Microelectronic Chips Research Articles

Rapid parallel mutation scanning of gene fragments using a microelectronic protein-DNA chip format.

We have developed a method for the de novo discovery of genetic variations, including single nucleotide polymorphisms and mutations, on microelectronic chip devices. The method combines the features of electronically controlled DNA hybridisation on open-format microarrays, with mutation detection by a fluorescence-labelled mismatch- binding protein. Electronic addressing of DNA strands to distinct test sites of the chip allows parallel analysis of several individuals, as demonstrated for mutations in different exons of the p53 gene. This microelectronic chip-based mutation discovery assay may substitute for time-consuming sequencing studies and will complement existing technologies in genomic research.

Dielectrophoretic cell separation and gene expression profiling on microelectronic chip arrays.

Cell membrane dielectric properties of five different cultivated cell lines and human peripheral blood mononuclear cells (PBMC) were determined from dielectrophoretic crossover frequency measurements on a 5 x 5 microelectronic chip array. Based on distinct dielectric property differences between individual cell types, efficient cell separations were achieved by dielectrophoresis on this 5 x 5 array, which included separation of monocytic cells (U937) or human T cell leukemia virus type 1 (HTLV-1) tax-transformed cells (Ind-2) from PBMC, as well as separation of neuroblastoma cells (SH-SY5Y) from glioma cells (HTB). The purity of dielectrophoretically separated cells can be greater than 95%. Expression profiles of IL-1, TNF-alpha, and TGF-beta genes for U937 cells mixed with PBMC before and after the separation were determined by a means of electric field-facilitated hybridization on a 10 x 10 microelectronic chip array. By using the expression levels of pure U937 cells as a control, it was shown that the gene expression profiles of the postseparation cells were significantly different from those of the preseparation cell mixtures. The increase in gene expression levels for U937 cells upon lipopolysaccharide induction could be accurately determined only in the postseparation cells, while the preseparation samples masked these changes. Furthermore, by cultivating the separated HTB and SH-SY5Y cells and measuring expression of the stress-related gene c-fos, dielectrophoretic forces were shown to have little effect on cell survival and stress. The presented approach of using microelectronic chip arrays for both cell separation and gene expression profiling provides a great potential for accurate genetic analysis of specific cell subpopulations in heterogeneous samples.

Trends in DNA forensic analysis.

The paper gives a historical perspective of forensic DNA analysis and overviews existing technologies implemented in forensic laboratories for DNA profiling. Short tandem repeat analysis, mitochondrial DNA and Y-chromosome analysis are described. The review also focuses on emerging new technologies, which represent an interest for the DNA forensic community. Short tandem repeat analysis, by microelectronic chip device, electrophoretic microdevice and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry are reviewed in this context.

Sheet conductor model of brain slices for stimulation and recording with planar electronic contacts.

Current and voltage in a brain slice are considered, taking into account the boundary conditions at the surface to an electrolyte bath and at the substrate of an electron conductor. A sheet conductor model is introduced with ohmic leak conductance to the bath and capacitive coupling to the substrate. It assigns a current-source density of neuronal activity to extracellular field potentials recorded by planar contacts, and it relates the current of planar capacitive contacts to the field potential that elicits neuronal activity. Two examples are analytically solved: the recording across a layered brain slice and the stimulation by a circular electrode. The study forms the basis for neurophysical experiments with brain slices or retinae on microelectronic chips.

Relationship of CF2 concentration to deposition rates in the pyrolytic chemical vapor deposition process

Polytetrafluoroethylene films have been deposited for use as low dielectric constant materials in microelectronic chips. Deposition is performed through pyrolysis of hexafluoropropylene oxide on a heated filament array to produce CF2, which can then polymerize and deposit as a thin film. The variation of CF2 concentration as a function of the pressure and filament temperature has been characterized by ultraviolet absorption spectroscopy. The CF2 concentration is seen to approach a constant as filament temperature approaches 400 °C, and an activation energy of 11.9 kcal/mol is measured at lower temperatures. Attempting to develop a specific relationship between the CF2 concentration and deposition rate yields a sticking coefficient of ∼4×10−5, which is consistent with what has been measured in a CF2 beam experiment. However, this result is not sufficient to explain deposition properties observed in other related work. This implies that it is possible for other properties of the deposition process to affect the sticking coefficient. A consistent alternative picture is also developed in which gas phase polymerization can produce (CF2)n species that are responsible for deposition.

