Showing papers in "Analyst in 2018"

Partial least squares-discriminant analysis (PLS-DA) for classification of high-dimensional (HD) data: a review of contemporary practice strategies and knowledge gaps

Abstract: Partial least squares-discriminant analysis (PLS-DA) is a versatile algorithm that can be used for predictive and descriptive modelling as well as for discriminative variable selection. However, versatility is both a blessing and a curse and the user needs to optimize a wealth of parameters before reaching reliable and valid outcomes. Over the past two decades, PLS-DA has demonstrated great success in modelling high-dimensional datasets for diverse purposes, e.g. product authentication in food analysis, diseases classification in medical diagnosis, and evidence analysis in forensic science. Despite that, in practice, many users have yet to grasp the essence of constructing a valid and reliable PLS-DA model. As the technology progresses, across every discipline, datasets are evolving into a more complex form, i.e. multi-class, imbalanced and colossal. Indeed, the community is welcoming a new era called big data. In this context, the aim of the article is two-fold: (a) to review, outline and describe the contemporary PLS-DA modelling practice strategies, and (b) to critically discuss the respective knowledge gaps that have emerged in response to the present big data era. This work could complement other available reviews or tutorials on PLS-DA, to provide a timely and user-friendly guide to researchers, especially those working in applied research.

Smartphone-based analytical biosensors

Abstract: The traditional analytical biosensor instruments are relatively bulky, expensive, and not easy to handle, thus their applications are largely limited in resource-limited settings. The recent development of microfluidic lab-on-a-chip (LOC) technology has provided a possible solution to miniaturize the conventional biosensing system, yet other accessory devices to detect, readout, analyze, transfer, and display results are still required. With the rapid development, mass production, and pervasive distribution of smartphones in recent years, they have provided people with portable, cost-effective, and easy-to-operate platforms to build analytical biosensors for point-of-care (POC) applications and mobile health. Based on the common analytical methods, this paper reviews the recent development of four types of smartphone based analytical biosensory systems at the POC, i.e., smartphone-based microscopic imaging, colorimetric, electrochemical, and electrochemiluminescence biosensor. The different bio-sensing strategies and analytical performance together with future perspectives are discussed.

Recent advances in nanoparticle-based lateral flow immunoassay as a point-of-care diagnostic tool for infectious agents and diseases

Abstract: Lateral flow immunoassay (LFIA) technology is a paper-based, point-of-care strip biosensor designed to detect a specific analyte in a given sample. This type of assay is now of great interest to researchers for its cost-effectiveness, simplicity, portability and rapidness of detection of analytes, including but not limited to areas such as agriculture, food, biomedicine and pathogen detection. Various nanoparticles (such as metal nanoparticles, carbon-based nanoparticles, quantum dots, lanthanides and up-converting phosphor) functionalized by an antibody to detect an analyte protein or molecular marker present in the surface of an infectious pathogen are used for in LFIAs. Herein, we review the principle of the assay and recent advancements made in terms of the different approaches and designs of the assay towards the detection of infectious agents and diseases.

Investigations on the interface of nucleic acid aptamers and binding targets.

Abstract: Nucleic acid aptamers are single-stranded DNA or RNA of 20-100 nucleotides in length that have attracted substantial scientific interest due to their ability to specifically bind to target molecules via the formation of three-dimensional structures. Compared to traditional protein antibodies, aptamers have several advantages, such as their small size, high binding affinity, specificity, flexible structure, being chemical synthesizable and modifiable, good biocompatibility, high stability and low immunogenicity, which all contribute to their widely applications in the biomedical field. To date, much progress has been made in the study and applications of aptamers, however, detailed information on how aptamers bind to their targets is still scarce. Over the past few decades, many methods have been introduced to investigate the aptamer-target binding process, such as measuring the main kinetic or thermodynamic parameters, detecting the structural changes of the binding complexes, etc. Apart from traditional physicochemical methods, various types of molecular docking programs have been applied to simulate the aptamer-target interactions, while these simulations also have limitations. To facilitate the further research on the interactions, herein, we provide a brief review to illustrate the recent advances in the study of aptamer-target interactions. We summarize the binding targets of aptamers, such as small molecules, macromolecules, and even cells. Their binding constants (KD) are also summarized. Methods to probe the aptamer-target binding process, such as surface plasmon resonance (SPR), circular dichroism spectroscopy (CD), isothermal titration calorimetry (ITC), footprinting assay, truncation and mutation assay, nuclear magnetic resonance spectroscopy (NMR), X-ray crystallography and molecular docking simulation are indicated. The binding forces mediating the aptamer-target interactions, such as hydrogen bonding, electrostatic interaction, the hydrophobic effect, π-π stacking and van der Waals forces are summarized. The challenges and future perspectives are also discussed.

