Remote-Controlled Sensing and Drug Delivery via 3D-Printed Hollow Microneedles.

Remote health monitoring and treatment serve as critical drivers for advancing health equity, bridging geographical and socioeconomic disparities, ensuring equitable access to quality healthcare for those in underserved or remote regions. By democratizing healthcare, this approach offers timely interventions, continuous monitoring, and personalized care independent of one's location or socioeconomic status, thereby striving for an equitable distribution of health resources and outcomes. Meanwhile, microneedle arrays (MNAs), characterized by micron-scaled needles, revolutionize painless and minimally invasive access to interstitial fluid for drug delivery and diagnostics. This paper introduces an integrated theranostic MNA system employing an array of colorimetric sensors to quantitatively measure interstitial fluid pH, glucose, and lactate, alongside a remotely-triggered system enabling on-demand drug delivery. Integration of an ultrasonic atomizer streamlines the MNA, facilitating rapid, pumpless, and point-of-care drug delivery, enhancing system portability while reducing complexities. An accompanying smartphone application interfaces the sensing and drug delivery components. Demonstrated capabilities include detecting pH (3 to 8), glucose (up to 16 mM), and lactate (up to 3.2 mM), showcasing on-demand drug delivery, and assessing delivery system performance via a scratch assay. This innovative approach confronts drug delivery challenges, particularly in managing chronic diseases requiring long-term treatment, while also offering avenues for non-invasive health monitoring through microneedle-based sensors. This article is protected by copyright. All rights reserved.

Nanomaterials in electrochemical nanobiosensors of miRNAs.

Nanomaterial-based biosensors have received significant attention owing to their unique properties, especially enhanced sensitivity. Recent advancements in biomedical diagnosis have highlighted the role of microRNAs (miRNAs) as sensitive prognostic and diagnostic biomarkers for various diseases. Current diagnostics methods, however, need further improvements with regards to their sensitivity, mainly due to the low concentration levels of miRNAs in the body. The low limit of detection of nanomaterial-based biosensors has turned them into powerful tools for detecting and quantifying these biomarkers. Herein, we assemble an overview of recent developments in the application of different nanomaterials and nanostructures as miRNA electrochemical biosensing platforms, along with their pros and cons. The techniques are categorized based on the nanomaterial used.

Recent advances in smart wearable sensors as electronic skin.

Flexible and multifunctional electronic devices and soft robots inspired by human organs, such as skin, have many applications. However, the emergence of electronic skins (e-skins) or textiles in biomedical engineering has made a great revolution in a myriad of people's lives who suffer from different types of diseases and problems in which their skin and muscles lose their appropriate functions. In this review, recent advances in the sensory function of the e-skins are described. Furthermore, we have categorized them from the sensory function perspective and highlighted their advantages and limitations. The categories are tactile sensors (including capacitive, piezoresistive, piezoelectric, triboelectric, and optical), temperature, and multi-sensors. In addition, we summarized the most recent advancements in sensors and their particular features. The role of material selection and structure in sensory function and other features of the e-skins are also discussed. Finally, current challenges and future prospects of these systems towards advanced biomedical applications are elaborated.

3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion.

Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction-diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model's predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion.

Nano drug-delivery systems for management of AIDS: liposomes, dendrimers, gold and silver nanoparticles.

AIDS causes increasing mortality every year. With advancements in nanomedicine, different nanomaterials (NMs) have been applied to treat AIDS and overcome its limitations. Among different NMs, nanoparticles (NPs) can act as nanocarriers due to their enhanced solubility, sustained release, targeting abilities and facilitation of drug-dose reductions. This review discusses recent advancements in therapeutics for AIDS/HIV using various NMs, mainly focused on three classifications: polymeric, liposomal and inorganic NMs. Polymeric dendrimers, polyethylenimine-NPs, poly(lactic-co-glycolic acid)-NPs, chitosan and the use of liposomal-based delivery systems and inorganic NPs, including gold and silver NPs, are explored. Recent advances, current challenges and future perspectives on the use of these NMs for better management of HIV/AIDS are also discussed.

