Solid-state Array Research Articles

Solid-State Digital Micro-Mirror Array Spectrometer for Hadamard Transform Measurements of Glucose and Lactate in Aqueous Solutions

A novel solid-state near-infrared spectrometer is presented based on a digital micro-mirror array device (DMD) that is well designed for Hadamard transform spectroscopy. This spectrometer is designed for the collection of transmission spectra over the C-H first overtone region of the near-infrared spectrum (6500-5500 cm(-1)). A spectral resolution of 2.2 nm (~11 cm(-1)) is realized by using a 25 μm diameter linear tungsten filament as the source. Such a thin filament reduces imaging aberrations into the micro-mirror array, thereby enhancing spectral resolution. After passing through the sample, the transmitted radiation is dispersed with a grating before being imaged onto the surface of the DMD. Hadamard transform masks are implemented through the DMD and the reflected light is monitored by a single-element photodiode detector. The analytical utility of this approach is demonstrated through the multivariate quantification of glucose and lactate in binary mixtures composed in an aqueous buffer solution. A signal-to-noise ratio of 35,000 is achieved through these aqueous samples, and the resulting quantitative measurements provide a standard error of prediction of 1.4 and 0.9 mM for glucose and lactate, respectively. The selectivity of the resulting calibration models is established by using both a pure component selectivity analysis as well as analysis of the net analyte signal for each component. These quantitative results from the DMD Hadamard transform spectrometer compare favorably to similar measurements performed with a commercial Fourier transform spectrometer.

FRET Detection of Proteins Using Fluorescently Doped Electrospun Nanofibers and Pattern Recognition

This paper reports the fabrication of solid-state nanofiber sensor arrays and their use for detection of multiple proteins using principal component analysis (PCA). Four cationic and anionic fluorescently embedded nanofibers are generated by an electrospinning method, yielding unique patterns of fluorescence change upon interaction with protein samples. Five metal and nonmetal containing proteins, i.e., hemoglobin, myoglobin, cytochrome c, BSA, and avidin, have been investigated; and the results show that distinct fluorescent patterns can be formed upon the addition of protein samples to the array of solid nanofiber substrates, allowing their unambiguous identification. The nanofiber films are highly repeatable with a batch-to-batch variation of approximately 5% and demonstrated outstanding reusability with less than a 15% loss of fluorescence intensity signal after 5 regenerations of test cycles. For a more practical visualization, a cluster map was generated using PCA of the change-in-fluorescence (ΔI) composite patterns, demonstrating the potential of the method for diagnostic applications.

Identification of a sequence in the matricellular protein SPARC that interacts with the scavenger receptor stabilin‐1

SPARC (osteonectin/BM-40), a secreted matricellular protein that promotes cellular deadhesion and motility in wound healing, carcinogenesis, and inflammation, binds to the scavenger receptor stabilin-1 in alternatively activated macrophages and undergoes endocytosis and clearance from the extracellular space. Both SPARC and stabilin-1 are expressed by endothelial cells during inflammation, but their interaction in this context is unknown. We have identified a binding site on SPARC for stabilin-1 by a solid-state peptide array coupled with a modified enzyme-linked immunosorbent assay. A monoclonal antibody that recognizes the identified binding site was also characterized that could be an inhibitor for the SPARC-stabilin-1 interaction in macrophages or endothelial cells.

