PURPOSE:MicroRNAs (miRNAs) are emerging as circulating biomarkers in germ cell tumors (GCT) with potential to guide management. Their role and expression patterns are more established in testicular GCTs, while lesser data exist in ovarian GCTs (OGCT). METHODS:Patients diagnosed with OGCT with plasma and tumor tissue available in our provincial biobank were included. Total RNA was extracted, and RT-qPCR was performed to measure miR-371-3 and miR-302/367 levels. Healthy plasma and ovarian tissue served as controls. Statistical analyses were performed using ANOVA and the Mann-Whitney U test. Clinicopathologic data was collected by chart review. RESULTS:From 2007 to 2022, 23 patients with OGCT were identified: 13 with viable non-teratoma germ cell (VNTGC) and 10 with immature teratoma germ cell (ITGC) tumors. Compared to healthy controls, all patients with VNTGC but not ITGC tumors had significantly higher miRNA levels in preoperative plasma and tumor tissue. Plasma miRNA kinetics correlated with disease burden, decreasing to undetectable levels following treatment, and increasing significantly upon relapse. CONCLUSION:MiR-371-3 and miR-302/367 are highly expressed in ovarian VNTGC but not ITGC tumors, and their plasma levels correlate with disease burden. Future studies validating these findings in a larger cohort are needed to develop miRNAs as circulating biomarkers for clinical use.

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.

Continuous glucose monitoring is valuable for people with diabetes but faces limitations due to enzyme–electrode interactions and biofouling from biological samples that reduce sensor sensitivity and the monitoring performance. We created an enzyme-based electrochemical system with a unique nanocomposite coating that incorporates the redox molecule, aminoferrocene (NH2-Fc). This coating enhances stability via electroactivity and reduces nonspecific binding, as demonstrated through cyclic voltammetry. Our approach enables real-time glucose detection via chronoamperometry with a calculated linear range of 0.5 to 20 mM and a 1 mM detection limit. Validated with plasma and saliva, this platform shows promise for robust metabolite detection in clinical and research contexts. This versatile platform can be applied to accurately monitor a wide range of metabolites in various biological matrices, improving patient outcomes.

PARP inhibitors olaparib, niraparib, rucaparib are approved for treatment of mCRPC harboring Homologous Recombination Deficiency (HRD). However, not all patients who receive these therapies respond and many ultimately develop resistance. This study aims to identify new PARP alternative targetable pathways to improve outcomes of HRD Prostate Cancer (PCa) patients.

Detecting specific metabolites and measuring their changing levels in various biofluids has played a key role in understanding health and diagnosing disease. While most metabolite measurements are performed via spectroscopic (colorimetric, UV, mass spectrometry-MS, nuclear magnetic resonance) methods, it is also possible to perform metabolite detection and quantification via metabolite-antibody interactions, such as those used in competitive enzyme-linked immunosorbent assays (ELISAs), and/or impedance measurements. While metabolite-specific antibodies are available, conjugated-metabolites needed for metabolite-antibody detection are rare. Here we describe a general method that allows for the efficient conjugation of different classes of metabolites (acids, amines, and aromatic compounds) to gold nanoparticles and liposomes. We also describe a method for the efficient insertion of metabolite-lipid complexes into liposomes. We extensively characterized these conjugates, confirming their identity and composition, using a wide variety of analytical (thermal gravimetric analysis), spectroscopic (dynamic light scattering, MS) and microscopic (transmission electron microscopy-TEM, cryo-EM, high resolution EM) techniques. We also demonstrated that these metabolite conjugates can successfully bind to their metabolite-specific antibodies. We used scanning electron microscopy, atomic force microscopy, and ELISA to confirm the successful binding of these NPs-conjugates (N1-acetyl-spermine (AcSpm), hippuric acid and creatinine) to metabolite-specific antibodies attached to silicon wafers and electrodes. We believe the methods developed here are quite general and could be used in the development of a number of different types of metabolite biosensors and portable metabolite assays.

Abstract Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment and components of the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific exosomal microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.

