Viscoelastic dynamics of a soft strip subject to a large deformation.

To produce sounds, we adjust the tension of our vocal folds to shape their properties and control the pitch. This efficient mechanism offers inspiration for designing reconfigurable materials and adaptable soft robots. However, understanding how flexible structures respond to a significant static strain is not straightforward. This complexity also limits the precision of medical imaging when applied to tensioned organs like muscles, tendons, ligaments and blood vessels among others. In this article, we experimentally and theoretically explore the dynamics of a soft strip subject to a substantial static extension, up to 180%. Our observations reveal a few intriguing effects, such as the resilience of certain vibrational modes to a static deformation. These observations are supported by a model based on the incremental displacement theory. This has promising practical implications for characterizing soft materials but also for scenarios where external actions can be used to tune properties.

Beating resonance patterns and extreme power flux skewing in anisotropic elastic plates.

Elastic waves in anisotropic media can exhibit a power flux that is not collinear with the wave vector. This has notable consequences for waves guided in a plate. Through laser-ultrasonic experiments, we evidence remarkable phenomena due to slow waves in a single-crystal silicon wafer. Waves exhibiting power flux orthogonal to their wave vector are identified. A pulsed line source that excites these waves reveals a wave packet radiated parallel to the line. Furthermore, there exist precisely eight plane waves with zero power flux. These so-called zero-group-velocity modes are oriented along the crystal's principal axes. Time acts as a filter in the wave-vector domain that selects these modes. Thus, a point source leads to beating resonance patterns with moving nodal curves on the surface of the infinite plate. We observe this pattern as it emerges naturally after a pulsed excitation.

Notes on osculations and mode tracing in semi-analytical waveguide modeling.

The dispersion curves of (elastic) waveguides frequently exhibit crossings and osculations (also known as veering, repulsion, or avoided crossing). Osculations are regions in the dispersion diagram where curves approach each other arbitrarily closely without ever crossing before veering apart. In semi-analytical (undamped) waveguide models, dispersion curves are obtained as solutions to discretized parameterized Hermitian eigenvalue problems. In the mathematical literature, it is known that such eigencurves can exhibit crossing points only if the corresponding matrix flow (parameter-dependent matrix) is uniformly decomposable. We discuss the implications for the solution of the waveguide problem. In particular, we make use of a simple algorithm recently suggested in the literature for decomposing matrix flows. We also employ a method for mode tracing based on approximating the eigenvalue problem for individual modes by an ordinary differential equation that can be solved by standard procedures.

Characterization of lipoproteins in human placenta and fetal circulation as well as gestational changes in lipoprotein assembly and secretion in human and mouse placentas.

In the maternal circulation, apoB-containing low-density lipoproteins (LDL) and apoA1-containing high-density lipoproteins (HDL) transport lipids. The production of lipoproteins in the placenta has been suggested, but the directionality of release has not been resolved. We compared apolipoprotein concentrations and size-exclusion chromatography elution profiles of lipoproteins in maternal/fetal circulations, and in umbilical arteries/veins; identified placental lipoprotein-producing cells; and studied temporal induction of lipoprotein-synthesizing machinery during pregnancy. We observed that maternal and fetal lipoproteins are different with respect to concentrations and elution profiles. Surprisingly, concentrations and elution profiles of lipoproteins in umbilical arteries and veins were similar indicating their homeostatic control. Human placental cultures synthesized apoB100-containing LDL-sized and apoA1-containing HDL-sized particles. Immunolocalization techniques revealed that ApoA1 was present mainly in syncytiotrophoblasts. MTP, a critical protein for lipoprotein assembly, was in these trophoblasts. ApoB was in the placental stroma indicating that trophoblasts secrete apoB-containing lipoproteins into the stroma. ApoB and MTP expressions increased in placentas from the 2nd trimester to term, whereas apoA1 expression was unchanged. Thus, our studies provide new information regarding the timing of lipoprotein gene induction during gestation, the cells involved in lipoprotein assembly and the gel filtration profiles of human placental lipoproteins. Next, we observed that mouse placenta produces MTP, apoB100, apoB48 and apoA1. The expression of genes gradually increased and peaked in late gestation. This information may be useful in identifying transcription factors regulating the induction of these genes in gestation and the importance of placental lipoprotein assembly in fetal development.

