Small Volumes Of Fluid Research Articles

A novel experimental approach for dynamic quantification of liquid saturation and capillary pressure in shale

Determination of dynamic fluid intrusion in tight oil reservoirs requires a very careful and precise estimation of changes in fluid volumes during spontaneous and forced imbibition. Because of the extremely low permeability of these mudrocks, only very small volumes of fluid can flow through the matrix. To overcome this limitation, the pressure decay method commonly used to estimate permeability and porosity in tight rocks is adapted to determine liquid saturation in tight rocks using a slightly compressible fluid as the confining medium. This adaptation uses the transient pressure drop within the bulk liquid surrounding the rock during confinement, to dynamically estimate the volume of fluid intrusion within the tight rock. Pressure decay data for shale samples from the Eagle Ford, Utica and Bakken formations, each of varying particle diameter were obtained experimentally from batch tests. The total pressure drop observed for each shale type was used to measure oil saturations and a pseudo capillary pressure curve was derived from the pressure and saturation data. These measurements were confirmed with NMR measurements made on the same samples (before and after oil saturation).The results show that shale formations with larger permeability tend to absorb more incremental oil during forced imbibition than that which it absorbs during spontaneous imbibition. Furthermore, it was observed that the duration of oil intrusion at lower initial pressures during forced imbibition was longer than the time interval observed for oil intrusion at higher initial pressures for the same particle size. Also, in relation to particle size, it was observed that a significant amount of oil intrusion occurred at lower pressures for large shale crushed samples during forced imbibition, in contrast to smaller oil intrusion observed for small sized particles at lower pressures. The reason for this is because larger sized samples possess micro cracks which serve as extra channels through which oil can penetrate.

Optofluidic microconvection with magnetic nanoparticles: Novel interaction of thermal diffusion and magnetic field

Light-matter interactions are exploited in many applications, whereas superparamagnetic nanoparticles allow to introduce magnetic field control in diverse fluid environments. We study the structure of laser-induced thermal lens in thin layers of ferromagnetic colloid and predict significant magnetoconvective motion around the beam spot. It was found that localized heating depletes/accumulates magnetic nanoparticles in the beam-spot by thermal diffusion and collective magnetic interactions of nanoparticles produce strong microconvective currents. This mode of mass transport can be controlled by magnetic field. We expect the novel magnetosolutal microconvective coupling, which we describe, can be a multifunctional approach for precision optical manipulation and mixing of small fluid volumes using magnetic nanoparticles within integrated microfluidic devices.

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity

Three-dimensional (3D) spheroidal cell cultures are now recognised as better models of cancers as compared to traditional cell cultures. However, established 3D cell culturing protocols and techniques are time-consuming, manually laborious and often expensive due to the excessive consumption of reagents. Microfluidics allows for traditional laboratory-based biological experiments to be scaled down into miniature custom fabricated devices, where cost-effective experiments can be performed through the manipulation and flow of small volumes of fluid. In this study, we characterise a 3D cell culturing microfluidic device fabricated from a 3D printed master. HT29 cells were seeded into the device and 3D spheroids were generated and cultured through the perfusion of cell media. Spheroids were treated with 5-Fluorouracil for five days through continuous perfusion and cell viability was analysed on-chip at different time points using fluorescence microscopy and Lactate dehydrogenase (LDH) assay on the supernatant. Increasing cell death was observed in the HT29 spheroids over the five-day period. The 3D cell culturing microfluidic device described in this study, permits on-chip anti-cancer treatment and viability analysis, and forms the basis of an effective platform for the high-throughput screening of anti-cancer drugs in 3D tumour spheroids.

Development of a Sensitive High-Resolution Mass Spectrometry Approach for Urea Nitrogen Quantitation in Small Volumes of Bronchoalveolar Lavage Fluid (BALF).

