Advances In Biosensors Research Articles

A Primer on Luminescence Sensing

AbstractThis Perspective provides a concise overview of the field of Luminescence Sensing, which enables highly sensitive, selective, and versatile measurements. The emergence of new luminescent nanomaterials and the prospective of deploying new luminescence‐based detection schemes for solving real‐world problems, e. g., in medical diagnosis, food safety, and environmental sciences, has led to a continuous growth of the field over recent years. The contributions to the Special Collection on Luminescence Sensing – with a focus on the versatility and advantages of lanthanide complexes for advanced biosensing – serve as an excellent foundation to highlight and discuss recent developments and challenges.

Biosensor integrated brain-on-a-chip platforms: Progress and prospects in clinical translation

Because of the brain's complexity, developing effective treatments for neurological disorders is a formidable challenge. Research efforts to this end are advancing as in vitro systems have reached the point that they can imitate critical components of the brain's structure and function. Brain-on-a-chip (BoC) was first used for microfluidics-based systems with small synthetic tissues but has expanded recently to include in vitro simulation of the central nervous system (CNS). Defining the system's qualifying parameters may improve the BoC for the next generation of in vitro platforms. These parameters show how well a given platform solves the problems unique to in vitro CNS modeling (like recreating the brain's microenvironment and including essential parts like the blood-brain barrier (BBB)) and how much more value it offers than traditional cell culture systems. This review provides an overview of the practical concerns of creating and deploying BoC systems and elaborates on how these technologies might be used. Not only how advanced biosensing technologies could be integrated with BoC system but also how novel approaches will automate assays and improve point-of-care (PoC) diagnostics and accurate quantitative analyses are discussed. Key challenges providing opportunities for clinical translation of BoC in neurodegenerative disorders are also addressed.

Nucleic Acids Enabled‐Interfacial Engineering for Biomarker Sensing with Distance Constraint Effects

AbstractControlling the distance of molecular recognition and signal transduction at the nano–bio interface plays a vital role in sensing molecular interactions, which significantly impacts how a biomarker sensor performs in terms of sensitivity, specificity, detection threshold, and response time. However, conventional biosensing interfaces without the design of distance constraint show limited molecular interactions, hindering target accessibility and mass transport. Nuclei acid‐enabled engineering of biosensing interfaces facilitates highly regulated orientation and programmable density control of biomolecules, providing an effective strategy to improve the performance of biosensing platforms for early diagnosis of diseases and regulation of cellular activities. This review summarizes the recent advances in nucleic acid‐based engineering of biosensing interfaces from a unique perspective of distance constraint effects. The roles of structural nucleic acids in delicately programmed assemblies, functional nucleic acids in molecular recognition, and sensor reactions at well‐controlled distances are highlighted. Then applications of advanced biosensing platforms with the effect of distance constraint are introduced. Finally, the current challenges and future directions for developing such biosensors that can compete effectively to meet the requirements of point‐of‐care testing are also discussed.

Simultaneous noninvasive monitoring of diabetes and hypoxia using core-shell nanozyme – oxidase enzyme biosensors

We report on advanced nanozyme-enzyme biosensors enabling noninvasive simultaneous monitoring of diabetes and hypoxia. Dip-coating with core-shell Prussian Blue – nickel hexacyanoferrate nanozymes results in both stable and sensitive hydrogen peroxide transducers. The best performance characteristics of the resulting biosensors are provided by nanoparticles of 50 nm in diameter containing 35–37 nm (ø) Prussian Blue core. The noninvasive monitor operated via continuous sweat analysis is based on a flow-through multibiosensor for the simultaneous detection of glucose and lactate. As shown, the elaborated glucose-lactate monitor being attached to the human skin surface returns the true concentration for both glucose and lactate in undiluted human sweat. The application of the wearable device incorporating developed biosensors would obviously open new horizons in noninvasive continuous monitoring of hypoxia and glycemia.

