Search

Abstract The analysis of the time profile of electrical signals produced by energy depositions in germanium detectors allows discrimination of events with different topologies. This is especially relevant for experiments searching for the neutrinoless double beta decay of $$^{76}$$ 76 Ge to distinguish the sought-after signal from other background sources. The standard calibration procedures used to tune the selection criteria for double-beta decay events use a $$^{228}$$ 228 Th source, because it provides samples of signal-like events. These samples exhibit energy spatial distributions with subtle different topologies compared to neutrinoless double-beta decay events. In this work, we will characterize these topological differences and, with the support of a $$^{56}$$ 56 Co source, evaluate biases and precision of calibration techniques which use such event samples. Our results will be particularly relevant for future experiments in which a solid estimation of the efficiency is required.

Abstract A large experimental program is being mounted to search for neutrinoless double-beta decay over the next decade. Multiple experiments using different target isotopes are being prepared to explore the whole parameter space allowed for inverted-ordered light neutrinos, and have the potential to make discoveries in several other scenarios, including normal-ordered light neutrinos and other exotic mechanisms. We investigate to what extent long-range and exotic short-range contributions may be distinguished by combining measurements of the decay half-life across isotopes in the framework of a global Bayesian analysis. We demonstrate how measurements in two isotopes will constrain the parameter space up to a two-fold degeneracy, and how a further measurement in a third isotope removes such a degeneracy. We also discuss the impact of uncertainties and correlations in nuclear matrix element calculations. Our work motivates an experimental program measuring neutrinoless double-beta decay in more than one isotope, as this would break parameter degeneracies and advance our understanding of particle physics beyond the Standard Model.

A rationally designed gold-functionalized surface capable of capturing a target protein is presented using the biotin–streptavidin pair as a proof-of-concept. We carried out multiscale simulations to shed light on the binding mechanism of streptavidin on four differently biotinylated surfaces. Brownian Dynamics simulations were used to reveal the preferred initial orientation of streptavidin over the surfaces, whereas classical molecular dynamics was used to refine the binding poses and to investigate the fundamental forces involved in binding, and the binding kinetics. We assessed the binding events and the stability of the streptavidin attachment through a quartz crystal microbalance with dissipation monitoring (QCM-D). The sensing element comprises of biotinylated polyethylene glycol chains grafted on the sensor’s gold surface via thiol-Au chemistry. Finally, we compared the results from experiments and simulations. We found that the confined biotin moieties can specifically capture streptavidin from the liquid phase and provide guidelines on how to exploit the microscopic parameters obtained from simulations to guide the design of further biosensors with enhanced sensitivity.

Biosensors based on surface acoustic waves (SAWs) offer unique advantages due to their high sensitivity, real-time response capability, and label-free detection. The typical SAW modes are the Rayleigh mode and the shear-horizontal mode. Both present pros and cons for biosensing applications and generally need different substrates and device geometries to be efficiently generated. This study investigates and characterizes SAW resonator biosensors on lithium niobate in terms of modes generated and biosensing performance. It reveals the simultaneous presence of two typical SAW modes, the first around 1.6 GHz and the second around 1.9 GHz, differently polarized and clearly separated in frequency, which we refer to as slow and fast modes. The two modes are studied by numerical simulations and biosensing experiments with the glial-fibrillary-acidic-protein (GFAP) biomarker. The slow mode is generally more sensitive to changes in surface properties, such as temperature and mass changes, by a factor of about 1.4 with respect to the fast mode.

BackgroundSARS-CoV-2 induces a spectrum of clinical conditions ranging from asymptomatic infection to life threatening severe disease. Host microRNAs have been involved in the cytokine storm driven by SARS-CoV-2 infection and proposed as candidate biomarkers for COVID-19.MethodsTo discover signatures of circulating miRNAs associated with COVID-19, disease severity and mortality, small RNA-sequencing was performed on serum samples collected from 89 COVID-19 patients (34 severe, 29 moderate, 26 mild) at hospital admission and from 45 healthy controls (HC). To search for possible sources of miRNAs, investigation of differentially expressed (DE) miRNAs in relevant human cell types in vitro.ResultsCOVID-19 patients showed upregulation of miRNAs associated with lung disease, vascular damage and inflammation and downregulation of miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis, and stress response. Compared with mild/moderate disease, patients with severe COVID-19 had a miRNA signature indicating a profound impairment of innate and adaptive immune responses, inflammation, lung fibrosis and heart failure. A subset of the DE miRNAs predicted mortality. In particular, a combination of high serum miR-22-3p and miR-21-5p, which target antiviral response genes, and low miR-224-5p and miR-155-5p, targeting pro-inflammatory factors, discriminated severe from mild/moderate COVID-19 (AUROC 0.88, 95% CI 0.80-0.95, p