Bose-Einstein condensation on a microelectronic chip.

Although Bose-Einstein condensates of ultracold atoms have been experimentally realizable for several years, their formation and manipulation still impose considerable technical challenges. An all-optical technique that enables faster production of Bose-Einstein condensates was recently reported. Here we demonstrate that the formation of a condensate can be greatly simplified using a microscopic magnetic trap on a chip. We achieve Bose-Einstein condensation inside the single vapour cell of a magneto-optical trap in as little as 700 ms-more than a factor of ten faster than typical experiments, and a factor of three faster than the all-optical technique. A coherent matter wave is emitted normal to the chip surface when the trapped atoms are released into free fall; alternatively, we couple the condensate into an 'atomic conveyor belt', which is used to transport the condensed cloud non-destructively over a macroscopic distance parallel to the chip surface. The possibility of manipulating laser-like coherent matter waves with such an integrated atom-optical system holds promise for applications in interferometry, holography, microscopy, atom lithography and quantum information processing.

Antimicrobial resistance and bacterial identification utilizing a microelectronic chip array.

Species-specific bacterial identification of clinical specimens is often limited to a few species due to the difficulty of performing multiplex reactions. In addition, discrimination of amplicons is time-consuming and laborious, consisting of gel electrophoresis, probe hybridization, or sequencing technology. In order to simplify the process of bacterial identification, we combined anchored in situ amplification on a microelectronic chip array with discrimination and detection on the same platform. Here, we describe the simultaneous amplification and discrimination of six gene sequences which are representative of different bacterial identification assays: Escherichia coli gyrA, Salmonella gyrA, Campylobacter gyrA, E. coli parC, Staphylococcus mecA, and Chlamydia cryptic plasmid. The assay can detect both plasmid and transposon genes and can also discriminate strains carrying antibiotic resistance single-nucleotide polymorphism mutations. Finally, the assay is similarly capable of discriminating between bacterial species through reporter-specific discrimination and allele-specific amplification. Anchored strand displacement amplification allows multiplex amplification and complex genotype discrimination on the same platform. This assay simplifies the bacterial identification process greatly, allowing molecular biology techniques to be performed with minimal processing of samples and practical experience.

Optical gain in silicon nanocrystals.

Adding optical functionality to a silicon microelectronic chip is one of the most challenging problems of materials research. Silicon is an indirect-bandgap semiconductor and so is an inefficient emitter of light. For this reason, integration of optically functional elements with silicon microelectronic circuitry has largely been achieved through the use of direct-bandgap compound semiconductors. For optoelectronic applications, the key device is the light source--a laser. Compound semiconductor lasers exploit low-dimensional electronic systems, such as quantum wells and quantum dots, as the active optical amplifying medium. Here we demonstrate that light amplification is possible using silicon itself, in the form of quantum dots dispersed in a silicon dioxide matrix. Net optical gain is seen in both waveguide and transmission configurations, with the material gain being of the same order as that of direct-bandgap quantum dots. We explain the observations using a model based on population inversion of radiative states associated with the Si/SiO2 interface. These findings open a route to the fabrication of a silicon laser.

Anchored multiplex amplification on a microelectronic chip array.

We have developed a method for anchored amplification on a microchip array that allows amplification and detection of multiple targets in an open format. Electronic anchoring of sets of amplification primers in distinct areas on the microchip permitted primer-primer interactions to be reduced and distinct zones of amplification created, thereby increasing the efficiency of the multiplex amplification reactions. We found strand displacement amplification (SDA) to be ideal for use in our microelectronic chip system because of the isothermal nature of the assay, which provides a rapid amplification system readily compatible with simple instrumentation. Anchored SDA supported multiplex DNA or RNA amplification without decreases in amplification efficiency. This microelectronic chip-based amplification system allows multiplexed amplification and detection to be performed on the same platform, streamlining development of any nucleic acid-based assay.

