Fluorescence sensing and imaging with carbon-based quantum dots for early diagnosis of cancer: A review.

This review discusses recent advances and the reported strategies over the last ten years on the use of carbon-based quantum dots (QDs), including carbon dots (CDs), graphene quantum dots (GQDs), and polymer dots (PDs) in the design of fluorescence imaging and biosensing system for early diagnosis of cancers. Besides, this study comprehensively reports the latest developments in these years in the fluorescence imaging (FI) area with special attention to carbon-based QDs that take advantage of the excellent properties offered by these zero-dimensional (0D) nanomaterials as fluorescent tags. The most remarkable advantages of these carbon nanomaterials in the development of fluorescence sensing and imaging strategies compared to the conventional dyes arise from sharp emission spectra, long photostability, low-cost synthesis, reliability, reproducibility, high fluorescent intensity, and high surface functional groups such as carboxyl and amide, which impart better solubility in many solvents and aqueous media and facilitate their easy functionalization with biological species. The final section discusses the main challenges to be met to take full advantage of these properties in fluorescence bio-sensing and imaging as well as the possible future trends in this field based on the great advances that have occurred in recent years.

Dual-modal label-free genosensor based on hemoglobin@gold nanocluster stabilized graphene nanosheets for the electrochemical detection of BCR/ABL fusion gene.

For the first time, we have successfully synthesized stable graphene nanosheets from graphite powder through sonication in the hemoglobin-capped gold nanoclusters (Hb@AuNCs) solution for biosensing application. This approach, as a simple method for the exfoliation and fragmentation of graphite in a nanocluster solution, enabled us to produce stable aqueous graphene dispersions at low cost and without the need for hazardous chemicals or tedious experimental procedures. In this method, Hb@AuNCs were used not only as stabilizing agent of graphene through non-covalent bonding, but also as dispersing agent of few-layer graphene nanosheets. The Hb@AuNCs stabilized graphene (Hb@AuNCs-G) was characterized by high resolution transmission electron microscopy (HRTEM), zeta-sizer and Raman spectroscopy. Then, the graphene nanosheets were applied as a novel versatile electrochemical platform for ultrasensitive biosensing of short DNA species of chronic myelogenous leukemia (CML) based on the "signal off" and "signal on" strategies. For this purpose, a single strand DNA (ssDNA) was immobilized on the Hb@AuNCs-G/AuNPs modified electrode surface and acted as the biorecognition element. Methylene blue (MB), as the signaling probe, was then intercalated into the ssDNA. The intercalated MB was liberated upon interaction with the synthetic complementary DNA (cDNA, target), thereby resulting in the apparent reduction of MB redox signal. This designed "signal off" sensing system enabled the voltammetric determination of the target cDNA over a dynamic linear range (DLR) of 0.1 fM to 10 pM with a limit of detection (LOD) of 0.037 fM. In the "signal on" strategy, the response to the cDNA was detected by monitoring the change in the electron transfer resistance (Rct) using the ferro/ferricyanide system as a redox probe. The charge transfer resistance of the probe was found to increase linearly with increasing concentration of target cDNA in the range of 0.1 fM-10 pM with a limit of detection of 0.030 fM. Finally, the selectivity and feasibility of genosensor was evaluated by the analysis of derived nucleotides from mismatched sequences and the clinical samples of patients with leukemia as real samples, respectively.

Biosensing strategies based on organic-scaffolded metal nanoclusters for ultrasensitive detection of tumor markers.

The recent rapid advances in the synthesis, functionalization and application of nanomaterials have enabled scientists to develop metal nanoclusters (MNCs) stabilized with a variety of scaffolds/protecting ligands including thiols, polymers, proteins, dendrimers and nucleic acids. Considering the unique optical, electronic and physical properties of MNCs, they have been successfully used for the tumor marker biosensing assays. In recent years, the ultrasensitive and accurate detection of tumor markers has been of critical importance for the screening or diagnosis of cancers at their early stages. Nanoclusters have revolutionized the design of biosensors and provided an opportunity for the selective and sensitive determination of tumor markers. Here, we review the synthesis, stabilization and promising applications of fluorescent MNCs, with particular focus on their potential for designing tumor marker biosensors. Finally, the current challenges and future perspectives on the emerging MNC-based biosensors are highlighted as well. Our intended audiences are the broader scientific communities interested in the nanomaterial-based biosensors, and our review paper will, hopefully, open up new horizons for those scientists who manipulae the biological properties of nanoclusters. This review is based on publications available up to January 2020.

HIV biosensors for early diagnosis of infection: The intertwine of nanotechnology with sensing strategies.