Fluorescent semiconductor nanocrystals (quantum dots) in protein biochips

Comprehension of biological processes in cells, tissues and organisms requires identification and analysis of numerous biological objects, mechanisms of their action and regulation. Microarray (biochips) technology is a rare tool to solve this problem. It is based on high-throughput recognition of a target to the probe and has the potential to measure simultaneously the presence of numerous molecules in multiplexed testes, all contained in a small drop of test fluid. Biochips allow the parallel analysis of genomic or proteomic content in healthy versus disease-affected or altered tissues or cells. The signals read-out from the biochips is done with organic dyes which often suffer from photobleaching, low brightness and background fluorescence. Recent data show that the use of fluorescent nanocrystals "quantum dots" (QDs) allows push away these restrictions. The QDs are sufficiently bright to be detected as individual particles, extremely resistant to photobleaching and provide unique possibilities for multiplexing thus supplying the microarray technology with the novel read-out option enabling the sensitivity of detection reaching the single molecule level. This paper is aimed at the development of the approaches to the QDs application in microarray-based detection. Possibilities of QDs application both in solid state (planar) biochips as well as intensively developing technique of suspension biochips (bead-based assays or liquid biochips) are demonstrated. The latter are more and more applied for simultaneous identification of very large numbers of molecules in proteomics, genomics, drug screening and clinical diagnostics. This assays base on spectral encoded elements (as a rule polymer microbeads). The benefits of using optically encoded microbeads (instead of the solid-state two-dimensional arrays) are derived from the freedom of bead to move in three dimensions. Polymeric beads optically encoded with organic dyes allow for a limited number of unique codes, whereas the use of semiconductor nanocrystals as fluorescent tags improves the beads multiplexed imaging capabilities, photostability and sensitivity of the biological objects detection. Additionally, an employment in suspension biochips of Frster resonance energy transfer (FRET) allows improving detection specificity. The absence of fluorescent background from non-interacting with the beads dye-labelled antibodies additionally increases the sensitivity of detection and further facilitates the multiplexing capabilities of nanocrystals-based detection and diagnostics. So the combination of the biochips and QDs techniques allow increasing detection sensitivity and significantly raising the number of detected objects (multiplexing capacities). Such combination should provide the breakthrough in proteomics, particularly in new drugs development, clinical diagnostics, new disease markers identification, better understanding of intracellular mechanisms.

Solid-state photon-counting hybrid detector array for high-resolution multi-energy X-ray imaging

We present in this article the development of a photon-counting, energy-discriminating modular detector based on a pixelated CdZnTe sensor coupled pixel-by-pixel to a novel Digital Pixel Sensor (DPS) readout. The detector is designed for munitions inspection, breast X-ray CT and SPECT/MRI. The current DPS design can also be used to read out other solid-state sensors. The prototype detector is 5.5 mm×5.5 mm in size, and consists of 19×19 pixels on a 250 μm pitch. The DPS is designed in a 0.35 μm process, and every pixel includes a preamplifier , a leakage-current subtraction circuit, an auto-zeroed programmable-gain stage, five comparators, a variable-delay reset circuit and five 16 bit counters. The module is expected to operate at high X-ray fluence exceeding 80 MHz/mm 2 , and to improve resolution and contrast in images, while significantly enhancing their signal-to-noise ratio, and assist in identifying material composition via dual-energy imaging. The detector design, fabrication and anticipated performance are discussed.

Engineered arrays of nitrogen-vacancy color centers in diamond based on implantation of CN− molecules through nanoapertures

We report a versatile method for engineering arrays of nitrogen-vacancy (NV) color centers in diamond at the nanoscale. The defects were produced in parallel by ion implantation through 80 nm diameter apertures patterned using electron beam lithography in a polymethyl methacrylate (PMMA) layer deposited on a diamond surface. The implantation was performed with CN− molecules that increased the NV defect-formation yield. This method could enable the realization of a solid-state coupled-spin array and could be used for positioning an optically active NV center on a photonic microstructure.

Research on Noise Sources in CMOS Image Sensors

CMOS (Complementary Metal Oxide Semiconductor) imagers as a solid state array develop rapidly. This article introduces various types of CMOS image sensors’ noises in detail, the cause of each noise, as well as a brief overview of current methods for reducing different noise.

Performance of Silicon Carbide Avalanche Photodiode Arrays and Photomultipliers

We present recent results on 4H-SiC avalanche photodiode arrays and SiC-based solid-state photomultiplier arrays suitable for ultraviolet and solar-blind light detection. A novel SiC-based photomultiplier array was demonstrated. An additional solar-blind filter enabled a solar photon rejection ratio of more than 106 in combination with 40% quantum efficiency at 280 nm.

