Design and fabrication of a centrifugally driven microfluidic disk for fully integrated metabolic assays on whole blood

For the first time, we present a novel and fully integrated centrifugal microfluidic “ lab-on-a-disk” for rapid metabolic assays in human whole blood. All essential steps comprising blood sampling, metering, plasma extraction and the final optical detection are conducted within t = 150 s in passive structures integrated on one disposable disk. Our technology features a novel plasma extraction structure (V = 500 nL, CV < 5%) without using any hydrophobic microfluidics where the purified plasma (cRBC< 0.11%) is centrifugally separated and subsequently extracted through a capillarily primed extraction channel into the detection chamber. While this capillary extraction requires precisely defined, narrow micro-structures, the reactive mixing and detection is most efficient within larger cavities. The corresponding manufacturing technique of these macro- and micro structures in the range of 30 µ m to 1000 µ m is also presented for the first time: A novel, cost-efficient hybrid prototyping technique of a multiscale epoxy master for subsequent hot embossing of polymer disks

Observation of an orbital interaction-induced Feshbach resonance in 173-Yb

We report on the experimental observation of a novel inter-orbital Feshbach resonance in ultracold 173-Yb atoms, which opens the possibility of tuning the interactions between the 1S0 and 3P0 metastable state, both possessing vanishing total electronic angular momentum. The resonance is observed at experimentally accessible magnetic field strengths and occurs universally for all hyperfine state combinations. We characterize the resonance in the bulk via inter-orbital cross-thermalization as well as in a three-dimensional lattice using high-resolution clock-line spectroscopy.Comment: 5 pages, 4 figure

Direct hemoglobin measurement by monolithically integrated optical beam guidance

We present a concept for optical beam guidance by total internal reflection (TIR) at V-grooves as retro reflectors which are monolithically integrated on a microfluidic "lab-on-a-disk". This way, the optical path length through a measurement chamber and thus the sensitivity of colorimetric assays is massively enhanced compared to direct (perpendicular) beam incidence. With this rugged optical concept, we determine the concentration of hemoglobin (Hb) in human whole blood. Outstanding features are a high degree of linearity (R2 = 0.993) between the optical signal and the Hb together with a reproducibility of CV= 2.9 %, and a time-to-result of 100 seconds, only

Optical beam guidance in monolithic polymer chips for miniaturized colorimetric assays

For the first time, we present a simple and robust optical concept to enable precise and sensitive read-out of colorimetric assays in flat lab-on-a-chip devices. The optical guidance of the probe beam through an incorporated measurement chamber to the detector is based on the total internal reflection at V-grooves in the polymer chip. This way, the optical path length through the flat measurement chamber and thus the performance of the measurements are massively enhanced compared to direct (perpendicular) beam incidence. This is demonstrated by a chip-based, colorimetric glucose-assay on serum. Outstanding features are an excellent reproducibility (CV= 1.91 %), a competitive lower limit of detection (cmin = 124 μM), and a high degree of linearity (R2 = 0.998) within a working range extending over nearly three orders of magnitude

Parallelization of chip-based fluorescence immuno-assays with quantum-dot labelled beads

This paper presents an optical concept for the read-out of a parallel, bead-based fluorescence immunoassay conducted on a lab-on-a-disk platform. The reusable part of the modular setup comprises a detection unit featuring a single LED as light source, two emission-filters, and a color CCD-camera as standard components together with a spinning drive as actuation unit. The miniaturized lab-on-a-disk is devised as a disposable. In the read-out process of the parallel assay, beads are first identified by the color of incorporated quantum dots (QDs). Next, the reaction-specific fluorescence signal is quantified with FluoSpheres-labeled detection anti-bodies. To enable a fast and automated read-out, suitable algorithms have been implemented in this work. Based on this concept, we successfully demonstrated a Hepatitis-A assay on our disk-based lab-on-a-chip

Observation of coherent multiorbital polarons in a two-dimensional Fermi gas

We report on the experimental observation of multiorbital polarons in a two-dimensional Fermi gas of $^{173}\mathrm{Yb}$ atoms formed by mobile impurities in the metastable $^3\mathrm{P}_0$ orbital and a Fermi sea in the ground-state $^1\mathrm{S}_0$ orbital. We spectroscopically probe the energies of attractive and repulsive polarons close to an orbital Feshbach resonance and characterize their coherence by measuring the quasiparticle residue. For all probed interaction parameters, the repulsive polaron is a long-lived quasiparticle with a decay rate more than 2 orders of magnitude below its energy. We formulate a many-body theory, which accurately treats the interorbital interactions in two dimensions and agrees well with the experimental results. Our work paves the way for the investigation of many-body physics in multiorbital ultracold Fermi gases.Comment: 6 pages, 4 figures; Supplementary Materia

Influence of Pacing Mode and Rate on Peripheral Levels of Atrial Natriuretic Peptide (ANP)

The effect of acute modifications of pacing mode and rate on plasma ANP levels was evaluated. ANP was determined in ten resting patients with ODD pacemokers due to binodal disease or intermittent second- and third-degree AV block. At 82/minute pacing rate the ANP plasma levels (normal range 2 to 30 fmol/mL) corresponded to those under AAI (4.05 ± 2.10 fmol/mL) and DDD (4.18 ± 2.02 fmol/mL) pacing, but increased significantly (P < 0.05) during VVI pacing (6.96 ± 3.70 fmol/mL). Acceleration of DDD stimulation frequency from 82 to 113/minutes led to significant increases of ANP levels by the factor of three in all chosen AV delays. The lowest ANP plasma levels were measured of 175 msec AV delay under 82/minute pacing rate in DDD mode. Under 113/minutes the differences of ANP concentration after variations of AV delays were less pronounced. The influences of altered atrial pressure and tension on ANP release are discussed to account for changes in ANP plasma levels following different modes and rates of pacemaker stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75366/1/j.1540-8159.1989.tb01862.x.pd

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies