The 50 most-cited articles in The Analyst, 2018

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…

Nucleic acid amplification has permeated every field in the life sciences since the introduction of the classic polymerase chain reaction (PCR) method in 1983. Yet, despite its fundamental reach, PCR has been constrained within the walls of a laboratory, due to its requirement for a sophisticated thermocycling machine, limiting external application in low-resource settings. New isothermal amplification strategies are seeking to break through traditional laboratory boundaries by providing nucleic acid replication at constant temperatures. Of these methods, recombinase polymerase amplification (RPA) is one of the fastest developing, experiencing rapid uptake and market, even though it was introduced comparatively late. Critically, RPA's technology potentiates highly accessible and sensitive nucleic acid amplification outside of laboratory, and even self-testing. Here we provide a comprehensive review of the equipment-free simplicity of RPA over its first decade of development. Our review includes key knowledge of RPA technology, such as its reaction components, mechanism,…

The testing and rapid detection of pathogenic organisms is a crucial protocol in the prevention and identification of crises related to health, safety and wellbeing. Pathogen detection has become one of the most challenging aspects in the food and water industries, because of the rapid spread of waterborne and foodborne diseases in the community and at significant costs. With the prospect of inevitable population growth, and an influx of tourism to certain water bodies testing will become a requirement to control and prevent possible outbreaks of potentially fatal illnesses. The legislation is already particularly rigorous in the food industry, where failure to detect pathogenic materials represents a catastrophic event, particularly for the elderly, very young or immune-compromised population types. In spite of the need and requirement for rapid analytical testing, conventional and standard bacterial detection assays may take up to seven days to yield a result. Given the advent of new technologies, biosensors, chemical knowledge and miniaturisation of instrumentation this timescale…

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…

Several biomedical analyses are performed on particular types of cells present in body samples or using functionalized microparticles. Success in such analyses depends on the ability to separate or isolate the target cells or microparticles from the rest of the sample. In conventional procedures, multiple pieces of equipment, such as centrifuges, magnets, and macroscale filters, are used for such purposes, which are time-consuming, associated with human error, and require several operational steps. In the past two decades, there has been a tendency to develop microfluidic techniques, so-called lab-on-a-chip, to miniaturize and automate these procedures. The processes used for the separation and isolation of the cells and microparticles are scaled down into a small microfluidic chip, requiring very small amounts of sample. Differences in the physical and biological properties of the target cells from the other components present in the sample are the key to the development of such microfluidic techniques. These techniques are categorized as filtration-, hydrodynamic-,…

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…

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.

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…

Metabolomics has grown into a prominent field contributing to the molecular understanding of complex biological processes in both health and disease. Furthermore, single-cells are known to display metabolic differences between seemingly homogeneous populations of cells. Single-cell metabolomics attempts to analyze many cellular metabolites from single cells to understand phenotypic heterogeneity, which is a significant challenge due to the low analyte abundances and limited sample volumes. Label-free metabolite detection can be achieved with mass spectrometry, which is capable of simultaneously analyzing hundreds of metabolites. Herein, we review the recent advances in mass spectrometry based single-cell metabolomics, highlighting the current state-of-the-art within the last three years, and identify the challenges to move the field forward.

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),…

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…

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.

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.

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…

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…

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…

Single cell analysis has become of great interest with unprecedented capabilities for the systematic investigation of cell-to-cell variation in large populations. Rapid and multi-parametric analysis of intercellular biomolecules at the single-cell level is imperative for the improvement of early disease diagnosis and personalized medicine. However, the small size of cells and the low concentration levels of target biomolecules are critical challenges for single cell analysis. In recent years, microfluidic platforms capable of handling small-volume fluid have been demonstrated to be powerful tools for single cell analysis. In addition, microfluidic techniques allow for precise control of the localized microenvironment, which yield more accurate outcomes. Many different microfluidic techniques have been greatly improved for highly efficient single-cell manipulation and highly sensitive detection over the past few decades. To date, microfluidics-based single cell analysis has become the hot research topic in this field. In this review, we particularly highlight the advances in this…

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…

for ENR. Satisfactory recoveries of the two FQs from spiked lake, sea and tap water samples at three concentration levels were attained in the range of 80.9-101.0% with relative standard deviations of 0.9-6.9%. The present study not only has great potential for applications in FQ determination, but will also enrich research into dual/multi-template imprinting.