Microfabricated elastomeric stencils for micropatterning cell cultures.

Here we present an inexpensive method to fabricate microscopic cellular cultures, which does not require any surface modification of the substrate prior to cell seeding. The method utilizes a reusable elastomeric stencil (i.e., a membrane containing thru holes) which seals spontaneously against the surface. The stencil is applied to the cell-culture substrate before seeding. During seeding, the stencil prevents the substrate from being exposed to the cell suspension except on the hole areas. After cells are allowed to attach and the stencil is peeled off, cellular islands with a shape similar to the holes remain on the cell-culture substrate. This solvent-free method can be combined with a wide range of substrates (including biocompatible polymers, homogeneous or nonplanar surfaces, microelectronic chips, and gels), biomolecules, and virtually any adherent cell type.

Active microelectronic chip devices which utilize controlled electrophoretic fields for multiplex DNA hybridization and other genomic applications

Active microelectronic chip devices which utilize controlled electrophoretic fields for multiplex DNA hybridization and other genomic applications

Active microelectronic chip devices which utilize controlled electrophoretic fields for multiplex DNA hybridization and other genomic applications

Microelectronic DNA chip devices that contain planar arrays of microelectrodes have been developed for multiplex DNA hybridization and a variety of genomic research and DNA diagnostic applications. These devices are able to produce almost any desired electric field configuration on their surface. This ability to produce well-defined electric fields allows charged molecules (DNA, RNA, proteins, enzymes, antibodies, nanobeads, and even micron scale semiconductor devices) to be electrophoretically transported to or from any microlocation on the planar surface of the device. Of key importance to the device function is the permeation layer which overcoats the microelectrodes. The permeation layer is generally a porous hydrogel material that allows water molecules and small ions (Na+, CI-, etc.) to freely contact the microelectrode surface, but impedes the transport of the larger analytes (oligonucleotides, DNA, RNA, proteins, etc.). The permeation layer prevents the destruction of DNA at the active microelectrode surface, ameliorates the adverse effects of electrolysis products on the sensitive hybridization reactions, and serves as a porous support structure for attaching DNA probes and other molecules to the array. In order to maintain rapid transport of DNA molecules, facilitate hybridization, and work within constrained current and voltage ranges, low conductance buffers and various electronic pulsing scenarios have also been developed. These active microelectronic array devices allow electrophoretic fields to be used to carry out accelerated DNA hybridization reactions and to improve selectivity for single nucleotide polymorphism (SNP), short tandem repeat (STR), and point mutation analysis.

Directed self-assembly of amphiphilic regioregular polythiophenes on the nanometer scale

Regioregular polythiophenes possessing alternating hydrophobic and hydrophilic substituents have been synthesized and fully characterized. The amphiphilic nature of the polymer allows it to assemble at the air-water interface forming highly ordered domains. Directed self-assembly of the resulting conducting monolayer into a microelectronic chip structure is described.

To bead or not to bead? That is the question when researchers make ultrathin coatings