Computing zero-group-velocity points in anisotropic elastic waveguides: Globally and locally convergent methods.

Dispersion curves of elastic waveguides exhibit points where the group velocity vanishes while the wavenumber remains finite. These are the so-called zero-group-velocity (ZGV) points. As the elastodynamic energy at these points remains confined close to the source, they are of practical interest for nondestructive testing and quantitative characterization of structures. These applications rely on the correct prediction of the ZGV points. In this contribution, we first model the ZGV resonances in anisotropic plates based on the appearance of an additional modal solution. The resulting governing equation is interpreted as a two-parameter eigenvalue problem. Subsequently, we present three complementary numerical procedures capable of computing ZGV points in arbitrary nondissipative elastic waveguides in the conventional sense that their axial power flux vanishes. The first method is globally convergent and guarantees to find all ZGV points but can only be used for small problems. The second procedure is a very fast, generally-applicable, Newton-type iteration that is locally convergent and requires initial guesses. The third method combines both kinds of approaches and yields a procedure that is applicable to large problems, does not require initial guesses and is likely to find all ZGV points. The algorithms are implemented in GEW ZGV computation (doi: 10.5281/zenodo.7537442).

Transit Time of Lamb Wave-Based Ultrasonic Flow Meters and the Effect of Temperature.

Transit-time flow meters need to compensate for cross-sensitivity to temperature. We show that Lamb wave-based setups are less affected by temperature. An optimality criterion is derived that allows to tune the meter into a zero local sensitivity to temperature. For this end, the flow-induced change in ultrasonic transit time is revisited first. While wetted piston transducer meters are directly sensitive to the change in propagation speed, the change in time of flight of Lamb wave-based systems is due to the beam displacement. Second, the effect of temperature is incorporated analytically. It is found that the temperature-dependent radiation angle of Lamb waves is able to compensate for changes in the speed of sound, leading to an (almost) unaffected overall time of flight. This effect is achievable with any fluid and in a wide temperature range. As an example, we discuss a water meter in the range from 0°C to 100°C. The model is validated against temperature and flow rate-dependent measurements obtained on a prototype. The measured data fits well to the developed model and confirms the reduced cross-sensitivity to temperature. Although an in-line meter is considered here, the results extend to clamp-on devices.

Intravenous propofol, ketamine (ketofol) and rocuronium after sevoflurane induction provides long lasting anesthesia in ventilated rats.

Rats are commonly used animals for laboratory experiments and many experiments require general anesthesia. However, the lack of published and reproducible intravenous anesthesia protocols for rats results in unnecessary animal use to establish new anesthesia techniques across institutions. We therefore developed an anesthesia protocol with propofol, ketamine, and rocuronium for mechanically ventilated rats, and evaluated vital parameters and plasma concentrations. 15 male Sprague-Dawley rats underwent inhalation induction with sevoflurane and tracheal, venous and arterial cannulation. After established venous access, sevoflurane was substituted by propofol and ketamine (ketofol). Rocuronium was added under mechanical ventilation for 7 h. Drug dosages were stepwise reduced to prevent accumulation. All animals survived the observation period and showed adequate depth of anesthesia. Mean arterial pressure and heart rate remained within normal ranges. Median propofol plasma concentrations remained stable: 1, 4, 7 h: 2.0 (interquartile range (IQR): 1.8-2.2), 2.1 (1.8-2.2), 1.8 (1.6-2.1) µg/ml, whereas median ketamine concentrations slightly differed after 7 h compared to 1 h: 1, 4, 7 h: 3.7 (IQR: 3.5-4.5), 3.8 (3.3-4.1), 3.8 (3.0-4.1) µg/ml. Median rocuronium plasma concentrations were lower after 4 and 7 h compared to 1 h: 1, 4, 7 h: 3.9 (IQR: 3.5-4.9), 3.2 (2.7-3.3), 3.0 (2.4-3.4) µg/ml. Our anesthesia protocol provides stable and reliable anesthesia in mechanically ventilated rats for several hours.

