Some hearing, vestibular, and vision disorders are imputable to voltage-gated Ca2+ channels of the sensory cells. These channels convey a large Ca2+ influx despite extracellular Na+ being 70-fold ...more concentrated than Ca2+; such high selectivity is lost in low Ca2+, and Na+ can permeate. Since the permeation properties and molecular identity of sensory Ca2+ channels are debated, in this paper, we examine the Na+ current flowing through the L- and R-type Ca2+ channels of labyrinth hair cells. Ion currents and cytosolic free Ca2+ concentrations were simultaneously monitored in whole-cell recording synchronous to fast fluorescence imaging. L-type and R-type channels were present with different densities at selected sites. In 10 nM Ca2+, the activation and deactivation time constants of the L-type Na+ current were accelerated and its maximal amplitude increased by 6-fold compared to physiological Ca2+. The deactivation of the R-type Na+ current was not accelerated, and its current amplitude increased by 2.3-fold in low Ca2+; moreover, it was partially blocked by nifedipine in a voltage- and time-dependent manner. In conclusion, L channel gating is affected by the ion species permeating the channel, and its selectivity filter binds Ca2+ more strongly than that of R channel; furthermore, external Ca2+ prevents nifedipine from perturbing the R selectivity filter.
Nowadays, most medical-diagnostic, environmental monitoring, etc. devices employ sensors whose fabrication reproducibility and response repeatability assessment are crucial. The former consists of ...large-scale sensor manufacture through a standardized process with almost identical morphology and behavior, while the latter consists of giving the same response upon repeating the same stimulus. The thermo-activated chemoresistive sensors, which change their conductance by interacting with the molecules composing the surrounding gas, are currently employed in many devices: in particular, thick-film (SnTiNb)O2 nanosensors were demonstrated to be particularly suitable in the medical and biological fields. Therefore, a set of thirteen of them, randomly selected from the same screen-printing deposition, were laboratory tested, and the outcomes were statistically analyzed in order to assess their consistency. At first, the working temperature that maximized both the sensor sensitivity and response repeatability was identified. Then, the sensors were subjected to different gas concentrations and humidities at this optimal working temperature. It resulted in the (SnTiNb)O2 nanosensors detecting and discriminating CO concentrations as low as 1 ppm and at high humidity degrees (up to 40%) with high repeatability since the response relative standard error ranged from 0.8 to 3.3% for CO and from 3.6 to 5.4% for water vapor.
To understand the working principles of the nervous system is key to figure out its electrical activity and how this activity spreads along the neuronal network. It is therefore crucial to develop ...advanced techniques aimed to record in real time the electrical activity, from compartments of single neurons to populations of neurons, to understand how higher functions emerge from coordinated activity. To record from single neurons, a technique will be presented to fabricate patch pipettes able to seal on any membrane with a single glass type and whose shanks can be widened as desired. This dramatically reduces access resistance during whole-cell recording allowing fast intracellular and, if required, extracellular perfusion. To simultaneously record from many neurons, biocompatible probes will be described employing multi-electrodes made with novel technologies, based on diamond substrates. These probes also allow to synchronously record exocytosis and neuronal excitability and to stimulate neurons. Finally, to achieve even higher spatial resolution, it will be shown how voltage imaging, employing fast voltage-sensitive dyes and two-photon microscopy, is able to sample voltage oscillations in the brain spatially resolved and voltage changes in dendrites of single neurons at millisecond and micrometre resolution in awake animals.
Colorectal cancer (CRC) represents 10% of the annual tumor diagnosis and deaths occurring worldwide. Given the lack of specific symptoms, which could determine a late diagnosis, the research for ...specific CRC biomarkers and for innovative low-invasive methods to detect them is crucial. Therefore, on the basis of previously published results, some volatile organic compounds (VOCs), detectable through gas sensors, resulted in particularly promising CRC biomarkers, making these sensors suitable candidates to be employed in CRC screening devices. A new device was employed here to analyze the exhalations of blood samples collected from CRC-affected patients at different stages of their pre- and post-surgery therapeutic path, in order to assess the sensor's capability for discriminating among these samples. The stages considered were: the same day of the surgical treatment (T1); before the hospital discharge (T2); after one month and after 10-12 months from surgery (T3 and T4, respectively). This device, equipped with four different sensors based on different metal-oxide mixtures, enabled a distinction between T1 and T4 with a sensitivity and specificity of 93% and 82%, respectively, making it suitable for clinical follow-up protocols, patient health status monitoring and to detect possible post-treatment relapses.
