PMMA/paper hybrid microfluidic chip for simultaneous determination of arginine and valine in human plasma.

The simultaneous determination is reported of arginine (Arg) and valine (Val) amino acids in plasma using flower-shaped µPADs and PMMA/paper hybrid microfluidic chip based on AuNPs capped with R-thiazolidine-4-carboxylic acid (THP). In this article, the evaluation procedure is based on the smartphone colorimetric detection mechanism that results from the aggregation of the THP-AuNPs with the addition of amino acids and visual color change from red to blue. Arg and Val were selectively determined with good reproducibility and an acceptable linearity range. The flower-shaped (µPADs) provides many advantages, including low cost, reasonable sensitivity, simple and fast performance, simultaneous detection, disposable use, and high sample throughput compared with conventional colorimetric method using cuvette cells. The ratios between the absorbance wavelength at (A650/A525) and (A685/A525) are linearly proportional to the concentration of Arg and Val. Under the optimum conditions, the calibration range in aqueous solutions is 0.0068-100.0 and 0.0056-75.0 µM with a limit of detection of 2.25 and 1.86 nM for Arg and Val at pH 7.0, respectively. In the case of µPADs, the calibration curves for Arg and Val showed good linearity in the concentration range 0.01-75.0 µM. The detection limits for the analytes were 3.51 nM and 3.44 nM for Arg and Val, respectively. In addition, a PMMA/paper hybrid microfluidic chip was successfully employed to determine Arg and Val in plasma samples with a relative error below 5%.

Smartphone-based microfluidic chip modified using pyrrolidine-1-dithiocarboxylic acid for simultaneous colorimetric determination of Cr3+ and Al3+ ions.

A portable µ-chip-based colorimetric device was developed for the determination of Cr3+ and Al3+ ions. The silver nanoparticles were modified with pyrrolidine-1-dithiocarboxylic acid ammonium salt as a novel ligand for the first time. The color of modified AgNPs in the test zone immediately changes after the addition of Cr3+ and Al3+ ions. The resulting color changes were detected by the naked eye or were taken by a smartphone camera. The obtained images were analyzed by RGB software to assay the Cr3+ and Al3+ ions concentration. Under optimized experimental conditions, the linear ranges are 0.1-220 and 0.01-250 µM for Cr3+ and Al3+ ions, respectively. The probe has a limit of detections of 10.66 and 3.55 nM for Cr3+ and Al3+ in an aqueous solution. In the case of µ-chip, the concentration ranges are 0.1-200 µM and 0.01-220 µM for Cr3+ and Al3+ ions, with detection limits of 9.18 and 2.30 nM, respectively. The µ-chip showed great potential as a fast detection tool for the monitoring of Cr3+ and Al3+ ions in real samples such as river water samples.

The colorimetric and microfluidic paper-based detection of cysteine and homocysteine using 1,5-diphenylcarbazide-capped silver nanoparticles.

We have prepared a microfluidic paper-based analytical device (µPAD) for the determination of cysteine and homocysteine based on 1,5-diphenylcarbazide-capped silver nanoparticles. The µPAD was developed to identify and quantify the levels of cysteine and homocysteine. The proposed µPAD enabled the detection of cysteine and homocysteine using a colorimetric reaction based on modified silver nanoparticles. The color of the modified AgNPs in the test zone immediately changed after the addition of cysteine and homocysteine. Based on this change, the quantification of these two amino acids was achieved using an RGB color model and ImageJ software. Under optimized conditions, the proposed device enabled the determination of cysteine in the 0.20-20.0 µM concentration range with a limit of detection (LOD) of 0.16 µM. In addition, the LOD of homocysteine was calculated to be 0.25 µM with a linear range of 0.50-20.0 µM. In this work, we focused on the use of the µPAD for the analysis of a series of human urine samples.

A nanocellulose-based colorimetric assay kit for smartphone sensing of iron and iron-chelating deferoxamine drug in biofluids.

