This review summarizes progress in the field of near-infrared (NIR) fluorophores achieved during the last decade from the viewpoint of chemistry. Those compounds are of wide interest in bioanalysis ...and bioimaging, such as in vivo fluorescence imaging. Particular focus is placed on the recent developments of BODIPY and rhodamine derivatives, which belong to the most evolved NIR fluorophores. The data compiled in this review, including the chemical structures and optical properties of all compounds introduced, provide readers of this article with an overview of the field of NIR fluorophores.
Rapid, precise, and reproducible deposition of a broad variety of functional materials, including analytical assay reagents and biomolecules, has made inkjet printing an effective tool for the ...fabrication of microanalytical devices. A ubiquitous office device as simple as a standard desktop printer with its multiple ink cartridges can be used for this purpose. This Review discusses the combination of inkjet printing technology with paper as a printing substrate for the fabrication of microfluidic paper‐based analytical devices (μPADs), which have developed into a fast‐growing new field in analytical chemistry. After introducing the fundamentals of μPADs and inkjet printing, it touches on topics such as the microfluidic patterning of paper, tailored arrangement of materials, and functionalities achievable exclusively by the inkjet deposition of analytical assay components, before concluding with an outlook on future perspectives.
Just inkjet it: Inkjet printing plays an important role as a process technology in the fast‐growing field of microfluidic devices made of paper. This Review introduces the basics, strengths, and weaknesses related to the inkjet printing of functional materials essential for paper‐based analytical devices. The discussion includes fundamental aspects as well as examples of analytical applications.
This paper presents an inkjet printing method for the fabrication of entire microfluidic multianalyte chemical sensing devices made from paper suitable for quantitative analysis, requiring only a ...single printing apparatus. An inkjet printing device is used for the fabrication of three-dimensional hydrophilic microfluidic patterns (550-μm-wide flow channels) and sensing areas (1.5 mm × 1.5 mm squares) on filter paper, by inkjet etching, and thereby locally dissolving a hydrophobic poly(styrene) layer obtained by soaking of the filter paper in a 1 wt % solution of poly(styrene) in toluene. In a second step, the same inkjet printing device is used to print “chemical sensing inks”, comprising the necessary reagents for colorimetric analytical assays, into well-defined areas of the patterned microfluidic paper devices. The arrangement of the patterns, printed inks, and sensing areas was optimized to obtain homogeneous color responses. The results are “all-inkjet-printed” chemical sensing devices for the simultaneous determination of pH, total protein, and glucose in clinically relevant concentration ranges for urine analysis (0.46−46 μM for human serum albumin, 2.8−28.0 mM for glucose, and pH 5−9). Quantitative data are obtained by digital color analysis in the L*a*b* color space by means of a color scanner and a simple computer program.
This paper describes a colorimetric sensor array for the discrimination of volatile amines. Analyte discrimination is achieved by combining two functional elements: (1) a “chemical class-selective” ...single chromogenic sensing dye with selectivity for amines in general, encapsulated into (2) polymer nanoparticles with different polarities. The resulting array has the ability to distinguish one closely related amine from another, relying on a polarity-based approach. In order to achieve reproducible, cost efficient, and flexible sensor array fabrication with the potential for mass production, inkjet-printing technology combined with standard copy paper as a sensor substrate is applied. Printing of 6 types of inks, which are prepared by mixing two dye encapsulating nanoparticles of different polarity in different mixture ratios, results in a colorimetric sensor array with a polarity gradient. Seven primary amines with increasing alkyl chain lengths have been selected to demonstrate the performance of the sensor array. The RGB color differences (ΔR, ΔG, ΔB) of the sensor array spots before and after gas exposure were analyzed by principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) analysis. Under the selected measurement conditions, results of PCA and AHC analysis indicated high discrimination ability with high reproducibility of the sensor array down to amine concentrations of 50 ppm. The discrimination ability was maintained at relative humidities between 10% and 80%. Furthermore, the sensor array showed no significant response to common volatile organic compounds, confirming the high selectivity toward amines. This is, to the best of our knowledge, the first report of a colorimetric sensor array with selectivity for a specific chemical class of analytes and the ability to discriminate compounds of the same class, which is obtained by simply mixing two types of single dye-encapsulating polymer nanoparticles.
This work reports on fully integrated “sample‐in‐signal‐out” microfluidic paper‐based analytical devices (μPADs) relying on bioluminescence resonance energy transfer (BRET) switches for analyte ...recognition and colorimetric signal generation. The devices use BRET‐based antibody sensing proteins integrated into vertically assembled layers of functionalized paper, and their design enables sample volume‐independent and fully reagent‐free operation, including on‐device blood plasma separation. User operation is limited to the application of a single drop (20–30 μL) of sample (serum, whole blood) and the acquisition of a photograph 20 min after sample introduction, with no requirement for precise pipetting, liquid handling, or analytical equipment except for a camera. Simultaneous detection of three different antibodies (anti‐HIV1, anti‐HA, and anti‐DEN1) in whole blood was achieved. Given its simplicity, this type of device is ideally suited for user‐friendly point‐of‐care testing in low‐resource environments.
