Biosensing Platforms for Cardiac Biomarker Detection.

Myocardial infarction (MI) is a cardiovascular disease that occurs when there is an elevated demand for myocardial oxygen as a result of the rupture or erosion of atherosclerotic plaques. Globally, the mortality rates associated with MI are steadily on the rise. Traditional diagnostic biomarkers employed in clinical settings for MI diagnosis have various drawbacks, prompting researchers to investigate fast, precise, and highly sensitive biosensor platforms and technologies. Biosensors are analytical devices that combine biological elements with physicochemical transducers to detect and quantify specific compounds or analytes. These devices play a crucial role in various fields including healthcare, environmental monitoring, food safety, and biotechnology. Biosensors developed for the detection of cardiac biomarkers are typically electrochemical, mass, and optical biosensors. Nanomaterials have emerged as revolutionary components in the field of biosensing, offering unique properties that significantly enhance the sensitivity and specificity of the detection systems. This review provides a comprehensive overview of the advancements and applications of nanomaterial-based biosensing systems. Beginning with an exploration of the fundamental principles governing nanomaterials, we delve into their diverse properties, including but not limited to electrical, optical, magnetic, and thermal characteristics. The integration of these nanomaterials as transducers in biosensors has paved the way for unprecedented developments in analytical techniques. Moreover, the principles and types of biosensors and their applications in cardiovascular disease diagnosis are explained in detail. The current biosensors for cardiac biomarker detection are also discussed, with an elaboration of the pros and cons of existing platforms and concluding with future perspectives.

Exploring the Versatility of Exosomes: A Review on Isolation, Characterization, Detection Methods, and Diverse Applications.

Extracellular vesicles (EVs) are crucial mediators of intercellular communication and can be classified based on their physical properties, biomolecular structure, and origin. Among EVs, exosomes have garnered significant attention due to their potential as therapeutic and diagnostic tools. Exosomes are released via fusion of multivesicular bodies on plasma membranes and can be isolated from various biofluids using methods such as differential ultracentrifugation, immune affinity capture, ultrafiltration, and size exclusion chromatography. Herein, an overview of different techniques for exosome characterization and isolation, as well as the diverse applications of exosome detection, including their potential use in drug delivery and disease diagnosis, is provided. Additionally, we discuss the emerging field of exosome detection by sensors, which offers an up-and-coming avenue for point-of-care diagnostic tools development. Overall, this review aims to provide a exhaustive and up-to-date summary of the current state of exosome research.

In situ synthesis and dynamic simulation of molecularly imprinted polymeric nanoparticles on a micro-reactor system.

Current practices in synthesizing molecularly imprinted polymers face challenges-lengthy process, low-productivity, the need for expensive and sophisticated equipment, and they cannot be controlled in situ synthesis. Herein, we present a micro-reactor for in situ and continuously synthesizing trillions of molecularly imprinted polymeric nanoparticles that contain molecular fingerprints of bovine serum albumin in a short period of time (5-30 min). Initially, we performed COMSOL simulation to analyze mixing efficiency with altering flow rates, and experimentally validated the platform for synthesizing nanoparticles with sizes ranging from 52-106 nm. Molecular interactions between monomers and protein were also examined by molecular docking and dynamics simulations. Afterwards, we benchmarked the micro-reactor parameters through dispersity and concentration of molecularly imprinted polymers using principal component analysis. Sensing assets of molecularly imprinted polymers were examined on a metamaterial sensor, resulting in 81% of precision with high selectivity (4.5 times), and three cycles of consecutive use. Overall, our micro-reactor stood out for its high productivity (48-288 times improvement in assay-time and 2 times improvement in reagent volume), enabling to produce 1.4-1.5 times more MIPs at one-single step, and continuous production compared to conventional strategy.

Aptamer-Based Point-of-Care Devices: Emerging Technologies and Integration of Computational Methods.