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients.

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column-ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power-a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.

Differential Response of Pentanal and Hexanal Exhalation to Supplemental Oxygen and Mechanical Ventilation in Rats.

High inspired oxygen during mechanical ventilation may influence the exhalation of the previously proposed breath biomarkers pentanal and hexanal, and additionally induce systemic inflammation. We therefore investigated the effect of various concentrations of inspired oxygen on pentanal and hexanal exhalation and serum interleukin concentrations in 30 Sprague Dawley rats mechanically ventilated with 30, 60, or 93% inspired oxygen for 12 h. Pentanal exhalation did not differ as a function of inspired oxygen but increased by an average of 0.4 (95%CI: 0.3; 0.5) ppb per hour, with concentrations doubling from 3.8 (IQR: 2.8; 5.1) ppb at baseline to 7.3 (IQR: 5.0; 10.8) ppb after 12 h. Hexanal exhalation was slightly higher at 93% of inspired oxygen with an average difference of 0.09 (95%CI: 0.002; 0.172) ppb compared to 30%. Serum IL-6 did not differ by inspired oxygen, whereas IL-10 at 60% and 93% of inspired oxygen was greater than with 30%. Both interleukins increased over 12 h of mechanical ventilation at all oxygen concentrations. Mechanical ventilation at high inspired oxygen promotes pulmonary lipid peroxidation and systemic inflammation. However, the response of pentanal and hexanal exhalation varies, with pentanal increasing by mechanical ventilation, whereas hexanal increases by high inspired oxygen concentrations.

Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury.

BACKGROUND: Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats. METHODS: A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL·kg-1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL·kg-1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL·kg-1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg-1 before returning to a tidal volume of 6 mL·kg-1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column-ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue. RESULTS: Exhaled pentanal concentrations increased by only 0.5 ppb·h-1 (95% confidence interval [CI], 0.3-0.6) when rats were ventilated at 6 mL·kg-1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb·h-1 (95% CI, 2.3-3.8) at tidal volumes of 20 mL·kg-1. Exhaled pentanal increased at average rates between 1.0 ppb·h-1 (95% CI, 0.3-1.7) and 2.5 ppb·h-1 (95% CI, 1.4-3.6) after the onset of 16 mL·kg-1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9-3.2), corresponding to a 38% (IQR, 31-43) reduction when tidal volume returned to 6 mL·kg-1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue. CONCLUSIONS: Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats.

Comparison of Transmission Measurement Methods of Elastic Waves in Phononic Band Gap Materials.

Periodic cellular structures can exhibit metamaterial properties, such as phononic band gaps. In order to detect these frequency bands of strong wave attenuation experimentally, several devices for wave excitation and measurement can be applied. In this work, piezoelectric transducers are utilized to excite two additively manufactured three-dimensional cellular structures. For the measurement of the transmission factor, we compare two methods. First, the transmitted waves are measured with the same kind of piezoelectric transducer. Second, a laser Doppler vibrometer is employed to scan the mechanical vibrations of the sample on both the emitting and receiving surfaces. The additional comparison of two different methods of spatial averaging of the vibrometer data, that is, the quadratic mean and arithmetic mean, provides insight into the way the piezoelectric transducers convert the transmitted signal. Experimental results are supported by numerical simulations of the dispersion relation and a simplified transmission simulation.

Host-parasite interactions of rodent hosts and ectoparasite communities from different habitats in Germany.

