Receptor Probes Research Articles

Selective, Intrinsically Fluorescent Trk Modulating Probes.

Neurotrophins (NTs) elicit the growth, survival, and differentiation of neurons and other neuroectoderm tissues via activation of Trk receptors. Hot spots for NT·Trk interactions involve three neurotrophin loops. Mimicry of these using "cyclo-organopeptides" comprising loop sequences cyclized onto endocyclic organic fragments accounts for a few of the low molecular mass Trk agonists or modulators reported so far; the majority are nonpeptidic small molecules accessed without molecular design and identified in random screens. It has proven difficult to verify activities induced by low molecular mass substances are due to Trk activation (rather than via other receptors), enhanced Trk expression, enhanced NT expression, or other pathways. Consequently, identification of selective probes for the various Trk receptors (e.g., A, B, and C) has been very challenging. Further, a key feature of probes for early stage assays is that they should be easily detectable, and none of the compounds reported to date are. In this work, we designed novel cyclo-organopeptide derivatives where the organic fragment is a BODIPY fluor and found ones that selectively, though not specifically, activate TrkA, B, or C. One of the assays used to reach this conclusion (binding to live Trk-expressing cells) relied on intrinsic fluorescence in the tested materials. Consequently, this work established low molecular mass Trk-selective probes exhibiting neuroprotective effects.

Novel 18F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging

Novel ¹⁸F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging

Enhanced Detection of Klebsiella Pneumoniae Using Electric-Double-Layer FET Sensor: Rapid, Temperature-Boosted Probe-Target Binding Analysis

Klebsiella pneumoniae demonstrates versatility in its pathogenicity, leading to diverse infections in humans such as pneumonia, urinary tract infections, bacteremia, wound infections, meningitis, endocarditis, and sepsis. The severity of these infections is contingent upon the patient's immune status, the site of infection, and the existence of underlying medical comorbidities. A sputum or urine culture, on the other hand, typically takes between 24 and 72 hours to produce results. Over recent years, various innovative methodologies have emerged, including optical and electrochemical techniques and molecular detection via PCR. Despite the diversity of available techniques, concerns persist regarding their sensitivity and specificity. Moreover, fluorescence-based methodologies and Surface Plasmon Resonance (SPR)-based sensors have been explored for bacterial detection. However, these existing methods have drawbacks such as elevated costs, prolonged turnaround times, the need for sophisticated instrumentation, and a demand for skilled personnel. Field-effect transistor (FET) sensors have garnered considerable scientific attention since their inception due to their remarkable sensitivity, facile signal readout, and the capability for label-free assays. The aim of this research is to detect the detect Klebsiella pneumoniae bacteria in blood serum by double electric layer (EDL) extended-gate field-effect transistor (FET) sensor. In this study, a preliminary investigation employed a single-step surface functionalization approach to immobilize receptor probes, specifically single-stranded DNA (ssDNA). This strategy aimed to enable the rapid detection of complementary DNA (cDNA) across varying concentrations, leveraging differential gate voltages to modulate the sensitivity of this analytical platform. The designed probes were successfully immobilized onto a disposable chip housing a pair of gold electrodes. A handheld reader, integrating enhancement-mode N-channel MOSFETs, established connectivity with a laptop via a USB port to facilitate the measurement of sensor signals. By applying pulsed gate voltage to the input electrode, which modulates the channel conductivity which behaves as a function of the charge distribution within the EDL structure, consequently influencing the drain current of the MOSFET. The immobilized probe, positioned on the gate electrode, underwent testing using varying concentrations of cDNA introduced into TE buffer. Detection of probe-target binding occurred through fluorescence alterations and electrically by assessing changes in drain current. In order to improve the response time, we elevated the temperature near the Tm enhances sensitivity and binding rates, in shorter time period of 1 minutes. Figure 1

Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD).

