Increasing the sensitivity and accuracy of detecting exosomes as biomarkers for cancer monitoring using optical nanobiosensors.

The advancement of nanoscience and material design in recent times has facilitated the creation of point-of-care devices for cancer diagnosis and biomolecule sensing. Exosomes (EXOs) facilitate the transfer of bioactive molecules between cancer cells and diverse cells in the local and distant microenvironments, thereby contributing to cancer progression and metastasis. Specifically, EXOs derived from cancer are likely to function as biomarkers for early cancer detection due to the genetic or signaling alterations they transport as payload within the cancer cells of origin. It has been verified that EXOs circulate steadily in bodily secretions and contain a variety of information that indicates the progression of the tumor. However, acquiring molecular information and interactions regarding EXOs has presented significant technical challenges due to their nanoscale nature and high heterogeneity. Colorimetry, surface plasmon resonance (SPR), fluorescence, and Raman scattering are examples of optical techniques utilized to quantify cancer exosomal biomarkers, including lipids, proteins, RNA, and DNA. Many optically active nanoparticles (NPs), predominantly carbon-based, inorganic, organic, and composite-based nanomaterials, have been employed in biosensing technology. The exceptional physical properties exhibited by nanomaterials, including carbon NPs, noble metal NPs, and magnetic NPs, have facilitated significant progress in the development of optical nanobiosensors intended for the detection of EXOs originating from tumors. Following a summary of the biogenesis, biological functions, and biomarker value of known EXOs, this article provides an update on the detection methodologies currently under investigation. In conclusion, we propose some potential enhancements to optical biosensors utilized in detecting EXO, utilizing various NP materials such as silicon NPs, graphene oxide (GO), metal NPs, and quantum dots (QDs).

Forty years of advances in optical biosensors-are "autonomous" biosensors in our future?

Optical biosensors have employed at least three distinct system architectures over the last 40 years, moving from "sample in-answer out" systems to completely embedding the optical biosensor into the sample to embedding the recognition module in the sample and optically interrogating the recognition module from outside of the sample. This trends article provides an overview of the evolution of these three system architectures and discusses how each architecture has been applied to solve the measurement challenges of a wide variety of applications. A fourth biosensor system architecture, that of an "autonomous" biosensor which "takes the user out of the loop" while both detecting target analytes and responding to that measurement, is currently under development for applications initially including environmental cleanup and "smart therapeutics." As is the case in many other areas of technology, it will be profoundly interesting to observe the further development and application of elegant, simpler (optical) biosensor systems to address tomorrow's measurement needs.

Electrochemical Sensors for Antibiotic Detection: A Focused Review with a Brief Overview of Commercial Technologies.

Antimicrobial resistance (AMR) poses a significant threat to global health, powered by pathogens that become increasingly proficient at withstanding antibiotic treatments. This review introduces the factors contributing to antimicrobial resistance (AMR), highlighting the presence of antibiotics in different environmental and biological matrices as a significant contributor to the resistance. It emphasizes the urgent need for robust and effective detection methods to identify these substances and mitigate their impact on AMR. Traditional techniques, such as liquid chromatography-mass spectrometry (LC-MS) and immunoassays, are discussed alongside their limitations. The review underscores the emerging role of biosensors as promising alternatives for antibiotic detection, with a particular focus on electrochemical biosensors. Therefore, the manuscript extensively explores the principles and various types of electrochemical biosensors, elucidating their advantages, including high sensitivity, rapid response, and potential for point-of-care applications. Moreover, the manuscript investigates recent advances in materials used to fabricate electrochemical platforms for antibiotic detection, such as aptamers and molecularly imprinted polymers, highlighting their role in enhancing sensor performance and selectivity. This review culminates with an evaluation and summary of commercially available and spin-off sensors for antibiotic detection, emphasizing their versatility and portability. By explaining the landscape, role, and future outlook of electrochemical biosensors in antibiotic detection, this review provides insights into the ongoing efforts to combat the escalating threat of AMR effectively.

An Integrated Photonic Biosensing Platform for Pathogen Detection in Aquaculture.

Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring the pathogen levels in aquaculture facilities. This paper describes a photonic biosensing platform based on silicon nitride waveguide technology with integrated active components, which could be used for such applications. Compared to the state of the art, the current system presents improvements in terms of miniaturization of the Photonic Integrated Circuit (PIC) and the development of wafer-level processes for hybrid integration of active components and for material-selective chemical and biological surface modification. Furthermore, scalable processes for integrating the PIC in a microfluidic cartridge were developed, as well as a prototype desktop readout instrument. Three bacterial aquaculture pathogens (Aeromonas salmonicida, Vagococcus salmoninarum, and Yersinia ruckeri) were selected for assay development. DNA biomarkers were identified, corresponding primer-probe sets designed, and qPCR assays developed. The biomarker for Aeromonas was also detected using the hybrid PIC platform. This is the first successful demonstration of biosensing on the hybrid PIC platform.

Wavelength Division Multiplexing-Based High-Sensitivity Surface Plasmon Resonance Imaging Biosensor for High-Throughput Real-Time Molecular Interaction Analysis.

In this study, we report the successful development of a novel high-sensitivity intensity-based Surface Plasmon Resonance imaging (SPRi) biosensor and its application for detecting molecular interactions. By optimizing the excitation wavelength and employing a wavelength division multiplexing (WDM) algorithm, the system can determine the optimal excitation wavelength based on the initial refractive index of the sample without adjusting the incidence angle. The experimental results demonstrate that the refractive index resolution of the system reaches 1.77×10-6 RIU. Moreover, it can obtain the optimal excitation wavelength for samples with an initial refractive index in the range of 1.333 to 1.370 RIU and accurately monitor variations within the range of 0.0037 RIU without adjusting the incidence angle. Additionally, our new SPRi technique realized real-time detection of high-throughput biomolecular binding processes, enabling analysis of kinetic parameters. This research is expected to advance the development of more accurate SPRi technologies for molecular interaction analysis.

Functional Nanomaterials for the Diagnosis of Alzheimer's Disease: Recent Progress and Future Perspectives.

Alzheimer's disease (AD) is one of the main causes of dementia worldwide, whereby neuronal death or malfunction leads to cognitive impairment in the elderly population. AD is highly prevalent, with increased projections over the next few decades. Yet current diagnostic methods for AD occur only after the presentation of clinical symptoms. Evidence in the literature points to potential mechanisms of AD induction beginning before clinical symptoms start to present, such as the formation of amyloid beta (Aß) extracellular plaques and neurofibrillary tangles (NFTs). Biomarkers of AD, including Aß 40, Aß 42, and tau protein, amongst others, show promise for early AD diagnosis. Additional progress is made in the application of biosensing modalities to measure and detect significant changes in these AD biomarkers within patient samples, such as cerebral spinal fluid (CSF) and blood, serum, or plasma. Herein, a comprehensive review of the emerging nano-biomaterial approaches to develop biosensors for AD biomarkers' detection is provided. Advances, challenges, and potential of electrochemical, optical, and colorimetric biosensors, focusing on nanoparticle-based (metallic, magnetic, quantum dots) and nanostructure-based biomaterials are discussed. Finally, the criteria for incorporating these emerging nano-biomaterials in clinical settings are presented and assessed, as they hold great potential for enhancing early-onset AD diagnostics.

Recent advances in nanomaterial-based optical biosensors for food safety applications: Ochratoxin-A detection, as case study.

Global population growth tremendously impacts the global food industry, endangering food safety and quality. Mycotoxins, particularly Ochratoxin-A (OTA), emerge as a food chain production threat, since it is produced by fungus that contaminates different food species and products. Beyond this, OTA exhibits a possible human toxicological risk that can lead to carcinogenic and neurological diseases. A selective, sensitive, and reliable OTA biodetection approach is essential to ensure food safety. Current detection approaches rely on accurate and time-consuming laboratory techniques performed at the end of the food production process, or lateral-flow technologies that are rapid and on-site, but do not provide quantitative and precise OTA concentration measurements. Nanoengineered optical biosensors arise as an avant-garde solution, providing high sensing performance, and a fast and accurate OTA biodetection screening, which is attractive for the industrial market. This review core presents and discusses the recent advancements in optical OTA biosensing, considering engineered nanomaterials, optical transduction principle and biorecognition methodologies. Finally, the major challenges and future trends are discussed, and current patented OTA optical biosensors are emphasized for a particular promising detection method.

Optical biosensors for environmental monitoring: Recent advances and future perspectives in bacterial detection.

The environmental contamination due to bacterial proliferation vs their identification is the major deciding factor in the spread of diseases leading to pandemics. The advent of drug-resistant pathogenic contaminants in our environment has further added to the load of complications associated with their diagnosis and treatment. Obstructing the spread of such infections, prioritizes the expansion of sensor-based diagnostics, effectuating, a sturdy detection of disease-causing microbes, contaminating our surroundings in shortest possible time, with minimal expenditure. Among many sensors known, optical biosensors promote the recognition of pathogens befouling the environment through a comparatively intuitive, brisk, portable, multitudinous, and thrifty approach. This article reviews the recent progresses in optical biosensor-based systems for effective environmental monitoring. The technical and methodological perspectives of fundamental optical-sensing platforms are reviewed, combined with the pros and cons of every procedure. Eventually, the obstacles lying in the path of development of an effective optical biosensor device for bio-monitoring and its future perspectives are highlighted in the present work.

Optimizing an Optical Cavity-Based Biosensor for Enhanced Sensitivity.

The rapid advancement of biosensor technology has revolutionized healthcare, offering improved sensitivity, specificity, and portability. We have developed an optical cavity-based biosensor (OCB) as a promising solution due to its label-free detection, high sensitivity, real-time monitoring, multiplexing capability, and versatility. The OCB consists of an optical cavity structure (OCS), optical components, and a low-cost camera. The OCS is created by two partially reflective surfaces separated by a small gap, where the interaction between target analytes and immobilized receptors leads to a shift in the resonance transmission spectrum, caused by minute changes in the local refractive index (RI). In our previous work, we successfully detected these small changes with a simple OCS and cost-effective components using a differential detection method. Building upon these achievements, this study focuses on optimizing the OCS, improving the camera settings, and enhancing the differential detection approach. By increasing the reflectance of the surfaces and optimizing the optical cavity widths correspondingly, we achieved an improved limit of detection (LOD). We also investigated how the charge-coupled device (CCD) camera shutter time affects the LOD. Additionally, we introduced a new differential equation to further enhance the sensitivity of our system. Through these advancements, we could improve the LOD of the OCB by 7.2 times, specifically for an OCS with a cavity thickness of 9.881 µm and a silver thickness of 46.87 nm. These findings not only contribute to the ongoing effort of optimizing the OCB, but also pave the way for the development of advanced point-of-care biosensors with enhanced detection capabilities.

Signaling strategies of silver nanoparticles in optical and electrochemical biosensors: considering their potential for the point-of-care.

Silver nanoparticles (AgNPs) have long been overshadowed by gold NPs' success in sensor and point-of-care (POC) applications. However, their unique physical, (electro)chemical, and optical properties make them excellently suited for such use, as long as their inherent higher instability toward oxidation is controlled. Recent advances in this field provide novel strategies that demonstrate that the AgNPs' inherent capabilities improve sensor performance and enable the specific detection of analytes at low concentrations. We provide an overview of these advances by focusing on the nanosized Ag (in the range of 1-100 nm) properties with emphasis on optical and electrochemical biosensors. Furthermore, we critically assess their potential for point-of-care sensors discussing advantages as well as limitations for each detection technique. We can conclude that, indeed, strategies using AgNP are ready for sensitive POC applications; however, research focusing on the simplification of assay procedures is direly needed for AgNPs to make the successful jump into actual applications.

Determining the Nutrient Content of Hydroponically-Cultivated Microgreens with Immersible Silicon Photonic Sensors: A Preliminary Feasibility Study.