User-friendly, low-cost equipment for preventive screening of severe or deadly pathologies are one of the most sought devices by the National Health Services, as they allow early disease detection ...and treatment, often avoiding its degeneration. In recent years more and more research groups are developing devices aimed at these goals employing gas sensors. Here, nanostructured chemoresistive metal oxide (MOX) sensors were employed in a patented prototype aimed to detect volatile organic compounds (VOCs), exhaled by blood samples collected from patients affected by colorectal cancer and from healthy subjects as a control. Four sensors, carefully selected after many years of laboratory tests on biological samples (cultured cells, human stools, human biopsies, etc.), were based here on various percentages of tin, tungsten, titanium, niobium, tantalum and vanadium oxides. Sensor voltage responses were statistically analyzed also with the receiver operating characteristic (ROC) curves, that allowed the identification of the cut-off discriminating between healthy and tumor affected subjects for each sensor, leading to an estimate of sensitivity and specificity parameters. ROC analysis demonstrated that sensors employing tin and titanium oxides decorated with gold nanoparticles gave sensitivities up to 80% yet with a specificity of 70%.
Preventive screening does not only allow to preemptively intervene on pathologies before they can harm the host; but also to reduce the costs of the intervention itself; boosting the efficiency of ...the NHS (National Health System) by saving resources for other purposes. To improve technology advancements in this field; user-friendly yet low-cost devices are required; and various applications for gas sensors have been tested and proved reliable in past studies. In this work; cell cultures and blood samples have been studied; using nanostructured chemoresistive sensors; to both verify if this technology can reliably detect tumor markers; and if correlations between responses from tumor line metabolites and the screening outcomes on human specimens could be observed. The results showed how sensors responded differently to the emanations from healthy and mutant (for cells) or tumor affected (for blood) samples, and how those results were consistent between them, since the tumoral specimens had higher responses compared to the ones of their healthy counterparts. Even though the patterns in the responses require a bigger population to be defined properly; it appeared that the different macro-groups between the same kind of samples are distinguishable from some of the sensors chosen in the study; giving promising outcomes for further research.
The necessity of detecting and recognizing gases is crucial in many research and application fields, boosting, in the last years, their continuously evolving technology. The basic detection principle ...of gas sensors relies on the conversion of gas concentration changes into a readable signal that can be analyzed to calibrate sensors to detect specific gases or mixtures. The large variety of gas sensor types is here examined in detail, along with an accurate description of their fundamental characteristics and functioning principles, classified based on their working mechanisms (electrochemical, resonant, optical, chemoresistive, capacitive, and catalytic). This review is particularly focused on chemoresistive sensors, whose electrical resistance changes because of chemical reactions between the gas and the sensor surface, and, in particular, we focus on the ones developed by us and their applications in the medical field as an example of the technological transfer of this technology to medicine. Nowadays, chemoresistive sensors are, in fact, strong candidates for the implementation of devices for the screening and monitoring of tumors (the second worldwide cause of death, with ~9 million deaths) and other pathologies, with promising future perspectives that are briefly discussed as well.
The phototransduction enzymatic cascade in cones is less understood than in rods, and the zebrafish is an ideal model with which to investigate vertebrate and human vision. Therefore, here, for the ...first time, the zebrafish green cone photoresponse is characterized also to obtain a firm basis for evaluating how it is modulated by exogenous molecules. To this aim, a powerful method was developed to obtain long-lasting recordings with low access resistance, employing pressure-polished patch pipettes. This method also enabled fast, efficient delivery of molecules via a perfusion system coupled with pulled quartz or plastic perfusion tubes, inserted very close to the enlarged pipette tip. Sub-saturating flashes elicited responses in different cells with similar rising phase kinetics but with very different recovery kinetics, suggesting the existence of physiologically distinct cones having different Ca2+ dynamics. Theoretical considerations demonstrate that the different recovery kinetics can be modelled by simulating changes in the Ca2+-buffering capacity of the outer segment. Importantly, the Ca2+-buffer action preserves the fast response rising phase, when the Ca2+-dependent negative feedback is activated by the light-induced decline in intracellular Ca2+.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chemoresistive nanostructured gas sensors are employed in many diverse applications in the medical, industrial, environmental, etc. fields; therefore, it is crucial to have a device that is able to ...quickly calibrate and characterize them. To this aim, a portable, user-friendly device designed to easily calibrate a sensor in laboratory and/or on field is introduced here. The device comprises a small hermetically sealed chamber (containing the sensor socket and a temperature/humidity sensor), a pneumatic system, and a custom electronics controlled by a Raspberry Pi 4 developing board, running a custom software (Version 1.0) whose user interface is accessed via a multitouch-screen. This device automatically characterizes the sensor heater in order to precisely set the desired working temperature, it acquires and plots the sensor current-to-voltage and Arrhenius relationships on the touch screen, and it can record the sensor responses to different gases and environments. These tests were performed in dry air on two representative sensors based on widely used SnO2 material. The device demonstrated the independence of the Arrhenius plot from the film applied voltage and the linearity of the I–Vs, which resulted from the voltage step length (1–30 min) and temperature (200–550 °C).
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