Analytical Methods (v.10, #25)
Front cover (2943-2944).
Contents list (2945-2951).
Recent advances in toner-based microfluidic devices for bioanalytical applications by Ellen F. M. Gabriel; Bruno G. Lucca; Gabriela R. M. Duarte; Wendell K. T. Coltro (2952-2962).
Toner-based microfluidic devices have emerged since 2003 as promising platforms for bioanalytical applications. The simplicity of the fabrication process, the low instrumental requirements and the global affordability of required consumables are some key features that encourage the use of this kind of substrate for chemical and biochemical assays. This review aims to cover the recent advances regarding the fabrication procedures involving the laser printing of microfluidic devices on polyester films as well as the association of printing, laser cutting and lamination to create devices assembled in a multi-layer architecture. Examples of applications involving electrophoresis, mixing, concentration, purification, extraction, amplification, rotation-driven fluidic transport, enzyme-linked immunoassays and colorimetric lateral assays on toner-based platforms will be presented and discussed. Lastly, the versatility of the toner-based fabrication technique to enable the production of hydrophobic valves, droplet generator devices, and mimetic vein-on-a-chip and hybrid devices will also be covered.
A turn-on fluorescent formaldehyde probe regulated by combinational PET and ICT mechanisms for bioimaging applications by Xueling Yang; Longwei He; Kaixin Xu; Yunzhen Yang; Weiying Lin (2963-2967).
An illuminating formaldehyde-responsive fluorescence probe (Naph-FA) with a turn-on emission signal was rationally designed and synthesized. The reaction-based probe undergoes successive condensation, 2-aza-Cope rearrangement and hydrolysis processes in response to formaldehyde, and the fluorescence signal was regulated by combinational PET and ICT mechanisms.
Ochratoxin A enhanced detection of cytochrome c with an aptamer-based microcantilever sensor by Xuejuan Chen; Chen Li; Yangang Pan; Bailin Zhang (2968-2971).
Cytochrome c is a globular heme protein which is known to adopt a variety of alternative conformations in addition to its natural structure. In this paper, we developed a microcantilever signal amplification strategy for detecting cytochrome c based on the interaction of cytochrome c with ochratoxin A.
Isothermal amplification of long DNA segments by quadruplex priming amplification by Levan Lomidze; Tyler H. Williford; Karin Musier-Forsyth; Besik Kankia (2972-2979).
Amplification of long DNA segments with the highest possible specificity and lowest bias is one of the main goals of modern genomics. Quadruplex priming amplification (QPA) is a single-primer isothermal method, which employs the free energy of quadruplex structures as the driving force for DNA amplification without any extra reaction components. As a result, QPA represents one of the simplest isothermal assays and was previously shown to be suitable for amplification of relatively short DNA sequences. The current study reveals that single-primer QPA can be used for both exponential and linear amplification of relatively long DNA segments (>100 nt), and switching between these modes can be accomplished by simple re-design of the primer used. While exponential amplification resulted in production of some undesired higher molecular weight species, linear QPA demonstrated highly specific amplification of the target molecules without any side products.
A novel method for geographical origin identification of Tetrastigma hemsleyanum (Sanyeqing) by near-infrared spectroscopy by Weiqun Lin; Qinqin Chai; Wu Wang; Yurong Li; Bin Qiu; Xin Peng; Tianyue Lai; Jie Huang; Zhenyu Lin (2980-2988).
Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum), also known as Sanyeqing in Chinese, is a rare medicinal herb. The quality of its crude drug highly depends on the geographical origin of the plants. The traditional supervised discrimination methods based on near-infrared spectroscopy (NIRS) construct a classifier to discriminate samples with previously trained geographical origins. Those methods have limited power since a lot of real samples are unknown and untrained by the classifier. It is necessary to develop a discrimination method that takes untrained geographical origins into consideration. In this study, a novel identification method is developed using an improved naive Bayesian classifier combined with a clustering algorithm by fast search and find of density peaks (INBC-CFSFDP). In detail, the INBC is proposed to distinguish samples with new geographical origins that are not given in the training database and the CFSFDP is used to further identify the interior categories of those samples with new geographical origins. The experimental results show that regardless of whether the geographical origins are indexed in the training database or not, they can be accurately identified using an INBC-CFSFDP, and they demonstrate that the proposed method is easy, effective, fast, and feasible to discriminate the geographical origin of T. hemsleyanum.
Fluorescent carbon dots directly derived from polyethyleneimine and their application for the detection of Co2+ by Bingyan Han; Ying Li; Tingting Peng; Mingbo Yu; Xixi Hu; Gaohong He (2989-2993).
In this paper, polyethyleneimine (PEI) was applied as a carbon source for synthesizing fluorescent carbon dots (CDs) through a facile and one-step hydrothermal route. Both the N-doping and the amino-functionalization of CDs were accomplished simultaneously. The CDs exhibited strong blue fluorescence and good dispersion in aqueous solution. A large number of amino groups on the surface of CDs greatly simplified the subsequent modification steps. Through an amide reaction, glutathione-functionalized CDs were successfully applied to the selective detection of Co2+, in the linear range from 2.0 × 10−5 to 1.0 × 10−4 mol L−1.
New paper-based microfluidic tools for the analysis of blood serum protein and creatinine built via aerosolized deposition of polycaprolactone by Christopher A. Heist; Gayan C. Bandara; David J. Bemis; Joel C. Pommerenck; Vincent T. Remcho (2994-3000).
This article describes a low-cost method for rapid fabrication of paper-based microfluidic devices using an aerosolized polymeric solution and substrates masked with painter's tape. This approach requires only a few simple tools and uses low-cost supplies to achieve fully functional microfluidic paper-based analytical devices. The method is capable of producing devices with minimum hydrophilic channel widths of 482 ± 4 μm, with the channel height being dictated by the substrate thickness. Complete hydrophobic barriers can be achieved with widths of only 257 ± 2 μm. This technique enables two dimensional (2D) fluidic pattern fabrication on a single membrane while complex three dimensional (3D) fluidic pattern fabrication is possible by simply incorporating a stack and lamination step. Devices built using this approach were applied in two clinical diagnostic applications: quantitative colorimetric assays for protein and for creatinine.
Application of dual-template molecularly imprinted polymer-based solid phase extraction for determination of phenothiazines and benzodiazepines in swine feed by Wan Qiu Xia; Peng Lei Cui; Geng Nan Wang; Jing Liu; Jian Ping Wang (3001-3010).
In this study, a novel dual-template molecularly imprinted polymer capable of simultaneously recognizing 4 phenothiazines and 5 benzodiazepines was synthesized. From the comparison of the 3D conformations of the two templates and the analytes, it was concluded that the shapes and sizes of the templates used in this study influenced the polymer's recognition ability. The polymer was used to prepare a solid phase extraction cartridge, which was used to purify the extract of the swine complete formula feed sample obtained with 10 mL acetonitrile/0.1% formic acid (3 : 7, v/v). The results were determined using ultra performance liquid chromatography. During the experiments, the flow rate, loading solvent, washing solvent and eluting solvent were optimized. The limits of detection for the 9 drugs were in the range of 1.5–10 ng g−1, and the recoveries from the fortified blank feed samples were in the range of 85.6–97.9%. This is the first study reporting the use of a molecularly imprinted polymer-based extraction method for determining the two classes of sedatives in animal feed.
Interval LASSO regression based extreme learning machine for nonlinear multivariate calibration of near infrared spectroscopic datasets by Peng Shan; Yuhui Zhao; Xiaopeng Sha; Qiaoyun Wang; Xiaoyong Lv; Silong Peng; Yao Ying (3011-3022).
As a nonlinear multivariate calibration method, extreme learning machine (ELM) has recently received increasing attention for its fast learning speed and excellent generalized performance. However, it is implemented normally under the empirical risk minimization scheme, and is prone to generate a large-scale and over-fitting model. Least absolute shrinkage and selection operator (LASSO) based ELM (LASSO-ELM) is a simple and efficient approach to avoid over-fitting and obtain an appropriate network structure. Unfortunately, when the initial hidden layer output matrix is in a high dimensional feature space, solving the LASSO problem remains a challenge. To improve the efficiency of solving high-dimension LASSO, we propose interval LASSO based ELM (iLASSO-ELM), which is generated by incorporating interval selection of hidden layer output matrix into original LASSO-ELM. The proposed model combines the coarse screening of interval selection and fine screening of LASSO. Thus, it can identify the relevant hidden nodes quickly and prevent over-fitting. A comparison of the proposed iLASSO-ELM with six other models, namely, ELM, partial least square based ELM (PLS-ELM), ridge regression based ELM (RR-ELM), elastic net based ELM (EN-ELM), LASSO-ELM and Least-Squares Support Vector Machines method (LS-SVM), was evaluated on four benchmark-near infrared (NIR) spectroscopic datasets. Additionally, the Wilcoxon signed rank test was used to statistically compare the predictive performance of the two competing calibration models. Experimental results show that iLASSO-ELM has the minimum root mean square errors of predictions and performs, at least statistically, not worse than other models.
Prediction of amino acids, caffeine, theaflavins and water extract in black tea using FT-NIR spectroscopy coupled chemometrics algorithms by Muhammad Zareef; Quansheng Chen; Qin Ouyang; Felix Y. H. Kutsanedzie; Md. Mehedi Hassan; Annavaram Viswadevarayalu; Ancheng Wang (3023-3031).
Fourier transform near-infrared spectroscopy (FT-NIRS), coupled with chemometrics techniques, was performed as a fast analysis technique to assess the quality of various components in black tea. Four PLS models, namely partial least square (PLS), synergy interval PLS (Si-PLS), genetic algorithm PLS (GA-PLS) and backward interval PLS (Bi-PLS), were established as calibration models for the quantitative prediction of amino acids, caffeine, theaflavins and water extract. The results are reported based on the lower root mean square error of cross prediction (RMSEP) and the root mean square error of cross-validation (RMSECV) as well as their correlation coefficient (R2) in the prediction set (RP) and the calibration set (RC). In addition, on the basis of fewer frequency variables, GA-PLS was found to be the best technique for the quantification of amino acids and water extract and Bi-PLS was found to be the best technique for the quantitative analysis of caffeine and theaflavins in this study. It was observed that NIR spectroscopy can be successfully combined with various chemometric techniques for the rapid identification of the chemical composition of black tea. This study demonstrates that FT-NIR spectroscopy, combined with chemometrics (GA-PLS and Bi-PLS), has the best stability and generalization performance for black tea analysis.
Ionic liquid-based air-assisted liquid–liquid microextraction combined with dispersive micro-solid phase extraction for the preconcentration of copper in water samples by Weimin Du; Li Yao; Jianfeng Bian; Yang Liu; Xie Wang; Jianhua Zhang; Liangyu Pang (3032-3038).
Ionic liquid-based air-assisted liquid–liquid microextraction (IL-AALLME) combined with dispersive micro-solid phase extraction (D-μ-SPE) was applied for the extraction and preconcentration of Cu prior to analysis by graphite furnace atomic absorption spectrometry. IL [Hmim][PF6] was used as the extractant, non-ionic surfactant Triton X-100 as the emulsifier and Fe3O4 nanoparticles as the sorbent. The emulsion was rapidly formed by pulling in and pushing out the mixture of aqueous sample solution and extraction solvent repeatedly using a 10 mL glass syringe. Then, the extractant phase was mixed with Fe3O4 magnetic nanoparticles and separated using a magnet. As a result, the conventional tedious procedure associated with AALLME such as centrifugation was eliminated and the analytical process was accelerated. The experimental parameters affecting the extraction efficiency of Cu such as pH, IL volume, Triton X-100 concentration, Fe3O4 amount, number of extraction times and ultrasound time were investigated and optimized. Under the optimal conditions, the calibration curve was linear in the range of 1.5–120 ng mL−1 for Cu with a correlation coefficient (R) of 0.9992. The limit of detection was 0.5 ng mL−1. Finally, the applicability of this newly developed method was investigated for the analysis of Cu in real water samples.
Sodium polytungstate as gravity separating fluid for polymeric blasting media evaluation by Patric Helbig; Cheryll D. Pitt (3039-3042).
Quality assessment of Plastic Blast Media (PBM) in order to determine heavy and light particulate contamination has been carried out traditionally using gravity separation in a medium prepared using 1,1,2-trifluorotrichloroethane (TFTCE) as high density compound. Environmental concerns require the assessment of viable alternatives to ozone depleting substances like TFTCE. Sodium polytungstate (SPT) can be used to increase the density of aqueous solutions, and has been used successfully in gravity separation of minerals and rocks. Some research was carried out into the literature regarding separating microplastics – a granular contaminant in water courses that is similar to PBM-revealing that it had been carried out using concentrated solutions of metal salts. Comparison of the results obtained from the TFTCE method with results obtained from a method using SPT revealed that there is no loss of analytical accuracy by changing to the SPT method.
ZnO nanoparticles doped polyamide nanocomposite coated on cellulose paper as a novel sorbent for ultrasound-assisted thin film microextraction of organophosphorous pesticides in aqueous samples by Zahra Ayazi; Fatemeh Shekari Esfahlan; Zahra Monsef Khoshhesab (3043-3051).
In this work, a novel thin film based on ZnO nanoparticles (ZnO NPs) incorporated into polyamide (PA) has been designed and prepared. For this purpose, the ex situ prepared ZnO NPs were dispersed into PA solution and the obtained solvent blend was deposited onto cellulose paper applying a solvent exchange method. The characterization of the prepared ZnO NPs/PA nanocomposite was performed applying energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The prepared thin film based on ZnO NPs/PA/cellulose paper was employed for ultrasound assisted thin film microextraction (USA-TFME) of some organophosphorous pesticides (OPPs) as model compounds including fenthion, chlorpyrifos, fenithrothion, phosalone, edifenphos and ethion in environmental water samples followed by gas chromatography-flame ionization detection (GC-FID) determination. The effect of the level of ZnO NP doping into the prepared nanocomposite on the extraction efficiency of the thin film was studied. The important parameters influencing the extraction and back-extraction steps of USA-TFME were optimized by applying a Taguchi orthogonal array design. The limits of detection (LODs) for the developed method were in the range of 0.05 to 0.3 ng mL−1 and its linear dynamic ranges (LDRs) were 0.2–1000, 0.3–1000 and 1–1000 ng mL−1 for different analytes. The method precision (RSD%) with three replicates was in the range of 2.1 to 9.8% using spiked distilled water (100 ng mL−1).
A sensitive three-signal assay for the determination of PFOS based on the interaction with Nile blue A by Qian Chen; Zhen Cheng; Lingling Du; Panpan Zhu; Kejun Tan (3052-3058).
In this work, a sensitive three-signal assay of perfluorooctanesulfonic acid (PFOS) was proposed. In pH 3.3 Britton–Robinson (BR) buffer solution, perfluorooctane sulfonate anions can react with Nile blue A (NBA) through electrostatic attraction and hydrophobic force to form 1 : 1 ion-association complexes resulting in intensity changes in the fluorescence, UV-vis absorption and resonance light scattering (RLS). There was found to be a certain relationship between the three signal changes dependent upon the concentration of PFOS. The change of absorption of NBA is proportional to the logarithm of the concentration of PFOS in the range of 0.1–4.0 μmol L−1 with a limit of detection (LOD) of 14.8 nmol L−1, and RLS intensity change is proportional to the concentration of PFOS in the range of 2.0–12.0 μmol L−1 with a LOD of 119.5 nmol L−1 and the change in the fluorescence is proportional to the logarithm of the concentration of PFOS in the range of 0.05–4.0 μmol L−1 with a LOD of 3.2 nmol L−1. Scanning electron microscopy (SEM) and zeta potential measurements were recorded in order to study the mechanism. This simple, sensitive and cost-effective fluorescence method was successfully applied in the determination of PFOS in real water samples with RSD values of ≤2.14%.
Quantification of combined color and shade changes in colorimetry and image analysis: water pH measurement as an example by Ying Wang; Yue Liu; Wen Liu; Wenhao Tang; Li Shen; Zhilin Li; Meikun Fan (3059-3065).
Color-based analysis has been widely used in many resource-limited situations. However, one of the challenges for this type of application is to quantify the color information, especially when the color changes and shade changes occur together. In this work, pH sensing with paper strips, where both the color and the shade vary with changing pH and are easily influenced by ambient illumination, was used as an example to develop a color quantification method based on image analysis. The images were obtained by photographing the pH strips in aqueous solution. The color information was then extracted from the images, and its relationship with pH was explored in both red, green, blue (RGB) and hue, saturation, value (HSV) color spaces. It was found that the hue of the HSV space has a good correlation with the pH, despite changes in both the shade and the color of the sensing strips. The color of the sensing strips was then quantified by transforming the color to hue and a reverse model to predict the pH of water was established. It was found that the R2 of the model is 0.952 and the root mean square error (RMSE) is 0.219, better than the visual interpretation precision of pH strips (0.5). Finally, the applicability of the model under different lighting conditions was discussed. Thus, color quantization with both color and shade changes has been achieved with high accuracy. We believe that this could find wide application in various point-of-use devices where both color and shade changes are encountered, such as in outdoor scenarios.
A low-cost integrated biosensing platform based on SiN nanophotonics for biomarker detection in urine by D. Martens; P. Ramirez-Priego; M. S. Murib; A. A. Elamin; A. B. Gonzalez-Guerrero; M. Stehr; F. Jonas; B. Anton; N. Hlawatsch; P. Soetaert; R. Vos; A. Stassen; S. Severi; W. Van Roy; R. Bockstaele; H. Becker; M. Singh; L. M. Lechuga; P. Bienstman (3066-3073).
We present a low-cost integrated nanophotonic lab-on-a-chip platform suitable for point-of-care (POC) biomarker analysis. The sensor chip included in the platform contains multiplexed Mach–Zehnder interferometers with an on-chip optical spectral analyser consisting of an arrayed-waveguide grating. The sensor chip is fabricated in silicon nitride material, which makes it compatible with consumer-electronics-grade sources and detectors, leading to the possibility of low-cost instrumentation. The nanophotonic sensor chip exhibits a detection limit of 6 × 10−6 RIU (Refractive Index Units), which is in the same order of magnitude as the reported values for state-of-the-art evanescent wave sensors. The sensor chip is biofunctionalised with specific bioreceptors and integrated into a polymer microfluidic cartridge. The POC instrumentation platform contains optical excitation and read-out sub-systems and dedicated on-board software for real-time analysis of patient samples. To demonstrate the versatility of the platform, we present results both on the detection of an antigen related to tuberculosis directly in urine samples using a laboratory prototype and on the detection of a protein biomarker (CRP) related to inflammation using the integrated instrument.
Development of an ultra-sensitive assay for the determination of an aminoalkyl glucosaminide 4-phosphate, GSK1795091, in plasma to support a first time in human study by Hermes Licea-Perez; Venkatraman Junnotula; Chester L. Bowen; Kasie Fang; Yanwen Qian; Christopher Matheny (3074-3080).
GSK1795091 (or CRX-601), an aminoalkyl glucosaminide 4-phosphate, is a potent TLR4 agonist in clinical development for the treatment of cancer. Bioanalysis of GSK1795091 is challenging as extremely low doses (<1 μg) are administered in clinical settings, requiring an assay with a quantitation limit of 2 pg mL−1 or below. Other challenges associated with the bioanalysis of GSK1795091 include carryover and nonspecific binding issues. Due to these compound characteristics and the lack of precedence, extensive method development was performed to address these challenges. A novel extraction protocol was developed that included sample clean up with an Ostro™ pass-through sample preparation plate and a double chemical derivatization approach targeting hydrophilic functional moieties. The method was validated over the concentration range of 2 to 100 pg mL−1 and employed to determine the exposure of GSK1795091 in a first time in human clinical study. Incurred sample reanalysis was also included and the results agreed with those of the original analysis. The method was found to be precise, accurate and robust, and the low LOQ was critical to adequately support clinical PK assessments.
A label-free ultrasensitive and selective strategy for Pb(ii) assay by a multifunctional DNA probe-mediated rolling-circle amplified synthesis of the G-quadruplexes by Xiao-Feng Wang; Yong-Sheng Wang; Xi-Lin Xiao; Wen-Bo Lan; Bin Zhou; Si-Han Chen; Jin-Hua Xue (3081-3088).
We report a label-free ultrasensitive and selective strategy for Pb(ii) assay by a multifunctional DNA probe (MDP)-mediated rolling-circle amplified synthesis of the G-quadruplexes. The MDP acted as a target recognition probe, a catalytic DNAzyme and a primer of rolling-circle amplification (RCA). The presence of Pb(ii) can induce the conformational switching of the MDP, resulting in the cleavage of the S-DNA in the MDP to release an E-DNA. The released E-DNA then initiated a RCA reaction with a reasonably devised padlock DNA template to produce an accumulated amount of repeated sequences. The RCA product in the present work was designed as a G-rich sequence, which could fold into thousands of G-quadruplex units. The G-quadruplex formed by RCA can specifically bind to NMM to result in an amplified fluorescence signal. Through these cascade amplifications, Pb(ii) ions can be detected at as low as 94.29 pM, which is much lower than those reported in related literature. We expect that this amplification strategy might be helpful in the design of a highly sensitive analytical platform for wide application in environmental and biomedical fields.
Development and comparison of regression models for the determination of quality parameters in margarine spread samples using NIR spectroscopy by Anita Rácz; Marietta Fodor; Károly Héberger (3089-3099).
Fat and dry material contents (connected to moisture) are one of the most important parameters in the quality control of butter, margarine and margarine spreads (dairy spreads). More than a hundred margarine samples were used to model their fat and dry material content based on Fourier transform-near infrared (FT-NIR) spectroscopy in transmission and reflectance modes for the quality control of margarine. We also carried out a systematic comparison of various modeling techniques such as PLS regression, principal component regression (PCR) and support vector machines (SVM). Moreover, three types of cross-validation, three types of variable selection and the effect of different spectral types (transmission and reflectance) were also compared with factorial ANOVA tests. We examined the effect of the applied datasets (calibration, test samples, and both sets) based on the original predicted values. Sum of ranking differences (SRD), a novel comparison tool, was applied for the task. We showed that the SRD values can be used as a promising and useful performance parameter for the ranking and evaluation of numerous regression models. Four datasets with 42–42 transmission and 34–34 reflectance models were used for the evaluations. Finally, we have found the best models in each case based on their SRD values. The properly validated SVM models proved to be the best for all of the four used datasets. Although the method comparison is data set dependent, the suggested methodology is applicable generally and unambiguously. These final models can be used for fast and easy quality control of margarine samples instead of the time-consuming original analytical techniques.
Monoclonal antibody sequence assessment using a hybrid quadrupole-Orbitrap mass spectrometer by Amy Farrell; Sara Carillo; Kai Scheffler; Ken Cook; Jonathan Bones (3100-3109).
Primary sequence determination is a key component in the development and characterisation of biotherapeutic drug substances. Although frequently performed using peptide mapping experiments, complementary methods are necessary to confirm full sequence identification. The requirement for a multi-faceted approach to sequence verification, ensuring single amino acid variations in the primary sequence are not overlooked, is highlighted in the data presented herein. A combination of liquid chromatography-mass spectrometry (LC-MS) strategies, including bottom-up peptide mapping, middle-up mass analysis of monoclonal antibody (mAb) IdeS digested subunits and intact protein analysis, were used to assess primary sequence for anti-interleukin 8 IgG1, a recombinantly expressed mAb from Chinese hamster ovary cells. This structured approach to primary sequence evaluation provides a framework for the evaluation of mAbs and biosimilar candidates and accentuates the importance of incorporating multiple analytical methods for therapeutic protein characterisation.
Back cover (3111-3112).