Research into diagnostic biosensors is a vibrant field that combines scientific challenge with translational opportunities; innovation in healthcare is of great societal interest and is an essential element of future healthcare provision. Photonic and electrochemical biosensors are the dominant modalities, both scientifically and commercially, yet the two scientific communities largely remain separated and siloed. It seems astute to better understand what the two fields can learn from one another so as to progress the key scientific, translational, and commercial challenges.
View Article and Find Full Text PDFNanopores are emerging as a powerful tool for the analysis and characterization of nanoparticles at the single entity level. Here, we report that a PEG-based polymer electrolyte present inside the nanopore enables the enhanced detection of nanoparticles at low ionic strength. We develop a numerical model that recapitulates the electrical response of the glass nanopore system, revealing the response to be sensitive to the position of the polymer electrolyte interface.
View Article and Find Full Text PDFIn allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing CMV-reactivation and associated disease. We report on a 63-year-old male patient with a D-/R+ CMV-serostatus, who showed ongoing low-level CMV-replication post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance.
View Article and Find Full Text PDFBackground: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH - even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines.
View Article and Find Full Text PDFRapid detection of protein and small-molecule analytes is a valuable technique across multiple disciplines, but most in vitro testing of biological or environmental samples requires long, laborious processes and trained personnel in laboratory settings, leading to long wait times for results and high expenses. Fusion of recognition with reporter elements has been introduced to detection methods such as enzyme-linked immunoassays (ELISA), with enzyme-conjugated secondary antibodies removing one of the many incubation and wash steps. Chimeric protein switch biosensors go further and provide a platform for homogenous mix-and-read assays where long wash and incubation steps are eradicated from the process.
View Article and Find Full Text PDFDNA origami synthesis is a well-established technique with wide-ranging applications. In most cases, the synthesized origami must be purified to remove excess materials such as DNA oligos and other functional molecules. While several purification techniques are routinely used, all have limitations, and cannot be integrated with robotic systems.
View Article and Find Full Text PDFDespite advances in monitoring and treatment, cytomegalovirus (CMV) infections remain one of the most common complications after solid organ transplantation (SOT). CMV infection may fail to respond to standard first- and second-line antiviral therapies with or without the presence of antiviral resistance to these therapies. This failure to respond after 14 days of appropriate treatment is referred to as "resistant/refractory CMV.
View Article and Find Full Text PDFNanopore sensing has been successfully used to characterize biological molecules with single-molecule resolution based on the resistive pulse sensing approach. However, its use in nanoparticle characterization has been constrained by the need to tailor the nanopore aperture size to the size of the analyte, precluding the analysis of heterogeneous samples. Additionally, nanopore sensors often require the use of high salt concentrations to improve the signal-to-noise ratio, which further limits their ability to study a wide range of nanoparticles that are unstable at high ionic strength.
View Article and Find Full Text PDFBiosens Bioelectron
October 2023
Multiple sclerosis (MS) is the most common demyelinating autoimmune disease of the central nervous system (CNS). Immune-mediated myelin and axonal damage that is accompanied by chronic axonal loss causing destruction of the myelin sheaths are hallmarks of MS. While great strides have been made in understanding the molecular underpinnings of re-/myelination, currently no remyelination therapy is available for MS.
View Article and Find Full Text PDFAdjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect carbapenem therapeutic drug monitoring (TDM) has on health outcomes, including the emergence of antimicrobial resistance (AMR). Four databases were searched for studies that reported health outcomes following adjustment to dosing regimens, according to measurements of carbapenem concentration.
View Article and Find Full Text PDFDNA nanotechnology has paved the way for new generations of programmable nanomaterials. Utilizing the DNA origami technique, various DNA constructs can be designed, ranging from single tiles to the self-assembly of large-scale, complex, multi-tile arrays. This technique relies on the binding of hundreds of short DNA staple strands to a long single-stranded DNA scaffold that drives the folding of well-defined nanostructures.
View Article and Find Full Text PDFPurpose Of Review: Double-stranded DNA (dsDNA) viruses remain important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As treatment options are limited, adoptive therapy with virus-specific T cells (VST) is promising in restoring immunity and thereby preventing and treating virus infections. Here we review current evidence and recent advances in the field of VST for dsDNA viruses in allogeneic HCT recipients.
View Article and Find Full Text PDFIntroduction: The unprecedented success of chimeric antigen receptor (CAR)-T-cell therapy in the management of B-cell malignancies comes with a price of specific side effects. Healthy B-cell depletion is an anticipated 'on-target' 'off-tumor' side effect and can contribute to severe and prolonged hypogammaglobulinemia. Evidence-based guidelines for the use of immunoglobulin replacement therapy (IGRT) for infection prevention are lacking in this population.
View Article and Find Full Text PDFBackground: Dosing regimens guided by therapeutic drug monitoring (TDM) may be able to improve penicillin exposure in patients, which could result in improved patient health outcomes.
Objectives: This systematic review aims to describe the impact penicillin TDM has on health outcomes, including antimicrobial resistance (AMR).
Methods: Studies measuring penicillins in patient samples that adjusted regimens according to the result, and reported health outcomes were selected.
Unlabelled: Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B-cell malignancies are immunocompromised and at risk for serious infections. Vaccine immunogenicity is unknown in this population. We conducted a prospective observational study of the humoral immunogenicity of 2019-2020 inactivated influenza vaccines (IIV) in children and adults immediately prior to (n=7) or 13-57 months after (n=15) CD19-, CD20-, or BCMA-targeted CAR-T-cell therapy, as well as controls (n=8).
View Article and Find Full Text PDFBACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay.
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