Raman-Activated, Interactive Sorting of Isotope-Labeled Bacteria.

Due to its high spatial resolution, Raman microspectroscopy allows for the analysis of single microbial cells. Since Raman spectroscopy analyzes the whole cell content, this method is phenotypic and can therefore be used to evaluate cellular changes. In particular, labeling with stable isotopes (SIPs) enables the versatile use and observation of different metabolic states in microbes.

Piloting delivery of PfSPZ vaccines for malaria through a cryogenic vaccine cold chain to travel and military medicine clinics.

Background: PfSPZ vaccines comprising Plasmodium falciparum (Pf) sporozoites (SPZ) have demonstrated > 90% protection against variant Pf malaria infections for at least 12 weeks; they are the only vaccines with the level of efficacy necessary to protect travellers. PfSPZ are eukaryotic cells stabilized by cryopreservation and distributed using a cryogenic (below -150 °C) cold chain. The Ebola vaccine and mRNA vaccines against SARS-CoV-2 pioneered uptake of vaccines requiring non-standard ultra-low temperature cold chains.

From Microtiter Plates to Droplets-There and Back Again.

Droplet-based microfluidic screening techniques can benefit from interfacing established microtiter plate-based screening and sample management workflows. Interfacing tools are required both for loading preconfigured microtiter-plate (MTP)-based sample collections into droplets and for dispensing the used droplets samples back into MTPs for subsequent storage or further processing. Here, we present a collection of Digital Microfluidic Pipetting Tips (DMPTs) with integrated facilities for droplet generation and manipulation together with a robotic system for its operation.

Multispectral Imaging Flow Cytometry with Spatially and Spectrally Resolving Snapshot-Mosaic Cameras for the Characterization and Classification of Bioparticles.

In the development and optimization of biotechnological cultivation processes the continuous monitoring through the acquisition and interpretation of spectral and morphological properties of bioparticles are challenging. There is therefore a need for the parallel acquisition and interpretation of spatially and spectrally resolved measurements with which particles can be characterized and classified in-flow with high throughput. Therefore, in this paper we investigated the scientific and technological connectivity of standard imaging flow cytometry (IFC) with filter-on-chip based spatially and spectrally resolving snapshot-mosaic cameras for photonic sensing and control in a smart and innovative microfluidic device.

An automated microfluidic platform for the screening and characterization of novel hepatitis B virus capsid assembly modulators.

To date, hepatitis B virus (HBV) capsid assembly modulators (CAMs), which target the viral core protein and induce the formation of non-functional viral capsids, have been identified and characterized in microtiter plate-based biochemical or cell-based assays. In this work, we developed an automated microfluidic screening assay, which uses convection-dominated Taylor-Aris dispersion to generate high-resolution dose-response curves, enabling the measurements of compound EC values at very short incubation times. The measurement of early kinetics down to 7.

Treatment resistance analysis reveals GLUT-1-mediated glucose uptake as a major target of synthetic rocaglates in cancer cells.

Rocaglates are natural compounds that have been extensively studied for their ability to inhibit translation initiation. Rocaglates represent promising drug candidates for tumor treatment due to their growth-inhibitory effects on neoplastic cells. In contrast to natural rocaglates, synthetic analogues of rocaglates have been less comprehensively characterized, but were also shown to have similar effects on the process of protein translation.

Review: tomographic imaging flow cytometry.

Within the last decades, conventional flow cytometry (FC) has evolved as a powerful measurement method in clinical diagnostics, biology, life sciences and healthcare. Imaging flow cytometry (IFC) extends the power of traditional FC by adding high resolution optical and spectroscopic information. However, the conventional IFC only provides a 2D projection of a 3D object.

Three step flow focusing enables image-based discrimination and sorting of late stage 1 Haematococcus pluvialis cells.

Label-free and gentle separation of cell stages with desired target properties from mixed stage populations are a major research task in modern biotechnological cultivation process and optimization of micro algae. The reported microfluidic sorter system (MSS) allows the subsequent investigation of separated subpopulations. The implementation of a viability preserving MSS is shown for separation of late stage 1 Haematococcus pluvialis (HP) cells form a mixed stage population.