A highly selective microfluidic integrated metal oxide gas sensor for THC detection is reported based on MIP nanoparticles (MIP NPs). We synthesized MIP NPs with THC recognition sites and coated them on a 3D-printed microfluidic channel surface. The sensitivity and selectivity of coated microfluidic integrated gas sensors were evaluated by exposure to THC, cannabidiol (CBD), methanol, and ethanol analytes in 300-700 ppm at 300 ?. For comparison, reference signals were obtained from a microfluidic channel coated with nonimprinted polymers (NIP NPs). The MIP and NIP NPs were characterized using scanning electron microscopy (SEM) and Raman spectroscopy. MIP and NIP NPs channels response data were combined and classified with 96.3% accuracy using the Fine KNN classification model in MATLAB R2021b Classification Learner App. Compared to the MIP NPs coated channel, the NIP NPs channel had poor selectivity towards THC, demonstrating that the THC recognition sites in the MIP structure enabled selective detection of THC. The findings demonstrated that the recognition sites of MIP NPs properly captured THC molecules, enabling the selective detection of THC compared to CBD, methanol, and ethanol.

Volatile organic compounds (VOCs) are major environmental pollutants. Exposure to VOCs has been associated with adverse health outcomes. The monitoring of hazardous VOCs is a vital step towards identifying their presence and preventing the risk of acute or chronic exposure and polluting the environment. One of the challenges associated with monitoring VOCs is selectivity of the sensor. Microfluidic gas sensors offer selective and sensitive detection capabilities that have been recently applied for detection of VOCs. In this study, we achieve improved selectivity for detection of a range of VOCs by adding micro- and nanofeatures to the microchannel of microfluidic gas sensors. First, microfeatures are embedded into the microchannel and their geometries are optimized using Taguchi design of experiment method. In the next step the microfeatures embedded microchannel is coated with graphene oxide, to increase the surface to volume ratio by introducing nanofeatures to the surfaces. The nano- and microfeatures are characterized by SEM, XPS, and water contact angle measurement. Finally, the changes in the sensor response are compared to plain microfluidic gas sensor, the results show an average of 64.4% and 120.9% improvement in the selectivity of the sensor with microfeatures and both nano- and microfeatures, respectively

Background: Parkinson’s disease (PD) is a long-term, degenerative, and neurological disease in which a person loses control of certain body functions. The formulation of novel effective therapeutics for PD as a neurodegenerative disease requires accurate and efficient diagnosis at the early stages. Objective: Analyzing data gathered by measurable signals converted from biological reactions allows for qualitative and quantitative evaluations. Among various approaches reported so far, biosensors are powerful analytical tools that have been used in detecting the biomarkers of PD. Methods: Biosensor’s biological recognition components include antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, and biomimetic structures. This review introduces electrochemical, optical, and optochemical detection of PD biomarkers based on recent advances in nanotechnology and material science, which resulted in the development of high-performance biosensors in this field. Results: PD biomarkers such as α-synuclein protein, dopamine (DA), urate, ascorbic acid, miRNAs, and their biological roles are summarized. Additionally, the advantages and disadvantages of the usual standard methods are reviewed. We compared electrochemical, optical, and optochemical biosensors' properties and novel strategies for higher sensitivity and selectivity. Conclusion: The development of novel biosensors is required for the early diagnosis of PD as sensitive, rapid, reliable, and cost-effective systems.

Monitoring volatile compounds in sewer systems is of high importance due to the toxic and corrosive nature of various nuisance chemicals generated such as hydrogen sulfide (H2S). Hotspot monitoring facilitates identification of the location of the generated H2S, and thereby targeted treatment can be applied which eventually minimizes the use of chemicals and lowers the environmental effect within the sewer system. Here, we developed a portable detector that automatically extracts and delivers sewer contents to a microfluidic-based detector, fabricated by a selective microchannel embedded with a metal oxide semiconductor (MOS) sensor. Using a wide concentration range of H2S and ammonia (NH3) dissolved in water (i.e., two components to which the MOS sensor has potential cross-selectivity), a database for a machine learning model was developed. The model could classify between NH3 and H2S with 96.4% and 96.9% overall recall in separate and mixture aqueous solutions, respectively. Overall regression precisions of 84.6% and 88.8% were obtained in separate and mixture aqueous solutions, respectively. The developed setup was used in a field test (at Annacis Island (Delta, BC)) wastewater treatment plant where the results showed that the device could identify H2S and NH3 in raw influent samples and measuring the concentrations via regression with 94.6% and 83.5% overall recall and precision for H2S and NH3, respectively. These results demonstrate the promise of the developed automated detector and machine-learning data processing methodology for applications in in-situ wastewater monitoring or treatment through the detection of H2S hotspots for targeted mitigation efforts.