Recent innovations in point-of-care (POC) diagnostic technologies have paved a critical road for the improved application of biomedicine through the deployment of accurate and affordable programs into resource-scarce settings. The utilization of antibodies as a bio-recognition element in POC devices is currently limited due to obstacles associated with cost and production, impeding its widespread adoption. One promising alternative, on the other hand, is aptamer integration, i.e., short sequences of single-stranded DNA and RNA structures. The advantageous properties of these molecules are as follows: small molecular size, amenability to chemical modification, low- or nonimmunogenic characteristics, and their reproducibility within a short generation time. The utilization of these aforementioned features is critical in developing sensitive and portable POC systems. Furthermore, the deficiencies related to past experimental efforts to improve biosensor schematics, including the design of biorecognition elements, can be tackled with the integration of computational tools. These complementary tools enable the prediction of the reliability and functionality of the molecular structure of aptamers. In this review, we have overviewed the usage of aptamers in the development of novel and portable POC devices, in addition to highlighting the insights that simulations and other computational methods can provide into the use of aptamer modeling for POC integration.

A surface plasmon resonance sensor with synthetic receptors decorated on graphene oxide for selective detection of benzylpenicillin.

Antibiotic residues in foods, water and the environment reveal antibiotic-resistant bacterial strains, disrupting the ecological balance and causing serious health problems. For these reasons, the detection of antibiotic residues is crucial for the protection of human health. Herein, the detection of benzylpenicillin antibiotic from aqueous and milk sample solutions was carried out by surface plasmon resonance (SPR) sensor using synthetic receptor-molecularly imprinted polymer. The benzylpenicillin-imprinted poly(hydroxyethyl methacrylate-graphene oxide-N-methacryloyl-l-phenylalanine) (MIP-GO) SPR sensor was prepared. Benzylpenicillin detection was performed by MIP-GO SPR sensor in a 1-100 ppb concentration range of benzylpenicillin with 0.9665 linear correlation and 0.021 ppb detection limit. Selectivity analysis showed that the MIP-GO SPR sensor detected the benzylpenicillin molecule 8.16 times more selectively than amoxicillin and 14.04 times more selectively than ampicillin. To examine the imprinting efficiency, non-imprinted poly(hydroxyethyl methacrylate-graphene oxide-N-methacryloyl-l-phenylalanine) (NIP-GO) SPR sensor was also prepared using the same procedure without benzylpenicillin addition. Since graphene oxide (GO) was added to enhance the sensor signal response by increasing sensitivity, the control analyses were performed by a poly(hydroxyethyl methacrylate-N-methacryloyl-l-phenylalanine) (MIP) SPR sensor without adding GO. Moreover, repeatability studies of MIP-GO SPR sensor were statistically evaluated and the RSD of intra-day assays less than 1% specified that there was no loss of performance for the benzylpenicillin detection ability even after four cycles. As a real food sample analysis, the benzylpenicillin spiked and unspiked milk samples were evaluated and high-performance liquid chromatography experiments were carried out for validation.

Recent Advances of Optical Sensors for Copper Ion Detection.

A trace element copper (Cu2+) ion is the third most plentiful metal ion that necessary for all living organisms and playing a critical role in several processes. Nonetheless, according to cellular needs, deficient or excess Cu2+ ion cause various diseases. For all these reasons, optical sensors have been focused rapid Cu2+ ion detection in real-time with high selectivity and sensitivity. Optical sensors can measure fluorescence in the refractive index-adsorption from the relationships between light and matter. They have gained great attention in recent years due to the excellent advantages of simple and naked eye recognition, real-time detection, low cost, high specificity against analytes, a quick response, and the need for less complex equipment in analysis. This review aims to show the significance of Cu2+ ion detection and electively current trends in optical sensors. The integration of optical sensors with different systems, such as microfluidic systems, is mentioned, and their latest studies in medical and environmental applications also are depicted. Conclusions and future perspectives on these advances is added at the end of the review.

