Optical Sensing and Imaging of pH Values: Spectroscopies, Materials, and Applications.

This is the first comprehensive review on methods and materials for use in optical sensing of pH values and on applications of such sensors. The Review starts with an introduction that contains subsections on the definition of the pH value, a brief look back on optical methods for sensing of pH, on the effects of ionic strength on pH values and pKa values, on the selectivity, sensitivity, precision, dynamic ranges, and temperature dependence of such sensors. Commonly used optical sensing schemes are covered in a next main chapter, with subsections on methods based on absorptiometry, reflectometry, luminescence, refractive index, surface plasmon resonance, photonic crystals, turbidity, mechanical displacement, interferometry, and solvatochromism. This is followed by sections on absorptiometric and luminescent molecular probes for use pH in sensors. Further large sections cover polymeric hosts and supports, and methods for immobilization of indicator dyes. Further and more specific sections summarize the state of the art in materials with dual functionality (indicator and host), nanomaterials, sensors based on upconversion and 2-photon absorption, multiparameter sensors, imaging, and sensors for extreme pH values. A chapter on the many sensing formats has subsections on planar, fiber optic, evanescent wave, refractive index, surface plasmon resonance and holography based sensor designs, and on distributed sensing. Another section summarizes selected applications in areas, such as medicine, biology, oceanography, bioprocess monitoring, corrosion studies, on the use of pH sensors as transducers in biosensors and chemical sensors, and their integration into flow-injection analyzers, microfluidic devices, and lab-on-a-chip systems. An extra section is devoted to current challenges, with subsections on challenges of general nature and those of specific nature. A concluding section gives an outlook on potential future trends and perspectives.

A MXene-Based Wearable Biosensor System for High-Performance In Vitro Perspiration Analysis.

Wearable electrochemical biosensors for sweat analysis present a promising means for noninvasive biomarker monitoring. However, sweat-based sensing still poses several challenges, including easy degradation of enzymes and biomaterials with repeated testing, limited detection range and sensitivity of enzyme-based biosensors caused by oxygen deficiency in sweat, and poor shelf life of sensors using all-in-one working electrodes patterned by traditional techniques (e.g., electrodeposition and screen printing). Herein, a stretchable, wearable, and modular multifunctional biosensor is developed, incorporating a novel MXene/Prussian blue (Ti3 C2 Tx /PB) composite designed for durable and sensitive detection of biomarkers (e.g., glucose and lactate) in sweat. A unique modular design enables a simple exchange of the specific sensing electrode to target the desired analytes. Furthermore, an implemented solid-liquid-air three-phase interface design leads to superior sensor performance and stability. Typical electrochemical sensitivities of 35.3 µA mm-1 cm-2 for glucose and 11.4 µA mm-1 cm-2 for lactate are achieved using artificial sweat. During in vitro perspiration monitoring of human subjects, the physiochemistry signals (glucose and lactate level) can be measured simultaneously with high sensitivity and good repeatability. This approach represents an important step toward the realization of ultrasensitive enzymatic wearable biosensors for personalized health monitoring.

Expression of Concern: Magnetic mesoporous polymelamine-formaldehyde resin as an adsorbent for endocrine disrupting chemicals.

The Editor-in-Chief is issuing an editorial expression of concern regarding the article Microchim Acta (2018) 185: 19.

Luminescent sensing and imaging of oxygen: fierce competition to the Clark electrode.

Luminescence-based sensing schemes for oxygen have experienced a fast growth and are in the process of replacing the Clark electrode in many fields. Unlike electrodes, sensing is not limited to point measurements via fiber optic microsensors, but includes additional features such as planar sensing, imaging, and intracellular assays using nanosized sensor particles. In this essay, I review and discuss the essentials of (i) common solid-state sensor approaches based on the use of luminescent indicator dyes and host polymers; (ii) fiber optic and planar sensing schemes; (iii) nanoparticle-based intracellular sensing; and (iv) common spectroscopies. Optical sensors are also capable of multiple simultaneous sensing (such as O2 and temperature). Sensors for O2 are produced nowadays in large quantities in industry. Fields of application include sensing of O2 in plant and animal physiology, in clinical chemistry, in marine sciences, in the chemical industry and in process biotechnology.