The development of lysergic acid diethylamide (LSD) derivatives and analogs continues to inform the design of novel receptor probes and potentially new medicines. On the other hand, a number of newly developed LSD derivatives have also emerged as recreational drugs, leading to reports of their detection in some countries. One position in the ergoline scaffold of LSD that is frequently targeted is the N1-position; numerous N1-alkylcarbonyl LSD derivatives have been reported where the acyl chain is attached to the indole nitrogen, for example, in the form of linear n-alkane substituents, which represent higher homologs of the prototypical 1-acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52). In this study, 1-hexanoyl-LSD (1H-LSD, SYN-L-027), a novel N1-acyl LSD derivative, was characterized analytically using standard techniques, followed by evaluation of its in vivo behavioral effects using the mouse head-twitch response (HTR) assay in C57BL/6J mice. 1H-LSD induced the HTR, with a median effective dose (ED50) of 192.4 μg/kg (equivalent to 387 nmol/kg), making it roughly equipotent to ALD-52 when tested previously under similar conditions. Similar to other N1-acylated analogs, 1H-LSD is anticipated to by hydrolyzed to LSD in vivo and acts as a prodrug. It is currently unknown whether 1H-LSD has appeared as on the research chemical market or is being used recreationally.

Recent Advancements in the Application of Circulating Tumor DNA as Biomarkers for Early Detection of Cancers.

Early detection of cancer is vital for increasing patient survivability chances. The three major techniques used to diagnose cancers are instrumental examination, tissue biopsy, and tumor biomarker detection. Circulating tumor DNA (ctDNA) has gained much attention in recent years due to advantages over traditional technology, such as high sensitivity, high specificity, and noninvasive nature. Through the mechanism of apoptosis, necrosis, and circulating exosome release in tumor cells, ctDNA can spread throughout the circulatory system and carry modifications such as methylations, mutations, gene rearrangements, and microsatellite instability. Traditional gene-detection technology struggles to achieve real-time, low-cost, and portable ctDNA measurement, whereas electrochemical biosensors offer low cost, high specificity alongside sensitivity, and portability for the detection of ctDNA. Therefore, this review focuses on describing the recent advancements in ctDNA biomarkers for various cancer types and biosensor developments for real-time, noninvasive, and rapid ctDNA detection. Further in the review, ctDNA sensors are also discussed in regards to their selections of probes for receptors based on the electrode surface recognition elements.

Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Additionally, obese and postmenopausal women are at higher risk of all-cause and breast cancer-specific mortality compared with non-obese women with breast cancer. In this context, increased levels of estrogens, excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, adipocyte-derived adipokines, hypercholesterolemia, and excessive oxidative stress contribute to the development of breast cancer in obese women. Genetic evaluation is an integral part of diagnosis and treatment for patients with breast cancer. Despite trimodality therapy, the four-year cumulative incidence of regional recurrence is significantly higher. Axillary lymph nodes as well as primary lesions have diagnostic, prognostic, and therapeutic significance for the management of breast cancer. In clinical setting, because of the obese population primary lesions and enlarged lymph nodes could be less palpable, the diagnosis may be challenging due to misinterpretation of physical findings. Thereby, a nomogram has been created as the "Breast Imaging Reporting and Data System" (BI-RADS) to increase agreement and decision-making consistency between mammography and ultrasonography (USG) experts. Additionally, the "breast density classification system," "artificial intelligence risk scores," ligand-targeted receptor probes," "digital breast tomosynthesis," "diffusion-weighted imaging," "18F-fluoro-2-deoxy-D-glucose positron emission tomography," and "dynamic contrast-enhanced magnetic resonance imaging (MRI)" are important techniques for the earlier detection of breast cancers and to reduce false-positive results. A high concordance between estrogen receptor (ER) and progesterone receptor (PR) status evaluated in preoperative percutaneous core needle biopsy and surgical specimens is demonstrated. Breast cancer surgery has become increasingly conservative; however, mastectomy may be combined with any axillary procedures, such as sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection whenever is required. As a rule, SLNB-guided axillary dissection in breast cancer patients who have clinically axillary lymph node-positive to node-negative conversion following neoadjuvant chemotherapy is recommended, because lymphedema is the most debilitating complication after any axillary surgery. There is no clear consensus on the optimal treatment of occult breast cancer, which is much discussed today. Similarly, the current trend in metastatic breast cancer is that the main palliative treatment option is systemic therapy.

