Recent advances in engineering microparticles and their nascent utilization in biomedical delivery and diagnostic applications

Lab Chip, 2017, Advance ArticleDOI: 10.1039/C6LC01023G, Critical ReviewAndrew Choi, Kyoung Duck Seo, Do Wan Kim, Bum Chang Kim, Dong Sung KimEngineered microparticles fabricated through recently developed methods for biomedical applications.To cite thi…



Reproducible in vitro model for dystrophic calcification of cardiac valvular interstitial cells: Insights into the mechanisms Calcific Aortic Valvular Disease

Lab Chip, 2017, Accepted ManuscriptDOI: 10.1039/C6LC01226D, PaperHeather Ann Cirka, Johana Uribe, Vivian Liang, Frederick J Schoen, Kristen BilliarCalcific aortic valvular disease (CAVD) is the most prevalent valvular pathology in the United States. De…



Versatile tissue lasers based on high-Q Fabry-Perot microcavities

Lab Chip, 2017, Advance ArticleDOI: 10.1039/C6LC01457G, PaperYu-Cheng Chen, Qiushu Chen, Tingting Zhang, Wenjie Wang, Xudong FanHighly versatile tissue laser platform.To cite this article before page numbers are assigned, use the DOI form of citation a…



Simultaneous determination of multiple bioactive components of Bu-zhong-yi-qi-tang in rat tissues by LC–MS/MS: Application to a tissue distribution study

Publication date: Available online 18 January 2017
Source:Journal of Chromatography B
Author(s): Min He, Wenwen Chen, Mengmeng Wang, Yu Wu, Jin Zeng, Zhirong Zhang, Shujiao Shen, Jian Jiang
A liquid chromatography coupled with electrospray ionization mass spectrometry method was developed and validated for simultaneous determination of seven bioactive constituents including astragaloside IV, calycosin, glycyrrhizic acid, enoxolone, saikosaponin D, ferulic acid and hesperiden in rats’ various tissues using diclofenac as the internal standard (IS). Biological samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid and 4mM ammonium acetate). All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. The mass transitions were as follows: m/z 829.7→783.3 for astragaloside IV, m/z 283.3→267.7 for calycosin, m/z 821.6→350.0 for glycyrrhizic acid, m/z 469.9→425.2 for enoxolone, m/z 825.7→779.6 for saikosaponin D, m/z 192.5→133.9 for ferulic acid, m/z 609.1→301.0 for hesperiden and m/z 293.6→249.9 for the IS, respectively. The lower limits of quantification for the seven analytes in different rat tissues were 0.2–20ng/mL. Bu-zhong-yi-qi-tang (Hochuekkito in Japan, Bojungikki-tang in Korea) is one of the most frequently prescribed traditional herbal formulas used in Korea, Japan, and China to treat gastrointestinal diseases, cancer and chronic fatigue syndrome. The validated method was successfully applied to a tissue distribution study of the seven components in rat tissue after oral administration of Bu-zhong-yi-qi-tang concentrated granule. The results of the tissue distribution study showed that the high concentration of seven components were mainly in the gastrointestinal tract.



Quantification of N-methylmalonamic acid in urine as metabolite of the biocides methylisothiazolinone and chloromethylisothiazolinone using gaschromatography-tandem mass spectrometry

Publication date: Available online 18 January 2017
Source:Journal of Chromatography B
Author(s): T. Schettgen, J. Bertram, T. Kraus
Methylisothiazolinone and the mixture of chloromethylisothiazolinone/methylisothiazolinone (MCI/MI, 3:1) are widespread biocides used in cosmetic and household products. Due to their skin permeability, they might be taken up by the general population via use of products containing these biocides. As both compounds are known skin sensitizers, the use of these products is under discussion by regulatory agencies.In order to evaluate the possible uptake of MI and/or MCI/MI by human biomonitoring, we have developed and validated a highly sensitive and specific GC/MS/MS-method for the quantification of N-methylmalonamic acid (NMMA), a known metabolite of MI and MCI in urine of rats. After freeze-drying of urine, the analyte is derivatised with pentafluorobenzyl bromide in anhydrous solution and the PFB-derivative is extracted into n-hexane. After concentration, the derivative is finally quantified by GC/MS/MS in EI-mode using 13C3-NMMA as internal standard. The limit of quantification for NMMA was 0.5ngmL−1 urine. Precision within and between-series was determined to range between 3.7 − 10.9% using native and spiked quality control samples. Accuracy ranged between 89–114%.In a pilot study we applied this method to spot urine samples of 63 persons not knowingly exposed to MI and/or MCI/MI. NMMA was quantifiable in every urine sample analysed, with no significant difference in urinary levels between male and female participants. The median (95th percentile) levels for urinary NMMA were 3.6 (7.4) ng mg−1 creatinine and 2.9 (9.1) ng mg−1 creatinine for males (n=32) and females (n=31), respectively. In a volunteer experiment, a relation of exposure to MI and/or MCI/MI and subsequent NMMA-excretion was shown. Our method is the first to report human urinary background levels of NMMA. However, the possibility of formation and urinary excretion of NMMA within physiological processes cannot be ruled out.