Enzyme-Based Test Strips for Visual or Photographic Detection and Quantitation of Gaseous Sulfur Mustard.

Sulfur mustard is a chemical agent of high military and terroristic significance. No effective antidote exists, and sulfur mustard can be fairly easily produced in large quantity. Rapid field testing of sulfur mustard is highly desirable. Existing analytical devices for its detection are available but can suffer from low selectivity, laborious sample preparation, and/or the need for complex instrumentation. We describe a new kind of test strip for rapid detection of gaseous sulfur mustard that is based on its degradation by the enzyme haloalkane dehalogenase that is accompanied by a change of local pH. This change can be detected using pH indicators contained in the strips whose color changes from blue-green to yellow within 10 min. In addition to visual read-out, we also demonstrate quantitative reflectometric readout by using a conventional digital camera based on red-green-blue data acquisition. Organic haloalkanes, such as 1,2-dichloroethane, have a negligible interfering effect. The visual limit of detection is 20 µg/L, and the one for red-green-blue read-out is as low as 3 µg/L. The assays have good reproducibility ±6% and ±2% for interday assays and intraday assays, respectively. The strips can be stored for at least 6 months without loss of function. They are disposable and can be produced fairly rapidly and at low costs. Hence, they represent a promising tool for in-field detection of sulfur mustard.

An overview of nanoparticles commonly used in fluorescent bioimaging.

This article gives an overview of the various kinds of nanoparticles (NPs) that are widely used for purposes of fluorescent imaging, mainly of cells and tissues. Following an introduction and a discussion of merits of fluorescent NPs compared to molecular fluorophores, labels and probes, the article assesses the kinds and specific features of nanomaterials often used in bioimaging. These include fluorescently doped silicas and sol-gels, hydrophilic polymers (hydrogels), hydrophobic organic polymers, semiconducting polymer dots, quantum dots, carbon dots, other carbonaceous nanomaterials, upconversion NPs, noble metal NPs (mainly gold and silver), various other nanomaterials, and dendrimers. Another section covers coatings and methods for surface modification of NPs. Specific examples on the use of nanoparticles in (a) plain fluorescence imaging of cells, (b) targeted imaging, (c) imaging of chemical species, and (d) imaging of temperature are given next. A final section covers aspects of multimodal imaging (such as fluorescence/nmr), imaging combined with drug and gene delivery, or imaging combined with therapy or diagnosis. The electronic supplementary information (ESI) gives specific examples for materials and methods used in imaging, sensing, multimodal imaging and theranostics such as imaging combined with drug delivery or photodynamic therapy. The article contains 273 references in the main part, and 157 references in the ESI.

A Phytic Acid Induced Super-Amphiphilic Multifunctional 3D Graphene-Based Foam.

Surfaces with super-amphiphilicity have attracted tremendous interest for fundamental and applied research owing to their special affinity to both oil and water. It is generally believed that 3D graphenes are monoliths with strongly hydrophobic surfaces. Herein, we demonstrate the preparation of a 3D super-amphiphilic (that is, highly hydrophilic and oleophilic) graphene-based assembly in a single-step using phytic acid acting as both a gelator and as a dopant. The product shows both hydrophilic and oleophilic intelligence, and this overcomes the drawbacks of presently known hydrophobic 3D graphene assemblies. It can absorb water and oils alike. The utility of the new material was demonstrated by designing a heterogeneous catalytic system through incorporation of a zeolite into its amphiphilic 3D scaffold. The resulting bulk network was shown to enable efficient epoxidation of alkenes without prior addition of a co-solvent or stirring. This catalyst also can be recovered and re-used, thereby providing a clean catalytic process with simplified work-up.

Upconversion nanoparticles: from hydrophobic to hydrophilic surfaces.