Rapid and Sensitive Pathogen Detection in Serum for Early Sepsis Diagnostics Using an Electrical-Double-Layer Gated Field-Effect Transistor-Based Sensor Array

Sepsis is a major medical inflammatory response to bloodstream infection caused bypathogens. Over 30 million infections occur due to sepsis in a year throughout the globe.With over 6 million deaths, sepsis treatment demands timely diagnosis and medicalinterventions to prevent large outspread of the infection. Rapid and sensitive detection ofinfectious bacteria plays an important role in disease control. However, fast and accuratediagnosis remains highly challenging for many hospitalized patients. Among variousbacterial diseases, Escherichia coli, (E. coli) a gram-negative bacterium, is the mostfrequently and extensively researched and has become a global concern of food safetyproblems. Traditional cell culture methods are considered as most accurate method forbacterial diagnosis. But some microorganisms like Bartonella spp, Treponema pallidum, etc.are difficult to grow on a culture plate, while some other virus species are unculturable, soeventually the traditional cell culture may take several days to a week for the diagnosticresults. Hence, over several years, different novel methods have been developed, such asoptical methods, electrochemical methods, molecular detection by PCR etc. Even thoughseveral techniques exist, concerns have been raised regarding their sensitivity, specificity etc.In addition, various fluorescence-based methods, and Surface Plasmon resonance (SPR)-based sensors have also been reported for bacterial detection. However, high cost, largeturnaround time, expensive instrumentation, and requirement of skilled personnel are some ofthe disadvantages of these existing techniques.FET biosensors have previously been used in different diagnosis areas. Nowadays, severalFET-based biosensors have been developed, which primarily concentrate on improving theoverall sensitivity of FET devices. However, the charge screening effect observed in aphysiological environment, and additional sample processing increase the complexity of thesensor platform. To overcome this hurdle, an electrical double layer (EDL) gated FETbiosensor has been proposed and explored in the detection of a variety of biological entities.Here, we proposed an EDL-FET sensor platform for the detection of Escherichia coliO157:H7 strain in blood serum. A single-step surface functionalization strategy was used forimmobilizing receptor probes as ssDNA. The probes were designed and immobilized over adisposable chip containing a pair of gold electrodes. A handheld reader which consists of anenhancement mode N-channel MOSFETs was connected to the laptop through a USB port tomeasure the sensor signals. Pulsed gate voltage was applied to the input electrode and whichmodulated the EDL capacitance and potential change eventually resulting in the drain currentof the MOSFET. The probe was immobilized on the gate electrode and tested with differentconcentrations of cDNA spiked in TE buffer. The probe-target binding was observed throughfluorescence change and electrically by measuring the change in drain current. In addition,surface potential change was also examined by performing KPFM test. Similarly, the BioFETdetections were validated for E. coli O157 variants by spiking with short and long DNAtarget sequences simultaneously in serum. The test results confirm selectivity by testingvarious non-complementary sequences, which ensures the potential of this BioFET as apoint-of-care sensing device. Figure 1

Imaging Cholinergic Receptors in the Brain by Positron Emission Tomography.

Cholinergic receptors represent a promising class of diagnostic and therapeutic targets due to their significant involvement in cognitive decline associated with neurological disorders and neurodegenerative diseases as well as cardiovascular impairment. Positron emission tomography (PET) is a noninvasive molecular imaging tool that has helped to shed light on the roles these receptors play in disease development and their diverse functions throughout the central nervous system (CNS). In recent years, there has been a notable advancement in the development of PET probes targeting cholinergic receptors. The purpose of this review is to provide a comprehensive overview of the recent progress in the development of these PET probes for cholinergic receptors with a specific focus on ligand structure, radiochemistry, and pharmacology as well as in vivo performance and applications in neuroimaging. The review covers the structural design, pharmacological properties, radiosynthesis approaches, and preclinical and clinical evaluations of current state-of-the-art PET probes for cholinergic receptors.

Development, synthesis and evaluation of novel fluorescent Endothelin-B receptor probes

The endothelin (ET) signaling system is comprised of three endothelin peptides (ET-1, -2 and -3) and two corresponding endothelin-A and -B receptors (ETAR and ETBR), which belong to the G-protein coupled receptor (GPCR) superfamily. The endothelin axis, as this system is also referred to, contributes to the maintenance of vascular tone, functions as regulator of inflammation and proliferation and helps in balancing water homeostasis. In pathological settings, the ET axis is known to contribute to endothelial activation in cardiovascular diseases, to cell proliferation, chemoresistance and metastasis in cancer and to inflammation and fibrosis in renal disease. Antagonists of ETAR and ETBR, either subtype-specific compounds or substances with high affinity to both receptors, have been developed for more than 30 years. In the preclinical context, in vivo imaging of endothelin receptor expression has been utilized to assess ET-axis contribution to e.g. cancer or myocardial infarction. In this work, we present the development and synthesis of two novel ETBR-specific fluorescent probes, based on the available antagonists BQ788 and IRL2500 and their preliminary evaluation in a breast cancer context.

