Infusion Micro-Pump Development Using MEMS Technology

International audienceDiabetes is a chronic condition that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. People having type 1 diabetes require insulin (10% of all diabetics). People with type 2 diabetes can be treated with oral medication, but may also require insulin; 10% of all type 2 diabetics require insulin. Among the actual different methods to administer insulin (syringes, pens and conventional infusion pumps) a possibility to increase infuser performances is offered by the utilization of silicon based MEMS pumps (Micro- Electro Mechanical Systems). The main two pump families are classified as mechanical and non-mechanical pumps. The former contains check-valve, peristaltic, rectification without valves and rotary ones (“Displacement Pumps”) or Ultrasonic and Centrifugal (“Dynamic Pumps”); the latter consists in Pressure, Concentration, Electrical Potential gradients and Magnetic Potential micro-pumps. The micro-pump described here is an electro-mechanical device actuated with a piezoelectric-element and based on MEMS technology, able to minimize size and costs, offering a high precision pharmacological dispense. Three slices are bonded to reach the final results: top and bottom caps and an intermediate SOI. In case of anodic bonding, top and bottom caps are constituted of micromachined borophosphosilicate wafers, whereas in case of metallic bonding three silicon slices are used. The paper deals with the fabrication evolution of the device according to the different items that had to be faced during development: design, fluidic, mechanical and electrical simulations and characterization, safety requirements and final testing. Built-in reliability is ensured by two inner sensors able to detect any occlusion or malfunctioning and informing so the patient. The result is a compact, core pump chip that can deliver from 0.02 Units of insulin up to 3.6 Units per minute with accuracy better than 5%

The Economic Impact of the Value Chain of a Marcellus Shale Well

The Economic Impact of the Value Chain of a Marcellus Shale Well Site examines the direct economic impact of a Marcellus Shale well located in Southwestern Pennsylvania. This study seeks to fill a critical information gap on the impact of gas drilling and extraction from Marcellus Shale deposits deep underground: an assessment of the economic impacts – emphasizing the direct economic impact, rather than just focusing on the perceived benefits and impacts affecting the region. Our analysis is based on extensive field research, including a site visit and interviews with industry participants. It is further cross-validated by examining similar costs for development of Marcellus Wells by a vertically-integrated exploration and production firm

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Magnétisme de quelques composés bidimensionnels de la famille AMO2 (A=Li, Na: M=Ni, Fe, Co)

We present a study of the magnetic properties of layered oxides that belong to the AMO2 family (A=Li, Na; M=Ni, Fe, Co). The compounds are very promising materials for battery applications. LiNiO2 is the subject of strong theoretical interest due to the possible coupling between spin and orbital degrees of freedom. Several works have been devoted to the magnetic properties of LiNiO2 but the results remain much debated. Since this is also crucial for battery capacity, solid state chemists have improved the synthesis and the characterisation of the samples these last years. It has been shown that both electrochemical and magnetic properties are very sensitive to the departure from the stoichiometry. The magnetic properties of the perfectly lamellar NaNiO2 system have been first studied by means of electron spin resonance, neutron diffraction, high field magnetization and low field susceptibility. NaNiO2 is an A-type antiferromagnetic insulator with a ferrodistorsive orbital ordering for T<210°C due to the cooperative Jahn-Teller effect of the Ni3+ ions in the low spin state S=1/2. A detailed study of the Li1-xNi1+xO2 solid solution is also provided, showing the fundamental role of extra Ni ions which induce magnetic clusters progressively formed and oriented with increasing x. Based on the determination of the magnetic interactions, we propose an original model of a cluster induced frustration which explains both the spin-glass like behaviour at low temperatures for the quasi-stoichiometric compound and the large spectrum of magnetic behaviours observed for Ni rich compounds. After a magnetic characterization of the lamellar LiFeO2, we finally consider the effect of cationic substitution of cobalt in LiFeO2 and iron in LiNiO2. We show that iron ions on the lithium site do not induce magnetic clusters. For all samples, the sign and the intensity of the magnetic interactions are given.Ce mémoire de thèse présente une étude des propriétés magnétiques de quelques oxydes lamellaires de la famille AMO2 (A=Li, Na; M=Ni, Fe, Co). Ces composés sont notamment utilisés en tant que matériaux pour électrodes positives dans les batteries lithium-ion. Les propriétés magnétiques de LiNiO2 avaient déjà fait l'objet de nombreuses études mais la grande disparité des résultats obtenus n'avait permis de dégager aucun consensus quant à la nature de son état fondamental. Le rôle joué par les degrés de liberté orbitaux sur la frustration magnétique est notamment fortement débattu. Afin d'améliorer les performances des batteries, les chimistes du solide ont de leur côté considérablement amélioré les conditions de synthèse et de caractérisations physico-chimiques au cours de ces dernières années. Il s'est révélé que l'écart à la stœchiométrie des matériaux étudiés avait des conséquences dramatiques à la fois sur les propriétés magnétiques et électrochimiques. Dans un premier temps, une étude complète des propriétés magnétiques et structurales du composé stœchiométrique NaNiO2 est présentée. Les techniques expérimentales utilisées sont la résonance électronique de spin, la diffraction neutronique, les mesures d'aimantation à hauts champs et de susceptibilité en champs faibles. NaNiO2 est un AF de type A qui présente un ordre orbital de type Ferro pour T<210°C du à l'effet Jahn-Teller coopératif des ions Ni3+ de spin S=1/2. Une étude détaillée des phases Li1-xNi1+xO2 en fonction de la concentration x nous a ensuite permis de montrer le rôle fondamental des ions Ni excédentaires qui forment des clusters magnétiques. A partir d'une détermination du signe des interactions magnétiques, nous proposons un modèle original de frustration magnétique induite par des clusters pour x petit qui rend compte de toutes les données expérimentales. La nature de l'ordre magnétique du composé lamellaire LiFeO2 a également été déterminée comme préliminaire à l'étude des effets de la substitution cationique du cobalt dans ce composé LiFeO2 ainsi que celle du fer dans LiNiO2. Nous montrons que le fer sur le site du lithium ne participe pas à la formation de clusters magnétiques. Pour chaque composé, la valeur et le signe des interactions ont été déterminés

