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Primary osteoporosis is rare in children and adolescents and its optimal pharmacological management is uncertain. Bisphosphonates are commonly used while denosumab has only been administered to a few children with osteogenesis imperfecta. We studied a treatment-naive 13.5-year-old boy with severe osteoporosis and multiple vertebral deformities who presented with back pain and difficulty in walking. Causes of secondary osteoporosis were excluded and there were no abnormalities in genes known to cause bone fragility. He was treated with denosumab 60 mg subcutaneously every 3 months for 30 months, and he was pain-free within 6 weeks after the first injection. Lumbar spine BMD and femoral neck BMD increased with treatment by 65.6% and 25.3%, respectively, and deformed vertebrae regained their normal shape; linear growth was not impaired. During the second year of treatment, transient hypercalcemia (maximum 3.09 mmol/l) before the denosumab injection was observed. In conclusion, denosumab was highly effective in this case of primary pediatric osteoporosis, with remarkable clinical and radiological response. Transient hypercalcemia was probably due to amplification of the effect of growth spurt and puberty on bone remodeling by the transient, short-term discontinuation of the drug. Furthermore, our data suggest that mobilization of calcium from treatment-induced sclerotic transverse lines in bone metaphyses may contribute to the development of hypercalcemia.

Background. HER2+/HR+ BC is heterogeneous and subgroups with different treatment sensitivities need to be identified. We previously reported a PAM50-based CES in HR+/HER2-negative BC (Prat et al. CCR 2016). Here, we evaluated the association of CES with pathologic complete response (pCR) following anti-HER2-based therapy in HR+/HER2+ BC across 6 NA studies. Methods. Intrinsic subtype and clinico-pathological data were obtained from 6 NA clinical studies (CHERLOB, OptiHERHEART[OHH], PAMELA, LPT109096, ICO and CALGB 40601 [CALGB is part of the Alliance for Clinical Trials in Oncology]). All patients (pts) received chemotherapy (CT) and trastuzumab, except for pts in the PAMELA study who did not receive CT. A second anti-HER2 agent (lapatinib or pertuzumab) was included in the NA of all pts in OHH and PAMELA and in one of the treatment arms in CHERLOB, LPT and C40601. CES was evaluated as a continuous variable, and categorically (CES-E[endocrine-sensitive], CES-U[uncertain] and CES-C[chemo-sensitive]) using the previously reported cut-offs. In all studies, except CHERLOB and C40601, ERBB2 mRNA levels were measured using the nCounter platform. pCR in the breast was the endpoint. We first performed statistical analyses in each dataset individually, and then in a dataset with combined patient-level data. Univariate and multivariable logistic regressions analyses were used. Results. A total of 345 pts were included in the analysis. In the combined cohort, CES-E, CES-U and CES-C were identified in 27.5%, 23.7% and 48.6% of the pts, respectively. Table 1 summarizes the distribution and pCR rates by CES groups. In the combined cohort, CES-C was associated with higher pCR rates compared to CES-U and CES-E independent of tumor size, nodal status, anti-HER2 treatment (single vs. dual HER2 blockade), intrinsic subtype (HER2-enriched [HER2E] versus not) and study (Table 2). In the PAMELA trial (no CT), CES-C was also found associated with higher pCR rates compared to CES-E (31.6% vs. 0%). Concordant with this finding, CES-C tumors showed higher ERBB2 mRNA levels than non-CES-C (P Conclusion. CES shows clinical validity for predicting CT/HER2-targeting sensitivity in HER2+/HR+ BC beyond intrinsic subtype and clinicopathologic characteristics. HER2+/HR+/CES-E tumors, which represent ˜20% of all HER2+ tumors, show low sensitivity to anti-HER2 regimens (with and without CT); other treatment strategies might be needed for this group. Support: U10CA180882;U10CA180821;U24CA196171;P50-CA58823;BCRF;Komen. Table 1. Distribution and pCR rates of CES-E, CES-U and CES-C groups across studies.n(%pCR)LPTCHERLOBOHHICOPAMELAC40601TOTALCES-E00/9(0)1/5(20)0/7(0)0/14(0)16/60(27)17/95 (18)CES-U0/1(0)4/15(27)5/7(71)4/13(30)2/25(8)10/21(47)25/82 (30)CES-C20/29(69)12/32(37)22/28(78)15/29(52)12/38(32)3/6(50)84/162(52)P0.330.080.040.03 Table 2. Association of CES, intrinsic subtype, clinicopathologic variables and study with pCR in a multivariable model (including type of study). OR95% CIPCES CES-E1 CES-U2.91.2-7.0 Citation Format: Pascual T, Tanioka M, Dieci MV, Pernas S, Gavila J, Guarnieri V, Cortes J, Llombart A, Conte P, Oliveira M, Paré L, Galván P, Perou CM, Prat A, Carey L. Independent validation of the PAM50-based chemo-endocrine score (CES) in hormonal receptor positive (HR+)/HER2+ breast cancer (BC) treated with neoadjuvant (NA) anti-HER2-based therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-05.