If an optical coating on a lens beads up or becomes filled with holes like a slice of Swiss cheese, the lens may become foggy or distort light. Similarly, an insulating glaze in a microelectronic chip may allow short circuits if the film breaks as it is deposited. In the eye, the fine coating of lubricating tears disintegrates too easily in some people, causing an uncomfortable dryness. The tendency of thin films of liquids to retract, or dewet, from surfaces challenges the ingenuity of engineers and designers of a wide range of technologies and products-from optics and microelectronics to eye drops, paints, and multilayer polymer packages for food. Thin films often are finicky little beasts, says Pierre Wiltzius of Lucent Technologies' Bell Labs in Murray Hill, N.J. Researchers have devised treatments for surfaces and coatings that promote the spread of uniform films even when the surface or the overlying film naturally resists such wetting, as they commonly do. To eliminate long-recognized seeds of dewetting such as dust and rough spots on surfaces, thin-film makers use clean-rooms and meticulously polish or chemically treat substrates on which the films will lie. Dutch chemist Anton Vrii hvDothesized more than 30 years ago that even in the absence of defects, extremely thin films of liquid spontaneously self-destruct under certain conditions. For soap films in air, he predicted that waves would arise unbidden from the thermal jiggling of molecules or atoms in the film and then amplify at a favored frequency until the waves broke through the surfaces. Other researchers later extended his theory to liquid films on solid surfaces, where the surface waves would shatter the film into droplets or riddle it with holes. Only in the past few years have experimenters found persuasive evidence that this phenomenon actually exists, and opinion remains divided on whether it has practical consequences. The extension of Vrij's theory dictates that a distinctive pattern of undulations on a film's surface would arise before the film disintegrated. The process is called spinodal dewetting because scientists noted sharp peaks, or spines, when they graphed properties of materials separating in a similar process. The predicted patterns of surface undulations were not seen with certainty, however, until Jorg Bischof and his colleagues at the University of Konstanz in Germany finally made a laser snapshot of them in melted metal foils. The German team reported its findings in the Aug. 19, 1996 PHYSIcAL REVIEW LETrERs. Since that discovery, researchers from

Film Boiling Incipience at the Departure From Natural Convection on Flat, Smooth Surfaces

The present research is an experimental study of pool boiling nucleation behavior using flat, smooth surfaces immersed in saturated highly wetting liquids, FC-72 and FC-87. A flush-mounted, copper surface of 10 mm × 10 mm is used as a heat transfer surface, simulating a microelectronic chip surface. At the nucleation incipient points of higher wall superheats with steady increase of heat flux, vapor film blankets the smooth surface and remains on the surface. To predict this film boiling incipience phenomenon from the smooth surface, an incipience map is developed over the boiling curve. When the incipient heat flux is higher than the minimum heat flux (MHF) and the incipient wall superheat value is higher than the transition boiling curve value at the incipient heat flux, the transition from single-phase natural convection to film boiling is observed at the incipient point. To prevent film boiling incipience, a microporous coating is applied over the smooth surface, which decreases incipient wall superheat and increases minimum heat flux. The film boiling incipience should be avoided to take advantage of highly efficient nucleate boiling heat transfer for the cooling of high-heat-flux applications.

The Effects of Interfaces on C-4 Solder Bump Reliability

ABSTRACTC-4 solder bump technology is used as an interconnect method between microelectronic chips and substrates because of four unique features; excellent electrical performance, large number of connections in area arrays, small size and superb reliability in properly fabricated terminals. C-4 terminals consist of chip metallization (BLM or UBM), solder, substrate metallization and underfill, if needed. The reliability of C-4 interconnections will be described in terms of the physical interfaces in the terminal which include insulator-metal, metal-intermetallic, grain boundary and, if needed, underfill-chip/substrate/solder interfaces. Some of these interfaces are present in the as-deposited materials while others form during the solder reflow operation. Reactive UBM's such as Ti/Cu/Au form layers of intermetallic compounds such as TiCu, TiCu2 and TiCu3 and react with hydrogen ambients to form TiH2. The solder reacts with the UBM copper to form Cu3Sn and Cu6Sn5. The solder also reacts with the substrate metallization (electroless Ni-Au as an example) to form Ni3Sn2 and Ni3Sn4. Reactions with Au also occur with the formation of TiAu4 and AuSn. These reactions can cause problems not because the intermetallics are brittle (intermetallics are relatively brittle compared to the solder but they are also very strong as compared to the solder), but because of the consequences of the reactions such as, stress increase, impurity snowplow, Kirkendall voids and intermetallic spalling. Non-reactive UBM's like Cr/Cu/Au require a “phased” region between the Cr and Cu to achieve mechanical adhesion because of the absence of reaction. Proper control of these reactions will eliminate early fails that are usually planar and occur at reaction interfaces. Long term wear-out will occur during power on-off cycling when creep/fatigue cracks nucleate and grow at the grain boundaries in the solder. If underfill is used, impurity assisted crack growth at underfill to chip/substrate/solder interfaces results in increased strain on the solder and failure. Reliability models for these various failure mechanisms will be discussed as well as methods of eliminating early interfacial failures.

