Tactile perception by friction induced vibrations

Cataloged from PDF version of article.When a finger moves to scan the surface of an object (haptic sensing), the sliding contact generates vibrations that propagate in the finger skin activating the receptors (mechanoreceptors) located in the skin, allowing the brain to identify objects and perceive information about their properties. The information about the surface of the object is transmitted through vibrations induced by friction between the skin and the object scanned by the fingertip. The mechanoreceptors transduce the stress state into electrical impulses that are conveyed to the brain. A clear understanding of the mechanisms of the tactile sensing is fundamental to numerous applications, like the development of artificial tactile sensors for intelligent prostheses or robotic assistants, and in ergonomics. While the correlation between surface roughness and tactile sensation has already been reported in literature, the vibration spectra induced by the finger-surface scanning and the consequent activation of the mechanoreceptors on the skin have received less attention. In this paper, frequency analysis of signals characterizing surface scanning is carried out to investigate the vibration spectrum measured on the finger and to highlight the changes shown in the vibration spectra as a function of characteristic contact parameters such as scanning speed, roughness and surface texture. An experimental set-up is developed to recover the vibration dynamics by detecting the contact force and the induced vibrations; the bench test has been designed to guarantee reproducibility of measurements at the low amplitude of the vibrations of interest, and to perform measurements without introducing external noise. Two different perception mechanisms, as a function of the roughness wavelength, have been pointed out. The spectrum of vibration obtained by scanning textiles has been investigated. (C) 2011 Elsevier Ltd. All rights reserved

An immature B cell population from peripheral blood serves as surrogate marker for monitoring tumor angiogenesis and anti-angiogenic therapy in mouse models

Tumor growth depends on the formation of new blood vessels (tumor angiogenesis) either from preexisting vessels or by the recruitment of bone marrow-derived cells. Despite encouraging results obtained with preclinical cancer models, the therapeutic targeting of tumor angiogenesis has thus far failed to deliver an enduring clinical response in cancer patients. One major obstacle for improving anti-angiogenic therapy is the lack of validated biomarkers, which allow patient stratification for suitable treatment and a rapid assessment of therapy response. Toward these goals, we have employed several mouse models of tumor angiogenesis to identify cell populations circulating in their blood that correlated with the extent of tumor angiogenesis and therapy response. Flow cytometry analyses of different combinations of cell surface markers that define subsets of bone marrow-derived cells were performed on peripheral blood mononuclear cells from tumor-bearing and healthy mice. We identified one cell population, CD45dimVEGFR1⁻CD31low, that was increased in levels during active tumor angiogenesis in a variety of transgenic and syngeneic transplantation mouse models of cancer. Treatment with various anti-angiogenic drugs did not affect CD45dimVEGFR1⁻CD31low cells in healthy mice, whereas in tumor-bearing mice, a consistent reduction in their levels was observed. Gene expression profiling of CD45dimVEGFR1⁻CD31low cells characterized these cells as an immature B cell population. These immature B cells were then directly validated as surrogate marker for tumor angiogenesis and of pharmacologic responses to anti-angiogenic therapies in various mouse models of cancer

Infrared Photodissociation Spectroscopy of C2n+1N− Anions with n = 1 – 5

The gas phase vibrational spectroscopy of cryogenically cooled C2n + 1N− anions with n = 1 − 5 is investigated in the spectral range of the C≡C and C≡N stretching modes (1850–2400 cm–1) by way of infrared photodissociation (IRPD) spectroscopy of messenger-tagged C2n+1N–· mD2 complexes. The IRPD spectra are assigned based on a comparison to previously reported anharmonic and harmonic CCSD(T) vibrational frequencies and intensities. Experimentally determined and predicted anharmonic vibrational transition energies lie within ± 21 cm–1. For the harmonic CCSD(T)/vqz+ vibrational frequencies a scaling factor of 0.9808 is determined, resulting in comparable absolute deviations. The influence of the D2-messenger molecules on the structure and the IRPD spectrum is found to be small. Compared to the results of previous IR matrix isolation studies additional, in particular weaker, IR-active transitions are identified

