Substrate Assembly Research Articles

Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly.

Enzymatic molecular in situ self-assembly (E-MISA) that enables the synthesis of high-order nanostructures from synthetic small molecules inside a living subject has emerged as a promising strategy for molecular imaging and theranostics. This strategy leverages the catalytic activity of an enzyme to trigger probe substrate conversion and assembly in situ, permitting prolonging retention and congregating many molecules of probes in the targeted cells or tissues. Enhanced imaging signals or therapeutic functions can be achieved by responding to a specific enzyme. This E-MISA strategy has been successfully applied for the development of enzyme-activated smart molecular imaging or theranostic probes for in vivo applications. In this Perspective, we discuss the general principle of controlling in situ self-assembly of synthetic small molecules by an enzyme and then discuss the applications for the construction of "smart" imaging and theranostic probes against cancers and bacteria. Finally, we discuss the current challenges and perspectives in utilizing the E-MISA strategy for disease diagnoses and therapies, particularly for clinical translation.

Electron‐Poor Acridones and Acridiniums as Super Photooxidants in Molecular Photoelectrochemistry by Unusual Mechanisms

AbstractElectron‐deficient acridones and in situ generated acridinium salts are reported as potent, closed‐shell photooxidants that undergo surprising mechanisms. When bridging acyclic triarylamine catalysts with a carbonyl group (acridones), this completely diverts their behavior away from open‐shell, radical cationic, ‘beyond diffusion’ photocatalysis to closed‐shell, neutral, diffusion‐controlled photocatalysis. Brønsted acid activation of acridones dramatically increases excited state oxidation power (by +0.8 V). Upon reduction of protonated acridones, they transform to electron‐deficient acridinium salts as even more potent photooxidants (*E1/2=+2.56–3.05 V vs SCE). These oxidize even electron‐deficient arenes where conventional acridinium salt photooxidants have thusfar been limited to electron‐rich arenes. Surprisingly, upon photoexcitation these electron‐deficient acridinium salts appear to undergo two electron reductive quenching to form acridinide anions, spectroscopically‐detected as their protonated forms. This new behaviour is partly enabled by a catalyst preassembly with the arene, and contrasts to conventional SET reductive quenching of acridinium salts. Critically, this study illustrates how redox active chromophoric molecules initially considered photocatalysts can transform during the reaction to catalytically active species with completely different redox and spectroscopic properties.

Electron-Poor Acridones and Acridiniums as Super Photooxidants in Molecular Photoelectrochemistry by Unusual Mechanisms.

Electron-deficient acridones and in situ generated acridinium salts are reported as potent, closed-shell photooxidants that undergo surprising mechanisms. When bridging acyclic triarylamine catalysts with a carbonyl group (acridones), this completely diverts their behavior away from open-shell, radical cationic, 'beyond diffusion' photocatalysis to closed-shell, neutral, diffusion-controlled photocatalysis. Brønsted acid activation of acridones dramatically increases excited state oxidation power (by +0.8 V). Upon reduction of protonated acridones, they transform to electron-deficient acridinium salts as even more potent photooxidants (*E1/2 =+2.56-3.05 V vs SCE). These oxidize even electron-deficient arenes where conventional acridinium salt photooxidants have thusfar been limited to electron-rich arenes. Surprisingly, upon photoexcitation these electron-deficient acridinium salts appear to undergo two electron reductive quenching to form acridinide anions, spectroscopically-detected as their protonated forms. This new behaviour is partly enabled by a catalyst preassembly with the arene, and contrasts to conventional SET reductive quenching of acridinium salts. Critically, this study illustrates how redox active chromophoric molecules initially considered photocatalysts can transform during the reaction to catalytically active species with completely different redox and spectroscopic properties.

Dual-Role Peptide with Capping and Cleavage Site Motifs in Nanoparticle-Based One-Pot Colorimetric and Electrochemical Protease Assay.

A new method for enzyme substrate assembly and its use in proteolytic enzyme assays with colorimetric and electrochemical detection is presented. The novelty of the method is the use of dual-function synthetic peptide containing both gold clustering and protease-sensitive moieties, which not only induces the simple formation of the peptide-decorated gold nanoparticle test substrates but also allows for the detection of proteolysis in the same batch. Protease-treated nanoparticles with a destabilized peptide shell became more prone to electroactivity, and thus, the model enzyme plasmin activity could be quantified with stripping square wave voltammetry analysis as well, giving an alternative method to conduct aggregation-based assays. Spectrophotometric and electrochemical calibration data proved to be linear within the 40-100 nM active enzyme concentration range, with possible extensions of the dynamic range by varying substrate concentration. The simple initial components and the ease of synthesis make the assay substrate preparation economic and easy to implement. The possibility of cross-check analytical results with two independent measurement techniques in the same batch greatly increases the applicability of the proposed system.