Abstract The time analysis of the signal induced by the drift of charge carriers in high purity germanium detectors provides information on the event topology. Millions of charge carriers are produced in a typical event. Their initial distribution, stochastic diffusion and Coulomb self-repulsion affect the time structure of the signal. We present a comprehensive study of these effects and evaluate their impact on the event discrimination capabilities for the three geometries which will be used in the Legend experiment for neutrinoless double-beta decay.

Abstract The frequentist statistical methods applied to search for short-baseline neutrino oscillations induced by a sterile neutrino with mass at the eV scale are reviewed and compared. The comparison is performed under limit setting and signal discovery scenarios, considering both when an oscillation would enhance the neutrino interaction rate in the detector and when it would reduce it. The sensitivity of the experiments and the confidence regions extracted for specific data sets change considerably according to which test statistic is used and the assumptions on its probability distribution. A standardized analysis approach based on the most general kind of hypothesis test is proposed.

Love surface acoustic wave (L-SAW) devices are ideal for real-time sensing applications. High miniaturization and sensitivity are desirable in particular for point of care diagnostics or on-site measurements. It is possible to enhance both these parameters by increasing the working frequency of these devices, but this is still a challenge. Indeed, the ultra-high frequency (UHF) range has not been explored yet for L-SAW sensing devices because it requires non-trivial fabrication and measurement setup. Here, we present a multiplexable, highly miniaturized UHF L-SAW device for real-time sensing applications. The sensor performance was first tested with mixtures of different volume percentages of isopropyl alcohol (IPA) in water. Measurements of phase and amplitude (related to change of density and viscosity, respectively) show higher sensitivity and dynamic range than a representative 100 MHz L-SAW sensor. Then, we measured the adsorption kinetics of three different concentrations of bovine serum albumin (BSA) in water on the sensor surface, demonstrating biomolecule detection. The all-electrical readout system as long as the small dimensions make the presented device particularly promising for portable UHF sensing platforms. Nonetheless, the higher sensitivity and dynamic range obtained with respect to a representative 100 MHz L-SAW sensor as long as the real-time measurements of the BSA adsorption (with an estimated limit of detection of 90 ng/mm2) show that UHF Love SAW sensors have the potential to be used for bio-sensing applications, such as point of care diagnostics.

Enzyme detection in liquid samples is a complex laboratory procedure, based on assays that are generally time- and cost-consuming, and require specialized personnel. Surface acoustic wave sensors can be used for this application, overcoming the cited limitations. To give our contribution, in this work we present the bottom-up development of a surface acoustic wave biosensor to detect active α-glycosidase in aqueous solutions. Our device, optimized to work at an ultra-high frequency (around 740 MHz), is functionalized with a newly synthesized probe 7-mercapto-1-eptyl-D-maltoside, bringing one maltoside terminal moiety. The probe is designed ad hoc for this application and tested in-cuvette to analyze the enzymatic conversion kinetics at different times, temperatures and enzyme concentrations. Preliminary data are used to optimize the detection protocol with the SAW device. In around 60 min, the SAW device is able to detect the enzymatic conversion of the maltoside unit into glucose in the presence of the active enzyme. We obtained successful α-glycosidase detection in the concentration range 0.15–150 U/mL, with an increasing signal in the range up to 15 U/mL. We also checked the sensor performance in the presence of an enzyme inhibitor as a control test, with a signal decrease of 80% in the presence of the inhibitor. The results demonstrate the synergic effect of our SAW Lab-on-a-Chip and probe design as a valid alternative to conventional laboratory tests.

