Design, fabrication, and characterization of a multimodal reconfigurable bioreactor for bone tissue engineering.

In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio-physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many stimulation systems into a single bioreactor led to the generation of several unimodal bioreactors, investigating one or at mostly two of the required biophysical stimuli. These systems miss the physiological mimicry of bone cells environment, and often produced contrasting results, thus making the knowledge of bone mechanotransduction fragmented and often inconsistent. To overcome this issue, in this study we developed a perfusion and electroactive-vibrational reconfigurable stimulation bioreactor to investigate the differentiation of SaOS-2 bone-derived cells, hosting a piezoelectric nanocomposite membrane as cell culture substrate. This multimodal perfusion bioreactor is designed based on a numerical (finite element) model aimed at assessing the possibility to induce membrane nano-scaled vibrations (with ~12 nm amplitude at a frequency of 939 kHz) during perfusion (featuring 1.46 dyn cm-2 wall shear stress), large enough for inducing a physiologically-relevant electric output (in the order of 10 mV on average) on the membrane surface. This study explored the effects of different stimuli individually, enabling to switch on one stimulation at a time, and then to combine them to induce a faster bone matrix deposition rate. Biological results demonstrate that the multimodal configuration is the most effective in inducing SaOS-2 cell differentiation, leading to 20-fold higher collagen deposition compared to static cultures, and to 1.6- and 1.2-fold higher deposition than the perfused- or vibrated-only cultures. These promising results can provide tissue engineering scientists with a comprehensive and biomimetic stimulation platform for a better understanding of mechanotransduction phenomena beyond cells differentiation.

Electrostatic Field-Driven Supercurrent Suppression in Ionic-Gated Metallic Superconducting Nanotransistors.

Recent experiments have shown the possibility of tuning the transport properties of metallic nanosized superconductors through a gate voltage. These results renewed the longstanding debate on the interaction between electrostatic fields and superconductivity. Indeed, different works suggested competing mechanisms as the cause of the effect: an unconventional electric field-effect or quasiparticle injection. Here, we provide conclusive evidence for the electrostatic-field-driven control of the supercurrent in metallic nanosized superconductors, by realizing ionic-gated superconducting field-effect nanotransistors (ISFETs) where electron injection is impossible. Our Nb ISFETs show giant suppression of the superconducting critical current of up to ∼45%. Moreover, the bipolar supercurrent suppression observed in different ISFETs, together with invariant critical temperature and normal-state resistance, also excludes conventional charge accumulation/depletion. Therefore, the microscopic explanation of this effect calls upon a novel theory able to describe the nontrivial interaction of static electric fields with conventional superconductivity.

Field-Effect Controllable Metallic Josephson Interferometer.

Gate-tunable Josephson junctions (JJs) are the backbone of superconducting classical and quantum computation. Typically, these systems exploit low-charge-concentration materials and present technological difficulties limiting their scalability. Surprisingly, electric field modulation of a supercurrent in metallic wires and JJs has been recently demonstrated. Here, we report the realization of titanium-based monolithic interferometers which allow tuning both JJs independently via voltage bias applied to capacitively coupled electrodes. Our experiments demonstrate full control of the amplitude of the switching current (Is) and of the superconducting phase across the single JJ in a wide range of temperatures. Astoundingly, by gate-biasing a single junction, the maximum achievable total Is is suppressed down to values much lower than the critical current of a single JJ. A theoretical model including gate-induced phase fluctuations on a single junction accounts for our experimental findings. This class of quantum interferometers could represent a breakthrough for several applications such as digital electronics, quantum computing, sensitive magnetometry, and single-photon detection.

Ultra-Efficient Superconducting Dayem Bridge Field-Effect Transistor.

Superconducting field-effect transitor (SuFET) and Josephson field-effect transistor (JoFET) technologies take advantage of electric-field-induced control of charge-carrier concentration to modulate the channel superconducting properties. Despite the fact that the field-effect is believed to be ineffective for superconducting metals, recent experiments showed electric-field-dependent modulation of the critical current ( IC) in a fully metallic transistor. However, the grounding mechanism of this phenomenon is not completely understood. Here, we show the experimental realization of Ti-based Dayem bridge field-effect transistors (DB-FETs) able to control the IC of the superconducting channel. Our easy fabrication process for DB-FETs show symmetric full suppression of IC for applied critical gate voltages as low as VGC ≃ ±8 V at temperatures reaching about the 85% of the record critical temperature, TC ≃ 550 mK, for titanium. The gate-independent TC and normal-state resistance ( RN) coupled with the increase of resistance in the superconducting state ( RS) for gate voltages close to the critical value ( VGC) suggest the creation of field-effect induced metallic puddles in the superconducting sea. Our devices show extremely high values of transconductance (| gmMAX| ≃ 15 µA/V at VG ≃ ±6.5 V) and variations of Josephson kinetic inductance ( LK) with VG of 2 orders of magnitude. Therefore, the DB-FET appears as an ideal candidate for the realization of superconducting electronics, superconducting qubits, and tunable interferometers as well as photon detectors.