Impact of FCBGA substrate stack-up on BLR performance

Board level reliability (BLR) temperature cycling is a metric for FCBGA field performance, where it is imperative to understand process variation holistically covering both substrate and / or assembly manufacturing process and its impact to product margin. This study focuses on technical reasoning a common FCBGA design manufactured with an identical substrate material set (i.e. core, dielectric, solder mask), assembly bill-of-materials (i.e. underfill, lid, etc.) and assembly site demonstrated different cycles to first failure during BLR testing. Although results far exceeded JESD22-A104 condition G requirements, BLR performance based on identical substrate designs (manufactured at different points in time) proved TV1 (test vehicle 1) performed ~2x better than its TV2 (test vehicle 2) counterpart. To elucidate the primary factor of the disparity in BLR performance, supplier feedback as well as a detailed package construction analysis ensued to compare build-up substrate layer thickness dimensions between TV1 and TV2. Discovery demonstrated a slightly larger volume of a specific layer in the build-up stack within TV2 that generated a higher degree of out-of-plane displacement as compared to TV1. Reproducing the cycles to first failure with the superior TV1 device via the TV1a and impact of substrate warpage was investigated as a factor in the BLR findings driving root cause.

Free Standing Dry and Stable Nanoporous Polymer Films Made through Mechanical Deformation.

A new straight forward approach to create nanoporous polymer membranes with well defined average pore diameters is presented. The method is based on fast mechanical deformation of highly entangled polymer films at high temperatures and a subsequent quench far below the glass transition temperature Tg . The process is first designed generally by simulation and then verified for the example of polystyrene films. The methodology does not need any chemical processing, supporting substrate, or self assembly process and is solely based on polymer inherent entanglement effects. Pore diameters are of the order of ten polymer reptation tube diameters. The resulting membranes are stable over months at ambient conditions and display remarkable elasticproperties.

A highly sensitive and specific fluorescent strategy for the detection of Visfatin based on nonlinear hybridization chain reaction

This study established a nonlinear hybridization chain reaction system in which trigger DNA initiates self-sustained assembly of double-stranded hairpin substrates labelled with Sulfo-Cyanine3 (Cy-3) into fluorescent dendritic nanostructures for visfatin detection. The trigger DNA chain initially bound with the anti-visfatin aptamer will be freed with visfatin, which induces continuous chain branching growth and results in an exponential increase in fluorescence signals. Under optimal conditions, the fluorescence intensity increased linearly with visfatin concentrations ranging from 1 ng mL−1 to 100 ng mL−1 (the limit of detection dropped to 0.028 ng mL−1). Furthermore, our study showed that magnetic bead separation minimizes the nonspecific signal of the method. The specificity, stability, and sensitivity of this method were also tested in the study. The results revealed excellent specificity, stability and sensitivity. In the aspect of application evaluation, we tested visfatin in clinical serum samples and obtained credible and accordant results so we suppose that our detection method might have bright prospects in biological molecule technology and early clinical discovery of type 2 diabetes (T2DM).

FEA Based Design and Stability Study of Electroless Ni-P Coating Plated over a Stepped Shaft under Thermal Load

ABSTRACT Modelling of Ni-P coating and substrate assembly is done using the finite element analysis framework. Coating having a thickness of 50 µm is applied over a stepped shaft made of stainless steel and analysed in Ansys Workbench at an elevated temperature of 200°C. The thermal effect on the system is studied and results are discussed in detail with respective figures. Elastic modulus of Ni-P coating required for the analysis is evaluated from the nanoindentation test under 10 mN load. The analysis focuses on the evaluation of the critical design parameters such as equivalent stress, total deformation, strain energy and thermal strain over the entire body. Besides, four separate paths are created on the model to study the difference of induced stress and strain energy between the contacting surfaces of the shaft and the coating. It is found that there is a sharp discontinuity in these values and this discontinuity is further interpreted as a measure of the stability of coating over the substrate. It is found that the higher the difference of stress and strain energy, lower is the stability of the assembly which is considered to be realistic and in accordance with the elasticity principles. .

