Direct measurement of cardiac stiffness using echocardiographic shearwave imaging during open-chest surgery: A pilot study in human.

PURPOSE: Cardiac stiffness is a marker of diastolic function with a strong prognostic significance in many heart diseases that is not measurable in clinical practice. This study investigates whether elastometry, a surrogate for organ stiffness, is measurable in the heart using ShearWave Imaging. METHODS: In 33 anesthetized patients scheduled for cardiac surgery, ShearWave imaging was acquired epicardially using a dedicated ultrasound machine on the left ventricle parallel to the left anterior descending coronary artery in a loaded heart following the last cardiac beat. Cardiac elastometry was measured offline using the Young modulus with customized software. RESULTS: Overall, the ejection fraction was 61 ± 10%. E/A and E/e' ratios were 1.0 ± 0.5 and 10.5 ± 4.1, respectively. Cardiac elastometry averaged 15.3 ± 5.3 kPa with a median of 18 kPa. Patients with high elastometry >18 kPa were older (P = .04), had thicker (P = .02) but smaller LV (P = .004), had larger left atria (P = .05) and a higher BNP level (P = .04). We distinguished three different transmural elastometry patterns: higher epicardial, higher endocardial, or uniformly distributed elastometry. CONCLUSION: Elastometry measurement was feasible for the human heart. This surrogate for cardiac stiffness dichotomized patients with low and high elastometry, and provided three different phenotypes of transmural elastometry with link to diastolic function.

Position measurement/tracking comparison of the instrumentation in a droplet-actuated-robotic platform.

This paper reports our work on developing a surface tension actuated micro-robotic platform supported by three bubbles (liquid environment) or droplets (gaseous environment). The actuation principle relies on the force developed by surface tension below a millimeter, which benefits from scaling laws, and is used to actuate this new type of compliant robot. By separately controlling the pressure inside each bubble, three degrees of freedom can be actuated. We investigated three sensing solutions to measure the platform attitude in real-time (z-position of each droplet, leading to the knowledge of the z position and Θx and Θy tilts of the platform). The comparison between optical, resistive, and capacitive measurement principles is hereafter reported. The optical technique uses SFH-9201 components. The resistive technique involves measuring the electrical resistance of a path flowing through two droplets and the platform. This innovative technique for sensing table position combines three pairs of resistances, from which the resistance in each drop can be deduced, thus determining the platform position. The third solution is a more usual high frequency (~200 MHz) capacitive measurement. The resistive method has been proven reliable and is simple to implement. This work opens perspectives toward an interesting sensing solution for micro-robotic platforms.

Automatic trajectory control of single cells using dielectrophoresis based on visual feedback.

This paper deals with the automatic control of the trajectory of T-lymphocytes using dielectrophoretic (DEP) actuation. Dielectrophoresis is a physical phenomenon induced by a non-uniform electric field enabling application of a force on a dielectric object. In most of the cases, it is used in a passive way. The electric field is in a steady state and the force applied on the cells depends on the cell's characteristics and position inside the channel. These systems are limited as cells with similar characteristics will undergo the same forces. To overcome this issue, active devices where the electric field changes over time were developed. However, the voltages that should be applied to generate the desired electric field are mostly computed offline using finite element methods. Thus, there is a low number of devices using automatic approaches with dielectrophoretic actuation where the electric field is computed and updated in real time based on the current position of the cell. We propose here an experimental bench used to study the automatic trajectory control of cells by dielectrophoresis. The computation of the dielectrophoretic force is done online with a model based on the Fourier series depending on the cell's characteristics, position and electric field. This model allows the use of a controller based on visual feedback running at 120 Hz to control the position of cells inside a microfluidic chip. As cells are sensitive to the electric field, the controller limits the norm of the electric field while maximizing the gradient to maximize the DEP force. Experiments have been performed and T-lymphocytes were successfully steered along several types of trajectories at a speed of five times their size per second. The mean error along those trajectories is below 2 µm. The viability of the cells has been checked after the experiments and confirms that this active DEP actuation does not harm the cells.

Microfluidic device combining hydrodynamic and dielectrophoretic trapping for the controlled contact between single micro-sized objects and application to adhesion assays.