Toward the Absolute Spin-Valve Effect in Superconducting Tunnel Junctions.

A superconductor with a spin-split excitation spectrum behaves as an ideal ferromagnetic spin-injector in a tunneling junction. It was theoretically predicted that the combination of two such spin-split superconductors with independently tunable magnetizations may be used as an ideal absolute spin-valve. Here, we report on the first switchable superconducting spin-valve based on two EuS/Al bilayers coupled through an aluminum oxide tunnel barrier. The spin-valve shows a relative resistance change between the parallel and antiparallel configuration of the EuS layers up to 900% that demonstrates a highly spin-polarized current through the junction. Our device may be pivotal for realization of thermoelectric radiation detectors, a logical element for a memory cell in cryogenics, superconductor-based computers, and superconducting spintronics in general.

Ultrasound-activated piezoelectric P(VDF-TrFE)/boron nitride nanotube composite films promote differentiation of human SaOS-2 osteoblast-like cells.

Piezoelectric films of poly(vinylidenedifluoride-trifluoroethylene) (P(VDF-TrFE)) and of P(VDF-TrFE)/boron nitride nanotubes (BNNTs) were prepared by cast-annealing and used for SaOS-2 osteoblast-like cell culture. Films were characterized in terms of surface and bulk features, and composite films demonstrated enhanced piezoresponse compared to plain polymeric films (d31 increased by ~80%). Osteogenic differentiation was evaluated in terms of calcium deposition, collagen I secretion, and transcriptional levels of marker genes (Alpl, Col1a1, Ibsp, and Sparc) in cells either exposed or not to ultrasounds (US); finally, a numerical model suggested that the induced voltage (~20-60 mV) is suitable for cell stimulation. Although preliminary, our results are extremely promising and encourage the use of piezoelectric P(VDF-TrFE)/BNNT films in bone tissue regeneration.

Ultrasound-Activated Piezoelectric Nanoparticles Trigger Microglia Activity Against Glioblastoma Cells.

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core a genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma-associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, "classically activated" M1 microglia could provide proinflammatory and antitumorigenic activity, expected to exert a beneficial effect in defeating glioblastoma. In this work, an immunotherapy approach based on proinflammatory modulation of the GAM phenotype is proposed, through a controlled and localized electrical stimulation. The developed strategy relies on the wireless ultrasonic excitation of polymeric piezoelectric nanoparticles coated with GBM cell membrane extracts, to exploit homotypic targeting in antiglioma applications. Such camouflaged nanotransducers locally generate electrical cues on GAM membranes, activating their M1 phenotype and ultimately triggering a promising anticancer activity. Collected findings open new perspectives in the modulation of immune cell activities through "smart" nanomaterials and, more specifically, provide an innovative auspicious tool in glioma immunotherapy.

Gate Control of Superconductivity in Mesoscopic All-Metallic Devices.

The possibility to tune, through the application of a control gate voltage, the superconducting properties of mesoscopic devices based on Bardeen-Cooper-Schrieffer metals was recently demonstrated. Despite the extensive experimental evidence obtained on different materials and geometries, a description of the microscopic mechanism at the basis of such an unconventional effect has not been provided yet. This work discusses the technological potential of gate control of superconductivity in metallic superconductors and revises the experimental results, which provide information regarding a possible thermal origin of the effect: first, we review experiments performed on high-critical-temperature elemental superconductors (niobium and vanadium) and show how devices based on these materials can be exploited to realize basic electronic tools, such as a half-wave rectifier. Second, we discuss the origin of the gating effect by showing gate-driven suppression of the supercurrent in a suspended titanium wire and by providing a comparison between thermal and electric switching current probability distributions. Furthermore, we discuss the cold field-emission of electrons from the gate employing finite element simulations and compare the results with experimental data. In our view, the presented data provide a strong indication regarding the unlikelihood of the thermal origin of the gating effect.

Gate Control of the Current-Flux Relation of a Josephson Quantum Interferometer Based on Proximitized Metallic Nanojuntions.

We demonstrate an Al superconducting quantum interference device in which the Josephson junctions are implemented through gate-controlled proximity Cu mesoscopic weak links. This specific kind of metallic weak links behaves analogously to genuine superconducting metals in terms of the response to electrostatic gating and provides a good performance in terms of current-modulation visibility. We show that through the application of a static gate voltage we can modify the interferometer current-flux relation in a fashion that seems compatible with the introduction of π-channels within the gated weak link. Our results suggest that the microscopic mechanism at the origin of the suppression of the switching current in the interferometer is apparently phase coherent, resulting in an overall damping of the superconducting phase rigidity. We finally tackle the performance of the interferometer in terms of responsivity to magnetic flux variations in the dissipative regime and discuss the practical relevance of gated proximity-based all-metallic SQUIDs for magnetometry at the nanoscale.