Microgreens have gained attention for their exceptional culinary characteristics and high nutritional value. The present study focused on a novel approach for investigating the easy extraction of plant samples and the utilization of immersible silicon photonic sensors to determine, on the spot, the nutrient content of microgreens and their optimum time of harvest. For the first time, it was examined how these novel sensors can capture time-shifting spectra caused by the molecules' dynamic adhesion onto the sensor surface. The experiment involved four types of microgreens (three types of basil and broccoli) grown in a do-it-yourself hydroponic installation. The sensors successfully distinguished between different plant types, showcasing their discriminative capabilities. To determine the optimum harvest time, this study compared the sensor data with results obtained through standard analytical methods. Specifically, the total phenolic content and antioxidant activity of two basil varieties were juxtaposed with the sensor data, and this study concluded that the ideal harvest time for basil microgreens was 14 days after planting. This finding highlights the potential of the immersible silicon photonic sensors for potentially replacing time-consuming analytical techniques. By concentrating on obtaining plant extracts, capturing time-shifting spectra, and assessing sensor reusability, this research paves the way for future advancements in urban farming.

Solid-Phase Optical Sensing Techniques for Sensitive Virus Detection.

Viral infections can pose a major threat to public health by causing serious illness, leading to pandemics, and burdening healthcare systems. The global spread of such infections causes disruptions to every aspect of life including business, education, and social life. Fast and accurate diagnosis of viral infections has significant implications for saving lives, preventing the spread of the diseases, and minimizing social and economic damages. Polymerase chain reaction (PCR)-based techniques are commonly used to detect viruses in the clinic. However, PCR has several drawbacks, as highlighted during the recent COVID-19 pandemic, such as long processing times and the requirement for sophisticated laboratory instruments. Therefore, there is an urgent need for fast and accurate techniques for virus detection. For this purpose, a variety of biosensor systems are being developed to provide rapid, sensitive, and high-throughput viral diagnostic platforms, enabling quick diagnosis and efficient control of the virus's spread. Optical devices, in particular, are of great interest due to their advantages such as high sensitivity and direct readout. The current review discusses solid-phase optical sensing techniques for virus detection, including fluorescence-based sensors, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), optical resonators, and interferometry-based platforms. Then, we focus on an interferometric biosensor developed by our group, the single-particle interferometric reflectance imaging sensor (SP-IRIS), which has the capability to visualize single nanoparticles, to demonstrate its application for digital virus detection.

Optimization of Silicon Nitride Waveguide Platform for On-Chip Virus Detection.

This work presents a rigorous and generic sensitivity analysis of silicon nitride on silicon dioxide strip waveguide for virus detection. In general, by functionalizing the waveguide surface with a specific antibodies layer, we make the optical sensor sensitive only to a particular virus. Unlike conventional virus detection methods such as polymerase chain reaction (PCR), integrated refractive index (RI) optical sensors offer cheap and mass-scale fabrication of compact devices for fast and straightforward detection with high sensitivity and selectivity. Our numerical analysis includes a wide range of wavelengths from visible to mid-infrared. We determined the strip waveguide's single-mode dimensions and the optimum dimensions that maximize the sensitivity to the virus layer attached to its surface at each wavelength using finite difference eigenmode (FDE) solver. We also compared the strip waveguide with the widely used slot waveguide. Our theoretical study shows that silicon nitride strip waveguide working at lower wavelengths is the optimum choice for virus detection as it maximizes both the waveguide sensitivity (Swg) and the figure of merit (FOM) of the sensor. The optimized waveguides are well suited for a range of viruses with different sizes and refractive indices. Balanced Mach-Zehnder interferometer (MZI) sensors were designed using FDE solver and photonic circuit simulator at different wavelengths. The designed sensors show high FOM at λ = 450 nm ranging from 500 RIU-1 up to 1231 RIU-1 with LMZI = 500 µm. Different MZI configurations were also studied and compared. Finally, edge coupling from the fiber to the sensor was designed, showing insertion loss (IL) at λ = 450 nm of 4.1 dB for the design with FOM = 500 RIU-1. The obtained coupling efficiencies are higher than recently proposed fiber couplers.