Selective Amplification of Plasmonic Sensor Signal for Cortisol Detection Using Gold Nanoparticles.

Herein, gold nanoparticles (AuNP)-modified cortisol-imprinted (AuNP-MIP) plasmonic sensor was developed for signal amplification and real-time cortisol determination in both aqueous and complex solutions. Firstly, the sensor surfaces were modified with 3-(trimethoxylyl)propyl methacrylate and then pre-complex was prepared using the functional monomer N-methacryloyl-L-histidine methyl ester. The monomer solution was made ready for polymerization by adding 2-hydroxyethyl methacrylate to ethylene glycol dimethacrylate. In order to confirm the signal enhancing effect of AuNP, only cortisol-imprinted (MIP) plasmonic sensor was prepared without AuNP. To determine the selectivity efficiency of the imprinting process, the non-imprinted (AuNP-NIP) plasmonic sensor was also prepared without cortisol. The characterization studies of the sensors were performed with atomic force microscopy and contact angle measurements. The kinetic analysis of the AuNP-MIP plasmonic sensor exhibited a high correlation coefficient (R2 = 0.97) for a wide range (0.01-100 ppb) with a low detection limit (0.0087 ppb) for cortisol detection. Moreover, the high imprinting efficiency (k' = 9.67) of the AuNP-MIP plasmonic sensor was determined by comparison with the AuNP-NIP plasmonic sensor. All kinetic results were validated and confirmed by HPLC.

Ion-Imprinted Polymer-on-a-Sensor for Copper Detection.

The accumulation of metal ions in the body is caused by human activities and industrial uses. Among these metal ions, copper is the third most abundant ion found in the human body and is indispensable for health because it works as a catalyst in the iron absorption processes. However, high doses of copper ions have been reported to generate various diseases. Different types of sensors are used to detect metal ions for several applications. To design selective and specific recognition sites on the sensor surfaces, molecular imprinting is one of the most used alteration methods to detect targets by mimicking natural recognition molecules. In this study, an ion-imprinted polymer-integrated plasmonic sensor was prepared to selectively detect copper (Cu(II)) ions in real-time. Following different characterization experiments, the Cu(II)-imprinted plasmonic sensor was employed for kinetic, selectivity, and reusability studies. According to the results, it was observed that this sensor can measure with 96% accuracy in the Cu(II) concentration range of 0.04-5 µM in buffer solution. The limit of detection and limit of quantification values were computed as 0.027 µM and 0.089 µM. The results also showed that this plasmonic sensor works successfully not only in a buffer solution but also in complex media such as plasma and urine.

Sensitive and real-time detection of IgG using interferometric reflecting imaging sensor system.

Considering the limitations of well-known traditional detection techniques, innovative research studies have focused on the development of new sensors to offer label-free, highly sensitive, real-time, low-cost, and rapid detection for biomolecular interactions. In this study, we demonstrate immunoglobulin G (IgG) detection in aqueous solutions by using real-time and label-free kinetic measurements of the Interferometric Reflectance Imaging Sensor (IRIS) system. By performing kinetic characterization experiments, the sensor's performance is comprehensively evaluated and a high correlation coefficient value (>0.94) is obtained in the IgG concentration range of 1-50 µg/mL with a low detection limit (0.25 µg/mL or 1.67 nM). Moreover, the highly sensitive imaging system ensures accurate quantification and reliable validation of recorded binding events, offering new perspectives in terms of direct biomarker detection for clinical applications.

Recent Advances in Microneedle-Based Sensors for Sampling, Diagnosis and Monitoring of Chronic Diseases.