Clinical applications of infrared and Raman spectroscopy: state of play and future challenges

Abstract: Vibrational spectroscopies, based on infrared absorption and/or Raman scattering provide a detailed fingerprint of a material, based on the chemical content. Diagnostic and prognostic tools based on these technologies have the potential to revolutionise our clinical systems leading to improved patient outcome, more efficient public services and significant economic savings. However, despite these strong drivers, there are many fundamental scientific and technological challenges which have limited the implementation of this technology in the clinical arena, although recent years have seen significant progress in addressing these challenges. This review examines (i) the state of the art of clinical applications of infrared absorption and Raman spectroscopy, and (ii) the outstanding challenges, and progress towards translation, highlighting specific examples in the areas of in vivo, ex vivo and in vitro applications. In addition, the requirements of instrumentation suitable for use in the clinic, strategies for pre-processing and statistical analysis in clinical spectroscopy and data sharing protocols, will be discussed. Emerging consensus recommendations are presented, and the future perspectives of the field are assessed, particularly in the context of national and international collaborative research initiatives, such as the UK EPSRC Clinical Infrared and Raman Spectroscopy Network, the EU COST Action Raman4Clinics, and the International Society for Clinical Spectroscopy.

Recent advances in microRNA detection

Abstract: The development of simple, robust, and reliable microRNA (miRNA) detection methods is of great significance in the studies of the biological function of miRNAs, molecular diagnostics, treatment of diseases, and targeted drugs. In recent years, with the increasing development of miRNA research, lots of novel approaches were developed for the detection of miRNA in terms of sensitivity, specificity, multiplicity, in situ imaging, etc. In particular, nucleic acid amplification-based methods and many detection techniques such as droplet digital PCR (ddPCR), electrochemiluminescence (ECL), surface-enhanced Raman spectroscopy (SERS), and mass spectrometry (MS) have been employed widely for the highly sensitive detection of miRNA. New progress in miRNA detection has accelerated miRNA functional research and clinical diagnostics. In this review, we summarize the recent progress in the development of miRNA detection methods and new applications. This review will provide guidelines for the development of more advanced miRNA detection methods with high sensitivity and specificity, and applicability to biochemical research, disease diagnosis and therapy.

Highly sensitive detection of exosomes by SERS using gold nanostar@Raman reporter@nanoshell structures modified with a bivalent cholesterol-labeled DNA anchor

Abstract: Exosomes, as important signal transmitters, play a key role in intercellular communication, especially in cancer metastasis. There is considerable evidence that exosomes can be used as an indicator of cancer. However, convenient and sensitive methods for detecting exosomes are still technically challenging. Here, we present a convenient and highly sensitive surface-enhanced Raman scattering (SERS) based method by combining immunoaffinity, SERS nanoprobes, and portable Raman devices for specific isolation and accurate quantification of exosomes. To construct the SERS-based biosensor, the surfaces of gold nanostar@4-mercaptobenzoic acid@nanoshell structures (AuNS@4-MBA@Au) are modified with a bivalent cholesterol (B-Chol)-labeled DNA anchor to prepare SERS nanoprobes. Exosomes are specifically captured by immunomagnetic beads, and then SERS nanoprobes are fixed on the surface of exosomes by hydrophobic interactions between cholesterol and lipid membranes, thus forming a sandwich-type immunocomplex. The immunocomplex can be magnetically captured and produce enhanced SERS signals. In the absence of exosomes, the sandwich-type immunocomplex cannot be formed, and thus negligible SERS signals are detected. The degree of immunocomplex assembly and the corresponding SERS signals are positively correlated with the exosome concentration over a wide linear range of 40 to 4 × 107 particles per μL and the limit of detection is as low as 27 particles per μL. Consequently, a sensitive and simple strategy for detection of exosomes is successfully constructed. We believe that our biosensor has considerable potential as a convenient and highly sensitive quantification tool to detect exosomes in biological samples.