The target of this work is the demonstration of advanced approaches able to provide non-silicon MEMS platforms for chemical sensor operating under harsh environmental conditions and, on the other hand, to assure microhotplate stable at high temperature, which can be used for the deposition of refractory gas-sensing materials, for example, oxides of gallium, zirconium, or hafnium. Non-silicon materials that can be used for these MEMS platforms include aluminum oxide, yttria-stabilized zirconia and thin borosilicate glass. It was shown that thin ceramic films made of oxide materials can withstand annealing temperature up to 1000 °C, MEMS sensor based on these films consumes

The monitoring of concentration of methane dissolved in water is important for the security of underwater pipelines, delineation of oil and gas fields, and optimization of proper location of oil and gas wells. The reported system consists of metal oxide gas sensor separated from water by hydrophobic pervaporation membrane. Methane MEMS sensor was based on multilayer SiO2/Si3N4 film equipped with platinum heater and coated with sensing layer made of nanoparticle SnO2/Pd (3 wt. %). Methane saturation of water leads to a decrease in sensor resistance by a factor of 6 – 7, the response time of the system is of 200–300 s.

This work reports the development and the characterization of a microthermoelectric generator (μTEG) based on planar technology using electrochemically deposited constantan and copper thermocouples on a micro machined silicon substrate with a SiO2/Si3N4/SiO2 thermally insulating membrane to create a thermal gradient. The μTEG has been designed and optimized by finite element simulation in order to exploit the different thermal conductivity of silicon and membrane in order to obtain the maximum temperature difference on the planar surface between the hot and cold junctions of the thermocouples. The temperature difference was dependent on the nitrogen (N2) flow velocity applied to the upper part of the device. The fabricated thermoelectric generator presented maximum output voltage and power of 118 mV/cm2 and of 1.1 μW/cm2, respectively, for a device with 180 thermocouples, 3 kΩ of internal resistance, and under a N2 flow velocity of 6 m/s. The maximum efficiency (performance) was 2 × 10−3 μW/cm2 K2.

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.

Fundamental and applied investigation of ZnO has been recently experiencing a renaissance due to its prospective use in various technological domains and, in particular, as transparent conductive oxide (TCO). In this respect, the present work aims to study the structural and physical properties of ZnO thin films deposited by RF sputtering in pure Ar and Ar–H2 plasmas, at various concentrations (0–50%). The plasma chemical species were followed in function of the different gas mixture settings by optical emission spectroscopy (OES). X-ray photoelectron spectroscopy (XPS) and ATR-FTIR (Attenuated Total Reflection Fourier-Transformed Infrared) spectroscopy were used to study the bulk and surface chemical composition of the films, X-ray Diffraction (XRD) analysis allowed lattice structure and grain size determination while samples morphology was checked with a scanning electron microscope (SEM). The films were also characterized for their electrical and optical properties. The introduction of hydrogen in the plasma phase strongly affected the structural, chemical and physical properties of the films. In particular a pronounced change in the film electrical behavior was observed which become conductive when H is added in the gas mixture ([H2] > 6%). The film transparency was on the other hand maintained. By combining XPS, ATR-FTIR and OES data we could correlate the established conductivity and its variations with intentional hydrogen incorporation in the crystal structure in the form of hydroxide species.

This work presents the design, fabrication and characterization of a Si-based microseparation module for liquid chromatography (LC), targeted for agrofood applications and in particular for wine quality monitoring. The microsystem chip is a Silicon/Pyrex structure realized by anodic bonding. The basic Si-chip modules are an open tubular microcolumn with inlet/outlet for fluidic connections, a platinum heater and a Pt three-electrode amperometric sensor. Analytical calculations and finite element analysis have been performed to optimize the microcolumn design. Microchannels and inlet/outlet have been fabricated by deep reactive ion etching (DRIE) and tetra methyl ammonium hydroxide (TMAH) wet etching, respectively. The column has been functionalized with n-octyltriethoxysilane (C8-TEOS). Preliminary characterization tests of the microcolumn have been performed by evaluating the capability of the system to retain test solutions of acetic acid.

Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D

This work presents the realization of a Si-based miniaturised device for liquid chromatography (LC), targeted for agrofood applications and in particular for wine quality monitoring. The main modules of the system are: (1) a Si-based separation column, functionalized by n-octyltriethoxysilane (C8-TEOS), with inlet/outlet for fluidic connections; (2) a three-microelectrode voltammetric sensor. The system has been properly packaged and the capability of the sensing module to detect acetic acid concentration changes has been verified.

The monitoring of concentration of methane dissolved in water is important for the security of underwater pipelines, delineation of oil and gas fields, and optimization of proper location of oil and gas wells. The reported system consists of metal oxide gas sensor separated from water by hydrophobic pervaporation membrane. Methane MEMS sensor was based on multilayer SiO 2 /Si 3 N 4 film equipped with platinum heater and coated with sensing layer made of nanoparticle SnO 2 /Pd (3 wt. %). Methane saturation of water leads to a decrease in sensor resistance by a factor of 6 – 7, the response time of the system is of 200–300 s.

A microsystem composed of a micromachined resistive flow sensor and a signal conditioning CMOS IC is proposed for biomedical applications. The device can be adapted to noninvasively monitor urinary dysfunctions in male patients. The flow sensor, thermally simulated with ANSYS, is based on the hot-film principle: A thin film of gold laid on a suspended micromachined silicon membrane is heated while the fluid under test flows through the duct mounted above the membrane. The flow rate is sensed by measuring the temperature difference between two of the four polysilicon temperature sensors realized on the membrane. Simulations of the flow sensor with flow rates within 0.1-18 ml/s evidence a maximum temperature difference of 20degC between the temperature sensors. Characterization of the fabricated flow sensor shows temperature coefficient of resistance (TCR) values of -1930 ppm/degC for the polysilicon resistors, i.e., a resistance variation of about 4% at high flow rates. The CMOS readout designed for the flow sensor is a resistive bridge-to-duty cycle converter based on a relaxation oscillator. The digital output of the circuit is duty-cycle modulated by the change in resistance of the flow sensor's elements. Experimental tests on the CMOS interface, conducted with a setup of 1% precision resistors, report a maximum nonlinearity below 0.9% and a resolution of 7 bits over the full range of 4% resistance variation. The CMOS integrated readout circuit, provided with a digital output, allows simple signal interfacing towards any standard PC for periodical data transfer and storage

The adherence of Platinum thin film on Si/SiO 2 wafer was studies using Chromium, Titanium or Alumina (Cr, Ti, Al 2O 3) as interlayer. The adhesion of Pt is a fundamental property in different areas, for example in MEMS devices, which operate at high temperature conditions, as well as in biomedical applications, where the problem of adhesion of a Pt film to the substrate is known as a major challenge in several industrial applications health and in biomedical devices, such as for example in the stents. (1)(-) (4) We investigated the properties of Chromium, Titanium, and Alumina (Cr, Ti, and Al 2O 3) used as adhesion layers of Platinum (Pt) electrode. Thin films of Chromium, Titanium and Alumina were deposited on Silicon/Silicon dioxide (Si/SiO 2) wafer by electron beam. We introduced Al 2O 3 as a new adhesion layer to test the behavior of the Pt film at higher temperature using a ceramic adhesion thin film. Electric behaviors were measured for different annealing temperatures to know the performance for Cr/Pt, Ti/Pt, and Al 2O 3/Pt metallic film in the gas sensor application. All these metal layers showed a good adhesion onto Si/SiO 2 and also good Au wire bondability at room temperature, but for higher temperature than 400 °C the thin Cr/Pt and Ti/Pt films showed poor adhesion due to the atomic inter-diffusion between Platinum and the metal adhesion layers. (5) The proposed Al 2O 3/Pt ceramic-metal layers confirmed a better adherence for the higher temperatures tested.