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 1.0 pM with a relative standard deviation (%RSD)…

Cardiac troponin I (cTnI) was considered as the "gold standard" for acute myocardial infarction (AMI) diagnosis owing to its superior cardiac specificity for cardiac damage and showing little or no changes in patients with a skeletal muscle disease or trauma. Herein, a new signal amplification surface-enhanced Raman scattering (SERS) platform was developed for recognition and detection of cTnI by using gold nanoparticles (AuNPs), graphene oxide (GO) and magnetic beads (MB). Here, antibody/Raman reporter labeled AuNP-functionalized GO were employed as both SERS nanotags and signal amplification carriers. Monoclonal antibody modified MB were applied as the capture probe and separation agents. In the presence of cTnI, sandwich type immunocomplexes, "capture probe/target/SERS nanotags", were formed through antibody-antigen-antibody interactions. Due to the strong SERS enhancement ability of the designed GO/AuNP complexes and a high binding chance between cTnI and the GO/AuNP complexes, the proposed SERS-based immunoassay could selectively detect cTnI with a high sensitivity (detection…

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.

In this paper, we have presented a novel strategy to fabricate Fe-doped carbon quantum dots (Fe-CQDs) for dopamine sensing applications. The Fe-CQDs are obtained by one step hydrothermal carbonization, using ethylenediamine tetraacetic acid salts and ferric nitrate as the carbon and iron source, which simultaneously incorporates Fe (dopamine-bonding site) and luminescent carbon quantum dots (fluorophores). The added dopamine containing catechol groups might form complexes with Fe ions (doped in CQDs) due to coordination. Subsequently, dopamine was oxidized to generate dopamine-quinone (a known potent electron acceptor) species by ambient O2. Thus, the coordination induced dopamine in proximity to the CQDs, which provided favourable electron acceptors in close proximity to the CQDs and produced high quenching efficiencies. Such fluorescence responses can be used for well quantifying dopamine in the range of 0.01-50 μM with a detection limit of 5 nM (S/N = 3). The proposed sensing system has been successfully used for the assay of dopamine in human urine samples. Preliminary cell…

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…

. 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.

Cells are the most basic structural units that play vital roles in the functioning of living organisms. Analysis of the chemical composition and content of a single cell plays a vital role in ensuring precise investigations of cellular metabolism, and is a crucial aspect of lipidomic and proteomic studies. In addition, structural knowledge provides a better understanding of cell behavior as well as the cellular and subcellular mechanisms. However, single-cell analysis can be very challenging due to the very small size of each cell as well as the large variety and extremely low concentrations of substances found in individual cells. On account of its high sensitivity and selectivity, mass spectrometry holds great promise as an effective technique for single-cell analysis. Numerous mass spectrometric techniques have been developed to elucidate the molecular profiles at the cellular level, including electrospray ionization mass spectrometry (ESI-MS), secondary ion mass spectrometry (SIMS), laser-based mass spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). In this…

Fully inkjet-printed and low-cost microfluidic paper-based analytical devices (μPADs) demonstrate the simple naked-eye colorimetric determination of calcium ions in drinking and tap water samples.

Rapid detection of pesticides in fruits is an ongoing challenge. The objective of the present study was to develop novel fluorescent microfluidic paper chips for specific recognition and sensitive detection of the pesticide 2,4-D through the electron-transfer-induced fluorescence quenching mechanism. CdTe quantum dots (QDs) were deposited onto cellulose paper (base material) to yield imprinted paper chips (paper@QDs@MIPs). This method allows the transferability of the molecularly imprinted fluorescence sensor from the liquid phase to the solid phase (paper base) for rapid and portable analysis. The resultant imprinted paper chips were effectively characterized, and they exhibited ideal ordered spatial network structure, chemical stability, and fluorescence property. The paper@QDs@MIPs showed that 2,4-D binding significantly reduced the fluorescence intensity within less than 18 min, and it achieved satisfactory linearity in the range of 0.83-100 μM and high detectability of 90 nM. The recognition specificity for 2,4-D relative to its analogues was shown, and the imprinting factor…

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.