Many approaches to diagnostic testing remain decades old. Well-established biosensing technologies (e.g., enzyme-linked immunosorbent assays and radio-immunoassays) typically cannot fulfill the requirements of portability and ease of use necessary for point-of-care purposes. Several alternatives have been proposed (e.g., quartz-crystal-microbalances, electrochemical sensors, cantilevers, and surface-plasmon-resonance sensors) but often lack high performance or still necessitate bulk ancillary instruments to operate. Here we present a highly sensitive, versatile, and easily integrable microfluidic lab-on-a-chip (LoC) for biosensing, fully based on surface acoustic waves (SAWs). By using ultra-high-frequency resonator-biosensors, we show that it is possible to perform highly sensitive assays in complex media. This all-electrical readout platform is benchmarked with the biotin-streptavidin binding in presence of non-specific binding proteins (serum albumin) at physiological concentration. The benchmark experiments were performed with the idea of mimicking a biological fluid, in which other molecular species at high concentration are present together with the analytes. We demonstrate that this LoC can detect sub-nanomolar concentrations of analytes in complex media. As a comparison with similar acoustic-wave-based systems, this full-SAW platform outperforms the standard commercial gravimetric sensors (i.e., quartz-crystal-microbalances) and the more common Love-SAW biosensors. This full-SAW LoC could be further developed for the detection of biomarkers in biological fluids.

The Standard Model of Particle Physics predicts the double-β decay of certain nuclei with the emission of two active neutrinos. In this letter, we argue that double-β decay experiments could be used to probe models with light exotic fermions through the search for spectral distortions in the electron spectrum with respect to the Standard Model expectations. We consider two concrete examples: models with light sterile neutrinos, singly produced in the double-β decay, and models with a light Z2-odd fermion, pair produced due to a Z2 symmetry. We estimate the discovery potential of a selection of double-β decay experiments and find that future searches will test for the first time a new part of the parameter space of interest at the MeV-mass scale.

Polyphenols are a family of compounds present in grapes, musts, and wines. Their dosage is associated with the grape ripening, correct must fermentation, and final wine properties. Owing to their anti-inflammatory properties, they are also relevant for health applications. To date, such compounds are detected mainly via standard chemical analysis, which is costly for constant monitoring and requires a specialized laboratory. Cheap and portable sensors would be desirable to reduce costs and speed up measurements. This paper illustrates the development of strategies for sensor surface chemical functionalization for polyphenol detection. We perform measurements by using a commercial quartz crystal microbalance with dissipation monitoring apparatus. Chemical functionalizations are based on proteins (bovine serum albumin and gelatin type A) or customized peptides derived from istatine-5 and murine salivary protein-5. Commercial oenological additives containing pure gallic tannins or proanthocyanidins, dissolved in water or commercial wine, are used for the analysis. Results indicate that selected functionalizations enable the detection of the two different tannin families, suggesting a relationship between the recorded signal and concentration. Gelatin A also demonstrates the ability to discriminate gallic tannins from proanthocyanidins. Outcomes are promising and pave the way for the exploitation of such devices for precision oenology.

In order to properly manipulate liquids into microfluidic networks, an accurate sealing of the device is of paramount importance. Polydimethylsiloxane (PDMS) is ubiquitously used for fabricating microfluidic components, owing to its low cost, easy and fast fabrication, and optical transparency. However, PDMS is characterized by low surface energy, making its bonding to many substrates not trivial. Here is presented a versatile technique for PDMS microchannel bonding on untreated plastic and metal surfaces. First, the PDMS surface is functionalized with (3-aminopropyl) triethoxysilane (APTES) for further cross-linking with epoxy groups. Then, the PDMS-APTES surface is coated with Norland Optical Adhesive 74 (NOA74). Finally, the PDMS-APTES-NOA74 is put in contact with the target material and the glue is cured under a UV light. In order to characterize the bonding strength, a complete PDMS-on-gold microfluidic device is fabricated and tested with increasing injection pressures. Different liquids and a gas (nitrogen) are applied without leakage up to 2 bars, a value comparable to the one reported for the standard glass-PDMS bonding through plasma oxygen activation. The same technique is then successfully replicated with other nonmetallic substrates of interest for microfluidics, i.e., glass, poly(methyl methacrylate), polystyrene, polyethylene terephthalate, cyclic olefin copolymer, demonstrating its great versatility and potential for, but not limited to, microfluidic applications and LOC engineering.

Abstract Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients’ osteoclast precursors. To evaluate the effect of coagulation factors on osteoclasts, we treated Healthy Donor-Peripheral Blood Mononuclear Cells (HD-PBMC) with Factor VIII (FVIII), von Willebrand Factor (VWF), FVIII/VWF complex, activated Factor IX (FIXa), activated Factor X (FXa) and Thrombin (THB). FVIII, VWF, FVIII/VWF, FXa and THB treatments reduced osteoclast differentiation of HD-PBMC and VWF affected also bone resorption. Interestingly, PBMC isolated from patients with moderate/severe haemophilia showed an increased osteoclastogenic potential due to the alteration of osteoclast precursors. Moreover, increased expression of genes involved in osteoclast differentiation/activity was revealed in osteoclasts of an adult patient with moderate haemophilia. Control osteoblasts treated with the coagulation factors showed that FVIII and VWF reduced ALP positivity; the opposite effect was observed following THB treatment. Moreover, FVIII, VWF and FVIII/VWF reduced mineralization ability. These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia.

