Sensors are key tools for monitoring the dynamic changes of biomolecules and biofunctions that encode valuable information that helps us understand underlying biological processes of fundamental importance. Because of their distinctive size-dependent physicochemical properties, materials with nanometer scales have recently emerged as promising candidates for biological sensing applications by offering unique insights into real-time changes of key physiological parameters. This review focuses on recent advances in imaging-based nanosensor developments and applications categorized by their signal transduction mechanisms, namely, fluorescence, plasmonics, MRI, and photoacoustics. We further discuss the synergy created by multimodal nanosensors in which sensor components work based on two or more signal transduction mechanisms.
Extracellular pH is important in clinical measurements due to its correlation to cell metabolism and disease progression. In MRI, T 1 /T 2 ratiometric analysis and other methods have been previously applied to quantify pH using conventional pulse sequences. However, for nanoparticle-based approaches, heterogeneity in size and surface functionalization tends toward qualitative rather than quantitative results. To address this limitation, we developed a novel DNA-based MRI contrast agent, pH-DMRCA, which utilizes a highly programmable and reproducible nanostructure. The pH-DMRCA is a dendritic DNA scaffold that is functionalized with a pH-responsive MRI-sensitive construct, Gd(NP-DO3A), at the end of each DNA arm. We first evaluated the r 1 and r 2 response of our pH-DMRCA over a range of pH values (pH = 5−9) to establish a relaxometric model of pH. These MRIbased assessments of pH were validated in a separate set of samples using a pH electrode (n = 18) and resulted in a good linear correlation (R 2 = 0.99, slope = 0.98, intercept = 0). A Bland−Altman analysis of the results also showed reasonable agreement between the calculated pH and measured pH. Moreover, these pH comparisons were consistent across three different pH-DMRCA concentrations, demonstrating concentration-independence of the method. This MRI-based pH quantification methodology was further verified in human blood plasma. Given the versatility of the DNA-based nanostructures, the contrast agent has a potential to be applied to a wide variety of imaging applications where extracellular pH is important including cancer, stroke, cardiovascular disease, and other important diseases.
While the co-existence of comammox bacteria with canonical nitrifiers is well documented in diverse ecosystems, there is still a dearth of knowledge about the mechanisms underpinning their interactions. Understanding these interaction mechanisms is important as they may play a critical role in governing nitrogen biotransformation in natural and engineered ecosystems. In this study, we tested the ability of two environmentally relevant factors (nitrogen source and availability) to shape interactions between strict ammonia and nitrite-oxidizing bacteria and comammox bacteria in continuous flow column reactors. The composition of inorganic nitrogen species in reactors fed either ammonia or urea was similar during the lowest nitrogen loading condition (1 mg-N/L), but higher loadings (2 and 4 mg-N/L) promoted significant differences in nitrogen species composition and nitrifier abundances. The abundance and diversity of comammox bacteria were dependent on both nitrogen source and loading conditions as multiple comammox bacterial populations were preferentially enriched in the urea-fed system. In contrast, their abundance was reduced in response to higher nitrogen loadings in the ammonia-fed system likely due to ammonia-based inhibition. The preferential enrichment of comammox bacteria in the urea-fed system could be associated with their ureolytic activity calibrated to their ammonia oxidation rates thus minimizing ammonia accumulation to inhibitory levels. However, an increased abundance of comammox bacteria was not associated with a reduced abundance of nitrite oxidizers in the urea-fed system while a negative correlation was found between them in the ammonia-fed system; the latter dynamic likely emerging from reduced availability of nitrite to strict nitrite oxidizers at low ammonia loading conditions.
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