Laser-assisted bumping for flip chip assembly

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Correlation between pattern density and linewidth variation in silicon photonics waveguides

We describe the correlation between the measured width of silicon waveguides fabricated with 193 nm lithography and the local pattern density of the mask layout. In the fabrication process, pattern density can affect the composition of the plasma in a dry etching process or the abrasion rate in a planarization step. Using an optical test circuit to extract waveguide width and thickness, we sampled 5841 sites over a fabricated wafer. Using this detailed sampling, we could establish the correlation between the linewidth and average pattern density around the test circuit, as a function of the radius of influence. We find that the intra-die systematic width variation correlates most with the pattern density within a radius of 200 gm, with a correlation coefficient of 0.57. No correlation between pattern density and the intra-die systematic thickness variation is observed. These findings can be used to predict photonic circuit yield or to optimize the circuit layout to minimize the effect of local pattern density. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

In situ mixing of organic matter decreases hydraulic conductivity of denitrification walls in sand aquifers

In a previous study, a denitrification wall was constructed in a sand aquifer using sawdust as the carbon substrate. Ground water bypassed around this sawdust wall due to reduced hydraulic conductivity. We investigated potential reasons for this by testing two new walls and conducting laboratory studies. The first wall was constructed by mixing aquifer material in situ without substrate addition to investigate the effects of the construction technique (mixed wall). A second, biochip wall, was constructed using coarse wood chips to determine the effect of size of the particles in the amendment on hydraulic conductivity. The aquifer hydraulic conductivity was 35.4 m/d, while in the mixed wall it was 2.8 m/d and in the biochip wall 3.4 m/d. This indicated that the mixing of the aquifer sands below the water table allowed the particles to re-sort themselves into a matrix with a significantly lower hydraulic conductivity than the process that originally formed the aquifer. The addition of a coarser substrate in the biochip wall significantly increased total porosity and decreased bulk density, but hydraulic conductivity remained low compared to the aquifer. Laboratory cores of aquifer sand mixed under dry and wet conditions mimicked the reduction in hydraulic conductivity observed in the field within the mixed wall. The addition of sawdust to the laboratory cores resulted in a significantly higher hydraulic conductivity when mixed dry compared to cores mixed wet. This reduction in the hydraulic conductivity of the sand/sawdust cores mixed under saturated conditions repeated what occurred in the field in the original sawdust wall. This indicated that laboratory investigations can be a useful tool to highlight potential reductions in field hydraulic conductivities that may occur when differing materials are mixed under field conditions

Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of organ-on-a-chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in OOC systems increases their biological complexity and therefore makes the analysis and monitoring of analytical parameters inside the device more difficult. In this work, we present an approach to integrate multiple sensors in an extremely thin, porous and delicate membrane inside a liver-on-a-chip device. Specifically, three electrochemical dissolved oxygen (DO) sensors were inkjet-printed along the microfluidic channel allowing local online monitoring of oxygen concentrations. This approach demonstrates the existence of an oxygen gradient up to 17.5% for rat hepatocytes and 32.5% for human hepatocytes along the bottom channel. Such gradients are considered crucial for the appearance of zonation of the liver. Inkjet printing (IJP) was the selected technology as it allows drop on demand material deposition compatible with delicate substrates, as used in this study, which cannot withstand temperatures higher than 130 °C. For the deposition of uniform gold and silver conductive inks on the porous membrane, a primer layer using SU-8 dielectric material was used to seal the porosity of the membrane at defined areas, with the aim of building a uniform sensor device. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes were performed, and oxygen consumption rate was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), accelerating the basal respiration of 0.23 ± 0.07 nmol s-1/106 cells up to 5.95 ± 0.67 nmol s-1/106 cells s for rat cells and the basal respiration of 0.17 ± 0.10 nmol s-1/106 cells by up to 10.62 ± 1.15 nmol s-1/106 cells for human cells, with higher oxygen consumption of the cells seeded at the outflow zone. These results demonstrate that the approach of printing sensors inside an OOC has tremendous potential because IJP is a feasible technique for the integration of different sensors for evaluating metabolic activity of cells, and overcomes one of the major challenges still remaining on how to tap the full potential of OOC systems.Peer ReviewedPostprint (author's final draft

Differential temperature sensors: Review of applications in the test and characterization of circuits, usage and design methodology

Differential temperature sensors can be placed in integrated circuits to extract a signature ofthe power dissipated by the adjacent circuit blocks built in the same silicon die. This review paper firstdiscusses the singularity that differential temperature sensors provide with respect to other sensortopologies, with circuit monitoring being their main application. The paper focuses on the monitoringof radio-frequency analog circuits. The strategies to extract the power signature of the monitoredcircuit are reviewed, and a list of application examples in the domain of test and characterizationis provided. As a practical example, we elaborate the design methodology to conceive, step bystep, a differential temperature sensor to monitor the aging degradation in a class-A linear poweramplifier working in the 2.4 GHz Industrial Scientific Medical—ISM—band. It is discussed how,for this particular application, a sensor with a temperature resolution of 0.02 K and a high dynamicrange is required. A circuit solution for this objective is proposed, as well as recommendations for thedimensions and location of the devices that form the temperature sensor. The paper concludes with adescription of a simple procedure to monitor time variability.Postprint (published version

Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology.

Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells

Heterogeneity in pure microbial systems: experimental measurements and modeling

Cellular heterogeneity influences bioprocess performance in ways that until date are not completely elucidated. In order to account for this phenomenon in the design and operation of bioprocesses, reliable analytical and mathematical descriptions are required. We present an overview of the single cell analysis, and the mathematical modeling frameworks that have potential to be used in bioprocess control and optimization, in particular for microbial processes. In order to be suitable for bioprocess monitoring, experimental methods need to be high throughput and to require relatively short processing time. One such method used successfully under dynamic conditions is flow cytometry. Population balance and individual based models are suitable modeling options, the latter one having in particular a good potential to integrate the various data collected through experimentation. This will be highly beneficial for appropriate process design and scale up as a more rigorous approach may prevent a priori unwanted performance losses. It will also help progressing synthetic biology applications to industrial scale

Optical Polarization and Spectral Variability in the M87 Jet

During the last decade, M87's jet has been the site of an extraordinary variability event, with one knot (HST-1) increasing by over a factor 100 in brightness. Variability was also seen on timescales of months in the nuclear flux. Here we discuss the optical-UV polarization and spectral variability of these components, which show vastly different behavior. HST-1 shows a highly significant correlation between flux and polarization, with P increasing from $\sim 20$ at minimum to >40% at maximum, while the orientation of its electric vector stayed constant. HST-1's optical-UV spectrum is very hard ($\alpha_{UV-O}\sim0.5$, $F_\nu\propto\nu^{-\alpha}$), and displays "hard lags" during epochs 2004.9-2005.5, including the peak of the flare, with soft lags at later epochs. We interpret the behavior of HST-1 as enhanced particle acceleration in a shock, with cooling from both particle aging and the relaxation of the compression. We set 2$\sigma$ upper limits of $0.5 \delta$ parsecs and 1.02$c$ on the size and advance speed of the flaring region. The slight deviation of the electric vector orientation from the jet PA, makes it likely that on smaller scales the flaring region has either a double or twisted structure. By contrast, the nucleus displays much more rapid variability, with a highly variable electric vector orientation and 'looping' in the $(I,P)$ plane. The nucleus has a much steeper spectrum ($\alpha_{UV-O} \sim 1.5$) but does not show UV-optical spectral variability. Its behavior can be interpreted as either a helical distortion to a steady jet or a shock propagating through a helical jet.Comment: 14 pages, 7 figures, ApJ, in pres