Chronic diseases (CDs) are noncommunicable illnesses with long-term symptoms accounting for ~70% of all deaths worldwide. For the diagnosis and prognosis of CDs, accurate biomarker detection is essential. Currently, the detection of CD-associated biomarkers is employed through complex platforms with certain limitations in their applicability and performance. There is hence unmet need to present innovative strategies that are applicable to the point-of-care (PoC) settings, and also, provide the precise detection of biomarkers. On the other hand, especially at PoC settings, microneedle (MN) technology, which comprises micron-size needles arranged on a miniature patch, has risen as a revolutionary approach in biosensing strategies, opening novel horizons to improve the existing PoC devices. Various MN-based platforms have been manufactured for distinctive purposes employing several techniques and materials. The development of MN-based biosensors for real-time monitoring of CD-associated biomarkers has garnered huge attention in recent years. Herein, we summarize basic concepts of MNs, including microfabrication techniques, design parameters, and their mechanism of action as a biosensing platform for CD diagnosis. Moreover, recent advances in the use of MNs for CD diagnosis are introduced and finally relevant clinical trials carried out using MNs as biosensing devices are highlighted. This review aims to address the potential use of MNs in CD diagnosis.

Plasmonic Sensors for Monitoring Biological and Chemical Threat Agents.

Sensors are excellent options owing to their ability to figure out a large number of problems and challenges in several areas, including homeland security, defense, medicine, pharmacology, industry, environment, agriculture, food safety, and so on. Plasmonic sensors are used as detection devices that have important properties, such as rapid recognition, real-time analysis, no need labels, sensitive and selective sensing, portability, and, more importantly, simplicity in identifying target analytes. This review summarizes the state-of-art molecular recognition of biological and chemical threat agents. For this purpose, the principle of the plasmonic sensor is briefly explained and then the use of plasmonic sensors in the monitoring of a broad range of biological and chemical threat agents is extensively discussed with different types of threats according to the latest literature. A conclusion and future perspectives are added at the end of the review.

Advances in Biomimetic Systems for Molecular Recognition and Biosensing.

Understanding the fundamentals of natural design, structure, and function has pushed the limits of current knowledge and has enabled us to transfer knowledge from the bench to the market as a product. In particular, biomimicry-one of the crucial strategies in this respect-has allowed researchers to tackle major challenges in the disciplines of engineering, biology, physics, materials science, and medicine. It has an enormous impact on these fields with pivotal applications, which are not limited to the applications of biocompatible tooth implants, programmable drug delivery systems, biocompatible tissue scaffolds, organ-on-a-chip systems, wearable platforms, molecularly imprinted polymers (MIPs), and smart biosensors. Among them, MIPs provide a versatile strategy to imitate the procedure of molecular recognition precisely, creating structural fingerprint replicas of molecules for biorecognition studies. Owing to their affordability, easy-to-fabricate/use features, stability, specificity, and multiplexing capabilities, host-guest recognition systems have largely benefitted from the MIP strategy. This review article is structured with four major points: (i) determining the requirement of biomimetic systems and denoting multiple examples in this manner; (ii) introducing the molecular imprinting method and reviewing recent literature to elaborate the power and impact of MIPs on a variety of scientific and industrial fields; (iii) exemplifying the MIP-integrated systems, i.e., chromatographic systems, lab-on-a-chip systems, and sensor systems; and (iv) closing remarks.

Molecularly imprinted polymer integrated plasmonic nanosensor for cocaine detection.

A molecularly imprinted polymeric nanofilm was prepared for cocaine detection and applied to plasmonic nanosensor for real-time kinetic, selectivity and reusability analyses. The sensing polymeric surface was fabricated by synthesizing a selective and specific nanofilm on the gold plasmonic nanosensor surface. After characterization experiments with atomic force microscopy, ellipsometer, and contact angle measurements, the kinetic studies of cocaine detection in aqueous solutions in a wide concentration range between 0.2-100 µg/mL were applied to plasmonic nanosensor system at 24 °C with a low limit of detection (0.1 µg/L) and quantification values (0.3 µg/L) and the results showed that this molecularly imprinted polymeric nanofilm integrated plasmonic nanosensor is providing a model for the fastest, most accurate and most precise identification of the cocaine molecule which constitutes a large part of the workload of forensic laboratories.