Shielding is the only practical countermeasure for the exposure to cosmic radiation during space travel. It is well known that light, hydrogenated materials, such as water and polyethylene, provide the best shielding against space radiation. Kevlar and Nextel are two materials of great interest for spacecraft shielding because of their known ability to protect human space infrastructures from meteoroids and debris. We measured the response to simulated heavy-ion cosmic radiation of these shielding materials and compared it to polyethylene, Lucite (PMMA), and aluminum. As proxy to galactic nuclei we used 1 GeV n iron or titanium ions. Both physics and biology tests were performed. The results show that Kevlar, which is rich in carbon atoms (about 50% in number), is an excellent space radiation shielding material. Physics tests show that its effectiveness is close (80-90%) to that of polyethylene, and biology data suggest that it can reduce the chromosomal damage more efficiently than PMMA. Nextel is less efficient as a radiation shield, and the expected reduction on dose is roughly half that provided by the same mass of polyethylene. Both Kevlar and Nextel are more effective than aluminum in the attenuation of heavy-ion dose.

Tetra-methyl ammonium hydroxide, or TMAH, is an anisotropic silicon etchant that is gaining more and more attention in the fabrication process of mechanical microstructures and device isolation, as an alternative to the more usual KOH and EDP etchants [1]: because of its high compatibility with conventional IC processes, due to the absence of metal ions in it. The possibility to passivate the aluminum metalisation in properly saturated TMAH solution has also been demonstrated by doping the solution with appropriate amounts of silicon or silicic acid [2, 3]. This increases the range of application of these etchants, simplifying both the post processing and the etch set-up configuration. In this paper we present some different technological solutions adopted for the fabrication of 3D structures using as anisotropic etchant doped TMAH solutions. The effects of the additives on etch uniformity and surface roughness are studied. Using the etching results under different doping conditions of the TMAH solutions, we obtained silicon bulk-micromachined structures with controlled surface roughness. Furthermore the aluminium passivation permits to etch devices with no protection of the metalisation layers as some applications require (i.e. bolometers).

The Altcriss project was submitted in response to ESA AO-2004. It was approved in March 2005 and begun in December 2005 with Progress 21-P launch from Baikonur. It is currently operating on board the International Space Station, performing a survey of the radiation environment and the effectiveness of shielding materials from cosmic rays. It uses the active silicon detector Sileye-3 and a series of passive dosimeters (CR-39, TLD). The detectors have currently been operational in different location of the Pirs (docking) and Service module of the Russian section of the Station. The project is expected to continue up to 2008.

During the last years nanotechnology has lead to the development of new methods of material deposition that have the very interesting feature of finely controlling the nanostructure of deposited thin films, tailoring the material properties to application-specific needs. One of the big challenges in the near future is to couple these deposition techniques to mature microfabrication technologies in order to realize microdevices with unique features that arise from the nano-world. Here we present a new method for the direct integration of nanostructured metal oxide layers on micromachined silicon platform batches, for the realization of solid-state conductometric gas sensors. Two cases have been investigated: deposition of nanostructured WO"3 on microhotplate arrays and deposition of nanostructured Fe"2O"3 on microbridges.

The experiment LAZIO-Sirad was placed on board the International Space Station (ISS) with a Progress cargo on the beginning of March 2005. It represents the continuation of previous experiments (also on board Mir station) with the Sileye devices. It was operational as part of the ”Eneide” mission for 10 days from April the 17th 2005. The experiment aimed to study and correlate measurements of cosmic ray and magnetic environment on board the ISS with two devices: the LAZIO detector, built for the mission and the Sileye-3/Alteino telescope fitted with special multimaterial shielding tiles

Experiment T2, carried out during the Euromir'95 mission, was an important step toward innovative methods for spacecraft microbial contamination monitoring. A new standard sampling technique permitted samples to be analysed by different means. On board, two analysis methods were tested in parallel: Bioluminescence and Miniculture. In turn, downloaded samples are being analysed by polymerase chain reaction (PCR), a powerful and promising method for the rapid detection, identification and quantification of pathogens and biofouling agents in closed manned habitats.

The growing interest in new under-water pipe lines for the delivery of natural gas (in Baltic Sea, Mediterranean region, Caspian Sea, Black Sea, etc.) needs a new instruments for the monitoring of leakage and/or possible destruction of the pipes, which could not only disturb fragile ecological systems of Baltic and other seas, but also can lead to the technological catastrophes. We plan to develop a prototype of the system consisting of pervaporation membrane and gas sensors. Overall system will be immersed into water and will be fabricated in two versions: as a stationary instrument dipped into sea water and as an instrument towed along the pipe line. Micromachined metal oxide semiconductor gas sensors used for the detection of methane concentrations is designed and fabricated using “nano-on-micro” approach. Overall system is optimized from the point of view of minimum power consumption, which is necessary to assure its long term operation under autonomous conditions.

Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D2 -receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory.

The problem of gas analyzers compatible with wireless networks can be solved by using sensors based on the “nano-on-micro” technology. The basis of this technology consists in nano-composite sensing metal oxide semiconductor or thermocatalytic materials deposited on a microhotplate fabricated using silicon or alumina microelectronic technology. As a result, the sensor combines the advantages of both technologies: on the one hand, high stability and sufficient selectivity of nano-composite materials, and, on the other hand, microprocessor compatibility, low-cost, mass-production possibilities, and low power consumption of microelectronic substrates. Two methods for the fabrication of microhotplates are the most promising: the silicon based technology of silicon oxide/silicon nitride membranes and the CeraMEMS technology of thin alumina films (TAF). The first technology enables the fabrication of microheaters with a power consumption around 20 mW for an operating temperature below 450°C. Advantages of CeraMEMS platforms are: (1) operation at temperature up to 600°C and, potentially, up to 800°C; (2) robustness compared with silicon chip with thin membrane; (3) perfect Pt and sensing layer adhesion without any adhesive layers; (4) low cost of middle scale production (104–107 chips per year) compared with the silicon technology. The CeraMEMS platform can be used for the fabrication of semiconductor and thermocatalytic gas sensors, as a source of IR radiation for optical gas sensors and as bolometers. The sensor withstands ∼7 × 106 on-off cycles. Heater resistance drift is below 3% per year at 550°C.

In this work, the performances of a Cr-doped WO3 sensor array are investigated for the application of this device as detector in gas chromatographic systems. Chromatographic separation modules combined with detectors based on semiconducting metal oxides enable the implementation of systems with both high selectivity and high sensitivity. Comparison of results of the sensor array and mass spectrometer detectors validates the use of this class of devices for low-cost systems for the determination of the volatile organic compounds contents in wines for quality assessment of alcoholic beverages.

This work presents the realization of a MEMS-based miniaturized system for liquid chromatography focused on agrofood applications, and in particular on the detection of wine defects. The main modules of the systems are: i.) a Si-based separation column with inlet/outlet for fluidic connections; ii.) a three-microelectrode voltammetric sensor. Moreover, a Platinum heater has been realized on the back side of the chip containing the Si column in order to operate at temperatures greater than the room temperature. The realized device consists of a Silicon/Pyrex structure realised by anodic bonding. Microchannels and inlet/outlet have been fabricated by Deep Reactive Ion Etching (DRIE) and Tetra Methyl Ammonium Hydroxide (TMAH) wet etching respectively. The column has been functionalised with n-octyltriethoxysilane (C8-TEOS). A lift-off technique has been developed for realizing the Pt heater and the Pt microelectrodes on-chip. In order to separately characterize the main modules of the device, a package of the system has been realized following a modular approach; appropriate tubing and nanovolume connections have been used in order to minimize dead volumes. Then other packages approaches have been considered in order to minimize dead volumes and to avoid leakage issues. Preliminary characterization tests of the two main modules have been performed. The capability of the system to correctly retain and detect Acetic acid has been tested.

This research work was aimed at finding an innovative process based on MEMS technologies to measure the alcoholic strength of hydro-alcoholic solutions. A new Si micromachined alcoholometer was developed. A microhotplate, based on a dielectric thin membrane, is used to heat and measure the temperature of droplets of hydro-alcoholic solution dispensed by a tiny capillary during an evaporation cycle. It was found that the alcoholic strength is correlated with the integration of the temperature of the droplet over time during its evaporation. Opposed to the old measurement methods, this new procedure takes advantage of many properties of the hydro-alcoholic solutions such as: superficial tension, latent heat of evaporation, boiling point and heat capacity. All these issues contribute together to give a good response in terms of good resolution and accuracy over a wide range of alcoholic degree.