Recent advances in the use of microfluidic technologies for single cell analysis

Abstract: The inherent heterogeneity in cell populations has become of great interest and importance as analytical techniques have improved over the past decades. With the advent of personalized medicine, understanding the impact of this heterogeneity has become an important challenge for the research community. Many different microfluidic approaches with varying levels of throughput and resolution exist to study single cell activity. In this review, we take a broad view of the recent microfluidic developments in single cell analysis based on microwell, microchamber, and droplet platforms. We cover physical, chemical, and molecular biology approaches for cellular and molecular analysis including newly emerging genome-wide analysis.

Microfluidic technologies for circulating tumor cell isolation

Abstract: Metastasis is the main cause of tumor-related death, and the dispersal of tumor cells through the circulatory system is a critical step in the metastatic process. Early detection and analysis of circulating tumor cells (CTCs) is therefore important for early diagnosis, prognosis, and effective treatment of cancer, enabling favorable clinical outcomes in cancer patients. Accurate and reliable methods for isolating and detecting CTCs are necessary to obtain this clinical information. Over the past two decades, microfluidic technologies have demonstrated great potential for isolating and detecting CTCs from blood. The present paper reviews current advanced microfluidic technologies for isolating CTCs based on various biological and physical principles, and discusses their fundamental advantages and drawbacks for subsequent cellular and molecular assays. Owing to significant genetic heterogeneity among CTCs, microfluidic technologies for isolating individual CTCs have recently been developed. We discuss these single-cell isolation methods, as well as approaches to overcoming the limitations of current microfluidic CTC isolation technologies. Finally, we provide an overview of future innovative microfluidic platforms.

Electrochemical microfluidics techniques for heavy metal ion detection

Abstract: Heavy metals refer to metals with a density above 5 × 103 kg m-3, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg). Even a trace amount of heavy metals is detrimental to human health. With the increasing significance of detection of heavy metals, the use of the electrochemical detection technique combined with microfluidics is a promising strategy and has thus attracted wide attention from academia and is the subject of this review. First, this review introduces the basics of electrochemical detection and microfluidics. Second, this review presents and evaluates a variety of electrochemical microfluidics technologies for heavy metal ions detection that are user friendly, portable, inexpensive, and easy to manufacture compared to traditional methods. The categorization is based on different detected ions in the order of Pb, Cd, As, Hg, Mn, and Zn. Finally, the author summarizes the development of detection technology in recent years and puts forward a perspective for the future prospects.

Advances in surface-enhanced Raman spectroscopy (SERS) substrates for lipid and protein characterization: sensing and beyond.

Abstract: Surface-enhanced Raman spectroscopy (SERS) has become an essential ultrasensitive analytical tool for biomolecular analysis of small molecules, macromolecular proteins, and even cells. SERS enables label-free, direct detection of molecules through their intrinsic Raman fingerprint. In particular, protein and lipid bilayers are dynamic three-dimensional structures that necessitate label-free methods of characterization. Beyond direct detection and quantitation, the structural information contained in SERS spectra also enables deeper biophysical characterization of biomolecules near metallic surfaces. Therefore, SERS offers enormous potential for such systems, although making measurements in a nonperturbative manner that captures the full range of interactions and activity remains a challenge. Many of these challenges have been overcome through advances in SERS substrate development, which have expanded the applications and targets of SERS for direct biomolecular quantitation and biophysical characterization. In this review, we will first discuss different categories of SERS substrates including solution-phase, solid-supported, tip-enhanced Raman spectroscopy (TERS), and single-molecule substrates for biomolecular analysis. We then discuss detection of protein and biological lipid membranes. Lastly, biophysical insights into proteins, lipids and live cells gained through SERS measurements of these systems are reviewed.