Optimization of a lab-on-a-chip rapid diagnostic test for malaria

LAUREA MAGISTRALELa malaria con 3.5 miliardi di persone ancora a rischio, 228 milioni di casi e 405 000 morti nel 2018, rimane la più importante malattia al mondo causata da puntura di zanzara. La malattia è causata dai parassiti del genere Plasmodium, che infettano i globuli rossi nutrendosi dell' emoglobina e trasformandola in nanocristalli di emozoina. Nonostante l' Organizzazione Mondiale della Sanità raccomandi una "pronta diagnosi, o con microscopio o usando test diagnostici rapidi (RDT), in tutti i pazienti sospetti di malaria prima che venga loro somministrato un trattamento", la qualità della diagnosi con microscopio è frequentemente inadeguata, mentre l'affidabilità degli RDT basati sull' individuazione di antigeni è ancora affetta da un considerevole numero di falsi positivi e falsi negativi. Questo progetto di tesi magistrale tratta l'ottimizzazione e la caratterizzazione di un lab-on-a-chip test diagnostico rapido pan-malarico che, basandosi sulle proprietà magnetiche dell'emozoina, combina la separazione magnetoforetica e la tecnica di misura impedenziometrica. Il test diagnostico presentato, sfruttando la competizione tra la gravità e le forze magnetiche, si basa sulla cattura locale dei globuli rossi infetti e dei cristalli di emozoina su concentratori micromagnetici e la seguente misura elettrica. L'attrazione su lungo raggio è data da magneti esterni permanenti di NdFeB, mentre una concentrazione sugli elettrodi è eseguita da strutture di Ni fabbricate nel chip. Infine, a causa del cambio di conduttività in una soluzione data la presenza di particelle, la quantità di cristalli di emozoina e globuli rossi infetti può essere valutata attraverso una misura impedenziometrica. Durante questo lavoro di tesi, sono state eseguite diverse attività in modo da caratterizzare e ottimizzare la piattaforma diagnostica precedente. In primo luogo è stato scritto un codice di analisi robusto e affidabile, usato poi durante la validazione clinica in Camerun. Dopodiché, altri importanti esperimenti sono stati condotti volti a dimostrare il valore minimo di parassitemia misurabile (LoD) di 10parassiti·μl^(-1) e una curva di calibrazione dal LoD fino a una concentrazione di 10^5parassiti·μl^(-1). Durante la tesi, è stato inoltre eseguito il primo esperimento di monitoraggio (follow up). Più tardi, un nuovo microchip con aree sensibili compenetrate è stato ideato, fabbricato e caratterizzato in modo da rimuovere il segnale spurio di drift tipico del chip precedente. Questa tesi è stata parte del progetto TMek. Le attività sperimentali sono state eseguite a PoliFAB, il centro di nano e micro tecnologia del Politecnico di Milano sotto la diretta supervisione dei Prof. Giorgio Ferrari e Prof. Riccardo Bertacco, direttore del gruppo "NABIS" del Dipartimento di Fisica del Politecnico di Milano, e all' Ospedale Luigi Sacco di Milano. Il sistema elettronico del dispositivo è stato sviluppato e caratterizzato in collaborazione con il gruppo "I3N" del Politecnico di Milano, diretto dai Prof. Marco Sampietro e Prof. Giorgio Ferrari. I campioni di sangue usati nei test di calibrazione sono stati forniti e trattati dal gruppo "μBS Lab" del Politecnico di Milano, guidato dal Prof. Gianfranco B. Fiore, mentre la campagna di validazione clinica è stata fatta nel laboratorio di diagnosi dell' Hôpital Saint Luc di Mbalmayo in Camerun.Malaria remains the most important mosquito-borne infectious disease worldwide, with 3.5 billion people still at risk, 228 million cases and 405 000 deaths in 2018. The disease is caused by parasites belonging to the genus of Plasmodium, which infect red blood cells by feeding on haemoglobin and transforming it into hemozoin nanocrystals. Despite the World Health Organization recommends “prompt parasite-based diagnosis in all patients suspected of malaria before treatment is administrated, either by microscopy or malaria rapid diagnostic test (RDTs)”, the quality of microscopy-based diagnosis is frequently inadequate while the reliability of RTDs based on antigens detection is still affected by a sizable number of false negative/positive results. This master’s thesis project is about the optimization and characterization of a lab-on-a-chip pan-malaria rapid diagnostic test, that, based on the paramagnetic properties of hemozoin nanocrystals, combines magnetophoretic separation and electrical impedance detection. The presented diagnostic test, exploiting the competition between gravity and magnetic forces, relies on the local capture of infected red blood cells and hemozoin crystals on micromagnetic concentrators and subsequent detection by electrical measurement. The long-range attraction is provided by external NdFeB permanent magnets, while a concentration on the electrodes is performed by Ni pillars fabricated in the chip. Finally, because of the presence of particles within a solution changes its conductivity, the amount of hemozoin crystals and infected red blood cells can be quantified through an impedance variation detection. During this thesis work, different activities have been carried out to characterize and optimize a diagnostic platform previously developed. First, a solid and reliable analysis code has been realized and used during a preclinical validation study carried out in Cameroon. Then, other important characterization experiments have been performed to demonstrate a limit of detection (LoD) of 10parasites·μl^(-1) and a measurement range from the LoD up to 10^(5)parasites·μl^(-1). During the thesis, the first follow up monitoring has also been carried out. Later, a new microchip with interpenetrated sensitive regions has been designed, fabricated and characterized in order to remove the spurious drift signal affecting the previous chip. This thesis work was part of the TMek project. The experimental activities have been performed in PoliFAB, the micro and nanotechnology centre of “Politecnico di Milano”, under the direct supervision of Prof. Giorgio Ferrari and Prof. Riccardo Bertacco, head of the Nanomagnetism for Biology and Spintronics group of the Department of Physics, and in “Luigi Sacco” hospital in Milan. The detection system has been developed in collaboration with the "I3N" group of “Politecnico di Milano”, directed by Prof. Marco Sampietro and Prof. Giorgio Ferrari, that designed, fabricated and characterized the electronics of the device. The blood samples used in the calibration tests have been provided and treated by "μBS Lab" of "Politecnico di Milano”, led by Prof. Gianfranco B. Fiore, while the preclinical validation campaign has been carried out in the diagnostic laboratory of Hôpital Saint Luc of Mbalmayo in Cameroon

Single bismuth atom transistor for solid state atomic clock applications

LAUREA MAGISTRALELo scopo di questa tesi magistrale è la realizzazione di un transistor multigate con un canale nanometrico interno, che vista la presenza di singoli atomi donori di bismuto nelle sue vicinanze, viene usato per applicazioni di orologi atomici. In questo lavoro sono mostrati nel dettaglio tutti gli step di fabbricazione che portano alla realizzazione del dispositivo, il cui scopo finale è di lavorare come un rilevatore elettrostatico di cariche usando il canale per osservare la carica degli atomi donori a 3 K. Il materiale usato è un silicon-on-insulator(SOI) di 145 nm, sul quale sono inizialmente praticate litografia elettronica e dry etching per creare la struttura base del transistor in silicio. Successivamente due impiantazioni con fascio di ioni son state fatte, la prima in antimonio per dopare le regioni del source e del drain; mentre la seconda, fatta a Melbourne, consisteva nell’ impiantare singoli atomi di bismuto in modo da posizionare i donori accanto al canale del transistor. Successivamente attraverso l’evaporatore sono stati creati i strati di ossido e di metallo per completare il dispositivo. Un altro efficace metodo di doping per il source e il drain è quello performato parallelamente con il cosiddetto Spin-on-Dopant (SOD). La caratterizzazione elettrica è stata svolta sia a temperatura ambiente che a temperature criogeniche. I risultati preliminari mostrano un corretto comportamento del transistor a 3 K che permette di avere alte aspettative riguardo le imminenti misure pianificate per rilavare la stato di carica degli atomi di bismuto.The purpose of this master thesis is the realization of a multigate transistor with a nanometric inner channel, used for atomic clock applications due to the single bismuth donor atoms implanted in its proximity. In this work are shown in detail all the fabrication steps that bring to the device realization, whose final aim is to work as an electrostatic detector by using the channel to take over the charge of the donor atoms at 3K. The material used is a silicon-on-insulator(SOI) of 145 nm, on which are performed at first electron beam lithography and dry etching for create the Si-based transistor structure. Then two ion beam implantations are done, one of Sb to obtain the doping of the source and the drain, the second one of single Bi atoms, performed in Melbourne, to place the donor atoms next to the transistor channel. After that e-beam evaporation tool create the oxide and the metal layers. Another successful doping method for source and drain regions is performed in parallel with the Spin-on-Dopant (SOD). The electrical characterization is done both at room temperature and at cryogenic temperature; the preliminary results shows a correct transistor behaviour at 3 K that gives high expectation on the next measurements for the detection of the charge state of bismuth atoms

Development of novel bioreactors for oesophageal and parenchymatous organs tissue engineering

