Paper-based optical nanosensors - A review.

Paper-based analytical devices (PADs) have shown great promise for point-of-care testing and on-site detection of analytes with chemical, biochemical, and environmental importance owing to their low cost, convenience, scalability, portability, and biocompatibility. The World Health Organization stated that sensors should meet the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable). Paper-based optical sensors meet most of these criteria, making them in high demand and applicable in remote areas. Optical PADs outputs are obtained by different means, such as dyes, nanostructures, redox agents, and pH indicators. The outstanding physical and chemical characteristics of nanostructures, their intense signals, and tunable optical properties make them ideal for many sensing platforms, including paper-based ones. This review focuses primarily on paper-based nanosensors using various nanostructures to fabricate and produce optical signals for visualization. We describe the fundamentals and state of the art of PADs and comprehensively explain the following topics: paper types as the substrate of PADs, PAD fabrication approaches, nanostructure stabilization on PADs, signal acquisition, data handling, interpretation of results, sensing mechanisms, and application areas. We also discuss future trends and strategies to enable PADs to reach their full potential and increase their commercialization opportunities.

Determination of spermine and spermidine in meat with a ratiometric fluorescence nanoprobe and a combinational logic gate.

A ratiometric fluorescent nanoprobe is developed with a wide color variation for visual determination of spermine (SP) and spermidine (SD) in meat samples. The green emission provided from the combination of yellow emissive quantum dots and blue emissive carbon dots turns into pink when SP or SD are present. The results show that the developed sensor has good linearity in the range of 0.5-10 and 0.5-80 µM for SP and SD and suitable detection limits were achieved including 0.2 and 2.1 µM for SP and SD. The probe was highly selective in the presence of amino acids and other biogenic amines. RGB indices were extracted to build a combinational logic gate for visual and simultaneous detection of SP and SD. The dual functional logic gate was easy to design and convenient to operate. Finally, a portable sensor was fabricated for visual, rapid and on-site assessment of meat freshness.

A Smartphone-Based Fluorescent Electronic Tongue for Tracing Dopaminergic Agents in Human Urine.

The importance of tracing dopaminergic agents in the progression assessment of Parkinson's disease has boosted the demand for fast, sensitive, and real-time multi-analyte detection. Herein, visual and fingerprint fluorimetric patterns have been created by an optical sensor array to simultaneously detect and discriminate among levodopa, carbidopa, benserazide, and entacapone, as important dopaminergic agents. A dual emissive nanoprobe consisting of red quantum dots and blue carbon dots with an overall pink emission has been fabricated to provide unique emission patterns in the presence of the target analytes. The sensor elements in the array come from it's differential response in the absence and presence of cetyltrimethylammonium bromide under alkaline conditions. A smartphone camera was used to take photos from the solutions in the wells. Distinct changes in the spectral profiles along with vivid and concentration-dependent color variations led to visual discrimination of dopaminergic agents in a broad concentration range. The results of linear discriminant analysis revealed great discrimination accuracies. Different concentrations of the target analytes were excellently recognized in human urine. The high sensitivity of the array, which is a bonus to rapid, on-site, and visual discrimination of dopaminergic agents, holds great promise for routine analysis of real-world clinical samples.

Providing Multicolor Plasmonic Patterns with Au@Ag Core-Shell Nanostructures for Visual Discrimination of Biogenic Amines.

Biogenic amines (BAs) are known as substantial indicators of the quality and safety of food. Developing rapid and visual detection methods capable of simultaneously monitoring BAs is highly desired due to their harmful effects on human health. In the present study, we have designed a multicolor sensor array consisting of two types of gold nanostructures (i.e., gold nanorods (AuNRs) and gold nanospheres (AuNSs)) for the discrimination and determination of critical BAs (i.e., spermine (SM), tryptamine (TT), ethylenediamine (EA), tyramine (TR), spermidine (SD), and histamine (HT)). The design principle of the probe was based on the metallization of silver ions on the surface of AuNRs and AuNSs in the presence of BAs, forming Au@Ag core-shell nanoparticles. Changes in the surface composition, size, and aspect ratio of AuNSs and AuNRs induced a blue shift in the plasmonic band, which was accompanied by sharp and rainbowlike color variations in the solution. The collected data were visually assessed and statistically analyzed by various data visualization and pattern recognition methods. Namely, linear discriminant analysis (LDA) and partial least squares (PLS) regression were employed for the qualitative and quantitative determination of BAs. The responses were linearly correlated to the concentrations of BAs in a wide range of 10-800, 20-800, 40-800, 40-800, 60-800, and 80-800 µmol L-1 with the limit of detections of 2.46, 4.79, 8.58, 14.26, 10.03, and 27.29 µmol L-1 for SD, SM, TT, HT, EA, and TR, respectively. Finally, the practical applicability of the sensor array was investigated by the determination of BAs in meat and fish samples by which the potential of the probe for on-site determination of food freshness/spoilage was successfully verified.