Recent advances in immunoassay technologies for the detection of human coronavirus infections.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the seventh coronavirus (CoV) that has spread in humans and has become a global pandemic since late 2019. Efficient and accurate laboratory diagnostic methods are one of the crucial means to control the development of the current pandemic and to prevent potential future outbreaks. Although real-time reverse transcription-polymerase chain reaction (rRT-PCR) is the preferred laboratory method recommended by the World Health Organization (WHO) for diagnosing and screening SARS-CoV-2 infection, the versatile immunoassays still play an important role for pandemic control. They can be used not only as supplemental tools to identify cases missed by rRT-PCR, but also for first-line screening tests in areas with limited medical resources. Moreover, they are also indispensable tools for retrospective epidemiological surveys and the evaluation of the effectiveness of vaccination. In this review, we summarize the mainstream immunoassay methods for human coronaviruses (HCoVs) and address their benefits, limitations, and applications. Then, technical strategies based on bioinformatics and advanced biosensors were proposed to improve the performance of these methods. Finally, future suggestions and possibilities that can lead to higher sensitivity and specificity are provided for further research.

Flexing frontiers: Pioneering advances in biosensors for instant health insights

Biosensors that incorporate a biological recognition element with a transducer offer a rapid, simple approach for selective detection of analytes. However, conventional rigid biosensors have limited capabilities for continuous on-body monitoring applications. The emergence of flexible electronics has opened new possibilities for developing conformal biosensing platforms that can intimately interface with soft, curvilinear surfaces like skin for non-invasive health tracking. This review covers the fundamentals of biosensor technologies and recent progress in flexible biosensors aimed at pointof- care diagnostics and medical monitoring. Key developments in materials, electrochemical sensing interfaces, microfluidics integration and wireless connectivity are highlighted. Examples of flexible biosensors for metabolites, electrolytes, proteins and nucleic acids are presented along with capabilities and limitations. Current challenges include improving biocompatibility, correlation with standard assays, wireless range, manufacturability, and regulatory requirements. Further research on translating flexible biosensor devices from initial proof-of-concepts to validated medical products is warranted. Overall, flexible biosensors hold immense promise to enable continuous personalized health monitoring.

Recent Advances in Biosensors for Detection of COVID-19 and Other Viruses.

This century has introduced very deadly, dangerous, and infectious diseases to humankind such as the influenza virus, Ebola virus, Zika virus, and the most infectious SARS-CoV-2 commonly known as COVID-19 and have caused epidemics and pandemics across the globe. For some of these diseases, proper medications, and vaccinations are missing and the early detection of these viruses will be critical to saving the patients. And even the vaccines are available for COVID-19, the new variants of COVID-19 such as Delta, and Omicron are spreading at large. The available virus detection techniques take a long time, are costly, and complex and some of them generates false negative or false positive that might cost patients their lives. The biosensor technique is one of the best qualified to address this difficult challenge. In this systematic review, we have summarized recent advancements in biosensor-based detection of these pandemic viruses including COVID-19. Biosensors are emerging as efficient and economical analytical diagnostic instruments for early-stage illness detection. They are highly suitable for applications related to healthcare, wearable electronics, safety, environment, military, and agriculture. We strongly believe that these insights will aid in the study and development of a new generation of adaptable virus biosensors for fellow researchers.

Acid-assisted polymerization: the novel synthetic route of sensing layers based on PANI films and chelating agents protected by non-biofouling layer for Fe2+ or Fe3+ potentiometric detection.

A new synthetic method for the fabrication of a sensing layer is presented. PANI films as an ion-to-electron transducer were prepared via acid-assisted polymerization in concentrated formic acid (HCOOH) in the presence of ethanol and ammonium persulfate (APS, as the initiator). The ratio of monomer to ammonium persulfate was 1 : 0.1. 2,2-Bipyridyl, 1,10-phenanthrolin-5-amine, and 8-hydroxyquinoline were used as chelating agents that can complex Fe2+ or Fe3+ ions. The proposed sensors demonstrated an appropriate reproducibility with a rapid response to the presence of Fe2+ or Fe3+ ions, even at T ∼ 37 °C. It was revealed that the method of deposition of a chelating molecule affects the response of sensors. The in situ deposition during acid-assisted polymerization leads to a fast response compared to the layer-by-layer deposition. PMeOx/X1-PANI@FTO and PMeOx/Z1-PANI@FTO sensors exhibit rapid response and are considered a promising detection layer for Fe2+ or Fe3+ ions respectively. We envision that this system can contribute to the next generation of advanced bio-sensors for the potentiometric detection of iron.