A sensitive, selective, and quantitative method incorporating high-resolution mass spectrometry was developed for the determination of blood urea nitrogen (BUN) in bronchoalveolar lavage fluid. The method requires no sample cleanup or derivatization prior to analysis. High-performance liquid chromatography (HPLC) on a Hypersil Gold PFP column (100 × 3 mm, 3 μm particle size) connected to a C18 guard column was employed for a 10 min chromatographic separation. The detection of urea was achieved using a Thermo Scientific Q-Exactive Plus instrument incorporating selected ion monitoring (SIM) modes for the protonated adduct of urea. The urea analytical measuring range for the method is 0.047-17.134 mg/dL, resulting in a BUN analytical measurement range of 0.022-8.007 mg/dL, which allows for quantitation over 3 orders of magnitude (R2 = 0.999). In addition, the method is suitable for small sample volumes (15 μL) with a high level of accuracy, precision, and specificity.

Cached Gaussian elimination for simulating Stokes flow on domains with repetitive geometry

Microfluidic “lab on a chip” devices are small devices that operate on small length scales on small volumes of fluid; these devices find uses in a variety of applications. Designs for microfluidic chips are generally composed of standardized and often repeated components connected by long, thin, straight fluid channels. We propose a novel meshing algorithm for use in simulating the linear incompressible stationary Stokes equations on geometry with these features, which produces sparse symmetric positive indefinite systems with many repeated matrix blocks. We use a discretization that is formally third order accurate for velocity and second order accurate for pressure in the L∞ norm. We also propose a novel linear system solver based on cyclic reduction, reordered sparse Gaussian elimination, and operation caching that is designed to efficiently solve systems with repeated matrix blocks. We demonstrate that the resulting fluid solver is significantly faster than existing methods up to resolutions of a few million degrees of freedom for microfluidic problems.

In vitro evaluation of a novel immediate-release formulation of oxy-codone (RoxyBond™) for the potential for abuse via injection.

Immediate-release (IR) oxycodone formulations may be manipulated for nonoral routes of administration. Oxycodone abuse-resistant immediate-release (ARIR) is a novel abuse-deterrent formulation (ADF) of IR oxycodone. This study aimed to assess the intravenous (IV) abuse potential of oxycodone ARIR relative to commercially available IR oxycodone tablets using in vitro laboratory studies. Intact or manipulated tablets were incubated in 5 or 10 mL of room temperature water for increasing amounts of time. For each timepoint, syringeability, defined as the ability to draw up water-immersed intact or manipulated tablets into a syringe, was assessed on a scale of 1 (very easy) to 10 (impossible). If the prepared sample could be drawn into a syringe, the proportion of syringeable oxycodone was measured analytically. In all conditions, it was nearly impossible to draw any liquid into a syringe from samples containing manipulated oxycodone ARIR tablets (N = 5/group), and most samples released very low concentrations (<10 percent) of their total oxycodone content, regardless of sample volume. In contrast, samples containing crushed IR oxycodone (N = 5/group) in small volumes of fluid were easily drawn into a syringe through the smallest needle, and more than 90 percent of the oxycodone content was released from relatively small sample volumes (5 mL). The difficulty required to prepare an injectable solution from oxycodone ARIR when manipulated suggests that oxycodone ARIR has abuse-deterrent properties that may deter IV abuse.

Minimally Invasive Platforms in Biosensing.

The interaction of sensing components with body fluids is a basic requirement for clinical diagnostics; a variety of novel platforms have recently been developed for invasive and non-invasive sensing. In this manuscript, recent advancements related to minimally invasive platform for biosensing are reviewed. Many approaches have been utilized for generating minimally invasive platforms that require a small volume of body fluid; for example, the use of small-scale needles known as microneedles for minimally invasive detection has been demonstrated. The use of capillary action in microneedle-assisted biosensing may facilitate the detection of analytes in body fluids. This review considers recent innovations in the structure and performance of minimally invasive sensos.