Application of NaYF4:Yb/Er/Tm UCNPs in Array-Based Sensing of Neurotransmitters: From a Single Particle to a Multichannel Sensor Array.

A novel multichannel sensor array has been designed using a single, yet multiemissive lanthanide-doped upconversion nanoparticle (UCNP). The energy levels of lanthanide ions gave rise to several emission bands which were exploited as individual sensor elements for the recognition of four important neurotransmitters (NTs): dopamine, norepinephrine, levodopa, and serotonin. At alkaline conditions, the oxidation products of these NTs quenched the fluorescence emissions of UCNPs with different quenching degrees. The resulting fingerprint multichannel emission profiles from NaYF4:Yb/Er/Tm UCNPs allowed the discrimination of NTs with excellent accuracy. The recognition was further verified in artificial cerebrospinal fluid, as a complex biological media. We believe that the designed UCNP-based multichannel sensor array offers innovative insights into the discrimination of various chemical signatures using a single measurement.

Optical nanoprobes for chiral discrimination.

Chiral discrimination has always been a hot topic in chemical, food and pharmaceutical industries, especially when dealing with chiral drugs. Enantiomeric recognition not only leads to better understanding of the mechanism of molecular recognition in biological systems, but may further assist in developing useful molecular devices in biochemical and pharmaceutical studies. By emerging nanotechnology and exploiting nanomaterials in sensing applications, a great deal of attention has been given to the design of optical nanoprobes that are able to discriminate enantiomers of chiral analytes. This review explains how engineering nanoparticles (NPs) with desired physicochemical properties allows developing novel optical nanoprobes for chiral recognition. Fundamental concepts related to the origin of chirality in NPs have been briefly presented. Colorimetric and fluorimetric assays in which different types of chiral NPs are used for enantioselective recognition, have been comprehensively described. The main types of nanomaterials described in this review consist of luminescent quantum dots (QDs), carbon dots (CDs), silicon NPs and metal nanoclusters (NCs), as well as plasmonic nanostructures. The mechanisms of sensing in these NP-based optical chiral assays along with relevant examples have been also discussed. Finally, the remaining challenges and future directions have been provided for researchers interested in this topic.

Identification of Catecholamine Neurotransmitters Using a Fluorescent Electronic Tongue.

Catecholamine neurotransmitters, specifically, dopamine (DA), epinephrine (EP), and norepinephrine (NE), are known as substantial indicators of various neurological diseases. Developing rapid detection methods capable of simultaneously screening their concentrations is highly desired for early clinical diagnosis of such diseases. To this aim, we have designed an optical sensor array using three fluorescent dyes with distinct emission bands and have monitored variations in their emission profiles upon the addition of DA, EP, and NE in the presence of gold ions. Because of the different reducing power of catecholamines, differently sized gold nanoparticles (GNPs) with different levels of aggregation were generated, resulting in different amounts of spectral overlap between the absorption band of the in situ generated plasmonic GNPs and the emission bands of the fluorescent dyes. These energy-transfer-based fingerprint profiles were used to discriminate the neurotransmitters by applying pattern recognition methods including linear discriminant analysis (LDA) and artificial neural networks (ANN) and to determine their concentration using multiple linear regression (MLR). Our proposed array also showed a good performance in the discrimination of DA, EP, and NE in complex biological media such as human urine.

Ratiometric fluorescent nanoprobes for visual detection: Design principles and recent advances - A review.

