Chemical Tongue Research Articles

Tuning multispectral fluorescence quantum dot–based identification of short-length amyloid β peptides by applying Cu(II) ions

Currently available methods for detecting amyloid β (Aβ) derivatives are mainly dedicated to determining the long forms Aβ1-42 and Aβ1-40. At the same time, the number of physiologically occurring Aβ analogs is much higher, including those truncated at the N- and C-termini. Their identification using standard methods is challenging due to the structural similarity of various Aβ analogs, but could highly benefit from both biomarkers discovery and pathophysiological studies of Alzheimer’s disease. Therefore a “chemical tongue” sensing strategy was employed for the detection of seven Aβ peptide derivatives: Aβ1-16, Aβ4-16, Aβ4-9, Aβ5-16, Aβ5-12, Aβ5-9, Aβ12-16. The proposed sensing system is based on competitive interactions between quantum dots, Cu(II) ions, and Aβ peptides, providing unique fluorescence fingerprints useful for the identification of analytes. After carefully evaluating the Aβ sample preparation protocol, perfect determination of all studied Aβ peptides was achieved using partial least square–discriminant analysis (PLS-DA). The developed PLS-DA models are characterized by excellent accuracy, sensitivity, precision, and specificity of analyte determination, emphasizing the potential of the proposed sensing strategy.Graphical abstract

Paper and nylon based optical tongues with poly(p-phenyleneethynylene)-fluorophores efficiently discriminate nitroarene-based explosives and pollutants

Discrimination of nitroarenes with hydrophobic dyes in a polar (H2O) environment is difficult but possible via a lab-on-chip, with polymeric dyes immobilized on paper or nylon membranes. Here arrays of 12 hydrophobic poly(p-phenyleneethynylene)s (PPEs), are assembled into a chemical tongue to detect/discriminate nitroarenes in water. The changes in fluorescence image of the PPEs when interacting with solutions of the nitroarenes were recorded and converted into color difference maps, followed by cluster analysis methods. The variable selection method for both paper and nylon devices selects a handful of PPEs at different pH-values that discriminate nitroaromatics reliably. The paper-based chemical tongue could accurately discriminate all studied nitroarenes whereas the nylon-based devices represented distinguishable optical signature for picric acid and 2,4,6-trinitrotoluene (TNT) with high accuracy.

Chemical tongues as multipurpose bioanalytical tools for the characterization of complex biological samples.

Chemical tongues are emerging powerful bioanalytical tools that mimic the mechanism of the human taste system to recognize the comprehensive characteristics of complex biological samples. By using an array of chromogenic or fluorogenic probes that interact non-specifically with various components in the samples, this tool generates unique colorimetric or fluorescence patterns that reflect the biological composition of a sample. These patterns are then analyzed using multivariate analysis or machine learning to distinguish and classify the samples. This review focuses on our efforts to provide an overview of the fundamental principles of chemical tongues, probe design, and their applications as versatile tools for analyzing proteins, cells, and bacteria in biological samples. Compared to conventional methods that rely on specific targeting (e.g., antibodies or enzymes) or comprehensive omics analyses, chemical tongues offer advantages in terms of cost and the ability to analyze samples without the need for specific biomarkers. The complementary use of chemical tongues and conventional methods is expected to enable a more detailed understanding of biological samples and lead to the elucidation of new biological phenomena.

Identification of Water-Soluble Polymers through Machine Learning of Fluorescence Signals from Multiple Peptide Sensors.

Recently, there has been growing concern about the discharge of water-soluble polymers (especially synthetic polymers) into the environment. Therefore, the identification of water-soluble polymers in water samples is becoming increasingly crucial. In this study, a chemical tongue system to simply and precisely identify water-soluble polymers using multiple fluorescently responsive peptide sensors was demonstrated. Fluorescence spectra obtained from the mixture of each peptide sensor and water-soluble polymer were changed depending on the combination of the polymer species and peptide sensors. Water-soluble polymers were successfully identified through the supervised or unsupervised machine learning of multidimensional fluorescence signals from the peptide sensors.