Dual II-scheme nanosheet-like Bi2S3/Bi2O3/Ag2S heterostructures for ultrasensitive PEC aptasensing of aflatoxin B1 coupled with catalytic signal amplification by dendritic nanorod-like Au@Pd@Pt nanozyme

As one of the most toxic chemical substances, aflatoxin B1 (AFB1) has a strong carcinogenic effect even at a trace level in human and animal, which severely threatens human health and even causes cancers. Therefore, ultrasensitive detection of AFB1 is of significant importance. For such analysis, dual II-scheme sheet-like Bi2S3/Bi2O3/Ag2S heterostructures were prepared by the in-situ growth method, which exhibited high separation efficiency for the electron-hole (e−-h+) pairs, prominent stability, and high photoactivity. Moreover, the dendritic nanorod-like Au@Pd@Pt (Au@Pd@Pt DNRs) nanozyme was homely synthesized, whose peroxidase-like activity was scrupulously investigated by catalytical oxidation of diaminobenzidine (DAB) in the presence of H2O2. Integration by the aptasensing strategy, a photoelectrochemical (PEC) “signal-on” aptasensor was prepared, which exhibited a broader linear range of 0.5 pg mL−1–100 ng mL−1 with a lower limit of detection (LOD = 0.09 pg mL−1, S/N = 3). This work provides a feasible strategy to develop advanced PEC biosensors for actual analysis of environmental pollutants.

Editorial: Advanced Biosensing Technologies in Medical Applications

The unprecedented pandemic over the past three years has accelerated the developments of many cutting-edge techniques to address the challenges raised in new medical frontiers [...].

Conformational switching of aptamer biointerfacing graphene-gold nanohybrid for ultrasensitive label-free sensing of cardiac Troponin I

The development of hybrid biofunctionalized nanomaterials has emerged as an attractive substitute for development of advanced biosensing platforms with superior synergistic properties. Herein, we report a label-free ultrasensitive electrochemical aptasensor comprising nanohybrid of graphene oxide (GO) and aptamer conjugated gold nanoparticles (GNP-A) for detection of cardiac biomarker Troponin I (TnI). The GNP-A are homogenously arranged by self-assembly on GO sheet to construct nanohybrid (GO@GNP-A) onto which the biomarker protein is analysed. TnI interactions at the aptamer biointerfaced nanohybrid surface causes electrochemical signal enhancement probed by using a redox active molecule. The consecutive increase in current signal is strongly attributed to conformational switching of aptamer and charge neutralization at the interface induced by TnI binding. The sensitivity of the nanohybrid aptasensor platform was found to be 0.001 pg/mL. The study has been further substantiated in Acute Myocardial Infarction (AMI) clinical samples for usage towards early, sensitive and efficient point-of-care detection of TnI.

Label-Free Bound-States-in-the-Continuum Biosensors.

Bound states in the continuum (BICs) have attracted considerable attentions for biological and chemical sensing due to their infinite quality (Q)-factors in theory. Such high-Q devices with enhanced light-matter interaction ability are very sensitive to the local refractive index changes, opening a new horizon for advanced biosensing. In this review, we focus on the latest developments of label-free optical biosensors governed by BICs. These BICs biosensors are summarized from the perspective of constituent materials (i.e., dielectric, metal, and hybrid) and structures (i.e., grating, metasurfaces, and photonic crystals). Finally, the current challenges are discussed and an outlook is also presented for BICs inspired biosensors.

Carbon Nanotubes (CNTs): Smart Theranostic Tools for the Recognition and Preclusion of SARS-COV-2 Variants

The current review article explores the binding empathy of carbon nanotubes (CNTs) for different molecular targets, in the context of their potential use to fight against severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). CNTs are touted as one of the most impending theranostic tools, owing to their exceptional mechanical, thermal and optical properties. Furthermore, their structural reliability and functional group flexibility make them especially useful for the design of advanced biosensing devices both for diagnostic and therapeutic applications against SARS-CoV-2. In addition, CNTs could also function both as an antigen carrier and an adjuvant when used concurrently with current and upcoming COVID-19 vaccines.

Advanced Lab-on-Fiber Optrodes Assisted by Oriented Antibody Immobilization Strategy.