Towards ideal separation by size-exclusion chromatography

Publication date: Available online 19 January 2017
Source:Journal of Chromatography A
Author(s): Miloš Netopilík
In analyses of polystyrene standards by size exclusion chromatography for polymers of molecular weight about thirty thousand and higher, the separation improved with decreasing flow-rate is in accord with Giddings observation of transversal diffusion as a factor decreasing the broadening of the band broadening function. The variance of the elution curves is larger than it corresponds to dispersity M¯w/M¯n and the shape of the elution curves depends on the experimental conditions which suggests that it reflects properties of the band broadening function. The skew and the excess kurtosis of the elution curves increases near the exclusion limit in accord with theoretical prediction for the band broadening function.



Plasmon-induced photoelectrochemical biosensor for in situ real-time measurement of biotin-streptavidin binding kinetics under visible light irradiation

Publication date: 8 March 2017 Source:Analytica Chimica Acta, Volume 957 Author(s): Jingchun Guo, Tomoya Oshikiri, Kosei Ueno, Xu Shi, Hiroaki Misawa We developed a localized surface plasmon-induced visible light-responsive p…



One-step synthesis of DNA functionalized cadmium-free quantum dots and its application in FRET-based protein sensing

Publication date: 8 March 2017 Source:Analytica Chimica Acta, Volume 957 Author(s): Cuiling Zhang, Caiping Ding, Guohua Zhou, Qin Xue, Yuezhong Xian DNA functionalized quantum dots (QDs) are promising nanoprobes for the fluor…



A label-free colorimetric isothermal cascade amplification for the detection of disease-related nucleic acids based on double-hairpin molecular beacon

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Dong Wu, Huo Xu, Haimei Shi, Weihong Li, Mengze Sun, Zai-Sheng Wu
K-Ras mutations at codon 12 play an important role in an early step of carcinogenesis. Here, a label-free colorimetric isothermal cascade amplification for ultrasensitive and specific detection of K-Ras point mutation is developed based on a double-hairpin molecular beacon (DHMB). The biosensor consists of DHMB probe and a primer-incorporated polymerization template (PPT) designed partly complementary to DHMB. In the presence of polymerase, target DNA is designed to trigger strand displacement amplification (SDA) via promote the hybridization of PPT with DHMB and subsequently initiates cascade amplification process with the help of the nicking endonuclease. During the hybridization and enzymatic reaction, G-quadruplex/hemin DNAzymes are generated, catalyzing the oxidation of ABTS2− by H2O2 in the presence of hemin. Utilizing the proposed facile colorimetric scheme, the target DNA can be quantified down to 4 pM with the dynamic response range of 5 orders of magnitude, indicating the substantially improved detection capability. Even more strikingly, point mutation in K-ras gene can be readily observed by the naked eye without the need for the labeling or expensive equipment. Given the high-performance for K-Ras analysis, the enhanced signal transduction capability associated with double-hairpin structure of DHMB provides a novel rout to screen biomarkers, and the descripted colorimetric biosensor seems to hold great promise for diagnostic applications of genetic diseases.