Solar neutrinos have played a central role in the discovery of the neutrino oscillation mechanism. They still are proving to be a unique tool to help investigate the fusion reactions that power stars and further probe basic neutrino properties. The Borexino neutrino observatory has been operationally acquiring data at Laboratori Nazionali del Gran Sasso in Italy since 2007. Its main goal is the real-time study of low energy neutrinos (solar or originated elsewhere, such as geo-neutrinos). The latest analysis of experimental data, taken during the so-called Borexino Phase-II (2011-present), will be showcased in this talk—yielding new high-precision, simultaneous wide band flux measurements of the four main solar neutrino components belonging to the “pp„ fusion chain (pp, pep, 7 Be, 8 B), as well as upper limits on the remaining two solar neutrino fluxes (CNO and hep).

Surface chemical and biochemical functionalization is a fundamental process that is widely applied in many fields to add new functions, features, or capabilities to a material’s surface. Here, we demonstrate that surface acoustic waves (SAWs) can enhance the chemical functionalization of gold films. This is shown by using an integrated biochip composed by a microfluidic channel coupled to a surface plasmon resonance (SPR) readout system and by monitoring the adhesion of biotin-thiol on the gold SPR areas in different conditions. In the case of SAW-induced streaming, the functionalization efficiency is improved ≈ 5 times with respect to the case without SAWs. The technology here proposed can be easily applied to a wide variety of biological systems (e.g., proteins, nucleic acids) and devices (e.g., sensors, devices for cell cultures).

Background: The objective of this study was to establish the age and sex-dependent reference intervals for coagulation assays evaluated in healthy children, ranging from 0 days to 16 years old. Methods: PT, aPTT, Fibrinogen (functional), Antithrombin activity, Protein C anticoagulant activity, Protein S free antigen, Thrombin time, D-Dimer, Von Willebrand Factor antigen, Lupus anticoagulant (screening), extrinsic and intrinsic pathway factors, and activated Protein C resistance were evaluated using STA-R Max2. Results: A total of 1280 subjects (671 males and 609 females) were divided into five groups, according to their age: 0–15 days (n = 280, 174 M and 106 F), 15–30 days (n = 208, 101 M and 107 F), 1–6 months (n = 369, 178 M and 191 F), 6–12 months (n = 214, 110 M and 104 F), and 1–16 years (n = 209, 108 M and 101 F). The 95% reference intervals and the 90% CI were established using the Harrell–Davis bootstrap method and the bootstrap percentile method, respectively. Conclusions: The present study supports the concept that adult and pediatric subjects should be evaluated using different reference intervals, at least for some coagulation tests, to avoid misdiagnosis, which can potentially lead to serious consequences for patients and their families, and ultimately the healthcare system.

Gorham-Stout disease (GSD) is a very rare syndrome displaying excessive bone erosion and vascular lesion. Due to the rarity of the disease and to the limited studies, its etiopathogenesis is not entirely known. The involvement of immune system in the progressive osteolysis was recently suggested. Indeed, extensive reciprocal interactions between the immune and skeletal systems have been demonstrated. This study aimed to evaluate alterations of immune cells in GSD. An increase of CD8+ cells and reduction of CD4+ and CD4+CD25+CD127low cells was revealed in patients. Interestingly, patients’ regulatory T cells maintain the ability to respond to extracellular stimuli and to regulate osteoclastogenesis; GSD cells proliferate under aCD3/CD28 signal reaching similar levels to those observed in control culture and exert their immunomodulatory activity on effector T cells. GSD Treg cells preserved their inhibitory effects on the osteoclastogenesis. These results suggest that stimulation of Treg cells could open the way for the identification and testing of new therapeutic approaches for patients affected by GSD.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed, it was shown that extracellular vesicles, including exosomes and microvesicles, released from tumor cells can modify the bone microenvironment, allowing the formation of osteolytic, osteosclerotic, and mixed mestastases. In turn, bone-derived EV can stimulate the proliferation of tumor cells. The inhibition of EV-mediated crosstalk between cancer and bone cells could represent a new therapeutic target for bone metastasis.