AIDS is a disease affecting many worldwide. Since it is difficult to cure AIDS, new therapies have been developed. Tiny materials called nanoparticles with promising features are used to carry different drugs to relevant organs in the body. There are various nanoparticles with different textures and shapes used in AIDS therapy. Branched nanoparticles, nanoparticles with repetitive building blocks and metal-based nanoparticles are three commonly used nanoparticles in AIDS treatment that are studied in this review. These tiny materials can find the exact place in the body to deliver drugs. They can also reduce the side effects of anti-AIDS drugs and help patients use fewer drugs while getting the same or better results.

Single-cell transcriptome analysis for cancer and biology of the pancreas: A review on recent progress.

Single-cell sequencing has become one of the most used techniques across the wide field of biology. It has enabled researchers to investigate the whole transcriptome at the cellular level across tissues, which unlocks numerous potentials for basic and applied studies in future diagnosis and therapy. Here, we review the impact of single-cell RNA sequencing, as the prominent single-cell technique, in pancreatic biology and cancer. We discuss the most recent findings about pancreatic physiology and pathophysiology owing to this technological advancement in the past few years. Using single-cell RNA sequencing, researchers have been able to discover cellular heterogeneity across healthy cell types, as well as cancer tissues of the pancreas. We will discuss the new immunological targets and new molecular mechanisms of progression in the microenvironment of pancreatic cancer studied using single-cell RNA sequencing. The scope is not limited to cancer tissues, and we cover novel developmental, evolutionary, physiological, and heterogenic insights that have also been achieved recently for pancreatic tissues. We cover all biological insights derived from the single-cell RNA sequencing data, discuss the corresponding pros and cons, and finally, conclude how future research can move better by utilizing single-cell analysis for pancreatic biology.

Alprazolam Detection Using an Electrochemical Nanobiosensor Based on AuNUs/Fe-Ni@rGO Nanocomposite.

Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L-1 and 1 to 50 mg L-1), low limit of detection (1 µg L-1), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.

Carbon nanostructures: a comprehensive review of potential applications and toxic effects.

There is no doubt that nanotechnology has revolutionized our life since the 1970s when it was first introduced. Nanomaterials have helped us to improve the current products and services we use. Among the different types of nanomaterials, the application of carbon-based nanomaterials in every aspect of our lives has rapidly grown over recent decades. This review discusses recent advances of those applications in distinct categories, including medical, industrial, and environmental applications. The first main section introduces nanomaterials, especially carbon-based nanomaterials. In the first section, we discussed medical applications, including medical biosensors, drug and gene delivery, cell and tissue labeling and imaging, tissue engineering, and the fight against bacterial and fungal infections. The next section discusses industrial applications, including agriculture, plastic, electronic, energy, and food industries. In addition, the environmental applications, including detection of air and water pollutions and removal of environmental pollutants, were vastly reviewed in the last section. In the conclusion section, we discussed challenges and future perspectives.

Nanocomposite of electrochemically reduced graphene oxide and gold nanourchins for electrochemical DNA detection.

A nanocomposite of graphene oxide and gold nanourchins has been used here to modify the surface of a screen-printed carbon electrode to enhance the sensitivity of the electrochemical DNA detection system. A specific single-stranded DNA probe was designed based on the target DNA sequence and was thiolated to be self-assembled on the surface of the gold nanourchins placed on the modified electrode. Doxorubicin was used as an electrochemical label to detect the DNA hybridisation using differential pulse voltammetry (DPV). The assembling process was confirmed using scanning electron microscopy (SEM) imaging, cyclic voltammetry (CV), and the EIS method. The high sensitivity of the proposed system led to a low detection limit of 0.16 fM and a wide linear range from 0.5 to 950.0 fM. The specificity of the DNA hybridisation and the signalling molecule (haematoxylin) caused very high selectivity towards the target DNA than other non-specific sequences.

Gold Nanorods for Drug and Gene Delivery: An Overview of Recent Advancements.