Sources and Effects of Fluids in Continental Retrograde Shear Zones: Insights from the Kuckaus Mylonite Zone, Namibia

Midcrustal rocks in retrograde metamorphic settings are typically H2O-undersaturated and fluid-absent and have low permeability. Exhumed continental retrograde faults, nonetheless, show evidence for the operation of fluid-mediated weakening mechanisms during deformation at midcrustal conditions. To explore the origin and effects of fluids in retrograde faults, we study the Kuckaus Mylonite Zone (KMZ), an exhumed crustal-scale, strike-slip shear zone in the southern Namibian Namaqua Metamorphic Complex. The KMZ deformed quartzofeldspathic migmatised gneisses at midcrustal retrograde conditions (450-480°C, 270-420 MPa) in the Mesoproterozoic, 40 Ma after granulite facies peak metamorphism at 825°C and 550 MPa. The mylonites contain fully hydrated retrograde mineral assemblages, predominantly adjacent to anastomosing high-strain zones, providing evidence of local H2O saturation and fluid presence during deformation. Whole rock and quartz veinδ18O values suggest that at least some of the fluids were meteoric in origin. The rocks across the shear zone retain the effect of different protoliths, implying little effect of fluid-rock interaction on whole rock major element chemistry. Together with a general scarcity of quartz veins, this suggests that fluid/rock ratios remained low in the KMZ. However, even small amounts of H2O allowed reaction weakening and diffusion-precipitation, followed by growth and alignment of phyllosilicates. In the ultramylonites, a fine grain size in the presence of fluids allowed for grain size sensitive creep. We conclude that the influx of even small volumes of fluids into retrograde shear zones can induce drastic weakening by facilitating grain size sensitive creep and retrograde reactions. In retrograde settings, these reactions consume fluids, and therefore elevated fluid pressures will only be possible after considerable weakening has already occurred. Our findings imply that the range of seismic styles recently documented at active retrograde transform faults may not require high fluid pressures but could also arise from other local weakening mechanisms.

Brain biomechanics: monitoring the biomechanical properties of the human craniospinal system

The existing methods of assessing the biomechanical properties of the human craniospinal system are reduced to the study of the dynamics of changes in intracranial pressure with a dosed increase in intracranial volume by introducing a certain volume of fluid into the cranial space. These studies are discrete, traumatic. In different neurosurgical clinics, retrospective analysis of 1732 studies of biomechanical properties of the human craniospinal system (compliance, pressure-volume ratio, elasticity) in the period 1988–2014 were conducted. In order to establish a diagnosis or clarify the tactics of surgical treatment, a relationship between the amplitude of the intracranial pressure oscillation at the pulse rate, intracranial pressure and the compliance of the craniospinal system was established. In a single classical test with the introduction of a bolus of a small volume of fluid, and the indicators of biomechanical properties of the human craniospinal system are numerically evaluated. It is assumed that between two pulse waves (in the second range), these indicators do not change significantly, that is, in fact, we are talking about monitoring biomechanical properties of the human craniospinal system. A mathematical model is proposed that formalizes the relationship between biomechanical properties of the human craniospinal system and the dynamics of intracranial pressure oscillations at the pulse rate. Comparison of the results of the assessment of the main biomechanical indicators by the classical method and the proposed method established their high correlation. On the basis of this, an algorithm is proposed that can be used to create the original biomechanical properties of the human craniospinal system and intracranial pressure monitor.