BACKGROUND: Small mammals are important maintenance hosts of ectoparasites as well as reservoir hosts for many arthropod-borne pathogens. In Germany, only a few studies have investigated ectoparasite communities on small mammals in their natural habitats. The aim of this study was to assess the species diversity and parameters influencing the mean intensity and prevalence of macroscopically visible ectoparasites, such as fleas, predatory mites and ticks. METHODS: A total of 779 small mammals and 3383 ticks were available from earlier investigations for the data analysis of the current study from three differently structured study sites. In addition, fleas and predatory mites were collected from the captured rodents and taxonomically identified. Regression analyses were conducted on the group (ticks/mites/fleas) and species levels using hurdle models for the abundance of ectoparasite groups and a negative binomial model for the abundance of species. RESULTS: Nearly 90% of the small mammals analyzed were infested with ectoparasites, with an average of 7.3 specimens per host. Hosts were infested with up to six species of ectoparasites simultaneously. In total, 12 flea, 11 mite and three tick species were detected. Ticks were more prevalent than fleas or mites, with > 80% of the hosts in urban and forest areas hosting ticks and around 60% of hosts presenting fleas, and only 20-40% of hosts presenting mites. Polyparasitism had a statistically significant influence on the prevalence of the investigated tick, mite and flea species, with odds ratios of > 1.0. Trapping location, season and host characteristics had significant influences on some-but not all-of the investigated species. CONCLUSIONS: The diversity of flea species was unexpectedly high and higher than that reported in comparable studies, which can be explained by the differently structured habitats and regions examined in this study. Polyparasitism was a key influencing factor and had a positive effect on the prevalence and/or abundance of the predominant tick, flea and mite species occurring on small mammals. Season, trapping location, host species and sex of the host species also had an influence on the prevalence and mean intensity of certain, but not all, ectoparasite species.

Exhaled Propofol Concentrations Correlate With Plasma and Brain Tissue Concentrations in Rats.

BACKGROUND: Propofol can be measured in exhaled gas. Exhaled and plasma propofol concentrations correlate well, but the relationship with tissue concentrations remains unknown. We thus evaluated the relationship between exhaled, plasma, and various tissue propofol concentrations. Because the drug acts in the brain, we focused on the relationship between exhaled and brain tissue propofol concentrations. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with propofol, ketamine, and rocuronium for 6 hours. Animals were randomly assigned to propofol infusions at 20, 40, or 60 mg·kg·h (n = 12 per group). Exhaled propofol concentrations were measured at 15-minute intervals by multicapillary column-ion mobility spectrometry. Arterial blood samples, 110 µL each, were collected 15, 30, and 45 minutes, and 1, 2, 4, and 6 hours after the propofol infusion started. Propofol concentrations were measured in brain, lung, liver, kidney, muscle, and fat tissue after 6 hours. The last exhaled and plasma concentrations were used for linear regression analyses with tissue concentrations. RESULTS: The correlation of exhaled versus plasma concentrations (R = 0.71) was comparable to the correlation of exhaled versus brain tissue concentrations (R = 0.75) at the end of the study. In contrast, correlations between plasma and lung and between lung and exhaled propofol concentrations were poor. Less than a part-per-thousand of propofol was exhaled over 6 hours. CONCLUSIONS: Exhaled propofol concentrations correlate reasonably well with brain tissue and plasma concentrations in rats, and may thus be useful to estimate anesthetic drug effect. The equilibration between plasma propofol and exhaled gas is apparently independent of lung tissue concentration. Only a tiny fraction of administered propofol is eliminated via the lungs, and exhaled quantities thus have negligible influence on plasma concentrations.

High average power transform limited picosecond laser with flexible repetition rate and pulse duration.