Molecularly Imprinted Polymer-Based Microfluidic Systems for Point-of-Care Applications.

Fast progress has been witnessed in the field of microfluidic systems and allowed outstanding approaches to portable, disposable, low-cost, and easy-to-operate platforms especially for monitoring health status and point-of-care applications. For this purpose, molecularly imprinted polymer (MIP)-based microfluidics systems can be synthesized using desired templates to create specific and selective cavities for interaction. This technique guarantees a wide range of versatility to imprint diverse sets of biomolecules with different structures, sizes, and physical and chemical features. Owing to their physical and chemical robustness, cost-friendliness, high stability, and reusability, MIP-based microfluidics systems have become very attractive modalities. This review is structured according to the principles of MIPs and microfluidic systems, the integration of MIPs with microfluidic systems, the latest strategies and uses for point-of-care applications and, finally, conclusions and future perspectives.

An Alternative Medical Diagnosis Method: Biosensors for Virus Detection.

Infectious diseases still pose an omnipresent threat to global and public health, especially in many countries and rural areas of cities. Underlying reasons of such serious maladies can be summarized as the paucity of appropriate analysis methods and subsequent treatment strategies due to the limited access of centralized and equipped health care facilities for diagnosis. Biosensors hold great impact to turn our current analytical methods into diagnostic strategies by restructuring their sensing module for the detection of biomolecules, especially nano-sized objects such as protein biomarkers and viruses. Unquestionably, current sensing platforms require continuous updates to address growing challenges in the diagnosis of viruses as viruses change quickly and spread largely from person-to-person, indicating the urgency of early diagnosis. Some of the challenges can be classified in biological barriers (specificity, low number of targets, and biological matrices) and technological limitations (detection limit, linear dynamic range, stability, and reliability), as well as economical aspects that limit their implementation into resource-scarce settings. In this review, the principle and types of biosensors and their applications in the diagnosis of distinct infectious diseases were comprehensively explained. The deployment of current biosensors into resource-scarce settings is further discussed for virus detection by elaborating the pros and cons of existing methods as a conclusion and future perspective.

Supermacroporous Composite Cryogels in Biomedical Applications.

Supermacroporous gels, called cryogels, are unique scaffolds that can be prepared by polymerization of monomer solution under sub-zero temperatures. They are widely used in many applications and have significant potential biomaterials, especially for biomedical applications due to their inherent interconnected supermacroporous structures and easy formation of composite polymers in comparison to other porous polymer synthesis techniques. This review highlights the fundamentals of supermacroporous cryogels and composite cryogels, and then comprehensively summarizes recent studies in preparation, functionalization, and utilization with mechanical, biological and physicochemical features, according to the biomedical applications. Furthermore, conclusions and outlooks are discussed for the use of these promising and durable supermacroporous composite cryogels.

Molecularly Imprinted Polymer Based Sensors for Medical Applications.

Sensors have been extensively used owing to multiple advantages, including exceptional sensing performance, user-friendly operation, fast response, high sensitivity and specificity, portability, and real-time analysis. In recent years, efforts in sensor realm have expanded promptly, and it has already presented a broad range of applications in the fields of medical, pharmaceutical and environmental applications, food safety, and homeland security. In particular, molecularly imprinted polymer based sensors have created a fascinating horizon for surface modification techniques by forming specific recognition cavities for template molecules in the polymeric matrix. This method ensures a broad range of versatility to imprint a variety of biomolecules with different size, three dimensional structure, physical and chemical features. In contrast to complex and time-consuming laboratory surface modification methods, molecular imprinting offers a rapid, sensitive, inexpensive, easy-to-use, and highly selective approaches for sensing, and especially for the applications of diagnosis, screening, and theranostics. Due to its physical and chemical robustness, high stability, low-cost, and reusability features, molecularly imprinted polymer based sensors have become very attractive modalities for such applications with a sensitivity of minute structural changes in the structure of biomolecules. This review aims at discussing the principle of molecular imprinting method, the integration of molecularly imprinted polymers with sensing tools, the recent advances and strategies in molecular imprinting methodologies, their applications in medical, and future outlook on this concept.