An experimental approach to manufacturability assessment of microfluidic devices produced by stereolithography

Lab-on-a-Chips integrate a variety of laboratory functions and embed microchannels for small fluid volume handling. These devices are used in medicine, chemistry, and biotechnology applications but a large diffusion is limited due to the manufacturing cost of traditional processes. Additive Manufacturing offers affordable alternatives for the production of microfluidic devices, because the fabrication of embedded micrometric channels is enabled. Stereolithography gained particular attention due to the low cost of both available machines and suitable polymeric materials to be processed. The main restriction to the adoption of this technique comes from the obtainable dimensional accuracy that depends not only on design, but also on process set-up. Firstly, the paper analyses theoretically the physics of stereolithographic processes and focuses on main phenomena related to microchannel manufacturing. Then, specific experimental activities are designed to investigate the combined effect of design and process parameters on the achievable dimensional accuracy of embedded microchannels manufactured through a commercial desktop stereolithography apparatus. In particular, the combined effect of channel nominal dimensions, build orientations and the layer thickness on the obtainable accuracy is examined by referring to a benchmark geometry. The collated experimental data showed that a number of combinations are successful. Besides, the experimental activity revealed that appropriate combinations of design, build orientation and manufacturing parameters can overcome the dimensional limitations reported in previous studies. Both binary logistic regression models to predict the manufacturability of microchannels and linear regression models to estimate the achievable accuracy for those geometries that can be produced successfully are developed.

896-P: Putting the Pieces Together: Building a Nonenzymatic Wearable Glucose Sensor Using Silicon Microneedle Arrays

We developed the technology to build a novel painless CGM that is an on-body, wirelessly transmitting device that extracts interstitial fluid with a dime-sized patch of microneedles and optically detects glucose from extremely small fluid volumes. We not only developed an innovative method for fabricating silicon microneedles, sharp and small enough to penetrate skin without pain (160 µm in height, 50 µm in diameter, and 100 µm in width), but also demonstrated that our microneedle fabrication is repeatable and reliable. Next we developed an entirely new, stable, non-enzymatic glucose-sensing method based on a variation of the well-known fluorescent-based boronic acid sensor, and further refined this sensor to allow for conductivity based sensing as well as ratiometric sensing of glucose (Figure 1, left). Finally, we built a novel integrated silicon buried dual-junction (BDJ) photodiode-based system with which to detect glucose with our sensor. The Figure attached shows our latest successes with ratiometric sensing of tartaric acid using our microfabricated device (Figure 1, right). Given our results, we believe this technology can now be transitioned to industry, and we are moving on to developing a wearable microfluidic-based patch pump that can allow for a truly affordable artificial pancreas based diabetes management solution. Disclosure S. Pennathur: Board Member; Self; Laxmi Therapeutic Devices. Employee; Self; Laxmi Therapeutic Devices. Research Support; Self; American Diabetes Association, Leona M. and Harry B. Helmsley Charitable Trust. Stock/Shareholder; Self; Laxmi Therapeutic Devices. H. Kim: None. B. Wang: None. B.N. Queenan: None. D. Huber: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-17-VSN-18 to S.P.)

Space-Occupying Lesions of the Retropharyngeal Space: An Anatomical Study With Application to Postoperative Retropharyngeal Hematomas.

Study Design:Cadaver study.Objective:The retropharyngeal space’s (RPS’s) clinical relevance is apparent in anterior cervical spine surgery with respect to postoperative hematoma, which can cause life-threatening airway obstruction. This cadaver study aims to establish guidance toward a better understanding of the tolerance of the RPS to accommodate fluid accumulation.Methods:Five fresh-frozen cadavers were dissected in the supine position. A digital manometer and a 20 Fr Foley catheter were inserted into the RPS via an anterolateral approach. While inflating the Foley catheter, the position of the esophagus/trachea was documented using fluoroscopy, and the retropharyngeal pressure was measured. We quantified the volume required to deviate the esophagus/trachea >1 cm from its original position using fluoroscopy. We also recorded the volume required to cause a visible change to the normal neck contour.Results:A mean volume of 12.5 mL (mean pressure 1.50 mm Hg) was needed to cause >1 cm of esophageal deviation. Tracheal deviation was encountered at a mean volume of 20.0 mL (mean pressure of 2.39 mm Hg). External visible clinical neck contour changes were apparent at a mean volume of 39 mL.Conclusion:A relatively small volume of fluid in the RPS can cause the esophagus/trachea to radiographically deviate. The esophagus is the structure in the RPS to be most influenced by mass effect. The mean volume of fluid required to cause clinically identifiable changes to the normal neck contour was nearly double the volume required to cause 1 cm of esophageal/tracheal deviation in a cadaver model.