Multiplex Label-Free Kinetic Characterization of Antibodies for Rapid Sensitive Cardiac Troponin I Detection Based on Functionalized Magnetic Nanotags.

Express and highly sensitive immunoassays for the quantitative registration of cardiac troponin I (cTnI) are in high demand for early point-of-care differential diagnosis of acute myocardial infarction. The selection of antibodies that feature rapid and tight binding with antigens is crucial for immunoassay rate and sensitivity. A method is presented for the selection of the most promising clones for advanced immunoassays via simultaneous characterization of interaction kinetics of different monoclonal antibodies (mAb) using a direct label-free method of multiplex spectral correlation interferometry. mAb-cTnI interactions were real-time registered on an epoxy-modified microarray glass sensor chip that did not require activation. The covalent immobilization of mAb microdots on its surface provided versatility, convenience, and virtually unlimited multiplexing potential. The kinetics of tracer antibody interaction with the "cTnI­capture antibody" complex was characterized. Algorithms are shown for excluding mutual competition of the tracer/capture antibodies and selecting the optimal pairs for different assay formats. Using the selected mAbs, a lateral flow assay was developed for rapid quantitative cTnI determination based on electronic detection of functionalized magnetic nanoparticles applied as labels (detection limit­0.08 ng/mL, dynamic range > 3 orders). The method can be extended to other molecular biomarkers for high-throughput screening of mAbs and rational development of immunoassays.

Optical Biosensors for Virus Detection: Prospects for SARS-CoV-2/COVID-19.

The recent pandemic of the novel coronavirus disease 2019 (COVID-19) has caused huge worldwide disruption due to the lack of available testing locations and equipment. The use of optical techniques for viral detection has flourished in the past 15 years, providing more reliable, inexpensive, and accurate detection methods. In the current minireview, optical phenomena including fluorescence, surface plasmons, surface-enhanced Raman scattering (SERS), and colorimetry are discussed in the context of detecting virus pathogens. The sensitivity of a viral detection method can be dramatically improved by using materials that exhibit surface plasmons or SERS, but often this requires advanced instrumentation for detection. Although fluorescence and colorimetry lack high sensitivity, they show promise as point-of-care diagnostics because of their relatively less complicated instrumentation, ease of use, lower costs, and the fact that they do not require nucleic acid amplification. The advantages and disadvantages of each optical detection method are presented, and prospects for applying optical biosensors in COVID-19 detection are discussed.

Recent advances in nanomaterials based biosensors for point of care (PoC) diagnosis of Covid-19 - A minireview.

Early diagnosis and ultrahigh sample throughput screening are the need of the hour to control the geological spread of the COVID-19 pandemic. Traditional laboratory tests such as enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR) and computed tomography are implemented for the detection of COVID-19. However, they are limited by the laborious sample collection and processing procedures, longer wait time for test results and skilled technicians to operate sophisticated facilities. In this context, the point of care (PoC) diagnostic platform has proven to be the prospective approach in addressing the abovementioned challenges. This review emphasizes the mechanism of viral infection spread detailing the host-virus interaction, pathophysiology, and the recent advances in the development of affordable PoC diagnostic platforms for rapid and accurate diagnosis of COVID-19. First, the well-established optical and electrochemical biosensors are discussed. Subsequently, the recent advances in the development of PoC biosensors, including lateral flow immunoassays and other emerging techniques, are highlighted. Finally, a focus on integrating nanotechnology with wearables and smartphones to develop smart nanobiosensors is outlined, which could promote COVID-19 diagnosis accessible to both individuals and the mass population at patient care.

High-Order Multimode Waveguide Interferometer for Optical Biosensing Applications.