CONSPECTUS: Photon upconversion nanoparticles (UCNPs) have emerged as a promising new class of nanomaterials due to their ability to convert near-IR light into visible luminescence. Unfortunately, most efficient methods for preparing UCNPs yield hydrophobic materials, but water-dispersibility is needed in the major fields of applications of UCNPs, that is, in bioimaging, labeling, and bioassays. Numerous methods therefore have been reported in the past years to convert the hydrophobic surface of UCNPs to a more hydrophilic one so to render them dispersible in aqueous systems. We present a classification respective for these strategies and assess the main methods. These include (A) chemical modification of the hydrophobic (typically oleate) ligand on the surface, (B) addition of an extra layer, (C) addition of a thin shell on top of the UCNP, and (D) complete replacement of the original ligand by another one. Chemical modification (A) involves oxidation of the oleate or oleylamine and leads to particles with terminal oxygen functions. This method is less often used because solutions of the resulting UCNPs in water have limited colloidal stability, protocols are time-consuming and often give low yields, and only a limited number of functional groups can be introduced. Methods B and C involve coating of UCNPs with amphiphiles or with shells made from silica oxide, titanium oxide, or metallic gold or silver. These methods are quite versatile in terms of further modifications, for example, by further cross-linking or by applying thiol-gold chemistry. Growing an extra shell is, however, often accompanied by a higher polydispersity. Method D can be divided into subgroups based on either (i) the direct (single-step) replacement of the native ligand by a new ligand or (ii) two-step protocols using nitrosyltetrafluoroborate (NOBF4) or strong acids as reagents to produce ligand-free UCNPs prior to the attachment of a new ligand. These methods are simple and versatile, and the distance between the new ligand and the luminescent particle can be well controlled. However, the particles often have limited stability in buffer systems. The methods described also are of wider interest because they are likely to be applicable to other kinds of nanomaterials. We additionally address the need for (a) a better control of particle size and homogeneity during synthesis, (b) more reproducible methods for surface loading and modification, (c) synthetic methods giving higher yields of UCNPs, (d) materials displaying higher quantum yields in water solution without the need for tedious surface modifications, (e) improved methods for workup (including the suppression of aggregation), (f) new methods for surface characterization, and (g) more affordable reagents for use in surface modification. It is noted that most synthetic research in the area is of the trial-and-error kind, presumably due to the lack of understanding of the mechanisms causing current limitations. Finally, all particles are discussed in terms of their biocompatibility (as far as data are available), which is quintessential in terms of imaging, the largest field of application.

Optical methods for sensing and imaging oxygen: materials, spectroscopies and applications.

We review the current state of optical methods for sensing oxygen. These have become powerful alternatives to electrochemical detection and in the process of replacing the Clark electrode in many fields. The article (with 694 references) is divided into main sections on direct spectroscopic sensing of oxygen, on absorptiometric and luminescent probes, on polymeric matrices and supports, on additives and related materials, on spectroscopic schemes for read-out and imaging, and on sensing formats (such as waveguide sensing, sensor arrays, multiple sensors and nanosensors). We finally discuss future trends and applications and summarize the properties of the most often used indicator probes and polymers. The ESI† (with 385 references) gives a selection of specific applications of such sensors in medicine, biology, marine and geosciences, intracellular sensing, aerodynamics, industry and biotechnology, among others.

Size dependence of the upconverted luminescence of NaYF4:Er,Yb microspheres for use in ratiometric thermometry.

The size-dependent temperature sensitivity is observed on the upconversion luminescence of NaYF4:Er,Yb microspheres with sizes between 0.7 and 2 µm that are prepared by a poly(acrylic acid)-assisted hydrothermal process. It is found that the fluorescence intensity ratio (FIR) of their green upconversion emissions (with peaks at 521 and 539 nm) is strongly size-dependent at temperatures between 223 and 403 K. As the size of the spheres increases from 0.7 to 1.6 µm, the maximum sensitivity decreases from 36.8 × 10(-4) to 24.7 × 10(-4) K(-1). This effect is mainly attributed to the larger specific surface area of the smaller spheres where a relatively large number of Er(III) ions are located at the surface. This results in an increase in the efficiency of the (4)S3/2 → (2)H11/2 population process of the Er(III) ions due to stronger electron-phonon interactions with increasing T. Heating of the spheres by NIR light is also supposed to cause enhanced electron-phonon interactions in such particles.

2D luminescence imaging of pH in vivo.