Signal generation techniques for visual detection of analytes have received a great deal of attention in various sensing fields. These approaches are considered to be advantageous when instrumentation cannot be employed, such as for on-site assays, point-of-care tests, and he althcare diagnostics in resource-constrained areas. Amongst various visual detection approaches explored for non-invasive quantitative measurements, ratiometric fluorescence sensing has received particular attention as a potential method to overcome the limitations of intensity-based probes. This technique relies on changes in the intensity of two or more emission bands (induced by an analyte), resulting in an effective internal referencing which improves the sensitivity of the detection. The self-calibration, together with the unique optophysical properties of nanoparticles (NPs) have made the ratiometric fluorescent nanoprobes more sensitive and reliable, which in turn, can result in more precise visual detection of the analytes. Over the past few years, a vast number of ratiometric sensing probes using nanostructured fluorophores have been designed and reported for a wide variety of sensing, imaging, and biomedical applications. In this work, a review on the NP-based ratiometric fluorescent sensors has been presented to meticulously elucidate their development, advances and challenges. With a special emphasis on visual detection, the most important steps in the design of fluorescent ratiometric nanoprobes have been given and based on different classes of analytes, recent applications of fluorescent ratiometric nanoprobes have been summarized. The challenges for the future use of the technique investigated in this review have been also discussed.

A rainbow ratiometric fluorescent sensor array on bacterial nanocellulose for visual discrimination of biothiols.

Considering the crucial role of biothiols in many biological processes, which turns them into highly valuable biomarkers for the early diagnosis of various diseases, the development of an affordable, sensitive and portable probe for the identification and discrimination of these compounds is of great importance. Herein, we developed a ratiometric fluorescent (RF) sensor array with a wide color emissive variation, on a bacterial cellulose (BC) nanopaper substrate for the visual discrimination of biothiols. To this aim, RF sensing elements including N-acetyl l-cysteine capped green CdTe quantum dots-rhodamine B (GQDs-RhB) and red CdTe QDs-carbon dots (RQDs-CDs) at two different NaOH concentrations (0 and 5 mM) were utilized as sensor elements for the discrimination of biothiols. Owing to the high affinity of the thiol group (SH) to the surface of CdTe QDs and the aggregation of the QDs, the fluorescence (FL) emission of the QDs changed while the emission of the CDs and rhodamine B remained almost unchanged upon the addition of biothiols. Accordingly, characteristic rainbow-like FL fingerprint patterns were created for each biothiol which were then distinguished both visually and spectroscopically. Hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA) pattern recognition techniques were employed for the identification and discrimination of biothiols. Based on the designed RF sensor array, convenient test strips were fabricated on BC nanopaper for the visual discrimination of biothiols. It has been shown that this probe can successfully identify biothiols in human plasma as well. Altogether, the developed nanopaper-based sensor array offers an efficient biothiol discrimination tool that can be potentially exploited in the near future in theranostic and point-of-care applications.

Nanoparticle-based optical sensor arrays.

As in many other methods that have integrated nanoparticles (NPs), the chemical nose/tongue strategy has also progressed greatly since the entrance of NPs into this field. The fascinating tunable physicochemical properties of NPs have made them powerful candidates for array-based sensing platforms and have enabled the development of real-time, sensitive and portable systems that are able to target complex mixtures of analytes. In particular, the unique optical properties of NPs have a key role in providing promising array-based sensing approaches. This review will describe the main aspects and processes of most common NP-based optical sensor arrays. The fundamental steps in the design of a sensor array together with details of each step would be provided. The review begins with the principles of optical sensor arrays and presents the concept of cross-reactivity as the main criterion in the selection of sensing elements. Changes in the absorption and emission properties of the assembled sensing elements are categorized into two main classes of optical signals (colorimetric and fluorometric). Popular chemometric methods used for analyzing the data acquired by a sensor array have also been briefly introduced. On the basis of the objective and the desired application, different types of plasmonic and fluorescent NP that possess unique opto-physical properties have been presented as available choices in the design of sensing elements. The vast number of applications of NP-based optical sensor arrays published throughout the literature have then been reviewed according to their mechanism of interaction and the type of optical signal. Finally, the remaining challenges and future directions in this topic have been highlighted.

Exploring Cellular Interactions of Liposomes Using Protein Corona Fingerprints and Physicochemical Properties.

To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome-protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure-activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the relationship between cellular interactions of a set of structurally diverse liposomal formulations and their physicochemical and PC properties has been investigated via linear and nonlinear QSAR models. Significant parameters affecting cellular uptake and cell viability of liposomes in two important cancer cell lines (PC3 and HeLa) have been identified. The developed QSARs have the capacity to be implemented in advanced targeted delivery of liposomal drugs.