Capillary-Assisted Molecular Pendulum Bioanalysis.

The development of robust biosensing strategies that can be easily implemented in everyday life remains a challenge for the future of modern biosensor research. While several reagentless approaches have attempted to address this challenge, they often achieve user-friendliness through sacrificing sensitivity or universality. While acceptable for certain applications, these trade-offs hinder the widespread adoption of reagentless biosensing technologies. Here, we report a novel approach to reagentless biosensing that achieves high sensitivity, rapid detection, and universality using the SARS-CoV-2 virus as a model target. Universality is achieved by using nanoscale molecular pendulums, which enables reagentless electrochemical biosensing through a variable antibody recognition element. Enhanced sensitivity and rapid detection are accomplished by incorporating the coffee-ring phenomenon into the sensing scheme, allowing for target preconcentration on a ring-shaped electrode. Using this approach, we obtained limits of detection of 1 fg/mL and 20 copies/mL for the SARS-CoV-2 nucleoproteins and viral particles, respectively. In addition, clinical sample analysis showed excellent agreement with Ct values from PCR-positive SARS-CoV-2 patients.

A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles.

Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.

Self-assembly of highly ordered micro- and nanoparticle deposits.

The evaporation of particle-laden sessile droplets is associated with capillary-driven outward flow and leaves nonuniform coffee-ring-like particle patterns due to far-from-equilibrium effects. Traditionally, the surface energies of the drop and solid phases are tuned, or external forces are applied to suppress the coffee-ring; however, achieving a uniform and repeatable particle deposition is extremely challenging. Here, we report a simple, scalable, and noninvasive technique that yields uniform and exceptionally ordered particle deposits on a microscale surface area by placing the droplet on a near neutral-wet shadow mold attached to a hydrophilic substrate. The simplicity of the method, no external forces, and no tuning materials' physiochemical properties make the present generic approach an excellent candidate for a wide range of sensitive applications. We demonstrate the utility of this method for fabricating ordered mono- and multilayer patternable coatings, producing nanofilters with controlled pore size, and creating reproducible functionalized nanosensors.

Emerging technologies and commercial products in exosome-based cancer diagnosis and prognosis.

Academic and industrial groups worldwide have reported technological advances in exosome-based cancer diagnosis and prognosis. However, the potential translation of these emerging technologies for research and clinical settings remains unknown. This work overviews the role of exosomes in cancer diagnosis and prognosis, followed by a survey on emerging exosome technologies, particularly microfluidic advances for the isolation and detection of exosomes in cancer research. The advantages and drawbacks of each of the technologies used for the isolation, detection and engineering of exosomes are evaluated to address their clinical challenges for cancer diagnosis and prognosis. Furthermore, commercial platforms for exosomal detection and analysis are introduced, and their performance and impact on cancer diagnosis and prognosis are assessed. Also, the risks associated with the further development of the next generation of exosome devices are discussed. The outcome of this work could facilitate recognizing deliverable Exo-devices and technologies with unprecedented functionality and predictable manufacturability for the next-generation of cancer diagnosis and prognosis.

Free convection of a suspension containing nano-encapsulated phase change material in a porous cavity; local thermal non-equilibrium model.