Luminescence imaging of biological parameters is an emerging field in biomedical sciences. Tools to study 2D pH distribution are needed to gain new insights into complex disease processes, such as wound healing and tumor metabolism. In recent years, luminescence-based methods for pH measurement have been developed. However, for in vivo applications, especially for studies on humans, biocompatibility and reliability under varying conditions have to be ensured. Here, we present a referenced luminescent sensor for 2D high-resolution imaging of pH in vivo. The ratiometric sensing scheme is based on time-domain luminescence imaging of FITC and ruthenium(II)tris-(4,7-diphenyl-1,10-phenanthroline). To create a biocompatible 2D sensor, these dyes were bound to or incorporated into microparticles (aminocellulose and polyacrylonitrile), and particles were immobilized in polyurethane hydrogel on transparent foils. We show sensor precision and validity by conducting in vitro and in vivo experiments, and we show the versatility in imaging pH during physiological and chronic cutaneous wound healing in humans. Implementation of this technique may open vistas in wound healing, tumor biology, and other biomedical fields.

Luminescent probes and sensors for temperature.

Temperature (T) is probably the most fundamental parameter in all kinds of science. Respective sensors are widely used in daily life. Besides conventional thermometers, optical sensors are considered to be attractive alternatives for sensing and on-line monitoring of T. This Review article focuses on all kinds of luminescent probes and sensors for measurement of T, and summarizes the recent progress in their design and application formats. The introduction covers the importance of optical probes for T, the origin of their T-dependent spectra, and the various detection modes. This is followed by a survey on (a) molecular probes, (b) nanomaterials, and (c) bulk materials for sensing T. This section will be completed by a discussion of (d) polymeric matrices for immobilizing T-sensitive probes and (e) an overview of the various application formats of T-sensors. The review ends with a discussion on the prospects, challenges, and new directions in the design of optical T-sensitive probes and sensors.

Photonic crystals for chemical sensing and biosensing.

This Review covers photonic crystals (PhCs) and their use for sensing mainly chemical and biochemical parameters, with a particular focus on the materials applied. Specific sections are devoted to a) a lead-in into natural and synthetic photonic nanoarchitectures, b) the various kinds of structures of PhCs, c) reflection and diffraction in PhCs, d) aspects of sensing based on mechanical, thermal, optical, electrical, magnetic, and purely chemical stimuli, e) aspects of biosensing based on biomolecules incorporated into PhCs, and f) current trends and limitations of such sensors.

Targetable phosphorescent oxygen nanosensors for the assessment of tumor mitochondrial dysfunction by monitoring the respiratory activity.

Cellular respiration is a worthwhile criterion to evaluate mitochondrial dysfunction by measuring the dissolved oxygen. However, most of the existing sensing strategies merely report extracellular (ec-) or intracellular (ic-) O2 rather than intramitochondrial (im-) O2 . Herein we present a method to assess tumor mitochondrial dysfunction with three phosphorescent nanosensors, which respond to ec-, ic-, and im-O2 . Time-resolved luminescence is applied to determine the respective oxygen consumption rates (OCRs) under varying respiratory conditions. Data obtained for the OCRs and on (intra)cellular O2 gradients demonstrate that mitochondria in tumor cells are distinctly less active than those of healthy cells, resulting from restrained glucose utilization of and physical injury to the mitochondria. We believe that such a site-resolved sensing strategy can be applied to numerous other situations, for example to evaluate the adverse effects of drug candidates.

Sensing and imaging of oxygen with parts per billion limits of detection and based on the quenching of the delayed fluorescence of (13)C70 fullerene in polymer hosts.

We report on a new method for sensing trace oxygen in the gas phase. It is based on the extreme efficiency of the quenching of the thermally activated delayed fluorescence of isotopically enriched carbon-13 fullerene C(70) ((13)C(70)). This fullerene was dissolved in polymer matrixes of varying oxygen permeability, viz., polystyrene (PS), ethyl cellulose (EC) and an organically modified silica gel ("ormosil"; OS). The sensor films (5-10 µm thick), on photoexcitation at 470 nm, display a strong delayed photoluminescence with peaks between 670 and 700 nm. Its quenching by molecular oxygen was studied at 25 and 60 °C and at concentrations from zero up to 150 ppmv of oxygen in nitrogen. The rapid lifetime determination (RLD) method was applied to determine oxygen-dependent lifetimes and for fluorescence lifetime imaging of oxygen. The lower limits of detection (at 1% quenching) vary with the polymer used (EC ∼250 ppbv, OS ∼320 ppbv, PS ∼530 ppbv at 25 °C) and with temperature. The oxygen sensors reported here are the most sensitive ones described so far.