An intelligent “chemical tongue” for high-order monitoring ATP-related physiological phosphates and ATP hydrolysis through diverse transduction principles

For discriminating diverse analytes and monitoring a specific chemical reaction, the emerging multi-channel “chemical nose/tongue” is challenging multi-material “chemical nose/tongue”. The former contributes greatly to integrating different transduction principles from a single sensing material, avoiding the need for complex design, high cost, and tedious operation involved with the latter. Therefore, this high-order sensing puts a particular emphasis on the effects of encapsulation. Herein, the plasmonic gold nanoparticles (Au NPs) are encapsulated as a core into the fluorescent guanine monophosphate-Tb3+ infinite coordination polymer nanoparticles (GMP-Tb ICPs) to obtain a core-shell nanocomposite named Au NPs@GMP-Tb ICPs. Hence, a dual-channel “chemical tongue” based on Au NPs@GMP-Tb ICPs is present to realize high-order sensing of adenosine triphosphate (ATP)-related physiological phosphates and the monitoring of ATP hydrolysis. Considering the affinity of Tb3+ towards P–O bonds, four inorganic phosphates and three nucleotide phosphates with different phosphate group numbers and steric hindrance effect directly regulate two stimulus responses (fluorescence intensity and UV–vis absorbance) of Au NPs@GMP-Tb ICPs. Robust statistical methods, such as linear discriminant analysis and hierarchical cluster analysis, are used to recognize each phosphate by the developed sensor array either in the aqueous solution or in complex media such as serum, together with efficiently monitored ATP hydrolysis at different intervals. These findings and blind test clarify that the designed “chemical tongue” guarantees interference resistance and strengthens analytical capacity, together with offering valuable insight into “lab-on-a-nanoparticle” development for monitoring specific chemical reactions.

Surface-engineered prussian blue nanozymes as artificial receptors for universal pattern recognition of metal ions and proteins

Pattern-based array sensing have emerged as an efficient and promising approach for detection of multiple analytes; however, it is still challenging but important to synthesize a range of materials as sensing elements. Surface engineering is a promising strategy for activity modulation or functional design for novel nanomaterials. Herein, we fabricate three Prussian blue (PB)-based nanomaterials by surface modification (pristine PB, PB@MoS2, and PB@Pt), which have exhibited distinct peroxidase-like activities due to varying surfaces. The three PB-based nanozymes have been successfully employed as artificial receptors to construct a cross-reactive colorimetric sensor array. According to the differential interactions between targets and the surface of PB-based nanozymes, the presented sensor array can achieve unique colorimetric response patterns and precisely discriminate 10 metal ions and 13 proteins. This sensor array is sufficiently sensitive to quantitatively analyze individual metal ion and protein with detection limit down to µM and µg/mL, respectively. Moreover, the recognition of metal ions and proteins in complex mixtures has also been achieved. Most importantly, the practical applications have been demonstrated by identifying metal ions in tap water and proteins in human serum samples, differentiating denatured and natural proteins, distinguishing blind samples, and even discriminating clinical samples for cancer identification. This work demonstrates an effective strategy of surface engineering of nanozyme for activity modulation, as well as shows a convenient and universal chemical tongue sensing platform.

A paper-based chemical tongue based on the charge transfer complex of ninhydrin with an array of metal-doped carbon dots discriminates natural amino acids and several of their enantiomers.

Simultaneous detection of multiple amino acids (AAs) instead of individual AAs is inherently worthwhile for improving diagnostic accuracy in clinical applications. Here, a facile and reliable colorimetric microfluidic paper-based analytical device (μPAD) using carbon dots doped with transition metals (Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, and Zn2+) has been provided to detect and discriminate 20 natural amino acids. To make the colourless metal-doped carbon dots suitable for colorimetric assays, they were mixed with ninhydrin to form a charge transfer complex. This optical tongue system, which was constructed by dropping mixtures of ninhydrin with a series of metal-doped carbon dots on a paper substrate in an array format, represented obvious but different colorimetric signatures for every examined amino acid. Since bovine serum albumin was used as a chiral selector reagent for synthesizing the CDs, the sensor device represented excellent selectivity to identify enantiomeric species of AAs. This is the first optical array device that can simultaneously discriminate AAs and several of their enantiomers. We employed various statistical and chemometric methods to analyze the digital data library collected by Image J software, including principal component analysis (PCA), linear discriminant analysis (LDA), and hierarchical cluster analysis (HCA). Twenty AAs could be well distinguished at various concentrations (10.00, 5.00, 2.50, and 1.25 mM). The colorimetric patterns were highly repeatable and were characteristic of individual AAs. Besides qualitative analysis, the designed μPAD-based optical tongue represented quantitative analysis ability, e.g., for lysine in the concentration ranges of 0.005-20.0 mM with a detection limit of 1.0 × 10-6 M and for arginine in the concentration range of 0.12-20.00 mM with a detection limit of 80.0 × 10-6 M. In addition, the binary, ternary, and quaternary mixtures of AAs could also be well recognized with this sensor.