Due to the instinctive temperature-dependent heat capacity of the Nano-Encapsulated Phase Change Material (NEPCM), there is a growing interest in the potential applications of such materials in heat transfer. As such, steady-state natural convection in a porous enclosure saturated with nanofluid using NEPCMs has been investigated in this study. The cavity is assumed to have constant hot and cold temperatures at the left and right vertical boundaries, respectively, and fully insulated from the bottom and top walls. Considering the Local Thermal Non-equilibrium (LTNE) approach for the porous structure, the governing equations are first non-dimensionalized and then solved by employing the finite element Galerkin method. The impact of different parameters, such as porous thermal conductivity (k s ), solid-fluid interface heat transfer (10 ≤ H ≤ 105), Stefan number (0.2 ≤ Ste ≤ 1), and volume fraction of nanoparticles (0.0 ≤ φ ≤ 0.05) on the patterns of the fluid and solid isotherms, streamlines and the contours of the heat capacity ratio, fusion temperature (0.05 ≤ θ f ≤ 1), local and average Nusselt numbers, and overall heat transfer ratio has been studied. It is shown that improving the porous thermal conductivity not only leads to an increase in the rate of heat transfer but also augments the fluid flow inside the cavity. For low values of the Ste, the rate of heat, transferred in the porous enclosure, is intensified. However, regardless of the amount of the Stefan number, the maximum rate of heat transfer is achievable when the non-dimensional fusion temperature is approximately 0.5. Employing NEPCMs in a highly conductive porous structure is more efficacious only when the phases are in the state of local thermal equilibrium. Nonetheless, the rate of heat transfer is higher when the Local thermal non-equilibrium is validated between the phases. Besides, for poor thermal conductivity of the porous medium like glass balls (LTE condition), adding 5% of the nano-encapsulated phase change materials to pure water can boost the rate of heat transfer up to 47% (for Ste = 0.2 and θ f = 0.5). This thermal investigation of NEPCMs shows in detail how advantageous are these nanoparticles in heat transfer and opens up an avenue for further application-based studies.

Label-free ultrasensitive detection of breast cancer miRNA-21 biomarker employing electrochemical nano-genosensor based on sandwiched AgNPs in PANI and N-doped graphene.

MicroRNAs (miRNAs) are small, endogenous, noncoding RNAs, shown to be expressed abnormally in many tumors and identified as predictive biomarkers for early diagnosis of several cancers including the breast. Therefore, the label-free and highly sensitive detection of miRNAs is of critical significance. In this work, a highly sensitive and label-free nano-genosensor is developed for the detection of miRNA-21, a known breast cancer biomarker, based on a specific architecture of nitrogen-doped functionalized graphene (NFG), silver nanoparticles (AgNPs), and polyaniline (PANI) that resulted in a remarkable effect on signal amplification. Following the successful functionalization of the nanocomposite and immobilization of the specific sequence of the aminated complementary oligonucleotide of miRNA-21, the detection was performed using differential pulse voltammetry (DPV). The oxidation peak current of the redox probe under optimal conditions was determined to monitor the event hybridization of miRNA-21 biomarker. Applying this highly sensitive and optimized nano-biosensor enabled detection of a wide dynamic range of 10 fM-10 µM with a sensitivity of 2.5 µA cm-2 and a low detection limit of 0.2 fM. This nano-biosensor also demonstrated highly reproducible results in the analysis of blood samples, with recoveries between 94% and 107%, and could be used for early detection of breast cancer by direct detection of the miRNA-21 in real clinical samples without any need to sample preparation, RNA extraction and/or amplification.

Nano-biosensor for highly sensitive detection of HER2 positive breast cancer.

Nanocomposite materials have provided a wide range of conductivity, sensitivity, selectivity and linear response for electrochemical biosensors. However, the detection of rare cells at single cell level requires a new class of nanocomposite-coated electrodes with exceptional sensitivity and specificity. We recently developed a construct of gold nanoparticle-grafted functionalized graphene and nanostructured polyaniline (PANI) for high-performance biosensing within a very wide linear response and selective performance. Further, replacing the expensive gold nanoparticles with low-cost silver nanoparticles as well as optimizing the nanocomposite synthesis and functionalization protocols on the electrode surface in this work enabled us to develop ultrasensitive nanocomposites for label-free detection of breast cancer cells. The sensor presented a fast response time of 30 min within a dynamic range of 10 - 5 × 106 cells mL-1 and with a detection limit of 2 cells mL-1 for the detection of SK-BR3 breast cancer cell. The nano-biosensor, for the first time, demonstrated a high efficiency of > 90% for the label-free detection of cancer cells in whole blood sample without any need for sample preparation and cell staining. The results demonstrated that the optimized nanocomposite developed in this work is a promising nanomaterial for electrochemical biosensing and with the potential applications in electro-catalysis and super-capacitances.