pH sensing IR-excited dye-linked upconversion nanoparticles, via inner field effect quenching at 540 nm referenced to emission at 650 nm.
a b s t r a c tMonte Carlo simulations were performed to obtain the phase behavior of binary H 2 O-CaCl 2 and ternary H 2 O-CaCl 2 -CO 2 mixtures over a range of conditions. The solubility of CO 2 in brines plays a key role in determining the amount that can be trapped via geological carbon storage. Isobaric-isothermal and Gibbs ensemble Monte Carlo simulations with several fixed-point charge force field models were used for the calculations of liquid densities and vapor pressures for the binary, and compositions of both phases for the ternary system. We used the SPC and SPC/E models for water; theÅqvist, Deublein et al., and Smith-Dang parameterizations for CaCl 2 ; and the EPM2, Murthy et al., and TraPPE models for CO 2 . While none of the model combinations were able to reproduce all the properties of interest, we found that some combinations produce accurate descriptions of individual properties. For the binary system, liquid densities are well represented by the SPC/E andÅqvist model combination, and vapor pressures are best described by the SPC andÅqvist model combination. For CO 2 solubility in aqueous CaCl 2 , the combination of SPC, Smith-Dang, and TraPPE models gives the best predictions, but all the models studied show good predictive capabilities, given that no intermolecular potential parameters were optimized in the present study. These results are broadly consistent with previous calculations for the H 2 O-NaCl-CO 2 system; CaCl 2 is found to have a stronger salting-out effect than NaCl at the same molality.
BackgroundCancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour’s genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing.MethodsHere we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network’s lung adenocarcinoma dataset to uncover recurrently mutated genomic loci.ResultsWe build a panel of 400 hotspot mutations and show that the coverage extends to more than 80% of the dataset at a median depth of 8 mutations per patient. Additionally, we uncover several novel single-nucleotide variants present in more than 5% of patients, often in genes not commonly associated with lung adenocarcinoma.ConclusionWith further optimisation, this hotspot panel could allow molecular diagnostics laboratories to build curated primer banks for ‘off-the-shelf’ monitoring of ctDNA by droplet-based digital PCR or similar techniques, in a time- and cost-effective manner.
Upconversion nanoparticles (UCNPs) should be particularly well suited for measurement inside cells because they can be imaged down to submicrometer dimensions in near real time using fluorescence microscopy, and they overcome problems, such as photobleaching, autofluorescence, and deep tissue penetration, that are commonly encountered in cellular imaging applications. In this study, the performance of an UCNP modified with a pH-sensitive dye (pHAb) is studied. The dye (emission wavelength 580 nm) was attached in a polyethylene imine (PEI) coating on the UCNP and excited via the 540-nm UCNP emission under 980-nm excitation. The UC resonance energy transfer efficiencies at different pHs ranged from 25 to 30% and a Förster distance of 2.56 nm was predicted from these results. Human neuroblastoma SH-SY5Y cells, equilibrated with nigericin H + /K + ionophore to equalize the intra-and extracellular pH‚ showed uptake of the UCNP-pHAb conjugate particles and, taking the ratio of the intensity collected from the pHAb emission channel (565-630 nm) to that from the UCNP red emission channel (640-680 nm), produced a sigmoidal pH response curve with an apparent pK a for the UCNP-pHAb of~5.1. The UCNP-pHAb were shown to colocalize with LysoBrite dye, a lysosome marker. Drug inhibitors such as chlorpromazine (CPZ) and nystatin (NYS) that interfere with clathrin-mediated endocytosis and caveolae-mediated endocytosis, respectively, were investigated to elucidate the mechanism of nanoparticle uptake into the cell. This preliminary study suggests that pH indicator-modified UCNPs such as UCNP-pHAb can report pH in SH-SY5Y cells and that the incorporation of the nanoparticles into the cell occurs via clathrinmediated endocytosis.
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