In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18-22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.
Exploiting the distinct excitation and emission properties of concomitant electrochemiluminophores in conjunction with the inherent color selectivity of a conventional digital camera, we create a new strategy for multiplexed electrogenerated chemiluminescence detection, suitable for the development of low-cost, portable clinical diagnostic devices. Red, green and blue emitters can be efficiently resolved over the three-dimensional space of ECL intensity versus applied potential and emission wavelength. As the relative contribution ratio of each emitter to the photographic RGB channels is constant, the RGB ECL intensity versus applied-potential curves could be effectively isolated to a single emitter at each potential.
Compared to tris(2-phenylpyridine)iridium(III) ([Ir(ppy)3 ]), iridium(III) complexes containing difluorophenylpyridine (df-ppy) and/or an ancillary triazolylpyridine ligand [3-phenyl-1,2,4-triazol-5-ylpyridinato (ptp) or 1-benzyl-1,2,3-triazol-4-ylpyridine (ptb)] exhibit considerable hypsochromic shifts (ca. 25-60 nm), due to the significant stabilising effect of these ligands on the HOMO energy, whilst having relatively little effect on the LUMO. Despite their lower photoluminescence quantum yields compared with [Ir(ppy)3 ] and [Ir(df-ppy)3 ], the iridium(III) complexes containing triazolylpyridine ligands gave greater electrogenerated chemiluminescence (ECL) intensities (using tri-n-propylamine (TPA) as a co-reactant), which can in part be ascribed to the more energetically favourable reactions of the oxidised complex (M(+) ) with both TPA and its neutral radical oxidation product. The calculated iridium(III) complex LUMO energies were shown to be a good predictor of the corresponding M(+) LUMO energies, and both HOMO and LUMO levels are related to ECL efficiency. The theoretical and experimental data together show that the best strategy for the design of efficient new blue-shifted electrochemiluminophores is to aim to stabilise the HOMO, while only moderately stabilising the LUMO, thereby increasing the energy gap but ensuring favourable thermodynamics and kinetics for the ECL reaction. Of the iridium(III) complexes examined, [Ir(df-ppy)2 (ptb)](+) was most attractive as a blue-emitter for ECL detection, featuring a large hypsochromic shift (λmax =454 and 484 nm), superior co-reactant ECL intensity than the archetypal homoleptic green and blue emitters: [Ir(ppy)3 ] and [Ir(df-ppy)3 ] (by over 16-fold and threefold, respectively), and greater solubility in polar solvents.
We examine the electrogenerated chemiluminescence (ECL) of three Ir(C^N) 2 (acac) complexes, where acac = acetylacetonate anion and C^N = 2-phenylpyridine (ppy), 2-phenylbenzothiazole (bt), or 2-phenylquinoline (pq) anions, with tri-n-propylamine co-reactant in acetonitrile under a range of chemical and instrumental conditions; this follows somewhat conflicting recent claims of the ECL intensities from complexes of this type. Relevant electrochemical, spectroscopic, and ECL properties are evaluated in direct comparison with those of Ir(ppy) 3 and [Ru(bpy) 3 ](PF 6 ) 2 , as well as data from previous publications. DFT calculations on the Ir(C^N) 2 (acac) complexes show the HOMOs to be composed of both the metal and the C^N ligand, and the LUMOs almost exclusively on the C^N ligand. The ECL intensities of the Ir(C^N) 2 (acac) complexes (relative to [Ru(bpy) 3 ](PF 6 ) 2 ) were dependent on experimental conditions and, in some cases, the ECL intensities reported for iridium complexes may have been derived using conditions that unintentionally disadvantaged the reference electrochemiluminophore.
We examine energy transfer and quenching within annihilation ECL systems comprising mixed metal-complexes in solution, and show the dependence of the emission intensities on luminophore concentration and the applied potentials.
Both injury-related and psychosocial factors were associated with the duration of time to RTW following acute unintentional injuries. This study replicated previously reported findings on social functioning and compensation from an independent acute trauma sample. Programs or policies to improve social functioning early post-injury may provide opportunities to improve the duration of time to RTW following injury.
A water-soluble Ir(iii) complex is shown to enhance the ‘remote’ mechanism of the most widely used co-reactant ECL reaction of tris(2,2′-bipyridine)ruthenium(ii) with tripropylamine.
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