The understanding of cell-cell and cell-matrix interactions via receptor and ligand binding relies on our ability to study the very first events of their contact. Of particular interest is the interaction between a T cell receptor and its cognate peptide-major histocompatibility complex. Indeed, analyzing their binding kinetics and cellular avidity in large-scale low-cost and fast cell sorting would largely facilitate the access to cell-based cancer immunotherapies. We thus propose a microfluidic tool able to independently control two types of micro-sized objects, put them in contact for a defined time and probe their adhesion state. The device consists of hydrodynamic traps holding the first type of cell from below against the fluid flow, and a dielectrophoretic system to force the second type of object to remain in contact with the first one. First, the device is validated by performing an adhesion frequency assay between fibroblasts and fibronectin coated beads. Then, a study is conducted on the modification of the cellular environment to match the dielectrophoretic technology requirements without modifying the cell viability and interaction functionalities. Finally, we demonstrate the capability of the developed device to put cancer cells and a population of T cells in contact and show the discrimination between specific and non-specific interactions based on the pair lifetime. This proof-of-concept device lays the foundations for the development of next generation fast cell-cell interaction technologies.

MiGriBot: A miniature parallel robot with integrated gripping for high-throughput micromanipulation.

Although robotic micromanipulation using microtweezers has been widely explored, the current manipulation throughput hardly exceeds one operation per second. Increasing the manipulation throughput is thus a key factor for the emergence of robotized microassembly industries. This article presents MiGriBot (Millimeter Gripper Robot), a miniaturized parallel robot with a configurable platform and soft joints, designed to perform pick-and-place operations at the microscale. MiGriBot combines in a single robot the benefits of a parallel kinematic architecture with a configurable platform and the use of soft joints at the millimeter scale. The configurable platform of the robot provides an internal degree of freedom that can be used to actuate microtweezers using piezoelectric bending actuators located at the base of the robot, which notably reduces the robot's inertia. The soft joints make it possible to miniaturize the mechanism and to avoid friction. These benefits enable MiGriBot to reach a throughput of 10 pick-and-place cycles per second of micrometer-sized objects, with a precision of 1 micrometer.

Dielectrophoretic Traps for Efficient Bead and Cell Trapping and Formation of Aggregates of Controlled Size and Composition.

We present a microfluidic dielectrophoretic-actuated system designed to trap chosen single-cell and form controlled cell aggregates. A novel method is proposed to characterize the efficiency of the dielectrophoretic trapping, considering the flow speed but also the heat generated by the traps as limiting criteria in cell-safe manipulation. Two original designs with different manufacturing processes are experimentally compared. The most efficient design is selected and the cell membrane integrity is monitored by fluorescence imaging to guarantee a safe-cell trapping. Design rules are suggested to adapt the traps to multiple-cells trapping and are experimentally validated as we formed aggregates of controlled size and composition with two different types of cells. We provide hereby a simple manufactured tool allowing the controlled manipulation of particles for the composition of multicellular assemblies.

Controlled transitions between metastable states of 2D magnetocapillary crystals.

Magnetocapillary interactions between particles allow to self-assemble floating crystals along liquid interfaces. For a fixed number of particles, different states possessing different symmetrical features, known as metastable states, coexist. In this paper, we demonstrate how to trigger the transition from one state to another, either by rearranging the crystal, or by controlling its growth. First, we show that externally controlled magnetic fields can squeeze the entire crystal to induce structural modifications, that upon relaxation can lead to a modified state. Second, we propose localized laser-induced thermocapillary flows that can be used to guide new particles towards an existing crystal in a desired direction, thus favoring a particular resulting state. The control of the formation of metastable states is a key ingredient to functionalize such assemblies, paving the way to self-assembled microrobots.

Path Planning for 3-D In-Hand Manipulation of Micro-Objects Using Rotation Decomposition.