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Water can be a probe for sensing glucose in aqueous solutions by temperature dependent near infrared spectra

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Xiaoyu Cui, Xiuwei Liu, Xiaoming Yu, Wensheng Cai, Xueguang Shao
Near infrared (NIR) spectra are sensitive to the variation on water structure caused by perturbations, such as temperature and additives. In this work, water was applied as a probe to detect glucose in aqueous glucose solutions and human serum samples. Spectral changes of water were captured from the temperature dependent NIR spectra using multilevel simultaneous component analysis (MSCA). The first and second level model were established to describe the quantitative spectra–temperature relationship (QSTR) and the quantitative spectra–concentration relationship (QSCR), i.e., the calibration curve, respectively. The score of the first level model shows that the content of free OH in water molecules increases with temperature elevation. The correlation coefficients (R2) of the QSTR model between the score and temperature are higher than 0.99, and that of the calibration model (QSCR) between the spectral features of water clusters and the concentration of glucose are 0.99 and 0.84 for glucose solutions and serum samples, respectively. External validation of the calibration model was further performed with human serum samples. The standard error of the prediction is 0.45. In addition, the linearity of the QSCR models may reveal that glucose interacts with small water clusters and enhances the formation of the hydration shell. Therefore, using water as a probe may provide a new way for quantitative determination of the analytes in aqueous solutions by NIR spectroscopy.

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Editorial board

Publication date: 8 March 2017 Source:Analytica Chimica Acta, Volume 957



A simple method to produce 2D and 3D microfluidic paper-based analytical devices for clinical analysis

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Ricardo A.G. de Oliveira, Fiamma Camargo, Naira C. Pesquero, Ronaldo Censi Faria
This paper describes the fabrication of 2D and 3D microfluidic paper-based analytical devices (μPADs) for monitoring glucose, total protein, and nitrite in blood serum and artificial urine. A new method of cutting and sealing filter paper to construct μPADs was demonstrated. Using an inexpensive home cutter printer soft cellulose-based filter paper was easily and precisely cut to produce pattern hydrophilic microchannels. 2D and 3D μPADs were designed with three detection zones each for the colorimetric detection of the analytes. A small volume of samples was added to the μPADs, which was photographed after 15 min using a digital camera. Both μPADs presented an excellent analytical performance for all analytes. The 2D device was applied in artificial urine samples and reached limits of detection (LODs) of 0.54 mM, 5.19 μM, and 2.34 μM for glucose, protein, and nitrite, respectively. The corresponding LODs of the 3D device applied for detecting the same analytes in artificial blood serum were 0.44 mM, 1.26 μM, and 4.35 μM.

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High-throughput untargeted screening of veterinary drug residues and metabolites in tilapia using high resolution orbitrap mass spectrometry

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Wei Jia, Xiaogang Chu, James Chang, Perry G. Wang, Ying Chen, Feng Zhang
An analytical method was developed and validated for simultaneous analysis of one hundred and thirty-seven veterinary drug residues and metabolites from sixteen different classes in tilapia utilizing an improved fully non-targeted way of data acquisition with fragmentation. The automated on-line extraction procedure was achieved in a simple disposable pipet extraction. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap) was used for the separation and detection of all the analytes. The methodology was validated by taking into consideration the guidelines specified in European SANCO/12571/2013 Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries ranged from 81% to 111%. The limits of decision ranged from 0.01 to 2.73 μg kg−1 and the detection capabilities ranged from 0.01 to 4.73 μg kg−1. The one hundred and thirty-seven compounds behave dynamic 0.1–500 μg kg−1, with correlation coefficient >0.99. The fully non-targeted data acquisition way improves both sensitivity and selectivity for the fragments, which is beneficial for screening performance and identification capability. This validated method has been successfully applied on screening of veterinary drug residues and metabolites in muscle of tilapia, an important and intensively produced fish in aquaculture.

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Enhanced aerodynamic reach of vapor and aerosol sampling for real-time mass spectrometric detection using Venturi-assisted entrainment and ionization

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Thomas P. Forbes, Matthew Staymates
Venturi-assisted ENTrainment and Ionization (VENTI) was developed, demonstrating efficient entrainment, collection, and transport of remotely sampled vapors, aerosols, and dust particulate for real-time mass spectrometry (MS) detection. Integrating the Venturi and Coandă effects at multiple locations generated flow and analyte transport from non-proximate locations and more importantly enhanced the aerodynamic reach at the point of collection. Transport through remote sampling probes up to 2.5 m in length was achieved with residence times on the order of 10−2 s to 10−1 s and Reynolds numbers on the order of 103 to 104. The Venturi-assisted entrainment successfully enhanced vapor collection and detection by greater than an order of magnitude at 20 cm stand-off (limit of simple suction). This enhancement is imperative, as simple suction restricts sampling to the immediate vicinity, requiring close proximity to the vapor source. In addition, the overall aerodynamic reach distance was increased by approximately 3-fold over simple suction under the investigated conditions. Enhanced aerodynamic reach was corroborated and observed with laser-light sheet flow visualization and schlieren imaging. Coupled with atmospheric pressure chemical ionization (APCI), the detection of a range of volatile chemical vapors; explosive vapors; explosive, narcotic, and mustard gas surrogate (methyl salicylate) aerosols; and explosive dust particulate was demonstrated. Continuous real-time Venturi-assisted monitoring of a large room (approximately 90 m2 area, 570 m3 volume) was demonstrated for a 60-min period without the remote sampling probe, exhibiting detection of chemical vapors and methyl salicylate at approximately 3 m stand-off distances within 2 min of exposure.