Immersion Cooling of a Simulated Microelectronic Chip with Artificial Re-entrant Cavities.

Pool boiling heat transfer results for a 10 mm×10 mm rectangular chip immersed in subcooled FC-72 were reported. Three kinds of surfaces were tested : an untreated silicon wafer surface, an etched surface of a thin SiO2 film that was sputtered on a silicon wafer, and the same kind of SiO2 surface with artificial cavities. The cavities were a re-entrant type with mouth diameters ranging from 0.7 to 1.4μm. These artificial cavities were effective in reducing the boiling incipience superheat. For degassed FC-72, the boiling incipience temperature agreed fairly well with the theoretical prediction of the heterogeneous nucleation theory. When the dissolved air content of the test liquid was sufficiently high, the chip temperatures at boiling incipience and at fully developed nucleate boiling were significantly decreased.

Oscillatory enhancement of the squeezing flow of yield stress fluids: a novel experimental result

The extrusion of a yield stress fluid from the space between two parallel plates is investigated experimentally. Oscillating the magnitude of the squeezing force about a mean value (F=f[1+αcos(ωt)]) was observed to significantly enhance the flow rate of yield stress fluids, while having no effect on the flow rate of Newtonian fluids. This is a novel result. The enhancement depends on the magnitude of the force, the oscillatory frequency and amplitude, the fluid being squeezed, and the thickness of the fluid layer. Non-dimensional results for the various flow quantities have been presented by using the flow predicted for the constant-force squeezing of a Herschel–Bulkley yield stress fluid as the reference. In the limit of constant-force squeezing, the present experimental results compare very well with those of our earlier theoretical model for this situation (Zwick, Ayyaswamy & Cohen 1996). The results presented in this paper have significance, among many applications, for injection moulding, in the adhesive bonding of microelectronic chips, and in surgical procedures employed in health care.

Printing and Publishing in Greece: ‘flexibility’ and the process of innovation, 1979-1991

Since the mid-1960s a large number of innovations has affected printing and publishing throughout the world. At the heart of what is now widely acknowledged as a technological revolution was the switch to photo-composition and offset lithography from ‘hot-metal’ techniques. Two principal developments may be identified — the shift from molten metal to photography pioneered in the USA, and the introduction of electronic—based processes of production and transmission (Moran, 1974: 147-261, 309-19; Clair, 1976; Marshall, 1983; Guy and Haywood, 1985). The early photo-setters were costly and were restricted to a relatively small number of sizes and typefaces. Origination remained fragmented and still had to be divided-up into a series of distinct tasks notably keyboarding, photo-typesetting, page paste-up, photographic work and final plate-making. Because of this constraint the take-up of electronic typesetting, particularly in small and medium-size printing firms, was slow. However, the arrival of micro-electronic chips paved the way for cheaper and more dependable photo-typesetting systems. Digitalisation of information enables a unification of the origination process and allows an author to prepare high quality graphics and sophisticated art work.

Jet-Flow Scavenging of a Curing Oven—Part I: Flow Visualization

A curing oven that is commonly used in microelectronic manufacturing has been analyzed to determine the causes of contamination of parts passing through the oven, and to eliminate this contamination. During the curing of microelectronic chip packages, a volatile component contained in the bonding epoxy is released as a vapor. This vapor is usually removed (scavenged) by blowing a process gas through jets. However, some condensation of this vapor may (and often does) occur on the chips, contaminating them and rendering them functionally useless. It is desirable to completely eliminate this condensation. This paper presents a flow visualization study of the complicated flow patterns within the oven created by the jet-flows. Vortices are produced due to jet interactions. These vortices inhibit scavenging (entrainment and removal) of the contaminant vapor and are undesirable. A new design that eliminates the vortices and enhances the scavenging is described. In Part II of this study, a numerical simulation of the process is described.