Lymphatic Valves Separate Lymph Flow Into a Central Stream and a Slow-Moving Peri-Valvular Milieu.

The lymphatic system plays a pivotal role in the transport of fats, waste, and immune cells, while also serving as a metastatic route for select cancers. Using live imaging and particle tracking, we experimentally characterized the lymph flow field distal from the inguinal lymph node in the vicinity of normal bileaflet and malformed unileaflet intraluminal valves. Particle tracking experiments demonstrated that intraluminal lymphatic valves concentrate higher velocity lymph flow in the center of the vessel, while generating adjacent perivalvular recirculation zones. The recirculation zones are characterized by extended particle residence times and low wall shear stress (WSS) magnitudes in comparison to the rest of the lymphangion. A malformed unileaflet valve skewed lymph flow toward the endothelium on the vessel wall, generating a stagnation point and a much larger recirculation zone on the opposite wall. These studies define physical consequences of bileaflet and unileaflet intraluminal lymphatic valves that affect lymph transport and the generation of a heterogeneous flow field that affects the lymphatic endothelium nonuniformly. The characterized flow fields were recreated in vitro connecting different flow environments present in the lymphangion to a lymphatic endothelial cell (LEC) pro-inflammatory phenotype. Unique and detailed insight into lymphatic flow is provided, with potential applications to a variety of diseases that affect lymph transport and drug delivery.

Microfluidic DNA-based potassium nanosensors for improved dialysis treatment.

BACKGROUND: Patients with end-stage renal disease (ESRD) have failed kidney function, and often must be treated with hemodialysis to extend the patient's life by artificially removing excess fluid and toxins from the blood. However, life-threatening treatment complications can occur because hemodialysis protocols are adjusted infrequently, as opposed to the kidneys which filter blood continuously. Infrequent blood tests, about once per month on average, are used to adjust hemodialysis protocols and as a result, patients can experience electrolyte imbalances, which can contribute to premature patient deaths from treatment complications, such as sudden cardiac death. Since hemodialysis can lead to blood loss, drawing additional blood for tests to assess the patient's kidney function and blood markers is limited. However, sampling multiple drops of blood per session using a microfluidic device has the potential to reduce not only the amount of blood drawn and avoid unnecessary venipuncture, but also reduce costs by limiting medical complications of hemodialysis and provide a more comprehensive assessment of the patient's health status in real time. RESULT: We present preliminary proof-of-concept results of a microfluidic device which uses DNA-based fluorescence nanosensors to measure potassium concentration in a flowing solution. In a matter of minutes, the flowing potassium solution reduced the fluorescence intensity of the nanosensors to a steady-state value. CONCLUSIONS: These proof-of-concept results demonstrate the ability of our DNA-based nanosensors to measure potassium concentration in a microfluidic device. The long-term goal is to integrate this technology with a device to measure potassium and eventually other blood contents multiple times throughout a hemodialysis session, enabling protocol adjustment similar to a healthy kidney.

Stent strut streamlining and thickness reduction promote endothelialization.

Stent thrombosis (ST) carries a high risk of myocardial infarction and death. Lack of endothelial coverage is an important prognostic indicator of ST after stenting. While stent strut thickness is a critical factor in ST, a mechanistic understanding of its effect is limited and the role of haemodynamics is unclear. Endothelialization was tested using a wound-healing assay and five different stent strut models ranging in height between 50 and 150 µm for circular arc (CA) and rectangular (RT) geometries and a control without struts. Under static conditions, all stent strut surfaces were completely endothelialized. Reversing pulsatile disturbed flow caused full endothelialization, except for the stent strut surfaces of the 100 and 150 µm RT geometries, while fully antegrade pulsatile undisturbed flow with a higher mean wall shear stress caused only the control and the 50 µm CA geometries to be fully endothelialized. Modest streamlining and decrease in height of the stent struts improved endothelial coverage of the peri-strut and stent strut surfaces in a haemodynamics dependent manner. This study highlights the impact of the stent strut height (thickness) and geometry (shape) on the local haemodynamics, modulating reendothelialization after stenting, an important factor in reducing the risk of stent thrombosis.