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High throughput online solid phase extraction-ultra high performance liquid chromatography-tandem mass spectrometry method for polyfluoroalkyl phosphate esters, perfluoroalkyl phosphonates, and other perfluoroalkyl substances in human serum, plasma, and whole blood

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Somrutai Poothong, Elsa Lundanes, Cathrine Thomsen, Line Småstuen Haug
A rapid, sensitive and reliable method was developed for the determination of a broad range of poly- and perfluoroalkyl substances (PFASs) in various blood matrices (serum, plasma, and whole blood), and uses only 50 μL of sample material. The method consists of a rapid protein precipitation by methanol followed by high throughput online solid phase extraction (SPE), ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), and negative electrospray ionization detection. The method was developed for simultaneous determination of twenty-five PFASs, including polyfluoroalkyl phosphate esters (PAPs; 6:2, 8:2, 6:2/6:2, and 8:2/8:2), perfluoroalkyl phosphonates (PFPAs; C6, C8, and C10), perfluoroalkyl sulfonates (PFSAs; C4, C6, C7, C8, and C10), perfluoroalkyl carboxylates (PFCAs; C5C14), and perfluoroalkyl sulfonamides (FOSAs; C8, N-methyl, and N-ethyl). High linearity of matrix-matched calibration standards (correlation coefficients, R = 0.99–0.999) were obtained in the range of 0.006–45 ng mL−1 blood. Excellent sensitivity was achieved with method detection limits (MDLs) between 0.0018 and 0.09 ng mL−1, depending on the compound and matrix. The method was validated for serum, plasma, and whole blood (n = 5 + 5) at six levels in the range 0.0180–30 ng mL−1. The accuracy (n = 5) was on average 102± 12%. The intermediate precision (n = 10) ranged from 2 to 40% with an average between-batch of analyses difference of 10± 10%. Two human serum samples from a former interlaboratory comparison were analyzed and the differences between the applied method and the consensus values were below ≤22% (n = 5). The method was also successfully applied to samples of human plasma and whole blood with coefficients of variation in the range 0.8–15.2% (n = 5).

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Dissolvable layered double hydroxide as an efficient nanosorbent for centrifugeless air-agitated dispersive solid-phase extraction of potentially toxic metal ions from bio-fluid samples

Publication date: 8 March 2017
Source:Analytica Chimica Acta, Volume 957
Author(s): Maryam Rajabi, Somayeh Arghavani-Beydokhti, Behruz Barfi, Alireza Asghari
In the present work, a novel nanosorbent namely layered double hydroxides with 4-amino-5-hydroxyl-2,7-naphthalendisulfonic acid monosodium salt interlayer anion (Mg-Al-AHNDA-LDH) was synthesized and applied as a dissolvable nanosorbent in a centrifugeless ultrasound-enhanced air-agitated dispersive solid-phase extraction (USE-AA-D-SPE) method. This method was used for the separation and preconcentration of some metal ions including Cd2+, Cr6+, Pb2+, Co2+, and Ni2+ prior to their determination using the micro-sampling flame atomic absorption spectrometry (MS-FAAS) technique. The most interesting aspect of this nanosorbent is its immediate dissolvability at pH values lower than 4. This capability drastically eliminates the elution step, leading to a great improvement in the extraction efficiency and a decrease in the extraction time. Also in this method, the use of a syringe nanofilter eliminates the need for the centrifugation step, which is time-consuming and essentially causes the analysis to be off-line. Several effective parameters governing the extraction efficiency including the sample solution pH, amount of nanosorbent, eluent condition, number of air-agitation cycles, and sonication time were investigated and optimized. Under the optimized conditions, the good linear dynamic ranges of 2–70, 6–360, 7–725, 7–370, and 8–450 ng mL−1 for the Cd2+, Cr6+, Pb2+, Co2+and Ni2+ ions, respectively, with the correlation of determinations (R2s) higher than 0.997 were obtained. The limits of detection (LODs) were found to be 0.6, 1.7, 2.0, 2.1, and 2.4 for the Cd2+, Cr6+, Pb2+, Co2+, and Ni2+ ions, respectively. The intra-day and inter-day precisions (percent relative standard deviations (%RSDs) (n = 5)) were below 7.8%. The proposed method was also successfully applied for the extraction and determination of the target ions in different biological fluid and tap water samples.

