Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of diluted whole blood, without labeling, enrichment or separation, at rates of 1000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in blood and adds a functional dimension to conventional blood analysis.

Handling of submicron-sized objects is important in many biochemical and biomedical applications, but few methods today can precisely manipulate this range of particles. We present gradient acoustic focusing that enables flow-through particle separation of submicron particles and cells and we apply it for separation of bacteria from blood lysate to facilitate their detection in whole blood for improved diagnostics. To control suspended objects below the classical 2µm size limit for acoustic focusing, we introduce a co-flowing acoustic impedance gradient to generate a stabilizing acoustic volume force that supresses acoustic streaming. the method is validated theoretically and experimentally using polystyrene particles, Staphylococcus aureus, Streptococcus pneumoniae and Escherichia coli. the applicability of the method is demonstrated by the separation of bacteria from selectively chemically lysed blood. Combined with downstream operations, this new approach opens up for novel methods for sepsis diagnostics.Microfluidic flow-through channel networks can be employed to separate or analyze biological particles by their fluorescent 1 , optical 2 , electrical 3-5 , magnetic 6,7 or bio-mechanical properties 8-12 . A major benefit with these technologies is the ability to integrate sample preparation with optical or chemical analyses on the same chip. Today, few microfluidic tools can handle suspensions containing objects below 1 µm. The main reason is that small objects have a large surface-to-volume-ratio, which makes it challenging to generate a sufficient force to drag them swiftly through a liquid.Acoustic fields can be employed inside microfluidic channels to generate strong acoustic radiation forces to spatially position suspended biological particles 13 . In acoustophoresis 14 cells are separated by their lateral displacement in response to an acoustic field while flowing through a microfluidic channel. For particles smaller than 2 µm the particle motion is normally dominated by acoustic streaming 15-17 which has been a major limitation for this technology. Several systems have been proposed that address this limitation using acoustic seed trapping 18 , acoustic vortices 19,20 or a different aspect ratio of the acoustic cavity [21][22][23][24] . Purification of small particles, e.g. bacteria and platelets [25][26][27][28] has been achieved by acoustically pushing away the larger particles from the smaller particles, but this approach does not enable isolation of sub-micron-sized biological particles from a complex background of molecules, particles or debris that are of smaller size, which is essential for purification protocols. Recently sub-micron particles were pushed away from 100-nm-particles by surface acoustic waves 29,30 and the same approach was applied to separate red blood cells and microvesicles from exosomes in a two-stage process 31 .We recently found that, for bulk acoustic waves, acoustic streaming can be greatly reduced by introducing a gradient in acoustic impedance (mass density times speed o...

Emerging antibiotic resistance demands identification of novel antibacterial compound classes. A bacterial whole-cell screen based on pneumococcal autolysin-mediated lysis induction was developed to identify potential bacterial cell wall synthesis inhibitors. A hit class comprising a 1-amino substituted tetrahydrocarbazole (THCz) scaffold, containing two essential amine groups, displayed bactericidal activity against a broad range of gram-positive and selected gram-negative pathogens in the low micromolar range. Mode of action studies revealed that THCz inhibit cell envelope synthesis by targeting undecaprenyl pyrophosphate–containing lipid intermediates and thus simultaneously inhibit peptidoglycan, teichoic acid, and polysaccharide capsule biosynthesis. Resistance did not readily develop in vitro, and the ease of synthesizing and modifying these small molecules, as compared to natural lipid II–binding antibiotics, makes THCz promising scaffolds for development of cell wall–targeting antimicrobials.

Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of whole blood, without labeling, enrichment or separation, at rates of 1,000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in whole blood and adds a functional dimension to conventional blood analysis.