Advanced Research and Development in Unconventional Use of Tracer Technology for EOR and IOR: What lies beyond?

Over the last few decades, tracers have provided crucial insights on fluid flow behavior assessing reservoir connectivity. For years, they had been viewed as mostly passive molecules that go with the flow of the injected fluid and uncover pathways between injectors and producers. The proposed paper sheds light on some interesting newer frontiers of tracer applications with unconventional uses to gain further flow insight from an oil and gas reservoir. Although primarily developed for interwell applications, newer and more sophisticated genres of tracers have found their way to assist with well fluid flow behavior. Inflow tracer applications, used for phase flow diagnostics, have been around for a few decades now. However, with several parameters like physical space restrictions, temperature, solid support selection, multi-phase flow, initial surge and target concentrations at play, it was soon realised that an extended lifetime was needed to provide techno-economic benefits during reservoir monitoring. Microencapsulation of tracer molecules is one of the newer developed techniques that has shown significant extension to tracer life in controlled release tracer applications as well as improved dispersibility within fracking fluid. Newer synthesis mechanisms like microencapsulation have been developed to linearize inflow tracer release profiles that has led to a substantial increase in tracer lifetime. As the research and development progressed, newer tracers such as frac bead tracers were developed allowing long term fluid flowback monitoring in fracture stimulated wells. In parallel, it is still an active field of investigation as to how tracers can be integrated with common downhole completion and topside equipment of a well to accurately detect early water breakthrough. The paper discusses the advances in these target areas where chemistry is constantly being upgraded to suit end user needs. Novel applications and ‘out-of-the-box’ uses have been developed in the last couple of years where inflow tracers have found a modified use within the gas lift system in a well and integrated with the top-side flow arm of the well, eradicating the need for individual sampling of wells and detection of water breakthrough at an early onset, thus aiding timely decision making and improved recovery from the well. Real time analysis of tracers have attracted attention for quite some time now. The paper also discusses the latest development in this area and the challenges associated with real field applications. While advancements in versatility of the tracer molecules have been published prior in literature, to the best of the authors’ knowledge, no work has been published to date that discusses the latest advances in unconventional uses of the tracer molecules aiding EOR and IOR processes.

Molecular-Level Interactions of Nanodisc-Forming Copolymers Dissected by EPR Spectroscopy

In this study, we focus on analyzing the non-covalent interaction patterns between three lipid-nanodisc-forming polymers and nitroxide radicals which are used as small organic tracer molecules. Besides the negatively charged polymers DIBMA and SMA(2:1), we characterize the solvation behavior of a new zwitterionic styrene/maleic amide sulfobetaine copolymer named SMA-SB. The used nitroxide spin probes vary in their respective chemical structure, allowing the report of different local micropolarities and nanoscopic regions by recording temperature-dependent continuous-wave electron paramagnetic resonance (CW EPR) spectra. In combination with dynamic light scattering (DLS) and electrophoretic light scattering (ELS) experiments, we are able to provide a nanoscopic interpretation of the dominant interaction patterns between the polymer and the chosen guest molecule.

Molecular-Level Interactions of Nanodisc-Forming Copolymers Dissected by EPR Spectroscopy

In this study, we focus on analyzing the non-covalent interaction patterns between three lipid-nanodisc-forming polymers and nitroxide radicals which are used as small organic tracer molecules. Besides the negatively charged polymers DIBMA and SMA(2:1), we characterize the solvation behavior of a new zwitterionic styrene/maleic amide sulfobetaine copolymer named SMA-SB. The used nitroxide spin probes vary in their respective chemical structure, allowing the report of different local micropolarities and nanoscopic regions by recording temperature-dependent continuous-wave electron paramagnetic resonance (CW EPR) spectra. In combination with dynamic light scattering (DLS) and electrophoretic light scattering (ELS) experiments, we are able to provide a nanoscopic interpretation of the dominant interaction patterns between the polymer and the chosen guest molecule.