The Parallel Structure-Activity Relationship Screening of Three Compounds Identifies the Common Agonist Pharmacophore of Pyrrolidine Bis-Cyclic Guanidine Melanocortin-3 Receptor (MC3R) Small-Molecule Ligands.

The melanocortin receptors are involved in numerous physiological pathways, including appetite, skin and hair pigmentation, and steroidogenesis. In particular, the melanocortin-3 receptor (MC3R) is involved in fat storage, food intake, and energy homeostasis. Small-molecule ligands developed for the MC3R may serve as therapeutic lead compounds for treating disease states of energy disequilibrium. Herein, three previously reported pyrrolidine bis-cyclic guanidine compounds with five sites for molecular diversity (R1-R5) were subjected to parallel structure-activity relationship studies to identify the common pharmacophore of this scaffold series required for full agonism at the MC3R. The R2, R3, and R5 positions were required for full MC3R efficacy, while truncation of either the R1 or R4 positions in all three compounds resulted in full MC3R agonists. Two additional fragments, featuring molecular weights below 300 Da, were also identified that possessed full agonist efficacy and micromolar potencies at the mMC5R. These SAR experiments may be useful in generating new small-molecule ligands and chemical probes for the melanocortin receptors to help elucidate their roles in vivo and as therapeutic lead compounds.

Development of Negative Controls for Fc-C-Type Lectin Receptor Probes.

Fc-C-type lectin receptor (Fc-CTLRs) probes are soluble chimeric proteins constituted of the extracellular domain of a CTLR fused with the constant fraction (Fc) of the human IgG. These probes are useful tools to study the interaction of CTLRs with their ligands, with applications similar to those of antibodies, often in combination with widely available fluorescent antibodies targeting the Fc fragment (anti-hFc). In particular, Fc-Dectin-1 has been extensively used to study the accessibility of β-glucans at the surface of pathogenic fungi. However, there is no universal negative control for Fc-CTLRs, making the distinction of specific versus nonspecific binding difficult. We describe here 2 negative controls for Fc-CTLRs: a Fc-control constituting of only the Fc portion, and a Fc-Dectin-1 mutant predicted to be unable to bind β-glucans. Using these new probes, we found that while Fc-CTLRs exhibit virtually no nonspecific binding to Candida albicans yeasts, Aspergillus fumigatus resting spores strongly bind Fc-CTLRs in a nonspecific manner. Nevertheless, using the controls we describe here, we were able to demonstrate that A. fumigatus spores expose a low amount of β-glucan. Our data highlight the necessity of appropriate negative controls for experiments involving Fc-CTLRs probes. IMPORTANCE While Fc-CTLRs probes are useful tools to study the interaction of CTLRs with ligands, their use is limited by the lack of appropriate negative controls in assays involving fungi and potentially other pathogens. We have developed and characterized 2 negative controls for Fc-CTLRs assays: Fc-control and a Fc-Dectin-1 mutant. In this manuscript, we characterize the use of these negative controls with zymosan, a β-glucan containing particle, and 2 human pathogenic fungi, Candida albicans yeasts and Aspergillus fumigatus conidia. We show that A. fumigatus conidia nonspecifically bind Fc-CTLRs probes, demonstrating the need for appropriate negative controls in such assays.

Recent advances in small-molecule fluorescent probes with the function of targeting cancer receptors.

Cancer is "the sword of Damocles" that threatens human life and health. Therefore, the diagnosis and treatment of cancer have been receiving much attention. Many overexpressed receptors on the surface of cancer cells provide us with an effective way to specifically identify the cancer cells, and receptor targeting strategies are becoming one of the hot ideas to enhance the ability of fluorescent probes to target tumors. Fluorescent probes connected to ligands are targeted at cancer cell surfaces through receptor-mediated endocytosis. Receptor-targeting probes can image and track cancer cells, determine tumor boundaries, monitor deep lesions, and play a role in clinical medicine, such as fluorescent imaging-guided surgery. In this review, based on the perspective of small molecule fluorescent probes, we reviewed the design ideas, photophysical properties, and applications of receptor-targeting probes for detecting biomarkers in imaging and tracing cancer cells and prospected the future developmental direction of such probes. We hope that this review will provide more ideas for the design and development of active targeting probes for receptors and lead to more applications in the medical field.