Special Issue on the Development of Microfluidic Devices for Medical Applications

Microfluidics refers to the science of handling fluids in microstructures and has been widely used in the medical field to miniaturize conventional drug delivery systems, bioassays, and diagnostics [...

Design and characterization of a passive flow control valve dedicated to the hydrocephalus treatment

International audienc

Dry Test Methods for Micropumps

The test in the production of microfluidic devices dedicated to medical applications poses several challenges in terms of contamination, reliability, and cost. The present article describes the Design-for-Testability approach used to make an insulin MEMS micropump that can be fully tested in production in a few seconds. Each key functional parameter of a positive displacement micropump with check valves is described together with detailed pneumatic test methods. The typical failure modes of the device are considered and tested experimentally to show that these methods can also be used for failure analysis and process control. A simplified Built-In-Self-Test is also presented. Finally, advanced methods to characterize the piezoelectric actuator are also described and tested

A Review of Passive Constant Flow Regulators for Microfluidic Applications

This review gives an overview of passive constant flow regulators dedicated to microfluidic applications. Without external control and energy consumption, these devices deliver a constant flow rate regardless of pressure variations, making them very attractive for various microfluidic applications, including drug delivery, flow chemistry, point-of-care tests, or microdialysis. This technical review examines progress over the last three decades in the development of these flow regulators and focuses on the working principle, fabrication methods, performance, and potential applications

Modeling of a Piezoelectric MEMS Micropump Dedicated to Insulin Delivery and Experimental Validation Using Integrated Pressure Sensors: Application to Partial Occlusion Management

International audienceA numerical model based on equivalent electrical networks has been built to simulate the dynamic behavior of a positive-displacement MEMS micropump dedicated to insulin delivery. This device comprises a reservoir in direct communication with the inlet check valve, a pumping membrane actuated by a piezo actuator, two integrated piezoresistive pressure sensors, an anti-free-flow check valve at the outlet, and finally a fluidic pathway up to the patient cannula. The pressure profiles delivered by the sensors are continuously analyzed during the therapy in order to detect failures like occlusion. The numerical modeling is a reliable way to better understand the behavior of the micropump in case of failure. The experimental pressure profiles measured during the actuation phase have been used to validate the numerical modeling. The effect of partial occlusion on the pressure profiles has been also simulated. Based on this analysis, a new management of partial occlusion for MEMS micropump is finally proposed

MAGNETISME DE QUELQUES OXYDES BIDIMENSIONNELS DE LA FAMILLE AMO 2 (A=LI, NA ; M=NI, FE, CO)

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