This paper describes an haptic system designed to vary the stiffness of threecontact points in an independent and controllable fashion, by suitably regulating the inner pressure of three pneumatic tactile displays. At the same time, the contact forces exerted by the user are measured by six degree-of-freedom force sensors placed under each finger. This device might be profitably used in hand rehabilitation and humangraspingstudies. We report and discuss preliminary results on device validation as well as some illustrative measurement examples.
More meaningful in-vitro models which simulate the physiological conditions of native tissue are becoming essential in the pharmaceutical field, for early and rapid screening of drug candidates. Here, we describe a multi-organ-on-plate system based on single and double flow mini bioreactor modules for dynamic in-vitro studies of intestinal drug absorption, drug metabolism and more relevant toxicity studies. The double flow module for membrane culture was firstly characterized using computational fluid dynamic models and measurements of pressure gradients, in order to indentify the optimal flow rates for maximizing the passage of solutes through the membrane. Then, cell culture experiments were performed with fully differentiated Caco-2 cells seeded on the semi-permeable membrane as a dynamic model of the intestinal epithelium, connected to a single flow chamber with metabolically competent human upcyte® hepatocytes (Medicyte GmbH, Germany) seeded on a 3D collagen cryogel. First we assessed the role of flow in modulating the passage of compounds across the epithelial barrier. Then toxicity tests were performed by administering different concentrations of hepatotoxic compounds (i.e. Diclofenac, Nimesulide, industrial nanoparticles) in the apical compartment of the MB, compared the data with cell cultures in transwells. Our results show: i) the presence of flow significantly increases translocation of all molecules tested across the membrane, ii) flow conditioned Caco-2 cells are more permeable to small hydrophilic compounds, despite having high TEER values iii) although they display higher levels of phenotypic markers (tight junctions, albumin expression etc), cells in the system are more susceptible to drug induced toxicity. In conclusion, the multi-organ-on-plate system predicts drug adsorption and toxicity better than traditional cell cultures and could be used to reduce, refine and eventually replace animal tests.
New relevant in-vitro models are priorities in pharmaco-toxicology, cosmetic and food research to reduce the animal tests. Therefore, invivo models show ethical issues, are not time and cost effective and are progressively showing scientific limitations: for instance they fail in detection of pathogens that are species specific (Mazzoleni et al., 2009). The search of more relevant pre-clinical models forced the researcher to move from 2D to 3D in-vitro models in order to maintain the phenotype of cells (Lovit et al., 2013; Mattei et al., 2014). Even if the significant progress in material science, the metabolic requirement of 3D tissues is higher than a 2D culture and the scaffold is a limitation in nutrients transport. Dynamic cell culture chambers are then required to assure the gas/nutrient supply, waste elimination, mechanical stimulation of cells, study of cross talk between different tissues and real time monitoring of cells. Nowadays the only systems that meet all these specifications are the Ivtech technologies. Ivtech is an innovative Italian start-up that grows up to solve the needs of in-vitro experts, offering and customizing several type of transparent, dynamic and modular cell culture systems, organizing workshops and training. The goal is to expand the 3D approach and permits a significant evolution towards highly relevant in-vitro models.
Advanced systems based on bioreactors and scaffolds are an essential step towards the development of more predictive and ethical alternatives to animal experiments. Size, modularity, automation, monitoring and essential design are crucial because these elements will ease the transition from old technology and accelerate their acceptance into mainstream research. Based on these requirements, the interconnected transparent sensorised “lego†bioreactors designed in our labs have been used to generate physiologically relevant disease and toxicity models which recapitulate systemic responses impossible to observe in standard cell cultures. The disease model is an interconnected bioreactor circuit with i) adipose tissue in 3D in 3 different concentrations representing normo-weight, over weight and obese body mass indices, ii) human hepatocytes on porous collagen scaffolds and iii) monolayers of human endothelial cells. High adiposity and elevated glucose levels induce systemic and endothelial inflammation in the circuit, as observed in overweight and diabetic humans (Iori et al., 2012). Using similar technology a three-tissue circuit for monitoring the absorption, distribution, metabolism and toxicity of nanoparticles was developed in the context of the EU project InLiveTox (Ucciferri et al., 2014). The results were strikingly similar to those observed in animal experiments demonstrating that the dynamic 3D in-vitro models are ethical, meaningful and economically viable replacements.