High-sensitivity, wide-dynamic-range avalanche photodiode pixel design for large-scale imaging arrays

We present a detailed design study for a novel solid-state focal plane array of silicon avalanche photodiodes (APDs), with each detector in the array capable of operating with wide dynamic range in linear or Geiger-mode. The detector array is based on back-illuminated, crystallographically etched, (100) epitaxial silicon on R-plane sapphire substrates using 27 µm pixels, although other sizes could be supported as well. Analysis of the APD pixel design, which includes the photoelectron noise, dark current noise, and electronic circuit noise, shows the capability of imaging with a signal-to-noise ratio greater than 7 at −30 °C and ultralow illuminance of 10−4 lux. The detector array design will enable large focal planes, capable of imaging with high sensitivity and high speed, over a wide range of natural illumination conditions from direct sunlight to a cloudy moonless night.

Facing the challenge of biosample imaging by FTIR with a synchrotron radiation source

Fourier-transform infrared (FTIR) synchrotron radiation (SR) microspectroscopy is a powerful molecular probe of biological samples at cellular resolution (<10 microm). As the brilliance of SR is 100-1000 times higher than that of a conventional Globar source, FTIR microscopes are now available in almost all advanced SR facilities around the world. However, in spite of this superior performance, the expected advances in IR SR microscopy have not yet been realised, particularly with regard to bio-analytical studies of single cells and soft tissues. In recent decades solid-state array detectors have revolutionized the fields of molecular spectroscopy and chemical imaging, and now new IR focal plane array detectors implemented at ultra-bright SR facilities will extend the performance and overcome the existing limitations, possibly allowing IR SR instrumentation to achieve the highest sensitivity and resolution of molecular imaging. The impact of IR imaging on large tissue area and the complexity of the analysis are discussed. In view of the high brilliance of SR sources, a comparison of published microscope images is given. Finally, it is briefly outlined how an optimized combination of IR instrumentation and SR optical systems could reach the expected advantages of a SR-based FTIR imaging system.

High-Speed, High Dynamic-Range Optical Sensor Arrays

A monolithic solid-state linear sensor array has been designed and fabricated in a 0.35 mum , 3.3 V, thin-oxide digital CMOS process. The sensor arrays are targetted at such instruments and applications as digital streak cameras, 2-D cameras for proton radiography, and fiber-optic array readout. The prototype consists of a 1-D linear array of 150 integrated photodiodes, followed by fast analog buffers and on-chip, 150-deep analog frame storage. Frame storage consists of 150 analog sample circuits per pixel, with each sample circuit including an n-channel sample switch, a 0.1 pF double-polysilicon sample capacitor, a reset switch to clear the capacitor, and a multiplexed source-follower readout buffer. Sampling speeds of 400 M-frames/s have been achieved using electrical input signals, and 100 MHz with optical input signals, both with a dynamic range of ~ 11.5 bits, rms. Circuit design details are presented, along with the results of electrical measurements and optical experiments with fast pulsed laser light sources at several wavelengths. A set of next-generation concept designs are also presented that aims to include PLL-based clock multiplication for 1 GHz continuous sampling, plus a new real-time trigger circuit technique that examines windowed regions of stored samples to form a sophisticated trigger decision.