Human immunodeficiency virus (HIV) is a lentivirus that leads to acquired immunodeficiency syndrome (AIDS). With increasing awareness of AIDS emerging as a global public health threat, different HIV testing kits have been developed to detect antibodies (Ab) directed toward different parts of HIV. A great limitation of these tests is that they can not detect HIV antibodies during early virus infection. Therefore, to overcome this challenge, a wide range of biosensors have been developed for early diagnosis of HIV infection. A significant amount of these studies have been focused on the application of nanomaterials for improving the sensitivity and accuracy of the sensing methods. Following an introduction into this field, a first section of this review covers the synthesis and applicability of such nanomaterials as metal nanoparticles (NPs), quantum dots (QDs), carbon-based nanomaterials and metal nanoclusters (NCs). A second larger section covers the latest developments concerning nanomaterial-based biosensors for HIV diagnosis, with paying a special attention to the determination of CD4+ cells as a hall mark of HIV infection, HIV gene, HIV p24 core protein, HIV p17 peptide, HIV-1 virus-like particles (VLPs) and HIV related enzymes, particularly those that are passed on from the virus to the CD4+ T lymphocytes and are necessary for viral reproduction within the host cell. These studies are described in detail along with their diverse principles/mechanisms (e.g. electrochemistry, fluorescence, electromagnetic-piezoelectric, surface plasmon resonance (SPR), surface enhanced Raman spectroscopy (SERS) and colorimetry). Despite the significant progress in HIV biosensing in the last years, there is a great need for the development of point-of-care (POC) technologies which are affordable, robust, easy to use, portable, and possessing sufficient quantitative accuracy to enable clinical decision making. In the final section, the focus is on the portable sensing devices as a new standard of POC and personalized diagnostics.

A review on nanomaterial-based electrochemical, optical, photoacoustic and magnetoelastic methods for determination of uranyl cation.

This review (with 177 refs) gives an overview on nanomaterial-based methods for the determination of uranyl ion (UO22+) by different types of transducers. Following an introduction into the field, a first large section covers the fundamentals of selective recognition of uranyl ion by receptors such as antibodies, aptamers, DNAzymes, peptides, microorganisms, organic ionophores (such as salophens, catechols, phenanthrolines, annulenes, benzo-substituted macrocyclic diamides, organophosphorus receptors, calixarenes, crown ethers, cryptands and ß-diketones), by ion imprinted polymers, and by functionalized nanomaterials. A second large section covers the various kinds of nanomaterials (NMs) used, specifically on NMs for electrochemical signal amplification, on NMs acting as signal tags or carriers for signal tags, on fluorescent NMs, on NMs for colorimetric assays, on light scattering NMs, on NMs for surface enhanced Raman scattering (SERS)-based assays and wireless magnetoelastic detection systems. We then discuss detection strategies, with subsections on electrochemical methods (including ion-selective and potentiometric systems, voltammetric systems and impedimetric systems). Further sections treat colorimetric, fluorometric, resonance light scattering-based, SERS-based and photoacoustic methods, and wireless magnetoelastic detection. The current state of the art is summarized, and current challenges are discussed at the end. Graphical abstract An overview is given on nanomaterial-based methods for the detection of uranyl ion by different types of transducers (such as electrochemical, optical, photoacoustic, magnetoelastic, etc) along with a critical discussion of their limitations, benefits and application to real samples.

Sub-femtomolar detection of HIV-1 gene using DNA immobilized on composite platform reinforced by a conductive polymer sandwiched between two nanostructured layers: A solid signal-amplification strategy.

This study introduces a signal amplification strategy rely on incorporating a specific polymer film between two typical nanostructured layers, aiming to improve the electrical properties of the platform to be able to transduce small binding event through sub-femtomolar detection of HIV-1 gene at the surface of the constructed biosensing device. The proposed composite was arrayed based on a conductive layer consist of p-aminobenzoic acid (PABA) sandwiched between the electrochemically reduced graphene oxide (ERGO) as the sub-layer, and the gold nanoparticles (AuNPs) as the interfacial layer. We computationally explored that how the use of such design enables the platform to transduce small changes in the interfacial properties of the biosensor, caused by low concentrations of HIV-1 gene, without needing any amplification strategy. Furthermore, it was found that the loin PABA conductive polymer sandwiched between two nanostructure layers play an artwork-ensemble role, which resulted in a good signal repeatability and stability during the relatively long successive incubation and detection procedures. The justification of using such an array of conductive layers was established on the attaining extra low-level of detection limit. The observed performance for probe-DNA immobilized on glassy carbon electrode (GC) modified with ERGO/PABA/AuNPs compared to the GC electrode modified with ERGO/AuNPs inspired us to perform computational calculations, a hybrid of ab-initio and semi-empirical quantum mechanics methods, to discover its probable molecular-scale reasons. A rapid single frequency impedance measurement (SFIM) was also employed to remarkably reduce the measurement time and diminish the probable nonspecific impedance changes. The proposed biosensor was used to evaluate the DNA target over an extremely wide concentration range from 0.1 fM to 10 nM, with a detection limit of 37 aM (S/N = 3).