In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro- and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described.
Permeability studies across epithelial barriers are of primary importance in drug delivery as well as in toxicology. However, traditional in vitro models do not adequately mimic the dynamic environment of physiological barriers. Here, we describe a novel two-chamber modular bioreactor for dynamic in vitro studies of epithelial cells. The fluid dynamic environment of the bioreactor was characterized using computational fluid dynamic models and measurements of pressure gradients for different combinations of flow rates in the apical and basal chambers. Cell culture experiments were then performed with fully differentiated Caco-2 cells as a model of the intestinal epithelium, comparing the effect of media flow applied in the bioreactor with traditional static transwells. The flow increases barrier integrity and tight junction expression of Caco-2 cells with respect to the static controls. Fluorescein permeability increased threefold in the dynamic system, indicating that the stimulus induced by flow increases transport across the barrier, closely mimicking the in vivo situation. The results are of interest for studying the influence of mechanical stimuli on cells, and underline the importance of developing more physiologically relevant in vitro tissue models. The bioreactor can be used to study drug delivery, chemical, or nanomaterial toxicity and to engineer barrier tissues.
In cardiac tissue engineering, the use of bioreactors is fundamental for applying controlled mechanical stimuli on the cells and recreate a physiological environment for cardiomyocytes cultures. This work is focused on an innovative Sensorized Squeeze PRessure (S2PR) bioreactor, able to apply a periodic contactless hydrodynamic pressures on 3D porous constructs. The fluid-dynamic environment inside the bioreactor was fully characterized using computational models, focusing on the pressures and fluid velocity profiles generated in the porous scaffold during the cyclic stimulation.
Patients affected by motor disorders of the hand and having residual voluntary movements of fingers or wrist can benefit from self-rehabilitation exercises performed with so-called dynamic hand splints. These systems consist of orthoses equipped with elastic cords or springs, which either provide a sustained stretch or resist voluntary movements of fingers or wrist. These simple systems are limited by the impossibility of modulating the mechanical stiffness. This limitation does not allow for customizations and real-time control of the training exercise, which would improve the rehabilitation efficacy. To overcome this limitation, 'active' orthoses equipped with devices that allow for electrical control of the mechanical stiffness are needed. Here, we report on a solution that relies on compact and light-weight electroactive elastic transducers that replace the passive elastic components. We developed a variable-stiffness transducer made of dielectric elastomers, as the most performing types of electromechanically active polymers. The transducer was manufactured with a silicone film and tested with a purposely-developed stiffness control strategy that allowed for electrical modulations of the force-elongation response. Results showed that the proposed new technology is a promising and viable solution to develop electrically controllable dynamic hand orthoses for hand rehabilitation. ? 2013 IPEM.
We describe here a wearable, wireless, compact, and lightweight tactile display, able to mechanically stimulate the fingertip of users, so as to simulate contact with soft bodies in virtual environments. The device was based on dielectric elastomer actuators, as high-performance electromechanically active polymers. The actuator was arranged at the user’s fingertip, integrated within a plastic case, which also hosted a compact high-voltage circuitry. A custom-made wireless control unit was arranged on the forearm and connected to the display via low-voltage leads. We present the structure of the device and a characterization of it, in terms of electromechanical response and stress relaxation. Furthermore, we present results of a psychophysical test aimed at assessing the ability of the system to generate different levels of force that can be perceived by users.
"There is a time to be born, and a time to die; a time to break down, and a time to build up; a time to weep, and a time to laugh; a time to keep silence, and a time to speak" (Ecclesiastes 3, 2?7). There was a time when automata were designed like clocks. Androids will have the time of their creators, the state of the art in technology, a wealth of experience to draw from, as well as the capacity to carry out actions as being endowed with meaning. The machine will undergo a long period of nurturing, from which it will learn to shape some sort of identity.