Nanomaterial based electrochemical sensors for the safety and quality control of food and beverages

Abstract: The issue of foodborne related illnesses due to additives and contaminants poses a significant challenge to food processing industries. The efficient, economical and rapid analysis of food additives and contaminants is therefore necessary in order to minimize the risk of public health issues. Electrochemistry offers facile and robust analytical methods, which are desirable for food safety and quality assessment over conventional analytical techniques. The development of a wide array of nanomaterials has paved the way for their applicability in the design of high-performance electrochemical sensing devices for medical diagnostics and environment and food safety. The design of nanomaterial based electrochemical sensors has garnered enormous attention due to their high sensitivity and selectivity, real-time monitoring and ease of use. This review article focuses predominantly on the synthesis and applications of different nanomaterials for the electrochemical determination of some common additives and contaminants, including hydrazine (N2H4), malachite green (MG), bisphenol A (BPA), ascorbic acid (AA), caffeine, caffeic acid (CA), sulfite (SO32−) and nitrite (NO2−), which are widely found in food and beverages. Important aspects, such as the design, fabrication and characterization of graphene-based materials, gold nanoparticles, mono- and bimetallic nanoparticles and metal nanocomposites, sensitivity and selectivity for electrochemical sensor development are addressed. High-performance nanomaterial based electrochemical sensors have and will continue to have myriad prospects in the research and development of advanced analytical devices for the safety and quality control of food and beverages.

An amplification-free electrochemical detection of exosomal miRNA-21 in serum samples

Abstract: Recent evidence suggests that small non-coding RNAs such as microRNA (miRNA) encapsulated in exosomes represent an important mechanism of communication between the cells Exosomal miRNAs play an important role in carcinogenesis via enhancing the cell to cell communication and targeting the cell growth molecular pathways which in turn facilitate metastasis in cancers Despite progressive advances, the current methods for the exosomal miRNA detection mostly rely on labor-intensive sequencing approaches which are often prone to amplification bias and require costly and bulky equipment Herein, we report an electrochemical approach for the detection of cancer-derived exosomal miRNAs in human serum samples by selectively isolating the target miRNA using magnetic beads pre-functionalized with capture probes and then directly adsorbing the targets onto a gold electrode surface The level of adsorbed miRNA is detected electrochemically in the presence of an [Fe(CN)6]4-/3- redox system This method enabled an excellent detection sensitivity of 10 pM with a relative standard deviation (%RSD) of <55% in cancer cells and serum samples (n = 8) collected from patients with colorectal adenocarcinoma (CRC) We believe that our approach could be useful in clinical settings for the quantification of exosomal miRNA in cancer patients

Chemical analysis in saliva and the search for salivary biomarkers – a tutorial review

Abstract: Biomarkers refer to analytes that can be used in the diagnosis of diseases or disorders. In saliva, there are many components that are potential biomarkers, and increasing research has focussed on the development of saliva as a diagnostic fluid. This review summarizes the existing uses of salivary biomarkers and highlights the importance of the choice of saliva collection as well as the storage procedures. A case study on the effect of collection tools on the concentrations of one of the potential biomarkers, glutathione, is highlighted. Moreover, molecular diagnosis requires reliable measurement assays. This review presents electroanalytical methods for the detection of salivary biomarkers. It further reviews approaches that can be taken to improve the selectivity of electroanalytical assays without the use of biologically selective materials, notably without the use of enzymes or antibodies.

Lipid metabolism in inflammation-related diseases

Abstract: There are thousands of lipid species existing in cells, which belong to eight different categories. Lipids are the essential building blocks of cells. Recent studies have started to unveil the important functions of lipids in regulating cell metabolism. However, we are still at a very early stage in fully understanding the physiological and pathological functions of lipids. The application of lipidomics for studying lipid metabolism can provide a direct readout of the cellular status and broadens our understanding of the mechanisms that underpin metabolic disease states. This review provides an introduction to lipid metabolism and its role in modulating homeostasis and immunity. We also describe representative applications of lipidomics for studying lipid metabolism in inflammation-related diseases.

Expanding the structural analysis capabilities on an Orbitrap-based mass spectrometer for large macromolecular complexes

Abstract: Native mass spectrometry can provide insight into the structure of macromolecular biological systems. As analytes under investigation get larger and more complex, instrument capabilities need to be advanced. Herein, modifications to an Orbitrap Q Exactive Plus mass spectrometer that increase signal intensity, mass resolution, and maximum m/z measurable are described.

Molecularly imprinted polymers’ application in pesticide residue detection

Abstract: Molecularly imprinted polymers (MIPs) are produced using molecular imprinting technology (MIT) and have specific analyte-binding abilities and unique properties, including chemical and thermal stability, reusability, high selectivity, and high sensitivity. The application of MIPs in the detection of pesticides represents an advance and a superior scientific approach owing to their detection and characterization of trace levels in comparison with other methods. In this review, we have summarized the pre-treatment extraction of pesticides with different types of molecularly imprinted polymer for the detection of single and multiple pesticides by elaborating upon their specific extraction efficiency. The importance of different polymerization methods, functional monomers and cross-linkers is highlighted. The aim of this study is to investigate the importance of the application of MIPs in the detection of pesticides and recent advances in the last few years to overcome the limitations of previously developed methods. Existing restrictions and required future aspects are discussed.

