Synthetic and Bio-Artificial Tactile Sensing: A Review
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paper_title: Effects of the elastic cover on tactile sensor arrays

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Tactile sensors are composed of two substantial parts, the sensory structure and its cover. The characteristics of a sensor are fundamentally set by the sensor design, but are also essentially modified by the elastic cover on top. In this paper we analyze the pure mechanical information-coding effects of the sheltering rubber layer, applied on single-crystalline silicon 3D-force sensors, capable to detect both normal and shear forces. We give instructions on how to enhance the sensor's sensitivity by mimicking human tactile perception with introducing hair- and fingerprint-like elements to the sensor design.
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paper_title: Biomimetic Tactile Sensor Array

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The performance of robotic and prosthetic hands in unstructured environments is severely limited by their having little or no tactile information compared to the rich tactile feedback of the human ...
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paper_title: The Role of Exploratory Conditions in Bio-Inspired Tactile Sensing of Single Topogical Features

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We investigate the mechanism of tactile transduction during active exploration of finely textured surfaces using a tactile sensor mimicking the human fingertip. We focus in particular on the role of exploratory conditions in shaping the subcutaneous mechanical signals. The sensor has been designed by integrating a linear array of MEMS micro-force sensors in an elastomer layer. We measure the response of the sensors to the passage of elementary topographical features at constant velocity and normal load, such as a small hole on a flat substrate. Each sensor’s response is found to strongly depend on its relative location with respect to the substrate/skin contact zone, a result which can be quantitatively understood within the scope of a linear model of tactile transduction. The modification of the response induced by varying other parameters, such as the thickness of the elastic layer and the confining load, are also correctly captured by this model. We further demonstrate that the knowledge of these characteristic responses allows one to dynamically evaluate the position of a small hole within the contact zone, based on the micro-force sensors signals, with a spatial resolution an order of magnitude better than the intrinsic resolution of individual sensors. Consequences of these observations on robotic tactile sensing are briefly discussed.
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paper_title: The role of fingerprints in the coding of tactile information probed with a biomimetic sensor

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In humans, the tactile perception of fine textures (spatial scale<200 micrometers) is mediated by skin vibrations generated as the finger scans the surface. To establish the relationship between texture characteristics and subcutaneous vibrations, a biomimetic tactile sensor has been designed whose dimensions match those of the fingertip. When the sensor surface is patterned with parallel ridges mimicking the fingerprints, the spectrum of vibrations elicited by randomly textured substrates is dominated by one frequency set by the ratio of the scanning speed to the interridge distance. For human touch, this frequency falls within the optimal range of sensitivity of Pacinian afferents, which mediate the coding of fine textures. Thus, fingerprints may perform spectral selection and amplification of tactile information that facilitate its processing by specific mechanoreceptors.
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paper_title: Coding and use of tactile signals from the fingertips in object manipulation tasks

paper_content:

During object manipulation tasks, the brain selects and implements action-phase controllers that use sensory predictions and afferent signals to tailor motor output to the physical properties of the objects involved. Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.
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paper_title: Roughness Encoding in Human and Biomimetic Artificial Touch: Spatiotemporal Frequency Modulation and Structural Anisotropy of Fingerprints

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The influence of fingerprints and their curvature in tactile sensing performance is investigated by comparative analysis of different design parameters in a biomimetic artificial fingertip, having straight or curved fingerprints. The strength in the encoding of the principal spatial period of ridged tactile stimuli (gratings) is evaluated by indenting and sliding the surfaces at controlled normal contact force and tangential sliding velocity, as a function of fingertip rotation along the indentation axis. Curved fingerprints guaranteed higher directional isotropy than straight fingerprints in the encoding of the principal frequency resulting from the ratio between the sliding velocity and the spatial periodicity of the grating. In parallel, human microneurography experiments were performed and a selection of results is included in this work in order to support the significance of the biorobotic study with the artificial tactile system.
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paper_title: Contact stability for two-fingered grasps

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Two types of grasp stability, spatial grasp stability and contact grasp stability, each with a different concept of the state of a grasp, are distinguished and characterized. Examples are presented to show that spatial stability cannot capture certain intuitive concepts of grasp stability and hence that any full understanding of grasp stability must include contact stability. A model of how the positions of the points of contact evolve in time on the surface of a grasped object in the absence of any external force or active feedback is then derived. From the model, a general measure of the contact stability of any two-fingered grasp is obtained. Finally, the consequences of this stability measure and a related measure of contact manipulability on strategies for grasp selection are discussed. >
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paper_title: The Uncanny Valley and the Search for Human Skin-Like Materials for a Prosthetic Fingertip

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The "Uncanny Valley", introduced nearly 40 years ago, has found its way through the mainstream robotics design theories. For the lack of soft tissue, warmth and poor controls, prosthetic hands were classified near the bottom of the "valley". Prosthetic hand designers were cautioned not to cross the "valley" by suggesting that prosthetic hands be made of wood, keep its natural wooden color and ignore features like the fingerprints to create elegant/fashionable prosthetic hands. This paper analyzes the feasibility of these suggestions from the "Uncanny Valley" in light of the recent trends in prosthetic hand design and the psychosocial studies regarding the impact of amputation to the lives of the patients. A bio-inspired materials selection method is suggested that points to an opposite direction from the "valley".
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paper_title: Soft materials for robotic fingers

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Three potential problems exist in multifingered hands. The impact forces that result during each instant of grasping a rigid object can affect the functioning of the finger tip sensor. A hand with hard fingers cannot securely grasp objects that have uneven surfaces due to the poor conformability of the fingers. Repetitive strains are induced into the fingers throughout manipulation task. Carefully chosen materials-plastic, rubber sponge, a fine powder, a paste, and a gel-were experimentally compared for their ability to overcome these three problems. Results showed that sponge is the most suitable and plastic is the least suitable for the application. For practical reasons, however, the gel was a good compromise over the sponge. It is recommended that future robotic hands constitute a soft finger or at least fingers with soft tips, constructed out of carefully chosen materials. >
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paper_title: Tactile Sensing—From Humans to Humanoids

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Starting from human ?sense of touch,? this paper reviews the state of tactile sensing in robotics. The physiology, coding, and transferring tactile data and perceptual importance of the ?sense of touch? in humans are discussed. Following this, a number of design hints derived for robotic tactile sensing are presented. Various technologies and transduction methods used to improve the touch sense capability of robots are presented. Tactile sensing, focused to fingertips and hands until past decade or so, has now been extended to whole body, even though many issues remain open. Trend and methods to develop tactile sensing arrays for various body sites are presented. Finally, various system issues that keep tactile sensing away from widespread utility are discussed.
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paper_title: Relationship between the Structure of Human Finger Tissue and the Location of Tactile Receptors.

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There are several tactile receptors in the tissue of human fingers.In this study we calculate in detail the deformation of finger tissue when a finger comes into contact with a rigid plate using a FE(finite element)model to clarify the reason for the precise location of the receptors.The FE model is constructed using measured geometry and meterial properties.As a result, we found that the strain energy is concentrated at the tactile receptor locations.When a frictional force is applied, the stress / strain is concentrated near the edge of the contact area.By calculating the stress / strain distribution using models with / without epidermal ridges / papillae, we found that the shape of the epidermal ridges / papillae influences the stress / strain distribution near the tactile receptors.
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paper_title: Neural coding mechanisms in tactile pattern recognition: the relative contributions of slowly and rapidly adapting mechanoreceptors to perceived roughness.

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Tactile pattern recognition depends on form and texture perception. A principal dimension of texture perception is roughness, the neural coding of which was the focus of this study. Previous studies have shown that perceived roughness is not based on neural activity in the Pacinian or cutaneous slowly adapting type II (SAII) neural responses or on mean impulse rate or temporal patterning in the cutaneous slowly adapting type I (SAI) or rapidly adapting (RA) discharge evoked by a textured surface. However, those studies found very high correlations between roughness scaling by humans and measures of spatial variation in SAI and RA firing rates. The present study used textured surfaces composed of dots of varying height (280-620 micron) and diameter (0.25-2.5 mm) in psychophysical and neurophysiological experiments. RA responses were affected least by the range of dot diameters and heights that produced the widest variation in perceived roughness, and these responses could not account for the psychophysical data. In contrast, spatial variation in SAI impulse rate was correlated closely with perceived roughness over the whole stimulus range, and a single measure of SAI spatial variation accounts for the psychophysical data in this (0.974 correlation) and two previous studies. Analyses based on the possibility that perceived roughness depends on both afferent types suggest that if the RA response plays a role in roughness perception, it is one of mild inhibition. These data reinforce the hypothesis that SAI afferents are mainly responsible for information about form and texture whereas RA afferents are mainly responsible for information about flutter, slip, and motion across the skin surface.
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paper_title: Human tactile perception as a standard for artificial tactile sensing—a review

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In this paper, we examine the most important features of human skin tactile properties with special emphasis on the characteristics which are vital in the design of artificial systems. Contrary to the visual and auditory senses, the touch signal is not a well-defined quantity. As a result, the researchers of this field are still dealing with the basics of collecting the most relevant data. Following this, mimicking the sense of touch by producing artificial tactile skin is a challenging process. Although the sense of touch is widely distributed all over the human body, the tactile perception in the human hand is of great importance in terms of surgical and medical robotics applications. In this study, the role of various mechanoreceptors in the human hand, such as, RA, SA I, SA II, and PC units are discussed in relation to the stimuli like force, position, softness, and surface texture. Taking human hand as a suitable tactile model, the necessary engineering features of an artificial tactile sensor, such as, spatial and temporal resolutions, force sensitivity, and linearity, are being reviewed. In this work, we also report on the current and possible future applications of tactile sensors in various surgical procedures. Copyright © 2004 Robotic Publications Ltd.
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paper_title: Tactile sensibility in the human hand: relative and absolute densities of four types of mechanoreceptive units in glabrous skin.