This Letter presents a pulsed, Fourier transform limited 1030 nm laser with a variable pulse duration between 47 and 733 ps resulting in a spectral bandwidth of roughly 1 to 10 GHz. The laser system is based on ytterbium-doped fiber amplifiers and acousto-optic and electro-optic modulation technology. The repetition rate can be set arbitrarily between 1 and 10 MHz. After three sequential amplifier stages, the average output power reaches a maximum of over 60 W. The particular fiber amplifier geometry allows to prevent the emergence of unwanted nonlinear effects. Due to its unique features, the laser system lends itself to a variety of applications wherever flexibility in terms of pulse duration and corresponding Fourier limited bandwidth are required, such as laser cooling at storage rings, lidar applications, or coherent molecular spectroscopy.

Bartonella spp. in Small Mammals and Their Fleas in Differently Structured Habitats From Germany.

Most Bartonella spp. are transmitted by fleas and harbored by small mammals which serve as reservoirs. However, little is known about the composition of fleas and their Bartonella spp. from small mammals in Central Europe. Therefore, the aims of this study were to investigate flea communities on small mammals from three differently structured sites (urban, sylvatic, renatured) in Germany as well as the prevalence of Bartonella spp. in small mammals and their parasitizing fleas. In total, 623 small mammals belonging to 10 different species (the majority were Myodes glareolus and Apodemus flavicollis) were available. Fleas were removed from the small mammals' fur, morphologically identified and DNA was extracted. To detect Bartonella spp., two conventional PCRs targeting the gltA gene and the 16S-23S rRNA intergenic spacer were carried out followed by sequencing. Obtained sequences were compared to those in GenBank. In total, 1,156 fleas were collected from 456 small mammals. Altogether, 12 different flea species (the majority were Ctenophthalmus agyrtes, Nosopsyllus fasciatus, and Megabothris turbidus) were detected. At the urban site mostly Leptopsylla segnis and N. fasciatus were collected which may be vectors of zoonotic pathogens to companion animals. The overall prevalence for Bartonella in small mammals was 43.3% and in fleas 49.1%. Five different Bartonella spp. were detected in small mammals namely B. grahamii, B. taylorii, B. doshiae, Bartonella sp. N40 and uncultured Bartonella sp. whereas in fleas four Bartonella spp. were found which were with the exception of B. doshiae identical to the Bartonella species detected in their small mammal hosts. While B. grahamii was the only zoonotic Bartonella sp. most Bartonella strains found in fleas and small mammals belonged to uncultured Bartonella spp. with unknown zoonotic potential. This study showed a high diversity of flea species on small mammals from Germany. Further, high prevalence rates of Bartonella species were detected both in fleas and in their mammalian hosts. Several different Bartonella species with a high genetic variability were discovered. Especially at the urban study sites, this may pose a risk for Bartonella transmission to companion animals and humans.

Simulation-Based Characterization of Mechanical Parameters and Thickness of Homogeneous Plates Using Guided Waves.

Properties of isotropic plates in terms of material constants and thickness are characterized by making use of dispersion characteristics of propagating Lamb waves. A numerical model is inversely optimized in order to match dispersion curves measured by laser vibrometry. This kind of material characterization has gained interest in recent research. Improvements in accuracy and efficiency of the optimization process are therefore important steps toward an industrial application of this technique to nondestructive testing and online monitoring. For this purpose, the use of a fast converging numerical model based on spectral collocation has been found to be well suited. Furthermore, we improved the signal-to-noise ratio by utilizing long-time broadband excitation signals for multimodal excitation of Lamb waves. The wavenumber spectrum up to 2.5 MHz is acquired by measurements with a laser-scanning vibrometer. In order to exploit the information contained in high-order modes, we present an algorithm to match the measured data to the calculated modes during the optimization process, leading to higher accuracy of the estimated model parameters. The characterization results are verified by comparison to measurements with a conventional ultrasonic method.

Calculating the full leaky Lamb wave spectrum with exact fluid interaction.