Effect of additives on the growth of HKUST-1 crystals synthesized by microfluidic chips with concentration gradient.

Metal-organic frameworks (MOFs) have attracted considerable attention as novel nanoporous materials that combine the properties of organic and inorganic porous materials. HKUST-1 is one of the most well-developed and representative MOFs with wide applications in gas storage and separation, adsorption, and capture. In this study, we used microfluidics, an advanced technique of manipulation of small fluid volumes in microscale or even nanoscale channels, to investigate the effect of sodium dodecyl sulfate (SDS) on the growth of HKUST-1 crystals. We directly observed the morphological evolution of HKUST-1 crystals through droplet arrays with the SDS concentration gradient. The morphology of HKUST-1 evolved from cubic to cuboctahedron and finally to octahedron with increasing SDS concentration. The study results demonstrated the important role played by anions in solution in the structural regulation of HKUST-1.

Understanding and extending the Starling principle.

The Starling Principle states that fluid movements between blood and tissues are determined by differences in hydrostatic and colloid osmotic (oncotic) pressures between plasma inside microvessels and fluid outside them. The Revised Starling Principle recognizes that, because microvessels are permeable to macromolecules, a balance of pressures cannot halt fluid exchange. In most tissues, steady oncotic pressure differences between plasma and interstitial fluid depend on low levels of steady filtration from plasma to tissues for which the Revised Principle provides the theory. Plasma volume is normally maintained by fluid losses from filtration being matched by fluid gains from lymph.Steady state fluid uptake into plasma only occurs in tissues such as intestinal mucosa and renal peri-tubular capillaries where a protein-free secretion of adjacent epithelia contributes significantly to interstitial fluid volume and keeps interstitial oncotic pressure low. Steady filtration rates in different tissues are disturbed locally by reflex changes in capillary pressure and perfusion. The rapid overall decline in capillary pressure after acute blood loss initiates rapid fluid uptake from tissue to plasma, that is, autotransfusion. Fluid uptake is transient, being rapid at first then attenuating but low levels may continue for more than an hour. The Revised Principle highlights the role of oncotic pressure of small volumes of interstitial fluid within a sub-compartment surrounding the microvessels rather than the tissue's mean interstitial fluid oncotic pressure. This maximizes oncotic pressure differences when capillary pressure are high and enhances initial absorption rates when pressures are low, accelerating short-term regulation of plasma volume.

MP60-07 DO POST-VOID DRIBBLING AND EJACULATORY DYSFUNCTION AFTER URETHROPLASTY SHARE THE SAME ETIOLOGY?