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1. Single unit impulses were recorded with percutaneously inserted tungsten needle electrodes from the median nerve in conscious human subjects. 2. A sample of 334 low threshold mechanoreceptive units innervating the glabrous skin area of the hand were studied. In accordance with earlier investigations, the units were separated into four groups on the basis of their adaptation and receptive field properties: RA, PC, SA I and SA II units. 3. The locations of the receptive fields of individual units were determined and the relative unit densities within various skin regions were calculated. The over-all density was found to increase in the proximo-distal direction. There was a slight increase from the palm to the main part of the finger and an abrupt increase from the main part of the finger to the finger tip. The relative densities in these three regions were 1, 1.6, 4.2. 4. The differences in over-all density were essentially accounted for by the two types of units characterized by small and well defined receptive fields, the RA and SA I units, whereas the PC and SA II units were almost evenly distributed over the whole glabrous skin area. 5. The spatial distribution of densities supports the idea that the RA and SA I units account for spatial acuity in psychophysical tests. This capacity is known to increase in distal direction along the hand. 6. On the basis of histological data regarding the number of myelinated fibres in the median nerve, a model of the absolute unit density was proposed. It was estimated that the density of low threshold mechanoreceptive units at the finger tip is as high as 241 u./cm2, whereas in the palm it is only 58 u./cm2.
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paper_title: Properties of cutaneous mechanoreceptors in the human hand related to touch sensation

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Summary. Recordings from single peripheral nerve fibres made it possible to analyse the functional properties of tac- tile afferent units supplying the glabrous skin of the human hand and to assess directly the relation between impulse dis- charge and perceptive experiences. The 17,000 tactile units in this skin area of the human hand are of four different types: two fast adapting types, FA I and FA I1 (formerly RA and PC), and two slowly adapting types, SA I and SA 11. The receptive field characteristics and the densities in the skin of the type I units (FA I and SA I) indicate that these account for the detailed spatial resolution that is of paramount im- portance for the motor skill and the explorative role of the hand. The relationship between the stimulus amplitude and perceived intensity during sustained skin indentations did not match the corresponding stimulus response functions of SA units suggesting non-linear transformations within the central nervous system. These transformations, in turn, appear to vary between subjects. A single impulse in a single FA I unit may be felt when originating from the most important tactile regions of the hand, indicating that the psychophysical detection may be set by the threshold of the sense organs. Moreover, no significant noise seems to be superimposed in the respective central sensory pathways.
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paper_title: Vibrotactile intensity and frequency information in the Pacinian system: A psychophysical model

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The objective of the study was to characterize the Pacinian representation of stimulus waveform. Subjects were presented with pairs of high-frequency vibrotactile stimuli that varied in intensity and/or frequency content and madesame—different judgments under conditions of low-frequency adaptation designed to minimize the contribution of the RA system. We wished to infer the nature of the information conveyed by the Pacinian system about the stimuli from measured sensitivity (d′) to stimulus differences. We first tested the hypothesis that the Pacinian system conveys only intensive information about vibratory stimuli and found that intensive cues could not account for much of the variance in the discrimination data. We then proposed a model characterizing the Pacinian-mediated representation of an arbitrary stimulus as a pattern of activation in a set of frequency-tuned minichannels. The model was shown to predict the discriminability of the stimulus pairs presented in the psychophysical experiments. Furthermore, the model parameters, optimized to fit the discrimination data, were compatible with analogous values obtained in other experimental contexts. One of the assumptions underlying the model is that information about individual spectral components is conveyed in parallel and quasi-independently. By simulating the response of a population of Pacinian afferents to a polyharmonic stimulus, we demonstrated that such a population can simultaneously convey information about multiple frequency components, despite having a homogeneous spectral profile.
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paper_title: SKIN MECHANORECEPTORS IN THE HUMAN HAND: RECEPTIVE FIELD CHARACTERISTICS

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Publisher Summary This chapter focuses on skin mechanoreceptors in the human hand. In a described in the chapter study, the subjects were healthy adults. Single-unit impulses were recorded from the median nerve. Well-controlled skin indentations were delivered with the stimulator. Triangular indentations with a slope of 4 mm/s were employed except for the PC units for which the velocity was 8 and 16 mm/s. The tip of the stimulus probe was 400 μm in diameter, and its contacting surface was rounded to a hemisphere. The receptive fields of single sensory units were mapped. Stimuli of constant displacement amplitude were delivered, while the position of the probe tip in the plane corresponding to the appropriate skin surface was traced with an X–Y-plotter. The results obtained in this study were in agreement with earlier reports regarding the glabrous skin mechanoreceptor units of primates showing that the RA and SA I units have small receptive fields with distinct borders, whereas the PC and SA II units have a single sensitive focus and receptive fields that are not sharply delimited.
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paper_title: Tactile Sensing—From Humans to Humanoids

paper_content:

Starting from human ?sense of touch,? this paper reviews the state of tactile sensing in robotics. The physiology, coding, and transferring tactile data and perceptual importance of the ?sense of touch? in humans are discussed. Following this, a number of design hints derived for robotic tactile sensing are presented. Various technologies and transduction methods used to improve the touch sense capability of robots are presented. Tactile sensing, focused to fingertips and hands until past decade or so, has now been extended to whole body, even though many issues remain open. Trend and methods to develop tactile sensing arrays for various body sites are presented. Finally, various system issues that keep tactile sensing away from widespread utility are discussed.
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paper_title: Mechanical transmission in a Pacinian corpuscle. An analysis and a theory

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1. An analysis is made of the transmission of mechanical forces through the Pacinian corpuscle. In particular, forces are analysed which produce pressure differences at the centre of the corpuscle and lead to excitation of the sensory nerve ending.2. The main structural elements in force transmission through the corpuscle are the lamellae, their interconnexions, and the interlamellar fluid. The two former provide the elastic elements and constraint for the fluid; and the latter, the viscous elements. The mechanical equivalent incorporating these elements is a system of dashpots (the lamellar surfaces and the interlamellar fluid) and springs (the lamellae and their interconnexions); it is a mechanical filter which suppresses low frequencies. The dynamic and static patterns of lamella displacements in the equivalent are in close agreement with those observed in Pacinian corpuscles.3. Steady-state and transient pressure fields were determined for the equivalent. Under static compression, only elastic forces exist in the corpuscle. Analysis shows that such forces are transmitted poorly from periphery to centre through the lamellated structure. The compliance of the lamellar interconnexions is so high in relation to that of the lamellae themselves, that most of the pressure load is carried by the outer lamellae. As a result, only a small fraction of the steady-state pressure at the outer surface reaches the centre of the corpuscle where the sensory ending is located. This is the mechanical basis of receptor adaptation.4. Under dynamic compression, viscous forces develop in the corpuscle; and these account for most of the pressure at times too early for development of elastic deformations. Analysis shows that such forces are transmitted well. For example, if a typical corpuscle of 500mu diameter is compressed by 20mu linearly during 2 msec, the pressure differences near to the centre of the corpuscle are initially as high as at the periphery, and stay within the same order throughout the process of compression. In general, pressure at the centre increases steeply with velocity of compression. This explains the marked velocity dependence of the generator response of the sensory ending.If, in the foregoing example, the 20mu compression is held fixed after 2 msec, the pressure differences at the centre fall abruptly to near zero with the onset of the static phase. The duration of pressure transients at the centre approximates that of the ;active' phase of the generator current of the sensory ending derived from experiments, as expected in a causal relationship: pressure difference --> generator current. Taken together with the earlier experimental finding of marked prolongation of generator response in corpuscles partially stripped of lamellae (Loewenstein & Mendelson, 1965), this result warrants the conclusion that the mechanical filter action of the corpuscle is the rate-limiting factor in generator response adaptation.5. When the corpuscle is released from compression, energy stored in the elastic elements during compression is released and consumed in viscous flow. Thus, viscous pressure is produced anew. The magnitude of this pressure depends on the velocity of release. The pressure distribution is rotated by 90 degrees with respect to that in compression; i.e. during release, compression occurs once again, but this time at right angles to the direction of initial compression. Experiments show that the sensory ending does not discriminate such a rotation; the polarity and order of magnitude of the generator response to compression in one plane are the same as in another. Analysis shows that considerable pressure differences may be developed at the centre of the corpuscle during releases at physiological velocities. For instance, in a passive return from a compression of 20mu, the pressure difference at the centre (and the generator current) is of the same order of magnitude as that in a compression of the velocity in 4. This accounts for the ;off'-response of the sensory ending in purely mechanical terms.
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paper_title: Factors Involved in Tactile Texture Perception Through Probes

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An understanding of texture perception by robotic systems can be gained by examining human texture perception through a probe. As with texture perception in direct touch with the finger, texture pe...
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paper_title: Encoding of Direction of Fingertip Forces by Human Tactile Afferents

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In most manipulations, we use our fingertips to apply time-varying forces to the target object in controlled directions. Here we used microneurography to assess how single tactile afferents encode ...
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paper_title: Coding and use of tactile signals from the fingertips in object manipulation tasks

paper_content:

During object manipulation tasks, the brain selects and implements action-phase controllers that use sensory predictions and afferent signals to tailor motor output to the physical properties of the objects involved. Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.
---
paper_title: Tactile Sensing—From Humans to Humanoids

paper_content:

Starting from human ?sense of touch,? this paper reviews the state of tactile sensing in robotics. The physiology, coding, and transferring tactile data and perceptual importance of the ?sense of touch? in humans are discussed. Following this, a number of design hints derived for robotic tactile sensing are presented. Various technologies and transduction methods used to improve the touch sense capability of robots are presented. Tactile sensing, focused to fingertips and hands until past decade or so, has now been extended to whole body, even though many issues remain open. Trend and methods to develop tactile sensing arrays for various body sites are presented. Finally, various system issues that keep tactile sensing away from widespread utility are discussed.
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paper_title: Biomimetic Tactile Sensor Array

paper_content:

The performance of robotic and prosthetic hands in unstructured environments is severely limited by their having little or no tactile information compared to the rich tactile feedback of the human ...
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paper_title: Development of a bioinspired MEMS based capacitive tactile sensor for a robotic finger

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Abstract This paper presents the development of a MEMS based capacitive tactile sensor intended to be incorporated into a tactile array as the core element of a biomimetic fingerpad. The use of standard microfabrication technologies in realising the device allowed a cost efficient fabrication involving only a few process steps. A low noise readout electronics system was developed for measuring the sensor response. The performance of both bare and packaged sensors was evaluated by direct probing of individual capacitive sensor units and characterising their response to load–unload indentation cycles.
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paper_title: A capacitive tactile sensor array for surface texture discrimination

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This paper presents a silicon MEMS based capacitive sensing array, which has the ability to resolve forces in the sub mN range, provides directional response to applied loading and has the ability to differentiate between surface textures. Texture recognition is achieved by scanning surfaces over the sensing array and assessing the frequency spectrum of the sensor outputs.
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paper_title: Tactile devices to sense touch on a par with a human finger.

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Our sense of touch enables us to recognize texture and shape and to grasp objects. The challenge in making an electronic skin which can emulate touch for applications such as a humanoid robot or minimally invasive and remote surgery is both in mimicking the (passive) mechanical properties of the dermis and the characteristics of the sensing mechanism, especially the intrinsic digital nature of neurons. Significant progress has been made towards developing an electronic skin by using a variety of materials and physical concepts, but the challenge of emulating the sense of touch remains. Recently, a nanodevice was developed that has achieved the resolution to decipher touch on a par with the human finger; this resolution is over an order of magnitude improvement on previous devices with a sensing area larger than 1 cm(2). With its robust mechanical properties, this new system represents an important step towards the realization of artificial touch.
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paper_title: A review of tactile sensing technologies with applications in biomedical engineering

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Abstract Any device which senses information such as shape, texture, softness, temperature, vibration or shear and normal forces, by physical contact or touch, can be termed a tactile sensor. The importance of tactile sensor technology was recognized in the 1980s, along with a realization of the importance of computers and robotics. Despite this awareness, tactile sensors failed to be strongly adopted in industrial or consumer markets. In this paper, previous expectations of tactile sensors have been reviewed and the reasons for their failure to meet these expectations are discussed. The evolution of different tactile transduction principles, state of art designs and fabrication methods, and their pros and cons, are analyzed. From current development trends, new application areas for tactile sensors have been proposed. Literature from the last few decades has been revisited, and areas which are not appropriate for the use of tactile sensors have been identified. Similarly, the challenges that this technology needs to overcome in order to find its place in the market have been highlighted.
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paper_title: Capacitive differential pressure sensor for harsh environments

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Abstract A capacitive differential pressure sensor for the pressure range of 0–1 bar has been developed. The primary field of application is hydrodynamic flow measurements in hot petroleum wells. In these harsh environments the sensor has to survive high common mode pressure in the range of 1000 bar and temperatures up to 180°C. The pressure element is formed in a triple-stack of fusion-bonded silicon wafers. A bossed diaphragm etched in the upper wafer bends due to the differential pressure across it. The capacitance to the middle wafer is measured. A reference capacitor insensitive to the differential pressure enables compensation for capacitance shifts caused by ambient pressure and temperature changes. The lower silicon wafer is included to minimise the diaphragm stress from the package. An ASIC, certified for 230°C, which is developed at SINTEF, is used for signal read-out. The sensor is measured to have a low zero pressure signal drift, smaller than 2.5% of full-scale output, when the temperature is varied in the range 0–200°C and the ambient pressure in the range 0–1000 bar. The sensitivity of the sensor is sufficient for the application.
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paper_title: Tactile sensing for dexterous in-hand manipulation in robotics-A review