Molecularly imprinted nanoparticles based plasmonic sensors for real-time Enterococcus faecalis detection.

Human fecal contamination poses a crucial environmental and health threat in recent years, resulting in the difficulties of access to clean water. According to the World Health Organization, several fecal bacteria, particularly Enterococci species, are present in human intestinal flora. Enterococcus faecalis (E. faecalis) is one of the indicator bacteria that have been utilized as a pollution indicator in water. However, existing technologies and detection strategies face multiple challenges in terms of low affinity for detection and labelling requirements that limit their access to large scale applications. Here, we present a label-free molecular fingerprinting strategy on a plasmonic sensor to detect E. fecalis from aqueous and seawater samples. The kinetic performance of platform was comprehensively evaluated and the platform provided four orders of magnitude detection range with a low limit of detection (down to ~100 bacteria/mL) and a high correlation coefficient value (> 0.99) in the range of 2 × 104-1 × 108 cfu/mL. The platform also denoted a selectivity and specificity while other bacteria (E. coli, B. subtilis, and S. aureus) samples were applied. Multiple time use and relatively long shelf-life are superior to the existing modality. The presented method is one of the fascinating surface modification technique that utilizes biotarget as a recognition element itself, providing a broad range of versatility to replica other biotargets with different molecular structure, size, and physicochemical properties. Such a reliable and versatile platform would hold potential applications from microbiome characterization to forensics by revitalizing obsolescent detection strategies.

Molecular Fingerprints of Hemoglobin on a Nanofilm Chip.

Hemoglobin is an iron carrying protein in erythrocytes and also an essential element to transfer oxygen from the lungs to the tissues. Abnormalities in hemoglobin concentration are closely correlated with health status and many diseases, including thalassemia, anemia, leukemia, heart disease, and excessive loss of blood. Particularly in resource-constrained settings existing blood analyzers are not readily applicable due to the need for high-level instrumentation and skilled personnel, thereby inexpensive, easy-to-use, and reliable detection methods are needed. Herein, a molecular fingerprints of hemoglobin on a nanofilm chip was obtained for real-time, sensitive, and selective hemoglobin detection using a surface plasmon resonance system. Briefly, through the photopolymerization technique, a template (hemoglobin) was imprinted on a monomeric (acrylamide) nanofilm on-chip using a cross-linker (methylenebisacrylamide) and an initiator-activator pair (ammonium persulfate-tetramethylethylenediamine). The molecularly imprinted nanofilm on-chip was characterized by atomic force microscopy and ellipsometry, followed by benchmarking detection performance of hemoglobin concentrations from 0.0005 mg mL-1 to 1.0 mg mL-1. Theoretical calculations and real-time detection implied that the molecularly imprinted nanofilm on-chip was able to detect as little as 0.00035 mg mL-1 of hemoglobin. In addition, the experimental results of hemoglobin detection on the chip well-fitted with the Langmuir adsorption isotherm model with high correlation coefficient (0.99) and association and dissociation coefficients (39.1 mL mg-1 and 0.03 mg mL-1) suggesting a monolayer binding characteristic. Assessments on selectivity, reusability and storage stability indicated that the presented chip is an alternative approach to current hemoglobin-targeted assays in low-resource regions, as well as antibody-based detection procedures in the field. In the future, this molecularly imprinted nanofilm on-chip can easily be integrated with portable plasmonic detectors, improving its access to these regions, as well as it can be tailored to detect other proteins and biomarkers.