Role of Bound Zn(II) in the CadC Cd(II)/Pb(II)/Zn(II)-responsive Repressor

The Staphylococcus aureus plasmid pI258 cadCA operon encodes a P-type ATPase, CadA, that confers resistance to Cd(II)/Pb(II)/Zn(II). Expression is regulated by CadC, a homodimeric repressor that dissociates from the cad operator/promoter upon binding of Cd(II), Pb(II), or Zn(II). CadC is a member of the ArsR/SmtB family of metalloregulatory proteins. The crystal structure of CadC shows two types of metal binding sites, termed Site 1 and Site 2, and the homodimer has two of each. Site 1 is the physiological inducer binding site. The two Site 2 metal binding sites are formed at the dimerization interface. Site 2 is not regulatory in CadC but is regulatory in the homologue SmtB. Here the role of each site was investigated by mutagenesis. Both sites bind either Cd(II) or Zn(II). However, Site 1 has higher affinity for Cd(II) over Zn(II), and Site 2 prefers Zn(II) over Cd(II). Site 2 is not required for either derepression or dimerization. The crystal structure of the wild type with bound Zn(II) and of a mutant lacking Site 2 was compared with the SmtB structure with and without bound Zn(II). We propose that an arginine residue allows for Zn(II) regulation in SmtB and, conversely, a glycine results in a lack of regulation by Zn(II) in CadC. We propose that a glycine residue was ancestral whether the repressor binds Zn(II) at a Site 2 like CadC or has no Site 2 like the paralogous ArsR and implies that acquisition of regulatory ability in SmtB was a more recent evolutionary event.

Novel Electro-Optical Coupling Technique for Magnetic Resonance-Compatible Positron Emission Tomography Detectors

A new magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) detector design is being developed that uses electro-optical coupling to bring the amplitude and arrival time information of high-speed PET detector scintillation pulses out of an MRI system. The electro-optical coupling technology consists of a magnetically insensitive photodetector output signal connected to a nonmagnetic vertical cavity surface emitting laser (VCSEL) diode that is coupled to a multimode optical fiber. This scheme essentially acts as an optical wire with no influence on the MRI system. To test the feasibility of this approach, a lutetium-yttrium oxyorthosilicate crystal coupled to a single pixel of a solid-state photomultiplier array was placed in coincidence with a lutetium oxyorthosilicate crystal coupled to a fast photomultiplier tube with both the new nonmagnetic VCSEL coupling and the standard coaxial cable signal transmission scheme. No significant change was observed in 511 keV photopeak energy resolution and coincidence time resolution. This electro-optical coupling technology enables an MRI-compatible PET block detector to have a reduced electromagnetic footprint compared with the signal transmission schemes deployed in the current MRI/PET designs.

Electrochemical ion transfer across liquid/liquid interfaces confined within solid-state micropore arrays – simulations and experiments

Miniaturised liquid/liquid interfaces provide benefits for bioanalytical detection with electrochemical methods. In this work, microporous silicon membranes which can be used for interface miniaturisation were characterized by simulations and experiments. The microporous membranes possessed hexagonal arrays of pores with radii between 10 and 25 microm, a pore depth of 100 microm and pore centre-to-centre separations between 99 and 986 microm. Cyclic voltammetry was used to monitor ion transfer across arrays of micro-interfaces between two immiscible electrolyte solutions (microITIES) formed at these membranes, with the organic phase present as an organogel. The results were compared to computational simulations taking into account mass transport by diffusion and encompassing diffusion to recessed interfaces and overlapped diffusion zones. The simulation and experimental data were both consistent with the situation where the location of the liquid/liquid (l/l) interface was on the aqueous side of the silicon membrane and the pores were filled with the organic phase. While the current for the forward potential scan (transfer of the ion from the aqueous phase to the organic phase) was strongly dependent on the location of the l/l interface, the current peak during the reverse scan (transfer of the ion from the organic phase to the aqueous phase) was influenced by the ratio of the transferring ion's diffusion coefficients in both phases. The diffusion coefficient of the transferring ion in the gelified organic phase was ca. nine times smaller than in the aqueous phase. Asymmetric cyclic voltammogram shapes were caused by the combined effect of non-symmetrical diffusion (spherical and linear) and by the inequality of the diffusion coefficient in both phases. Overlapping diffusion zones were responsible for the observation of current peaks instead of steady-state currents during the forward scan. The characterisation of the diffusion behaviour is an important requirement for application of these silicon membranes in electroanalytical chemistry.