Construction of broom-like Ag@N,O-C sensing interface for electrochemical detection of circulating tumor DNA using entropy-driven DNA walker

In human peripheral blood, circulating tumor DNA (ctDNA) is an excellent tumor biomarker for noninvasive diagnosis, therapy and prognosis of cancer. Herein, an innovative enzyme-free electrochemical sensor sensitized with broom-like Ag@N,O-C hierarchical nanomaterials and entropy-driven DNA walker was designed for PIK3CA E545K ctDNA assay. In this work, N, O-doped carbon layers were used to completely coat Ag nanoparticles, and then were assembled into three-dimensional broom-like nanomaterials with hierarchical structure. The application of Ag@N,O-C broom-like hierarchical nanomaterials (Ag@N,O-C BLHS) as electrode material not only facilitated electron transfer, but also increased functional active sites for a high-density assembly of DNA walking substrates. Via the entropy-driven catalytic reaction of DNA walker, one target ctDNA initiated the dissociation of abundant electroactive tags from the electrode surface, achieving a one-to-multiple amplification effect. By measuring electrochemical responses, PIK3CA E545K ctDNA was quantified with 10 aM detection limit. Additionally, the enzyme-free amplified sensing interface achieved the direct detection of ctDNA in plasma samples from breast cancer patients and healthy human. Overall, the good selectivity, reproducibility and practical application ability confirmed a promising potential of the sensor for disease diagnosis.

Performance Evaluation of Different Coating Materials in Delamination for Micro-Milling Applications on High-Speed Steel Substrate.

The objective of the present work is to carry out analytical and finite element analysis for commonly used coating materials for micro-milling applications on high-speed steel substrate and evaluate the effects of different parameters. Four different coating materials were selected for micro-milling applications: titanium nitride (TiN), diamond-like carbon (DLC), aluminium titanium nitride (AlTiN) and titanium silicon nitride (TiSiN). A 3D finite element model of coating and substrate assembly was developed in Abaqus to find the Hertzian normal stress when subjected to normal load of 4 N, applied with the help of a rigid ball. The radius of the rigid ball was 200 µm. For all the coating materials, the length was 3 mm, the width was 1 mm, and the thickness was 3 µm. For the high-speed steel substrate, the length was 3 mm, the width was 1 mm, and the thickness was 50 µm. Along the length and width, coating and substrate both were divided into 26 equal parts. The deformation behaviour of all the coating materials was considered as linear–elastic and that of the substrate was characterized as elastic–plastic. The maximum normal stress developed in the FEA model was 12,109 MPa. The variation of the FEA result from the analytical result (i.e., 12,435.97 MPa is 2.63%) which is acceptable. This confirms that the FEA model of coating–substrate assembly is acceptable. The results shows that the TiSiN coating shows least plastic equivalent strain in the substrate, which serves the purpose of protecting the substrate from plastic deformation and the TiSiN of 3 micron thickness is the most optimum coating thickness for micro-milling applications.

Design of Shape Memory Micro-Actuator Modules with Sequential Actuation

Shape memory alloy film-based micro-actuators have their behaviour controlled by a change in the thermomechanical stress that occurs in the bimorph - shape memory alloy film plus substrate assembly. The modification of the composition of the shape memory alloy leads to a change of the transformation temperature and implicitly of the temperature at which the stress change takes place in the bimorph. The design of micro-actuator blocks in which the composition and/or the temperature control mode of each micro-actuator in the block allows to obtain successive or sequential transformation sequences. The paper analyses the case of cantilever actuator modules with films of different compositions, deposited on the same substrate. It is highlighted how the composition of the alloy film with shape memory influences the modification of the curvature of bimorph cantilever type actuators in the studied block.

Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone.

DNAJB6 is a prime example of an anti‐aggregation chaperone that functions as an oligomer. DNAJB6 oligomers are dynamic and subunit exchange is critical for inhibiting client protein aggregation. The T193A mutation in the C‐terminal domain (CTD) of DNAJB6 reduces both chaperone self‐oligomerization and anti‐aggregation of client proteins, and has recently been linked to Parkinson's disease. Here, we show by NMR, including relaxation‐based methods, that the T193A mutation has minimal effects on the structure of the β‐stranded CTD but increases the population and rate of formation of a partially folded state. The results can be rationalized in terms of β‐strand peptide plane flips that occur on a timescale of ≈100 μs and lead to global changes in the overall pleat/flatness of the CTD, thereby altering its ability to oligomerize. These findings help forge a link between chaperone dynamics, oligomerization and anti‐aggregation activity which may possibly lead to new therapeutic avenues tuned to target specific substrates.