The current work describes the development of a "nanopaper-based analytical device (NAD)", through the embedding of curcumin in transparent bacterial cellulose (BC) nanopaper, as a colorimetric assay kit for monitoring of iron and deferoxamine (DFO) as iron-chelating drug in biological fluids such as serum blood, urine and saliva. The iron sensing strategy using the developed assay kit is based on the decrease of the absorbance/color intensity of curcumin-embedded in BC nanopaper (CEBC) in the presence of Fe(III), due to the formation of Fe(III)-curcumin complex. On the other hand, releasing of Fe(III) from Fe(III)-CEBC upon addition of DFO as an iron-chelating drug, due to the high affinity of this drug to Fe(III) in competition with curcumin, which leads to recovery of the decreased absorption/color intensity of Fe(III)-CEBC, is utilized for selective colorimetric monitoring of this drug. The absorption/color changes of the fabricated assay kit as output signal can be monitored by smartphone camera or by using a spectrophotometer. The results of our developed sensor agreed well with the results from a clinical reference method for determination of Fe(III) concentration in human serum blood samples, which revealed the clinical applicability of our developed assay kit. Taken together, regarding the advantageous features of the developed sensor as an easy-to-use, non-toxic, disposable, cost-effective and portable assay kit, along with those of smartphone-based sensing, it is anticipated that this sensing bioplatform, which we name lab-on-nanopaper, will find utility for sensitive, selective and easy diagnosis of iron-related diseases (iron deficiency and iron overload) and therapeutic drug monitoring (TDM) of iron-chelating drugs in clinical analysis as well.

Spectrophotometric and visual determination of zoledronic acid by using a bacterial cell-derived nanopaper doped with curcumin.

A nanopaper-based analytical device (NAD) is described for a colorimetric metal-complexing indicator-displacement assay (M-IDA) for zoledronic acid (ZA). Bacterial cellulose nanopaper was doped with curcumin to obtain a chemosensor on which hydrophilic test zones were patterned via laser printing of hydrophobic walls. The color intensity of the test zones decreases in the presence of Fe(III) due to the formation of Fe(III)-curcumin complex. However, upon addition of ZA, Fe(III) ions preferably binds ZA. Subsequently, the color of the zone changes from light yellow to dark yellow. The changes in the absorption (measured at 427 nm) and of the color of the test stripe can be monitored visually, by using a digital camera, or by a spectrophotometer. Under optimal conditions, the analytical signals increase linearly in the 0.01-100 µM ZA concentration range, and the detection limits are 8.8 and 8.0 nM for smartphone and spectrophotometer-based methods, respectively. The method was employed to the determination of ZA in (spiked) urine, serum, saliva, and in pharmaceutical samples. Graphical abstract Schematic representation of a nanopaper-based analytical device based on curcumin-doped BC nanopaper (CDBC) integrated with smartphone for metal-complexing indicator-displacement assay of zoledronic acid (ZA). High affinity of ZA to Fe(III) on the NAD/CDBC leads to color change.

A paper-based optical probe for chromium by using gold nanoparticles modified with 2,2'-thiodiacetic acid and smartphone camera readout.

A paper based analytical device is presented for the determination of Cr(III) and Cr(VI) using gold nanoparticles (AuNPs) modified with 2,2'-thiodiacetic acid. The modified AuNPs were characterized using UV-Vis spectrophotometry, Fourier transform infrared, dynamic light scattering, zeta potential, energy dispersive spectroscopy and transmission electron microscopy. Cr(III) ions induce the aggregation of the modified AuNPs, and the color of the nanoprobe changes from red to blue. This can be detected visually, or by colorimetry, or with a camera. No interference is observed in the presence of 19 other cations and anions. Cr(VI) (chromate) can be determined by after reduction to Cr(III) by using ascorbic acid and then quantified total Cr(III). The concentration of Cr(VI) is obtained by subtracting the concentration of Cr(III) from that of total chromium. Under optimal conditions, the ratio of the absorbances measured at 670 (blue) and 522 (red) increases linearly in the 1.0 nM to 22.1 µM chromium concentration range, with 0.66 nM (0.034 ppb) limit of detection (LOD) in solution. In case of the paper device, the linear range extends from 1.0 nM to 0.1 mM, and the LOD is 0.64 nM (0.033 ppb). The method was applied to the determination of chromium in spiked water, urine and dilutes human plasma, and results were confirmed by GF-AAS analysis. This method is highly selective, fast and portable, requires minimum volume of reagents and samples and no washing steps. Graphical abstract A paper based analytical device is presented for determination of Cr(III) and Cr(VI) using gold nanoparticles modified with 2,2'-thiodiacetic acid. In paper optical probe, linear range and limit of detection are 1.0 nM to 0.1 mM and 0.64 nM, respectively. The method was applied to the determination of total chromium in spiked water, urine and dilutes human plasma, and results were confirmed by GF-AAS analysis.

Toxic compounds from tobacco in placenta samples analyzed by UPLC-QTOF-MS.

Polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs) and aromatic amines are carcinogens present in cigarette smoke. These compounds are distributed in the human body and they could be transferred to the foetus during the pregnancy. Placenta is the main barrier to these toxic compounds and its study is the objective of this work. A method based on solid-phase extraction (SPE) with ultra-performance liquid chromatography-tandem quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) has been examined and optimized for the analysis of 9 target analytes (4 tobacco-specific nitrosamines and some of their metabolites, 3 aromatic amines, nicotine and cotinine) in 26 placenta samples from smoking and non-smoking women. Limits of detection (LODs) were in the range of 3-27ng/g of placenta. Nicotine, cotinine, N-nitrosoanatabine (NAT) and 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK) metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were detected in the placenta samples of smoking woman. Nicotine was detected in 3 out of 8 placentas from smoking women, always below the limit of quantification (88ng/g). This could be expected, as the half-life of nicotine in the body is limited to about 0.5-3h. Cotinine, the main metabolite from nicotine, was detected in all placentas from smoking women at concentrations between 17.2 and 61.8ng/g, reaching the highest values for those women that smoked the highest number of cigarettes. NAT and NNAL were detected in all placentas from smoking women, always below the limit of quantification (40ng/g and 33ng/g respectively).

Colorimetric detection of biothiols based on aggregation of chitosan-stabilized silver nanoparticles.

We have described a simple and reliable colorimetric method for the sensing of biothiols such as cysteine, homocysteine, and glutathione in biological samples. The selective binding of chitosan capped silver nanoparticles to biothiols induced aggregation of the chitosan-Ag NPs. But the other amino acids that do not have thiol group cannot aggregate the chitosan-Ag NPs. Aggregation of chitosan-Ag NPs has been confirmed with UV-vis absorption spectra, zeta potential and transmission electron microscopy images. Under optimum conditions, good linear relationships existed between the absorption ratios (at A500/A415) and the concentrations of cysteine, homocysteine, and glutathione in the range of 0.1-10.0µM with detection limits of 15.0, 84.6 and 40.0nM, respectively. This probe was successfully applied to detect these biothiols in biological samples (urine and plasma).

Colorimetric detection of Bi (III) in water and drug samples using pyridine-2,6-dicarboxylic acid modified silver nanoparticles.

A new selective, simple, fast and sensitive method is developed for sensing assay of Bi (III) using pyridine-2,6-dicarboxylic acid or dipicolinic acid (DPA) modified silver nanoparticles (DPA-AgNPs). Silver nanoparticles (AgNPs) were synthesized by reducing silver nitrate (AgNO3) with sodium borohydride (NaBH4) in the presence of DPA. Bismuth detection is based on color change of nanoparticle solution from yellow to red that is induced in the presence of Bi (III). Aggregation of DPA-AgNPs has been confirmed with UV-vis absorption spectra and transmission electron microscopy (TEM) images. Under the optimized conditions, a good linear relationship (correlation coefficient r=0.995) is obtained between the absorbance ratio (A525/A390) and the concentration of Bi (III) in the 0.40-8.00 µM range. This colorimetric probe allows Bi (III) to be rapidly quantified with a 0.01 µM limit of detection. The present method successfully applied to determine bismuth in real water and drug samples. Recoveries of water samples were in the range of 91.2-99.6%.

Continuous sample drop flow-based microextraction method as a microextraction technique for determination of organic compounds in water sample.

Continuous sample drop flow-based microextraction (CSDF-ME) is an improved version of continuous-flow microextraction (CFME) and a novel technique developed for extraction and preconcentration of benzene, toluene, ethyl benzene, m-xylene and o-xylene (BTEXs) from aqueous samples prior to gas chromatography-flame ionization detection (GC-FID). In this technique, a small amount (a few microliters) of organic solvent is transferred to the bottom of a conical bottom test tube and a few mL of aqueous solution is moved through the organic solvent at relatively slow flow rate. The aqueous solution transforms into fine droplets while passing through the organic solvent. After extraction, the enriched analyte in the extraction solvent is determined by GC-FID. The type of extraction solvent, its volume, needle diameter, and aqueous sample flow rate were investigated. The enrichment factor was 221-269 under optimum conditions and the recovery was 89-102%. The linear ranges and limits of detection for BTEXs were 2-500 and 1.4-3.1 µg L(-1), respectively. The relative standard deviations for 10 µg L(-1) of BTEXs in water were 1.8-6.2% (n=5). The advantages of CSDF-ME are its low cost, relatively short sample preparation time, low solvent consumption, high recovery, and high enrichment factor.