P. De Moor

Study of steroid-protein binding by means of competitive adsorption: Application to cortisol binding in plasma

The distribution of a steroid between a solution of steroid-binding proteins and a steroid-adsorbing solid added to this solution, depends not only on the properties of the adsorbent but also on the properties of the binding proteins and thus may be used for the study of steroid-protein interactions. Different types of distribution can be distinguished and were applied to the study of cortisol binding in plasma. 1. (1) Endogenous steroids were removed from plasma by incubation with a rather large amount of adsorbent. 2. (2) The cortisol-binding capacity of plasma transcortin was measured after incubation with a balanced amount of adsorbent and cortisol. 3. (3) A relative index of cortisol-protein binding proportional to the ratio of bound to unbound cortisol, was determined by incubation of charcoal-treated plasma with a trace of [1,2-3H]cortisol and appropriate amounts of adsorbent. 4. (4) From this relative index of cortisol—protein binding in plasma an estimate of the cortisol-binding affinity of plasma transcortin was derived.

3D integration by Cu-Cu thermo-compression bonding of extremely thinned bulk-Si die containing 10 μm pitch through-Si vias

Using standard single damascene type techniques on bulk-Si, combined on one hand with extreme wafer thinning and on the other with Cu-Cu thermo-compression bonding technology, the paper demonstrate yielding 10k through-wafer 3D-via chains with a via pitch of 10μm for a via diameter of 5μm. The bonded contacts exhibit shear strengths exceeding 40MPa. Measurements indicate there is no significant contact resistance at the Cu-Cu bonded interface: within measurement accuracy, the 4-point via chain resistance is consistent with bulk Cu resistivity

Thyroid function in patients with hyperemesis gravidarum

An increased free thyroxine (T4) index was observed in 73% of 33 consecutive pregnancies complicated by severe hyperemesis gravidarum. The free triiodothyronine (T3) index was increased in only four of 11 hyperthyroxinemic patients. In five hyperthyroxinemic patients tested, no increase in serum thyrotropin was observed after the injection of thyrotropin-releasing hormone (THR). Goiter, exophthalmos, or previous history of hyperthyroidism was absent in all patients. The thyroxinemia returned to normal in one to several weeks, whether or not it was treated with antithyroid drugs. The thyroid function during the period of hyperemesis had no influence on the subsequent rate of abortion or duration of pregnancy. A lower birth weight, however, was observed in children born to hyperthyroxinemic mothers. Hyperemesis gravidarum should be included in the differential diagnosis of elevations in free T4 index during pregnancy and included in the differential diagnosis of hyperthyroidism.

Investigation of the hermeticity of BCB-sealed cavities for housing (RF-)MEMS devices

This paper reports on the hermeticity testing of MEMS cavities using BCB as the sealing and bonding material. Hermeticity has been tested according to the MIL-STD-883D. Gross leak testing based on liquid fluorocarbons revealed that BCB sealed cavities are leak tight, which means that the MEMS devices are well protected during handling and back-end processing (e.g., wafer dicing). Further, it is shown that the He fine leak testing of the MIL-STD is not fully applicable to small volumes (<1000 nl), typically encountered for MEMS. The problem is that the undefined regime normally existing in the MIL-STD is largely extended for small cavity volumes. Microbolometers have been used as test vehicles to confirm this. Large (>10,000 nl) cavities are needed to cover the entire leakage spectrum.

DIAGNOSIS OF THE LUTEINIZED UNRUPTURED FOLLICLE SYNDROME BY STEROID HORMONE ASSAYS ON PERITONEAL FLUID

The luteinized unruptured follicle syndrome is a frequent phenomenon, occurring in half of our women with regular cycles and infertility. Progesterone concentrations and 17p‐oestradiol concentrations were assayed in peritoneal fluid of women during the luteal phase. Up to day 20 of the cycle, the concentrations were significantly higher in women with an ovulation stigma than in women without an ovulation stigma on their corpus luteum. The range of concentrations was sufficiently different in the early luteal phase to be used diagnostically, the only limitation being the presence of a cystic corpus luteum. We suggest that the assay of progesterone and 17β‐oestradiol in peritoneal fluid should be done in all women with infertility and biphasic basal body temperature charts in order to diagnose the luteinized unruptured follicle syndrome.

Through-silicon via and die stacking technologies for microsystems-integration

The highest integration density of microsystems can be obtained using a 3D-stacking approach, where each layer of the stack is realized using a different technology, which may include sensors, imagers, rf and MEMS technologies. A key challenge is however to perform such stacking in a cost-effective manner. In this paper, a novel 3D TSV and 3D stacking technologies will be presented. Application examples are MEMS packaging and heterogeneous integration of imaging devices.

A 3(17)β-hydroxysteroid dehydrogenase in raterythrocytes: Conversion of 5α-dihydrotestosterone into 5α-androstane-3β,17β-diol and purification of the enzyme by affinity chromatography

Abstract Rat erythrocytes contain a 3β-hydroxysteroid dehydrogenase, which converts 5α-dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) reversibly into 5α-androstane-3β,17β-diol. This enzyme has a molecular weight of approx. 70 000, as estimated by Sephadex G-100 chromatography and is precipitated by (NH4)2SO4 (25–33 g/100 ml). It is unstable under slightly alkaline conditions but stabilized by the addition of coenzyme. The K m value for 5α-dihydrotestosterone was approx. 0.14 mM, for NADP+ 9 μM and for NADPH 1.8 μM. Very similar properties were found for the 17β-hydroxysteroid dehydrogenase of rat erythrocytes. By application of affinity chromatography on Cibacron Blue F3G-A coupled to Sepharose and other techniques a 7200-fold purification of the enzyme, with respect to crude hemolysate was obtained. Since the resulting preparation still has 3β-hydroxy- and 17β-hydroxysteroid dehydrogenase activities, which coincide on polyacrylamide-gel electrophoresis, both activities are probably expressions of a single enzyme.

Mechanical and electrical characterization of BCB as a bond and seal material for cavities housing (RF-)MEMS devices

This paper reports on the mechanical and electrical characterization of benzo-cyclo-butene (BCB) as a bonding and sealing material for 0-level packages (cavities) housing (RF-)MEMS devices. Shear strength and hermeticity of BCB-sealed cavities are experimentally investigated as functions of the geometrical parameters of the BCB sealing ring and the bonding conditions. The leak rate of BCB-sealed cavities strongly depends on the BCB width, and leak rates as low as 10−11 mbar l s−1 are measured for large BCB widths (>800 µm), dropping to 10−8 mbar l s−1 for BCB widths of around 100 µm. Depending on the bonding conditions, shear strengths as high as 150 MPa are achieved. BCB is also used in 0-level packaging of RF-MEMS devices, such as RF-switches and coplanar waveguides (CPWs). The electrical influence of the 0-level package is studied for different capping materials. It is experimentally shown that a 0-level package using capping chips made of low-loss high-resistivity materials (AF45 glass and high-resistivity silicon) and having a cavity height larger than about 45 µm above RF-MEMS devices, has a negligible impact on the microwave characteristics of an RF-MEMS device. Finally, some reliability testing is performed on BCB-sealed 0-level packages in order to study the influence of temperature and humidity on the mechanical properties of BCB. After testing in relatively harsh conditions, the BCB seal stays gross leak tight and shear strengths as high as 30 MPa are measured. BCB turns out to be a very robust and reliable material to encapsulate MEMS devices.

Sloped Through Wafer Vias for 3D Wafer Level Packaging

Through silicon via (TSV) technology is one of the critical and enabling technologies for 3D chip stacking. Many TSV approaches that have been demonstrated are application specific; and there is a great need for generic solutions. This work describes the design, fabrication and characterization of a TSV technology for silicon substrates where the interconnects are fabricated typically after standard CMOS processing and can be applied to any silicon based technology. This so-called 3D Wafer Level Packaging (3D-WLP) technology die stacking is based on a the thinning first, via last approach: the via is fabricated from the backside of a thinned wafer. Plasma etching of the wafer is used to achieve sloped profde which allows the conformal deposition of the dielectric layer and copper seed metallization. The vias are isolated from the substrate using polymer dielectrics; and spray coating of photoresist is used to pattern the dielectric within the vias. Electrical connection between the front and the back of the wafer is achieved by partial filling of the vias with copper. All processes employed in the fabrication of sloped through wafer vias are performed using standard wafer handling and at low temperature (< 250degC) for post CMOS compatibility. Various dimensions of TSVs are fabricated and electrically characterized by four point measurements. The measurements and calculations on daisy chains connecting a number vias in series show that the via resistance is in the range of 20-30mOmega depending on the via size. We believe that this generic 3D-WLP via approach is suitable for many 3D applications.

Etiology of hypercalcemia in a patient with Addison's disease

SummaryA case is reported of a hypercalcemic patient with primary Addisons disease. A combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney accounted for the hypercalcemia. The mechanisms responsible for the reduction in calcium removal were decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors were secondary to volume depletion and improved rapidly during rehydration with saline infusion. The enhanced calcium mobilization was probably of skeletal origin. It persisted irrespective of volume status until hydrocortisone treatment was instituted. Serum 1,25-dihydroxyvitamin D3 levels were below 10 pg/ml, even after normalization of the glomerular filtration rate, but returned slowly to the normal range during corticosteroid substitution. Serum 25-hydroxyvitamin D3 and parathyroid hormone levels were within the normal range. Our case report therefore demonstrates that physiological amounts of glucocorticoids reduce bone resorption, normalize serum calcium, and restore the production of 1,25-dihydroxyvitamin D3.