Polycaprolactone solution–based ink for designing microfluidic channels on paper via 3D printing platform for biosensing application

This work reports a novel fabrication technique for development of channels on paper‐based microfluidic devices using the syringe module of a 3D printing syringe–based system. In this study, printing using polycaprolactone (PCL)‐based ink (Mw 70 000‐90 000) was employed for the generation of functional hydrophobic barriers on Whatman qualitative filter paper grade 1 (approximate thickness of 180 μm and pore diameter of 11 μm), which would effectively channelize fluid flow to multiple assay zones dedicated for different analyte detection on a microfluidic paper‐based analytical device (μPAD). The standardization studies reveal that a functional hydrophilic channel for sample conduction fabricated using the reported technique can be as narrow as 460.7 ± 20 μm and a functional hydrophobic barrier can be of any width with a lower limit of about 982.2 ± 142.75 μm when a minimum number of two layers of the ink is extruded onto paper. A comparison with the hydrodynamic model established for writing with ink is used to explain the width of the line printed by this system. A fluid flow analysis through a single channel system was also carried out to establish its conformity with the Washburn model, which governs the fluid flow in two‐dimensional μPAD. The presented fabrication technique proves to be a robust strategy that effectively taps the advantages of this 3D printing technique in the production of μPADs with enhanced speed and reproducibility.     

A modified quick,easy, cheap,effective, rugged,and safe method with hydrophobic natural deep eutectic solvent as extractant and analyte protectant for analyzing pyrethroid residues in tomatoes

In this work, a novel quick, easy, cheap, effective, rugged, and safe technique with hydrophobic natural deep eutectic solvent as both extractant and analyte protectant was developed and combined with gas chromatography–tandem mass spectrometry to analyze pyrethroid residues in tomatoes. Eight hydrophobic natural deep eutectic solvents were first evaluated as analyte protectants and those with decanoic acid or lactic acid as hydrogen bond donor were demonstrated to be effective in compensating for the matrix effects of pyrethroids in the gas chromatography system. Hence, they were added to solvent standards for correcting the quantitation errors instead of matrix‐matched calibration standards. Then the abilities of these acid‐based deep eutectic solvents to extract pyrethriods from tomatoes were evaluated. Results showed the recoveries of all pyrethroids reached to over 80% with only 5 mL menthol:decanoic acid (1:1) used, and good phase separation was easily achieved without the addition of inorganic salt in the extraction step, indicating hydrophobic natural deep eutectic solvent could be a green substitute for acetonitrile in the quick, easy, cheap, effective, rugged, and safe extraction. Compared with the conventional method, the proposed protocol improved the recoveries, reduced the matrix effects, and simplified the extraction step, demonstrating to be an effective, fast, and green method.     

A three‐phase solvent extraction system combined with deep eutectic solvent‐based dispersive liquid–liquid microextraction for extraction of some organochlorine pesticides in cocoa samples prior to gas chromatography with electron capture detection

A sample pretreatment method based on the combination of a three‐phase solvent extraction system and deep eutectic solvent‐based dispersive liquid–liquid microextraction has been introduced for the extraction of four organochlorine pesticides in cocoa samples before their determination by gas chromatography‐electron capture detection. A mixture of sodium chloride, acetonitrile, and potassium hydroxide solution is added to cocoa bean or powder. After vortexing and centrifugation of the mixture, the collected upper phase (acetonitrile) is removed and mixed with a few microliters of N,N‐diethanol ammonium chloride: pivalic acid deep eutectic solvent. Then it is rapidly injected into deionized water and a cloudy solution is obtained. Under optimum conditions, the limits of detection and quantification were found to be 0.011‐0.031 and 0.036‐0.104 ng/g, respectively. The obtained extraction recoveries varied between 74 and 92%. Also, intra‐ (n = 6) and interday (n = 4) precisions were less than or equal to 7.1% for the studied pesticides at a concentration of 0.3 ng/g of each analyte. The suggested method was applied to determine the studied organochlorine pesticide residues in various cocoa powders and beans gathered from groceries in Tabriz city (Iran) and aldrin and dichlobenil were found in some of them.     

