Enhanced biosensing of tumor necrosis factor-alpha based on aptamer-functionalized surface plasmon resonance substrate and Goos-Hänchen shift.

Tumor necrosis factor-alpha (TNF-α) serves as a crucial biomarker in various diseases, necessitating sensitive detection methodologies. This study introduces an innovative approach utilizing an aptamer-functionalized surface plasmon resonance (SPR) substrate together with an ultrasensitive measure, the Goos-Hänchen (GH) shift, to achieve sensitive detection of TNF-α. The developed GH-aptasensing platform has shown a commendable figure-of-merit of 1.5 × 104 µm per RIU, showcasing a maximum detectable lateral position shift of 184.7 ± 1.2 µm, as characterized by the glycerol measurement. Employing aptamers as the recognition unit, the system exhibits remarkable biomolecule detection capabilities, including the experimentally obtained detection limit of 1 aM for the model protein bovine serum albumin (BSA), spanning wide dynamic ranges. Furthermore, the system successfully detects TNF-α, a small cytokine, with an experimental detection limit of 1 fM, comparable to conventional SPR immunoassays. This achievement represents one of the lowest experimentally derived detection limits for cytokines in aptamer-based SPR sensing. Additionally, the application of the GH shift marks a ground breaking advancement in aptamer-based biosensing, holding significant promise for pushing detection limits further, especially for small cytokine targets.

Porous carbon film/WO3-x nanosheets based SERS substrate combined with deep learning technique for molecule detection.

The Surface-enhanced Raman scattering (SERS) is an attractive optical detecting method with high sensitivity and detectivity, however challenges on large-area signal uniformity and complex spectra analysis methods always retards its wide application. Herein, a highly sensitive and uniform SERS detection strategy supported by porous carbon film/WO3-x nanosheets (PorC/WO3-x) based noble-metal-free SERS substrate and deep learning algorithm are reported. Experimentally, the PorC/WO3-x substrate was prepared by high-temperature annealing the PorC/WO3 films under the argon atmosphere. The defect density of the WO3 was controlled by tuning the reducing reaction time during the annealing process. The SERS performance was evaluated by using R6G as the Raman reporter, it showed that the SERS intensity obtained on the substrate with the optimal annealing time of 3 h was about 8 times as high as that obtained on the PorC/WO3 substrate without annealing treatment. And detection limit of 10-7 M and Raman enhancement factor of 106 could be achieved. Moreover, the above optimal SERS substrate was utilized to detect flavonoids of quercetin, 3-hydroxyflavone and flavone, and a deep learning algorithms was incorporated to identify the quercetin. It revealed that quercetin can be accurately detected within the above flavonoids, and lowest detectable concentration of 10-5 M can be achieved.

Label-free biosensing with singular-phase-enhanced lateral position shift based on atomically thin plasmonic nanomaterials.

Rapid plasmonic biosensing has attracted wide attention in early disease diagnosis and molecular biology research. However, it was still challenging for conventional angle-interrogating plasmonic sensors to obtain higher sensitivity without secondary amplifying labels such as plasmonic nanoparticles. To address this issue, we developed a plasmonic biosensor based on the enhanced lateral position shift by phase singularity. Such singularity presents as a sudden phase retardation at the dark point of reflection from resonating plasmonic substrate, leading to a giant position shift on reflected beam. Herein, for the first time, the atomically thin layer of Ge2Sb2Te5 (GST) on silver nanofilm was demonstrated as a novel phase-response-enhancing plasmonic material. The GST layer was not only precisely engineered to singularize phase change but also served as a protective layer for active silver nanofilm. This new configuration has achieved a record-breaking largest position shift of 439.3 µm measured in calibration experiments with an ultra-high sensitivity of 1.72 × 108 nm RIU-1 (refractive index unit). The detection limit was determined to be 6.97 × 10-7 RIU with a 0.12 µm position resolution. Besides, a large figure of merit (FOM) of 4.54 × 1011 µm (RIU∙°)-1 was evaluated for such position shift interrogation, enabling the labelfree detection of trace amounts of biomolecules. In targeted biosensing experiments, the optimized sensor has successfully detected small cytokine biomarkers (TNF-α and IL-6) with the lowest concentration of 1 × 10-16 M. These two molecules are the key proinflammatory cancer markers in clinical diagnosis, which cannot be directly screened by current clinical techniques. To further validate the selectivity of our sensing systems, we also measured the affinity of integrin binding to arginylglycylaspartic acid (RGD) peptide (a key protein interaction in cell adhesion) with different Mn2+ ion concentrations, ranging from 1 nM to 1 mM.