Exploiting hand kinematic synergies and wearable under-sensing for hand functional grasp recognition
Publication Type
Conference Paper
Year of Publication
2014
Conference Name
4th International Conference on Wireless Mobile Communication and Healthcare - "Transforming healthcare through innovations in mobile and wireless technologies"
Despite some prematurely optimistic claims, the ability of robots to grasp general objects in unstructured environments still remains far behind that of humans. This is not solely caused by differences in the mechanics of hands: indeed, we show that human use of a simple robot hand (the Pisa/IIT SoftHand) can afford capabilities that are comparable to natural grasping. It is through the observation of such human-directed robot hand operations that we realized how fundamental in everyday grasping and manipulation is the role of hand compliance, which is used to adapt to the shape of surrounding objects. Objects and environmental constraints are in turn used to functionally shape the hand, going beyond its nominal kinematic limits by exploiting structural softness. In this paper, we set out to study grasp planning for hands that are simple — in the sense of low number of actuated degrees of freedom (one for the Pisa/IIT SoftHand) — but are soft, i.e. continuously deformable in an infinity of possible shapes through interaction with objects. After general considerations on the change of paradigm in grasp planning that this setting brings about with respect to classical rigid multi-dof grasp planning, we present a procedure to extract grasp affordances for the Pisa/IIT SoftHand through physically accurate numerical simulations. The selected grasps are then successfully tested in an experimental scenario.
Virtual Reality (VR) is increasingly being used in combination with psycho-physiological measures to improve assessment of distress in mental health research and therapy. However, the analysis and interpretation of multiple physiological measures is time consuming and requires specific skills, which are not available to most clinicians. To address this issue, we designed and developed a Decision Support System (DSS) for automatic classification of stress levels during exposure to VR environments. The DSS integrates different biosensor data (ECG, breathing rate, EEG) and behavioral data (body gestures correlated with stress), following a training process in which self-rated and clinical-rated stress levels are used as ground truth. Detected stress events for each VR session are reported to the therapist as an aggregated value (ranging from 0 to 1) and graphically displayed on a diagram accessible by the therapist through a web-based interface.
XIM-Engine: a software framework to support the development of interactive applications that uses conscious and unconscious reactions in immersive mixed reality
The development of systems that allow multimodal interpretation of human-machine interaction is crucial to advance our understanding and validation of theoretical models of user behavior. In particular, a system capable of collecting, perceiving and interpreting unconscious behavior can provide rich contextual information for an interactive system. One possible application for such a system is in the exploration of complex data through immersion, where massive amounts of data are generated every day both by humans and computer processes that digitize information at different scales and resolutions thus exceeding our processing capacity. We need tools that accelerate our understanding and generation of hypotheses over the datasets, guide our searches and prevent data overload. We describe XIM- engine, a bio-inspired software framework designed to capture and analyze multi-modal human behavior in an immersive environment. The framework allows performing studies that can advance our understanding on the use of conscious and unconscious reactions in interactive systems.
This paper presents the first step toward the study of minimum timetrajectories for a differentialdrive robot, which is equipped with a fixed and limited Field-Of-View (FOV) camera, towards a desired configuration while keeping a given landmark in sight during maneuvers. While several previous works have provided a complete synthesis of shortest paths in case of both nonholonomic and FOV constraints, to the best of our knowledge, this paper represents the first analysis of minimum timetrajectories with the two constraints. After showing the extremals of the problem at hand, i.e. straight lines, rotations on the spot, logarithmic spirals and involute of circles, we provide the optimal control laws that steer the vehicle along the path and the cost in terms of time along each extremal. Moreover, we compare some concatenations of extremals in order to reduce the complexity of the problem toward the definition of a sufficient finite set of optimal maneuvers.
Collagen-gelatin-genipin-hydroxyapatite composite scaffolds colonized by human primary osteoblasts are suitable for bone tissue engineering applications: In vitro evidences
The objective of the EU project INTERACTION is to develop an unobtrusive and modular sensing system for objective monitoring of daily-life motor performance of stroke survivors. This will enable clinical professionals to advise their patients about their continued daily-life activity profile and home training, and evaluate and optimize rehabilitation programs.A modular textile-integrated sensing system was developed and performance and capacity measures were proposed and clinically tested in stroke subject.Telemonitoring facilities were developed and tested. In the last stage of the project, the system will be tested during daily-life.
