Advanced personalized medical diagnostics depend on the availability of high-quality biological samples. These are typically biofluids, such as blood, saliva, or urine; and their collection and storage is critical to obtain reliable results. Without proper temperature regulation, protein biomarkers in particular can degrade rapidly in blood samples, an effect that ultimately compromises the quality and reliability of laboratory tests. Here, we present the use of silk fibroin as a solid matrix to encapsulate blood analytes, protecting them from thermally induced damage that could be encountered during nonrefrigerated transportation or freeze-thaw cycles. Blood samples are recovered by simple dissolution of the silk matrix in water. This process is demonstrated to be compatible with a number of immunoassays and provides enhanced sample preservation in comparison with traditional air-drying paper approaches. Additional processing can remediate interactions with conformational structures of the silk protein to further enhance blood stabilization and recovery. This approach can provide expanded utility for remote collection of blood and other biospecimens empowering new modalities of temperature-independent remote diagnostics.lood contains a variety of proteins, enzymes, lipids, metabolites, and peptides, which can be interrogated as biomarkers for health screening, monitoring, and diagnostics. The integrity of these blood components and thus the quality of information attained from their analysis is determined by the storage conditions from sampling until analysis, or the so-called pre-analytical phase (1, 2). This phase often includes time-consuming processing steps and the requirement for a continuous cold storage. Without temperature regulation, blood-derived biospecimens degrade quickly, accounting for up to 67% of all laboratory testing errors (2, 3). Further, when blood-derived materials are frozen, decreases in thermodynamic free energy and unfavorable ice crystal-protein interactions (4) can occur during subsequent thawing (5, 6), which can further compromise analyte integrity as a gold-standard methodology.As an alternative route, blood and blood derivatives can be dried via newer approaches such as isothermal vitrification (7), lyophilization (8), or on silica chips (9). Isothermal vitrification and lyophilization are inherently resource-intensive techniques and thus not suitable for field use. Silica chips are designed for enrichment of selected fractions of the low-molecular-weight serum proteome, but are not broadly protective at elevated temperature (10). An inexpensive alternative used since the 1960s are dried blood spots (DBS) (11), a paper card system which captures blood components among cellulose fibers as the water phase evaporates. These drying measures decrease sample weight by >90%, thus decreasing transport burden, and in theory can enhance long-term sample stability by decreasing water-dependent analyte degradation caused by hydrolysis and enzyme activity (12). Unfortunately, DBS stored in ...
Storage of silk proteins in liquid form can lead to excessive waste from premature gelation, thus an alternative storage strategy is proposed using lyophilization to generate soluble and shelf-stable powder formats for on-demand use. Initial solution stability studies highlighted instabilities of higher-molecular-weight silks that could not be resolved by solution modifications such as autoclaving, pH increases, dilution, or combinations thereof. Conversely, shelf-stable lyophilized stock powders of silk fibroin of moderate to low molecular weights were developed that could be fully constituted even after 1 year of storage at elevated temperatures. Increasing dried silk powder loading in aqueous solution facilitated increased silk solution concentrations−here up to 80 mg/mL solubility was demonstrated across a range of formulations. Powders generated from silk solutions with highermolecular-weight distributions were less soluble than moderate or lower-molecular-weight versions, despite no differences in their solution glass-transition temperatures. Instead, the aggregation and β-sheet content of lyophilized higher molecular weight stock solutions were identified as the cause of the reduced powder solubility by circular dichroism and dynamic light scattering analyses. The solubility and molecular weight profiles of all formulations investigated were preserved after storing the lyophilized materials over 1 year, even at 37 °C. No long-term powder stability behaviors were influenced by the addition of a secondary drying step in the lyophilization procedure, suggesting that this protocol could be scaled without the burden of lengthy process times. Taken together, these findings provide a very flexible and potentially cost-saving approach to producing shelf-stable silk fibroin stock materials based on the use of moderate to lower-molecular-weight lyophilized preparations. This utility is demonstrated with the formation of silk material formats from the stored powders, including films, gels, and salt-leached porous scaffolds. In turn, a more efficient system allowing full resolubilization will enable stockpiling powder for on-demand usage and for deployment of dried silks for application demands in field settings.
At the In-Tank Precipitation Facility of the Savannah River Site, strontium and other radionuclides are removed from high-level radioactive waste and sent to the Defense Waste Processing Facility. Strontium removal is accomplished by adsorption using a slurry that includes monosodium titanate, which forms strontium titanate with unknown lung solubility characteristics. The purpose of this study was to determine the solubility of strontium titanate in the form created at the In-Tank Precipitation facility. An in vitro dissolution study was done with a slurry simulant and with several types of strontium titanate, and the results were compared. An in vivo study was also performed with high-fired SrTiO3 in rats. Strontium and titanium were measured by inductively-coupled plasma/atomic emission spectrometry. The data from both studies were used independently to assign the compounds to an absorption type based on criteria specified in ICRP 71. Results of the in vitro studies showed that the Defense Waste Processing Facility simulant should be assigned to Type M and the strontium titanate should be assigned to Type S. Results of the in vivo study verified that SrTiO3 should be assigned to Type S. Lung clearance data of SrTiO3 from rats showed that 85% cleared within the first 24 h and the remaining 15% cleared with a half-time of 130 d. The initial rapid clearance is attributed to deposition in airways as compared to the alveolar region.
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