Two-dimensional nanomaterials as enhanced surface plasmon resonance sensing platforms: Design perspectives and illustrative applications.

Both increasing demand for ultrasensitive detection in the scientific community and significant new breakthroughs in materials science field have inspired and promoted the development of new-generation multifunctional plasmonic sensing platforms by adopting promising plasmonic nanomaterials. Recently, high-quality surface plasmon resonance (SPR) sensors, assisted by two dimensional (2D) nanomaterials including 2D van der Waals (vdWs) materials (such as graphene/graphene oxide, transition metal dichalcogenides (TMDs), phosphorene, antimonene, tellurene, MXenes, and metal oxides), 2D metal-organic frameworks (MOFs), 2D hyperbolic metamaterials (HMMs), and 2D optical metasurfaces, have emerged as a class of novel plasmonic sensing platforms that show unprecedented detection sensitivity and impressive performance. This review of recent progress in 2D nanomaterials-enhanced SPR platforms will highlight their compelling plasmonic enhancement features, working mechanisms, and design methodologies, as well as discuss illustrative practical applications. Hence, it is of great importance to describe the latest research progress in 2D nanomaterials-enhanced SPR sensing cases. In this review, we present some concepts of SPR enhanced by 2D nanomaterials, including the basic principles of SPR, signal modulation approaches, and working enhancement mechanisms for various 2D materials-enhanced SPR systems. In addition, we also demonstrate a detailed categorization of 2D nanomaterials-enhanced SPR sensing platforms and comment on their ability to realize ultrasensitive SPR detection. Finally, we conclude with future perspectives for exploring a new generation of 2D nanomaterials-based sensors.

Symmetrical anisotropy enables dynamic diffraction control in photonics.

Despite the steady advancements in nanofabrication made over the past decade that had prompted a plethora of intriguing applications across various fields, achieving compatibility between miniaturized photonic devices and electronic dimensions remains unachievable due to the inherent diffraction limit of photonic devices. Herein, we present an approach based on anisotropic scaling of the shapes of photonic crystals (PhCs) to overcome the diffraction limit and achieve controlled diffraction limit along the ΓX direction. Thus, we demonstrate that scaling the direction perpendicular to the wave's propagation (y-direction) by 1/2 and 1/4 significantly improves the diffraction limit by two and four orders of magnitude, respectively. This approach opens up possibilities for high-frequency wave guiding in a cermet configuration, which was previously unachievable. Furthermore, we illustrate the existence of a quasi-bound state in the continuum (QBICs) in asymmetric dimer network-type photonic crystals (PhCs).

Ag NC and Ag NP/PorC Film-Based Surface-Enhanced Raman Spectroscopy-Type Immunoassay for Ultrasensitive Prostate-Specific Antigen Detection.

Surface-enhanced Raman scattering (SERS) is a spectral detection technology with high sensitivity and detectivity and can be used to detect the fingerprint information of the molecules with ultralow concentration. Herein, a kind of immunostructure constructed by Ag nanoparticle/porous carbon (Ag NP/PorC) films as the immunosubstrate and Ag NCs as the immunoprobes was presented for ultralow level prostate-specific antigen (PSA) detection. Experimentally, the Ag NP/PorC film was first prepared with a facile method by carbonizing the gelatin-AgNO3 film in air, and Ag NCs were synthesized by the hydrothermal method. Then, the Ag NP/PorC film was modified by PSA antibodies as the substrate, while Ag NCs were decorated by R6G and PSA antibodies for probes. The sandwiched SERS detection embodiment was constructed by the immunoreaction between the PSA and PSA antibody predecorated on the substrate and probes. Our results show that the proposed SERS-type immunoassay is highly sensitive and selective to a wide range of PSA concentrations from 10-5 to 10-12 g/mL. Thereafter, it was also implemented to detect the PSA level in human serum, and the results successfully reproduce the PSA levels as those measured by the chemiluminescence method with a recovery rate above 90%. All in all, this SERS-type immunoassay provides a promising method for the early diagnosis of prostate cancer.