A single drop of blood on paper: Bioluminescent sensing proteins integrated into a multi‐layer paper‐based device allow the user‐friendly and simple quantification of monoclonal antibodies from a single drop of blood by simple color change monitoring.
The newly synthesized Keio Fluors, which are based on boron-dipyrromethene (BDP), have excellent and useful optical properties: vivid colors and sharp emission in the visible−near-infrared region ...(583−738 nm), high quantum yields (Φ: 0.56−0.98), high extinction coefficients (185000−288000 M-1 cm-1), and good photostabilities. These optical properties are superior to many of the existing fluorescent dyes such as rhodamines, cyanines, or other BDP-based fluorescent dyes.
This paper describes a new method for the fabrication of microfluidic paper-based analytical devices ( mu PADs) by inkjet printing alone. Microfluidic structures are patterned within less than 5 min ...on the surface of untreated filter paper by printing a hydrophobic UV curable acrylate composition made of non-volatile and not readily flammable compounds. After ink penetration into the paper and UV curing for 60 s, hydrophobic barriers are formed. Microfluidic channels as narrow as 272 plus or minus 19 mu m are achieved. Printed patterns retain their aqueous liquid guiding functionality for at least 6 months when stored at room temperature and for at least 72 h at 50 degree C. Printing a thin uniform film on the top of the paper allows the creation of protective layers, resulting in "tunnel-like" sections of microfluidic channels entirely surrounded by inkjet printed hydrophobic barriers. Finally, the same inkjet printer is used to print reagents necessary for colorimetric sensing, which is demonstrated in the example of an enzymatic H sub(2)O sub(2) sensor. The detection limit of the mu PAD for aqueous H sub(2)O sub(2) is 14.4 mu M when applying colorimetric data processing. The only equipment required for the entire mu PAD fabrication process is an off-the-shelf inkjet printer and a UV light source. This is the first application of standard printing technology for the fully integrated fabrication (microfluidic pattern, back cover, variable pattern depth, enclosed microfluidic structures, biosensor) of entire mu PADs.
“Distance-based” detection motifs on microfluidic paper-based analytical devices (μPADs) allow quantitative analysis without using signal readout instruments in a similar manner to classical analogue ...thermometers. To realize a cost-effective and calibration-free distance-based assay of lactoferrin in human tear fluid on a μPAD not relying on antibodies or enzymes, we investigated the fluidic mobilities of the target protein and Tb3+ cations used as the fluorescent detection reagent on surface-modified cellulosic filter papers. Chromatographic elution experiments in a tear-like sample matrix containing electrolytes and proteins revealed a collapse of attractive electrostatic interactions between lactoferrin or Tb3+ and the cellulosic substrate, which was overcome by the modification of the paper surface with the sulfated polysaccharide ι-carrageenan. The resulting μPAD based on the fluorescence emission distance successfully analyzed 0–4 mg mL–1 of lactoferrin in complex human tear matrix with a lower limit of detection of 0.1 mg mL–1 by simple visual inspection. Assay results of 18 human tear samples including ocular disease patients and healthy volunteers showed good correlation to the reference ELISA method with a slope of 0.997 and a regression coefficient of 0.948. The distance-based quantitative signal and the good batch-to-batch fabrication reproducibility relying on printing methods enable quantitative analysis by simply reading out “concentration scale marks” printed on the μPAD without performing any calibration and using any signal readout instrument.
Although microfluidic paper-based analytical devices (μPADs) get a lot of attention in the scientific literature, they rarely reach the level of commercialization. One possible reason for this is a ...lack of application of machine learning techniques supporting the design, optimization and fabrication of such devices. This work demonstrates the potential of two chemometric techniques including design of experiments (DoE) and digital image processing to support the production of μPADs. On the example of a simple colorimetric assay for isoniazid relying on the protonation equilibrium of methyl orange, the experimental conditions were optimized using a D-optimal design (DO) and the impact of multiple factors on the μPAD response was investigated. In addition, this work demonstrates the impact of automatic image processing on accelerating color value analysis and on minimizing errors caused by manual detection area selection. The employed algorithm is based on morphological recognition and allows the analysis of RGB (red, green, and blue) values in a repeatable way. In our belief, DoE and digital image processing methodologies are keys to overcome some of the remaining weaknesses in μPAD development to facilitate their future market entry.
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•Optimization of device geometry and amount of assay reagent using D-optimal design.•Investigation of seven factors at three levels by only performing 44 trials.•MATLAB-based morphological recognition algorithm for signal readout.
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