A Tactile Sensor Device Exploiting the Tunable Sensitivity of Copper-PDMS Piezoresistive Composite

Abstract A low cost and highly mechanically flexible 8x8 pressure matrix sensor with dedicated electronics has been fabricated with an innovative metal-elastomer composite material. Under the action of a compressive stress the material exhibits a giant piezoresistive effect varying its electrical resistance of several orders of magnitude. This phenomenon can be tuned by changing the material composition parameters, directly modifying the sensitivity of the sensor. The micro casting fabrication technique, used for the preparation of self standing sheet of functional material, gives the possibility of easily fabricating complex-shaped structure suitable for integration on robot surface for tactile sensing. The sensor has been tested with a customized electronic circuit after an exhaustive characterization of the functional properties of the material

Ultrasensitive Piezoresistive and Piezocapacitive Cellulose-Based Ionic Hydrogels for Wearable Multifunctional Sensing

Tactile sensors, namely, flexible devices that sense physical stimuli, have received much attention in the last few decades due to their applicability in a wide range of fields like the world of wearables, soft robotics, prosthetics, and e-skin. Nevertheless, achieving a trade-off among stretchability, good sensitivity, easy manufacturability, and multisensing ability is still a challenge. Herein, an extremely flexible strain sensor composed of a cellulose-based hydrogel is presented. A natural biocompatible carboxymethylcellulose (CMC) hydrogel endowed with ionic conductivity by sodium chloride (NaCl) was used as the sensitive part. Both the sensible layer and electrodes were investigated with an innovative approach for wearable sensor applications based on electrochemical impedance spectroscopy to find the best device configuration. The sensor, exploitable both as a piezoresistor and as a piezocapacitor, presents high sensitivity to external stimuli, together with an extreme stretchability of up to 600%, showing the best strain and temperature sensitivity among the ionic conductive hydrogel-based devices presented in the literature. The very high strain sensitivity enables the hydrogel to be implemented in wearable strain sensors to monitor different human motions and physiological signals, representing a valid solution for the realization of transparent, easily manufacturable, and low-environmental-impact devices

Ultrasensitive Piezoresistive and Piezocapacitive Cellulose-Based Ionic Hydrogels for Wearable Multifunctional Sensing

Tactile sensors, namely, flexible devices that sense physical stimuli, have received much attention in the last few decades due to their applicability in a wide range of fields like the world of wearables, soft robotics, prosthetics, and e-skin. Nevertheless, achieving a trade-off among stretchability, good sensitivity, easy manufacturability, and multisensing ability is still a challenge. Herein, an extremely flexible strain sensor composed of a cellulose-based hydrogel is presented. A natural biocompatible carboxymethylcellulose (CMC) hydrogel endowed with ionic conductivity by sodium chloride (NaCl) was used as the sensitive part. Both the sensible layer and electrodes were investigated with an innovative approach for wearable sensor applications based on electrochemical impedance spectroscopy to find the best device configuration. The sensor, exploitable both as a piezoresistor and as a piezocapacitor, presents high sensitivity to external stimuli, together with an extreme stretchability of up to 600%, showing the best strain and temperature sensitivity among the ionic conductive hydrogel-based devices presented in the literature. The very high strain sensitivity enables the hydrogel to be implemented in wearable strain sensors to monitor different human motions and physiological signals, representing a valid solution for the realization of transparent, easily manufacturable, and low-environmental-impact devices

Microenvironment in neuroblastoma: Isolation and characterization of tumor-derived mesenchymal stromal cells

Background: It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods: Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. inhibition of phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cytotoxic function, was examined. Gene expression profiles, known to be related to tumor cell stemness, Wnt pathway activation, epithelial-mesenchymal transition (EMT) and tumor metastasis were also evaluated. Healthy donor bone marrow-derived MSCs (BM-MSC) were employed as controls. Results: NB-MSCs presented the typical MSC morphology and phenotype. They showed a proliferative capacity superimposable to BM-MSCs. Stemness marker expression (Sox2, Nanog, Oct3/4) was comparable to BM-MSCs. NB-MSC in vitro osteogenic and chondrogenic differentiation was similar to BM-MSCs, but NB-MSCs lacked adipogenic differentiation capacity. NB-MSCs reached senescence phases at a median passage of P7 (range, P5-P13). NB-MSCs exhibited greater immunosuppressive capacity on activated T lymphocytes at a 1:2 (MSC: PBMC) ratio compared with BM-MSCs (p = 0.018). NK cytotoxic activity was not influenced by co-culture, either with BM-MSCs or NB-MSCs. Flow-cytometry cell cycle analysis showed that NB-MSCs had an increased number of cells in the G0-G1 phase compared to BM-MSCs. Transcriptomic profiling results indicated that NB-MSCs were enriched with EMT genes compared to BM-MSCs. Conclusions: We characterized the biological features, the immunomodulatory capacity and the gene expression profile of NB-MSCs. The NB-MSC gene expression profile and their functional properties suggest a potential role in promoting tumor escape, invasiveness and metastatic traits of NB cancer cells. A better understanding of the complex mechanisms underlying the interactions between NB cells and NB-derived MSCs should shed new light on potential novel therapeutic approaches

Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform.

Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-∆e8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a speci c siRNA that spares the Hipk2-∆e8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant- negative effect of Hipk2-FL over the ∆e8 isoform. From this observation, we sought to take advantage and assessed the therapeutic potential of generating Hipk2 isoform unbalance in tumor-initiating cells derived from colorectal cancer patients. Strong reduction of cell viability was induced in vitro and in vivo by the originally described exon 8-speci c siRNA, supporting a potential therapeutic application. However, validation analyses performed with additional exon8-speci c siRNAs with different stabilities showed that all exon8-targeting siRNAs can induce comparable Hipk2 isoform unbalance but only the originally reported e8-siRNA promotes cell death. These data show that loss of viability does not depend on the prevalence of Hipk2- ∆e8 isoform but it is rather due to microRNA-like off-target effects

A versatile ultrasound system for in vitro experiments

Objective One of the most difficult tasks to achieve with the available instrumentations used to study the interaction between ultrasound (US) and cellular model systems is to design an experiment, where only the effects of one physical parameter at a time is evaluated, while all the others are kept constant. The set-ups are usually custom-made, often by means of clinical instrument intended for a different therapeutic purpose. Furthermore, the results are not strictly comparable with others obtained with techniques considered standard in molecular and cellular biology at this time, because there is the need to use non-standard devices to contain biological samples. Sterility, as well as temperature, is not well controlled and reproducibility is usually a major concern. In our study we show the effects of ultrasound treatments on different cellular systems. The experiments are performed with a versatile bench-top US apparatus to be adapted for several in vitro experiments and that allows easy and robust reproducibility using standard set-ups for the cell samples. Methods One main feature of our bench-top US system is that it has been designed in order to use standard plasticware commonly used in molecular biology labs, ensuring the temperature control and sterility conditions needed in the field. We present a set-up where the simultaneous use of a set of transducers operating at different frequencies on the same plate, allows the comparison of the deposition of the same acoustic pressure, whilst evaluating the effect of frequency alone on the readout of the cell experiments. The apparatus modular design also allows the use of a set of transducers operating at the same frequency, in experiments where the throughput is a relevant factor. We demonstrate that it is possible to define the position of the target within all the achievable areas of the acoustic field with sub-millimetric accuracy. Tests for several applications based on biologic effects by ultrasound have been carried out by varying the acoustic parameters such as power, frequency range, sonication time and duty cycle, all controlled within robust protocols executed in automation. Results The resulting data proves that it is possible to perform in vitro experiments for different purposes (i.e. drug delivery, cellular sonoporation, nanoparticles or microbubbles swelling, tissue regeneration, neuronal cell stimulation etc.) keeping the relevant physical parameters of sonication constant, for instance acoustic pressure, but varying the others parameters (i.e. frequency, pulse length or duty cycle etc) one at the time. Conclusions We show that with our apparatus it is possible to obtain robust and reproducible results on cellular experiments, using all the standard devices that are commonly available in biological labs. The improvement on the side of reproducibility and portability of the experiments allows a straightforward comparison between our results and those obtained with other techniques

Cancer stem cell biomarkers predictive of radiotherapy response in rectal cancer: A systematic review

Background: Rectal cancer (RC) is one of the most commonly diagnosed and particularly challenging tumours to treat due to its location in the pelvis and close proximity to critical genitouri-nary organs. Radiotherapy (RT) is recognised as a key component of therapeutic strategy to treat RC, promoting the downsizing and downstaging of large RCs in neoadjuvant settings, although its therapeutic effect is limited due to radioresistance. Evidence from experimental and clinical studies indicates that the likelihood of achieving local tumour control by RT depends on the complete eradica-tion of cancer stem cells (CSC), a minority subset of tumour cells with stemness properties. Methods: A systematic literature review was conducted by querying two scientific databases (Pubmed and Scopus). The search was restricted to papers published from 2009 to 2021. Results: After assessing the quality and the risk of bias, a total of 11 studies were selected as they mainly focused on biomarkers predictive of RT-response in CSCs isolated from patients affected by RC. Specifically these studies showed that elevated levels of CD133, CD44, ALDH1, Lgr5 and G9a are associated with RT-resistance and poor prognosis. Conclusions: This review aimed to provide an overview of the current scenario of in vitro and in vivo studies evaluating the biomarkers predictive of RT-response in CSCs derived from RC patients

CdO-based nanostructures as novel CO2 gas sensors

Crystalline Cd(OH)2/CdCO3 nanowires, having lengths in the range from 0.3 up to several microns and 5–30 nm in diameter, were synthesized by a microwave-assisted wet chemical route and used as a precursor to obtain CdO nanostructures after a suitable thermal treatment in air. The morphology and microstructure of the as-synthesized and annealed materials have been investigated by scanning electron microscopy, transmission electron microscopy, x-ray diffraction and thermogravimetry–differential scanning calorimetry. The change in morphology and electrical properties with temperature has revealed a wire-to-rod transformation along with a decreases of electrical resistance. Annealed samples were printed on a ceramic substrate with interdigitated contacts to fabricate resistive solid state sensors. Gas sensing properties were explored by monitoring CO2 in synthetic air in the concentration range 0.2–5 v/v% (2000–50 000 ppm). The effect of annealing temperature, working temperature and CO2 concentration on sensing properties (sensitivity, response/recovery time and stability) were investigated. The results obtained demonstrate that CdO-based thick films have good potential as novel CO2 sensors for practical applications