Multiplex Assay for Rapid Detection and Analysis of Nucleic Acid Using Barcode Receptor Encoded Particle (BREP).

Several multiplex nucleic acid assay platforms have been developed in response to the increasing importance of nucleic acid analysis, but these assays should be optimized as per the requirements of point-of-care for clinical diagnosis. To achieve rapid and accurate detection, involving a simple procedure, we propose a new concept in the field of nucleic acid multiplex assay platforms using hydrogel microparticles, called barcode receptor-encoded particles (BREPs). The BREP assay detects multiple targets in a single reaction with a single fluorophore by analyzing graphically encoded hydrogel particles. By introducing sets of artificially synthesized barcode receptor and barcode probes, the BREP assay is easily applicable in multiplexing any genetic target; sets of barcode receptors and barcode probes should be designed delicately for universal application. The performance of the BREP assay was successfully verified in a multiplex assay for the identification of different malaria species with high sensitivity, wide dynamic range, fast detection time, and multiplexibility.

Detection of tomato leaf curl New Delhi virus DNA using U-bent optical fiber-based LSPR probes

The detection of Tomato leaf curl New Delhi virus (ToLCNDV) DNA has been presented using U-bent fiber optic sensor (FOS) by an evanescent wave absorption method in the visible region. The localized surface plasmon resonance (LSPR) based FOS was developed by immobilizing gold nanoparticles on the amine-functionalized surface and the receptor probe was prepared by attaching a short segment of the complementary DNA (cDNA) on this surface. Further, the cDNA attachment was confirmed by monitoring the real-time change in LSPR absorption spectra. The conjugation protocol of single-strand DNA (ssDNA) from the viral genome of ToLCNDV was established like antibody-antigen-based assays by observing the real-time change in absorption kinetics. Consequently, a linear correlation between ssDNA concentration and the conjugation-dependent change in refractive index (RI) has been observed. The limit of detection (LOD) using two different cDNA immobilized FOS probes was determined to be 50±10 ng/μL and the change in RI was found 12.5±1.3×10−4 RIU/Abs. From this systematic binding study, a straightforward target-specific sensor has been constructed using a digital electronic logic gate analogy. This device has significant commercial potential for the development of a portable LSPR sensor for real-time detection of plant pathogens in addition to the possibility of multi-target environments.

Electrochemical Biosensors for Circulating Tumor DNA Detection.

Early diagnosis and treatment have always been highly desired in the fight against cancer, and detection of circulating tumor DNA (ctDNA) has recently been touted as highly promising for early cancer-screening. Consequently, the detection of ctDNA in liquid biopsy is gaining much attention in the field of tumor diagnosis and treatment, which has also attracted research interest from industry. However, it is difficult to achieve low-cost, real-time, and portable measurement of ctDNA in traditional gene-detection technology. Electrochemical biosensors have become a highly promising solution to ctDNA detection due to their unique advantages such as high sensitivity, high specificity, low cost, and good portability. Therefore, this review aims to discuss the latest developments in biosensors for minimally invasive, rapid, and real-time ctDNA detection. Various ctDNA sensors are reviewed with respect to their choices of receptor probes, designs of electrodes, detection strategies, preparation of samples, and figures of merit, sorted by type of electrode surface recognition elements. The development of biosensors for the Internet of Things, point-of-care testing, big data, and big health is analyzed, with a focus on their portable, real-time, and non-destructive characteristics.

P-269 - 18F-labeled indole-based analogs with chiral 2,3-dihydroxyfluorobutoxy side chain as highly selective sigma-2 receptor probes for tumor imaging

P-269 - 18F-labeled indole-based analogs with chiral 2,3-dihydroxyfluorobutoxy side chain as highly selective sigma-2 receptor probes for tumor imaging

Snake Toxins Labeled by Green Fluorescent Protein or Its Synthetic Chromophore are New Probes for Nicotinic acetylcholine Receptors.