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…

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…

SERS (Surface Enhanced Raman Spectroscopy) can realize fingerprint recognition of molecular samples with high detection accuracy and sensitivity. However, rapid and convenient measurement of the Raman spectra of analytes for a point-of-care test (POCT) has put forward a high demand for portable Raman spectrometers, as well as reliable SERS substrates. Hereby, we first utilize a smartphone as a miniaturized Raman spectral analyzer, which has the revolutionary advantages of a friendly human-machine interface, fast measurement time, and good sensitivity. Meanwhile, a paper-based SERS chip was prepared based on commonly used filter paper and silver nanoparticles (AgNP), which was successfully used to detect low concentrations of typical SERS analyte model molecules including rhodamine 6G and crystal violet. The current method of smartphone-based SERS spectroscopy as a POCT device will greatly promote the application of Raman technology in a variety of scenarios, such as safety inspections, pesticide residue detection, water pollution monitoring, and so on. Coupled with paper-based SERS…

AFM-IR is a photothermal technique that combines AFM and infrared (IR) spectroscopy to unambiguously identify the chemical composition of a sample with tens of nanometer spatial resolution. So far, it has been successfully used in contact mode in a variety of applications. However, the contact mode is unsuitable for soft or loosely adhesive samples such as polymeric nanoparticles (NPs) of less than 200 nm of wide interest for biomedical applications. We describe here the theoretical basis of the innovative tapping AFMIR mode that can address novel challenges in imaging and chemical mapping. The new method enables gaining information not only on NP morphology and composition, but also reveals drug location and core-shell structures. Whereas up to now the locations of NP components could only be hypothesized, tapping AFM-IR allows accurately visualizing both the location of the NPs' shells and that of the incorporated drug, pipemidic acid. The preferential accumulation of the drug in the NPs' top layers was proved, despite its low concentration (<1 wt%). These studies pave the way…

Current methods for cancer detection rely on tissue biopsy, chemical labeling/staining, and examination of the tissue by a pathologist. Though these methods continue to remain the gold standard, they are non-quantitative and susceptible to human error. Fourier transform infrared (FTIR) spectroscopic imaging has shown potential as a quantitative alternative to traditional histology. However, identification of histological components requires reliable classification based on molecular spectra, which are susceptible to artifacts introduced by noise and scattering. Several tissue types, particularly in heterogeneous tissue regions, tend to confound traditional classification methods. Convolutional neural networks (CNNs) are the current state-of-the-art in image classification, providing the ability to learn spatial characteristics of images. In this paper, we demonstrate that CNNs with architectures designed to process both spectral and spatial information can significantly improve classifier performance over per-pixel spectral classification. We report classification results after…

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,…

Bacterial biofilms are among the oldest and most prevalent multicellular life forms on Earth and are increasingly relevant in research areas related to industrial fouling, medicine and biotechnology. The main hurdles to obtaining definitive experimental results include time-varying biofilm properties, structural and chemical heterogeneity, and especially their strong sensitivity to environmental cues. Therefore, in addition to judicious choice of measurement tools, a well-designed biofilm study requires strict control over experimental conditions, more so than most chemical studies. Due to excellent control over a host of physiochemical parameters, microfluidic flow cells have become indispensable in microbiological studies. Not surprisingly, the number of lab-on-chip studies focusing on biofilms and other microbiological systems with expanded analytical capabilities has expanded rapidly in the past decade. In this paper, we comprehensively review the current state of microfluidic bioanalytical research applied to bacterial biofilms and offer a perspective on new approaches that are…

