Miniaturized paper-based analytical device for the portable analysis of phyto-cannabinoids in plant and oral fluids.

In this work, a low-cost and eco-friendly paper-based analytical device (PAD) method is described for the determination of phyto-cannabinoids in cannabis and oral fluids based on a simple colorimetric reaction. The PAD was able to distinguish tetrahydrocannabinol (THC)- and cannabidiol (CBD)-rich plant samples by using 4-aminophenol (4-AP) and later on to quantify total phyto-cannabinoid content (THC + CBD + CBN) in plant and oral fluids by using the Fast Corinth V reagent. The chemical and physical properties regarding paper type and reagent concentration in the PAD were optimized to achieve the best analytical performance. After that, analytical features were obtained, including a linear range of 0.01-0.1 mg mL-1, a limit of detection (LOD) of 0.003 mg mL-1, and a suitable precision, expressed as relative standard deviation (RSD) lower than 10%. Furthermore, no significant interferences were observed in colorimetric reactions when tea, herbs, and drug samples were analyzed. Additionally, the PAD proved color stability up to 1 month after the sampling at 25 °C. The developed PAD was suitable for determining total phyto-cannabinoid content in plants and oral fluids, obtaining good results compared to GC-MS. Overall, this method showed good reliability resulting in an operational on-site device for drug monitoring.

Micro-paper-based analytical device decorated with metal-organic frameworks for the assay of synthetic cannabinoids in oral fluids coupled to ion mobility spectrometry.

A new concept of paper-based device has been developed combining the advantages of cellulose supports and the rich surface chemistry of metal-organic frameworks (MOFs). The composite, named as NH2-UiO-66@paper, has been developed for the isolation of synthetic cannabinoid receptor agonists (SCRAs) in oral fluids, trying to mimic the interactions of those compounds with the human CB1R and CB2R receptors, mainly governed by hydrogen bonding and π-interactions with serine and histidine residues. MOF selection (UiO-66) and functionalization of the ligand (2-aminoterephthalic acid) has been done according to the following criteria: (i) water stability of the selected MOF, and (ii) promoting appropriate interactions with SCRAs due to the MOF nature. NH2-UiO-66@paper composite has been characterized in depth and the results confirmed that the material is stable at the temperature selected for thermal desorption (230 °C). Furthermore, the developed method provided appropriate precision values (RSD < 12%) and a limit of detection as low as 10 ng using ion mobility spectrometry as analytical technique. Lastly, the method has been successfully applied to the isolation of several synthetic cannabinoids from oral fluids. This method claims to be an interesting approach for expanding the combination of MOFs with sustainable support and represents a promising alternative to sophisticated and non-portable systems due to the negligible sample treatment required and the simplicity of the operation, which can be applied with screening purposes.

Super-Stable Metal-Organic Framework (MOF)/Luciferase Paper-Sensing Platform for Rapid ATP Detection.

Adenosine triphosphate (ATP) determination has been used for many decades to assess microbial contamination for hygiene monitoring in different locations and workplace environments. Highly sophisticated methods have been reported, yet commercially available kits rely on a luciferase-luciferin system and require storage and shipping at controlled temperatures (+4 or -20 °C). The applicability of these systems is limited by the need for a secure cold chain, which is not always applicable, especially in remote areas or low-resource settings. In this scenario, easy-to-handle and portable sensors would be highly valuable. Prompted by this need, we developed a bioluminescence paper biosensor for ATP monitoring in which a new luciferase mutant was combined with a metal-organic framework (MOF); i.e., zeolitic imidazolate framework-8 (ZIF-8). A paper biosensor was developed, ZIF-8@Luc paper sensor, and interfaced with different portable light detectors, including a silicon photomultiplier (SiPM) and smartphones. The use of ZIF-8 not only provided a five-fold increase in the bioluminescence signal, but also significantly improved the stability of the sensor, both at +4 and +28 °C. The ATP content in complex biological matrices was analyzed with the ZIF-8@Luc paper sensor, enabling detection down to 7 × 10-12 moles of ATP and 8 × 10-13 moles in bacterial lysates and urine samples, respectively. The ZIF-8@Luc sensor could, therefore, be applied in many fields in which ATP monitoring is required such as the control of microbial contamination.

Metal-organic frameworks as promising solid-phase sorbents for the isolation of third-generation synthetic cannabinoids in biological samples.