Over the past few decades, gold nanomaterials have shown great promise in the field of nanotechnology, especially in medical and biological applications. They have become the most used nanomaterials in those fields due to their several advantageous. However, rod-shaped gold nanoparticles, or gold nanorods (GNRs), have some more unique physical, optical, and chemical properties, making them proper candidates for biomedical applications including drug/gene delivery, photothermal/photodynamic therapy, and theranostics. Most of their therapeutic applications are based on their ability for tunable heat generation upon exposure to near-infrared (NIR) radiation, which is helpful in both NIR-responsive cargo delivery and photothermal/photodynamic therapies. In this review, a comprehensive insight into the properties, synthesis methods and toxicity of gold nanorods are overviewed first. For the main body of the review, the therapeutic applications of GNRs are provided in four main sections: (i) drug delivery, (ii) gene delivery, (iii) photothermal/photodynamic therapy, and (iv) theranostics applications. Finally, the challenges and future perspectives of their therapeutic application are discussed.

microRNAs and long non-coding RNAs as biomarkers for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and diagnostic emphasized the role of non-coding regulatory RNAs as molecular biomarkers in studying, diagnosing and even as therapeutics of PCOS. This review discusses a comparative summary of research into microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that are molecularly or statistically related to PCOS. We categorize the literature in terms of centering on either miRNAs or lncRNAs and discuss the combinatory studies and promising ideas as well. Additionally, we compare the pros and cons of the prominent research methodologies used for each of the abovementioned research themes and discuss how errors can be stopped from propagation by selecting correct methodologies for future research. Finally, it can be concluded that research into miRNAs and lncRNAs has the potential for identifying functional networks of regulation with multiple mRNAs (and hence, functional proteins). This new understanding may eventually afford clinicians to control the molecular course of the pathogenesis better. With further research, RNA (with statistical significance and present in the blood) may be used as biomarkers for the disease, and more possibilities for RNA therapy agents can be identified.

Pathogen detection with electrochemical biosensors: Advantages, challenges and future perspectives.

Detection of pathogens, e.g., bacteria and viruses, is still a big challenge in analytical medicine due to their vast number and variety. Developing strategies for rapid, inexpensive, specific, and sensitive detection of the pathogens using nanomaterials, integrating with microfluidics devices, amplification methods, or even combining these strategies have received significant attention. Especially, after the health-threatening COVID-19 outbreak, rapid and sensitive detection of pathogens became very critical. Detection of pathogens could be realized with electrochemical, optical, mass sensitive, or thermal methods. Among them, electrochemical methods are very promising by bringing different advantages, i.e., they exhibit more versatile detection schemes and real-time quantification as well as label-free measurements, which provides a broader application perspective. In this review, we discuss the recent advances for the detection of bacteria and viruses using electrochemical biosensors. Moreover, electrochemical biosensors for pathogen detection were broadly reviewed in terms of analyte, bio-recognition and transduction elements. Different fabrication techniques, detection principles, and applications of various pathogens with the electrochemical biosensors were also discussed.

Microfluidic-Based Oxygen (O2) Sensors for On-Chip Monitoring of Cell, Tissue and Organ Metabolism.

Oxygen (O2) quantification is essential for assessing cell metabolism, and its consumption in cell culture is an important indicator of cell viability. Recent advances in microfluidics have made O2 sensing a crucial feature for organ-on-chip (OOC) devices for various biomedical applications. OOC O2 sensors can be categorized, based on their transducer type, into two main groups, optical and electrochemical. In this review, we provide an overview of on-chip O2 sensors integrated with the OOC devices and evaluate their advantages and disadvantages. Recent innovations in optical O2 sensors integrated with OOCs are discussed in four main categories: (i) basic luminescence-based sensors; (ii) microparticle-based sensors; (iii) nano-enabled sensors; and (iv) commercial probes and portable devices. Furthermore, we discuss recent advancements in electrochemical sensors in five main categories: (i) novel configurations in Clark-type sensors; (ii) novel materials (e.g., polymers, O2 scavenging and passivation materials); (iii) nano-enabled electrochemical sensors; (iv) novel designs and fabrication techniques; and (v) commercial and portable electrochemical readouts. Together, this review provides a comprehensive overview of the current advances in the design, fabrication and application of optical and electrochemical O2 sensors.