Fluorescence can be exploited to monitor intermolecular interactions in real time and at a resolution up to a single molecule. It is a method of choice to study ligand-receptor interactions. However, at least one of the interacting molecules should possess good fluorescence characteristics, which can be achieved by the introduction of a fluorescent label. Gene constructs with green fluorescent protein (GFP) are widely used to follow the expression of the respective fusion proteins and monitor their function. Recently, a small synthetic analogue of GFP chromophore (p-HOBDI-BF2) was successfully used for tagging DNA molecules, so we decided to test its applicability as a potential fluorescent label for proteins and peptides. This was done on α-cobratoxin (α-CbTx), a three-finger protein used as a molecular marker of muscle-type, neuronal α7 and α9/α10 nicotinic acetylcholine receptors (nAChRs), as well as on azemiopsin, a linear peptide neurotoxin selectively inhibiting muscle-type nAChRs. An activated N-hydroxysuccinimide ester of p-HOBDI-BF2 was prepared and utilized for toxin labeling. For comparison we used a recombinant α-CbTx fused with a full-length GFP prepared by expression of a chimeric gene. The structure of modified toxins was confirmed by mass spectrometry and their activity was characterized by competition with iodinated α-bungarotoxin in radioligand assay with respective receptor preparations, as well as by thermophoresis. With the tested protein and peptide neurotoxins, introduction of the synthetic GFP chromophore induced considerably lower decrease in their affinity for the receptors as compared with full-length GFP attachment. The obtained fluorescent derivatives were used for nAChR visualization in tissue slices and cell cultures.

Self-assembled quinoxaline derivative: Insight into disaggregation induced selective detection of nitro-aromatics in aqueous medium and live cell imaging

Advancement in fluorescent chemosensor for discriminative and precise detection of picric acid (PA) in aqueous medium is highly desirable owing to its alarming impact on the natural environment via soil and groundwater pollution. To this end, we have successfully fabricated a quinoxaline-based receptor (Probe 1) to detect PA in 100% aqueous medium. Probe 1 self-assembled to form leaf-like structures in pure water as micro aggregates (∼940 nm) and transformed entirely into smaller spherical shape (∼354 nm) upon addition of PA. DFT analysis and lifetime experiment validated that both PET and FRET from the electron-rich Probe 1 to electron-deficient PA are concurrently responsible for effective fluorescence quenching. The self-assembled probe exhibited excellent selectivity towards PA (Ksv of 22.6 × 106 M−1) with a ∼56 ppb detection limit. Importantly, PA detection on solution-coated paper strips was achieved at the picogram level. Furthermore, to evaluate the practical usefulness, the probe has been used to detect PA in actual water and soil samples. Interestingly, Probe 1 was non-toxic to cultured HeLa cells and rendered detection of intracellular picric acid through live cell imaging.

Novel medium-sized di(het)areno-fused 1,4,7-(oxa)thiadiazecines as probes for aminergic receptors

Di(het)areno-fused 1,4,7-(oxa)thiadiazecanes were synthesized by the reduction of the corresponding ten-membered lactams obtained, in turn, via the ‘hydrated imidazoline ring expansion’ (HIRE) methodology. Two of them displayed micromolar agonistic activity towards trace amine-associated receptor 1 (TAAR1) and no affinity towards a panel of dopamine (D2) and serotonin (5-HT1A, 5-HT2A and 5-HT7) receptors. These findings validate compounds of this chemotype as scaffolds for the design of selective aminergic receptor modulators.

A Case Study on Pathogen Transport, Deposition, Evaporation and Transmission: Linking High-Fidelity Computational Fluid Dynamics Simulations to Probability of Infection

A high-fidelity, low-Mach computational fluid dynamics simulation tool that includes evaporating droplets and variable-density turbulent flow coupling is well-suited to ascertain transmission probability and supports risk mitigation methods development for airborne infectious diseases such as COVID-19. A multi-physics large-eddy simulation-based paradigm is used to explore droplet and aerosol pathogen transport from a synthetic cough emanating from a kneeling humanoid. For an outdoor configuration that mimics the recent open-space social distance strategy of San Francisco, maximum primary droplet deposition distances are shown to approach 8.1 m in a moderate wind configuration with the aerosol plume transported in excess of 15 m. In quiescent conditions, the aerosol plume extends to approximately 4 m before the emanating pulsed jet becomes neutrally buoyant. A dose–response model, which is based on previous SARS coronavirus (SARS-CoV) data, is exercised on the high-fidelity aerosol transport database to establish relative risk at eighteen virtual receptor probe locations.