Crews of future exploration missions will be exposed for long time to a unique powerful mix of cosmic radiation. Starting from REMSIM study for ESA, we are focusing on short and long term shielding experiments aboard ISS (ESCHILO, ALTCRISS, SOFOCLE) by comparing the materials used in inflatable structures with the typical rigid materials used in current spacecraft, and optimizing and validating the radiation shielding solutions in LEO. To assess shielding strategies, tests in flight are always supported by calculations and laboratory experiments. The paper reports descriptions and available results of the above experiments. Copyright © 2006 SAE International.

In this work we describe the design implementation, validated by experimental results, of an innovative gas sensor array for wine quality monitoring. The main innovation of this integrated array deals with the simultaneous outputs, from a single chip on custom SMD socket, of eight different signals coming from a WO 3 thin film structure heated in a linear temperature gradient mode, allowing an overall evaluation of gas sensing properties of the material in a 100 °C-wide window, typically from 300 to 400 °C. The implemented sensitive layer is a WO 3 film deposed by RF-sputtering. Preliminary tests of gas sensing showed good responses to the target analytes for the specific application (1-heptanol, 3-methylbutanol, benzaldehyde and ethyl-hexanoate).

In this work, we describe the design implementation, validated by experimental results, of an innovative gas sensor array for wine quality monitoring. The main innovation of this integrated array deals with the simultaneous outputs, from a single chip on TO-12 socket, of 8 different signals coming from a WO3 thin film structure heated in a linear temperature gradient mode, allowing an overall evaluation of gas sensing properties of the material in a 100°C-wide window, typically from 300 to 400°C. The implemented sensitive layer is a WO3 film deposed by RF-sputtering. Preliminary tests of gas sensing showed good responses to the target analytes for the specific application (1-heptanol, 3-methyl butanol, benzaldehyde and ethyl-hexanoate).

In this work, the stress of electroplated gold films has been analyzed versus plating current density and bath temperature. Two different plating solutions have been adopted, one being based on cyanide-gold salt, the other on sulfite-gold. Gold surface quality was investigated in the experimented range of plating temperature and current density, in order to control the limit conditions for plating: surface roughness and non-uniformity appear whenever deposition parameters are brought to the limit (typically below 2 mA/cm/sup 2/ and above 5 mA/cm/sup 2/). Plated gold stress measurement was carried out by wafer curvature comparison, before and after deposition, using Stoney's formula for thin films/sup 1,2/. A current density range between 1.5 and 6 mA/cm/sup 2/ and temperature range between 50 and 70/spl deg/C was investigated. Stress analysis was also carried out on a Cr-Au multilayer, which actually is the structural layer employed for gold microstructures: the multilayer consists of a chromium adhesion layer, a PVD gold seed layer and a plated gold layer, with thickness respectively 10 nm, 150 nm and 1500 nm. A range of stress was obtained, varying from tensile to compressive: cyanide bath yielded stress from -30 MPa to about 0 MPa, and sulfite bath showed stress between -90 MPa and 110 MPa. Stress variation induced by thermal treatments after deposition was also investigated, by examining the effect of photoresist sacrificial etching on the internal stress of chromium-gold structural layers: the final stress was about 180 MPa tensile for all samples, regardless the as-deposited stress, with a variation ranging from about 80 MPa to more than 200 MPa.

The accurate determination of biological parameters by means of rapid, on-line measurements at low-concentrations is an important task within the fields of pharmaceutical screening and medical diagnostic. Nevertheless, in biological samples, the analytes of interest are present as minor components in complex mixtures and with interfering species. Biosensors are the best candidates for these applications providing a direct solution to this need of accuracy, but their intrinsic selectivity often excludes all the other components in the sample. A separation step introduced prior to the sensing component could allow both the increase of selectivity with respect the interfering species and the identification of a large spectrum of molecular components in the sample. This work reports the development of a silicon-based integrated separation microsystem for gas chromatography aimed to biomedical applications, with particular emphasis to monitor the homovanillic acid (HVA) and vanillylmandelic acid (VMA) ratios in mass population screening for neuroblastoma diagnosis and prognosis. The miniaturised system consists of two main modules: (i) a metal oxide semiconductor detector and (ii) a micromachined separation capillary column. As first step, the metal oxide semiconductor capability to detect HVA and VMA has been demonstrated. Then, a technology for a silicon separation capillary microcolumn including the on-chip gas sensor housing has been proposed and a first prototype has been developed. The proposed microsystem is an analytical device with biosensing capabilities for diagnostic and biomedical applications, which yield an electronic signal proportional to the concentration of a specific analyte or group of analytes.