Establishment of a chemical tongue injury-recovery mouse model

Tongue epithelium is one of the most proliferative and regenerative epithelia in our body. However, tongue stem cell research is hampered partly by the lack of optimal animal models to study tongue injury, repair, and regeneration. Here, we establish a novel chemically induced tongue injury-recovery mouse model. Focal application of sodium hydroxide for a limited time led to the denudation of suprabasal layers, leaving the basal layer. Time course study revealed that tongue epithelial cells robustly proliferate over one week after the tongue injury. Importantly, we demonstrated that our novel mouse model could be employed in the lineage tracing of the tongue stem cells under the injury and repair process and further showed that tongue stem cells proliferate faster and generate larger clones in the injury condition than in the steady state condition. Our data indicate the development of a novel chemically induced tongue injury-recovery mouse model for tongue stem cell research, which will significantly facilitate the preclinical study for the pathogenesis and treatment of caustic ingestion.

A colorimetric chemical tongue detects and distinguishes between multiple analytes.

The rate-limiting step for diagnostics development is the discovery and validation of biomarker analytes. We describe a new analyte-agnostic and label-free approach based on colorimetric reactions involving type I polymerization photoinitiators. We demonstrate that a chemically diverse array of hydrogels embedded with cleaved type I photoinitiators could act as microreactors, undergoing colorimetric reactions with bound analytes. The colorimetric signatures produced were visually distinctive and readable with a flatbed document scanner. Signatures of a broad range of sample types were accurately differentiated by unsupervised clustering without knowledge of any analytes bound to the array. The principles described have the potential to enable scalable and cost-effective analysis of complex samples.

A polymer-based chemical tongue for the non-invasive monitoring of osteogenic stem-cell differentiation by pattern recognition of serum-supplemented spent media

The development of non-invasive techniques to characterize cultured cells is invaluable not only to ensure the reproducibility of cell research, but also for quality assurance of industrial cell products for purposes such as regenerative medicine. Here, we present a polymer-based 'chemical tongue', i.e., a biosensing technique that mimics the human taste system, that is capable of non-invasively generating fluorescence response patterns that reflect the proteins secreted, and also partially consumed, by cultured cells, even from serum-supplemented media containing abundant interferants. Analysis of the spent media collected during cell culture using our chemical tongue, which consists of cationic polymers of different scaffolds appended with environmentally responsive dansyl fluorophores, led to the successful (i) identification of human-derived cell lines, (ii) monitoring of the differentiation process of stem cells, even at the stage when conventional staining was negative, and (iii) detection of cancer-cell contamination in stem cells. Since the characterization of cultured cells is usually performed via invasive methods that result in cell death, our chemical-tongue approach, which is of high practical utility, will offer a new means of addressing the growing demand for highly controlled cell production in the medical and environmental fields.

A simple sensor ensemble-based chemical tongue for powerful fingerprint identification of multiple thiols and juice powder

A powerful discriminative sensor for identifying different thiols and their mixtures was developed. The sensor was easily constructed by using surfactant CTAB assemblies encapsulating two commercially available fluorophores, namely, tetrafluoroterephthalonitrile (4F-2CN) and rhodamine B (RhB). UV–vis absorption and ESI-MS measurements revealed 4F-2CN can react with different thiols and yields different products with diverse absorption behaviors. Fluorescence measurements and control experiments showed that this single-system based sensor exhibits typical multiple-wavelength cross-reactive responses to multiple thiols, and RhB plays an important role in the process. This single sensor platform can not only distinguish 8 structurally similar thiols, but also differentiate their mixtures and be applied for identifying various commercial juice powder of different brands or tastes and even commercially available liquid juice of different tastes.

A Biomimetic Sensor Array Based on a Single Fluorescent Block-copolymer for the Pattern Recognition of Proteins

A strategy for easily constructing a sensor array that mimics a biological sensory mechanism, i.e., a so-called chemical tongue, based on a single material is reported. An array of aqueous solution...