Robotic manipulation and assembly of micro and nanocomponents in confined spaces is still a challenge. Indeed, the current proposed solutions that are highly inspired by classical industrial robotics are not currently able to combine precision, compactness, dexterity, and high blocking forces. In a previous work, we proposed 2-D in-hand robotic dexterous manipulation methods of arbitrary shaped objects that considered adhesion forces that exist at the micro and nanoscales. Direct extension of the proposed method to 3-D would involve an exponential increase in complexity. In this paper, we propose an approach that allows to plan for 3-D dexterous in-hand manipulation with a moderate increase in complexity. The main idea is to decompose any 3-D motion into a 3-D translation and three rotations about specific axes related to the object. The obtained simulation results show that 3-D in-hand dexterous micro-manipulation of arbitrary objects in presence of adhesion forces can be planned in just few seconds.

Positional dependence of particles and cells in microfluidic electrical impedance flow cytometry: origin, challenges and opportunities.

Microfluidic electrical impedance flow cytometry is now a well-known and established method for single-cell analysis. Given the richness of the information provided by impedance measurements, this non-invasive and label-free approach can be used in a wide field of applications ranging from simple cell counting to disease diagnostics. One of its major limitations is the variation of the impedance signal with the position of the cell in the sensing area. Indeed, identical particles traveling along different trajectories do not result in the same data. The positional dependence can be considered as a challenge for the accuracy of microfluidic impedance cytometers. On the other hand, it has recently been regarded by several groups as an opportunity to estimate the position of particles in the microchannel and thus take a further step in the logic of integrating sensors in so-called "Lab-on-a-chip" devices. This review provides a comprehensive overview of the physical grounds of the positional dependence of impedance measurements. Then, both the developed strategies to reduce position influence in impedance-based assays and the recent reported technologies exploiting that dependence for the integration of position detection in microfluidic devices are reviewed.

Control-oriented model of dielectrophoresis and electrorotation for arbitrarily shaped objects.

The most popular modeling approach for dielectrophoresis (DEP) is the effective multipole (EM) method. It approximates the polarization-induced charge distribution in an object of interest by a set of multipolar moments. The Coulombic interaction of these moments with the external polarizing electric field then gives the DEP force and torque acting on the object. The multipolar moments for objects placed in arbitrary harmonic electric fields are, however, known only for spherical objects. This shape restriction significantly limits the use of the EM method. We present an approach for online (in real time) computation of multipolar moments for objects of arbitrary shapes having even arbitrary internal composition (inhomogeneous objects, more different materials, etc.). We exploit orthonormality of spherical harmonics to extract the multipolar moments from a numerical simulation of the polarized object. This can be done in advance (offline) for a set of external electric fields forming a basis so that the superposition principle can then be used for online operation. DEP force and torque can thus be computed in fractions of a second, which is needed, for example, in model-based control applications. We validate the proposed model against reference numerical solutions obtained using Maxwell stress tensor. We also analyze the importance of the higher-order multipolar moments using a sample case of a Tetris-shaped micro-object placed inside a quadrupolar microelectrode array and exposed to electrorotation. The implementation of the model in Matlab and Comsol is offered for free download.

Cinemotion, a Program of Cognitive Remediation to Improve the Recognition and Expression of Facial Emotions in Schizophrenia: A Pilot Study.

Objective: Patients with schizophrenia exhibit impaired social cognition, especially in the recognition and expression of facial emotions, aspects of communication profoundly interlinked in an embodied approach of cognition. Nevertheless, many training programs have been developed that focus on either of these deficits but not both. We therefore designed a training program, Cinemotion, intended to remedy the 2 deficits and investigated its feasibility and effects in patients with schizophrenia. Design: Thirty-one patients undergoing treatment for schizophrenia and presenting deficit in emotion recognition were randomized to a group of 16 to undergo Cinemotion training, delivered in weekly group sessions, and to a control treatment group of 15. At the conclusion of training or after 10 weeks in controls, we reassessed and compared original and final results to determine improvement. Methods: Facial emotions recognition (TREF), empathy (Questionnaire of Cognitive and Affective Empathy, QCAE), and attributional style (Ambiguous Intentions Hostility Questionnaire, AIHQ) were assessed before (T0) and after (T1) the program. External evaluators also assessed ability and accuracy of Cinemotion participants to self-generate facial emotion expression in response to verbal instruction. Results: Between T0 and T1, Cinemotion participants significantly improved total TREF, sadness, disgust, and anger scores, compared to findings in control treatment group. They also improved their ability and accuracy to self-generate facial expressions, especially sadness and fear, with no significant improvement in other components of social recognition. Conclusions: Our findings show the apparent efficacy of training using the Cinemotion program to improve the recognition and expression of facial emotions in schizophrenia.

