Optical fiber technology is gaining increasing importance in all those fields requiring reliable, miniaturized, compact, and plug‐and‐play devices, with a special relevance in life science ...applications. Here, optical fibers are adopted to measure the fluids viscosity, by detecting the transit time (related to viscosity) of a steel bead moving through the tested fluid in a microfluidic channel under constant pressure. The proposed optofluidic system is designed by defining a theoretical model, here experimentally validated in the viscosity range of 5–110 cP, well resembling main blood flow features. The achieved results demonstrate the capability to work in multi‐point and single‐point detection modalities with a trade‐off between resolution (minimum of 10−1 and 1 cP respectively) and measurement time (tens of seconds and milliseconds range, respectively). An optimum accuracy close to 1.5% has been achieved, with room for further optimization by reducing bead size uncertainty. The proposed platform features simple, low‐cost, reliable, and fast measurements and ensures the integration with microfluidics chip in a miniaturized and disposable system. The low volumes required (scalable down to µL range) and the ease of use enable the translation of the proposed platform in clinical scenarios involving real‐time blood and plasma viscosity measurements under physiological conditions.
An optofluidic device is developed using optical fibers to measure biofluids viscosity via amicrofluidic channel and experimentally validated in the blood viscosity range. The system allows for both multi‐point and single‐point detection, balancing resolution (10−1/1 cP) and measurement times. With an accuracy of 1.5%, it is ideal for clinical applications, providing real‐time viscosity measurements in a user‐friendly, low‐volume operation.
Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by ...α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE–AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.
Integrating multi-responsive polymers such as microgels onto optical fiber tips, in a controlled fashion, enables unprecedented functionalities to Lab-on-fiber optrodes. The creation of a uniform ...microgel monolayer with a specific coverage factor is crucial for enhancing the probes responsivity to a pre-defined target parameter. Here we report a reliable fabrication strategy, based on the dip coating technique, for the controlled realization of microgel monolayer onto unconventional substrates, such as the optical fiber tip. The latter was previously covered by a plasmonic nanostructure to make it sensitive to superficial environment changes. Microgels have been prepared using specific Poly(
-isopropylacrylamide)-based monomers that enable bulky size changes in response to both temperature and pH variations. The formation of the microgel monolayer is efficiently controlled through the selection of suitable operating pH, temperature and concentration of particle dispersions used during the dipping procedure. The effect of each parameter has been evaluated, and the validity of our procedure is confirmed by means of both morphological and optical characterizations. We demonstrate that when the coverage factor exceeds 90%, the probe responsivity to microgels swelling/collapsing is significantly improved. Our study opens new paradigms for the development of engineered microgels assisted Lab-on-Fiber probes for biochemical applications.
Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to ...assess the content of HNE, α1-antitrypsin (AAT) and HNE-AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by Liquid Chromatography-Mass Spectrometry. NETs' release was analyzed by confocal microscopy. Both HNE and AAT were clearly detectable in BALf at high levels. Contrary to what was previously observed in other settings, the formation of HNE-AAT complex was not detected in COVID-19. Rather, HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free AAT to bind to histones. While confirming this binding, AAT was not able to inhibit NET formation. In conclusion, despite the finding of a high burden of free and bound HNE, the lack of the HNE-AAT inhibitory complex in COVID-19 BALf demonstrates that AAT is not able to block HNE activity. Furthermore, while binding to histones, AAT does not prevent NET formation nor their noxious activity.
In this retrospective study, we report the effectiveness and safety of a dedicated extracorporeal carbon dioxide removal (ECCO
R) device in critically ill patients.
Adult patients on mechanical ...ventilation due to acute respiratory distress syndrome (ARDS) or decompensated chronic obstructive pulmonary disease (dCOPD), who were treated with a dedicated ECCO
R device (CO2RESET, Eurosets, Medolla, Italy) in case of hypercapnic acidemia, were included. Repeated measurements of CO
removal (VCO
) at baseline and 1, 12, and 24 h after the initiation of therapy were recorded.
Over a three-year period, 11 patients received ECCO
R (median age 60 43-72 years) 3 (2-39) days after ICU admission; nine patients had ARDS and two had dCOPD. Median baseline pH and PaCO
levels were 7.27 (7.12-7.33) and 65 (50-84) mmHg, respectively. With a median ECCO
R blood flow of 800 (500-800) mL/min and maximum gas flow of 6 (2-14) L/min, the VCO
at 12 h after ECCO
R initiation was 157 (58-183) mL/min. Tidal volume, respiratory rate, and driving pressure were significantly reduced over time. Few side effects were reported.
In this study, a dedicated ECCO
R device provided a high VCO
with a favorable risk profile.