In this work, metal-organic frameworks (MOFs) were used for the first time as solid-phase extraction (SPE) sorbents for the isolation of synthetic cannabinoids (SCs) from oral fluids and subsequently quantified by LC-fluorescence detection (FLD). In this context, different MOF families were synthesized and tested under SPE mode. UiO-66 was the family selected, being the amino functionalized (NH2-UiO-66) the best candidate in terms of extraction performance. After the method optimization, several analytical parameters of interest were obtained, reaching limits of detection (LODs) as low as 0.6-0.8 µg L-1 and precision values (expressed as RSD) lower than 10.6%. The developed method was successfully applied to the determination of 8 SCs in different oral fluids at three spiked levels with recoveries between 67 and 114%. This method claims to be a real alternative for screening purposes, being a cost-effective procedure due to the price of the sorbent (<0.5 €/cartridge) and its recyclability (up to 12 uses), among others good features.

(Multivariate)-Metal-Organic Framework for Highly Efficient Antibiotic Capture from Aquatic Environmental Matrices.

Contamination of aquatic environments by pharmaceuticals used by modern societies has become a serious threat to human beings. Among them, antibiotics are of particular concern due to the risk of creating drug-resistant bacteria and, thus, developing efficient protocols for the capture of this particular type of drug is mandatory. Herein, we report a family of three isoreticular MOFs, derived from natural amino acids, that exhibit high efficiency in the removal of a mixture of four distinct families of antibiotics, such as fluoroquinolones, penicillins, lincomycins, and cephalosporins, as solid-phase extraction (SPE) sorbents. In particular, a multivariate (MTV)-MOF, prepared using equal percentages of amino acids l-serine and l-methionine, also exhibits outstanding recyclability, surpassing the benchmark material activated carbon. The good removal performance of the MTV-MOF was rationalized by means of single-crystal X-ray diffraction. These results highlight the situation of MOFs as a real and promising alternative for the capture of antibiotics from environmental matrices, especially wastewater streams.

Novel Nanozeolitic Imidazolate Framework (ZIF-8)-Luciferase Biocomposite for Nanosensing Applications.

The identification of new strategies to improve the stability of proteins is of utmost importance for a number of applications, from biosensing to biocatalysis. Metal-organic frameworks (MOFs) have been shown as a versatile host platform for the immobilization of proteins, with the potential to protect proteins in harsh conditions. In this work, a new thermostable luciferase mutant has been selected as a bioluminescent protein model to investigate the suitability of MOFs to improve its stability and prompt its applications in real-world applications, for example, ATP detection in portable systems. The luciferase has been immobilized onto zeolitic imidazolate framework-8 (ZIF-8) to obtain a bioluminescent biocomposite with enhanced performance. The biocomposite ZIF-8@luc has been characterized in harsh conditions (e.g., high temperature, non-native pH, etc.). Bioluminescence properties confirmed that MOF enhanced the luciferase stability at acidic pH, in the presence of organic solvents, and at -20 °C. To assess the feasibility of this approach, the recyclability, storage stability, precision, and Michaelis-Menten constants (Km) for ATP and d-luciferin have been also evaluated. As a proof of principle, the suitability for ATP detection was investigated and the biocomposite outperformed the free enzyme in the same experimental conditions, achieving a limit of detection for ATP down to 0.2 fmol.

A Luciferase Mutant with Improved Brightness and Stability for Whole-Cell Bioluminescent Biosensors and In Vitro Biosensing.

The availability of new bioluminescent proteins with tuned properties, both in terms of emission wavelength, kinetics and protein stability, is highly valuable in the bioanalytical field, with the potential to improve the sensitivity and analytical performance of the currently used methods for ATP detection, whole-cell biosensors, and viability assays among others. We present a new luciferase mutant, called BgLuc, suitable for developing whole-cell biosensors and in vitro biosensors characterized by a bioluminescence maximum of 548 nm, narrow emission bandwidth, favorable kinetic properties, and excellent pH- and thermo-stabilities at 37 and 45 °C and pH from 5.0 to 8.0. We assessed the suitability of this new luciferase for whole-cell biosensing with a cell-based bioreporter assay for Nuclear Factor-kappa B (NF-kB) signal transduction pathway using 2D and 3D human embryonic kidney (HEK293T) cells, and for ATP detection with the purified enzyme. In both cases the luciferase showed suitable for sensitive detection of the target analytes, with better or similar performance than the commercial counterparts.

Reticular framework materials in miniaturized and emerging formats in analytical chemistry.

In recent years, important efforts have been put into miniaturization, coming on the scene formats such as chips, 3D-printed objects and paper-based devices. These systems have been applied to biological and chemical processes taking profit of their advantages such as waste reduction, low cost, portability, etc. Despite their benefits, there is a need to continue developing easier-to-use devices with enhanced performance addressed to face the current analytical challenges. In this sense, reticular porous materials such as metal- (MOFs) and covalent- (COFs) organic frameworks with unique features including tailorable porous architectures and tunable chemistry have attracted a lot of attention in various fields. Nevertheless, the combination of these materials with miniaturized and emerging formats has been scarcely investigated. This review is intended to bridge this gap and highlight the recent contributions of these materials in these analytical formats. Thus, this work aims to provide a comprehensive review of the field, highlighting incorporation strategies into the functional supports available to date, and the applications of the resulting systems in both off-site laboratory studies (mostly dedicated to (micro)extraction purposes) and on-site analysis. Finally, a discussion of challenges and future directions in this field is also given.