Impedimetric biosensors for measuring small molecules based on weak/transient interactions between bioreceptors and target analytes are a challenge for detection electronics, particularly in field studies or in the analysis of complex matrices. Protein-ligand binding sensors have enormous potential for biosensing, but achieving accuracy in complex solutions is a major challenge. There is a need for simple post hoc analytical tools that are not computationally expensive, yet provide near real time feedback on data derived from impedance spectra. Here, we show the use of a simple, open source support vector machine learning algorithm for analyzing impedimetric data in lieu of using equivalent circuit analysis. We demonstrate two different protein-based biosensors to show that the tool can be used for various applications. We conclude with a mobile phone-based demonstration focused on the measurement of acetone, an important biomarker related to the onset of diabetic ketoacidosis. In all conditions tested, the open source classifier was capable of performing as well as, or better, than…

High-throughput profiling/sensing of nucleic acids has recently emerged as a highly promising strategy for the early diagnosis and improved prognosis of a broad range of pathologies, most notably cancer. Among the potential biomarker candidates, microRNAs (miRNAs), a class of non-coding RNAs of 19-25 nucleotides in length, are of particular interest due to their role in the post-transcriptional regulation of gene expression. Developing miRNA sensing technologies that are quantitative, ultrasensitive and highly specific has proven very challenging because of their small size, low natural abundance and the high degree of sequence similarity among family members. When compared to optical based methods, electrochemical sensors offer many advantages in terms of sensitivity and scalability. This non-comprehensive review aims to break-down and highlight some of the most promising strategies for electrochemical sensing of microRNA biomarkers.

High throughput screening (HTS) of molecular analytes is in high demand from and implemented in many areas of chemistry, medicine and industrial biotechnology including the discovery of biomarkers and the development of new chemical entities. Despite its prevalence, technical challenges remain in many of the new application areas of HTS which require rapid results from complex mixtures, for example in: screening biotransformations; targeted metabolomics; and in locating drugs and/or metabolites in biological matrices. Common to all of these are lengthy and costly sample preparation stages, involving recovery from cell cultures, extractions followed by low throughput LC-MS/MS methods or specific fluorescence measurements. In the latter the target molecules need to be inherently fluorescent or to include a fluorescent label or tag which can adversely influence a cellular system. Direct infusion mass spectrometry coupled with robotic sample infusion is a viable contender for information rich HTS with sub-second analysis times, and recent developments in ambient ionisation have heralded…

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)…

The current lack of an accurate, cost-effective and non-invasive test that would allow for screening and diagnosis of gynaecological carcinomas, such as endometrial and ovarian cancer, signals the necessity for alternative approaches. The potential of spectroscopic techniques in disease investigation and diagnosis has been previously demonstrated. Here, we used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to analyse urine samples from women with endometrial (n = 10) and ovarian cancer (n = 10), as well as from healthy individuals (n = 10). After applying multivariate analysis and classification algorithms, biomarkers of disease were pointed out and high levels of accuracy were achieved for both endometrial (95% sensitivity, 100% specificity; accuracy: 95%) and ovarian cancer (100% sensitivity, 96.3% specificity; accuracy 100%). The efficacy of this approach, in combination with the non-invasive method for urine collection, suggest a potential diagnostic tool for endometrial and ovarian cancers.

Access to safe water has a significant impact on all parts of society, its growth and sustainability, both politically and socioeconomically. Consequently, the preservation of water and wastewater treatment have become a global challenge. A major contributor to water pollution is improperly or untreated industrial emissions; water resources can be contaminated with harmful pollutants, toxins or pathogenic microorganisms. Carbon's unique chemistry and its evolution due to recent advances in carbon-based technologies such as nanomaterials, offer significant potential for a variety of water purification strategies. This work details the application of carbon materials in combination with nanotechnology in the form of graphene, graphene composites, electrospun membranes and improved activated carbon in a myriad of water treatment systems with an emphasis on the removal of heavy metals, pesticides and harmful bacteria.

