In this work, we report the plasmonic properties of aluminum films as substrate materials for multiple analytical platforms, including surface plasmon resonance (SPR) and MALDI-MS. The intrinsic optical sensitivity was characterized with ionic polymer coatings, lipid vesicles, and medically relevant biomarkers. In SPR imaging mode, the aluminum film allowed for the sensitive quantification of kinetic differences of binding interactions between the ionic polymer and biomarker peptides of CXCL8 and CXCL10. The binding was found to be correlated to the charge densities of the biomarkers and the polymer coating, and the use of an artificial urine matrix could alter the association behavior. The e-beam fabricated Al film was also shown to be effective for enriching phosphorylated peptides from milk proteins for mass spectrometric profiling. The surface-assisted ionization process was further investigated by comparing MALDI spectra of biomarkers obtained on conventional stainless steel plates, Au films, and Al films. Results indicate that aluminum films have m/z intensity values significantly higher than those on a steel plate and Au film, suggesting the electronic and plasmonic properties of aluminum thin films, especially those under UV conditions, may lead to an improved performance in MALDI signals. We believe that Al thin films have great potential as substrates for developing bioanalytical methods and can have vast benefits for the future study of biophysical interactions.

A majority of biomimetic membranes used for current biophysical studies rely on planar structures such as supported lipid bilayer (SLB) and self-assembled monolayers (SAMs). While they have facilitated key information collection, the lack of curvature makes these models less effective for the investigation of curvature-dependent protein binding. Here, we report the development and characterization of curved membrane mimics on a solid substrate with tunable curvature and ease in incorporation of cellular membrane components for the study of protein-membrane interactions. The curved membranes were generated with an underlayer lipid membrane composed of DGS-Ni-NTA and POPC lipids on the substrate, followed by the attachment of histidine-tagged cholera toxin (his-CT) as a capture layer. Lipid vesicles containing different compositions of gangliosides, including GA(1), GM(1), GT(1b), and GQ(1b), were anchored to the capture layer, providing fixation of the curved membranes with intact structures. Characterization of the curved membrane was accomplished with surface plasmon resonance (SPR), fluorescence recovery after photobleaching (FRAP), and nano-tracking analysis (NTA). Further optimization of the interface was achieved through principal component analysis (PCA) to understand the effect of ganglioside type, percentage, and vesicle dimensions on their interactions with proteins. In addition, Monte Carlo simulations were employed to predict the distribution of the gangliosides and interaction patterns with single point and multipoint binding models. This work provides a reliable approach to generate robust, component-tuning, and curved membranes for investigating protein interactions more pertinently than what a traditional planar membrane offers.

A Surface Plasmon Resonance (SPR) biosensor based on an inhibition immunoassay was developed for the detection of diclofenac (DCF) in aqueous solution. Due to the small size of DCF, an hapten-protein conjugate was produced by coupling DCF to bovine serum albumin (BSA). DCF-BSA conjugate formation was confirmed via MALDI-TOF mass spectrometry. The resulting conjugate was immobilized onto the surface of a sensor fabricated via e-beam deposition of a 2 nm chromium adhesion layer followed by a 50 nm gold layer onto precleaned BK7 glass slides. Immobilization onto the nano thin gold surface was accomplished by covalent amide linkage through a self-assembled monolayer. Samples were composed of a mixture of antibody at a fixed concentration and DCF at different known concentrations in deionized water, causing the inhibition of anti-DCF on the sensor. The DCF-BSA was obtained with a ratio of 3 DCF molecules per BSA. A calibration curve was performed using concentrations between 2 and 32 μg L−1. The curve was fitted using the Boltzmann equation, reaching a limit of detection (LOD) of 3.15 μg L−1 and limit of quantification (LOQ) of 10.52 μg L−1, the inter-day precision was calculated and an RSD value of 1.96% was obtained; and analysis time of 10 min. The developed biosensor is a preliminary approach to the detection of DCF in environmental water samples, and the first SPR biosensor developed for DCF detection using a hapten-protein conjugate.