Fluorescence polarization immunoassay for the determination of diclofenac in wastewater

Pharmacologically active compounds are often detected in wastewater and surface waters. The nonsteroidal anti-inflammatory drug diclofenac (DCF) was included in the European watch list of substances that requires its environmental monitoring in the member states. DCF may harmfully influence the ecosystem already at concentrations ≤ 1 μg L−1. The fast and easy quantification of DCF is becoming a subject of global importance. Fluorescence polarization immunoassay (FPIA) is a homogeneous mix-and-read method which does not require the immobilization of reagents. FPIA can be performed in one phase within 20–30 min, making it possible to analyse wastewater without any complicated pre-treatment. In this study, new tracer molecules with different structures, linking fluorophores to derivatives of the analyte, were synthesized, three homologous tracers based on DCF, two including a C6 spacer, and one heterologous tracer derived from 5-hydroxy-DCF. The tracer molecules were thoroughly assessed for performance. Regarding sensitivity of the FPIA, the lowest limit of detection reached was 2.0 μg L−1 with a working range up to 870 μg L−1. The method was validated for real wastewater samples against LC-MS/MS as reference method with good agreement of both methods.

Optotracing for selective fluorescence-based detection, visualization and quantification of live S. aureus in real-time

Methods for bacterial detection are needed to advance the infection research and diagnostics. Based on conformation-sensitive fluorescent tracer molecules, optotracing was recently established for dynamic detection and visualization of structural amyloids and polysaccharides in the biofilm matrix of gram-negative bacteria. Here, we extend the use of optotracing for detection of gram-positive bacteria, focussing on the clinically relevant opportunistic human pathogen Staphylococcus aureus. We identify a donor-acceptor-donor-type optotracer, whose binding-induced fluorescence enables real-time detection, quantification, and visualization of S. aureus in monoculture and when mixed with gram-negative Salmonella Enteritidis. An algorithm-based automated high-throughput screen of 1920 S. aureus transposon mutants recognized the cell envelope as the binding target, which was corroborated by super-resolution microscopy of bacterial cells and spectroscopic analysis of purified cell wall components. The binding event was essentially governed by hydrophobic interactions, which permitted custom-designed tuning of the binding selectivity towards S. aureus versus Enterococcus faecalis by appropriate selection of buffer conditions. Collectively this work demonstrates optotracing as an enabling technology relevant for any field of basic and applied research, where visualization and detection of S. aureus is needed.

Determinants of Intraparenchymal Infusion Distributions: Modeling and Analyses of Human Glioblastoma Trials

Intra-parenchymal injection and delivery of therapeutic agents have been used in clinical trials for brain cancer and other neurodegenerative diseases. The complexity of transport pathways in tissue makes it difficult to envision therapeutic agent distribution from clinical MR images. Computer-assisted planning has been proposed to mitigate risk for inadequate delivery through quantitative understanding of infusion characteristics. We present results from human studies and simulations of intratumoral infusions of immunotoxins in glioblastoma patients. Gd-DTPA and 124I-labeled human serum albumin (124I-HSA) were co-infused with the therapeutic, and their distributions measured in MRI and PET. Simulations were created by modeling tissue fluid mechanics and physiology and suggested that reduced distribution of tracer molecules within tumor is primarily related to elevated loss rates computed from DCE. PET-tracer on the other hand shows that the larger albumin molecule had longer but heterogeneous residence times within the tumor. We found over two orders of magnitude variation in distribution volumes for the same infusion volumes, with relative error ~20%, allowing understanding of even anomalous infusions. Modeling and measurement revealed that key determinants of flow include infusion-induced expansion and loss through compromised BBB. Opportunities are described to improve computer-assisted CED through iterative feedback between simulations and imaging.