Cancer is one of the deadliest diseases worldwide, and there is a critical need for diagnostic platforms for applications in early cancer detection. The diagnosis of cancer can be made by identifying abnormal cell characteristics such as functional changes, a number of vital proteins in the body, abnormal genetic mutations and structural changes, and so on. Identifying biomarker candidates such as DNA, RNA, mRNA, aptamers, metabolomic biomolecules, enzymes, and proteins is one of the most important challenges. In order to eliminate such challenges, emerging biomarkers can be identified by designing a suitable biosensor. One of the most powerful technologies in development is biosensor technology based on nanostructures. Recently, graphene and its derivatives have been used for diverse diagnostic and therapeutic approaches. Graphene-based biosensors have exhibited significant performance with excellent sensitivity, selectivity, stability, and a wide detection range. In this review, the principle of technology, advances, and challenges in graphene-based biosensors such as field-effect transistors (FET), fluorescence sensors, SPR biosensors, and electrochemical biosensors to detect different cancer cells is systematically discussed. Additionally, we provide an outlook on the properties, applications, and challenges of graphene and its derivatives, such as Graphene Oxide (GO), Reduced Graphene Oxide (RGO), and Graphene Quantum Dots (GQDs), in early cancer detection by nanobiosensors.

5-Fluorouracil (5-FU) is an antimetabolite drug widely used for the treatment of skin cancer. Despite its proven efficacy in treating malignancies, its systemic administration is limited due to severe side effects. To address this issue, topical delivery of 5-FU has been proposed as an alternative approach for the treatment of skin cancer, however, the poor permeability of 5-FU through the skin is still a challenge. Here, we introduced a pH-responsive micellar hydrogel system based on deoxycholic acid micelle (DCA Mic) and carboxymethyl chitosan hydrogel (CMC Hyd) to enhance 5-FU efficacy against skin cancer and reduce its systemic side effects by improving its delivery into the skin. The properties of the Mic/Hyd system were determined by Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta sizer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Drug release studies showed pH-dependent properties of the Hyd. The final formulation was demonstrated to have enhanced anticancer activity than 5-FU against the growth of melanoma cells. The 5-FU@Mic-Hyd could be a promising delivery platform with enhanced efficacy in the management of skin cancer without systemic toxicity.

In this study, we analyzed the application of potentiodynamic electrochemical impedance spectroscopy (PDEIS) for a selective in situ recognition of biological trace elements, i.e., Cr (III), Cu (II), and Fe (III). The electrochemical sensor was developed using the electropolymerization of aniline (Ani) on the surface of the homemade pencil graphite electrodes (PGE) using cyclic voltammetry (CV). The film was overoxidized to diminish the background current. A wide range of potential (V = −0.2 V to 1.0 V) was investigated to study the impedimetric and capacitive behaviour of the PAni/modified PGE. The impedance behaviors of the films were recorded at optimum potentials through electrochemical impedance spectroscopy (EIS) and scrutinized by means of an appropriate equivalent circuit at different voltages and at their corresponding oxidative potentials. The values of the equivalent circuit were used to identify features (charge transfer-resistant and double layer capacitance) that can selectivity distinguish different trace elements with the concentration of 10 μM. The PDEIS spectra represented the highest electron transfer for Cu (II) and Cr (III) in a broad potential range between +0.1 and +0.4 V while the potential V = +0.2 V showed the lowest charge transfer resistance for Fe (III). The results of this paper showed the capability of PDEIS as a complementary tool for conventional CV and EIS measurement for metallic ion sensing.

Probiotics are a promising prevention and treatment strategy for several diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), atopic diseases, acute infectious diarrhea, and antibioticassociated diarrhea. Although probiotics are associated with many health benefits, their application is limited due to reductions in the viability of probiotic cells during processing, storage, and delivery to the targeted site of the gastrointestinal tract (GIT). Microencapsulation technology can improve the delivery of probiotics by protecting products from environmental and physiological factors (e.g., pH, oxygen, and temperature) and facilitating their delivery to the colon. Encapsulating materials have a significant influence on the survivability of encapsulated probiotic bacteria. This review article paints a comprehensive picture of encapsulating materials used for the microencapsulation of probiotic bacteria, provides a comprehensive comparison of all food-grade encapsulation materials. Furthermore, an overview of the relevant scientific literature on the characterization of encapsulated probiotics delivery systems are provided.