Multiple sclerosis (MS) is the most common autoimmune disease observed in young adults and is known to be exceptionally difficult to diagnose accurately. Current diagnostic methods are considered unreliable and inefficient, and they typically lack the needed specificity that allows for routine monitoring of disease progression. In this work, we report a surface plasmon resonance imaging (SPRi) method in combination with carbohydrate microarrays for the detection of multiple sclerosis biomarkers in undiluted serum. A working range of 1–100 ng/mL was demonstrated with the limit of detection (LODs) below 7 ng/mL. The microarrays utilized in this work were coated with perfluorodecyltrichlorosilane (PFDTS) to interact strongly with the hydrophobic tails of the ganglioside antigens, allowing for desirable antigenic display in a manner mimicking a myelin sheath. Machine learning (ML) algorithms were applied to the carbohydrate array/SPRi data analysis to understand and characterize the cross reactivities observed between the antibodies. Both endpoint results and SPRi sensorgrams were analyzed with statistical models for the evaluation of binding events that include kinetic and steady state components. In addition, K-nearest neighbor (kNN) and neural net (nnet) were utilized to examine specific and cross-reactive binding, yielding higher accuracy than what traditional methods can achieve. The combination of ML models and microarray data provides a comprehensive understanding of complex interactions and could be used to differentiate and identify closely behaving biomarkers in a clinical setting.

The introduction of copper as wire bonding material brings about a new challenge of aluminum bond pad bimetallic corrosion at the copper/aluminum galvanic interface. Aluminum is well known to undergo pitting corrosion under halide-contaminated environments, even in slightly acidic conditions. This paper aims to study the corrosion morphology and progression of aluminum influenced by different halide contaminations in the presence and absence of galvanic contact with copper. We used a new corrosion characterization platform of the micropattern corrosion screening to simulate the copper wire bonding on the aluminum bond pad. The corrosion screening data and subsequent SEM–EDX analyses showed a striking difference in morphology and progression between chloride-induced and fluoride-induced aluminum corrosion. The corrosion products formed play a vital role in the resulting morphology and in sustaining further aluminum corrosion.

A new amino acid-based ionic liquid of 1-methyl-3-dodecane imidazolium aspartic acid ([Cnmim]Asp IL, n = 4, 6, 8, 12, 14) was reported as a soft matrix to be used as a novel electrochemical glucose...

Aluminum has recently attracted considerable interest as a plasmonic material due to its unique optical properties, but most work has been limited to nanostructures. We report here SPR biosensing with aluminum thin-films using the standard Kretschmann configuration that has previously been dominated by gold films. Electron-beam physical vapor deposition (EBPVD)-prepared Al films oxidize in air to form a nanofilm of Al2O3, yielding robust stability for sensing applications in buffered solutions. FDTD simulations revealed a sharp plasmonic dip in the visible range that enables measurement of both angular shift and reflection intensity change at a fixed angle. Bulk and surface tests indicated that Al films exhibited superb sensitivity performance in both categories. Compared to Au, the Al/Al2O3 layer showed a marked effect of suppressing nonspecific binding from proteins in human serum. Further characterization indicated that Al film demonstrated a higher sensitivity and a wider working range than Au films when used for SPR imaging analysis. Combined with its economic and manufacturing benefits, the Al thin-film has the potential to become a highly advantageous plasmonic substrate to meet a wide range of biosensing needs in SPR configurations.

We reported the synthesis of novel platinumnanoparticle-decorated reduced graphene oxide@polystyrene nanospheres (PtNPs@rGO@PS NSs) and their use in developing a novel label-free electrochemical immunosensor for tumor markers. The PtNPs@rGO@PS NSs were fabricated via the electrostatic self-assembly of negatively charged graphene oxide nanosheets onto positively charged PS nanospheres, followed by hydrazine reduction of the GO outer layer and the in situ deposition of PtNPs. The PtNPs@rGO@PS NSs were characterized by scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The PtNPs@rGO@PS NSs show a large specific surface area, high electrical conductivity, and good hydrophilicity. The nanospheres were further biofunctionalized with streptavidin and a biotinylated antibody for use as a highly sensitive electrochemical immunosensor for the label-free determination of tumor marker carcinoembryonic antigen (CEA). The fabricated immunosensor detected concentrations of CEA ranging from 0.05 to 70 ng/mL with a detection limit of 0.01 ng/mL, presenting high sensitivity comparable to standard commercial techniques. The nanospheres also showed excellent specificity against other tumor markers and reliability in detection with clinical samples.

Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheaths of nerve cells in the central nervous system. An individual suffering from MS produces increased levels of antibodies that target cell membrane components, such as phospholipids, gangliosides, and membrane proteins. Among them, anti-ganglioside antibodies are considered as important biomarkers to differentiate MS from other diseases that exhibit similar symptoms. We report here a label-free method for detecting a series of antibodies against gangliosides in serum by surface plasmon resonance imaging (SPRi) in combination with a carbohydrate microarray. The ganglioside array was fabricated with a plasmonically tuned, background-free biochip, and coated with a perfluorodecyltrichlorosilane (PFDTS) layer for antigen attachment as a self-assembled pseudo-myelin sheath. The chip was characterized with AFM and matrix-assisted laser desorption ionization mass spectrometry, demonstrating effective functionalization of the surface. SPRi measurements of patients' mimicking blood samples were conducted. A multiplexed detection of antibodies for anti-GT1b, anti-GM1, and anti-GA1 in serum was demonstrated, with a working range of 1 to 100 ng/mL, suggesting that it is well suited for clinical assessment of antibody abnormality in MS patients. Statistical analyses, including PLS-DA and PCA show the array allows comprehensive characterization of cross reactivity patterns between the MS specific antibodies and can generate a wide range of information compared to traditional end point assays. This work uses PFDTS surface functionalization and enables direct MS biomarker detection in serum, offering a powerful alternative for MS assessment and potentially improved patient care.

Microelectronics are used in virtually all electronic equipment’s nowadays ranging from medical instruments, automobiles, computers, cell phones and home appliances. Wirebonding process which connects the chip to the lead frame in IC packaging plays a very important role in the commercial production of IC’s. Chip usually consists of Al bond pads with Cu/Au wires. Thin film Al bond pads are easily vulnerable to corrosion in presence of contaminants and moisture. Bond pad corrosion is one of the common modes of corrosion failure in wire-bonded devices IC packaging. Improper rinsing, packaging and passivation defects allows moisture and contaminants into bondpads resulting in severe corrosion. Most common source of this corrosion comes from the presence of halide ions contamination as (Cl-, F-, Br- etc.) However, the corrosion morphology and the severity varies from different ions contamination as the chemistry governing the corrosion differs from one ion to another. Our research is focused on key findings on corrosion of Aluminum bond pad due to chloride (Cl-) and fluoride (F-) contamination. Our central motivation is to identify this F- corrosion mechanism, so that it will help to develop a strategy to prevent it and study the comparison between Cl- and F- Corrosion using Micro-pattern corrosion screening technique, Wire-bonded device (WBD) and other characterization technique such as GC-MS, SEM and tafel. GC-MS reveals that H2 gas evolution is observed during Cl- corrosion of the WBD, whereas little or no H2 evolution is observed during F- corrosion. SEM and EDX reveals no presence of Cl- in the corroded areas of its corrosion, whereas strong F- signal is observed in F- corrosion of the bondpads revealing, that the corrosion products formed on the surface has very poor solubility showing that Cl- and F- has a complete different corrosion morphology. Striking contrasts in corrosion morphology observed during the Cl- and F- corrosion were explained in the present work and will lead to better understanding of factors influencing the bond pad corrosion leading to the wire bond failure in IC packaging devices. [Fig. 1] Figure 1

The explosion of microelectronics use in automobiles has made the microelectronic corrosion control more critical over the past decade. Wire bonded devices form an integral part of the microelectronic systems used in automobiles. With the reliability requirements of automobile microelectronics pushing towards ppb levels of failure, halide induced corrosion issues have to be controlled to achieve such high reliability goals. The corrosion of Aluminum bond pads in slightly acidic chloride solutions (ppm level) has been one of the main modes of wire-bonding failure in wire bonded devices. Earlier researches pointed out the possibility of intermetallic compound formation as the main reason for this corrosion. However, our investigation of the electrochemical nature of the corrosion led to the discovery that bimetallic contact of the aluminum bond pads with copper wires is the main reason for this type of corrosion. Copper and Aluminum being apart in the galvanic series can act as a galvanic corrosion cell under suitable conditions. Furthermore, the presence of halides causes de-passivation of Aluminum oxide layer making the Aluminum bond pad more susceptible to corrosion. In this report we introduce corrosion screening as a mimicking platform for studying wire-bond device corrosion. For the first time we reported that Hydrogen evolution is the cathodic reaction and is responsible for the explosive nature of this bond pad corrosion. By selective surface treatment of the Cu wires (cathodic part), we were able to prevent the corrosion by blocking the cathodic reaction and thereby stopping the electron flow required for the corrosion cycle to continue. The prevention treatment was then applied to commercial wire-bonded device and excellent corrosion prevention was observed. The corrosion inhibition coating exhibited high thermal stability up to 260 O C. We also report a novel testing method for corrosion testing of molded wire-bonded device with internal chloride ion contamination. Electrical continuity and delamination analysis showed that the chosen method of inhibition treatment was able to prevent corrosion even in cases of high chloride contamination and severe delamination. The results of the Pressure Cooker Test showed that the inhibitor coating is suitable for prevention of corrosion in even 100% Relative Humidity environments. Work is now in progress to apply these treatments to Palladium coated Copper wire bonded devices to check corrosion prevention ability of the reported corrosion prevention treatment.