Recent advances in designing nanomaterial based biointerfaces for electrochemical biosensing cardiovascular biomarkers.

Early diagnosis of cardiovascular disease (CVD) is critically important for successful treatment and recovery of patients. At present, detection of CVD at early stages of its progression becomes a major issue for world health. The nanoscale electrochemical biosensors exhibit diverse outstanding properties, rendering them extremely suitable for the determination of CVD biomarkers at very low concentrations in biological fluids. The unique advantages offered by electrochemical biosensors in terms of sensitivity and stability imparted by nanostructuring the electrode surface together with high affinity and selectivity of bioreceptors have led to the development of new electrochemical biosensing strategies that have introduced as interesting alternatives to conventional methodologies for clinical diagnostics of CVD. This review provides an updated overview of selected examples during the period 2005-2018 involving electrochemical biosensing approaches and signal amplification strategies based on nanomaterials, which have been applied for determination of CVD biomarkers. The studied CVD biomarkers include AXL receptor tyrosine kinase, apolipoproteins, cholesterol, C-reactive protein (CRP), D-dimer, fibrinogen (Fib), glucose, insulin, interleukins, lipoproteins, myoglobin, N-terminal pro-B-type natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α) and troponins (Tns) on electrochemical transduction format. Identification of new specific CVD biomarkers, multiplex bioassay for the simultaneous determination of biomarkers, emergence of microfluidic biosensors, real-time analysis of biomarkers and point of care validation with high sensitivity and selectivity are the major challenges for future research.

Advances in the design of nanomaterial-based electrochemical affinity and enzymatic biosensors for metabolic biomarkers: A review.

This review (with 340 refs) focuses on methods for specific and sensitive detection of metabolites for diagnostic purposes, with particular emphasis on electrochemical nanomaterial-based sensors. It also covers novel candidate metabolites as potential biomarkers for diseases such as neurodegenerative diseases, autism spectrum disorder and hepatitis. Following an introduction into the field of metabolic biomarkers, a first major section classifies electrochemical biosensors according to the bioreceptor type (enzymatic, immuno, apta and peptide based sensors). A next section covers applications of nanomaterials in electrochemical biosensing (with subsections on the classification of nanomaterials, electrochemical approaches for signal generation and amplification using nanomaterials, and on nanomaterials as tags). A next large sections treats candidate metabolic biomarkers for diagnosis of diseases (in the context with metabolomics), with subsections on biomarkers for neurodegenerative diseases, autism spectrum disorder and hepatitis. The Conclusion addresses current challenges and future perspectives. Graphical abstract This review focuses on the recent developments in electrochemical biosensors based on the use of nanomaterials for the detection of metabolic biomarkers. It covers the critical metabolites for some diseases such as neurodegenerative diseases, autism spectrum disorder and hepatitis.

Signalling probe displacement electrochemical aptasensor for malignant cell surface nucleolin as a breast cancer biomarker based on gold nanoparticle decorated hydroxyapatite nanorods and silver nanoparticle labels.

Nucleolin is a multifunctional protein that is markedly overexpressed on the surface of most cancer cells. By taking advantage of the high affinity and specificity of the AS1411 aptamer for nucleolin, a signalling probe displacement electrochemical aptasensor was developed. The thiolated AS1411 aptamer was conjugated to hydroxyapatite nanorods (HApNRs) decorated with gold nanoparticles (AuNPs). To further increase the electrical conductivity of the interface, the ionic liquid 1-ethyl-3-methylimidazolium alanine with its high ion conductivity was placed on the electrode surface. Then, the aptamer was immobilized on the modified electrode and conjugated to signalling c-DNA tagged with AgNPs (c-DNA@AgNPs). In the presence of the MCF7 target cells, the signalling probe is displaced and released from the electrode surface. This leads to a decrease in the current that is proportional to the concentration of cancer cells in the range from 10 to 106 cells mL-1, with a detection limit as low as 8 ± 2 cells mL-1 (n = 3) (based as 3σ/m, where σ is the standard deviation of the blank and m is the slope of the calibration plot). This method presents a promising tool for highly sensitive and selective detection of surface nucleolin on MCF7 cancer cells. Graphical abstract HApNR-AuNP-AS1411 aptamer nanocomposite as an electrochemical sensing interface was immobilized on the gold electrode surface and conjugated to signaling c-DNA tagged with AgNPs for determination of surface nucleolin on MCF7 cancer cells.