Rapid Prototyping of Multi-Functional and Biocompatible Parafilm®-Based Microfluidic Devices by Laser Ablation and Thermal Bonding.

In this paper, we report a simple, rapid, low-cost, biocompatible, and detachable microfluidic chip fabrication method for customized designs based on Parafilm®. Here, Parafilm® works as both a bonding agent and a functional membrane. Its high ultimate tensile stress (3.94 MPa) allows the demonstration of high-performance actuators such as microvalves and micropumps. By laser ablation and the one-step bonding of multiple layers, 3D structured microfluidic chips were successfully fabricated within 2 h. The consumption time of this method (~2 h) was 12 times less than conventional photolithography (~24 h). Moreover, the shear stress of the PMMA-Parafilm®-PMMA specimens (0.24 MPa) was 2.13 times higher than that of the PDMS-PDMS specimens (0.08 MPa), and 0.56 times higher than that of the PDMS-Glass specimens (0.16 MPa), showing better stability and reliability. In this method, multiple easily accessible materials such as polymethylmethacrylate (PMMA), PVC, and glass slides were demonstrated and well-incorporated as our substrates. Practical actuation devices that required high bonding strength including microvalves and micropumps were fabricated by this method with high performance. Moreover, the biocompatibility of the Parafilm®-based microfluidic devices was validated through a seven-day E. coli cultivation. This reported fabrication scheme will provide a versatile platform for biochemical applications and point-of-care diagnostics.

Asymmetrical Dimer Photonic Crystals Enabling Outstanding Optical Sensing Performance.

The exploration of the propensity of engineered materials to bring forward innovations predicated on their periodic nanostructured tailoring rather than the features of their individual compounds is a continuous pursuit that has propelled optical sensors to the forefront of ultra-sensitive bio-identification. Herein, a numerical analysis based on the Finite Element Method (FEM) was used to investigate and optimize the optical properties of a unidirectional asymmetric dimer photonic crystal (PhC). The proposed device has many advantages from a nanofabrication standpoint compared to conventional PhCs sensors, where integrating defects within the periodic array is imperative. The eigenvalue and transmission analysis performed indicate the presence of a protected, confined mode within the structure, resulting in a Fano-like response in the prohibited states. The optical sensor demonstrated a promising prospect for monitoring the DNA hybridization process, with a quality factor (QF) of roughly 1.53×105 and a detection limit (DL) of 4.4×10-5 RIU. Moreover, this approach is easily scalable in size while keeping the same attributes, which may potentially enable gaze monitoring.

A Composite-Type MEMS Pirani Gauge for Wide Range and High Accuracy.

To achieve a wide range and high accuracy detection of the vacuum level, for example, in an encapsulated vacuum microcavity, a composite-type MEMS Pirani gauge has been designed and fabricated. The Pirani gauge consists of two gauges of different sizes connected in series, with one gauge having a larger heat-sensitive area and a larger air gap for extending the lower measurable limit of pressure (i.e., the high vacuum end) and the other gauge having a smaller heat-sensitive area and a smaller air gap for extending the upper measurable limit. The high-resistivity titanium metal was chosen as the thermistor; SiNx was chosen as the dielectric layer, considering the factors relevant to simulation and manufacturing. By simulation using COMSOL Multiphysics and NI Multisim, a range of measurement of 2 × 10-2 to 2 × 105 Pa and a sensitivity of 52.4 mV/lgPa were obtained in an N2 environment. The performance of the fabricated Pirani gauge was evaluated by using an in-house made vacuum test system. In the test, the actual points of measurement range from 6.6 × 10-2 to 1.12 × 105 Pa, and the highest sensitivity is up to 457.6 mV/lgPa. The experimental results are better in the range of measurement, sensitivity, and accuracy than the simulation results. The Pirani gauge proposed in this study is simple in structure, easy to manufacture, and suitable for integration with other MEMS devices in a microcavity to monitor the vacuum level therein.