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II (MP60)1 Apr 2020MP60-07 DO POST-VOID DRIBBLING AND EJACULATORY DYSFUNCTION AFTER URETHROPLASTY SHARE THE SAME ETIOLOGY? Ayman Soubra*, Shawn Grove, Joseph Pariser, Bryan Voelzke, Jeremy Myers, Bradley Erickson, Nejd Alsikafi, Benjamin Breyer, Alex Vanni, Jill Buckley, Joshua Broghammer, Keith Rourke, and Sean Elliott Ayman Soubra*Ayman Soubra* More articles by this author , Shawn GroveShawn Grove More articles by this author , Joseph PariserJoseph Pariser More articles by this author , Bryan VoelzkeBryan Voelzke More articles by this author , Jeremy MyersJeremy Myers More articles by this author , Bradley EricksonBradley Erickson More articles by this author , Nejd AlsikafiNejd Alsikafi More articles by this author , Benjamin BreyerBenjamin Breyer More articles by this author , Alex VanniAlex Vanni More articles by this author , Jill BuckleyJill Buckley More articles by this author , Joshua BroghammerJoshua Broghammer More articles by this author , Keith RourkeKeith Rourke More articles by this author , and Sean ElliottSean Elliott More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000929.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Post-void dribbling (PVD) and ejaculatory dysfunction (EjD) are common after urethroplasty (UP). Although the etiology remains unknown, they are thought to share a similar etiology because they are both due to a failure to express small volumes of urethral fluid. Theories include damage to the bulbospongiosus muscle (BS) or adjacent nerves, graft sacculation and loss of urethral elasticity. We sought to determine whether post-UP PVD and EjD are associated with each other and whether that association varies with BS damage or graft placement. METHODS: From the TURNS database, we included men who underwent anterior UP with ≥1 follow-up visit, 2-12 months after surgery, with completed questionnaires. We excluded men with prior UP or hypospadias repair. From the Male Sexual Health Questionnaire we used question 2 (“How would you rate the strength or force of your ejaculation”). From the Jackson et al urethral stricture patient reported outcome measure we used question 6 (“How often have you had a slight wetting of your pants a few minutes after you had finished urinating and had dressed yourself?”). The association between the frequency distribution of scores on these questions was compared using Chi square. Subset analysis compared the frequency distribution in bulbar UP (as a surrogate for BS damage), penile UP, and bulbar UP with graft vs. excision and primary anastomosis (EPA). RESULTS: Among 772 men who met the inclusion criteria, PVD and EjD were associated (p< 0.01; Figure). The association persisted in all of the following subsets: bulbar UP (p< 0.01), penile UP (p= 0.03), bulbar onlay graft UP (p= 0.03), penile onlay graft UP (p= 0.3) and bulbar EPA (p< 0.01). There were too few ventral graft procedures to compare dorsal vs. ventral onlay. CONCLUSIONS: Post-UP PVD and EjD are associated, supporting the theory of a common etiology. The association persists whether the UP is in the penile or bulbar urethra, suggesting that BS damage is not the primary cause. The association persists whether the bulbar UP is done with a graft vs EPA, suggesting that graft placement is not the cause; but we were unable to compare dorsal vs. ventral graft. By exclusion, these symptoms may be due to a loss of elasticity that is inherent to any UP (with or without a graft) or due to a neurologic cause. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e891-e892 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ayman Soubra* More articles by this author Shawn Grove More articles by this author Joseph Pariser More articles by this author Bryan Voelzke More articles by this author Jeremy Myers More articles by this author Bradley Erickson More articles by this author Nejd Alsikafi More articles by this author Benjamin Breyer More articles by this author Alex Vanni More articles by this author Jill Buckley More articles by this author Joshua Broghammer More articles by this author Keith Rourke More articles by this author Sean Elliott More articles by this author Expand All Advertisement PDF downloadLoading ...

Coalescence of lenticular anticyclones in a linearly stratified rotating fluid

This study is devoted to laboratory experiments on the coalescence of two lenticular anticyclones in a linearly stratified rotating fluid. These anticyclones are generated by injecting small volumes of fluid at the centre of a rotating tank where a linearly stratified layer was previously prepared with salt. The characteristics of the interaction between the vortices are studied by visualisation and Particle Image Velocimetry (PIV) as a function of the initial separation distance between the vortices, the Coriolis parameter of the rotating table and the Brünt-Väisälä frequency of the density stratification. Our results show that the merging critical distance depends drastically on the Rossby radius of deformation of the vortices and are in complete agreement with previous numerical modelling of vortex coalescence. We have also observed that mergers involve three-dimensional processes as the vortices intertwine together possibly because of the presence of an elliptic instability that tilts the vortex cores. They are also accompanied by the emission of vorticity filaments and internal gravity waves radiation although we cannot prove that in our experiments these waves are solely due to the merging process.