Convective forces increase rostral delivery of intrathecal antisense oligonucleotides in the cynomolgus monkey nervous system

ABSTRACTBackgroundThe intrathecal (IT) dosing route introduces drugs directly into the CSF to bypass the blood-brain barrier and gain direct access to the CNS. We evaluated the use of convective forces acting on the cerebrospinal fluid as a means for increasing rostral delivery of IT dosed radioactive tracer molecules and antisense oligonucleotides (ASO) in the monkey CNS. We also measured the cerebral spinal fluid (CSF) volume in a group of cynomolgus monkeys.MethodsThere are three studies presented, in each of which cynomolgus monkeys were injected into the IT space with radioactive tracer molecules and/or ASO by lumbar puncture in either a low or high volume. The first study used the radioactive tracer 64Cu-DOTA and PET imaging to evaluate the effect of the convective forces. The second study combined the injection of the radioactive tracer 99mTc-DTPA and ASO, then used SPECT imaging and ex vivo tissue analysis of the effects of convective forces to bridge between the tracer and the ASO distributions. The third experiment evaluated the effects of different injection volumes on the distribution of an ASO. In the course of performing these studies we also measured the CSF volume in the subject monkeys by Magnetic Resonance Imaging.ResultsIt was consistently found that larger bolus dose volumes produced greater rostral distribution along the neuraxis. Thoracic percussive treatment also increased rostral distribution of low volume injections. There was little added benefit on distribution by combining the thoracic percussive treatment with the high-volume injection. The CSF volume of the monkeys was found to be 11.9 ± 1.6 cm3.ConclusionsThese results indicate that increasing convective forces after IT injection increases distribution of molecules up the neuraxis. In particular, the use of high IT injection volumes will be useful to increase rostral CNS distribution of therapeutic ASOs for CNS diseases in the clinic.

Use of Immunohistochemistry to Establish Ethiology in the Case of Primary Spontaneous Pneumotorax Patients

Primary spontaneous pneumothorax has a complex morphopathological substrate, in which active smoking plays an essential etiopathogenic role. Inflammation of the distal airways, bronchial anomalies, perivascular eosinophilic infiltrate associated with hereditary factors and physiognomy (longilli patients) lead to obstruction of distal airwayswhich is the essential element in the emergence of emphysematous changes. Immunohistochemistry (IHC) is a technique used to identify cellular or tissue (antigens) constituents by Ag-Ac, the Ac link site being identified either by direct labeling of the antibody or by a secondary labeling method. IHC reactions are based on tissue-antibody antigen binding, the latter being evidenced by direct conjugation to tracer molecules (direct reaction) or by another chain of other labeled free antibody linkages. We can consider the immunohistochemical method as having a potential utility, especially in selected patients, where there are sufficient clinical and epidemiological reasons to suspect a pneumothorax-causing disease but where the classical investigations did not provide diagnostic performance.

The lens internal microcirculation system delivers solutes to the lens core faster than would be predicted by passive diffusion

It has been proposed that optical properties of the lens are actively maintained by an internal microcirculation system that utilizes ionic and fluid fluxes to deliver nutrients to deeper regions of the lens tissue via the extracellular space faster than would occur by passive diffusion alone. To test this hypothesis, we utilized a range of commercially available magnetic resonance imaging (MRI) reagents of varying molecular sizes that served as tracers of extracellular solute delivery. The penetration of these tracers into bovine lenses incubated in the absence and presence of solutions that inhibit the microcirculation was monitored in real time over a 4-h period using T1-weighted MRI. We found that only the smaller contrast agents were delivered to the core of the lens and that the rate of solute penetration was significantly faster than that calculated simple diffusion. Next, the lenses were first incubated in either high extracellular K+to depolarize the lens potential or ouabain to inhibit the Na+pump. These two perturbations are known to inhibit the circulating ionic and fluid fluxes that are proposed to drive solute delivery into the lens core. Both perturbations inhibited the delivery of the extracellular tracer molecules to the lens core. Our findings suggest that the microcirculation system can potentially be harnessed to deliver exogenous antioxidants to the lens core to afford mature fiber cells protection against oxidative damage that ultimately manifests as age-related nuclear cataract.