Cell Engineering with Functional Poly(oxanorbornene) Block Copolymers

Cell‐based therapies are gaining prominence in treating a wide variety of diseases and using synthetic polymers to manipulate these cells provides an opportunity to impart function that could not be achieved using solely genetic means. Herein, we describe the utility of functional block copolymers synthesized by ring‐opening metathesis polymerization (ROMP) that can insert directly into the cell membrane via the incorporation of long alkyl chains into a short polymer block leading to non‐covalent, hydrophobic interactions with the lipid bilayer. Furthermore, we demonstrate that these polymers can be imbued with advanced functionalities. A photosensitizer was incorporated into these polymers to enable spatially controlled cell death by the localized generation of ¹O₂ at the cell surface in response to red‐light irradiation. In a broader context, we believe our polymer insertion strategy could be used as a general methodology to impart functionality onto cell‐surfaces.     

Ionothermal Synthesis of Imide‐Linked Covalent Organic Frameworks

Covalent organic frameworks (COFs) are an extensively studied class of porous materials, which distinguish themselves from other porous polymers in their crystallinity and high degree of modularity, enabling a wide range of applications. COFs are most commonly synthesized solvothermally, which is often a time‐consuming process and restricted to well‐soluble precursor molecules. Synthesis of polyimide‐linked COFs (PI‐COFs) is further complicated by the poor reversibility of the ring‐closing reaction under solvothermal conditions. Herein, we report the ionothermal synthesis of crystalline and porous PI‐COFs in zinc chloride and eutectic salt mixtures. This synthesis does not require soluble precursors and the reaction time is significantly reduced as compared to standard solvothermal synthesis methods. In addition to applying the synthesis to previously reported imide COFs, a new perylene‐based COF was also synthesized, which could not be obtained by the classical solvothermal route. In situ high‐temperature XRPD analysis hints to the formation of precursor–salt adducts as crystalline intermediates, which then react with each other to form the COF.     

Combining convolutional neural networks and in‐line near‐infrared spectroscopy for real‐time monitoring of the chromatographic elution process in commercial production of notoginseng total saponins

The chromatographic elution process is a key step in the production of notoginseng total saponins. Due to quality variability of loading samples and resin capacity decreasing over cycle time, saponins, especially the five main saponins of notoginseng total saponins, need to be monitored in real time during the elution process. In this study, convolutional neural networks, one of the most popular deep learning methods, were used to develop quantitative calibration models based on in‐line near‐infrared spectroscopy for notoginsenoside R₁, ginsenosides Rg₁, Re, Rb₁ and Rd, and their sum concentration, with root mean square error of prediction values of 0.87, 2.76, 0.60, 1.57, 0.28, and 4.99 mg/mL, respectively. Partial least squares calibration models were also developed for model performance comparison. Results show predicted concentration profiles outputted by both the convolutional neural network models and partial least squares models show agreements with the real trends defined by reference measurements, and can be used for elution process monitoring and endpoint determination. To the best of our knowledge, this is the first reported case study of combining convolutional neural networks and in‐line near‐infrared spectroscopy for monitoring of the chromatographic elution process in commercial production of botanical drug products.     

Evaluation of hydrophobic‐interaction chromatography resins for purification of antibody‐drug conjugates using a mimetic model with adjustable hydrophobicity

Antibody drug conjugates are cytotoxic pharmaceuticals, designed to destroy malignant cells. A cytotoxic molecule is attached to an antibody that binds specific to a cancer‐cell surface. Given the high toxicity of the drugs, strict safety standards have to be kept. For this reason, an antibody drug conjugates model was developed with fluorescein 5‐isothiocyanate as the nontoxic payload surrogate. Due to the similar hydrophobicity, this model is used to establish a suitable purification process and characterization method for antibody drug conjugates. Because of the pH dependent solubility of fluorescein, the hydrophobicity of conjugates can be modulated by the pH value. Based on the complex heterogeneity and hydrophobicity of the conjugates a chromatographic purification is challenging. Hydrophobic interaction chromatography is used for analytical as well as for preparative separation. Because of the increased hydrophobicity of the conjugates compared to native antibody, hydrophobic interaction chromatography often suffer from resolution and recovery problems. Conjugates were separated differing on the number of payloads attached to the antibody. For this matter, the drug–antibody ratio is determined and used as a quantitative term. The conjugates are purified at high recoveries and resolution by step gradients using suitable resins, allowing the separation of the target drug–antibody ratio.     

Development of a stir bar sorptive extraction method coupled to solidification of floating droplets dispersive liquid–liquid microextraction based on deep eutectic solvents for the extraction of acidic pesticides from tomato samples

A stir bar sorptive extraction method coupled with deep eutectic solvent based solidification of floating organic droplets–dispersive liquid–liquid microextraction has been used for the simultaneous derivatization and extraction of some acidic pesticides in tomato samples. In this method, initially the analytes are adsorbed on a coated stir bar from tomato juice filled in a narrow tube. After extraction, the stir bar is removed and a water–miscible deep eutectic solvent is used to elute the analytes. Afterward, a derivatization agent and a water–immiscible deep eutectic solvent (as an extraction solvent) with melting point near to room temperature are added to the obtained eluant at µL–levels and the obtained mixture is rapidly injected into deionized water. Under the optimum conditions, the introduced method indicated high enhancement (1543–3353) and enrichment (2530–2999) factors, low limits of detection (7–14 ng/L) and quantification (23–47 ng/L), good linearity (r² ≥ 0.9982), and satisfactory repeatabilities (relative standard deviation ≤12% for intra– and inter–day precisions at a concentration of 100 ng/L of each analyte). Finally, the proposed method was applied in analysis of the analytes in tomato samples.     

Ligandless,deep eutectic solvent‐based ultrasound‐assisted dispersive liquid‐liquid microextraction with solidification of the aqueous phase for preconcentration of lead,cadmium, cobalt and nickel in water samples

A green and efficient sample preparation method using a deep eutectic solvent‐based ultrasounds‐assisted dispersive liquid–liquid microextraction with solidification of the aqueous phase followed by high performance liquid chromatography analysis was developed for preconcentration and determination of heavy metals in environmental samples. In the proposed method, a novel, low density deep eutectic solvent was prepared by mixing trihexyl(tetradecyl)phosphonium chloride and thiosalicylic acid at a molar ratio of 1:2 and used both as an extractant and complexing agent. Ultrasound was used to disperse the extractant in the aqueous phase of the sample. Then, the phases were separated by centrifugation, after which the aqueous phase was frozen and the surface extractant phase was dissolved in a small volume of acetonitrile and subjected to liquid chromatographic analysis. The proposed method provided precisions (relative standard deviation, n = 5) in the range of 2.6–4.7%. The limit of detection were 0.05, 0.13, 0.06, and 0.11 µg/L for Pb(II), Cd(II), Co(II), Ni(II), respectively. The enhancement factors were equal to 154, 159, 162, and 158 for lead(II), cadmium(II), cobalt(II), and nickel(II), respectively. The accuracy of the proposed method was evaluated using certified reference materials (CA011b – hard drinking water, NIST 1643e – trace elements in water, TMRAIN‐04 – simulated rain sample).     

顶空气相色谱法测定盐酸托莫西汀中有机溶剂残留量的研究

建立了盐酸托莫西汀中有机溶剂残留量的顶空气相色谱分析方法.选用大口径HP-快速GC残留溶剂柱为分离柱,FID为检测器,外标法进行定量,并对顶空平衡温度、平衡时间、供试品溶液的制备方法对残留有机溶剂测定的影响进行了研究.甲醇、乙醚、正己烷、乙酸乙酯、四氢呋喃的线性范围分别为 0.41～8.10 μg/mL(r=0.9999)、0.15～3.00 μg/mL(r=0.9995)、0.20～4.01 μg/mL(r=0.9991)、0.32～6.35 μg/mL(r=0.9999)、0.36～7.11 μg/mL(r=0.9999);平均回收率范围96.30%～105.47%,精密度RSD(n=6)2.1%～3.7%;检出限分别为0.2、0.008、0.003、0.04、0.04 μg/mL.