Hemostasis-on-a-chip: Impedance spectroscopy meets microfluidics for hemostasis evaluation

In the case of vascular injury, a complex process (of clotting) starts, involving mainly platelets and coagulation factors. This process in healthy humans is known as hemostasis, but when it is deregulated (thrombosis), it can be the cause of important cardiovascular diseases. Nowadays, the aging of the population and unhealthy lifestyles increase the impact of thrombosis, and therefore there is a need for tools to provide a better understanding of the hemostasis mechanisms, as well as more cost-e ective diagnosis and control devices. This study proposes a novel microflow chamber, with interchangeable biomimetic surfaces to evaluate global hemostasis, using reduced amounts of blood sample and reagents, and also a minimized time required to do the test. To validate the performance of this novel device, a study on the new oral anticoagulant Apixaban (APIX) has been performed and compared to previous conventional techniques. The test shows an excellent agreement, while the amount of the required sample has been reduced (only 100 L is used), and the amount of reagent as well. An imprinted electrode embedded in the chamber in order to measure the impedance during the coagulation process. This approach distinguishes the impedance behavior of plasma poor in platelets (PPP) and plasma rich in platelets (PRP) for the first timePostprint (published version

Methods for immobilizing receptors in microfluidic devices: A review

In this review article, we discuss state-of-the-art methods for immobilizing functional receptors in microfluidic devices. Strategies used to immobilize receptors in such devices are essential for the development of specific, sensitive (bio)chemical assays that can be used for a wide range of applications. In the first section, we review the principles and the chemistry of immobilization techniques that are the most commonly used in microfluidics. We afterward describe immobilization methods on static surfaces from microchannel surfaces to electrode surfaces with a particular attention to opportunities offered by hydrogel surfaces. Finally, we discuss immobilization methods on mobile surfaces with an emphasis on both magnetic and non-magnetic microbeads, and finally, we highlight recent developments of new types of mobile supports

Nanogap capacitive biosensor for label-free aptamer-based protein detection

Recent advances in nanotechnology offer a new platform for the label free detection of biomolecules at ultra-low concentrations. Nano biosensors are emerging as a powerful method of improving device performance whilst minimizing device size, cost and fabrication times. Nanogap capacitive biosensors are an excellent approach for detecting biomolecular interactions due to the ease of measurement, low cost equipment needed and compatibility with multiplex formats.This thesis describes research into the fabrication of a nanogap capacitive biosensor and its detection results in label-free aptamer-based protein detection for proof of concept. Over the last four decades many research groups have worked on fabrication and applications of these type of biosensors, with different approaches, but there is much scope for the improvement of sensitivity and reliability. Additionally, the potential of these sensors for use in commercial markets and in everyday life has yet to be realized.Initial work in the field was limited to high frequency (>100 kHz) measurements only, since at low frequency there is significant electronic thermal noise (=4kBTR) from the electrical double layer (EDL). This was a significant drawback since this noise masked most of the important information from biomolecular interactions of interest. A novel approach to remove this parasitic noise is to minimize the EDL impedance by reducing the capacitor electrode separation to less than the EDL thickness. In the case of aptamer functionalized electrodes, this is particularly advantageous since device sensitivity is increased as the dielectric volume is better matched to the size of the biomolecules and their binding to the electrode surface. This work has demonstrated experimentally the concepts postulated theoretically.In this work we have fabricated a large area (100 x 5 μm x 5 μm) vertically oriented capacitive nanogap biosensor with a 40 nm electrode separation between two gold electrodes. A silicon dioxide support layer separates the two electrodes and this is partially etched (approximately 800 nm from both sides of each 5 μm x 5 μm capacitor), leaving an area of the gold electrodes available for thiol-aptamer functionalization.AC impedance spectroscopy measurements were performed with the biosensor in the presence of air, D.I. water, various ionic strength buffer solutions and aptamer/protein pairs inside the nanogap. Applied frequencies were from 1Hz to 500 kHz at 20 mV AC voltage with 0 DC. We obtained relative permittivity results as a function of frequency for air (ɛ=1) and DI water (ɛ~80) which compares very favorably with previous works done by different research groups.The sensitivity and response of the sensors to buffer solution (SSC buffer) with various ionic strengths (0.1x SSC, 0.2x SSC, 0.5x SSC and 1x SSC) was studied in detail. It was found that in the low frequency region (<1 kHz) the relative permittivity (capacitance) was broadly constant, that means it is independent from the applied frequency in this range. With increasing buffer concentration, the relative permittivity starts to increase (from ɛ=170 for 0.1x SSC to ɛ=260 for 1x SSC).The sensor performance was further investigated for aptamer-based protein detection, human alpha thrombin aptamers and human alpha thrombin protein pairs were selected for proof of concept. Aptamers were functionalized into the gold electrode surface with the Self-Assembly-Monolayer (SAM) method and measurements were performed in the presence of 0.5x SSC buffer solution (ɛ=180). Then the hybridization step was carried out with 1 μM of human alpha thrombin protein followed by measurements in the presence of the same buffer (ɛ=130). The response of the sensors with different solutions inside the nanogap was studied at room temperature (5 working devices were tested for each step). The replacement of the buffer solution (ɛ=250) with lower relative permittivity biomolecules (aptamer ɛ=180) and further binding proteins to immobilized aptamer (ɛ=130) was studied. To validate these results, a control experiment was carried out using different aptamers, in this case which are not able to bind to human alpha thrombin protein. It was found that the relative permittivity did not change after the hybridization step compared to the aptamer functionalization step, which indicates that the sensors performance is highly sensitive and reliable.This work serves as a proof of concept for a novel nanogap based biosensor with the potential to be used for many applications in environmental, food industry and medical industry. The fabrication method has been shown to be reliable and consistent with the possibility of being easily commercialized for mass production for use in laboratories for the analysis of a wide range of samples