A highly K(+)-selective phenylaza-[18]crown-6-lariat-ether-based fluoroionophore and its application in the sensing of K+ ions with an optical sensor film and in cells.

Herein, we report the synthesis of two phenylaza-[18]crown-6 lariat ethers with a coumarin fluorophore (1 and 2) and we reveal that compound 1 is an excellent probe for K(+) ions under simulated physiological conditions. The presence of a 2-methoxyethoxy lariat group at the ortho position of the anilino moiety is crucial to the substantially increased stability of compounds 1 and 2 over their lariat-free phenylaza-[18]crown-6 ether analogues. Probe 1 shows a high K(+)/Na(+) selectivity and a 2.5-fold fluorescence enhancement was observed in the presence of 100 mM K(+) ions. A fluorescent membrane sensor, which was prepared by incorporating probe 1 into a hydrogel, showed a fully reversible response, a response time of 150 s, and a signal change of 7.8% per 1 mM K(+) within the range 1-10 mM K(+). The membrane was easily fabricated (only a single sensing layer on a solid polyester support), yet no leaching was observed. Moreover, compound 1 rapidly permeated into cells, was cytocompatible, and was suitable for the fluorescent imaging of K(+) ions on both the extracellular and intracellular levels.

Tyrosine specific sequential labeling of proteins.

We report (a) on the synthesis of a long-wavelength fluorescent coumarin containing an allyloxy acetate moiety, (b) the synthesis of two linkers containing an allyloxy acetate and an alkyne or azide function, respectively, and (c) the selective modification human serum albumin by a sequential method involving Pd(II) catalyzed modification of the phenolic side chain of tyrosine residues with an alkyne bearing linker and a subsequent azide-alkyne click reaction with an azide functionalized long-wavelength emitting coumarin dye. The method is likely to be applicable to various kinds of azido-modified fluorophores, and the Pd(II)-catalyzed modification of the tyrosines may also be used to introduce other kinds of tags. With these reagents, tyrosine specific modulation of proteins and peptides becomes possible either directly or in a sequential manner.

Long time monitoring of the respiratory activity of isolated mitochondria.

We have investigated the ability of optical oxygen sensors incorporated in a microplate to determine the respiratory activity of cell fractions. Different cell fractions were monitored, in particular to evaluate the long term functionality of isolated mitochondria. It is possible to continuously sense respiratory activity of isolated mitochondria over time. We found that they are functional for three hours but stop respiring at a critical limit of 20% air saturation in the system. Furthermore, inhibition and enhancement of respiratory activity were detected. In conclusion, oxygen sensors are a powerful tool to evaluate the functionality of isolated mitochondria.

Photon-upconverting nanoparticles for optical encoding and multiplexing of cells, biomolecules, and microspheres.

Photon-upconverting nanoparticles (UCNPs) are lanthanide-doped nanocrystals that emit visible light under near-infrared excitation (anti-Stokes emission). This unique optical property precludes background fluorescence and light scattering from biological materials. The emission of multiple and narrow emission lines is an additional hallmark of UCNPs that opens up new avenues for optical encoding. Distinct emission signatures can be obtained if the multiple emission of UCNPs is tuned by their dopant composition or by surface modification with dyes. Tuning the intensity of only one of the multiple emission lines and using another one as a constant reference signal enables the design of ratiometric codes that are resistant to fluctuations in absolute signal intensities. Combining several UCNPs each displaying a distinct set of emission lines expands the coding capacity exponentially and lays the foundation for highly multiplexed analyte detection. This Review highlights the potential of UCNPs for labeling and encoding biomolecules, microspheres, and even whole cells.