Monolayer assembly of gold nanodots on polyelectrolyte support: A multifunctional electrocatalyst for reduction of oxygen and oxidation of sulfite and nitrite

AbstractThe present work demonstrates a monolayer self‐assembly of methionine‐capped gold nanodots (AuNDs) on the glassy carbon electrode (GCE) and its application in various electrocatalytic reactions. Positively charged poly(acrylamide‐co‐diallyldimethylammonium chloride) (PADA)‐modified GCE was used as electrode substrate and monolayer assembly of negatively charged AuNDs was performed over PADA‐modified GCE by simple dipping method. The successful modification of AuNDs on GCE was confirmed by characteristic cyclic voltammetry behavior of gold oxidation and reduction. Further to optimize the dipping time duration of AuNDs self‐assembly, dipping time‐dependent electrocatalysis was performed. Interestingly, the prepared AuNDs self‐assembled electrodes exhibit very good electrocatalytic activity in the reduction of oxygen with excellent methanol tolerance and simultaneous electrooxidation of pollutants and food additives, nitrite, and sulfite ions.

CMG helicase activity on G4-containing DNA templates.

G-quadruplexes (G4s) are non-canonical nucleic acid structures that form in G-rich regions of the genome and threaten genome stability by interfering with DNA replication. However, the underlying mechanisms are poorly understood. We have recently found that G4s can stall eukaryotic replication forks by blocking the progression of replicative DNA helicase, CMG. In this paper, we detail the methodology of DNA unwinding assays to investigate the impact of G4s on CMG progression. The method details the purification of recombinantly expressed CMG from the budding yeast, Saccharomyces cerevisiae, purification of synthetic oligonucleotides, and covers various aspects of DNA substrate preparation, reaction setup and result interpretation. The use of synthetic oligonucleotides provides the advantage of allowing to control the formation of G4 structures in DNA substrates. The methods discussed here can be adapted for the study of other DNA helicases and provide a general template for the assembly of DNA substrates with distinct G4 structures.

Millimeter wave-terahertz substrate integrated waveguide transition structure based on low temperature co-fired ceramic

In a microwave circuit system, the discontinuity caused by electromagnetic wave entering into another transmission medium from one transmission medium will greatly affect the transmission performance of the system, which has always been the focus of microwave circuit design. When the electromagnetic wave band enters into the millimeter wave and terahertz band, how to realize the efficient and low loss transmission of electromagnetic wave from the metal rectangular waveguide interface to the dielectric substrate is the key to the realization of millimeter wave terahertz communication system. Substrate integrated waveguide to rectangular waveguide transition structure is an important structure connecting waveguide interface and planar circuit in millimeter wave and terahertz communication system, and it is the basis of designing planar antenna array. In this paper, a W-band and D-band substrate integrated waveguide to rectangular waveguide transition structure is designed, which improves the transmission performance and expands the bandwidth through the stepped structure. On this basis, a one-in-two divider structure is designed, with an empty cavity structure used to reduce the loss and expand the bandwidth. These two structures have the characteristics of simple structure and easy processing, and their practicalities are verified by simulation optimization and actual low temperature co-fired ceramic substrate processing and assembly test. The actual test results show that the substrate integrated waveguide to rectangular waveguide transition structure can achieve a return loss of less than –10 dB in a frequency ranges of 126–149 GHz and 112–139 GHz, the one-in-two divider structure can achieve a return loss of less than –10 dB in the frequency band of 132–155 GHz.

Erosion of focus rings in capacitively coupled plasma etching reactors

In plasma etching reactors, the structure surrounding the wafer, often called a focus ring (FR), plays an important role in maintaining uniform fluxes of reactants across the wafer. The FR is typically made of dielectric materials. During the plasma etching process, the sheath that forms over the wafer to accelerate ions anisotropically into the surface extends over the FR. Electrical charging of the FR modifies the sheath relative to that over the wafer. On the one hand, one wants the sheath to be uniform across the wafer-FR boundary to enable uniform fluxes to the edge of the wafer. On the other hand, maintaining a high voltage sheath over the FR will erode the FR, which is undesirable as the FR is a consumable component that must be periodically replaced in high volume manufacturing. In this work, we computationally investigated the consequences of dielectric constant ɛr of the FR materials on erosion of the FR. The series capacitance of the FR and its underlying structure is typically smaller than that of the wafer and its underlying structure. As a result, the FR charges quickly relative to the wafer, which then reduces the voltage across the sheath on top of the FR. The ion energy and angular distributions (IEADs) striking the FR are, therefore, generally lower in energy with a broader angular distribution. With ɛr = 2, the ion energies striking the middle to the outer edge of the FR are 30–180 eV, whereas for ɛr = 100, the ion energies are 120–380 eV. At the transition between the wafer and the FR, there is a skew in the IEAD as large as 15° that results from the difference in sheath thickness above the wafer and the FR. This skew and the erosion rate across the FR are functions of the dielectric constant of the FR material. With low ɛr, the FR charges quickly, less plasma is produced above the FR, and there is less voltage across the sheath that results in less FR erosion. Increasing ɛr of the FR produces a higher sheath voltage as well as higher ion fluxes over the FR, which increases erosion, while the skew at the edge of the wafer is less severe. The material of the subsurface portion of the FR, which dominates its capacitance, is an important consideration in the design of the substrate assembly.