Microfluidic platform for multiple parameters readouts in a point-of-care

The research is motivated by real applications, such as pasteurization plant, water networks and autonomous system, which each of them require a specific control system to provide proper management able to take into account their particular features and operating limits in presence of uncertainties related to their operation and failures from component breakdowns. According to that most of the real systems have nonlinear behaviors, it can be approximated them by polytopic linear uncertain models such as Linear Parameter Varying (LPV) and Takagi-Sugeno (TS) models. Therefore, a new economic Model Predictive Control (MPC) approach based on LPV/TS models is proposed and the stability of the proposed approach is certified by using a region constraint on the terminal state. Besides, the MPC-LPV strategy is extended based on the system with varying delays affecting states and inputs. The control approach allows the controller to accommodate the scheduling parameters and delay change. By computing the prediction of the state variables and delay along a prediction time horizon, the system model can be modified according to the evaluation of the estimated state and delay at each time instant. To increase the system reliability, anticipate the appearance of faults and reduce the operational costs, actuator health monitoring should be considered. Regarding several types of system failures, different strategies are studied for obtaining system failures. First, the damage is assessed with the rainflow-counting algorithm that allows estimating the component’s fatigue and control objective is modified by adding an extra criterion that takes into account the accumulated damage. Besides, two different health-aware economic predictive control strategies that aim to minimize the damage of components are presented. Then, economic health-aware MPC controller is developed to compute the components and system reliability in the MPC model using an LPV modeling approach and maximizes the availability of the system by estimating system reliability. Additionally, another improvement considers chance-constraint programming to compute an optimal list replenishment policy based on a desired risk acceptability level, managing to dynamically designate safety stocks in flow-based networks to satisfy non-stationary flow demands. Finally, an innovative health-aware control approach for autonomous racing vehicles to simultaneously control it to the driving limits and to follow the desired path based on maximization of the battery RUL. The proposed approach is formulated as an optimal on-line robust LMI based MPC driven from Lyapunov stability and controller gain synthesis solved by LPV-LQR problem in LMI formulation with integral action for tracking the trajectory

Microfluidic platform for multiple parameters readouts in a point-of-care

The research is motivated by real applications, such as pasteurization plant, water networks and autonomous system, which each of them require a specific control system to provide proper management able to take into account their particular features and operating limits in presence of uncertainties related to their operation and failures from component breakdowns. According to that most of the real systems have nonlinear behaviors, it can be approximated them by polytopic linear uncertain models such as Linear Parameter Varying (LPV) and Takagi-Sugeno (TS) models. Therefore, a new economic Model Predictive Control (MPC) approach based on LPV/TS models is proposed and the stability of the proposed approach is certified by using a region constraint on the terminal state. Besides, the MPC-LPV strategy is extended based on the system with varying delays affecting states and inputs. The control approach allows the controller to accommodate the scheduling parameters and delay change. By computing the prediction of the state variables and delay along a prediction time horizon, the system model can be modified according to the evaluation of the estimated state and delay at each time instant. To increase the system reliability, anticipate the appearance of faults and reduce the operational costs, actuator health monitoring should be considered. Regarding several types of system failures, different strategies are studied for obtaining system failures. First, the damage is assessed with the rainflow-counting algorithm that allows estimating the component’s fatigue and control objective is modified by adding an extra criterion that takes into account the accumulated damage. Besides, two different health-aware economic predictive control strategies that aim to minimize the damage of components are presented. Then, economic health-aware MPC controller is developed to compute the components and system reliability in the MPC model using an LPV modeling approach and maximizes the availability of the system by estimating system reliability. Additionally, another improvement considers chance-constraint programming to compute an optimal list replenishment policy based on a desired risk acceptability level, managing to dynamically designate safety stocks in flow-based networks to satisfy non-stationary flow demands. Finally, an innovative health-aware control approach for autonomous racing vehicles to simultaneously control it to the driving limits and to follow the desired path based on maximization of the battery RUL. The proposed approach is formulated as an optimal on-line robust LMI based MPC driven from Lyapunov stability and controller gain synthesis solved by LPV-LQR problem in LMI formulation with integral action for tracking the trajectory