LAUREA MAGISTRALELa maggior parte delle anomalie congenite del tratto gastrointestinale sono caratterizzate da ostruzioni di vario tipo, che si manifestano frequentemente con difficoltà nell’alimentazione, distensione addominale ed emesi, alla nascita nei primi giorni di vita successivi. L’atresia esofagea è il tipo di atresia più comune del tratto gastrointestinale, con un’incidenza stimata di 1 su 3500 nativi vivi. L’atresia è un’assenza o una chiusura congenita di un orifizio o una struttura tubulare normalmente aperti, ed è associata con vari disordini in altre parti del corpo. Pull-up gastrico, trasposizione del colon e del digiuno rappresentano ad oggi i trattamenti più utilizzati nel caso di atresia esofagea di tipo long-gap. A questi interventi sono però associate severe complicazioni che possono successivamente portare ad ulteriori problemi nel corso della vita dei bambini operati. Inoltre, spesso è necessaria una terapia immunosoppressiva a vita. Queste controindicazioni hanno spinto nella direzione della ricerca di terapie alternative, ed è in questo ambito che l’ingegneria tissutale fa la sua comparsa. Il lavoro principale che viene presentato in questa tesi è incentrato sullo sviluppo originale di un bioreattore utilizzato nella coltura dinamica di un esofago di maiale. Il bioreattore permette di essere regolato sulla base delle dimensioni dell’organo in coltura. La coltura dinamica prevedeva l’estrazione chirurgica dell’esofago, la relativa decellularizzazione al fine di rimuovere il contenuto cellulare nativo, e il successivo ripopolamento dello scaffold decellularizzato con mesoangioblasti e fibroblasti, entrambi di provenienza umana. Il processo di decellularizazione di un organo mira a scartare la gran parte del materiale cellulare originale mantenendo però l’architettura nativa dell’organo, ottenendo uno scaffold. Lo scaffold può essere seminato con determinate cellule e coltivato in vitro per ottenere un tessuto funzionale adatto al trapianto. Il bioreattore sviluppato in questo lavoro è stato usato sia per la decellularizzazione che per la ricellularizzazione. Il tessuto analizzato alla fine della coltura ha mostrato la presenza di agglomerati di cellule in determinate zone, in corrispondenza delle quali era rilevabile un iniziale rimodellamento delle strutture interne native dell’organo. Il bioreattore realizzato permette la coltura di esofagi di differenti dimensioni e in future la sua applicazione potrebbe essere estesa all’intera classe degli organi luminali. In questa tesi viene presentato anche un lavoro aggiuntivo che comprendeva il design di un bioreattore rivolto alla coltura dinamica di tutti gli organi parenchimatosi. Il lavoro eseguito è relative al design, alla costruzione e alla valutazione della sterilità di tale bioreattore. In una prospettiva futura, l’utilizzo di questo bioreattore nell’effettiva coltura dinamica di un organo parenchimatoso (e.g. fegato o reni) può condurre a ulteriori valutazioni sulla sua idoneità all’uso nell’ambito dell’ingegneria tissutale.Most congenital gastrointestinal anomalies result in some type of obstruction, frequently manifesting with feeding difficulties, abdominal distention, and emesis at birth or within the first days. Oesophageal atresia is the most common gastrointestinal atresia, with an estimated incidence of 1 in 3500 live births. Atresia is a congenital absence or closure of a normal body opening or tubular structure and is associated with disorders present in different parts of the body. Gastric pull-up, colon transposition and jejunum transposition represent the most endorsed treatments for long-gap oesophageal atresia. However, these procedures are afflicted by common severe complications that most often lead to later life further problems in operated children. Besides, a life-long immunosuppression is often needed. These problems leaded to the search for alternative therapeutic strategies, and tissue engineering comes within this context. The main work presented in this thesis involves the development of a novel bioreactor used in the dynamic culture of a porcine-derived oesophagus. The bioreactor allows an adjustable set-up for the culture, basing on the organ’s size. The dynamic culture included the harvesting of the oesophagus, the decellularization of the organ in order to remove the native cellular content, and successive re-population of the decellularized scaffold with human mesoangioblasts and human fibroblasts. The decellularization process of an organ discharges most of the original cellular material while aiming to retain the native organ architecture, obtaining a scaffold. The scaffold can be seeded with suitable cells and cultured in vitro to obtain a functional tissue suitable to transplantation. The bioreactor developed in this work was used for both decellularization and recellularization. The tissue analysed at the end of the dynamic culture showed clusters of cells re-populating areas of the scaffold where they started a local remodelling of the organ’s internal structures. The realized bioreactor allows different size oesophagi to be cultured and its application could in the future be extended to all luminal organs. In this thesis is also presented an additional work comprising the design of a bioreactor addressed to the dynamic culture of all parenchymatous organs. The work performed is relative to the design, construction and assessment of the sterility properties of the bioreactor. In a future perspective, the inclusion of this bioreactor in a dynamic culture of a parenchymatous organ (e.g. liver or kidney), can bring further assessments on its suitability for tissue engineering purposes

Impact of plug-in hybrid electric vehicles (PHEV) in the electricity market optimization

LAUREA SPECIALISTIC

Cryogenic Ion Vibrational Spectroscopy of Gas-Phase Clusters: Structure, Anharmonicity and Fluxionality