Impact of primer dimers and self-amplifying hairpins on reverse transcription loop-mediated isothermal amplification detection of viral RNA.

Abstract: Loop-mediated isothermal amplification (LAMP), coupled with reverse transcription (RT), has become a popular technique for detection of viral RNA due to several desirable characteristics for use in point-of-care or low-resource settings. The large number of primers in LAMP (six per target) leads to an increased likelihood of primer dimer interactions, and the inner primers in particular are prone to formation of stable hairpin structures due to their length (typically 40-45 bases). Although primer dimers and hairpin structures are known features to avoid in nucleic acid amplification techniques, there is little quantitative information in literature regarding the impact of these structures on LAMP or RT-LAMP assays. In this study, we examine the impact of primer dimers and hairpins on previously published primer sets for dengue virus and yellow fever virus. We demonstrate that minor changes to the primers to eliminate amplifiable primer dimers and hairpins improves the performance of the assays when monitored in real time with intercalating dyes, and when monitoring a fluorescent endpoint using the QUASR technique. We also discuss the thermodynamic implications of these minor changes on the overall stability of amplifiable secondary structures, and we present a single thermodynamic parameter that can be correlated to the probability of non-specific amplification associated with LAMP primers.

Fabrication of a self-assembled and flexible SERS nanosensor for explosive detection at parts-per-quadrillion levels from fingerprints

Abstract: Apart from high sensitivity and selectivity of surface-enhanced Raman scattering (SERS)-based trace explosive detection, efficient sampling of explosive residue from real world surfaces is very important for homeland security applications. Herein, we demonstrate an entirely new SERS nanosensor fabrication approach. The SERS nanosensor was prepared by self-assembling chemically synthesized gold triangular nanoprisms (Au TNPs), which we show display strong electromagnetic field enhancements at the sharp tips and edges, onto a pressure-sensitive flexible adhesive film. Our SERS nanosensor provides excellent SERS activity (enhancement factor = ∼6.0 × 106) and limit of detection (as low as 56 parts-per-quadrillions) with high selectivity by chemometric analyses among three commonly military high explosives (TNT, RDX, and PETN). Furthermore, the SERS nanosensors present excellent reproducibility (<4.0% relative standard deviation at 1.0 μM concentration) and unprecedentedly high stability with a “shelf life” of at least 5 months. Finally, TNT and PETN were analyzed and quantified by transferring solid explosive residues from fingerprints left on solid surfaces to the SERS nanosensor. Taken together, the demonstrated sensitivity, selectivity, and reliability of the measurements as well as with the excellent shelf life of our SERS nanosensors obviate the need for complicated sample processing steps required for other analytical techniques, and thus these nanosensors have tremendous potential not only in the field of measurement science but also for homeland security applications to combat acts of terror and military threats.

Graphene-based aptasensors: from molecule–interface interactions to sensor design and biomedical diagnostics

Abstract: Graphene-based nanomaterials have been widely utilized to fabricate various biosensors for environmental monitoring, food safety, and biomedical diagnostics The combination of aptamers with graphene for creating biofunctional nanocomposites improved the sensitivity and selectivity of fabricated biosensors due to the unique molecular recognition and biocompatibility of aptamers In this review, we highlight recent advances in the design, fabrication, and biomedical sensing application of graphene-based aptasensors within the last five years (2013-current) The typical studies on the biomedical fluorescence, colorimetric, electrochemical, electrochemiluminescence, photoelectrochemical, electronic, and force-based sensing of DNA, proteins, enzymes, small molecules, ions, and others are demonstrated and discussed in detail More attention is paid to a few key points such as the conjugation of aptamers with graphene materials, the fabrication strategies of sensor architectures, and the importance of aptamers on improving the sensing performances It is expected that this work will provide preliminary and useful guidance for readers to understand the fabrication of graphene-based biosensors and the corresponding sensing mechanisms in one way, and in another way will be helpful to develop novel high performance aptasensors for biological analysis and detection