Sensor Array Based Determination of Edman Degradated Amino Acids Using Poly(p‐phenyleneethynylene)s

A cross‐reactive optical sensor array based on poly(p‐phenyleneethynylene)s (PPEs) determines Edman degraded amino acids. We report a sensor array composed of three anionic PPEs P1–P3, and their electrostatic complexes with metal ions (Fe2+, Cu2+, Co2+). We recorded distinct fluorescence intensity response patterns as “fingerprints” of this chemical tongue toward standard phenylthiohydantoin (PTH) amino acids—degradation products of the Edman process. These “fingerprints” were converted into canonical scores by linear discrimination analysis (LDA), which differentiates all of the PTH‐amino acids. This array discriminates PTH‐amino acid residues degraded from an oligopeptide through Edman sequencing. This approach is complementary to chromatography approaches which rely on mass spectrometry; our array offers the advantage of simplicity.

DNA-MnO2 nanosheets as washing- and label-free platform for array-based differentiation of cell types

Accurate and facile differentiation of cell types is essential for accurate diagnosis and therapy of diseases. However, it remains challenging due to low specificity, requirement of sophisticated instruments, and tedious operation steps. Herein, a simple, washing- and label-free chemical tongue was constructed for differentiation of cell types. In the array-based sensing platform, DNA-ligand ensembles adsorbed on the surface of MnO2 nanosheets were used as sensing probes. Instead of aptamers from cell-SELEX, the randomly designed DNA strands were used, offering versatile interactions with cells. The property that MnO2 nanosheets can be degraded by intracellular glutathione makes the platform avoid the washing step. Eight types of cell lines were distinguished from each other after the data were treated with principal component analysis (PCA). In addition, a 95% of identification accuracy for the randomly selected unknown samples was achieved. The strategy shows an excellent performance not only in distinguishing cell lines but also in the identification of unknown cell samples.

A gold nanocluster chemical tongue sensor array for Alzheimer's disease diagnosis.

Alzheimer's disease (AD) is a common neurodegenerative disorder in elderly people, and is associated with a heavy financial burden on our society. The use of serologic biomarkers is an attractive method to diagnose AD. Although the determination of blood-based biomarkers for AD has been explored in many studies, few practical diagnosis methods have been used in the clinic. In this work, we constructed a "chemical tongue" sensor array that is easy to use and based on four kinds of fluorescent gold nanoclusters (Au NCs) for discriminating between multiple proteins at nanomolar concentrations. The device utilizes a linear discrimination analysis based on fluorescence intensity response patterns. Using this chemical tongue sensor array, multiple proteins can be confidently identified even in complex biological systems, such as human urine. Most importantly, sera of AD patients could be effectively discriminated from those of osteoarthritis patients, or of healthy people. Also, the results obtained for the AD patients by the chemical tongue sensor array were validated by CSF determination. We conclude that the chemical tongue sensor array manufactured in this work paves the way for designing an auxiliary diagnosis method for AD that is less invasive and more convenient for the large-scale screening of patients.

Gold Nanorod-Based Chrono-Colorimetric Sensor Arrays: A Promising Platform for Chemical Discrimination Applications.

Most array-based sensing platforms, to date, utilize static response patterns for discrimination of a wide variety of analytes, but only a few studies have focused on the important task of quantitatively resolving structural isomers, which are nowadays important because of their broad usage in medicines and industries. A possible way of accomplishing this feat is to combine kinetic (rather than static) sensor response profiles with the chemical tongue strategy to allow the development of array-based sensors for isomeric discrimination. Here, by adding the time dimension, a simple and novel gold nanorod (AuNR)-based chrono-colorimetric sensor array is proposed for chemical discrimination applications. Because of their similar structure but different redox potentials, dihydroxybenzene (DHB) structural isomers have been chosen, as models, to evaluate the applicability of the proposed array. The principle of the array relies on various growth rates of silver shells on AuNRs at different silver ion/AuNR concentration ratios owing to the different kinetic behaviors of DHBs, which can be used as fingerprints to identify DHBs with the help of multivariate analysis methods. The combinatorial colorimetric response of AuNRs upon DHB addition has been analyzed by linear discriminant analysis and hierarchical cluster analysis. Finally, identification of individual DHBs or their mixtures in real samples confirms the potential application of the proposed array.