Surgical Performance with Head-Mounted Displays in Laparoscopic Surgery

The difficulties of laparoscopic surgery include two-dimensional image projection and loss of alignment between the surgeon's hands and visual field. Head-mounted displays (HMDs) allow freedom from gazing at a stationary overhead monitor, thus improving ergonomics. Modern HMDs offer greatly improved image quality and reduced bulk and weight. We compared two types of HMDs with conventional overhead image display. Twelve preclinical medical students (i.e., laparoscopic novices) completed the standardized bead-passing task in a Fundamentals of Laparoscopic Surgery box trainer, using a wall-mounted monitor(WALL), a solid-state high-resolution dual full-visual graphic array (VGA) HMD (HIGH-HMD), or a lightweight commercial 1/4 VGA HMD (LOW-HMD). Participants performed each task by using the three image displays. The order in which they performed each test was randomly assigned to minimize the carryover effect.Students were then asked to grade comfort and image quality on a scale from 1 (worst) to 5 (best). Statistical comparison of the time per bead was performed with the Kruskal-Wallis test, and P < 0.05 was considered significant. Average time per bead (total beads = 12/participant/test) was 14.2 seconds for WALL, 13.2 seconds for LOW-HMD, and 12.5 seconds for HIGH-HMD (P 0.05). The comfort ratings were 3.67 +/- 0.82, 3.50 +/- 1.38,and 3.83 +/- 0.75, respectively, and image quality was rated as 3.00 +/- 0.63, 2.83 +/- 1.47 and 4.67 +/- 0.52, respectively. The high-resolution HMD offered significantly better image quality and allowed faster task performance than a lower resolution model of HMD, and both performed better than the overhead display. The high-resolution HMD was not significantly more comfortable than the low-resolution model, given its added weight. HMDs alone may only be of incremental benefit in improving performance in laparoscopic surgery.However, their greatest promise is in their combination with other advances in imaging and image manipulation technology, as they open the door to individualized image display.

Solid-state supramolecular array through cooperative π–π interactions of 1-(2-methoxyphenyl)- o-carborane

Dicarba- closo-dodecaborane (carborane) has received much attention as a building block for supramolecular assemblies and bioactive compounds. Among the carborane isomers, 1,2-dicarba- closo-dodecaborane ( o-carborane) has unique chemical properties, including the ability of the o-carborane C–H hydrogens to form H-bonds. We have designed and synthesized 1-(2-methoxyphenyl)- o-carborane 1a to study its ability to form an intramolecular H-bond between the o-carborane C–H hydrogen and various H-bond acceptors both in solution and in the solid state. Intramolecular H-bonding ability in solution was evaluated by means of 1H NMR spectroscopic measurements of the C–H hydrogen signal. The signal of the C–H hydrogen of 1a showed a remarkable downfield shift in CDCl 3 and various other solvents, i.e., the shift was almost solvent-independent. We suggest that 1a forms an intramolecular H-bond in these solvents. Crystal structure analysis of 1a showed a C–H⋯O distance of 2.05 Å and a nearly planar torsion angle C(2)–C(1)–C(7)–C(8) of 6.5°, indicating intramolecular C–H⋯O H-bond formation in the solid state. The crystal packing of 1a indicates that a supramolecular array is stabilized by cooperative π–π stacking interactions among the methoxyphenyl groups and by hydrophobic interactions of the o-carborane cages. DFT calculations indicate that the strength of the intramolecular H-bond of 1a is about 3.53 kcal/mol. These observations indicate the potential value of o-carborane in supramolecular chemistry and materials chemistry; it should be possible to design novel materials by utilizing both the H-bonding ability of the o-carborane C–H hydrogen and the high hydrophobicity of the o-carborane cage.