Lamb waves are elastodynamic guided waves in plates and are used for non-destructive evaluation, sensors, and material characterization. These applications rely on the knowledge of the dispersion characteristics, i.e., the frequency-dependent wavenumbers. The interaction of a plate with an adjacent fluid leads to a nonlinear differential eigenvalue problem with a square root term describing exchange of energy with the surrounding medium, e.g., via acoustic radiation. In this contribution, a spectral collocation scheme is applied to discretize the differential eigenvalue problem. A change of variable is performed to obtain an equivalent polynomial eigenvalue problem of fourth order, which is linear in state-space and can reliably be solved using modern numerical methods. Traditionally, the leaky Lamb wave problem has been solved by finding the roots of the characteristic equations, a numerically ill-conditioned problem. In contrast to root-finding, the approach described in this paper is inherently able to find all modes and naturally handles complex wavenumbers. The full phase velocity dispersion diagram and attenuation curves are presented and are shown to be in excellent agreement with solutions of the characteristic equation as well as computations made with a perturbation method. The procedure is applicable to anisotropic, viscoelastic, inhomogeneous, and layered plates coupled to an inviscid fluid.

Simultaneous quantification of propofol, ketamine and rocuronium in just 10 µL plasma using liquid chromatography coupled with quadrupole mass spectrometry and its pilot application to a pharmacokinetic study in rats.

The combination of propofol, ketamine and rocuronium can be used for anesthesia of ventilated rats. However, reliable pharmacokinetic models of these drugs have yet to be developed in rats, and consequently optimal infusion strategies are also unknown. Development of pharmacokinetic models requires repeated measurements of drug concentrations. In small animals, samples must be tiny to avoid excessing blood extraction. We therefore developed a drug assay system using high-performance liquid chromatography coupled with quadrupole mass spectrometry that simultaneously determines the concentration of all three drugs in just 10 µL rat plasma. We established a plasma extraction protocol, using acetonitrile as the precipitating reagent. Calibration curves were linear with R2 = 0.99 for each drug. Mean recovery from plasma was 91-93% for propofol, 89-93% for ketamine and 90-92% for rocuronium. The assay proved to be accurate for propofol 4.1-8.3%, ketamine 1.9-7.8% and rocuronium -3.6-4.7% relative error. The assay was also precise; the intra-day precisions were propofol 2.0-4.0%, ketamine 2.7-2.9% and rocuronium 2.9-3.3% relative standard deviation. Finally, the method was successfully applied to measurement the three drugs in rat plasma samples. Mean plasma concentrations with standard deviations were propofol 2.0 µg/mL ±0.5%, ketamine 3.9 µg/mL ±1.0% and rocuronium 3.2 µg/mL ±0.8% during ventilation.

Design and validation of an automated solid phase extraction liquid chromatography coupled mass spectrometry method for the quantification of propofol in plasma.

Propofol concentration in human plasma can be quantified by liquid chromatography coupled mass spectrometry. Sample preparation usually requires solid phase extraction to remove matrix components and enrich the analyte. To facilitate user-independent measurements and speed extraction, we developed and validated a fully automated high throughput in-line sample preparation system with direct injection into liquid chromatography coupled mass spectrometry. We assessed linearity of each method over the clinically relevant concentration range from 0.5µg/mL to 8µg/mL plasma concentration. R2 values were 0.99 for the automated process and 0.98 for manual sample preparation. The limit of detection was 6ng/mL and the lower limit of quantification was 18ng/mL for the automated method; for the manual process, the limit of detection was 1.58ng/mL and the lower limit of quantification was 4.79ng/mL. Intra-day precision for low, medium and high concentration range of the automated method was validated 4.14%, 9.68% and 3.04% relative standard deviation and 0.29%, 0.12% and 0.52% for the manual process. Carry over was 0.4% with the automated method, whereas there was no carry over with the manual method. Stability of plasma samples was tested with the manual method at concentrations of 1, 4, and 6µg/mL propofol and found to be stable over 150days at -20°C. The manual sample preparation method has successfully been transferred to a fully automated process with appropriate sensitivity and precision but the automatization failed with regard to trueness and working time due to lengthy sample preparation runtime. Therefore it is not suitable for daily use in a hospital laboratory e.g. for brain death diagnosis in the intensive care unit.