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International Interlaboratory Digital PCR Study Demonstrating High Reproducibility for the Measurement of a Rare Sequence Variant

Analytical ChemistryDOI: 10.1021/acs.analchem.6b03980



One single, fast and robust capillary electrophoresis method for the direct quantification of intact adenovirus particles in upstream and downstream processing samples

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Ewoud van Tricht, Lars Geurink, Harold Backus, Marta Germano, Govert W. Somsen, Cari E. Sänger–van de Griend
During development of adenovirus-based vaccines, samples have to be analyzed in order to either monitor the production process or control the quality and safety of the product. An important quality attribute is the total concentration of intact adenoviruses, which currently is determined by quantitative polymerase chain reaction (qPCR) or anion exchange-HPLC. Capillary Electrophoresis (CE) was evaluated as alternative to the current methods with the aim to have one single method that allows reliable and fast quantification of adenovirus particles throughout the full process. Intact adenoviruses samples from downstream processing and upstream processing were analyzed directly by CE with UV-detection at 214nm. Only the samples with high amounts of DNA required a simple sample pretreatment by benzonase. Adenovirus particles were separated from matrix components such as cell debris, residual cell DNA, and/or proteins on a PVA-coated capillary using a BGE consisting of 125mM Tris, 338mM tricine and 0.2% v/v polysorbate-20 at pH 7.7. Full factorial design of experiments was used for method optimization as part of the analytical quality by design (AQbD) method development approach. The method was validated for the quantification of adenoviruses on five representative samples from the manufacturing process in the range of 0.5×1011–1.5×1011 adenovirus particles per ml (~80 to 250pmol/l). The CE method showed intermediate precision of 7.8% RSD on concentration and an accuracy (spiked recovery) of 95–110%. CE proved highly useful for process development support and is being implemented for in-process control testing for adenovirus vaccine manufacturing.

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Spinel-type manganese ferrite (MnFe2O4) microspheres: A novel affinity probe for selective and fast enrichment of phosphopeptides

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Xing-Yu Long, Jia-Yuan Li, Dong Sheng, Hong-Zhen Lian
The spinel-type magnetic manganese ferrite (MnFe2O4) microspheres synthesized by simple solvothermal method were used as a novel adsorbent for selective enrichment and effective isolation of phosphopeptides. The uniform MnFe2O4 magnetic affinity microspheres (MAMSs) had a narrow particle size distribution between 250 and 260nm, and displayed superparamagnetism with a saturation magnetization value of 67.0emu/g. Comprehensively, the possible formation mechanism of MnFe2O4 microspheres with ferric and manganous sources as dual precursors was elucidated by comparison with those of Fe3O4 nanoparticles and MnOOH nanosheets respectively with either ferric or manganous source as single precursor. It was suggested that the spherical or sheet nanostructures could be achieved via secondary recrystallization or Ostwald ripening. The MnFe2O4 MAMSs probe exhibited excellent dispersibility in aqueous solution, and rapid magnetic separation within 15s, as well as good reusability. More importantly, MnFe2O4 was highly selective for phosphopeptides because of the strong coordination interaction between metal ions (Fe3+ and Mn2+) and phosphate groups of phosphopeptdies. This high specificity was demonstrated by effectively enriching phosphopeptides from digest mixture of β-casein and bovine serum albumin (BSA) with high content of non-phosphopeptides, and embodied further in phosphopeptides enrichment from non-fat milk digests and human serum. Consequently, the prepared MnFe2O4 affinity materials are expected to possess great potential in phosphoproteome research.

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Raman Spectroscopy Based Analysis Inside Photonic-Crystal Fibers

Publication date: Available online 17 January 2017 Source:TrAC Trends in Analytical Chemistry Author(s): Alexey V. Markin, Natalia E. Markina, Irina Yu. Goryacheva Application of photonic crystals and photonic crystal fibers (PCF…