A novel fluorescent aptasensor for ultrasensitive and selective detection of acetamiprid pesticide based on the inner filter effect between gold nanoparticles and carbon dots

Abstract: This paper reports a novel fluorescent aptasensor for the detection of acetamiprid pesticide with high sensitivity and selectivity based on the inner filter effect (IFE) of gold nanoparticles (AuNPs) toward fluorescent carbon dots (CDs). The aptasensor employs S-18 aptamer as the specific target recognition molecule and CDs as the signal transmission element. Free S-18 aptamer sequences can wrap the surfaces of AuNPs and enable their dispersion state even in the presence of high amounts of Tris-HCl salt, which can effectively quench the fluorescence of the CDs through the IFE. Upon adding acetamiprid pesticide, the free S-18 aptamer sequences are firstly exhausted to form some complexes; thus, the AuNPs tend to aggregate and their absorption spectrum no longer overlaps with the fluorescence emission spectrum of the CDs, which leads to obvious fluorescence recovery of the aptasensor. The properties of the CDs were extensively characterized, and the fluorescence quenching effects of the AuNPs toward the CDs were fully investigated. Additionally, the effects of some vital parameters, such as the type and amount of AuNPs, on the fluorescent aptasensor were also investigated. The proposed aptasensor has a detection limit as low as 1.08 μg L-1 with a linear range of 5 to 100 μg L-1 and shows high selectivity for acetamiprid over other control pesticides. Moreover, the aptasensor displays excellent accuracy and recovery in the detection of spiked real samples, suggesting that this fluorescent aptasensor can play important roles in the fields of food analysis and environmental detection.

A novel reduced graphene oxide/molybdenum disulfide/polyaniline nanocomposite-based electrochemical aptasensor for detection of aflatoxin B1.

Abstract: In this study, we developed a novel reduced graphene oxide/molybdenum disulfide/polyaniline@gold nanoparticles-based electrochemical aptasensor (termed as RGO/MoS2/PANI@AuNPs/Apt) for detection of aflatoxin B1 (AFB1). The RGO/MoS2/PANI nanocomposites were synthesized and characterized by multiple techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared spectroscopy (FTIR), UV-visible spectroscopy, and X-ray photoelectron spectroscopy (XPS). A glassy carbon electrode (GCE) was then modified by the RGO/MoS2/PANI nanocomposites, coated with a chitosan (Cs) film, and followed by AuNPs attachment for immobilizing the AFB1 aptamers. In the presence of AFB1, the AFB1 binding-induced conformation change of the immobilized aptamer on the electrode surface results in the reduction of the electron transfer from a [Fe(CN)6]3-/4- redox couple in the solution to the GCE surface. Therefore, the aptamer-AFB1 binding event can be easily monitored by the peak current change of the RGO/MoS2/PANI@AuNPs/Apt through differential pulse voltammetry (DPV) measurement. Under the optimized conditions, the as-developed RGO/MoS2/PANI@AuNPs/Apt exhibits a wide linear range from 0.01 fg mL-1 to 1.0 fg mL-1 and a remarkably low detection limit (3σ) of 0.002 fg mL-1. The aptasensor also has good reproducibility as well as shows high selectivity against other fungal toxins, such as OTA and FB1. Moreover, the practicability of the RGO/MoS2/PANI@AuNPs/Apt was demonstrated by the analysis of AFB1 in the spiked wine samples.

A novel electrochemical aptamer–antibody sandwich assay for the detection of tau-381 in human serum

Abstract: Tau protein plays a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the assay to detect low concentrations of tau protein is a great challenge for the early diagnosis of AD. We will outline a novel aptamer-antibody sandwich assay based on an electrochemical biosensor for the detection of tau-381 in human serum. To improve the detection sensitivity, the aptamer-antibody sandwich assay for the detection of tau-381 was developed by using a tau antibody (anti-tau) and an aptamer specific to tau-381 as the recognition element and cysteamine-stabilized gold nanoparticles (AuNPs) for signal amplification. Differential pulse voltammetry (DPV) was employed to record the signal response of tau-381 with different concentrations. The tau-381 concentration ranged from 0.5 pM to 100 pM. The responses of DPV measurements showed excellent results in this dynamic range. This simple, rapid, highly sensitive and specific assay gave a low limit of detection (LOD) of 0.42 pM for tau-381. The feasibility and reliability of the assay were verified by testing tau-381 in human serum from patients with AD. Thus, this method could prove valuable in diagnosing AD within the early stages of the disease.