Re: Results of a randomized trial of treatment modalities in patients with low or early‑intermediate risk prostate cancer (PREFERE trial).

The authors of this "Letter to the Editors" express their major concern about selective and biased reporting in this paper.

Microfluidic Chamber Design for Controlled Droplet Expansion and Coalescence.

The defined formation and expansion of droplets are essential operations for droplet-based screening assays. The volumetric expansion of droplets causes a dilution of the ingredients. Dilution is required for the generation of concentration graduation which is mandatory for many different assay protocols.

3-Step flow focusing enables multidirectional imaging of bioparticles for imaging flow cytometry.

Multidirectional imaging flow cytometry (mIFC) extends conventional imaging flow cytometry (IFC) for the image-based measurement of 3D-geometrical features of particles. The innovative core is a flow rotation unit in which a vertical sample lamella is incrementally rotated by 90 degrees into a horizontal lamella. The required multidirectional views are generated by guiding all particles at a controllable shear flow position of the parabolic velocity profile of the capillary slit detection chamber.

Translation Inhibition by Rocaglates Activates a Species-Specific Cell Death Program in the Emerging Fungal Pathogen Candida auris.

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen has caused considerable concern because most isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against , we screened 2,454 compounds from a diversity-oriented synthesis collection.

Rocaglates Induce Gain-of-Function Alterations to eIF4A and eIF4F.

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action.

Loop-mediated amplification as promising on-site detection approach for Legionella pneumophila and Legionella spp.

Recently Legionella pneumophila is the main causative waterborne organism of severe respiratory infections. Additionally, other Legionella species are documented as human pathogens. In our work, we describe a rapid detection method which combines two advantages for sensitive and specific detection of the genus Legionella: the fast isothermal amplification method "Loop-mediated isothermal AMPlification" (LAMP), and a colorimetric detection method using the metal indicator hydroxynaphtol blue (HBN) which allows to determine an optical signal with a simple readout (with the naked eye).

Application of High-Throughput Screening Raman Spectroscopy (HTS-RS) for Label-Free Identification and Molecular Characterization of Pollen.

Pollen studies play a critical role in various fields of science. In the last couple of decades, replacement of manual identification of pollen by image-based methods using pollen morphological features was a great leap forward, but challenges for pollen with similar morphology remain, and additional approaches are required. Spectroscopy approaches for identification of pollen, such as Raman spectroscopy has potential benefits over traditional methods, due to the investigation of the intrinsic molecular composition of a sample.

Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors.

Rocaglates share a common cyclopenta[b]benzofuran core that inhibits eukaryotic translation initiation by modifying the behavior of the RNA helicase, eIF4A. Working as interfacial inhibitors, rocaglates stabilize the association between eIF4A and RNA, which can lead to the formation of steric barriers that block initiating ribosomes. There is significant interest in the development and expansion of rocaglate derivatives, as several members of this family have been shown to possess potent anti-neoplastic activity in vitro and in vivo.

Genetic toxicity studies of glycolipids from Dacryopinax spathularia.

A series of in vitro studies were conducted to assess the genetic toxicity of jelly mushroom glycolipids from Dacryopinax spathularia (herein referred to as "AM-1"). In the bacterial reverse mutation assay (Ames test), there was no evidence of mutagenic activity in any Salmonella typhimurium strains tested or in Escherichia coli strain WP2uvrA, at dose levels up to 5000 μg/plate. In the micronucleus (MN) test using human lymphocytes, AM-1 did not show a statistically significant increase in the number of binucleated cells containing micronuclei when compared to concurrent control cultures at all time points and at any of the concentrations analyzed (up to 900 μg/ml of culture medium).

Developmental and reproduction toxicity studies of glycolipids from Dacryopinax spathularia.