Nanomaterial-enabled chemiluminescence (CL) detection has become a growing area of interest in recent years. We review the development of nanomaterial-based CL detection strategies and their applications in bioanalysis. Much progress has been achieved in the past decade, but most attempts still remain in the proof-of-concept stage. This review highlights recent advances in nanomaterials in CL detection and organizes them into three groups based on their role in detection: as a sensing platform, as a signal probe, and applications in homogeneous systems. Furthermore, we have discussed the critical challenges we are facing and future prospects of this field.

The continuously increasing demand for innovation in the miniaturization of microelectronics has driven the need for ever more precise fabrication strategies for device packaging, especially for printed circuit boards (PCBs). Subtractive copper etching is a fundamental step in this processes, requiring very precise control of etch rate and etch profile. Cu etching baths are typically monitored with several parameters including oxidation-reduction potential, conductivity, and specific gravity. However, the etch rate and etch profile can be difficult to control even under strict engineering controls of those monitoring parameters. The basic understanding of the Cu etching is shown in the figure below [Fig 1], whereas the reality is that the mechanism of acidic cupric chloride etching, regeneration and recovery is complex [Fig 1], and the current monitoring strategies can have difficulty controlling the complex interlocking chemical equilibria. We report that thin-film UV-Vis spectroscopy has the capability to effectively monitor the electrochemical processes and its complex redox changes to the etch bath from beginning to end. We report that the complex equilibria has direct control on the etch rate and its regeneration process. UV-Vis spectroscopy also reveals various underlying mechanism reasons for etch bath behavior and illuminates the roles of H+ and Cl- to the etch bath while also providing a means to monitor the Cl-. By implementing thin film UV-Vis, we are able to probe and monitor the equilibria in real time to maintain a consistent etch rate throughout while also achieving proper regeneration and recovery for repeated use. Additionally, we’ve shown that this technique is sufficient in supplementing oxidation-reduction potential, conductivity, and specific gravity methods. This addition be can utilized to improve current monitoring strategies as it can identify and predict etching behavior that the current standard methodologies may have difficulty predicting. Figure 1

The continuously increasing demand for innovation in the miniaturization of microelectronics has driven the need for ever more precise fabrication strategies for device packaging, especially for printed circuit boards (PCBs). Subtractive copper etching is a fundamental step in this processes, requiring very precise control of etch rate and etch profile. Cu etching baths are typically monitored with several parameters including oxidation-reduction potential, conductivity, and specific gravity. However, the etch rate and etch profile can be difficult to control even under strict engineering controls of those monitoring parameters. The mechanism of acidic cupric chloride etching, regeneration and recovery is complex, and the current monitoring strategies can have difficulty controlling the complex interlocking chemical equilibria. We report that thin-film UV-Vis spectroscopy has the capability to effectively monitor the complex changes to the etch bath. UV-Vis also reveals various underlying mechanism reasons for etch bath behavior and illuminates the roles of H+ and Cl− to the etch bath while also providing a means to monitor the Cl−. Furthermore, UV-Vis can be utilized to improve current monitoring strategies, as it can identify and predict etching behavior that the current standard methodologies may have difficulty predicting.

The recent explosion of 3D printing applications in scientific literature has expanded the speed and effectiveness of analytical technological development. 3D printing allows for manufacture that is simply designed in software and printed in house with nearly no constraints on geometry, and analytical methodologies can thus be prototyped and optimized with little difficulty. The versatility of methods and materials available allows the analytical chemist or biologist to fine tune both the structural and functional portions of their apparatus. This flexibility has more recently extended to optical-based bioanalysis, with higher resolution techniques and new printing materials opening the door for a wider variety of optical components, plasmonic surfaces, optical interfaces and biomimetic systems that can be made in lab. There have been discussions and reviews of various aspects of 3D printing technologies in analytical chemistry: this review highlights recent literature and trends in their applications to optical sensing and bioanalysis.