Lab-on-fiber (LoF) optrodes offer several advantages over conventional techniques for point-of-care platforms aimed at real-time and label-free detection of clinically relevant biomarkers. Moreover, the easy integration of LoF platforms in medical needles, catheters, and nano endoscopes offer unique potentials for in vivo biopsies and tumor microenvironment assessment. The main barrier to translating the vision close to reality is the need to further lower the final limit of detection of developed optrodes. For immune-biosensing purposes, the assay sensitivity significantly relies on the capability to correctly immobilize the capture antibody in terms of uniform coverage and correct orientation of the bioreceptor, especially when very low detection limits are requested as in the case of cancer diagnostics. Here, we investigated the possibility to improve the immobilization strategies through the use of hinge carbohydrates by involving homemade antibodies that demonstrated a significantly improved recognition of the antigen with ultra-low detection limits. In order to create an effective pipeline for the improvement of biofunctionalization protocols to be used in connection with LoF platforms, we first optimized the protocol using a microfluidic surface plasmon resonance (mSPR) device and then transferred the optimized strategy onto LoF platforms selected for the final validation. Here, we selected two different LoF platforms: a biolayer interferometry (BLI)-based device (commercially available) and a homemade advanced LoF biosensor based on optical fiber meta-tips (OFMTs). As a clinically relevant scenario, here we focused our attention on a promising serological biomarker, Cripto-1, for its ability to promote tumorigenesis in breast and liver cancer. Currently, Cripto-1 detection relies on laborious and time-consuming immunoassays. The reported results demonstrated that the proposed approach based on oriented antibody immobilization was able to significantly improve Cripto-1 detection with a 10-fold enhancement versus the random approach. More interestingly, by using the oriented antibody immobilization strategy, the OFMTs-based platform was able to reveal Cripto-1 at a concentration of 0.05 nM, exhibiting detection capabilities much higher (by a factor of 250) than those provided by the commercial LoF platform based on BLI and similar to the ones shown by the commercial and well-established bench-top mSPR Biacore 8K system. Therefore, our work opened new avenues into the development of high-sensitivity LoF biosensors for the detection of clinically relevant biomarkers in the sub-ng/mL range.

A bent fiber optic sensor based on gold nanoparticle-decorated silver film for integration of cytosensor and plasmonic photothermal therapy: A simulation study

The fiber optic surface plasmonic resonance (SPR), with the unique characteristic of miniaturized devices, high refractive index sensitivity, and intense plasmonic photothermal effect, is a promising technique for advanced biosensors in clinical medicine. Studies on the synergistic influence factors of the dual performance of refractive index sensitivity and surface heat field are benefitted for integration of cytosensor and phototherapy. Herein, a gold nanoparticle-decorated silver film (AuNPs-AgFM) was simulated as the coating to construct a bent fiber optic surface plasmonic resonance (SPR) through a Finite Element Method (FEM). Bending leads core mode to shift away from the center of curvature into the fiber cladding, which further reacted with the AgFM and AuNPs to generate the short wavelength peaks for cytosensor and long wavelength peaks for plasmonic photothermal therapy, respectively. Furthermore, the parameters of bent radius, AuNPs’ size, and thickness of AgFM were optimized considering both refractive index sensitivity and surface temperature. Under the optimal condition, the designed SPR biosensor exhibit high amplification sensitivity (AS) of − 2301.6 (1/RIU), wavelength sensitivity (WS) of 3120 (nm/RIU), and surface temperature of 54.9 ℃ under irradiation of near-infrared ray (NIR) laser. The proposed AuNPs-AgFM-based fiber optic SPR biosensor provides an alternative scheme to integrate cytosensor and phototherapy, further pushing fiber optics to clinical application.

MXene-Based Nucleic Acid Biosensors for Agricultural and Food Systems.

MXene is a two-dimensional (2D) nanomaterial that exhibits several superior properties suitable for fabricating biosensors. Likewise, the nucleic acid (NA) in oligomerization forms possesses highly specific biorecognition ability and other features amenable to biosensing. Hence the combined use of MXene and NA is becoming increasingly common in biosensor design and development. In this review, MXene- and NA-based biosensors are discussed in terms of their sensing mechanisms and fabrication details. MXenes are introduced from their definition and synthesis process to their characterization followed by their use in NA-mediated biosensor fabrication. The emphasis is placed on the detection of various targets relevant to agricultural and food systems, including microbial pathogens, chemical toxicants, heavy metals, organic pollutants, etc. Finally, current challenges and future perspectives are presented with an eye toward the development of advanced biosensors with improved detection performance.