An Integrated ddPCR Lab-on-a-Disc Device for Rapid Screening of Infectious Diseases.

Digital droplet PCR (ddPCR) is a powerful amplification technique for absolute quantification of viral nucleic acids. Although commercial ddPCR devices are effective in the lab bench tests, they cannot meet current urgent requirements for on-site and rapid screening for patients. Here, we have developed a portable and fully integrated lab-on-a-disc (LOAD) device for quantitively screening infectious disease agents. Our designed LOAD device has integrated (i) microfluidics chips, (ii) a transparent circulating oil-based heat exchanger, and (iii) an on-disc transmitted-light fluorescent imaging system into one compact and portable box. Thus, droplet generation, PCR thermocycling, and analysis can be achieved in a single LOAD device. This feature is a significant attribute for the current clinical application of disease screening. For this custom-built ddPCR setup, we have first demonstrated the loading and ddPCR amplification ability by using influenza A virus-specific DNA fragments with different concentrations (diluted from the original concentration to 107 times), followed by analyzing the droplets with an external fluorescence microscope as a standard calibration test. The measured DNA concentration is linearly related to the gradient-dilution factor, which validated the precise quantification for the samples. In addition to the calibration tests using DNA fragments, we also employed this ddPCR-LOAD device for clinical samples with different viruses. Infectious samples containing five different viruses, including influenza A virus (IAV), respiratory syncytial virus (RSV), varicella zoster virus (VZV), Zika virus (ZIKV), and adenovirus (ADV), were injected into the device, followed by analyzing the droplets with an external fluorescence microscope with the lowest detected concentration of 20.24 copies/µL. Finally, we demonstrated the proof-of-concept detection of clinical samples of IAV using the on-disc fluorescence imaging system in our fully integrated device, which proves the capability of this device in clinical sample detection. We anticipate that this integrated ddPCR-LOAD device will become a flexible tool for on-site disease detection.

Stabilization of Copper-Based Biochips with Alumina for Biosensing Application.

Surface plasmon resonance devices typically rely on the use of gold-coated surfaces, but the use of more abundant metals is desirable for the long-term development of plasmonic biochips. As a substitute for gold, thin copper films have been deposited on glass coverslips by thermal evaporation. As expected, these films immersed in a water solution initially exhibit an intense plasmonic resonance comparable to gold. However, without protection, an angle-resolved optical analysis shows a rapid degradation of the copper, characterized by a continuous angular shift of the plasmonic resonance curve. We show that copper films protected with a thin layer of aluminum oxide of a few nanometers can limit the oxidation rate for a sufficient time to perform some standard measurements. As the process is simple and compatible with the current biochip production technique, such an approach could pave the way for the production of alternative and more sustainable biochips.

Sensitivity Enhanced Plasmonic Biosensor Using Bi2Se3-Graphene Heterostructures: A Theoretical Analysis.

This study provided a theoretical insight for designing novel plasmonic biosensors using bismuth selenide (Bi2Se3)-Graphene heterostructures. It was a van der Waals (vdWs) stacked configuration composed of gold (Au) film, few quintuple layer (QL) Bi2Se3 and few-layered graphene. In particular, the proposed biosensor was created by Goos-Hänchen (GH) shift rather than phase, resulting in a more sensitive biosensing response. Under the excitation of 632.8 nm, significant sensitivity enhancement performance was obtained via varying the thickness of Bi2Se3-Graphene heterostructures. The best configuration was 32 nm Au film-2-QL Bi2Se3-3-layer graphene, generating the largest GH shift, as high as -1.0202 × 104 µm. Moreover, the highest detection sensitivity was determined to be 8.5017 × 106 µm/RIU, responding to a tiny refractive index (RI) change of 0.0012 RIU (RIU, refractive index unit). More importantly, our proposed biosensor has shown a theoretical feasibility of monitoring virus samples. For example, there was an efficient linear detection range for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 0~13.44 nanomole (nM)) and its Spike (S) glycoprotein (0~59.74 nM), respectively. It is expected that our proposed plasmonic biosensor has a potential application in performing sensitive detection of SARS-CoV-2.