Experimental and theoretical study for miR-155 detection through resveratrol interaction with nucleic acids using magnetic core-shell nanoparticles.

A novel electrochemical nanobiosensor for the detection of miR-155 (as breast cancer biomarker) is introduced . Fe3O4NPs@Ag core-shell nanoparticles were synthesized and their shape and characteristics were confirmed by scanning electron microscope (SEM) imaging, Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) methods. Synthesized nanoparticles were applied onto the magnetic bar carbon paste electrode and then the amine-modified anti-miR-155 (single-stranded probes) was applied on the modified electrode surface and upon hybridization with target miR-155, resveratrol (RSV) was eventually applied as an electrochemical label on the double-strand oligonucleotide. Differential pulse voltammetry (DPV) of the oxidation peak of RSV was assumed as the final signal by sweeping potential from 0 to 0.6 V (vs. Ag/AgCl). The fabrication process was optimized through a series of experiments and the optimized process was confirmed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The linear range of the fabricated nanobiosensor was 0.5 fM to 1.0 nM and the detection limit was 0.15 fM. The nanobiosensor was able to pass reproducibility and specificity tests using different types of mismatched target sequences.Spiked real samples of human serum were used to confirm that the nanobiosensor enables detection of miR-155 without any significant interferences from other moieties and molecules. Finally, the molecular dynamics simulation of the RSV interaction with single- and double-stranded oligonucleotide was performed and confirmed the preferential binding of RSV to double-stranded DNA; therefore, it can be used as the electrochemical label of DNA and/or miRNA hybridization-based biosensors. Graphical abstract.

Optical, electrochemical and electrical (nano)biosensors for detection of exosomes: A comprehensive overview.

Exosomes are small extracellular vesicles involved in many physiological activities of cells in the human body. Exosomes from cancer cells have great potential to be applied in clinical diagnosis, early cancer detection and target identification for molecular therapy. While this field is gaining increasing interests from both academia and industry, barriers such as supersensitive detection techniques and highly-efficient isolation methods remain. In the clinical settings, there is an urgent need for rapid analysis, reliable detection and point-of-care testing (POCT). With these challenges to be addressed, this article aims to review recent developments and technical breakthroughs including optical, electrochemical and electrical biosensors for exosomes detection in the field of cancer and other diseases and demonstrate how nanobiosensors could enhance the performance of conventional sensors. Working strategies, limit of detections, advantages and shortcomings of the studies are summarized. New trends, challenges and future perspectives of exosome-driven POCT in liquid biopsy have been discussed.

Recent developments in electrochemical sensors for detecting hydrazine with different modified electrodes.

The detection of hydrazine (HZ) is an important application in analytical chemistry. There have been recent advancements in using electrochemical detection for HZ. Electrochemical detection for HZ offers many advantages, e.g., high sensitivity, selectivity, speed, low investment and running cost, and low laboriousness. In addition, these methods are robust, reproducible, user-friendly, and compatible with the concept of green analytical chemistry. This review is devoted to the critical comparison of electrochemical sensors and measuring protocols used for the voltammetric and amperometric detection of the most frequently used HZ in water resources with desirable recovery. Attention is focused on the working electrode and its possible modification which is crucial for further development.

Electrochemical sensors and biosensors based on the use of polyaniline and its nanocomposites: a review on recent advances.

Polyaniline and its composites with nanoparticles have been widely used in electrochemical sensor and biosensors due to their attractive properties and the option of tuning them by proper choice of materials. The review (with 191 references) describes the progress made in the recent years in polyaniline-based biosensors and their applications in clinical sensing, food quality control, and environmental monitoring. A first section summarizes the features of using polyaniline in biosensing systems. A subsequent section covers sensors for clinical applications (with subsections on the detection of cancer cells and bacteria, and sensing of glucose, uric acid, and cholesterol). Further sections discuss sensors for use in the food industry (such as for sulfite, phenolic compounds, acrylamide), and in environmental monitoring (mainly pesticides and heavy metal ions). A concluding section summarizes the current state, highlights some of the challenges currently compromising performance in biosensors and nanobiosensors, and discusses potential future directions. Graphical abstract Schematic presentation of electrochemical sensor and biosensors applications based on polyaniline/nanoparticles in various fields of human life including medicine, food industry, and environmental monitoring. The simultaneous use of suitable properties polyaniline and nanoparticles can provide the fabrication of sensing systems with high sensitivity, short response time, high signal/noise ratio, low detection limit, and wide linear range by improving conductivity and the large surface area for biomolecules immobilization.