Microfluidic platform for multiple parameters readouts in a point-of-care

Tesi amb una secció retallada per drets de l'editorThe research is motivated by real applications, such as pasteurization plant, water networks and autonomous system, which each of them require a specific control system to provide proper management able to take into account their particular features and operating limits in presence of uncertainties related to their operation and failures from component breakdowns. According to that most of the real systems have nonlinear behaviors, it can be approximated them by polytopic linear uncertain models such as Linear Parameter Varying (LPV) and Takagi-Sugeno (TS) models. Therefore, a new economic Model Predictive Control (MPC) approach based on LPV/TS models is proposed and the stability of the proposed approach is certified by using a region constraint on the terminal state. Besides, the MPC-LPV strategy is extended based on the system with varying delays affecting states and inputs. The control approach allows the controller to accommodate the scheduling parameters and delay change. By computing the prediction of the state variables and delay along a prediction time horizon, the system model can be modified according to the evaluation of the estimated state and delay at each time instant. To increase the system reliability, anticipate the appearance of faults and reduce the operational costs, actuator health monitoring should be considered. Regarding several types of system failures, different strategies are studied for obtaining system failures. First, the damage is assessed with the rainflow-counting algorithm that allows estimating the component’s fatigue and control objective is modified by adding an extra criterion that takes into account the accumulated damage. Besides, two different health-aware economic predictive control strategies that aim to minimize the damage of components are presented. Then, economic health-aware MPC controller is developed to compute the components and system reliability in the MPC model using an LPV modeling approach and maximizes the availability of the system by estimating system reliability. Additionally, another improvement considers chance-constraint programming to compute an optimal list replenishment policy based on a desired risk acceptability level, managing to dynamically designate safety stocks in flow-based networks to satisfy non-stationary flow demands. Finally, an innovative health-aware control approach for autonomous racing vehicles to simultaneously control it to the driving limits and to follow the desired path based on maximization of the battery RUL. The proposed approach is formulated as an optimal on-line robust LMI based MPC driven from Lyapunov stability and controller gain synthesis solved by LPV-LQR problem in LMI formulation with integral action for tracking the trajectory.Postprint (published version

An Exploration of Paul Bowles\u27 Piano-Solo Pieces

This research paper provides a general overview of the piano-solo literature by the American composer Paul Frederic Bowles (1910-1999). Thanks to recent contributions, this repertoire is now available in recordings and musical scores as it has never been before.;This paper is divided into two sections. The first covers the biography of Paul Bowles and his musical achievements as a composer, along with his research into the folk music of Morocco and his literary writings as a music critic for the journal Modern Music and for The New Herald Tribune. The second part is about Bowles\u27 piano-solo output, divided thematically into pieces with similar forms and structures.;For Bowles\u27 solo piano music, theoretical analysis and a review of existing literature help to reveal style traits; these include his preference for short character pieces, in which Bowles employs neoclassical elements, such as melodies with classical harmonies that display bitonal and pandiatonal tendencies, along with ostinato patterns and Alberti-bass accompaniments. Bowles\u27 music often displays ternary or free structures, with motivic development techniques through which themes or passages are derived from previous motives. Jazz and folk idioms are also an important aspect of Bowles\u27 piano music, particularly in his dancelike pieces, many of which display a Latin-American flavor

Microfluidics for Biosensing and Diagnostics

Efforts to miniaturize sensing and diagnostic devices and to integrate multiple functions into one device have caused massive growth in the field of microfluidics and this integration is now recognized as an important feature of most new diagnostic approaches. These approaches have and continue to change the field of biosensing and diagnostics. In this Special Issue, we present a small collection of works describing microfluidics with applications in biosensing and diagnostics

Sensors and Biosensors for C-Reactive Protein, Temperature and pH, and Their Applications for Monitoring Wound Healing: A Review

Wound assessment is usually performed in hospitals or specialized labs. However, since patients spend most of their time at home, a remote real time wound monitoring would help providing a better care and improving the healing rate. This review describes the advances in sensors and biosensors for monitoring the concentration of C-reactive protein (CRP), temperature and pH in wounds. These three parameters can be used as qualitative biomarkers to assess the wound status and the effectiveness of therapy. CRP biosensors can be classified in: (a) field effect transistors, (b) optical immunosensors based on surface plasmon resonance, total internal reflection, fluorescence and chemiluminescence, (c) electrochemical sensors based on potentiometry, amperometry, and electrochemical impedance, and (d) piezoresistive sensors, such as quartz crystal microbalances and microcantilevers. The last section reports the most recent developments for wearable non-invasive temperature and pH sensors suitable for wound monitoring