Real-Time Detection of Circulating Tumor Cells in Bloodstream Using Plasmonic Fiber Sensors.

Circulating tumor cells (CTCs) are single cancer cells or cancer cell clusters that are present in the circulatory system. Assessing CTC levels in patients can aid in the early detection of cancer metastasis and is essential for the purposes of accurate cancer prognosis. However, current in vitro blood tests are limited by the insufficient blood samples and low concentration levels of CTCs, which presents a major challenge for practical biosensing devices. In this work, we propose the first surface plasmon resonance (SPR) fiber probe to work intravenously, which offers a real-time detection of CTCs in bloodstreams. By exposing the protein-functionalized fiber probe to circulating blood, a continuous capture of CTCs ensures a constant increase in enrichment and hence greatly enhances enumeration accuracy. The performance of our plasmonic fiber probe was demonstrated to specifically detect Michigan Cancer Foundation-7 (MCF-7) breast cancer cells in flowing whole mouse blood. Further, a detection limit of ~1.4 cells per microliter was achieved by using an epithelial cell adhesion molecule (EpCAM) antibody-based receptor layer and a 15 minute enrichment period. This pilot study validates real-time CTC detection directly in the bloodstream by using plasmonic fiber probes, which exhibit promising clinical potential for in vivo diagnostic tests involving low concentration biomarkers in circulating blood.

Sensitivity Enhancement of Hybrid Two-Dimensional Nanomaterials-Based Surface Plasmon Resonance Biosensor.

In this work, we designed structures based on copper nanosubstrate with graphene and two-dimensional transition metal dichalcogenides (TMDC) in order to achieve an ultrasensitive surface plasmon resonance biosensor. This system contains seven components: SF11 triangular prism, BK-7 glass, Chromium (Cr) adhesion layer, thin copper film, layers of one of the types of transition metal dichalcogenides: MoS2, MoSe2, WS2 or WSe2 (defined as MX2), graphene, sensing layer with biomolecular analyte. Copper was chosen as a plasmonic material because it has a higher conductivity than gold which is commonly used in plasmonic sensors. Moreover, copper is a cheap and widespread material that is easy to produce on a large scale. We have carried out both theoretical and numerical sensitivity calculations of these kinds of structures using the Goos-Hänchen (GH) shift method. GH shift is lateral position displacement of the p-polarized reflected beam from a boundary of two media having different indices of refraction under total internal reflection condition and its value can be retrieved from the phase change of the beam. The SPR signal based on the GH shift is much more sensitive compared to other methods, including angular and wavelength scanning, due to much more abrupt phase change of the SPR reflected light than its intensity ones. By optimizing the parameters of the SPR sensing substrate, such as thickness of copper, number of layers of 2D materials and excitation wavelength, we theoretically showed an enhanced sensitivity with a detection limit 10-9 refractive index unit (RIU).

Highly Sensitive Plasmonic Biosensors with Precise Phase Singularity Coupling on the Metastructures.

In this paper, we demonstrated the ability of a plasmonic metasensor to detect ultra-low refractive index changes (in the order of ∆n = 10-10 RIU), using an innovative phase-change material, vanadium dioxide (VO2), as the sensing layer. Different from current cumbersome plasmonic biosensing setups based on optical-phase-singularity measurement, our phase signal detection is based on the direct measurement of the phase-related lateral position shift (Goos-Hänchen) at the sensing interface. The high sensitivity (1.393 × 108 µm/RIU for ∆n = 10-10 RIU), based on the Goos-Hänchen lateral shift of the reflected wave, becomes significant when the sensor is excited at resonance, due to the near-zero reflectivity dip, which corresponds to the absolute dark point (lower than 10-6). GH shifts in the order of 2.997 × 103 µm were obtained using the optimal metasurface configuration. The surface plasmon resonance (SPR) curves (reflectivity, phase, GH) and electromagnetic simulations were derived using the MATLAB programming algorithm (by the transfer matrix method) and Comsol modeling (by finite element analysis), respectively. These results will provide a feasible way for the detection of cancer biomarkers.

