statistical analyses of different dynamic parameters such as the mean lifetime and the unwinding probability of the duplex conformation. In comparison with conventional polymerase chain reaction and optical methods, this convenient and label-free method is complementary to existing optical methods and also shows several advantages, such as simple operation and no requirement for fluorescent labeling, thus promising a futuristic route toward the next-generation genotyping technique.

Visual Prosthesis: Interfacing Stimulating Electrodes with Retinal Neurons to Restore Vision.

The bypassing of degenerated photoreceptors using retinal neurostimulators is helping the blind to recover functional vision. Researchers are investigating new ways to improve visual percepts elicited by these means as the vision produced by these early devices remain rudimentary. However, several factors are hampering the progression of bionic technologies: the charge injection limits of metallic electrodes, the mechanical mismatch between excitable tissue and the stimulating elements, neural and electric crosstalk, the physical size of the implanted devices, and the inability to selectively activate different types of retinal neurons. Electrochemical and mechanical limitations are being addressed by the application of electromaterials such as conducting polymers, carbon nanotubes and nanocrystalline diamonds, among other biomaterials, to electrical neuromodulation. In addition, the use of synthetic hydrogels and cell-laden biomaterials is promising better interfaces, as it opens a door to establishing synaptic connections between the electrode material and the excitable cells. Finally, new electrostimulation approaches relying on the use of high-frequency stimulation and field overlapping techniques are being developed to better replicate the neural code of the retina. All these elements combined will bring bionic vision beyond its present state and into the realm of a viable, mainstream therapy for vision loss.

Multi-Wire Tri-Gate Silicon Nanowires Reaching Milli-pH Unit Resolution in One Micron Square Footprint.

The signal-to-noise ratio of planar ISFET pH sensors deteriorates when reducing the area occupied by the device, thus hampering the scalability of on-chip analytical systems which detect the DNA polymerase through pH measurements. Top-down nano-sized tri-gate transistors, such as silicon nanowires, are designed for high performance solid-state circuits thanks to their superior properties of voltage-to-current transduction, which can be advantageously exploited for pH sensing. A systematic study is carried out on rectangular-shaped nanowires developed in a complementary metal-oxide-semiconductor (CMOS)-compatible technology, showing that reducing the width of the devices below a few hundreds of nanometers leads to higher charge sensitivity. Moreover, devices composed of several wires in parallel further increase the exposed surface per unit footprint area, thus maximizing the signal-to-noise ratio. This technology allows a sub milli-pH unit resolution with a sensor footprint of about 1 µm², exceeding the performance of previously reported studies on silicon nanowires by two orders of magnitude.

Strongly enhanced light trapping in a two-dimensional silicon nanowire random fractal array.

We report on the unconventional optical properties exhibited by a two-dimensional array of thin Si nanowires arranged in a random fractal geometry and fabricated using an inexpensive, fast and maskless process compatible with Si technology. The structure allows for a high light-trapping efficiency across the entire visible range, attaining total reflectance values as low as 0.1% when the wavelength in the medium matches the length scale of maximum heterogeneity in the system. We show that the random fractal structure of our nanowire array is responsible for a strong in-plane multiple scattering, which is related to the material refractive index fluctuations and leads to a greatly enhanced Raman scattering and a bright photoluminescence. These strong emissions are correlated on all length scales according to the refractive index fluctuations. The relevance and the perspectives of the reported results are discussed as promising for Si-based photovoltaic and photonic applications.

Silicon nanostructures for cancer diagnosis and therapy.

The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy.

Electrical characteristics of metal catalyst-assisted etched rough silicon nanowire depending on the diameter size.

The dependence of electrical properties of rough and cylindrical Si nanowires (NWs) synthesized by diameter-controllable metal catalyst-assisted etching (MCE) on the size of the NW's diameter was demonstrated. Using a decal-printing and transfer process assisted by Al2O3 sacrificial layer, the Si NW field effect transistor (FET) embedded in a polyvinylphenol adhesive and dielectric layer were fabricated. As the diameter of Si NW increased, the mobility of FET increased from 80.51 to 170.95 cm(2)/V·s and the threshold voltage moved from -7.17 to 0 V because phonon-electron wave function overlaps, surface scattering, and defect scattering decreased and gate coupling increased as the ratio of surface-to-volume got reduced.

The utilization of SiNWs/AuNPs-modified indium tin oxide (ITO) in fabrication of electrochemical DNA sensor.

This work describes the incorporation of SiNWs/AuNPs composite as a sensing material for DNA detection on indium tin-oxide (ITO) coated glass slide. The morphology of SiNWs/AuNPs composite as the modifier layer on ITO was studied by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The morphological studies clearly showed that SiNWs were successfully decorated with 20 nm-AuNPs using self-assembly monolayer (SAM) technique. The effective surface area for SiNWs/AuNPs-modified ITO enhanced about 10 times compared with bare ITO electrode. SiNWs/AuNPs nanocomposite was further explored as a matrix for DNA probe immobilization in detection of dengue virus as a bio-sensing model to evaluate its performance in electrochemical sensors. The hybridization of complementary DNA was monitored by differential pulse voltammetry (DPV) using methylene blue (MB) as the redox indicator. The fabricated biosensor was able to discriminate significantly complementary, non-complementary and single-base mismatch oligonucleotides. The electrochemical biosensor was sensitive to target DNA related to dengue virus in the range of 9.0-178.0 ng/ml with detection limit of 3.5 ng/ml. In addition, SiNWs/AuNPs-modified ITO, regenerated up to 8 times and its stability was up to 10 weeks at 4°C in silica gel.

Point decoration of silicon nanowires: an approach toward single-molecule electrical detection.

Probing interactions of biological systems at the molecular level is of great importance to fundamental biology, diagnosis, and drug discovery. A rational bioassay design of lithographically integrating individual point scattering sites into electrical circuits is capable of realizing real-time, label-free biodetection of influenza H1N1 viruses with single-molecule sensitivity and high selectivity by using silicon nanowires as local reporters in combination with microfluidics. This nanocircuit-based architecture is complementary to more conventional optical techniques, but has the advantages of no bleaching problems and no fluorescent labeling. These advantages offer a promising platform for exploring dynamics of stochastic processes in biological systems and gaining information from genomics to proteomics to improve accurate molecular and even point-of-care clinical diagnosis.

Ultra-sensitive nucleic acids detection with electrical nanosensors based on CMOS-compatible silicon nanowire field-effect transistors.

Silicon nanowire field-effect transistors (SiNW-FETs) have recently emerged as a type of powerful nanoelectronic biosensors due to their ultrahigh sensitivity, selectivity, label-free and real-time detection capabilities. Here, we present a protocol as well as guidelines for detecting DNA with complementary metal oxide semiconductor (CMOS) compatible SiNW-FET sensors. SiNWs with high surface-to-volume ratio and controllable sizes were fabricated with an anisotropic self-stop etching technique. Probe DNA molecules specific for the target DNA were covalently modified onto the surface of the SiNWs. The SiNW-FET nanosensors exhibited an ultrahigh sensitivity for detecting the target DNA as low as 1 fM and good selectivity for discrimination from one-base mismatched DNA.