Biology subjects

Hartl, B.

Publications and source records attributed to Hartl, B..

4 recordsLinked to original sources

bioRxiv2026

Quantification of microbubble-induced streaming across ultrasound frequencies using particle image velocimetry

Functional microbubbles are widely used in therapeutic ultrasound for drug delivery, blood-brain barrier opening, clot lysis, and other biomedical interventions. Their therapeutic effects arise largely from acoustic microstreaming, which generates localized shear stresses and enhances transport around oscillating bubbles. Despite the central role of microstreaming, its dependence on ultrasound excitation conditions is not well defined. Existing studies use diverse and often incomparable frequencies, pressures, and duty cycles, leaving a gap in systematic understanding of how these parameters govern the streaming velocity and shear fields produced by functional microbubbles under physiologically relevant conditions. In this study, we employ particle image velocimetry (PIV) in a popliteal-vein lab-on-chip model to directly quantify the microstreaming velocity and shear-rate fields generated by microbubbles across a wide range of ultrasound conditions including frequency, duty cycle, and acoustic pressure. Measurements at 150 kHz, 300 kHz, 500 kHz, and 1 MHz reveal a pronounced frequency dependence. Counterintuitively, the strongest microstreaming is observed at 150 kHz, with progressively weaker streaming at 300 and 500 kHz, and the weakest flows at 1 MHz. This trend contrasts with the common assumption that microbubble oscillations peak near their [~]1 MHz resonance frequency. Duty cycle further modulated the response: 10% duty cycle generated the weakest fields, whereas 100% duty cycle produced maximal streaming. The results reveal a strong nonlinear pressure dependence at low frequencies, particularly at 300 kPa where flow amplification was most pronounced. These findings underscore that acoustic frequency plays a substantial role in intensity of microbubble-induced streaming, with low-frequency excitation in the 150-300 kHz range producing markedly more efficient streaming and associated shear. Adopting acoustic parameters that maximize microstreaming within this low-frequency window while avoiding conditions that promote inertial cavitation may improve both the efficacy and safety of microbubble-mediated treatments.

bioengineering↗

bioRxiv2025

Investigation of the Synergistic Effect of Enzymatic and Ultrasound-Induced Amyloid Microclot Degradation

Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In this study we examine the effects of three fibrinolytic enzymes rtPA, Lumbrokinase, and Nattokinase on plasma-derived amyloid microclots, in combination with ultrasound-induced microstreaming and microbubbles. A lab-on-chip platform was used to expose the clots to ultrasound at 150, 300, and 500 kHz. Quantitative analysis revealed that ultrasound alone significantly disrupted clot structures, particularly at 150 kHz, where mean clot diameter was reduced by over 60% and large-clot count (>30 {micro}m) dropped by more than 80% compared to controls. The addition of fibrinolytic enzymes, however, did not produce statistically significant effects at 150 or 300 kHz which indicates that mechanical forces were the dominant contributors to clot disruption. At 500 kHz, where ultrasound alone was less effective, enzymatic treatment moderately enhanced the reduction in large-clot burden. These results show the potential of low-frequency ultrasound as a primary method of amyloid microclot breakdown, with enzyme co-treatment offering limited but measurable effect.

bioengineering↗

bioRxiv2025

Detection of Long COVID Microclots using Pulsed Speckle Contrast Optical Spectroscopy

Circulating microclots are increasingly linked to long COVID as well as its persistent symptoms such as fatigue, cognitive deficits, and cardiovascular complications. These conditions can become debilitating or even life-threatening, which create an urgent need for rapid and reliable detection and monitoring tools. In this study we investigate pulsed speckle contrast optical spectroscopy (p-SCOS) as a non-invasive and label-free method to detect microclots in biofluids. Microclots at four concentrations (21k, 91k, 400k, and 1.7M microclots/mL), representing levels from healthy individuals to acute coagulopathic states, were generated using a freeze-thaw method. We measured speckle contrast under flowing conditions in a custom-made flow phantom. In phosphate-buffered saline (PBS) and plasma, increasing microclot concentration consistently led to measurable decreases in speckle contrast. The measurement differentiated between low and high clot burdens in transparent media which highlights its potential for microclot monitoring. In comparison, no detectable changes were observed in whole blood, likely due to dominant scattering from red blood cells masking microclot effects. Overall, our findings demonstrate the feasibility of p-SCOS as a rapid and label-free tool for microclot detection and monitoring in transparent biofluids.

bioengineering↗

bioRxiv2025

Low-Intensity Ultrasound Lysis of Amyloid Microclots in a Lab-on-Chip Model

Amyloid fibrin(ogen) microclots are misfolded protein aggregates with {beta}-sheet structures that have been associated with Long COVID and numerous thrombo-inflammatory diseases. These microclots persist in circulation and obstruct microvasculature, impair oxygen transport and promote chronic inflammation. Conventional thrombolytic therapies such as recombinant tissue plasminogen activator (rtPA) show limited efficacy against these aggregates due to their structure and composition. In this study, we assess the impact of low intensity focused ultrasound (LIFU) stimulation on amyloid microclot fragmentation, the role of cavitation in this process and investigate whether microbubble-assisted ultrasound can enhance their lysis. Amyloid microclot models were generated using freeze-thaw cycles followed by incubation. Microclots were exposed to ultrasound waves at 150 kHz, 300 kHz, 500 kHz, and 1 MHz under four conditions: ultrasound alone (US), ultrasound with microbubbles (MB + US), ultrasound with rtPA (rtPA + US), and ultrasound with both microbubbles and rtPA (MB + rtPA + US). Low-frequency ultrasound at 150 kHz resulted in a significant clot lysis with up to three-fold reduction in both clot size and the number of large clots. The addition of microbubbles enhanced clot lysis at 150 kHz, 300 kHz, and 500 kHz. These findings suggest that ultrasound, particularly at 150 kHz, is a promising method for amyloid microclot lysis. The combination of ultrasound with microbubbles and rtPA further improved clot fragmentation, rendering it a potential therapeutic tool for conditions like Long COVID.

bioengineering↗