Toxicity of carbon-based nanomaterials: Reviewing recent reports in medical and biological systems.

Application of nanomaterials in our daily life is increasing, day in day out and concerns have raised about their toxicity for human and other organisms. In this manner, carbon-based nanomaterials have been applied to different products due to their unique physicochemical, electrical, mechanical properties, and biological compatibility. But, there are several reports about the negative effects of these materials on biological systems and cellular compartments. This review article describes the various types of carbon-based nanomaterials and methods that use for determining these toxic effects that are reported recently in the papers. Then, extensively discussed the toxic effects of these materials on the human and other living organisms and also their toxicity routs including Neurotoxicity, Hepatotoxicity, Nephrotoxicity, Immunotoxicity, Cardiotoxicity, Genotoxicity and epigenetic toxicity, Dermatotoxicity, and Carcinogenicity.

Dual-aptamer based electrochemical sandwich biosensor for MCF-7 human breast cancer cells using silver nanoparticle labels and a poly(glutamic acid)/MWNT nanocomposite.

This paper reports on a sensitive and selective method for the detection of Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells and MUC1 biomarker by using an aptamer-based sandwich assay. A biocompatible nanocomposite consisting of multiwall carbon nanotubes (MWCNT) and poly(glutamic acid) is placed on a glassy carbon electrode (GCE). The sandwich assay relies on the use of a mucin 1 (MUC1)-binding aptamer that is first immobilized on the surface of modified GCE. Another aptamer (labeled with silver nanoparticles) is applied for secondary recognition of MCF-7 cells in order to increase selectivity and produce an amplified signal. Differential pulse anodic stripping voltammetry was used to follow the electrochemical signal of the AgNPs. Under the optimal condition, the sensor responds to MCF-7 cells in the concentration range from 1.0 × 102 to 1.0 × 107 cells·mL-1 with a detection limit of 25 cells. We also demonstrate that the MUC1 tumor marker can be detected by the present biosensor. The assay is highly selective and sensitive, acceptably stable and reproducible. This warrants the applicability of the method to early diagnosis of breast cancer. Graphical abstract Schematic of the fabrication of an aptamer-based sandwich biosensor for Michigan Cancer Foundation-7 cells (MCF-7). A MWCNT-poly(glutamic acid) nanocomposite was used as a biocompatible matrix for MUC1-aptamer immobilization. Stripping voltammetry analysis of AgNPs was performed using aptamer conjugated AgNPs as signalling probe.

Nano-biosensor based on reduced graphene oxide and gold nanoparticles, for detection of phenylketonuria-associated DNA mutation.

Phenylketonuria (PKU)-associated DNA mutation in newborn children can be harmful to his health and early detection is the best way to inhibit consequences. A novel electrochemical nano-biosensor was developed for PKU detection, based on signal amplification using nanomaterials, e.g. gold nanoparticles (AuNPs) decorated on the reduced graphene oxide sheet on the screen-printed carbon electrode. The fabrication steps were checked by field emission scanning electron microscope imaging as well as cyclic voltammetry analysis. The specific alkanethiol single-stranded DNA probes were attached by self-assembly methodology on the AuNPs surface and Oracet blue was used as an intercalating electrochemical label. The results showed the detection limit of 21.3 fM and the dynamic range of 80-1200 fM. Moreover, the selectivity results represented a great specificity of the nano-biosensor for its specific target DNA oligo versus other non-specific sequences. The real sample simulation was performed successfully with almost no difference than a synthetic buffer solution environment.