Gas-phase clusters are aggregates of a countable number of particles, which exhibit size-dependent physical and chemical properties that typically lie in the non-scalable size regime. These properties can be systematically characterized at a molecular level with respect to composition, size and charge state. This allows studying how macroscopic properties of condensed matter, e.g. phase transitions or metallic behavior, emerge from the atomic or molecular properties as a function of cluster size. Furthermore, smaller clusters are also amenable to high-level quantum chemical calculations, making them ideal model systems for understanding phenomena in more complex heterogeneous matter. The main advantage here is that clusters can be studied with a very high degree of selectivity and sensitivity, under well-defined conditions and in the absence of perturbing interaction with an environment. The studies presented in this theses focus on the structure characterization of ionic clusters using cryogenic ion vibrational spectroscopy. This technique combines cryogenic ion trapping with mass spectrometric schemes and infrared photodissociation (IRPD) spectroscopy. It makes use of an ion-trap triple mass spectrometer in combination with various light sources that grant access to a wide range of the infrared spectrum (210-4000 cm-1). Structures are typically assigned by comparing experimental IRPD spectra with computed vibrational spectra. The structures of aluminum oxide clusters and their interaction with water are studied in the framework of the collaborative research center CRC1109 "Understanding of Metal Oxide / Water Systems at the Molecular Scale: Structural Evolution, Interfaces, and Dissolution". This project aims at gaining a molecular level understanding of the mechanisms involved in oxide formation and dissolution. Section 4.1 and 4.2 present results of IRPD spectroscopy experiments on small mono and dialuminum oxide anions and on the anionic cluster series (Al2O3)nAlO2- with n = 0 to 6. These studies discuss the effects of the distribution of the excess charge on the cluster structure, analyze how structural properties evolve with size and how these relate to those of nanoparticles and crystal surfaces. The dissociative adsorption of water by Al-oxide clusters is investigated in Section 4.3.2. Boron exhibits a rich variety of polymorphs with the B12 icosahedron as a common building block. This three dimensional (3D) structure is retained in the halogenated closo-dodecaborate dianions (B12X122-). On the other hand, small pure boron clusters are essentially planar. The study presented in Section 5.2 investigates the 3D to 2D structural transition by probing the vibrational spectra of partially deiodinated B12In2- clusters as a function of decreasing n. The results presented in Section 5.1 show that B13+ has a planar structure consisting of two concentric rings. As a result of delocalized aromatic bonding, this structure is particularly stable without being rigid as it permits an almost free rotation of the inner ring. Protonated water clusters are model systems for understanding protons in aqueous solutions. The interpretation of their vibrational spectra is a challenge for state-of-the-art electronic structure calculations and therefore often prone to controversies. The results presented in Chapter 6 clear existing doubts over the assignment of the protonated water pentamer structure and the vibrational fingerprints of the embedded distorted H3O+. This study laid the foundation for a subsequent series of measurements which provided crucial new insights into the proton transfer mechanism in water

Muscle cell derived angiopoietin-1 contributes to both myogenesis and angiogenesis in the ischemic environment

Recent strategies to treat peripheral arterial disease (PAD) have focused on stem cell based therapies, which are believed to result in local secretion of vascular growth factors. Little is known, however, about the role of ischemic endogenous cells in this context. We hypothesized that ischemic muscle cells (MC) are capable of secreting growth factors that act as potent effectors of the local cellular regenerative environment. Both muscle and endothelial cells (ECs) were subjected to experimental ischemia, and conditioned medium (CM) from each was collected and analyzed to assess myogenic and/or angiogenic potential. In muscle progenitors, mRNA expression of VEGF and its cognate receptors (Nrp1, Flt, Flk) was present and decreased during myotube formation in vitro, and EC CM or VEGF increased myoblast proliferation. Angiopoietin-1 (Ang-1), Tie1, and Tie2 mRNA increased during MC differentiation in vitro. Exogenous Ang-1 enhanced myogenic (MyoD and Myogenin) mRNA in differentiating myoblasts and increased myosin heavy chain protein. Myotube formation was enhanced by MC CM and inhibited by EC CM. Ang-1 protein was present in CM from MCs isolated from both the genetically ischemia-susceptible BALB/c and ischemia-resistant C57BL/6 mouse strains, and chimeric Tie2 receptor trapping in situ ablated Ang-1's myogenic effects in vitro. Ang-1 or MC CM enhanced myotube formation in a mixed isolate of muscle progenitors as well as a myoblast co-culture with pluripotent mesenchymal cells (10T1/2) and this effect was abrogated by viral expression of the extracellular domain of Tie2 (AdsTie2). Furthermore, mesh/tube formation by HUVECs was enhanced by Ang-1 or MC CM and abrogated by Tie2 chimeric receptor trapping. Our results demonstrate the ability of muscle and endothelial cell-derived vascular growth factors, particularly Ang-1, to serve as multi-functional stimuli regulating crosstalk between blood vessels and muscle cells during regeneration from ischemic myopathy