Analytical Formulation of the Electric Field Induced by Electrode Arrays: Towards Automated Dielectrophoretic Cell Sorting.

Dielectrophoresis is defined as the motion of an electrically polarisable particle in a non-uniform electric field. Current dielectrophoretic devices enabling sorting of cells are mostly controlled in open-loop applying a predefined voltage on micro-electrodes. Closed-loop control of these devices would enable to get advanced functionalities and also more robust behavior. Currently, the numerical models of dielectrophoretic force are too complex to be used in real-time closed-loop control. The aim of this paper is to propose a new type of models usable in this framework. We propose an analytical model of the electric field based on Fourier series to compute the dielectrophoretic force produced by parallel electrode arrays. Indeed, this method provides an analytical expression of the electric potential which decouples the geometrical factors (parameter of our system), the voltages applied on electrodes (input of our system), and the position of the cells (output of our system). Considering the Newton laws on each cell, it enables to generate easily a dynamic model of the cell positions (output) function of the voltages on electrodes (input). This dynamic model of our system is required to design the future closed-loop control law. The predicted dielectrophoretic forces are compared to a numerical simulation based on finite element model using COMSOL software. The model presented in this paper enables to compute the dielectrophoretic force applied to a cell by an electrode array in a few tenths of milliseconds. This model could be consequently used in future works for closed-loop control of dielectrophoretic devices.

Adhesion control for micro- and nanomanipulation.

The adhesion between a micro/nano-object and a microgripper end-effector is an important problem in micromanipulation. Canceling or reducing this force is a great challenge. This force is directly linked to the surface chemical structure of the object and the gripper. We propose to predict this force between a structuring surface and a micro-object with a multisphere van der Waals force model. The surface was structured by polystyrene latex particles (PS particles) with radii from 35 to 2000 nm. The model was compared with experimental pull-off force measurements performed by AFM with different natures of spheres materials glued on the tipless. A wide range of applications, in the field of telecommunications, bioengineering, and more generaly speaking MEMS can be envisaged for these substrates.

Reducing the adhesion between surfaces using surface structuring with PS latex particle.

The adhesion between a micro-object and a microgripper end-effector is an important problem in micromanipulation. Canceling or reducing this force is a great challenge. This force is directly linked to the surface chemical structure of the object and the gripper. We propose to reduce the adhesion force by using a self-assembled monolayer structuring on one surface. The surface was structured by polystyrene latex particles (PS particles) with radii from 100 to 1500 nm. The adhesion force measurements obtained by AFM were compared to a multisphere van der Waals force model. The model suggests the existence of an optimal value of the sphere radius which minimizes the adhesion. In that case, the pull-off force is reduced to 20 nN by the PS particles layer with a radius of 45 nm. A wide range of applications in the field of telecommunications, bioengineering, and more generally speaking, MEMS can be envisaged for these substrates.

Adhesion forces controlled by chemical self-assembly and pH: application to robotic microhandling.

Robotic microhandling is a promising way to assemble microcomponents in order to manufacture a new generation of hybrid microelectromechanical systems. However, at the scale of several micrometers, the adhesion phenomenon highly perturbs the micro-object release and positioning. This phenomenon is directly linked to both the object and the gripper surface chemical composition. We propose to control the adhesion by using a chemical self-assembled monolayer on both surfaces. Different types of chemical functionalization have been tested, and this paper focuses on the presentation of aminosilane-grafted 3-(ethoxydimethylsilyl)propylamine and (3-aminopropyl)triethoxysilane. We show that the liquid pH can be used to modify the adhesion and to switch from an attractive behavior to a repulsive behavior. The pH control can thus be used to increase the adhesion during handling and cancel the adhesion during release. Experiments have shown that the pH control is able to control the release of a micro-object. This paper shows the relevance of a new type of reliable submerged robotic microhandling principle, which is based on adjustment of the chemical properties of the liquid.