Development of a solid-state multi-sensor array camera for real time imaging of magnetic fields

The development of a real-time magnetic field imaging camera based on solid-state sensors is described. The final laboratory comprises a 2D array of 33 x 33 solid state, tri-axial magneto-inductive sensors, and is located within a large current-carrying coil. This may be excited to produce either a steady or time-varying magnetic field. Outputs from several rows of sensors are routed to a sub-master controller and all sub-masters route to a master-controller responsible for data coordination and signal pre-processing. The data are finally streamed to a host computer via a USB interface and the image generated and displayed at a rate of several frames per second. Accurate image generation is predicated on a knowledge of the sensor response, magnetic field perturbations and the nature of the target respecting permeability and conductivity. To this end, the development of the instrumentation has been complemented by extensive numerical modelling of field distribution patterns using boundary element methods. Although it was originally intended for deployment in the nondestructive evaluation (NDE) of reinforced concrete, it was soon realised during the course of the work that the magnetic field imaging system had many potential applications, for example, in medicine, security screening, quality assurance (such as the food industry), other areas of nondestructive evaluation (NDE), designs associated with magnetic fields, teaching and research.

Molecular and Electronic Structures of the Long-Bonded π-Dimers of Tetrathiafulvalene Cation-Radical in Intermolecular Electron Transfer and in (Solid-State) Conductivity

Tetrathiafulvalene (TTF) as the prototypical electron donor for solid-state (electronics) applications is converted to the unusual cation-radical salt, TTF+* CB- (where CB- is the non-coordinating closo-dodecamethylcarboranate), for crystallographic and spectral analyses. Near-IR studies establish the spontaneous self-association of TTF+* to form the diamagnetic [TTF+,TTF+] dication and to also undergo the equally rapid cross-association with its parent donor to form the mixed-valence [TTF+*,TTF] cation-radical. The latter, most importantly, represents the first (dyad) member of a series of p-doped tetrathiafulvalene (stacked) arrays, and the thorough scrutiny of its electronic structure with the aid of Mulliken-Hush (two-state) analysis of the diagnostic (intervalence) NIR band reveals Robin-Day Class II behavior. The theoretical consequences of the unique structure of the mixed-valence [TTF+*,TTF] dyad on (a) the electron-transfer mechanism for self-exchange, (b) the molecular-orbital analysis of the Marcus reorganization energy, and (c) the ab initio computation of the coupling element or transfer integral in p-doped (solid-state) arrays are discussed.

Proteomics in human cancer research

Proteomics is now widely employed in the study of cancer. Many laboratories are applying the rapidly emerging technologies to elucidate the underlying mechanisms associated with cancer development, progression, and severity in addition to developing drugs and identifying patients who will benefit most from molecular targeted compounds. Various proteomic approaches are now available for protein separation and identification, and for characterization of the function and structure of candidate proteins. In spite of significant challenges that still exist, proteomics has rapidly expanded to include the discovery of novel biomarkers for early detection, diagnosis and prognostication (clinical application), and for the identification of novel drug targets (pharmaceutical application). To achieve these goals, several innovative technologies including 2-D-difference gel electrophoresis, SELDI, multidimensional protein identification technology, isotope-coded affinity tag, solid-state and suspension protein array technologies, X-ray crystallography, NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulation have evolved, and are being used in different combinations. This review provides an overview of the field of proteomics and discusses the key proteomic technologies available to researchers. It also describes some of the important challenges and highlights the current pharmaceutical and clinical applications of proteomics in human cancer research.

Single-photon imaging at 20,000 frames∕s

A complete two-dimensional imaging system based on a silicon monolithic array of 60 single-photon counters is presented. The fabricated solid-state array is rugged and operates at low voltages. Detection efficiency is higher than 40% in the visible range, and cross talk among 50 microm pixels is lower than 10(-4). The complete system provides a maximum throughput of 20 kframes/s with truly parallel readout and nanosecond gating, thanks to the use of an integrated active quenching circuit for each pixel of the array. We report optical and electrical characterizations of the whole imaging system.