An impedance-transducer sensor was developed for in situ detection of hydrogen sulfide (H2S) and ammonia (NH3) in aqueous media. Using cyclic voltammetry (CV), polypyrrole (PPy) was deposited on the surface of the microfabricated interdigitated gold electrode. Due to the proton acid doping effect of H2S on PPy and ionic conduction of the film, the sensor showed a decreasing impedance response to H2S unlike other reducing chemicals, i.e., ammonia (NH3). The recorded faradaic data was then associated with an equivalent circuit and compared with that of NH3 to examine the selectivity of the sensor. An electrochemical impedance spectroscopy (EIS) analysis was applied to the mixture of H2S and NH3 prepared at different ratios for the concentrations ranging from 2 ppm to 20 ppm (below 2-ppm, no response was observed due to the formation of NH4HS, not sensible with PPy). The principal component analysis (PCA) was used to train a real-time prediction model for both classification (for the type of the analyte) and regression (the concentration of the analyte). The results showed the high performance of the sensor in determining individual analytes while the model was able to accurately predict the amount of H2S and NH3 in the mixture.

Micromixers are critical components within microfluidic fluid handling and analysis systems. When it comes to micromixing of biological samples, the hydrodynamical forces acting on biological specimens are of great importance besides mixing quality. Although adding rigid obstacles to the microchannels has shown to improve the mixing performance, they create a considerable pressure drop and impose a significant shear force on biological specimens. To address these problems, deformable baffles have been introduced here as a novel tuning tool for controlling the mixing characteristics. To optimize the device performance (maximizing the mixing performance and minimizing the pressure loss), two optimization algorithms have been employed to find out the suitable baffle geometry and material property. The Taguchi method was proposed as a fast and cost-effective approach for single-objective optimization of the mixing index or the pressure drop, and the Pareto optimality concept was introduced for parallel optimization of the mixing efficiency and the pressure loss. The results show that replacing the rigid with deformable baffles significantly reduces the pressure drop (by approximately 50%), causing a significant reduction in the shear stress on biological samples while a small reduction on the mixing efficiency (10 to 15%) was observed.

Coaxial electrospinning is a robust technique to prepare core-shell nanofibers for various biomedical applications such as tissue engineering. In this study, the coaxial electrospinning method was used to prepare two different core-shell nanofibers based on polycaprolactone/polyvinyl alcohol (PCL/PVA) and polycaprolactone/collagen (PCL/Col). The mechanical (e.g., shear viscosity and surface tension) and chemical properties of the nanofibers were characterized and compared. The results showed that PCL/Col nanofibers have higher stability and better coverage of the core compared to PCL/PVA nanofibers due to the high viscosity and low spinnability of the core polymer, collagen. The optimum voltage and feeding rate for the fabrication of nanofibers were found to be 16 kV and 1:3 (core:shell), respectively. Due to their secondary structure and their promising properties, PCL/Col nanofibers exhibited great potential for biomedical applications such as wound healing and drug delivery platforms.

Among the gas sensing technologies, microfluidic gas sensors have garnered attention because of their sensitivity, compact size, and low cost. In this study, we demonstrate improved selectivity of microfluidic gas sensors toward volatile organic compounds by increasing the effect of adsorption of analytes on the surface of the sensor’s microchannel through increasing the ratio of the surface area (in contact with analyte) to the volume of the microchannel. First, the effect of microchannel geometry modification (reduction of width) is studied through a computational parametric approach (which is validated experimentally). The results show an average improvement of 93.44 % and 60.1 % in selectivity toward polar and nonpolar VOCs, respectively. In the next step, the surface of the microchannel is modified with graphene quantum dots, which has a two-fold effect on VOCs adsorption: (i) increasing the surface area, and (ii) adding functional groups. The experimental results of this step show an average improvement of 101.45 % and 98.82 % in the sensor’s selectivity for the smallest widths toward polar and nonpolar VOCs, respectively. These results indicate that increasing the ratio of surface area (in contact with analyte) to the volume of the microchannel and adding functionalized nanofeatures to the microchannel surface area are promising ways to enhance the selectivity of microfluidic gas sensors.

Micro�uidic on-chip production of microgels employing external gelation has numerous biological and pharmaceutical applications, particularly for the encapsulation of delicate cargos, however, the on-chip production of microgels in micro�uidic devices can be challenging due to problems such as clogging caused by accelerated progress in precursor solution viscosity. Here, we introduce a novel micro�uidic design incorporating two consecutive co-ow geometries for micro�uidic droplet generation. A shielding oil phase is employed to avoid emulsi�cation and gelation stages from occurring simultaneously, thereby preventing clogging. The results revealed that the micro�uidic device could generate highly monodispersed spherical droplets (coe�cient of variation < 3%) with an average diameter in the range of 60–200 μm. Additionally, it was demonstrated that the device could appropriately create a shelter of the oil phase around the inner aqueous phase regardless of the droplet formation regime and �ow conditions. The ability of the proposed micro�uidic device in the generation of microgels was validated by producing alginate microgels utilizing an aqueous solution of calcium chloride as the continuous phase.