The developmental and reproduction toxicity potential of jelly mushroom glycolipids from Dacryopinax spathularia was studied in Crl:CD (SD) rats by daily oral gavage administration at doses of 150, 500 or 1000 mg/kg/day. Pregnant female rats in the developmental study received the test article from Gestation Days 6-19. F and F parental animals in the 2-generation reproduction toxicity study were dosed for a minimum of 70 days prior to mating and throughout mating, gestation, and lactation, until the day prior to euthanasia (following weaning of litters on postnatal day 21).

UV Absorption Spectroscopy in Water-Filled Antiresonant Hollow Core Fibers for Pharmaceutical Detection.

Due to a worldwide increased use of pharmaceuticals and, in particular, antibiotics, a growing number of these substance residues now contaminate natural water resources and drinking supplies. This triggers a considerable demand for low-cost, high-sensitivity methods for monitoring water quality. Since many biological substances exhibit strong and characteristic absorption features at wavelengths shorter than 300 nm, UV spectroscopy presents a suitable approach for the quantitative identification of such water-contaminating species.

A droplet-based microfluidic chip as a platform for leukemia cell lysate identification using surface-enhanced Raman scattering.

A new approach is presented for cell lysate identification which uses SERS-active silver nanoparticles and a droplet-based microfluidic chip. Eighty-nanoliter droplets are generated by injecting silver nanoparticles, KCl as aggregation agent, and cell lysate containing cell constituents, such as nucleic acids, carbohydrates, metabolites, and proteins into a continuous flow of mineral oil. This platform enables accurate mixing of small volumes inside the meandering channels of the quartz chip and allows acquisition of thousands of SERS spectra with 785 nm excitation at an integration time of 1 s.

Pharmacokinetics, excretion balance, and tissue distribution of [C]-labeled glycolipids and long chain fatty acids from Dacryopinax spathularia in rats.

The pharmacokinetics, excretion balance, and tissue distribution of [C]-labeled glycolipids from Dacryopinax spathularia (herein referred to as "AM-1") and [C]-LCFA equivalents following single or repeated administration to Sprague Dawley rats were evaluated to support the safety assessment of these naturally derived jelly mushroom glycolipids for use as a food ingredient. Rats received equimolar doses of either [C]-AM-1 or [C]-LCFA via oral or intravenous administration followed by collection of biological samples at specified intervals. Approximately 88%-101% of the administered dose was recovered in expired air, urine, feces, and carcass following single or repeated oral administration of [C]-AM-1 at 100 mg/kg or equimolar doses of [C]-LCFA at 46 mg/kg.

Interlaboratory concordance of PD-L1 immunohistochemistry for non-small-cell lung cancer.

Aims: Programmed death ligand 1 (PD-L1) immunohistochemistry has become a mandatory diagnostic test in the treatment of lung cancer. Several research initiatives have started to harmonise the five PD-L1 immunohistochemistry assays that have been used in clinical trials. Here, we report data on interlaboratory and interassay concordance for commercial assays ('assays') and laboratory-developed tests (LDTs) at 10 German testing sites.

A 90-day oral toxicity study of glycolipids from Dacryopinax spathularia in Beagle dogs.

The subchronic toxicity of glycolipids from Dacryopinax spathularia (herein referred to as "AM-1") was studied in male and female Beagle dogs administered AM-1 by oral capsule at doses of 150, 500 or 1000 mg/kg/day for 90 days. AM-1 was well tolerated at all dosages and there were no test article-related effects on survival, clinical observations, neurological screening (functional observational battery) parameters, clinical pathology parameters, organ weights, macroscopic or microscopic evaluations. Test article-related changes were limited to minimal effects on food consumption and body weight changes in the 1000 mg/kg/day group females.

A 90-day oral toxicity study of glycolipids from Dacryopinax spathularia in CD rats.

The subchronic toxicity of jelly mushroom glycolipids from Dacryopinax spathularia (herein referred to as "AM-1") was studied in Crl:CD(SD) rats. The test item was administered via the drinking water at concentrations of 1.5, 5.