Recent advances in ambient mass spectrometry of trace explosives.

Abstract: Ambient mass spectrometry has evolved rapidly over the past decade, yielding a plethora of platforms and demonstrating scientific advancements across a range of fields from biological imaging to rapid quality control. These techniques have enabled real-time detection of target analytes in an open environment with no sample preparation and can be coupled to any mass analyzer with an atmospheric pressure interface; capabilities of clear interest to the defense, customs and border control, transportation security, and forensic science communities. This review aims to showcase and critically discuss advances in ambient mass spectrometry for the trace detection of explosives.

Aptamer immobilization on amino-functionalized metal–organic frameworks: an ultrasensitive platform for the electrochemical diagnostic of Escherichia coli O157:H7

Abstract: Herein, we report the development of an electrochemical biosensor for Escherichia coli O157:H7 diagnostic based on amino-functionalized metal-organic frameworks (MOFs) as a new generation of organic-inorganic hybrid nanocomposites. The electrical and morphological properties of MOFs were enhanced by interweaving each isolated MOF crystal with polyaniline (PANI). Subsequent attachment of the amine-modified aptamer to the polyanilinated MOFs was accomplished using glutaraldehyde (GA) as a cross-linking agent. The prepared biocompatible platform was carefully characterized by means of field-emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), and X-ray powder diffraction (XRD) techniques. The biosensor fabrication and its electrochemical characterizations were monitored by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Differential pulse voltammetry (DPV) was applied to monitoring and quantitation of the interaction between the aptamer and E. coli O157:H7 using methylene blue (MB) as an electrochemical indicator. Changes in the reduction peak current of MB in the presence of E. coli O157:H7 was recorded as an analytical signal and indicated a relationship with the logarithm of the E. coli O157:H7 concentration in the range of 2.1 × 101 to 2.1 × 107 CFU mL-1 with a LOQ of 21 CFU mL-1 and LOD of 2 CFU mL-1. The electrochemical aptasensor displayed good recovery values for the detection of E. coli O157:H7 in environmental real samples and also could act as a smart device to investigate the effects of antibacterial agents against E. coli O157:H7.

Paper-based nucleic acid amplification tests for point-of-care diagnostics

Abstract: There has been a recent resurgence in the use of paper as a substrate for developing point-of-care medical diagnostic tests, possibly triggered by expiring patents published in the 1990s. A hallmark of this resurgence has been the development of advanced shapes and structures made from paper to conduct multi-step fluidic operations using the wicking action of porous materials. Such devices indicate a distinct improvement over lateral flow immunoassays, which are restricted to conducting one-step operations. New developments in paper-based diagnostic devices have triggered interest in the development of paper-based point-of-care nucleic acid amplification tests (NAATs). NAATs can identify extremely low levels of specific nucleic acid sequences from clinical samples and are the most sensitive of all available tests for infectious disease diagnosis. Because traditional PCR-based NAATs require expensive instruments, the development of portable paper-based NAAT's has become an exciting field of research. This article aims to review and analyse the current state of development of paper-based NAATs. We project paper-based NAATs as miniaturized chemical processes and shed light on various schemes of operation used for converting the multiple steps of the chemical processes into paper microfluidic devices. We conclude by elaborating on the challenges that must be overcome in the near future so that progress can be made towards the development of fully functional and commercial paper-based NAATs.

Emerging biosensor platforms for the assessment of water-borne pathogens

Abstract: Pathogens are key contaminants in water that are responsible for the generation of various water-borne diseases, and include viruses, fungi, bacteria, and protozoan parasites. The pathogenic effects of these species in water depend on their shape, size, composition, and structure. The resulting water-borne diseases are a serious threat to the environment, including to humans and animals, and are directly responsible for environmental deterioration and pollution. The potential presence of these pathogens requires sensitive, powerful, efficient, and ideally real-time monitoring methods for their reproducible quantification. Conventional methods for pathogen detection mainly rely on time-consuming enrichment steps followed by biochemical identification strategies, which require assay times ranging from 24 h to up to a week. However, in recent years, significant efforts have been made towards the development of biosensing technologies enabling rapid and close-to-real-time detection of water-borne pathogens. This review summarizes recent developments in biosensors and sensing systems based on a variety of transducer technologies for water-quality monitoring, with specific focus on rapid pathogen detection.