We have successfully developed a target-responsive aptamer cross-linked hydrogel for the visual detection of glucose, an important biomedical analyte. In this work, the glucose-responsive hydrogel was prepared using the target aptamer and its two short complementary DNA strands grafted onto a linear polyacrylamide chain as cross-linkers. Gold nanoparticles (AuNPs) modified with thiol-PEG were encapsulated in the gel and used as the output signal for visible detection. The complex of glucose and its ligand of boronic acid derivatives (Shinkai's receptor) can bind with the aptamer to disrupt the hydrogel, leading to the release of AuNPs with a distinct red colour in the supernatant. By this method glucose can be detected with the naked eye, and the sensor has a detection limit of 0.44 mM in buffer with the help of UV-Vis spectrophotometry. Furthermore, glucose spiked in 50% urine and 30% serum could also be detected respectively with the naked eye, and glucose was quantitatively detected in 50% urine. The hydrogel system provides a non-enzymatic and visual method for glucose…

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…

A simple off-the-shelf dye molecule, 1,4-dihydroxy-9,10-anthraquinone or quinizarin (1), has been investigated for the effective detection of moisture in organic solvents and building materials. Anion-induced deprotonation of 1 to 1.F followed by re-protonation with water is the working principle of the sensor system. Changes in colour, UV-Vis spectra and emission intensity indicate the moisture detection of 1.F in various organic solvents. The probe 1.F is more effective at the detection of water in acetonitrile and THF with a LOD of 0.0011 and 0.0026 wt%. Probe 1.F is reversible, reusable, highly selective, and sensitive and has a fast response time both in solution phase and in test papers. Probe 1.F is also applied for the detection of unknown moisture content in raw building materials such as cement, fly ash, foundry sand, and limestone. 1.F incorporated cellulose-based papers are applicable for inkless writing and stamping in the read-erase manner. Furthermore, these papers are also suitable for fingerprint imaging and sweat pore mapping by the simple colour change method.

Mass-spectrometry based omics technologies - namely proteomics, metabolomics and lipidomics - have enabled the molecular level systems biology investigation of organisms in unprecedented detail. There has been increasing interest for gaining a thorough, functional understanding of the biological consequences associated with cellular heterogeneity in a wide variety of research areas such as developmental biology, precision medicine, cancer research and microbiome science. Recent advances in mass spectrometry (MS) instrumentation and sample handling strategies are quickly making comprehensive omics analyses of single cells feasible, but key breakthroughs are still required to push through remaining bottlenecks. In this review, we discuss the challenges faced by single cell MS-based omics analyses and highlight recent technological advances that collectively can contribute to comprehensive and high throughput omics analyses in single cells. We provide a vision of the potential of integrating pioneering technologies such as Structures for Lossless Ion Manipulations (SLIM) for improved…

Mid-infrared spectroscopy has been applied to research in biology and medicine for more than 20 years and conceivable applications have been identified. More recently, these applications have been shown to benefit from the use of quantum cascade lasers due to their specific properties, namely high spectral power density, small beam parameter product, narrow emission spectrum and, if needed, tuning capabilities. This review provides an overview of the achievements and illustrates some applications which benefit from the key characteristics of quantum cascade laser-based mid-infrared spectroscopy using examples such as breath analysis, the investigation of serum, non-invasive glucose monitoring in bulk tissue and the combination of spectroscopy and microscopy of tissue thin sections for rapid histopathology.

Recent advances in single-cell analysis have unraveled substantial heterogeneity among seemingly identical cells at genomic and transcriptomic levels. These discoveries have urged scientists to develop new tools that are capable of investigating single cells from a broader set of "omics". Proteomics and metabolomics, for instance, are of particular interest as they are closely correlated with a dynamic picture of cellular behaviors and phenotypic identities. The development of such tools requires highly efficient isolation and processing of a large number of individual cells, where techniques such as microfluidics are extremely useful. Here, we review the recent advances in single-cell proteomics and metabolomics, with a focus on microfluidics-based platforms. We highlight a vast array of emerging microfluidic formats for single-cell isolation and manipulation, and how the state-of-the-art analytical tools are coupled with such platforms for proteomic and metabolomic profiling.

. The performance of the biosensor chip was validated with an enzyme-linked immunosorbent assay technique with a regression coefficient as high as 0.940. The advantages of the newly developed saliva-PSA electrical biosensor over previously reported serum-PSA electrochemical biosensors include a faster response time (3-5 min) to achieve a stable electrical signal for PSA detection, high selectivity, improved sensitivity, no additional requirement of a redox electrolyte for electron exchange and excellent shelf life. The presented sensor is aimed for clinical commercialization to detect PSA in human saliva.

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…