Highly Sensitive Plasmonic Waveguide Biosensor Based on Phase Singularity-Enhanced Goos-Hänchen Shift.

The detection for small molecules with low concentrations is known to be challenging for current chemical and biological sensors. In this work, we designed a highly sensitive plasmonic biosensor based on the symmetric metal cladding plasmonic waveguide (SMCW) structure for the detection of biomolecules. By precisely designing the configuration and tuning the thickness of the guiding layer, ultra-high order modes can be excited, which generates a steep phase change and a large position shift from the Goos−Hänchen effect (with respect to refractive index changes). This position shift is related to the sharpness of the optical phase change from the reflected signal of the SPR sensing substrate and can be directly measured by a position sensor. Based on our knowledge, this is the first experimental study done using this configuration. Experimental results showed a lateral position signal change > 90 µm for glycerol with a sensitivity figure-of-merit of 2.33 × 104 µm/RIU and more than 15 µm for 10−4 M biotin, which is a low molecular weight biomolecule (less than 400 Da) and difficult to be detected with traditional SPR sensing techniques. Through integrating the waveguide with a guiding layer, a strong improvement in the electric field, as well as sensitivity have been achieved. The lateral position shift has been further improved from 14.17 µm to 284 µm compared with conventional SPR substrate with 50 nm gold on single side. The as-reported sensing technique allows for the detection of ultra-small biological molecules and will play an important role in biomedical and clinical diagnostics.

Development and Validation of a 7-Gene Inflammatory Signature Forecasts Prognosis and Diverse Immune Landscape in Lung Adenocarcinoma.

Background: Inflammatory responses are strongly linked with tumorigenesis and cancer development. This research aimed to construct and validate a novel inflammation response-related risk predictive signature for forecasting the prognosis of patients with LUAD. Methods: Differential expression analysis, univariate Cox, LASSO, and multivariate Cox regression analyses of 200 inflammatory response-related genes (IRRG) were performed to establish a risk predictive model in the TCGA training cohort. The performance of the IRRG model was verified in eight GEO datasets. GSEA analysis, ESTIMATE algorithms, and ssGSEA analysis were applied to elucidate the possible mechanisms. Furthermore, the relationship analysis between risk score, model genes, and chemosensitivity was performed. Last, we verified the protein expression of seven model genes by immunohistochemical staining or Western blotting. Results: We constructed a novel inflammatory response-related 7-gene signature (MMP14, BTG2, LAMP3, CCL20, TLR2, IL7R, and PCDH7). Patients in the high-risk group presented markedly decreased survival time in the TCGA cohort and eight GEO cohorts than the low-risk group. Interestingly, multiple pathways related to immune response were suppressed in high-risk groups. The low infiltration levels of B cell, dendritic cell, natural killer cell, and eosinophil can significantly affect the unsatisfactory prognosis of the high-risk group in LUAD. Moreover, the tumor cells' sensitivity to anticancer drugs was markedly related to risk scores and model genes. The protein expression of seven model genes was consistent with the mRNA expression. Conclusion: Our IRRG prognostic model can effectively forecast LUAD prognosis and is tightly related to immune infiltration.

Clinical Study of a Q-Switched Neodymium-Doped Yttrium Aluminum Garnet Laser with Different Parameters in the Treatment of Chloasma: A Randomized-Controlled Trial.