A hybrid nano-MOF/polymer material for trace analysis of fluoroquinolones in complex matrices at microscale by on-line solid-phase extraction capillary electrophoresis.

A hybrid material (nano-metal organic framework@organic polymer, named as nano-MOF@polymer) was applied for the first time as sorbent for on-line solid-phase extraction capillary electrophoresis with ultraviolet detection (SPE-CE-UV). The resulting material was prepared building layer-by-layer a HKUST-1 (Hong Kong University of Science and Technology-1) nano-MOF onto the polymer surface, which allowed controlling the thickness and maximizing the active surface area. The sorbent was widely characterized at micro- and nano-scale to validate the synthesis and to establish the material properties. Then, fritless microcartridges (2 mm) were assembled by packing only a few micrograms of sorbent particles and investigated for preconcentration of fluoroquinolones (FQs) in several real samples (river water, human urine and whole cow milk). Under the optimized conditions, the sample (ca. 60 µL) was loaded in separation background electrolyte (BGE, 50 mM phosphate (pH 7)), and retained analytes were eluted using a small volume of 2% v/v formic acid in methanol (ca. 50 nL). The SPE-CE-UV method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), repeatability, reproducibility and reusability. The developed method showed a LOD decreasing until 1 ng L-1 when larger volumes of sample were loaded (ca. 180 µL), which was 500,000 times lower than by CE-UV. This undescribed sensitivity enhancement would arise from the homogenous and populated MOF nano-domains and the appropriate permeability of the hybrid material, which would promote high extraction efficiency and loading capacity. Furthermore, the sorbent showed appropriate selectivity regardless the analyzed complex environmental, biological or food matrix samples, achieving excellent detectability and recoveries (>90%).

Highly Efficient Removal of Neonicotinoid Insecticides by Thioether-Based (Multivariate) Metal-Organic Frameworks.

Circumventing the impact of agrochemicals on aquatic environments has become a necessity for health and ecological reasons. Herein, we report the use of a family of five eco-friendly water-stable isoreticular metal-organic frameworks (MOFs), prepared from amino acids, as adsorbents for the removal of neonicotinoid insecticides (thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid) from water. Among them, the three MOFs containing thioether-based residues show remarkable removal efficiency. In particular, the novel multivariate MOF {SrIICuII6[(S,S)-methox]1.5[(S,S)-Mecysmox]1.50(OH)2(H2O)}·36H2O (5), featuring narrow functional channels decorated with both -CH2SCH3 and -CH2CH2SCH3 thioalkyl chains-from l-methionine and l-methylcysteine amino acid-derived ligands, respectively-stands out and exhibits the higher removal efficiency, being capable to capture 100% of acetamiprid and thiacloprid in a single capture step under dynamic solid-phase extraction conditions-less than 30 s. Such unusual combination of outstanding efficiency, high stability in environmental conditions, and low-cost straightforward synthesis in 5 places this material among the most attractive adsorbents reported for the removal of this type of contaminants.

Zeolitic imidazolate framework-8 decorated with gold nanoparticles for solid-phase extraction of neonicotinoids in agricultural samples.

A composite built with aminated zeolitic imidazolate framework and gold nanoparticles (AuNPs) for solid-phase extraction (SPE) of neonicotinoids in agricultural samples is presented. The composite was prepared through the assembly of AuNPs onto the surface of metal-organic framework based on the strong interaction between the amino group and AuNP. These metallic surfaces provided additional interactions based on the affinity of amino and cyano groups present in the target compounds. The composite was characterized by scanning electron microscopy, powder X-ray diffraction, Fourier-transform infrared spectroscopy, and surface area measurements. Regarding the SPE protocol, several parameters that can influence the extraction performance were optimized, such as sample volume or composition of elution solvent, among others. After elution, the analytes were determined via HPLC with diode-array detection. Under the selected conditions, satisfactory recoveries of five pesticides (thiamethoxan, clothianidin, imidacloprid, acetamiprid, and thiacloprid) were obtained (between 80 and 110%) in real samples, whereas the limits of detection ranged from 0.019 to 0.041 µg L-1 in aqueous samples and 0.3 to 0.8 µg g-1 in solid samples.

Determination of benzomercaptans in environmental complex samples by combining zeolitic imidazolate framework-8-based solid-phase extraction and high-performance liquid chromatography with UV detection.