Luminescent switch sensors for the detection of biomolecules based on metal–organic frameworks

Abstract: Metal-organic frameworks (MOFs) as sensing materials have experienced explosive growth in recent years due to their intrinsic merits, such as structural diversity, high porosity, large surface area, extraordinary adsorption affinities, etc. Biomolecules such as DNA, protein, and vitamins play vital roles in metabolism. Moreover, the sensitive detection of biomolecules is of importance in the disease prevention and treatment. This review intends to provide an update on the recent progress in the detection of various biomolecules via MOF-based luminescent sensors. MOFs are successful in the detection of DNA, RNA, protein, and other biomolecules. MOF-based luminescent sensors function by utilizing different mechanisms, including luminescent responses of enhancement and quenching, which are defined as "turn-on" and "turn-off" responses, respectively. Then, a short comparison of the "turn-on" and "turn-off" types of sensors is also made.

SERS-based lateral flow assay for quantitative detection of C-reactive protein as an early bio-indicator of a radiation-induced inflammatory response in nonhuman primates

Abstract: In accidental irradiation situations, rapid in-field evaluation of acute radiation syndrome is critical for effective triage and timely medical treatment of irradiated individuals. A surface-enhanced Raman scattering (SERS)-based lateral flow assay was developed for the quantitative detection of C-reactive protein (CRP) as an early bio-indicator of a radiation-induced inflammatory response in nonhuman primates. Raman reporter-embedded gold-core silver-shell nanoparticles with built-in hot spots were synthesized and conjugated with a CRP detection antibody to serve as SERS tags in the lateral flow assay. The proposed SERS-based lateral flow assay can rapidly detect CRP with a limit of detection of 0.01 ng mL−1 and quantitative analysis ability. Furthermore, the assay was applied to evaluate the CRP levels in plasma samples of irradiated nonhuman primates at 0 to 80 h after exposure to sublethal (4 Gy) and lethal (8 Gy) doses of total body irradiation (n = 3 animals per group). The plasma CRP levels increase rapidly within few hours after irradiation. The CRP level peaks are observed at 12 or 24 h after irradiation, with a concentration of 201.30, 386.06 and 475.18 μg mL−1 for the 4 Gy irradiated animals and 197.14, 69.52 and 358.03 μg mL−1 for the 8 Gy irradiated animals. The results indicate the potential application of the proposed SERS-based lateral flow assay to serve as a rapid and accurate point-of-care biodosimetry assay for the quantitative detection of bio-indicators to triage irradiated individuals in the field of a radiation accident.

A dinitro-functionalized metal-organic framework featuring visual and fluorogenic sensing of H2S in living cells, human blood plasma and environmental samples.

Abstract: Here, we describe a new dinitro-functionalized Zr(iv) MOF (MOF = metal-organic framework) having a UiO-66 (UiO = University of Oslo) framework topology called UiO-66-(NO2)2 (1). It shows fluorescence turn-on behavior towards H2S in simulated biological medium (HEPES buffer, pH = 7.4). By employing solvothermal conditions, 1 was successfully synthesized by reacting ZrCl4, H2BDC-(NO2)2 [H2BDC-(NO2)2 = 2,5-dinitro-1,4-benzenedicarboxylic acid] ligand and benzoic acid with a molar ratio of 1 : 1 : 10 in DMF (DMF = N,N-dimethylformamide) at 130 °C for 24 h. The material was characterized by infrared spectroscopy, X-ray powder diffraction (XRPD) and thermogravimetric (TG) analyses. The compound not only displays highly sensitive fluorometric sensing of H2S but also exhibits a visually detectable colorimetric change towards H2S in daylight. Moreover, the high selectivity of 1' towards H2S is retained even when several other biologically intrusive species co-exist in the sensing medium. The limit of detection (LOD) of the compound is 14.14 μM which lies in the range of the H2S concentration found in biological systems. Fluorescence microscopy studies on J774A.1 cells revealed the efficacy of the probe for imaging H2S in living cells. Moreover, this material can detect H2S in human blood plasma (HBP) and monitor the sulfide concentration in real water samples. All these features clearly demonstrate that the material has huge potential for highly selective sensing of both extracellular and intracellular H2S.