Fluorescent Binary Ensemble Based on Pyrene Derivative and Sodium Dodecyl Sulfate Assemblies as a Chemical Tongue for Discriminating Metal Ions and Brand Water.

Enormous effort has been put to the detection and recognition of various heavy metal ions due to their involvement in serious environmental pollution and many major diseases. The present work has developed a single fluorescent sensor ensemble that can distinguish and identify a variety of heavy metal ions. A pyrene-based fluorophore (PB) containing a metal ion receptor group was specially designed and synthesized. Anionic surfactant sodium dodecyl sulfate (SDS) assemblies can effectively adjust its fluorescence behavior. The selected binary ensemble based on PB/SDS assemblies can exhibit multiple emission bands and provide wavelength-based cross-reactive responses to a series of metal ions to realize pattern recognition ability. The combination of surfactant assembly modulation and the receptor for metal ions empowers the present sensor ensemble with strong discrimination power, which could well differentiate 13 metal ions, including Cu2+, Co2+, Ni2+, Cr3+, Hg2+, Fe3+, Zn2+, Cd2+, Al3+, Pb2+, Ca2+, Mg2+, and Ba2+. Moreover, this single sensing ensemble could be further applied for identifying different brands of drinking water.

Chemical Tongues and Noses Based upon Conjugated Polymers

We report the uses of conjugated polymers in multisensory applications and in chemical and optoelectronic tongues. We look at the potential of single polymers to discriminate multiple analytes and into small libraries of conjugated polymers that represent sensors. These small libraries combine several barely selective, promiscuous sensor elements and react with the analytes in a fairly non-selective fashion by change of color, emission wavelength, or emission intensity. In such optoelectronic noses and tongues, response of a single element is not specific or particularly useful at all, but the response pattern after the combination of several sensor elements is often specific for an analyte and allows discrimination and identification without any problem. These types of tongues and noses are well suited for quality control of foodstuff, beverages, and biological species such as proteins or cells. The discriminative process is often not well understood but it is powerful, particularly if the obtained data are analyzed by sophisticated statistical methods, i.e., linear discriminant analysis and/or principal component analysis. This added layer of analysis extracts the hidden information/patterns out of the data and allows visualization of the results.

Truxene-Based Hyperbranched Conjugated Polymers: Fluorescent Micelles Detect Explosives in Water.

We report two hyperbranched conjugated polymers (HCP) with truxene units as core and 1,4-didodecyl-2,5-diethynylbenzene as well as 1,4-bis(dodecyloxy)-2,5-diethynylbenzene as comonomers. Two analogous poly(para-phenyleneethynylene)s (PPE) are also prepared as comparison to demonstrate the difference between the truxene and the phenyl moieties in their optical properties and their sensing performance. The four polymers are tested for nitroaromatic analytes and display different fluorescence quenching responses. The quenching efficiencies are dependent upon the spectral overlap between the absorbance of the analyte and the emission of the fluorescent polymer. Optical fingerprints are obtained, based on the unique response patterns of the analytes toward the polymers. With this small sensor array, one can distinguish nine nitroaromatic analytes with 100% accuracy. The amphiphilic polymer F127 (a polyethylene glycol-polypropylene glycol block copolymer) carries the hydrophobic HCPs and self-assembles into micelles in water, forming highly fluorescent HCP micelles. The micelle-bound conjugated polymers detect nitroaromatic analytes effectively in water and show an increased sensitivity compared to the sensing of nitroaromatics in organic solvents. The nitroarenes are also discriminated in water using this four-element chemical tongue.

Continuously evolving ‘chemical tongue’ biosensor for detecting proteins

We developed a unique continuously evolving colorimetric sensor array based on AuNPs decorated by two single-stranded oligonucleotides with different molar ratios for protein discrimination. The number of differential receptors in this sensor array could be easily extended by adjusting the molar ratios of two DNA, resulting in continuously improved discrimination ability. The continuous response data of target samples against our sensing system could be easily obtained and exclude abnormal signals. The sensing system could discriminate twelve proteins at the concentration of 200nM in the presence of 50% human urine with accuracy of 100%, showing feasible potential for diagnostic applications. Remarkably, HSA at various concentrations, the pure Lys and HSA, and the mixture of these two proteins with different molar ratios had been successfully discriminated in LDA plot as well in the presence of human urine sample. This novel strategy will be very promising for the design of cheaper and more reliable sensor arrays for target samples.