Electronic module assembly

Electronics is the vital basis for innovations and the essential enabler for global trends like connectivity, electro mobility and renewable energies. These applications require high performance and reliability of the electronic modules. Their assembly combines very heterogeneous process chains like remarkable productive and diminutive surface mount technology (SMT), powerful and robust power electronic interconnection techniques, as well as pioneering reel-to-reel based organic electronic printing. After briefly outlining the enormous global economic impact of electronic modules, this paper presents the state of the art of electronic module assembly including substrate materials, electronic components, packaging and assembly processes as well as quality and reliability testing methods.

Metal Nanoparticle Film Deposition by Femtosecond Laser Ablation at Atmospheric Pressure.

Nanoparticle gold films were deposited using femtosecond laser ablation in argon at atmospheric pressure in an arrangement where a flat Au target was irradiated through a transparent substrate in close proximity. Spatially extended films were made by rastering the target and substrate assembly together in the laser beam. Fast imaging clearly showed pronounced narrowing of the ablation plume, which can be understood in terms of laser induced multiphoton ionisation and heating of the gas near the ablation site. Deposition was possible for target-substrate separation up to 2 mm. The equivalent thickness of the nanoparticle film was controlled in the range 0.4–28 nm by changing the target-substrate separation and the shot-to-shot spacing of ablation spot raster. The mean Feret diameter varied in the range 14–40 nm depending on the deposition conditions, and all the films showed a surface plasmon resonance at about 525 nm, which was nearly independent of the equivalent thickness. The technique can readily be applied to other materials for the fabrication of nanoparticulate films at atmospheric pressure.

Enzyme-Free Electrochemical Biosensor Based on Localized DNA Cascade Displacement Reaction and Versatile DNA Nanosheets for Ultrasensitive Detection of Exosomal MicroRNA.

MicroRNA existing in exosomes (exo-miRNA) is a crucial and reliable biomarker for cancer screening and diagnosis. However, accurate detection of ultralow exo-miRNA amounts in real samples remains a challenge. Herein, a robust and ultrasensitive electrochemical biosensor was developed based on localized DNA cascade displacement reaction (L-DCDR) and versatile DNA nanosheets (DNSs) for enzyme-free analysis of exo-miRNA. The target activated L-DCDR repeatedly by consecutive toehold-mediated strand displacement, which released plentiful P strands to hybridize with capture probes immobilized on the electrode surface and DNS tags, generating an amplified electrochemical signal for the detection of exo-miRNA. The DNS could label-free load various electroactive molecules. The electrochemical biosensor revealed high sensitivity ranging from 0.1 fM to 1 nM with a limit of detection of 65 aM and good specificity. The constructed biosensor was demonstrated to be able to detect exo-miRNA derived from gastric cancer cell line (SGC-7901) and gastric cancer patients. In addition, the developed biosensor possessed several considerable advantages including simple substrate assembly, improved reaction rate, and high signal-to-noise ratio. Therefore, this strategy has great potential in bioanalysis and clinical diagnostics.

ZnO Nanowalls/Si Substrate Heterojunction Assembly: Morphological, Optical and Electrical Properties

In this paper, a film of n-ZnO nanowalls was deposited over p-silicon (Si) substrate by thermally evaporating metallic zinc powder in oxygen gas environment. Several techniques were used to examine various properties of prepared ZnO nanowalls. The morphological study confirmed that the grown ZnO film possesses nanowalls shaped morphologies containing three dimensional (3D) interconnected nanowalls forming large voids with irregular shapes. Interestingly, whole Si substrate was covered with nanowalls shaped morphologies. The structural characterizations examined by x-ray diffraction (XRD) confirmed that the deposited nanowalls possess wurtzite hexagonal crystal structure. The presence of a strong UV and suppressed green emissions at room-temperature photoluminescence (PL) spectrum exhibited good optical properties of the deposited nanowalls. The electrical properties of the deposited n-ZnO nanowalls over p-silicon substrate assembly was examined in both forward and reverse bias conditions at room-temperature. The fabricated heterojunction device exhibits a standard rectifying behavior which manifests itself in an exponential increase of the current with increase in voltage at forward bias condition. Also, it has a good quality factor similar to an ideal diode.