A generalization of the concept of multimode interference sensors is presented here for the first time, to the best of our knowledge. The existing bimodal and trimodal sensors correspond to particular cases of those interference sensors. A thorough study of the properties of the multimode waveguide section provided a deeper insight into the behavior of this class of sensors, which allowed us to establish new criteria for designing more sensitive structures. Other challenges of using high-order modes within the sensing area of the device reside in the excitation of these modes and the interpretation of the output signal. To overcome these, we developed a novel structure to excite any desired high-order mode along with the fundamental mode within the sensing section, while maintaining a fine control over the power distribution between them. A new strategy to detect and interpret the output signal is also presented in detail. Finally, we designed a high-order sensor for which numerical simulations showed a theoretical limit of detection of 1.9×10-7 RIU, making this device the most sensitive multimode interference sensor reported so far.

Photoelectro-Enzymatic Glucose Reusable Biosensor by Using Dithienylethene Mediators.

In the development of colorimetric biosensors, the use of electrochromic mediators has been accepted and widely used during decades. The main drawback of these types of enzymatic substrates is the difficult recovery of the initial redox state of the molecule, which can be done electrochemically or by antioxidants addition, complicating the initially simple structure of the biosensor. those strategies are rarely followed Actually, being the disposable biosensor configuration the most extended for this detection mechanisms. Alternatively, we propose the first reported use of a diacid dithienylethene 1,2-bis(5-carboxy-2-methylthien-3-yl)cyclopentene (DTE) photoelectrochromic compound as a substrate of the horseradish peroxidase (HRP). The photoisomerization between the open (DTEo) and closed (DTEc) forms of the molecule and the respective shift in the redox potential allowed the light-induced enzymatic detection of glucose in the glucose oxidase [(GOx)]-HRP cascade system. This fast and easy control over the enzymatic substrate availability by light pulses permits a gradually consumption and the light-regeneration of the biosensor for a number of cycles. We consider the presented results transcendent in the development of reusable and light-controlled photonic biosensing systems.

Development of the Correction Algorithm to Limit the Deformation of Bacterial Colonies Diffraction Patterns Caused by Misalignment and Its Impact on the Bacteria Identification in the Proposed Optical Biosensor.

Recently proposed methods of bacteria identification in optical biosensors based on the phenomenon of light diffraction on macro-colonies offer over 98% classification accuracy. However, such high accuracy relies on the comparable and repeatable spatial intensity distribution of diffraction patterns. Therefore, it is essential to eliminate all non-species/strain-dependent factors affecting the diffraction patterns. In this study, the impact of the bacterial colony and illuminating beam misalignment on the variation of classification features extracted from diffraction patterns was examined. It was demonstrated that misalignment introduced by the scanning module significantly affected diffraction patterns and extracted classification features used for bacteria identification. Therefore, it is a crucial system-dependent factor limiting the identification accuracy. The acceptable misalignment level, when the accuracy and quality of the classification features are not affected, was determined as no greater than 50 µm. Obtained results led to development of image-processing algorithms for determination of the direction of misalignment and concurrent alignment of the bacterial colonies' diffraction patterns. The proposed algorithms enable the rigorous monitoring and controlling of the measurement's conditions in order to preserve the high accuracy of bacteria identification.

An Optical Urate Biosensor Based on Urate Oxidase and Long-Lifetime Metalloporphyrins.

Gout is a condition that affects over 8 million Americans. This condition is characterized by severe pain, and in more advanced cases, bone erosion and joint destruction. This study explores the fabrication and characterization of an optical, enzymatic urate biosensor for gout management, and the optimization of the biosensor response through the tuning of hydrogel matrix properties. Sensors were fabricated through the co-immobilization of oxygen-quenched phosphorescent probes with an oxidoreductase within a biocompatible copolymer hydrogel matrix. Characterization of the spectral properties and hydrogel swelling was conducted, as well as evaluation of the response sensitivity and long-term stability of the urate biosensor. The findings indicate that increased acrylamide concentration improved the biosensor response by yielding an increased sensitivity and reduced lower limit of detection. However, the repeatability and stability tests highlighted some possible areas of improvement, with a consistent response drift observed during repeatability testing and a reduction in response seen after long-term storage tests. Overall, this study demonstrates the potential of an on-demand, patient-friendly gout management tool, while paving the way for a future multi-analyte biosensor based on this sensing platform.