In this work, the synthesis of zeolitic imidazolate framework-8 (ZIF-8) crystals and their subsequent application as effective sorbents for extraction and preconcentration of several benzomercaptans from environmental complex samples is described. These materials were prepared by solvothermal approach varying the concentration of n-butylamine modulator to modify the surface of the metal-organic framework. The resulting materials were characterized by scanning and transmission electron microscopy, powder X-ray diffraction and Fourier transform infrared spectroscopy. The ZIF-8 material that gave the best features was selected as extractive phase and the influence of various parameters (sample pH and elution solvent composition, among others) on the extraction efficiency of target compounds were investigated. Under the optimal conditions of the method, the tested analytes (2-mercaptobenzothiazole, 2-mercaptobenzoxazole and 2-mercapto-6-nitrobenzothiazole) were retained and eluted quantitatively with alkaline 50:50 (v:v) methanol-water mixture. Using the proposed method, low limits of detection, in the range of 16-21 ng L-1 for aqueous samples and 0.4-0.5 µg kg-1 for soil samples, were achieved whereas the precision (expressed as relative standard deviation) was lower than 7%. The resulting solid-phase extraction protocol, using the zeolitic material as sorbent, was combined with liquid chromatography and ultraviolet-vis detector and successfully applied to determine traces of these organic pollutants in environmental samples.

Selective solid-phase extraction of organophosphorus pesticides and their oxon-derivatives from water samples using molecularly imprinted polymer followed by high-performance liquid chromatography with UV detection.

A molecularly imprinted polymer was synthesized and characterized to be used as solid-phase extraction sorbent for simultaneous chlorpyrifos and diazinon and their oxon derivatives. Several imprinted polymers were prepared and evaluated in a retention study of these analytes compared with a non-printed polymer. Several parameters affecting the extraction of imprinted polymer such as washing solvent, composition and volume of the eluting solvent and sample volume, were also investigated. Under the optimum conditions, the developed method provided satisfactory limits of detection ranging between 0.07 µg L-1 to 0.12 µg L-1 and the material showed an excellent reusability (> 50 reuses). The method was applied to the extraction and preconcentration of these analytes in water samples. The average recoveries ranged from 79 ± 6 to 104 ± 3 %.

In situ growth of metal-organic framework HKUST-1 in an organic polymer as sorbent for nitrated and oxygenated polycyclic aromatic hydrocarbon in environmental water samples prior to quantitation by HPLC-UV.

An in situ preparation of metal-organic framework (HKUST-1) on the surface of an organic polymer is reported. The hybrid material was evaluated as sorbent for solid-phase extraction (SPE) of oxygenated and nitrated polycyclic aromatic hydrocarbons (PAHs). The growth of HKUST-1 on MAA-based polymer was accomplished using a layer-by-layer assembly strategy. The HKUST-1-polymer was characterized using powder X-ray diffraction and scanning electron microscopy to demonstrate the incorporation of MOF crystals onto the polymer surface. The MOF (nano)crystals were characterized using high-resolution transmission electron microscopy and high-angle annular-dark-field scanning transmission electron microscopy. The water-stable MOF-polymer was evaluated as SPE sorbent, and several variables that can influence the extraction recoveries of PAH derivatives were investigated. Under the selected conditions, the detection limits varied between 4 and 21 ng·L-1, and the precision (relative standard deviation) was below 12%. The recovery values for spiked solutions ranged from 95 to 104%, and the enrichment factor achieved was close to 1000-fold using a high sample volume (100 mL) and very low desorption volume (100 µL). The SPE enrichment combined with HPLC and DAD detector was successfully applied to the extraction and determination of polycyclic hydrocarbons in environmental water samples. Graphical abstract A layer-by-layer synthesis of HKUST-1 onto polymer surface was performed and applied to isolation of PAH derivatives in environmental water samples.

Solid-phase extraction of phospholipids using mesoporous silica nanoparticles: application to human milk samples.

In this study, mesoporous silica materials (MSMs) with bimodal pore systems (namely, UVM-7), MCM-41 silica, and a commercial silica-based material were evaluated as solid-phase extraction (SPE) sorbents for the isolation of phospholipids (PLs) using phosphatidylcholine as a test compound. Morphological characterization (including TEM, surface, and size pore measurements) of these materials was carried out. The mechanism of interaction of the target analyte with the MSMs was also studied. With regard to the SPE process, several experimental parameters that affect the extraction performance (e.g., loading and elution solvent, breakthrough volume, loading capacity, and reusability) were investigated. The recommended protocol was applied to the extraction of PLs in human milk fat samples. The extracted PLs were then determined by hydrophilic interaction liquid chromatography (HILIC) using evaporative light scattering detection (ELSD). This work reports the first application of silica-based mesoporous materials to preconcentrate PLs in these complex matrices. Graphical abstract ᅟ.