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Abstract As the field of robotics is expanding from the fixed environment of a production line to complex human environments, robots are required to perform increasingly human-like manipulation tasks, moving the state-of-the-art in robotics from grasping to advanced in-hand manipulation tasks such as regrasping, rotation and translation. To achieve advanced in-hand manipulation tasks, robotic hands are required to be equipped with distributed tactile sensing that can continuously provide information about the magnitude and direction of forces at all contact points between them and the objects they are interacting with. This paper reviews the state-of-the-art in force and tactile sensing technologies that can be suitable within the specific context of dexterous in-hand manipulation. In previous reviews of tactile sensing for robotic manipulation, the specific functional and technical requirements of dexterous in-hand manipulation, as compared to grasping, are in general not taken into account. This paper provides a review of models describing human hand activity and movements, and a set of functional and technical specifications for in-hand manipulation is defined. The paper proceeds to review the current state-of-the-art tactile sensor solutions that fulfil or can fulfil these criteria. An analytical comparison of the reviewed solutions is presented, and the advantages and disadvantages of different sensing technologies are compared.
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paper_title: A flexible capacitive tactile sensing array with floating electrodes

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In this work, we present the development of a capacitive tactile sensing array realized by using MEMS fabrication techniques and flexible printed circuit board (FPCB) technologies. The sensing array, which consists of two micromachined polydimethlysiloxane (PDMS) structures and a FPCB, will be used as the artificial skin for robot applications. Each capacitive sensing element comprises two sensing electrodes and a common floating electrode. The sensing electrodes and the metal interconnect for signal scanning are implemented on the FPCB, while the floating electrode is patterned on one of the PDMS structures. This special design can effectively reduce the complexity of the device structure and thus makes the device highly manufacturable. The characteristics of the devices with different dimensions are measured and discussed. The corresponding scanning circuits are also designed and implemented. The tactile images induced by the PMMA stamps of different shapes are also successfully captured by a fabricated 8 × 8 array.
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paper_title: Miniature pressure acquisition microsystem for wireless in-vivo measurements

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Improvement of therapies and diagnosis methods require the acquisition of clinical data with optimal accuracy and reliability. Combination of recent progresses in SOI micromachining and telemetry lead to the development of a new miniature pressure sensor acquisition microsystem to be inserted as close as possible to the organ or the targeted area. Moreover a wireless RF powering and data transmission has been optimized in order to allow a non-invasive acquisition chain.
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paper_title: Tactile Sensing—From Humans to Humanoids

paper_content:

Starting from human ?sense of touch,? this paper reviews the state of tactile sensing in robotics. The physiology, coding, and transferring tactile data and perceptual importance of the ?sense of touch? in humans are discussed. Following this, a number of design hints derived for robotic tactile sensing are presented. Various technologies and transduction methods used to improve the touch sense capability of robots are presented. Tactile sensing, focused to fingertips and hands until past decade or so, has now been extended to whole body, even though many issues remain open. Trend and methods to develop tactile sensing arrays for various body sites are presented. Finally, various system issues that keep tactile sensing away from widespread utility are discussed.
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paper_title: Effects of the elastic cover on tactile sensor arrays

paper_content:

Tactile sensors are composed of two substantial parts, the sensory structure and its cover. The characteristics of a sensor are fundamentally set by the sensor design, but are also essentially modified by the elastic cover on top. In this paper we analyze the pure mechanical information-coding effects of the sheltering rubber layer, applied on single-crystalline silicon 3D-force sensors, capable to detect both normal and shear forces. We give instructions on how to enhance the sensor's sensitivity by mimicking human tactile perception with introducing hair- and fingerprint-like elements to the sensor design.
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paper_title: An integrated MEMS three-dimensional tactile sensor with large force range

paper_content:

Abstract An integrated three-dimensional tactile sensor with robust MEMS structure and soft contact surface suitable for robotic applications was developed. The sensor has a maximum force range of 50 N in the vertical direction and ±10 N in the x and y horizontal directions. The tactile sensor includes 4×8 sensing cells each exhibiting an independent, linear response to the three components of forces applied on the cells. By finite element analysis, optimal cell structures and piezoresistor positions were determined. Post bulk-micromachining was performed on foundry-fabricated CMOS chips to produce the sensor cells. With neural network training, the tactile sensor produced reliable three-dimensional force measurements and repeatable response on tactile images. Design analysis, fabrication procedures, and experimental results are presented in this paper.
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paper_title: Design and fabrication of a hybrid silicon three-axial force sensor for biomechanical applications

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This paper presents the design and development of a silicon-based three-axial force sensor to be used in a flexible smart interface for biomechanical measurements. Normal and shear forces are detected by combining responses from four piezoresistors obtained by ion implantation in a high aspect-ratio cross-shape flexible element equipped with a 525 m high silicon mesa. The mesa is obtained by a subtractive dry etching process of the whole handle layer of an SOI wafer. Piezoresistor size ranges between 6 and 10m in width, and between 30 and 50m in length. The sensor configuration follows a hybrid integration approach for interconnection and for future electronic circuitry system integration. The sensor ability to measure both normal and shear forces with high linearity ( ∼99%) and low hysteresis is demonstrated by means of tests performed by applying forces from 0 to 2 N. In this paper the packaging design is also presented and materials for flexible sensor array preliminary assembly are described. © 2005 Elsevier B.V. All rights reserved.
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paper_title: Piezoelectric polyimide tactile sensors

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An important application of piezoelectric materials is for tactile sensing. For non-planar applications, polymer materials offer the potential to provide flexible tactile sensors conforming to a variety of surface geometries. We have demonstrated a fabrication process for fabricating MEMS tactile sensor structures using a novel high-temperature piezoelectric polyimide as the sensing material. The process consists of conventional lithography and metallization processes and uses a sacrificial layer of photoresist. Electrodes are fabricated on the upper and lower surfaces of the suspended bridge and cantilever structures and a self-test electrode is fabricated underlying each suspended component for testing. Prototype structures have been fabricated on silicon substrates for the purposes of process demonstration and characterization.
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paper_title: A Polymer-Based Flexible Tactile Sensor for Both Normal and Shear Load Detections and Its Application for Robotics

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This paper proposes and demonstrates a novel flexible tactile sensor for both normal and shear load detections. For the realization of the sensor, polyimide and polydimethylsiloxane are used as a substrate, which makes it flexible. Thin metal strain gauges, which are incorporated into the polymer, are used for measuring normal and shear loads. The salient feature of this tactile sensor is that it has no diaphragm-like structures. The unit tactile cell characteristics are evaluated against normal and shear loads. The fabricated tactile sensor can measure normal loads of up to 4 N, and the sensor output signals are saturated against loads of more than 4 N. Shear loads can be detected by different voltage drops in strain gauges. The device has no fragile structures; therefore, it can be used as a ground reaction force (GRF) sensor for balance control in humanoid robots. Four tactile unit sensors are assembled and placed in the four corners of the robots sole. By increasing bump dimensions, the tactile unit sensor can measure loads of up to 2 kgf. When loads are exerted on the sole, the GRF can be measured by these four sensors. The measured forces can be used in the balance control of biped locomotion systems.
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paper_title: A silicon-based shear force sensor: development and characterization

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Abstract A silicon-based shear force sensitive sensor is developed using microfabrication technology. Four ion-implanted piezoresistors are embedded in a silicon diaphragm and used as independent strain gauges. An epoxy mesa is built-up on top of the diaphragm to convert an applied force to a distributed stress. Both the normal and the shear components of an applied force can be resolved from the resistance changes induced by the stress. The sensor is tested when with a 0–3 N variant force is applied at elevation angles of 0°, 30°, 45° and 60°. At each elevation angle, the sensor is rotated from 0° to 360° at increments of 30°. Good linearity ( R ≈0.98) and good repeatability (STD≈3%) are observed. A sensor model is established in order to investigate the shear sensing ability and force measurement mechanism. The experimental results are in good agreement with the sensor model. Shear force sensing ability is demonstrated. In this paper, the sensor's design, fabrication and characterization are described. Based on the experimental data and the model, the sensor's shear sensitivity is discussed in detail.
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paper_title: Tactile sensor based on piezoelectric resonance

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We discuss the realization of tactile sensor based on the principle of change in piezoelectric resonance frequency with applied pressure. An array of electrodes has been adopted on either side of the PZT material to achieve independent resonators. The common areas sandwiched between the electrodes and excitable at the resonance frequency of the PZT material are used to form the sensitive area of the tactile sensor. The electrodes were deposited using a sputtering technique. Tactile sensors with 3/spl times/3, 7/spl times/7 and 15/spl times/15 array of electrodes are developed with different electrode dimensions and separation between the electrodes. The tactile sensor has been interfaced to a computer for the convenience of automatic scanning and making it more user interactive. The tactile sensors developed with different spatial resolution were tested for different shaped objects placed in contact with the sensor. The 3/spl times/3 matrix tactile sensor showed relatively poor spatial resolution whereas 15/spl times/15-matrix tactile sensor showed improved spatial resolution. The sensor with 7/spl times/7 matrix elements was tested for its sensitivity to different extents of applied force/pressure. The output response study carried out on the sensors indicated that these sensors can provide information not only about the extent of force/pressure applied on the object, but also the contour of the object which is in contact with the sensor.
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paper_title: High-Resolution Thin-Film Device to Sense Texture by Touch

paper_content:

Touch (or tactile) sensors are gaining renewed interest as the level of sophistication in the application of minimum invasive surgery and humanoid robots increases. The spatial resolution of current large-area (greater than 1 cm 2 ) tactile sensor lags by more than an order of magnitude compared with the human finger. By using metal and semiconducting nanoparticles, a ∼100-nm-thick, large-area thin-film device is self-assembled such that the change in current density through the film and the electroluminescent light intensity are linearly proportional to the local stress. A stress image is obtained by pressing a copper grid and a United States 1-cent coin on the device and focusing the resulting electroluminescent light directly on the charge-coupled device. Both the lateral and height resolution of texture are comparable to the human finger at similar stress levels of ∼10 kilopascals.
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paper_title: Ultrasonic emission tactile sensing

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This article describes an ongoing study for a new type of tactile sensing device which is based on instantaneous localization of acoustic emissions caused by touch and/or contact movement. The authors assume a sensor structure which consists of a flexible, spherical, fingertip-like body and a quadruple polyvinylidene fluoride (PVDF, a kind of piezoelectric polymer) sound-sensing matrix embedded at the center of the body. Any points on the spherical surface work as emission sources when touched, and the body transmits the waves inward. The PVDF matrix works as a wideband acoustic emission (AE) transducer which is capable of detecting arrival directions of the waves, packet by packet. This means it can independently resolve and localize a series of ultrasonic emissions caused by a touch and slip. In order to realize this type of tactile sensor, the authors consider two important questions: 1) What kind of ultrasonic emissions appear by touch, and are they detectable? 2) How can the multiple wave packets be resolved and localized instantaneously? For the first question, the authors develop a theory of wave generation at collision, and examine detectability by several experiments. For the second question, the authors show how their sound localization algorithm for an auditory sensor is applied. By assuming the use of this algorithm, and from several experiments under various contact and slip conditions, the authors confirm that the following features and tactile information are obtainable: 1) quick localization of touch and separation; 2) sensation of surface roughness under movements; and 3) quick detection of precursor of slip. >
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paper_title: Magnetic actuation of a micro-diaphragm structure for an active tactile sensor

paper_content:

We previously proposed an active tactile sensor that detects both the contact force and hardness of objects such as fingertips. We validated the device principle by using a pneumatic actuation system [1-2]. As a new method for driving the sensor element, we proposed the idea of using a magnetic force working between a permanent magnet on the sensor element and a microfabricated flat coil. We developed the flat coil by using thick photoresist as a mold and electroplated copper as a conductor. We assembled the sensor element and the flat coil, and constructed a hybrid active tactile sensor system. When we dynamically drove the sensor with the magnetic actuator, we could drive the sensor element around its mechanical resonance frequency. We expect that this active tactile sensor can detect a variety of information about an object, such as its hardness and damping factor.
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paper_title: Optoelectronic-Based Flexible Contact Sensor for Prosthetic Hand Application

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This paper presents a flexible contact sensor for application on robotic fingers of prosthetic hand. The sensor is intended to provide contact sensing functionality when the finger is interacting with the environment. The sensor is based on optoelectronic infrared components mounted on a flexible substrate and connected by means of elastic electrical wires. The adopted configuration allows high sensitivities and fast responses. An important feature of the sensor is that the activation thresholds for contact sensing can be simply and precisely tuneable.
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paper_title: Elastomeric Skin Selection for a Fluid-Filled Artificial Fingertip

paper_content:

Biomimetic fingertips for robots and prostheses need to combine compliant grip and tactile sensing with robustness in diverse environments. We have evaluated materials for use in a compliant, fluid-filled artificial fingertip that incorporates multimodal sensing of contact, texture and thermal properties. A variety of silicone elastomers were tested for hardness, wear-rate, and stress-strain relationships. Diffusion rates of several aqueous and nonaqueous solvents through elastomeric membranes were analyzed to ensure that the sensor could maintain proper fluid volume and function for an extended period. A solution of sodium bromide in poly(ethylene glycol)-200 and water combined with a Silastic S silicone elastomeric cosmesis produced a stable and robust solution. V C 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 000: 000-000, 2012
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paper_title: Planar and finger-shaped optical tactile sensors for robotic applications

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Progress is described regarding the development of optical tactile sensors specifically designed for application to dexterous robotics. These sensors operate on optical principles involving the frustration of total internal reflection at a waveguide/elastomer interface and produce a grey-scale tactile image that represents the normal (vertical) forces of contact. The first tactile sensor discussed is a compact, 32*32 planar sensor array intended for mounting on a parallel-jaw gripper. Optical fibers were employed to convey the tactile image to a CCD camera and microprocessor-based image analysis system. The second sensor had the shape and size of a human fingertip and was designed for a dexterous robotic hand. It contained 257 sensing sites (taxels) distributed in a dual-density pattern that included a tactile fovea near the tip measuring 13*13 mm and containing 169 taxels. The design and construction details of these tactile sensors are presented, in addition to photographs of tactile imprints. >
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paper_title: Discretely Loaded Beam-Type Optical Fiber Tactile Sensor for Tissue Manipulation and Palpation in Minimally Invasive Robotic Surgery

paper_content:

In traditional open surgery, surgeons use their fingertip palpation to investigate the hidden anatomical structures of tissue. However, in the current commercially available minimally invasive robotic surgery (MIRS) systems, while surgical instruments interact with tissues, surgeons do not sense any tactile information. Therefore, tactile sensors are required to be integrated into the tips of surgical instruments to mimic the perception of the surgeon's fingertips. The electrically based tactile sensors that exist at present cannot usually operate under static loading conditions. In addition, they are not compatible with magnetic resonance imaging (MRI) devices. Therefore, this research was aimed at restoring tactile information by developing an MRI compatible optical fiber tactile sensor. The sensor consists of only one single moving part. Thanks to this novel design, the sensor does not require the use of an array of sensors to measure the distributed tactile information. This capability simplifies the integration of the sensor into any suitable space available at the tips of surgical instruments. In addition, the sensor performs under both static and dynamic loading conditions. A theoretical model of the sensor and a finite-element model of the sensor-tissue interaction were developed. To validate the sensor, a prototype of the sensor was fabricated and tested.
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paper_title: Flexible piezoelectric tactile sensor with structural electrodes array for shape recognition system

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This study provides an efficient and feasible solution to enhance the sensitivity of traditional piezoelectric tactile sensor based on introducing structural electrode upon the sensing material. A sandwich structure for flexible tactile sensor consists of top and bottom soft substrates made of Polystyrene, and in between of two soft substrates a piezoelectric thin film, PVDF, and a PDMS microstructures array are utilized as sensing material and microstructures, respectively. The experimental results showed the output voltage was linear with contact force from 10N to 0.5 N and good reliability within low frequency range 1 ~ 100 Hz. In addition, the shape recognition also can be achieved as the objective contacted with the 4 by 4 electrodes array. The effects of structural electrode on the enhancement of sensitivity were also numerically simulated by finite element method (FEM) and verified experimentally by dynamic measurement system, respectively. In general, the flexible tactile sensor developed in this study is not only applied for detecting contact force but also for the human physiology monitoring system, such as pulsation, heart rate and blood pressure, etc.
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paper_title: Anthropomorphic Robotic Soft Fingertip with Randomly Distributed Receptors

paper_content:

Abstract To improve the manipulation ability of robotic fingers, this paper proposes a design of an anthropomorphic soft fingertip with distributed receptors. The fingertip consists of two silicon rubber layers of different hardness containing two kinds of receptors, strain gauges and PVDF (polyvinylidene fluoride) films. The structure of the fingertip is similar to that of a human’s; it consists of a bone, a body, a skin layer, and randomly distributed receptors inside. Experimental results demonstrate the discriminating ability of the fingertip: it can discriminate five different materials by pushing and rubbing the objects.
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paper_title: Development of fingertip tactile sensing chips for humanoid robots

paper_content:

This paper presents the development of tactile sensing chips, for the fingertips of humanoid robots. In the first phase of development, piezoelectric polymer-MEA (microelectrode array) based test chips have been realized. Each chip comprises of 32 microelectrodes, epoxy-adhered with a thin piezoelectric polymer (PVDF-TrFE) film. The diameter of each microelectrode or ‘taxel’ (tactile element) is 500 µm and the center to center distance between taxels is 1 mm. The tactile sensing chips have been experimentally evaluated over a wide range (0.02 – 4N or ∼ 2 gmf- 400 gmf) of dynamic normal forces and frequencies (2 Hz – 5 KHz) by applying variable force with constant frequency in the first case and constant force with variable frequency in latter. The cross-talk, among adjacent taxels on the chips, is found to be approximately 20%. Finally, the ability of the chips to identify object material on the basis of their hardness is also demonstrated.
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paper_title: Development of a 3D tactile sensor

paper_content:

Abstract This paper is a study on the development of a sensor for detecting the catheter's contact conditions. The sensor is composed of a rubber layers, cupper plates and three strain gauges. The sensor is assumed to be mounted on the tip of a catheter, and it is hollowed for the work space of the catheter. The equations relating the sensor output with the contact conditions are formulated in the three gauges output. The obtained results show the good correspondence of the estimated contact information with the applied conditions.
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paper_title: Tactile sensing-processing: interface-cover geometry and the inverse-elastic problem

paper_content:

Abstract The skin-like elastic cover of a tactile-sensor array plays a fundamental role in determining how the sensor is responding to an arbitrary surface stimulus. Indeed, this cover is the first spatial–temporal sensory instruction in a tactile cellular wave-computer, or in living, neural-tactile signal-processing organs. While the sensor under the elastic layer measures the local strain/stress, we are interested in the stimulating force distribution at the contacting surface. This paper deals with the described inverse problem in the stationary case over a three-axial tactile-sensor array, measuring three components of the local strain tensor of the elastic cover. Our goal here is to design an interface flexible cover to enhance specific capabilities, sensitivity and accuracy, when using the three-axial sensor array. First, on the simplest, flat rubber surface, we create a kind of tactile hyper-accuracy by giving a simple analytical solution to the case when the cover is indented by an arbitrary point load. Second, instead of generalizing our solution to more complex indentation profiles, we try to abolish the need for the complex inverse solution by specifying our cover's geometry and thus reducing the complexity of the sensor's coding mechanism. We create hemispherical bumps over the elastic surface and use a finite-element model to show that with the bumps we can localize the (otherwise continuous) input over the taxels and detect normal and shear force components independently. Finally, we confirm our theoretical results with real-time experimental data and use the measurements for sensor calibration and texture classification.
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paper_title: A magnetic type tactile sensor using a two-dimensional array of inductors

paper_content:

A novel tactile sensor based on electromagnetic induction that can detect slippage in addition to three-axis force is proposed. The structure of this sensor is simple, and the sensor, which is essentially a displacement gauge, consists of a two-dimensional array of inductors and an elastic body containing a permanent magnet. Formulas to transform the output voltage of the proposed sensor into a force vector are derived, and analyses of both deformation of the proposed structure and magnetic field generated by a cylindrical permanent magnet are carried out to extract transformation parameters. In addition, it is shown that the sensor sensitivity can be designed using the aspect ratio of the cylindrical magnet. A prototype unit-cell of a tactile sensor is developed with four chip inductors, silicon gel as an elastic body and a neodymium magnet, and experiments are undertaken with a six-axis force/torque sensor as a reference. The contributions of inductors to sensor output are observed experimentally to be in agreement with analytical prediction and the reference sensor. Experimental results show that the proposed tactile sensor is useful for three-axis force measurement and slip detection.
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paper_title: Design and fabrication of a flexible three-axial tactile sensor array based on polyimide micromachining

paper_content:

This paper describes the design and fabrication of a flexible three-axial tactile sensor array using advanced polyimide micromachining technologies. The tactile sensor array is comprised of sixteen micro force sensors and it measures 13 mm × 18 mm. Each micro force sensor has a square membrane and four strain gauges, and its force capacity is 0.6 N in the three-axial directions. The optimal positions of the strain gauges are determined by the strain distribution obtained form finite element analysis (FEA). The normal and shear forces are detected by combining responses from four thin-film metal strain gauges embedded in a polyimide membrane. In order to acquire force signals from individual micro force sensors, we fabricated a PCB based on a multiplexer, operational amplifier and microprocessor with CAN network function. The sensor array is tested from the evaluation system with a three-component load cell. The developed sensor array can be applied in robots’ fingertips, as well as to other electronic applications with three-axial force measurement and flexibility keyword requirements.
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paper_title: Flexible Dome and Bump Shape Piezoelectric Tactile Sensors Using PVDF-TrFE Copolymer

paper_content:

In this paper, a new mold-transfer method to pattern piezoelectric polymer has been developed and applied to fabricate innovative dome and bump shape polyvinylidene-fluoride-trifluoroethylene (PVDF-TrFE) films. The dome and bump shape PVDF-TrFE films have been successfully fabricated and characterized as a sensing component for flexible tactile sensors. The tactile sensors developed using these polymer microstructures show a high sensitivity which can measure as small as 40 mN force for bump shape sensors and 25 mN for dome shape sensors. The newly developed fabrication method provides a flexible way to pattern the piezoelectric polymer with different shapes and dimensions, including bump and dome shape piezoelectric polymer microstructures. In addition, a selective dc poling method for the PVDF-TrFE film has been developed for fabricating precisely located piezoelectric sensors with minimum crosstalk. The bump and dome shape PVDF-TrFE films developed in this paper can have numerous applications for microcatheters or other minimally invasive biomedical devices.
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paper_title: Flexible and tactile sensor based on a photosensitive polymer

paper_content:

This paper presents a novel design of tactile sensing arrays with integrated strain gauges for the measurement of contact force. Surface stress or strain changes on the sensor area due to applied force are measured by the encapsulated Au gauges. The fabricated tactile sensors are highly flexible and durable so that they can conform to more complex surfaces without damaging the skin structure and the metal interconnects on the sensing array. The experimental results show the output characteristics are linear with contact force from 0 to 700gf and a sensitivity of 3%/100gf within the full scale range of 700gf. The effect of electrode structure and position on the enhancement of sensitivity are also numerically simulated by a finite element method and verified experimentally. The measured tactile sensors are robust enough for direct contact with human and contaminants without undue care.
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paper_title: Cell Culture on MEMS Platforms: A Review

paper_content:

Microfabricated systems provide an excellent platform for the culture of cells, and are an extremely useful tool for the investigation of cellular responses to various stimuli. Advantages offered over traditional methods include cost-effectiveness, controllability, low volume, high resolution, and sensitivity. Both biocompatible and bio- incompatible materials have been developed for use in these applications. Biocompatible materials such as PMMA or PLGA can be used directly for cell culture. However, for bio- incompatible materials such as silicon or PDMS, additional steps need to be taken to render these materials more suitable for cell adhesion and maintenance. This review describes multiple surface modification strategies to improve the biocompatibility of MEMS materials. Basic concepts of cell-biomaterial interactions, such as protein adsorption and cell adhesion are covered. Finally, the applications of these MEMS materials in Tissue Engineering are presented.
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paper_title: A BioMEMS review: MEMS technology for physiologically integrated devices

paper_content:

MEMS devices are manufactured using similar microfabrication techniques as those used to create integrated circuits. They often, however, have moving components that allow physical or analytical functions to be performed by the device. Although MEMS can be aseptically fabricated and hermetically sealed, biocompatibility of the component materials is a key issue for MEMS used in vivo. Interest in MEMS for biological applications (BioMEMS) is growing rapidly, with opportunities in areas such as biosensors, pacemakers, immunoisolation capsules, and drug delivery. The key to many of these applications lies in the leveraging of features unique to MEMS (for example, analyte sensitivity, electrical responsiveness, temporal control, and feature sizes similar to cells and organelles) for maximum impact. In this paper, we focus on how the biological integration of MEMS and other implantable devices can be improved through the application of microfabrication technology and concepts. Innovative approaches for improved physical and chemical integration of systems with the body are reviewed. An untapped potential for MEMS may lie in the area of nervous and endocrine system actuation, whereby the ability of MEMS to deliver potent drugs or hormones, combined with their precise temporal control, may provide new treatments for disorders of these systems.
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paper_title: A mechatronic platform for human touch studies

paper_content:

The development of a mechatronic tactile stimulation platform for touch studies is presented. The platform was developed for stimulation of the fingertip using textured surfaces, providing repeatable tangential sliding motion of stimuli with controlled indentation force. Particular requirements were addressed to make the platform suitable for neurophysiological studies in humans with particular reference to electrophysiological measurements, but allowing a variety of other studies too, such as psychophysical, tribological and artificial touch ones. The design of the mechatronic tactile stimulator is detailed, as well as the performance in tracking reference trajectories. Using microneurography, we recorded from human tactile afferents and validated the platform compatibility with the exacting demands of electrophysiological methods, comprising the absence of spurious vibrations and the lack of relevant electromagnetic interference.
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paper_title: Biodegradable Elastomeric Polymers and MEMS in Tissue Engineering

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Within the past decade, researchers in the field of tissue engineering have recognized the need for newmaterials with soft and elastic properties. As a result, many groups have focused on the synthesis, characterization, and application of materials with a wide range of biodegradable and elastomeric properties.1 The combination of these polymers with Micro–Electro–Mechanical Systems (MEMS) technologies has sparked a new area of research with increasing practical applications.2 The following chapter discusses important design criteria for creating polymers with elastomeric properties, recently researched biodegradable elastomers, and the use of MEMS in combination with biodegradable elastomers in tissue engineering applications.
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paper_title: Bio-hybrid tactile sensor for the study of the role of mechanoreceptors in human tactile perception

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In this paper, the design and fabrication of a bio-hybrid tactile sensor is described. The device is designed to sustain the viability of cell-cultures and biological tissues for sufficient time as to allow experimentation in ordinarily non-ideal conditions. This is achieved by ensuring the cells have sufficient nutrients, oxygen and heat. It has an open configuration and is equipped with a local conductivity sensor which is sensitive to variations in the ion concentrations in the extracellular matrix. This allows secondary messengers in the form of the ion output from the cells to be monitored whilst contact stresses are applied to the tissue surface. Initial experiments are also described whereby the local conductivity sensor is submerged in solutions of various concentrations of different salts commonly found in mammalian cells. The sensor response is modelled analytically using complex mapping which lead to expressions detailing the sensitivity of the sensor. At concentrations found in mammalian cells, it was found that the sensor can detect changes in concentration of potassium chloride in solution as small as [email protected]
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paper_title: Development of a Biomimetic MEMS based Capacitive Tactile Sensor

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This paper presents the development of a low4cost MEMS based biomimetic tactile device intended to be incorporated as the core element in a biomimetic fingerpad. The developed silicon based sensing devices consist of an array of capacitive sensors with optimized design to measure force ranges encountered during tactile exploration of surfaces with different textures. As with the biological finger, the sensor array contains sensors of different sensitivity and position/orientation, guaranteeing a high informative content of data obtained from surface4finger interaction. This paper presents the design of the device, fabrication processes used and experimental results of sensor performance.
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paper_title: Incorporation of Novel MEMS Tactile Sensors into Tissue Engineered Skin

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Tactile sensation is important for the performance of daily tasks and prevention of injury. Full thickness wounds of greater than 4cm diameter will not spontaneously heal. Tissue engineering can be used to replace the lost skin, but this skin will often fail to be reinnervated. This results in loss of tactile sensations. Here we have developed a novel, silicon based MicroElectroMechanical Systems (MEMS) sensor array that is capable of detecting tactile experiences of the tissue engineered skin. Tissue engineered skin with tactile experiences can also be useful in the replacement of animal testing in the pharmaceutical industry.
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paper_title: Development and characterization of a bio-hybrid skin-like stretchable electrode

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This work presents the design, fabrication and characterization of a polymer based stretchable electrode for cell monitoring. The final goal is the development of innovative bio-hybrid skin-like tactile sensors with mammalian cells as core biological elements; to achieve such aim the enabling technological approach is pursued in this investigation. Electrodes are needed to detect cells response, thus the first step of the bio-hybrid system fabrication is the development of a platform able to record such response and transmit it to the external world. The stretchable electrode is composed by a conductive layer (few @? of Ti plus 90nm of Au) on a polymeric substrate (1mm thick PDMS membrane). Cellular adhesion was verified and cellular response to an induced electrode strain of 1% was detected through fluorescence microscopy. Fluorescence intensities were 104.82+/-9.64a.u. and 129.66+/-13.06a.u. prior and during electrode strain, respectively. Electromechanical characterization of the stretchable electrode revealed excellent stability and reliability within the 1% strain, which is the operative range identified for the future tactile sensor application. Results showed that the electrode was conductive up to 14% of strain. Furthermore, frequency impedance measurements demonstrated the electrode capability of detecting presence of cells.
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paper_title: Integration of Cell Culture and Microfabrication Technology

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Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.
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paper_title: Study of gelatin-containing artificial skin V: fabrication of gelatin scaffolds using a salt-leaching method.

paper_content:

Abstract Porous gelatin scaffolds were prepared using a salt-leaching method and these were compared to scaffolds fabricated using a freeze-drying method. The salt-leached gelatin scaffolds were easily formed into desired shapes with a uniformly distributed and interconnected pore structure with an average pore size of around 350 μm. The mechanical strength and the biodegradation rate of the scaffolds increased with the porosity, and were easily modulated by the addition of salt. After 1 week of in vitro culturing, the fibroblasts in salt-leached scaffolds were mainly attached on the surface of the pores in the scaffold, whereas cells seeded on freeze-dried scaffolds were widely distributed and aggregated on the top and the bottom of the scaffold. After 14 d of culturing, the fibroblasts showed a good affinity to, and proliferation on, the gelatin scaffolds without showing any signs of biodegradation. An in vivo study of cultured artificial dermal substitutes showed that an artificial dermis containing the fibroblasts enhanced the re-epithelialization of a full-thickness skin defect when compared to an acellular scaffold after 1 week.
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paper_title: Hydrogels for Soft Machines

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Hydrogels have applications in surgery and drug delivery, but are never considered alongside polymers and composites as materials for mechanical design. This is because synthetic hydrogels are in general very weak. In contrast, many biological gel composites, such as cartilage, are quite strong, and function as tough, shock-absorbing structural solids. The recent development of strong hydrogels suggests that it may be possible to design new families of strong gels that would allow the design of soft biomimetic machines, which have not previously been possible.
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paper_title: Study on gelatin-containing artificial skin: I. Preparation and characteristics of novel gelatin-alginate sponge.

paper_content:

An absorbable sponge, composed of gelatin and alginate, was prepared by new crosslinking method that improved the efficiency of crosslinking. The crosslinking degree was characterized by trinitrobenzenesulfonic acid (TNBS) assay. A water uptake ability test, in vitro drug release and collagenase degradation tests, and an in vivo animal test were employed to confirm the applicability of this gelatin-alginate sponge as a wound dressing material. As the alginate content in the sponge increased, the porosity increased, resulting in an enhanced water uptake ability. Sponges loaded with silver sulfadiazine or gentamicin sulfate slowly released drugs for up to four days. The crosslinked sponge resisted in vitro collagenase digestion for up to three days. An in vivo animal test using witar rat showed rather good wound healing effect of gelatin-alginate sponge containing AgSD than vaseline gauze in our full-thickness skin defect model.
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paper_title: In vitro engineering of human skin-like tissue

paper_content:

Coverage of large, full-thickness burns presents a challenge for the surgeon due to the lack of availability of the patient's own skin. Currently, tissue engineering offers the possibility of performing a suitable therapeutic wound coverage after early burn excision by using cultured keratinocyte sheets supported by a dermal layer. The aim of this study was to develop and characterize a skin substitute composed of both epidermal and dermal elements. For this purpose we grew keratinocytes and fibroblasts separately for 15 days within two different types of biomaterials. Cells then were co-cultured for an additional period of 15 days, after which samples were taken and processed with either classic or immunohistochemical stainings. Results showed that (1) human fibroblasts and keratinocytes can be cultured on hyaluronic acid-derived biomaterials and that (2) the pattern of expression of particular dermal–epidermal molecules is similar to that found in normal skin. The data from this study suggest that our skin equivalent might be useful in the treatment of both burns and chronic wounds. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 187–194, 1998.
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paper_title: A Comparative Evaluation of Chondrocyte/Scaffold Constructs for Cartilage Tissue Engineering

paper_content:

This study aimed to evaluate three biodegradable scaffolds as cell carriers for in vitro cartilage regeneration using mature human chondrocyte cells. We compared cell distribution, viability and morphology and we evaluated the mechanical properties of the constructs after 2 weeks of in vitro culture. The materials used as scaffolds were fibrin glue, a collagen sponge and a polyurethane foam (DegraPol®). Fibrin glue was found unsuitable as a chondrocyte carrier vehicle after culture times longer than a few days, probably due to significant barriers to nutrients and oxygen diffusion, and the material weakened rapidly. The collagen-based sponge was found to be unsuitable to support chondrocyte survival in vitro, although the presence of newly synthesized collagen was observed in these constructs. The synthetic biodegradable scaffold was more adequate in supporting cell survival and mechanical properties. After 2 weeks of static culture, the storage modulus obtained by dynamic shear testing was in the order of 0.7 kPa in fibrin constructs, 3.7 kPa in collagen constructs and 105 kPa in DegraPol® constructs. The better mechanical stability of the synthetic foam supports further investigation in the possible use of synthetic biomaterials as biodegradable scaffolds for in vitro cartilage regeneration. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 55–64)
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paper_title: Tissue-engineered skin. Current status in wound healing.

paper_content:

Tissue-engineered skin is a significant advance in the field of wound healing and was developed due to limitations associated with the use of autografts. These limitations include the creation of a donor site which is at risk of developing pain, scarring, infection and/or slow healing. A number of products are commercially available and many others are in development. Cultured epidermal autografts can provide permanent coverage of large area from a skin biopsy. However, 3 weeks are needed for graft cultivation. Cultured epidermal allografts are available immediately and no biopsy is necessary. They can be cryopreserved and banked, but are not currently commercially available. A nonliving allogeneic acellular dermal matrix with intact basement membrane complex (Alloderm) is immunologically inert. It prepares the wound bed for grafting allowing improved cultured allograft 'take' and provides an intact basement membrane. A nonliving extracellular matrix of collagen and chondroitin-6-sulfate with silicone backing (Integra) serves to generate neodermis. A collagen and glycosaminoglycan dermal matrix inoculated with autologous fibroblasts and keratinocytes has been investigated but is not commercially available. It requires 3 to 4 weeks for cultivation. Dermagraft consists of living allogeneic dermal fibroblasts grown on degradable scaffold. It has good resistance to tearing. An extracellular matrix generated by allogeneic human dermal fibroblasts (TransCyte) serves as a matrix for neodermis generation. Apligraf is a living allogeneic bilayered construct containing keratinocytes, fibroblasts and bovine type I collagen. It can be used on an outpatient basis and avoids the need for a donor site wound. Another living skin equivalent, composite cultured skin (OrCel), consists of allogeneic fibroblasts and keratinocytes seeded on opposite sides of bilayered matrix of bovine collagen. There are limited clinical data available for this product, but large clinical trials are ongoing. Limited data are also available for 2 types of dressing material derived from pigs: porcine small intestinal submucosa acellular collagen matrix (Oasis) and an acellular xenogeneic collagen matrix (E-Z-Derm). Both products have a long shelf life. Other novel skin substitutes are being investigated. The potential risks and benefits of using tissue-engineered skin need to be further evaluated in clinical trials but it is obvious that they offer a new option for the treatment of wounds.
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paper_title: Cell encapsulation using biopolymer gels for regenerative medicine

paper_content:

There has been a consistent increase in the mean life expectancy of the population of the developed world over the past century. Healthy life expectancy, however, has not increased concurrently. As a result we are living a larger proportion of our lives in poor health and there is a growing demand for the replacement of diseased and damaged tissues. While traditionally tissue grafts have functioned well for this purpose, the demand for tissue grafts now exceeds the supply. For this reason, research in regenerative medicine is rapidly expanding to cope with this new demand. There is now a trend towards supplying cells with a material in order to expedite the tissue healing process. Hydrogel encapsulation provides cells with a three dimensional environment similar to that experienced in vivo and therefore may allow the maintenance of normal cellular function in order to produce tissues similar to those found in the body. In this review we discuss biopolymeric gels that have been used for the encapsulation of mammalian cells for tissue engineering applications as well as a brief overview of cell encapsulation for therapeutic protein production. This review focuses on agarose, alginate, collagen, fibrin, hyaluronic acid and gelatin since they are widely used for cell encapsulation. The literature on the regeneration of cartilage, bone, ligament, tendon, skin, blood vessels and neural tissues using these materials has been summarised.
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paper_title: Enhancing the vascularization of three‐dimensional porous alginate scaffolds by incorporating controlled release basic fibroblast growth factor microspheres

paper_content:

Site-specific delivery of angiogenic growth fac- tors from tissue-engineered devices should provide an effi- cient means of stimulating localized vessel recruitment to the cell transplants and would ensure cell survival and function. In the present article, we describe the construction of a novel porous alginate scaffold that incorporates tiny poly (lactic-co-glycolic acid) microspheres capable of con- trolling the release of angiogenic factors, such as basic fibro- blast growth factor (bFGF). The microspheres are an integral part of the solid alginate matrix, and their incorporation does not affect the scaffold porosity or pore size. In vitro, bFGF was released from the porous composite scaffolds in a controlled manner and it was biologically active as assessed by its ability to induce the proliferation of cardiac fibro- blasts. The controlled delivery of bFGF from the three-di- mensional scaffolds accelerated the matrix vascularization after implantation on the mesenteric membrane in rat peri- toneum. The number of penetrating capillaries into the bFGF-releasing scaffolds was nearly fourfold higher than into the control scaffolds (those incorporating microspheric BSA and heparin but not bFGF). At day 10 posttransplanta- tion, capillary density in the composite scaffolds was 45 3/mm 2 and it increased to 70 7/mm 2 by day 21. The released bFGF induced the formation of large and matured blood vessels, as judged by the massive layer of mural cells surrounding the endothelial cells. The control over bFGF delivery and localizing its effects to areas of need, may aid in the wider application of bFGF in therapeutic angiogenesis as well as in tissue engineering. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 489 - 497, 2003
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paper_title: Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge.

paper_content:

This study was conducted to develop a new sponge type of biomaterial to be used for either wound dressing or scaffold for tissue engineering. We were able to prepare an insoluble matrix composed of gelatin and sodium hyaluronate (HA) by dipping the soluble sponge into 90% (w/v) acetone/water mixture containing a small amount of cross-linking agent, 1-ethyl-3-3-dimethylaminoproplycarbodiimide hydrochloride, EDC. To characterize the sponge, Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and Instron analysis were performed. The obtained results indicate that the chemically cross-linked sponge shows a cross-linking degree of 10-35%, a mean pore size of 40-160 microm, porosity of 35-67%, and a tensile strength of 10-30 gf/cm(2). Especially, the porosity measured by image analysis showed a tendency to increase with HA content, resulting in an increased water uptake. The resistance to collagenase degradation in vitro increased for up to 2 days. Silver sulfadiazine (AgSD)-impregnated gelatin-HA sponge was also prepared and compared with conventional vaseline gauze by applying it onto a dorsal skin defect of wistar rat for 5, 12, and 21 days. Histological results showed an enhancement of wound healing in AgSD-impregnated gelatin-HA sponge.
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paper_title: An alginate hydrogel matrix for the localised delivery of a fibroblast/keratinocyte co-culture.

paper_content:

There is significant interest in the development of tissue-engineered skin analogues, which replace both the dermal and the epidermal layer, without the use of animal or human derived products such as collagen or de-epidermalised dermis. In this study, we proposed that alginate hydrogel could be used to encapsulate fibroblasts and that keratinocytes could be cultured on the surface to form a bilayered structure, which could be used to deliver the co-culture to a wound bed, initially providing wound closure and eventually expediting the healing process. Encapsulation of fibroblasts in 2 and 5% w/v alginate hydrogel effectively inhibited their proliferation, whilst maintaining cell viability allowing keratinocytes to grow uninhibited by fibroblast overgrowth to produce a stratified epidermal layer. It was shown that the alginate degradation process was not influenced by the presence of fibroblasts within the hydrogel and that lowering the alginate concentration from 5 to 2% w/v increased the rate of degradation. Fibroblasts released from the scaffold were able to secrete extracellular matrix (ECM) and thus should replace the degrading scaffold with normal ECM following application to the wound site. These findings demonstrate that alginate hydrogel may be an effective delivery vehicle and scaffold for the healing of full-thickness skin wounds.
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paper_title: A biosensor based on micromechanical interrogation of living cells.

paper_content:

The authors have demonstrated that living cells can be reliably cultured directly onto atomic force microscope (AFM) cantilevers. The cells are inclined to grow on both sides of the surface, and the cantilevers must be treated to deter such two-sided growth. Preliminary data acquired with the AFM demonstrate that these integrated cell/cantilevers are capable of detecting the response of Madine Darby canine kidney (MDCK) cells to different toxins, with response time on the order of several seconds. These results suggest the feasibility of real-time, rapid, and sensitive biomechanical sensors. A separate fluid chamber has been built, which is capable of detecting fluid temperature changes of tenths of a degree. The initial temperature results from the fluid chamber prototype indicate the potential for a low-cost dedicated system.
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paper_title: Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane).

paper_content:

One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 μm to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs.
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paper_title: Bio-artificial skin composed of gelatin and (1→3), (1→6)-β-glucan

paper_content:

Porous scaffolds composed of gelatin and β-glucan were prepared using the freeze-drying method. The scaffold had an inter-connected pore structure with average pore size of 90–150 μm. Results for the contact angle and cell attachment revealed that a high gelatin content was suitable for cellular attachment and distribution in two- or three-dimensional fibroblast cultures, because the gelatin had acidic residues, and arginine–glycine–aspartic acid groups. To prepare a stratified wound dressing to mimic the normal human skin, fibroblasts and keratinocyte cells were isolated from a child's foreskin, and were co-cultured in gelatin/β-glucan scaffolds were cross-linked using 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide hydrochloride. An in vivo study showed that after 1 week, the artificial dermis containing the fibroblasts enhanced the re-epithelialization of a full-thickness skin defect rather than the acellular scaffold.
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paper_title: Live cell-based sensor cells.

paper_content:

Abstract Biosensors utilizing live cells have attracted a great deal of attention because of their high specificity and sensitivity to their targets. We established cytotoxic sensor cells that were transfected with GFP plasmids derived from HSP70B′ and BTG2 promoters. These sensor cells have significant advantages in both speed and sensitivity for the detection of cytotoxicity. We created a live cell-based sensorchip fabricated with microfluidic channels. Fluorescence in the sensor cells increased in a CdCl 2 dose-dependent manner in the microfluidic channels. With this system, cytotoxic reagents can be quantitatively detected in a quick, sensitive, and high-throughput manner. The combination of sensor cells and microfluidic systems will provide an important basis for the development of μ-TAS technology that can be applied to numerous fields such as biomaterials, nanotoxicology, environmental assessment, and drug screening.
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paper_title: Tissue Engineered Artificial Skin Composed of Dermis and Epidermis

paper_content:

: We made an artificial skin comprised of a stratified layer of keratinocytes and a dermal matrix with a type I collagen containing fibroblasts. In this work, we showed keratinocyte behavior under primary culture, gel contractions varying with concentration of collagen solution, and cell growth plots in the collagen gel. The optimum behavior of dermal equivalent could be obtained using 3.0 mg/ml collagen solution and attached gel culture. The attached gel culture had a jumping effect of growth factor on cell growth at the lag phase. To develop the artificial skin, 1× 105 cells/cm2 of keratinocytes were cultured on the dermal equivalent at air-liquid interface. Finally, to overcome the problem that artificial skin of collagen gel was torn easily during suturing of grafting, we prepared histocompatible collagen mesh and attached the mesh to the bottom of the gel. Cultured artificial skins were successfully grafted onto rats.
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paper_title: Study on gelatin-containing artificial skin IV: a comparative study on the effect of antibiotic and EGF on cell proliferation during epidermal healing

paper_content:

Gelatin-hyaluronate sponge with and without antibiotic and epidermal growth factor (EGF) were prepared and compared. Four types of sponges were applied on the full-thickness dorsal skin defect of Wistar rat. The effects of antibiotic and EGF in gelatin-hyaluronate sponge on wound healing were investigated by light microscopy and image analyzer at postoperative days of 5, 12 and 21. An immunohistochemical technique, employing PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was applied to wounded tissue sections. The number of PC10-positive cells was very high for the sponge with EGF at postoperative day 5, then gradually decreased with time. Also we found that antibiotics restrained the cell proliferation during the migratory phase. The sponge with both antibiotic and EGF showed good wound healing performances on the whole for a healing period. The epithelium was regenerated fast with EGF-impregnated sponges at day 5, but each sample had nearly the same length of regenerated epithelium at day 12.
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paper_title: Co-culture of cells in PDMS microsystem for sensitized artificial skin

paper_content:

In this work a PDMS microsystem was conceived and fabricated for the development and study of an artificial skin-equivalent that includes nerve endings. A cellular co-culture of keratinocytes, dorsal root ganglia neurons and spinal cord cells in micro wells was developed. Microstructures were included in the microsystems, allowing infiltration of neuronal extensions to the skin-equivalent compartment. Electrophysiological measurements were conducted to measure electrical responses of the neurons in response to external stimulation of the skin.
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paper_title: An organotypic culture system of Merkel cells using isolated epidermal sheets

paper_content:

BACKGROUND ::: Merkel cells (MCs) exist in the epidermal basal layer, in contact with keratinocytes. This direct contact seems critical for maintaining MCs in vitro. ::: ::: ::: OBJECTIVES ::: To estimate the effects of nerve cells on the maintenance of MCs within epidermal sheets in a new organotypic culture system of MCs. ::: ::: ::: METHODS ::: We developed a new organotypic culture system of MCs, using MC-containing epidermal sheets embedded in collagen gel. To estimate the effects of nerve cells on the maintenance of MCs within the epidermal sheets, we cocultured nerve cells and MC-containing epidermal sheets. In these culture assemblies, cellular behaviour was analysed by histochemistry, immunohistochemistry, electron microscopy and enzyme-linked immunosorbent assay. ::: ::: ::: RESULTS ::: This culture, even in the absence of neurotrophin (NT)-3 and nerve growth factor (NGF) (which are crucial for MC biology), retained cytokeratin (CK)-20-positive and neuroendocrine granule-containing MCs within the sheets for over 2 weeks. Coculture of MCs with PC-12 nerve cells significantly increased the number of MCs within the epidermal sheets, and the keratinocytes had almost identical expression levels of CK1, CK10, CK14 and the progenitor marker p63 to those produced by keratinocytes in vivo. Uptake of the growth marker bromodeoxyuridine by MCs and levels of NT-3 and NGF in the culture supernatants were undetectable in this system, regardless of the presence or absence of PC-12. ::: ::: ::: CONCLUSIONS ::: The data suggest, first, that direct contact between MCs and keratinocytes may be critical for retaining MCs in vitro; second, that nerve cell-affected maintenance of keratinocyte differentiation, but not NT-3 and NGF, may contribute to MC maintenance; and third, that MCs are not able to grow, at least in our system. Our method would be useful for studying MC biology.
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paper_title: Merkel Cell-Nerve Cell Interaction Undergoes Formation of a Synapse-like Structure in a Primary Culture

paper_content:

Merkel cells have been assumed to guide nerve fibers to the skin. However, there has been little in vitro evidence that supports this hypothesis, because there is no suitable established culture system of Merkel cells. Here we show that Merkel cells isolated from rat footpad skin were successfully cultured in a monolayer with keratinocytes. Keratinocytes did not affect any structural changes in Merkel cells. When nerve cells (NG108-15 or PC12) were added to the culture system, both nerve fibers and cytoplasmic processes of Merkel cells outgrew and cooperatively organized synapse-like structures at their contact points. Nerve cells promoted Merkel cell survival, compared with keratinocytes only. Merkel cell proliferation was not detected in all conditions, even with nerve growth factor, neurotrophin-3, interleukin-6 and tumor necrosis factor-α. The data suggest, firstly, that Merkel cells may guide nerve fibers to the skin by interacting with nerve cells; and, secondly, that nerve cells, but not keratinocytes, may produce some survival factors other than the cytokines above for Merkel cells, although Merkel cells may be a terminally differentiated cell type. Our method could open a way to study Merkel cell biology.
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paper_title: Designing cell-compatible hydrogels for biomedical applications.

paper_content:

Hydrogels are polymeric materials distinguished by high water content and diverse physical properties. They can be engineered to resemble the extracellular environment of the body's tissues in ways that enable their use in medical implants, biosensors, and drug-delivery devices. Cell-compatible hydrogels are designed by using a strategy of coordinated control over physical properties and bioactivity to influence specific interactions with cellular systems, including spatial and temporal patterns of biochemical and biomechanical cues known to modulate cell behavior. Important new discoveries in stem cell research, cancer biology, and cellular morphogenesis have been realized with model hydrogel systems premised on these designs. Basic and clinical applications for hydrogels in cell therapy, tissue engineering, and biomedical research continue to drive design improvements using performance-based materials engineering paradigms.
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paper_title: Studies on gelatin-based sponges. Part III: a comparative study of cross-linked gelatin/alginate, gelatin/hyaluronate and chitosan/hyaluronate sponges and their application as a wound dressing in full-thickness skin defect of rat.

paper_content:

Novel cross-linked sponges composed of gelatin/alginate and gelatin/hyaluronate and chitosan/hyaluronate (GH, GA and CH, respectively) were prepared and compared. Six different sponges with or without silver sulfadiazine (AgSD) were applied on the full-thickness dorsal skin defect of Wistar rat. The histology and epidermal wound healing rates of the skin defects were investigated by light microscopy and computerized morphometry 5 and 12 days post-operatively. In our full-thickness wound model (diameter 1 cm), the AgSD-impregnated sponges showed good wound healing performances on the whole. However, there appeared meaningful differences of wound healing between the gelatin-based sponges (GH, GA) and the CH. GH with AgSD was found to show the best wound healing properties as a wound dressing resulting from histological findings and computerized morphometric analysis of epidermal healing.
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paper_title: Normal human Merkel cells are present in epidermal cell populations isolated and cultured from glabrous and hairy skin sites.

paper_content:

The Merkel cell is a highly specialized cell that primarily acts as a slowly adapting mechanoreceptor. Merkel cells are scarce in normal skin but can be identified by the expression of distinct keratin filaments. Merkel cells constitute a very unique population and many questions still remain as to their origin, number, proliferative capacity, and functions in cutaneous biology. The dissociation of epidermal cells from skin is a widely used technique to extract and culture keratinocytes. We took advantage of a two-step extraction method to quantify keratin-20-expressing Merkel cells among total cutaneous cells obtained from either hairy or glabrous skin biopsies. Flow cytometry analysis revealed that keratin-20-labeled Merkel cells represent between 3.6% and 5.7% of freshly dissociated basal epidermal cells. No significant differences were seen between samples derived from glabrous palmar and hairy anatomic sites, from children and adult, respectively. We also report on the presence of Merkel cells in primary and first subcultures of epidermal cells indicating their capacity to remain viable after extraction from skin of various anatomic sites. To our knowledge, this is the first demonstration of nontumorigenic human Merkel cells in culture in vitro. The persistence of a small number of Merkel cells in culture suggests that, with the development of appropriate culture conditions, these cells could be amplified and further studied to unravel long-standing questions relative to their paracrine function or epithelial origin.
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paper_title: Fabrication and characteristics of polyHEMA artificial skin with improved tensile properties

paper_content:

Abstract PolyHEMA-based hydrogel synthesized by the UV-radiation induced polymerization technique is used to prepare the strength-proved artificial skin in order to improve the handling procedure for curing the burned wound. The tensile strength of the artificial skin membrane is measured following the ASTM standard. The strength decreases with increasing amount of the initial water added to the mixture of HEMA (2-hydroxyethyl methacrylate) monomer, ethylene glycol dimethacrylate (EGDMA) cross linker and benzoin isobutyl ether (BIE) initiator. The maximum strength of the artificial skin membrane reaches 9 kg/cm 2 , as the hydrogel contains equilibrium water around 30 wt%. The artificial skin so fabricated presents several additional characteristics including good wettability, complete transparency and dimensional change during water absorption and evaporation.
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paper_title: The nerve-dependency of Merkel cell proliferation in cultured human fetal glabrous skin.

paper_content:

Merkel cells are thought to function as slowly adapting mechanoreceptors and are known as targets for sensory nerves. However, the nerve-dependency of Merkel cells remains controversial. In this respect, some investigators have found interregional differences between hairy and glabrous skin and others have shown intraregional differences within denervated rat touch domes. Differences between species have also been reported. This study was performed to determine whether Merkel cells proliferate in vitro in the absence of the systemic factors, blood vessels and the intact nerves in human skin. Suspension organ culture was performed using fetal digits to investigate their in vitro proliferation. Merkel cells and cutaneous nerves were identified using antibodies to cytokeratin 20 and protein gene product 9.5 (PGP 9.5), respectively. Fetal digits of 56-82 day gestational age were cultured in serum free medium in a high O2 (45%) environment. Tissues were harvested before starting culture (D0) and 1, 4, 7, 14, 28 d after culture. Merkel cells were observed in the volar pads and dorsal nail matrices at D0. After 28 d of suspension organ culture, digits looked healthy structurally and the number of Merkel cells had increased. However, PGP 9.5-immunoreactive nerves were markedly diminished after 1 day of culture and almost disappeared after 4 days. Merkel cell proliferation in vitro suggested that Merkel cell development is probably nerve-independent in human fetal glabrous skin.
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paper_title: Cultured skin as a 'smart material' for healing wounds: experience in venous ulcers.

paper_content:

The healing of chronic wounds is a difficult and varied problem. The engineering of a cultured skin tissue offers an adaptive therapy for chronic wounds. Our hypothesis has been that living tissue can act as a ‘smart material’ to heal wounds. We have examined the healing characteristics of a bilayered cultured skin equivalent (GraftskinTM) in a controlled study and present clinical data from interim analyses for 233 patients over 6 months of treatment. All venous ulcer patients will be followed for up to 1 year. We report on three basic scenarios of healing: (i) promotion of healing by secondary intention, (ii) persistent biological wound closure with stimulation of underlying healing, and (iii) healing by frank graft take of the cultured material with remodelling of the tissue over time. Our results indicate that the cultured skin equivalent is responsive to individual wound conditions and thus acts as a ‘smart material’ in the chronic wound.
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paper_title: Cell Culture on MEMS Platforms: A Review

paper_content:

Microfabricated systems provide an excellent platform for the culture of cells, and are an extremely useful tool for the investigation of cellular responses to various stimuli. Advantages offered over traditional methods include cost-effectiveness, controllability, low volume, high resolution, and sensitivity. Both biocompatible and bio- incompatible materials have been developed for use in these applications. Biocompatible materials such as PMMA or PLGA can be used directly for cell culture. However, for bio- incompatible materials such as silicon or PDMS, additional steps need to be taken to render these materials more suitable for cell adhesion and maintenance. This review describes multiple surface modification strategies to improve the biocompatibility of MEMS materials. Basic concepts of cell-biomaterial interactions, such as protein adsorption and cell adhesion are covered. Finally, the applications of these MEMS materials in Tissue Engineering are presented.
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paper_title: A BioMEMS review: MEMS technology for physiologically integrated devices

paper_content:

MEMS devices are manufactured using similar microfabrication techniques as those used to create integrated circuits. They often, however, have moving components that allow physical or analytical functions to be performed by the device. Although MEMS can be aseptically fabricated and hermetically sealed, biocompatibility of the component materials is a key issue for MEMS used in vivo. Interest in MEMS for biological applications (BioMEMS) is growing rapidly, with opportunities in areas such as biosensors, pacemakers, immunoisolation capsules, and drug delivery. The key to many of these applications lies in the leveraging of features unique to MEMS (for example, analyte sensitivity, electrical responsiveness, temporal control, and feature sizes similar to cells and organelles) for maximum impact. In this paper, we focus on how the biological integration of MEMS and other implantable devices can be improved through the application of microfabrication technology and concepts. Innovative approaches for improved physical and chemical integration of systems with the body are reviewed. An untapped potential for MEMS may lie in the area of nervous and endocrine system actuation, whereby the ability of MEMS to deliver potent drugs or hormones, combined with their precise temporal control, may provide new treatments for disorders of these systems.
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paper_title: Biodegradable Elastomeric Polymers and MEMS in Tissue Engineering

paper_content:

Within the past decade, researchers in the field of tissue engineering have recognized the need for newmaterials with soft and elastic properties. As a result, many groups have focused on the synthesis, characterization, and application of materials with a wide range of biodegradable and elastomeric properties.1 The combination of these polymers with Micro–Electro–Mechanical Systems (MEMS) technologies has sparked a new area of research with increasing practical applications.2 The following chapter discusses important design criteria for creating polymers with elastomeric properties, recently researched biodegradable elastomers, and the use of MEMS in combination with biodegradable elastomers in tissue engineering applications.
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paper_title: A review of tactile sensing technologies with applications in biomedical engineering

paper_content:

Abstract Any device which senses information such as shape, texture, softness, temperature, vibration or shear and normal forces, by physical contact or touch, can be termed a tactile sensor. The importance of tactile sensor technology was recognized in the 1980s, along with a realization of the importance of computers and robotics. Despite this awareness, tactile sensors failed to be strongly adopted in industrial or consumer markets. In this paper, previous expectations of tactile sensors have been reviewed and the reasons for their failure to meet these expectations are discussed. The evolution of different tactile transduction principles, state of art designs and fabrication methods, and their pros and cons, are analyzed. From current development trends, new application areas for tactile sensors have been proposed. Literature from the last few decades has been revisited, and areas which are not appropriate for the use of tactile sensors have been identified. Similarly, the challenges that this technology needs to overcome in order to find its place in the market have been highlighted.
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paper_title: Decoding Information From Neural Signals Recorded Using Intraneural Electrodes: Toward the Development of a Neurocontrolled Hand Prosthesis

paper_content:

The possibility of controlling dexterous hand prostheses by using a direct connection with the nervous system is particularly interesting for the significant improvement of the quality of life of patients, which can derive from this achieve- ment. Among the various approaches, peripheral nerve based intrafascicular electrodes are excellent neural interface candi- dates, representing an excellent compromise between high selectivity and relatively low invasiveness. Moreover, this approach has undergone preliminary testing in human volun- teers and has shown promise. In this paper, we investigate whether the use of intrafascicular electrodes can be used to decode multiple sensory and motor information channels with the aim to develop a finite state algorithm that may be employed to control neuroprostheses and neurocontrolled hand prosthe- ses. The results achieved both in animal and human experiments show that the combination of multiple sites recordings and advanced signal processing techniques (such as wavelet denois- ing and spike sorting algorithms) can be used to identify both sensory stimuli (in animal models) and motor commands (in a human volunteer). These findings have interesting implications, which should be investigated in future experiments.
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paper_title: Learning tactile skills through curious exploration

paper_content:

We present curiosity-driven, autonomous acquisition of tactile exploratory skills on a biomimetic robot finger equipped with an array of microelectromechanical touch sensors. Instead of building tailored algorithms for solving a specific tactile task, we employ a more general curiosity-driven reinforcement learning approach that autonomously learns a set of motor skills in absence of an explicit teacher signal. In this approach, the acquisition of skills is driven by the information content of the sensory input signals relative to a learner that aims at representing sensory inputs using fewer and fewer computational resources. We show that, from initially random exploration of its environment, the robotic system autonomously develops a small set of basic motor skills that lead to different kinds of tactile input. Next, the system learns how to exploit the learned motor skills to solve supervised texture classification tasks. Our approach demonstrates the feasibility of autonomous acquisition of tactile skills on physical robotic platforms through curiosity-driven reinforcement learning, overcomes typical difficulties of engineered solutions for active tactile exploration and underactuated control, and provides a basis for studying developmental learning through intrinsic motivation in robots.
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paper_title: Roughness Encoding for Discrimination of Surfaces in Artificial Active-Touch

paper_content:

A 2 × 2 array of four microelectromechanical system (MEMS) tactile microsensors is integrated with readout electronics in the distal phalanx of an anthropomorphic robotic finger. A total of 16 sensing elements are available in a 22.3-mm area (i.e., 72 units/cm ) of the artificial finger, thus achieving a density comparable with human Merkel mechanoreceptors. The MEMS array is covered by a polymeric packaging with biomimetic fingerprints enhancing the sensitivity in roughness encoding. This paper shows the ability of the sensor array to encode roughness for discrimination of surfaces, without requiring dedicated proprioceptive sensors for end-effector velocity. Three fine surfaces with 400-, 440-, and 480- μm spatial periods are quantitatively evaluated. Core experiments consisted in active-touch exploration of surfaces by the finger executing a stereotyped human-like movement. A time-frequency analysis on pairs of tactile array outputs shows a clustering of the fundamental frequency, thus yielding 97.6% worst-case discrimination accuracy with a k -nearest-neighbor (k-NN) classifier. Hence, surfaces differing down to 40 μm are identified in active-touch by both hardware and processing methods based on exteroceptive tactile information. Finally, active-touch results with five textiles (which differ in texture or orientation) are shown as a preliminary qualitative assessment of discrimination in a more realistic tactile-stimulation scenario.
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paper_title: Live Cell-Based Sensor Devices

paper_content:

Living cells maintain life functions by responding quickly and with great sensitivity to changes in the external environment. Consequently, sensors using cells as active elements are thought to be able to perform analyses faster and with more sensitivity than previously possible. Cell-based sensors can be roughly divided into two types. The first uses microorganisms such as Escherichia coli or yeast as active elements (Microbial cells). The second type uses human and animal cells (Mammalian cells). The first type can be cultivated rather easily and has the advantages of being inexpensive and portable. The second type is more complex but has the advantage of potentially being used with human subjects. Most research in this area is concentrated on the first type, microbial sensors, but research on sensors that use mammalian cells has recently become more widespread. We are exploring the modification of mammalian cells using genetic engineering techniques and developing next- generation cell sensors that can visually represent specific reactions. Recently, few researchers, including our group, have successfully produced devices from sensor cells that can process a variety of specimens using MEMS, NEMS, and other nano/micro processing technologies. In this review, we will introduce our research and describe recent trends in this field.
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paper_title: Direct neural sensory feedback and control of a prosthetic arm

paper_content:

Evidence indicates that user acceptance of modern artificial limbs by amputees would be significantly enhanced by a system that provides appropriate, graded, distally referred sensations of touch and joint movement, and that the functionality of limb prostheses would be improved by a more natural control mechanism. We have recently demonstrated that it is possible to implant electrodes within individual fascicles of peripheral nerve stumps in amputees, that stimulation through these electrodes can produce graded, discrete sensations of touch or movement referred to the amputee's phantom hand, and that recordings of motor neuron activity associated with attempted movements of the phantom limb through these electrodes can be used as graded control signals. We report here that this approach allows amputees to both judge and set grip force and joint position in an artificial arm, in the absence of visual input, thus providing a substrate for better integration of the artificial limb into the amputee's body image. We believe this to be the first demonstration of direct neural feedback from and direct neural control of an artificial arm in amputees.
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paper_title: Soft-neuromorphic artificial touch for applications in neuro-robotics

paper_content:

We propose an artificial mechanotransduction system based on a 2×2 MEMS array touch sensor, and evaluate a neural model which is designed to convert raw sensor outputs into neural spike-trains. We show that core tactile information is preserved in the neural representation, and that the resulting modulation via spikes can be used in surface discrimination tasks. In this research study the first neural stage (i.e., at mechanoreceptor level) of somatosensory system was mimicked in a soft-neuromorphic fashion, while future works will target the implementation of the 2nd order stage (Cuneate neurons) to further understand the biological mechanisms underlying maximum transfer and fast processing of tactile information.
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paper_title: Guest Editorial Special Issue on Biorobotics

paper_content:

The focus of this special issue is to show how the main achievements on different technical topics relevant to the development of bioinspired and bioapplied mechatronic devices and robotic systems. The 19 articles in this special issue are summarized here.
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paper_title: Cells on chips

paper_content:

Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.
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Title: Synthetic and Bio-Artificial Tactile Sensing: A Review

Section 1: Introduction
Description 1: Write about the human sense of touch, its importance for robots, and the objective of developing artificial skin-like sensory systems. Mention the classification of synthetic skin and bio-artificial skins, and the focus of the review.

Section 2: Definitions
Description 2: Explain the different touch modalities, focusing on mechanical touch and its sensory capabilities such as cutaneous, kinaesthetic, and haptic senses.

Section 3: Mechanoelectrotransduction of Tactile Information by Human Glabrous Skin and Mechano-Receptors
Description 3: Describe how the human hand mediates tactile sensation through mechanoreceptors and the skin's structure, focusing on mechanotransduction and the various mechanoreceptors involved in tactile sensing.

Section 4: Human T tactile Perception
Description 4: Elaborate on how mechanoreceptors transmit tactile information to the CNS and the different ways humans perceive properties like force, form, texture, and curvature.

Section 5: Artificial Tactile Sensing
Description 5: Analyze the state of artificial tactile sensing systems, including synthetic skin and transduction mechanisms, bio-hybrid tactile sensing, and fully-biological tactile sensing. Discuss the technologies and approaches used for these systems.

Section 6: Synthetic Skin and Transduction Mechanisms
Description 6: Provide a detailed overview of common synthetic tactile transduction techniques such as capacitive, piezoelectric, piezoresistive, inductive, optoelectric, and strain gauge methods, illustrating their characteristics, advantages, and disadvantages.

Section 7: Bio-Hybrid Tactile Sensing
Description 7: Explain the concept of bio-hybrid tactile sensing systems, including the integration of synthetic sensors into tissue-engineered skins. Discuss related microfabrication technologies and examples of bio-hybrid sensors.

Section 8: Fully-Biological Tactile Sensing
Description 8: Discuss fully-biological tactile sensing systems, focusing on tissue-engineered, hydrogel-based, and gelatin-containing artificial skins. Highlight the use of living cells in transduction mechanisms and recent research developments.

Section 9: Discussion, Application Domains, and Conclusions
Description 9: Summarize the benefits and challenges of synthetic and bio-artificial tactile sensing systems. Discuss potential application domains such as robotics and neural prosthetics, and highlight future directions and open research topics in this field.