Using Microfluidic Set-Up to Determine the Adsorption Rate of Sporosarcina pasteurii Bacteria on Sandstone

Microbial-induced carbonate precipitation (MICP) in porous media is a two-step procedure: First, the suspension of bacteria is injected and some of the bacteria get stuck on the grains. The second stage consists in the injection of a calcifying solution that triggers the calcite precipitation and creates a calcite shell around the bacteria. In the present article, we describe a novel method to measure the adhesion rate of Sporosarcina pasteurii bacteria on sandstone and that, additionally, allows to obtain information about local position of the calcite crystals on the sandstone grains. The method is based on the detection of the crystals developed on grains placed inside a microfluidic cell. The potential of the technique was evaluated and demonstrated by studying the influence of the injection time and ionic strength on the adhesion rate and on the spatial distribution of the crystals. The values of the adhesion rates are in good agreement with values determined using column experiments. We find, for example, an increase in the adhesion rate with the NaCl in solution, with a rate of the order of 0.005 min$$^{-1}$$ for a concentration of 3 g/L. with a maximum of 0.03 min$$^{-1}$$ for experiments realized with a salt concentration of 20 g/L. Our work shows it is possible to use small volumes of fluid to determine quantities accurately, such as adhesion rate or crystals spatial repartition, avoiding the waste of a large quantity of fluids. The method also opens the possibility to screen different fluid compositions and flow conditions to optimize the MICP process.

Resolution of sclerosing encapsulating peritonitis in a young dog

An eight-month-old Labrador retriever presented with abdominal effusion. Abdominal ultrasonography revealed significant free fluid and a linear hyperechoic band surrounding the abdominal organs. CT showed the gastrointestinal organs to be...

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is particularly important in COVID-19, as patients can deteriorate rapidly. Despite the advantages, these routes of administration face challenges including a relatively small surface area for effective drug absorption, small volume of fluid for drug dissolution and the presence of a mucus barrier, thereby limiting the number of drugs that are suitable to be delivered through the transmucosal route. In this review, the merits, challenges and limitations of each of these transmucosal routes are discussed. The goals are to provide insights into using transmucosal drug delivery to bring about the best possible symptom management for patients at the end of life, and to inspire scientists to develop new delivery systems to provide effective symptom management for this group of patients.

A rapid, automatic and accurate assay for quantifying temocillin in human serum and CSF using turbulent flow liquid chromatography coupled to high-resolution mass spectrometry. Clinical application.

Temocillin is a β-lactamase-resistant penicillin used for the treatment of multiple drug-resistant Gram-negative bacteria. To maximize efficacy and avoid adverse effects, the dose regimen has to be quickly adjusted to the clinical situations. This necessitates the development of a rapid, reliable and accurate analytical method. Temocillin and the stable isotopically labeled internal standard ([13 C6 ]-amoxicillin) were extracted from either serum or cerebrospinal fluid by a turbulent flow liquid chromatographic method and eluted onto an octadecyl-silica phase with polar endcapping. Mass spectrometry was conducted using an exact mass determination method by electrospray positive ionization high-resolution mass spectrometry. The LLOQ and ULOQ of the present method were determined to be 0.4 and 200 μg/ml for serum and cerebrospinal fluid samples, respectively. The total analysis time was <7 min. The recovery ranged from 87.7 to 120.8%. Intra- and inter-day precision and trueness were tested at four concentration levels: 0.4, 8, 40 and 160 μg/ml. Values were 6.33 ± 1.53, 8.8 ± 1.3, 8.8 ± 0.36 and 2.1 ± 0.76%, and 5.0 ± 0.54, 9.9 ± 1.0, 5.8 ± 1.6 and 0.1 ± 1.1%, for inter- and intra-day analysis, respectively. Temocillin was found to be stable under all relevant laboratory conditions. The method was cross-validated with a microbiological assay. This method is suitable for accurate measurement of temocillin concentration in small volumes of serum or cerebrospinal fluid. Thanks to the online extraction procedure, the overall analytical time is compatible with high-throughput analysis for clinical application.