The need for miniaturized biological sensors which can be easily integrated into medical needles and catheters for in vivo liquid biopsies with ever-increasing performances has stimulated the ...interest of researchers in lab-on-fiber (LOF) technology. LOF devices arise from the integration of functional materials at the nanoscale on the tip of optical fibers, thus endowing a simple optical fiber with advanced functionalities and enabling the realization of high-performance LOF biological sensors. Consequently, in 2017, we demonstrated the first optical fiber meta-tip (OFMT), consisting of the integration of plasmonic metasurfaces (MSs) on the optical fiber end-face which represented a major breakthrough along the LOF technology roadmap. Successively, we demonstrated that label-free biological sensors based on the plasmonic OFMT are able to largely overwhelm the performance of a standard plasmonic LOF sensor, in view of the extraordinary light manipulation capabilities of plasmonic array exploiting phase gradients. To further improve the overall sensitivity, a labelled sensing strategy is here suggested. To this end, we envision the possibility to realize a novel class of labelled LOF optrodes based on OFMT, where an all-dielectric MS, designed to enhance the fluorescence emission by a labelled target molecule, is integrated on the end-face of a multimode fiber (MMF). We present a numerical environment to compute the fluorescence enhancement factor collected by the MMF, when on its tip a Silicon MS is laid, consisting of an array of cylindrical nanoantennas, or of dimers or trimers of cylindrical nanoantennas. According to the numerical results, a suitable design of the dielectric MS allows for a fluorescence enhancement up to three orders of magnitudes. Moreover, a feasibility study is carried out to verify the possibility to fabricate the designed MSs on the termination of multimode optical fibers using electron beam lithography followed by reactive ion etching. Finally, we analyze a real application scenario in the field of biosensing and evaluate the degradation in the fluorescence enhancement performances, taking into account the experimental conditions. The present work, thus, provides the main guidelines for the design and development of advanced LOF devices based on the fluorescence enhancement for labelled biosensing applications.
The combination of responsive microgels and Lab-on-Fiber devices represents a valuable technological tool for developing advanced optrodes, especially useful for biomedical applications. Recently, we ...have reported on a fabrication method, based on the dip coating technique, for creating a microgels monolayer in a controlled fashion onto the fiber tip. In the wake of these results, with a view towards industrial applications, here we carefully analyze, by means of both morphological and optical characterizations, the effect of each fabrication step (fiber dipping, rinsing, and drying) on the microgels film properties. Interestingly, we demonstrate that it is possible to significantly reduce the duration (from 960 min to 31 min) and the complexity of the fabrication procedure, without compromising the quality of the microgels film at all. Repeatability studies are carried out to confirm the validity of the optimized deposition procedure. Moreover, the new procedure is successfully applied to different kinds of substrates (patterned gold and bare optical fiber glass), demonstrating the generality of our findings. Overall, the results presented in this work offer the possibility to improve of a factor ~30 the fabrication throughput of microgels-assisted optical fiber probes, thus enabling their possible exploitation in industrial applications.
Key Clinical Message
After risk assessment, veno‐venous extracorporeal membrane oxygenation (ECMO) has been achieved in a superobese adult patient as a bridge to recovery of respiratory failure, ...despite the weight‐related difficulties. Early v‐v ECMO implantation could be considered to support and to conduct weaning both from sedation and from invasive mechanical ventilation, with the goal to perform physiokinesitherapy during awake ECMO.
After risk assessment, veno‐venous extracorporeal membrane oxygenation (ECMO) has been achieved in a superobese adult patient as a bridge to recovery of respiratory failure, despite the weight‐related difficulties. Early v‐v ECMO implantation could be considered to support and to conduct weaning both from sedation and from invasive mechanical ventilation, with the goal to perform physiokinesitherapy during awake ECMO.
Small molecular weight species such as miRNAs and other nucleic acid fragments are gaining an increased interest as biomarkers for relevant diseases. Also, cheap and rapid assays for their routine ...detection are becoming an urgent need. We have investigated the usability and convenience of a price affordable, label free and fast technique for their detection on a laboratory scale small device based on Bio-Layer Interferometry. Using a model DNA fragment (7 kDa), we have found that the technique is effectively fast and sensitive enough for the detection of nucleic acid fragments having a MW below the stated molecular size detection limit (10 kDa). The test molecule has been detected in solution at 100 nM in a direct capture experiment and up to about 10 nM following an improved approach where an enhancing probe is used to increase the apparent molecular dimensions of the analyte. The technique, following further optimizations, can be applied for the routine, cheap and fast analysis of small nucleic acid fragments that have a relevance in diagnosis and in therapy.
Display omitted
•Label free and fast technique for nucleic acid detection on a laboratory scale.•Rapid and sensitive detection of DNA with MW below the BLI instrumental limits.•Applicability in routine qualitative and quantitative analyses combined with PCR.
Display omitted
•Design, synthesis and spectral characterization of a set of dansyl-amino acids for Hg2+ ions detection.•Analysis of the binding features of the different chemosensors.•N-dansylated ...methionine as a best performing chemosensor in terms of sensitivity with a LOD of 140nM.•Validation of a portable experimental set-up based on optical fiber probes.•LOD improvement of the new device to about 5nM, well above the Environmental Protection Agency (EPA) limits imposed for drinkable water.
Mercury is a pollutant extremely toxic to the environment and human health. Although numerous methods have been reported for the analysis of Hg2+ ions in water, the development of simple, rapid, inexpensive, and sensitive sensors still represents a challenge. Here, we describe the design, synthesis and spectral characterization of a set of dansyl-amino acids able to recognize Hg2+ ions via different fluorescence emission modes. The analysis of the binding features of the different chemosensors shows that the stoichiometry of the sensor–Hg2+ complex depends on the concentration of the sensor and Hg2+ since it plays an important role in the type of response for Hg2+ ions. Among those studied here N-dansylated methionine is the best performing chemosensor in terms of sensitivity with a LOD of 140nM. To improve the LOD of this chemosensor, we evaluated the response of a portable experimental set-up based on optical fiber probes. The new device shows an increase of LOD from 140nM to about 5nM, which can meet the requirements imposed by the Environmental Protection Agency for monitoring Hg2+ in drinkable water. We also show that the chemosensors are not applicable to marine water-based matrices because of the significant coordinating ability of chloride anions with Hg2+.
PDF