The recent explosion of 3D printing applications in scientific literature has expanded the speed and effectiveness of analytical technological development. 3D printing allows for manufacture that is simply designed in software and printed in-house with nearly no constraints on geometry, and analytical methodologies can thus be prototyped and optimized with little difficulty. The versatility of methods and materials available allows the analytical chemist or biologist to fine-tune both the structural and functional portions of their apparatus. This flexibility has more recently been extended to optical-based bioanalysis, with higher resolution techniques and new printing materials opening the door for a wider variety of optical components, plasmonic surfaces, optical interfaces, and biomimetic systems that can be made in the laboratory. There have been discussions and reviews of various aspects of 3D printing technologies in analytical chemistry; this Review highlights recent literature and trends in their applications to optical sensing and bioanalysis.

Sensitive detection and monitoring of biological interactions in a high throughput, multiplexed array format has numerous advantages. We report here a method to enhance detection sensitivity in surface plasmon resonance (SPR) spectroscopy and SPR imaging via the effect of accumulation of conjugated nanoparticles of varying sizes. Bacterial cholera toxin (CT) was chosen for the demonstration of enhanced immunoassay by SPR After immobilization of CT on a gold surface, specific recognition is achieved by biotinylated anti-CT. The signal is amplified by the attachment of biotinylated 20 nm AuNP via streptavidin bridge, followed by attachment of 5 nm streptavidin-functionalized Fe3O4 NP to the AuNP-biotin surface. The continuous surface binding of two differently sized conjugated nanoparticles effectively increases their packing density on surface and significantly improves SPR detection sensitivity, allowing quantitative measurement of CT at very low concentration. The dense packing of conjugated nanoparticles on the surface was confirmed by atomic force microscopy characterization. SPR imaging of the immunoassay for high-throughput analysis utilized an Au-well microarray that attenuated the background resonance interference on the resulting images. A calibration curve of conjugated nanoparticle binding signal amplification for CT detection based on surface coverage has been obtained that shows a correlation in a range from 6.31 X 10(-16) to 2.51 X 10(-13) mol/cm(2) with the limit of detection of 5.01 x 10(-16) mol/cm(2). The absolute quantity of detection limit using SPR imaging was 0.25 fmol. The versatile nanoparticles and biotin-streptavidin interaction used here should allow adaptation of this enhancement method to many other systems that include DNA, RNA, peptides, and carbohydrates, opening new avenues for ultrasensitive analysis of biomolecules.

Quantitative detection of multiple chicken cytokines is a good evaluation of cell-mediated immunity in chickens after disease infection or vaccination. However, current assay methods for chicken cytokines cannot meet the needs of clinical diagnosis due to unsatisfactory sensitivity and low assay throughput. Herein, a sensitive chemiluminescence (CL) imaging immunosensor array has been developed for high-throughput detection of multiple chicken cytokines. The chicken cytokines immunosensor array was prepared by assembling different cytokine capture antibodies onto a disposable silanized glass chip, where horseradish peroxidase and antibody-conjugated gold nanoparticles were used as multienzymatic amplification probe for CL imaging signal amplification. By using a sandwich assay mode, the amplified CL signals from each sensing array cell were collected for quantitation. Using chicken interleukin-4 and chicken interferon-γ as model cytokines, this novel multiplexed and amplified method demonstrated simultaneous measurement of the two chicken cytokines in the linear ranges of 0.008-0.12 ng/mL and 0.005-0.20 ng/mL, respectively, which yields limits of detection down to 2 pg/mL and 3 pg/mL. The CL imaging array method reported here also demonstrated high specificity, good repeatability, and high stability and accuracy, providing a novel multiplex immunoassay strategy for highly sensitive and high-throughput detection of chicken cytokines and further disease diagnosis in poultry.

Subtractive copper etching is a central process in fabricating advanced printed circuit boards, where ever-shrinking features demand precise control of etch rate and etch factor. Copper etching baths, using cupric chloride, involve complex chemical equilibria that the currently used semi-chemical monitoring tools, including oxidation–reduction potential, conductivity, and specific gravity, can have difficulty controlling precisely. We report a new monitoring tool, thin-film UV–vis spectroscopy, to support and enhance the existing monitoring parameters. UV–vis can distinguish specific chemical contributions to the etch bath performance and to monitoring parameters, and can contribute to significant improvements in the control of the copper etching system.