Gate-Controlled Suspended Titanium Nanobridge Supercurrent Transistor.

Under standard conditions, the electrostatic field-effect is negligible in conventional metals and was expected to be completely ineffective also in superconducting metals. This common belief was recently put under question by a family of experiments that displayed full gate-voltage-induced suppression of critical current in superconducting all-metallic gated nanotransistors. To date, the microscopic origin of this phenomenon is under debate, and trivial explanations based on heating effects given by the negligible electron leakage from the gates should be excluded. Here, we demonstrate the control of the supercurrent in fully suspended superconducting nanobridges. Our advanced nanofabrication methods allow us to build suspended superconducting Ti-based supercurrent transistors which show ambipolar and monotonic full suppression of the critical current for gate voltages of VGC ≃ 18 V and for temperatures up to ∼80% of the critical temperature. The suspended device architecture minimizes the electron-phonon interaction between the superconducting nanobridge and the substrate, and therefore, it rules out any possible contribution stemming from charge injection into the insulating substrate. Besides, our finite element method simulations of vacuum electron tunneling from the gate to the bridge and thermal considerations rule out the cold-electron field emission as a possible driving mechanism for the observed phenomenology. Our findings promise a better understanding of the field effect in superconducting metals.

Josephson Field-Effect Transistors Based on All-Metallic Al/Cu/Al Proximity Nanojunctions.

We demonstrate proximity-based all-metallic mesoscopic superconductor-normal metal-superconductor (SNS) field-effect controlled Josephson transistors (SNS-FETs) and show their full characterization from the critical temperature Tc down to 50 mK in the presence of both electric and magnetic fields. The ability of a static electric field-applied by means of a lateral gate electrode-to suppress the critical current Is in a proximity-induced superconductor is proven for both positive and negative gate voltage values. Is reached typically about one-third of its initial value, saturating at high gate voltages. The transconductance of our SNS-FETs obtains values as high as 100 nA/V at 100 mK. On the fundamental physics side, our results suggest that the mechanism at the basis of the observed phenomenon is quite general and does not rely on the existence of a true pairing potential, but rather the presence of superconducting correlations is enough for the effect to occur. On the technological side, our findings widen the family of materials available for the implementation of all-metallic field-effect transistors to synthetic proximity-induced superconductors.

Metallic supercurrent field-effect transistor.

In their original formulation of superconductivity, the London brothers predicted1 the exponential suppression of an electrostatic field inside a superconductor over the so-called London penetration depth2-4, λL. Despite a few experiments indicating hints of perturbation induced by electrostatic fields5-7, no clue has been provided so far on the possibility to manipulate metallic superconductors via the field effect. Here, we report field-effect control of the supercurrent in all-metallic transistors made of different Bardeen-Cooper-Schrieffer superconducting thin films. At low temperature, our field-effect transistors show a monotonic decay of the critical current under increasing electrostatic field up to total quenching for gate voltage values as large as ±40 V in titanium-based devices. This bipolar field effect persists up to ~85% of the critical temperature (~0.41 K), and in the presence of sizable magnetic fields. A similar behaviour is observed in aluminium thin-film field-effect transistors. A phenomenological theory accounts for our observations, and points towards the interpretation in terms of an electric-field-induced perturbation propagating inside the superconducting film. In our understanding, this affects the pairing potential and quenches the supercurrent. These results could represent a groundbreaking asset for the realization of all-metallic superconducting field-effect electronics and leading-edge quantum information architectures8,9.

A surface-acoustic-wave-based cantilever bio-sensor.

A scalable surface-acoustic-wave- (SAW-) based cantilevered device for portable bio-chemical sensing applications is presented. Even in the current, proof-of-principle implementation this architecture is shown to outperform commercial quartz-crystal microbalances in terms of sensitivity. Adhesion of analytes on a functionalized surface of the cantilever shifts the resonant frequency of a SAW-generating transducer due to the stress-induced variation of the speed of surface acoustic modes. We discuss the relevance of this approach for diagnostics applications based on miniaturized devices.

Interaction-free, automatic, on-chip fluid routing by surface acoustic waves.

By exploiting the resonant coupling between a travelling wave and the stationary modes of a cavity, we present the first scheme for integrated automatic interaction-free surface acoustic wave routing of fluids. Our scheme opens the way to the implementation of logic gates based on instantaneous liquid distribution.