Shadi Karimi

The correct interpretation of threat and reward is important for animal survival. Often, the decisions underlying these behavioral programs are mediated by volatile compounds in the animal's environment, which they detect and discriminate with specialized olfactory neurons along their body. Caenorhabditis (C.) elegans senses chemical stimuli with neurons located in the head and the tail of the animal, which mediate either attractive or aversive behaviors. How conflicting stimuli are processed in animals navigating different chemical gradients is poorly understood. Here, we conceived, created, and capitalized on a novel microfluidic device to enable automated and precise stimulation of head and tail neurons, either simultaneously or sequentially, while reading out neuronal activity in sensory and interneurons using genetically encoded calcium indicators. We achieve robust and programmable chemical pulses through the modulation of inlet pressures. To evaluate the device performance, we synchronized the flow control with microscopy data acquisition and characterized the flow properties in the fabricated devices. Together, our design has the potential to provide insight into the neural circuits and behavior of C. elegans simulating the experience of natural environments.

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.

How sensory perception is processed by the two sexes of an organism is still only partially understood. Despite some evidence for sexual dimorphism in auditory and olfactory perception, whether touch is sensed in a dimorphic manner has not been addressed. Here we find that the neuronal circuit for tail mechanosensation in C. elegans is wired differently in the two sexes and employs a different combination of sex-shared sensory neurons and interneurons in each sex. Reverse genetic screens uncovered cell- and sex-specific functions of the alpha-tubulin mec-12 and the sodium channel tmc-1 in sensory neurons, and of the glutamate receptors nmr-1 and glr-1 in interneurons, revealing the underlying molecular mechanisms that mediate tail mechanosensation. Moreover, we show that only in males, the sex-shared interneuron AVG is strongly activated by tail mechanical stimulation, and accordingly is crucial for their behavioral response. Importantly, sex reversal experiments demonstrate that the sexual identity of AVG determines both the behavioral output of the mechanosensory response and the molecular pathways controlling it. Our results present for the first time extensive sexual dimorphism in a mechanosensory circuit at both the cellular and molecular levels.

Microfluidic paper-based analytical devices (µPADs) are a promising technology to enable accurate and quantitative in situ assays. Paper’s inherent hydrophilicity drives the fluids without the need for external pressure sources. However, controlling the flow in the porous medium has remained a challenge. This study addresses this problem from the nature of the paper substrate and its design. A computational fluid dynamic model has been developed, which couples the characteristics of the porous media (fiber length, fiber diameter and porosity) to the fluidic performance of the diffusion-based µPAD sensor. The numerical results showed that for a given porous membrane, the diffusion, and therefore the sensor performance is affected not only by the substrate nature but also by the inlets’ orientation. Given a porous substrate, the optimum performance is achieved by the lowest inlets’ angle. A diffusion-based self-referencing colorimetric sensor was built and validated according to the design. The device is able to quantify the hydronium concentration in wines by comparison to 0.1–1.0 M tartaric acid solutions with a 41.3 mM limit of detection. This research showed that by proper adjustments even the simplest µPADs can be used in quantitative assays for agri-food applications.

Micro Electro Mechanical Systems (MEMS) and microfluidic devices have found numerous applications in the industrial sector. However, they require a fast, cost-effective and reliable manufacturing process in order to compete with conventional methods. Particularly, at the sub-micron scale, the manufacturing of devices are limited by the dimensional complexity. A proper bonding and stiction prevention of these sub-micron channels are two of the main challenges faced during the fabrication process of low aspect ratio channels. Especially, in the case of using flexible materials such as polydimethylsiloxane (PDMS). This study presents a direct laser microfabrication method of sub-micron channels using an infrared (IR) ultrashort pulse (femtosecond), capable of manufacturing extremely low aspect ratio channels. These microchannels are manufactured and tested varying their depth from 0.5 μ m to 2 μ m and width of 15, 20, 25, and 30 μ m. The roughness of each pattern was measured by an interferometric microscope. Additionally, the static contact angle of each depth was studied to evaluate the influence of femtosecond laser fabrication method on the wettability of the glass substrate. PDMS, which is a biocompatible polymer, was used to provide a watertight property to the sub-micron channels and also to assist the assembly of external microfluidic hose connections. A 750 nm depth watertight channel was built using this methodology and successfully used as a blood plasma separator (BPS). The device was able to achieve 100% pure plasma without stiction of the PDMS layer to the sub-micron channel within an adequate time. This method provides a novel manufacturing approach useful for various applications such as point-of-care devices.

A passive portable microfluidic blood–plasma separator for simultaneous determination of direct and indirect ABO/Rh blood typing.

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-effective 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 µL 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 time.

A novel type of spiral micromixer with expansion and contraction parts is presented in order to enhance the mixing quality in the low Reynolds number regimes for point-of-care tests (POCT). Three classes of micromixers with different numbers of loops and modified geometries were studied. Numerical simulation was performed to study the flow behavior and mixing performance solving the steady-state Navier–Stokes and the convection-diffusion equations in the Reynolds range of 0.1–10.0. Comparisons between the mixers with and without expansion parts were made to illustrate the effect of disturbing the streamlines on the mixing performance. Image analysis of the mixing results from fabricated micromixers was used to verify the results of the simulations. Since the proposed mixer provides up to 92% of homogeneity at Re 1.0, generating 442 Pa of pressure drop, this mixer makes a suitable candidate for research in the POCT field.

A novel single-layer passive mixer is designed which takes advantage of gradually increasing the radius of curvature of a spiral micro mixer.