Objective: To explore the clinical efficacy of a Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with different parameters in the treatment of chloasma. Methods: In this study, 30 patients with chloasma, symmetrically distributed on the left and right sides of the face and who were treated with a Fayton Q-switched 1064 nm Nd:YAG laser, were recruited. The patients were randomly selected for the treatment of facial lesions on the left and right sides of the face using a spot diameter of 9 mm and an energy density of 0.8 J/cm2 on one side, and, on the opposite side, a spot diameter of 6 mm with an energy density of 1.2 J/cm2. The laser frequency was 5 Hz and treatment was conducted once every 7-10 days and repeated eight times as a course of treatment. At the end of the course of treatment, as well as 1, 3, and 6 months after treatment, front-facing images and 45° left- and right-side images were taken, respectively. The curative effect of the treatment was evaluated using the Melasma Area Severity Index (MASI) score. Results: The results of this study showed that the total effective rate of a Fayton Q-switched 1064 nm Nd:YAG laser in the treatment of chloasma was 60%. Conclusions: Using a Q-switched 1064 nm Nd:YAG laser represents a safe and effective approach for the treatment of chloasma. The therapeutic effects of the parameter sets, that is, a spot diameter of 9 mm and an energy density of 0.8 J/cm2, and a spot diameter of 6 mm with an energy density of 1.2 J/cm2, were similar. The treatment time and average effective times of the latter were relatively shortened. Clinical Trial Registration number researchregistry6799.

Process Optimization and Performance Evaluation of TSV Arrays for High Voltage Application.

In order to obtain high-quality through-silicon via (TSV) arrays for high voltage applications, we optimized the fabrication processes of the Si holes, evaluated the dielectric layers, carried out hole filling by Cu plating, and detected the final structure and electric properties of the TSVs. The Si through-hole array was fabricated in an 8-inch Si substrate as follows: First, a blind Si hole array was formed by the Si deep reactive etching (DRIE) technique using the Bosch process, but with the largest width of the top scallops reduced to 540 nm and the largest notch elimidiameternated by backside grinding, which also opens the bottom ends of the Si blind holes and forms 500-µm-deep Si through holes. Then, the sidewalls of the Si holes were further smoothed by a combination of thermal oxidation and wet etching of the thermal oxide. The insulating capability of the dielectric layers was evaluated prior to metal filling by using a test kit. The metal filling of the through holes was carried out by bottom-up Cu electroplating and followed by annealing at 300 °C for 1 h to release the electroplating stress and to prevent possible large metal thermal expansion in subsequent high-temperature processes. The TSV arrays with different hole diameters and spacing were detected: no visible defects or structure peeling was found by scanning electron microscopy (SEM) observations, and no detectable interdiffusion between Cu and the dielectric layers was detected by energy dispersive X-ray (EDX) analyses. Electric tests indicated that the leakage currents between two adjacent TSVs were as low as 6.80 × 10-10 A when a DC voltage was ramped up from 0 to 350 V, and 2.86 × 10-9 A after a DC voltage was kept at 100 V for 200 s.

Molybdenum Oxide/Tungsten Oxide Nano-heterojunction with Improved Surface-Enhanced Raman Scattering Performance.

By virtue of their high uniformity and stability, metal oxide-based surface-enhanced Raman spectroscopy (SERS) substrates have attracted enormous attention for molecular trace detection. However, strategies for further enhancing the SERS sensitivity are still desired. Herein, MoOx/WOx nano-heterojunctions are constructed by mixing MoOx and WOx together (MoOx/WOx hybrid) with diverse weight ratios. Using a 532 nm laser as the excitation source and R6G as the Raman reporter, it is shown that the Raman signal intensity (for the peak @ 1360 cm-1) obtained on the optimal MoOx/WOx hybrid (MoOx/WOx = 1:1/3) is twice that observed on a pure MoOx or WOx substrate. Moreover, a limit of detection of 10-8 M and an enhancement factor of 108 are achieved. In the SERS enhancement mechanism investigation, it is revealed that MoOx and WOx form a staggered band structure. During the SERS measurement, electron-hole pairs are generated in the nano-heterojunction using the incident laser. They are then separated by the built-in potential with the electrons moving toward WOx. The accumulated electrons on WOx are further transferred to the R6G molecules through the coupling of orbitals. Consequently, the molecular polarizability is amplified, and SERS performance is enhanced. The abovementioned explanation is supported by the evidence that the contribution of the chemical enhancement mechanism in the optimal MoOx/WOx hybrid substrate is about 2.5 times or 5.9 times that in the pure WOx or MoOx substrate.