SARS-CoV-2-on-Chip for Long COVID Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a “wicked evil” in this century due to its extended progression and huge human mortalities. Although the diagnosis of SARS-CoV-2 viral infection is made simple and practical by employing reverse transcription polymerase chain reaction (RT-PCR) investigation, the process is costly, complex, time-consuming, and requires experts for testing and the constraints of a laboratory. Therefore, these challenges have raised the paradigm of on-site portable biosensors on a single chip, which reduces human resources and enables remote access to minimize the overwhelming burden on the existing global healthcare sector. This article reviews the recent advancements in biosensors for long coronavirus disease (COVID) management using a multitude of devices, such as point-of-care biosensors and lab-on-chip biosensors. Furthermore, it details the shift in the paradigm of SARS-CoV-2-on-chip biosensors from the laboratory to on-site detection with intelligent and economical operation, representing near-future diagnostic technologies for public health emergency management.

State-of-the-art advancements in Liver-on-a-chip (LOC): Integrated biosensors for LOC

Liver models are vital for the liver diseases and drug research as many novel drugs. However, traditional liver models cannot meet this need, mainly because they cannot replicate the complex physiological structure and microenvironment of the liver, especially the O2 and nutrient gradients. Liver-on-a-chip (LOC), based on microfluidic technology, can not only closely simulate the physiological structure and microenvironment of the liver through the design of suitable microchannels, but can also incorporate advanced biosensors with high sensitivity and potential for rapid responses to microenvironmental signals and liver function indicators. Nevertheless, LOCs have not been widely exploited for liver disease research or the screening of drugs for hepatotoxicity because of considerable professional barriers. In this review, we comprehensively summarize recent progress in LOC development and the embedding of biosensors into LOCs. We first introduce the physiological characteristics and microenvironment of the liver and then summarize the fabrication process and advantages of LOCs. We subsequently focus on recent advances relating to three-dimensional (3D) hepatocyte organization and the simulation of hepatic sinusoids and lobules in LOCs and further systematically summarize the research progress in biosensor-integrated LOCs. Finally, we discuss the potential value of LOCs and the challenges facing their exploitation. In conclusion, this review provides insights into the design and development of biosensor-integrated LOCs aiming to promote further research into this promising platform.

A brief review on novel biomarkers identified and advanced biosensing technologies developed for rapid diagnosis of Japanese Encephalitis Virus

Advanced biosensor technology research is imperative for the management of infectious disease outbreaks such as Japanese Encephalitis (JE), a zoonotic disease caused by the flavivirus JE virus (JEV) which is transmitted to humans (dead-end hosts) from the amplification host, pigs, via mosquitoes. To avoid future pandemic scenarios, proactive research rather than responsive research in the field of diagnostics is a requirement for development of rapid, sensitive and specific screening detection methods. In this mini-review, we have critically compared and evaluated the different types of biomarkers (antigen, antibody, nucleic acid) identified for JEV diagnostics and their specific roles in the manifestation of the infection which may be potentially used for therapeutics and drug development as no treatment is available for JE. Furthermore, different biosensors developed for the detection of JEV biomarkers have been discussed in detail to give an overview of the working principles (electrochemical, optical, etc.), fabrication components (signal amplifier, bioreceptor, etc.), detection limits and response times. This review provides a compact compiled base on available JEV diagnostic research work being currently carried out along with their limitations, future prospective, and major challenges faced. This will enable future development of rapid point-of-care diagnostic screening methods for JEV infection management, which may help reduce number of fatalities.

Organic small molecule semiconductor materials for OFET-based biosensors

Biosensors is an advanced detection and monitoring device for the development of biotechnology, and is also a rapid and microanalytical device at the molecular level. Demands for high sensitivity, high flexibility, good biocompatibility, easy chemical modification and low cost offer incentive for exploring new materials to develop the next-generation biosensors. With the vigorous development of organic electronics, the performances of organic devices have been effectively improved, leading to organic semiconductor materials with low cost, good flexibility, easy chemical modification and good biocompatibility for biosensors. Biosensors based on organic field-effect transistors (OFETs) have become one of the most advanced biosensor platforms because of their inherent ability to amplify received signals. Furthermore, OFET-based biosensors have been widely used in the detection of DNA, protein, cell, glucose and other biological substances due to its high sensitivity, fast analysis speed, label-free detection, small size and simple operation. This mini review briefly discusses the organic small molecule semiconductor materials, device configurations, basic principles and application fields of OFETs-based biosensors.