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Biomedical subjects

Dorian Liepmann

Publications and source records attributed to Dorian Liepmann.

9 recordsLinked to original sources

Traditional Foley drainage systems--do they drain the bladder?

PURPOSE: Foley catheters are assumed to drain the bladder to completion. Drainage characteristics of Foley catheter systems are poorly understood. To investigate unrecognized retained urine with Foley catheter drainage systems, bladder volumes of hospitalized patients were measured with bladder scan ultrasound volumetrics. Additionally, an in vitro bench top mock bladder and urinary catheter system was developed to understand the etiology of such residual volumes. A novel drainage tube design that optimizes indwelling catheter drainage was also designed. MATERIALS AND METHODS: Bedside bladder ultrasound volumetric studies were performed on patients hospitalized in ward and intensive care unit. If residual urine was identified the drainage tubing was manipulated to facilitate drainage. An ex vivo bladder-urinary catheter model was designed to measure flow rates and pressures within the drainage tubing of a traditional and a novel drainage tube system. RESULTS: A total of 75 patients in the intensive care unit underwent bladder ultrasound volumetrics. Mean residual volume was 96 ml (range 4 to 290). In 75 patients on the hospital ward mean residual volume was 136 ml (range 22 to 647). In the experimental model we found that for every 1 cm in curl height, obstruction pressure increased by 1 cm H2O within the artificial bladder. In contrast, the novel spiral-shaped drainage tube demonstrated rapid (0.5 cc per second), continuous and complete (100%) reservoir drainage in all trials. CONCLUSIONS: Traditional Foley catheter drainage systems evacuate the bladder suboptimally. Outflow obstruction is caused by air-locks that develop within curled redundant drainage tubing segments. The novel drainage tubing design eliminates gravity dependent curls and associated air-locks, optimizes flow, and minimizes residual bladder urine.

Drainage↗

Microneedles and transdermal applications.

With the limitations of oral drug delivery and the pain and needle phobias associated with traditional injections, drug delivery research has focused on the transdermal delivery route. A formidable barrier to transdermal drug delivery is the stratum corneum, the superficial layer of the skin. In the last 10 years, microneedles were proposed as a mechanical tool to pierce through the stratum corneum, in order to create drug delivery channels without stimulating underlying pain nerves. Since then, the field of microneedles has rapidly evolved to spawn a plethora of potential transdermal applications. In this review, the authors provide an overview of the progress in microneedle research and design, and the advancements that have been made in employing this technology for transdermal applications.

Administration, Cutaneous↗

Effects of shear stress on endothelial cell haptotaxis on micropatterned surfaces.

Endothelial cell (EC) migration plays a critical role in vascular remodeling. Here we investigated the interactions between haptotaxis (induced by extracellular matrix gradient) and mechanotaxis (induced by mechanical forces) during EC migration. A micropatterning technique was used to generate step changes of collagen surface density. Due to haptotaxis, ECs developed focal adhesions and migrated into the area with higher surface density of collagen. Different levels of fluid shear stress were applied on ECs in the direction perpendicular to collagen strips. Shear stress at 2 dyn/cm2 did not affect haptotaxis, while shear stress at 3 dyn/cm2 or higher was sufficient to drive the migration of most ECs in the flow direction and against haptotaxis. Immunostaining revealed the increase of focal adhesions and lamellipodial protrusion in the direction of flow. These results suggest that shear stress beyond a certain threshold can be a predominant factor to determine the direction of EC migration.

Animals↗

Microdialysis microneedles for continuous medical monitoring.

Enzyme based biosensors suffer from loss of activity and sensitivity through a variety of processes. One major reason for the loss is through large molecular weight proteins settling onto the sensor and affecting sensor signal stability and disrupting enzyme function. One way to minimize loss of sensor activity is to filter out large molecular weight compounds before sensing small biochemicals such as glucose. A novel microdialysis microneedle is introduced that is capable of excluding large MW compounds based on size. Preliminary experimental evidence of membrane permeability is shown, as well as diffusion and permeability modeling. Microdialysis microneedles present an attractive first step towards decreasing size, patient discomfort and energy consumption of portable medical monitors over existing technologies.

Equipment Design↗

Clinical microneedle injection of methyl nicotinate: stratum corneum penetration.

BACKGROUND/PURPOSE: In recent years, microneedles were proposed as a method to painlessly deliver drugs past the stratum corneum. Microneedles have been fabricated in several designs, but limited studies have tested microneedle injections in humans. In this work, we compare microneedle injections with topical application (TA) to investigate if microneedles enhance in vivo drug delivery past the stratum corneum. METHOD: In vitro tests were used to measure microneedle pressures and injection volumes. In vivo microneedle injections were performed on the volar forearm of 11 healthy volunteers. Two sets of microneedles, pointed and symmetric, were used to develop microneedle/syringe apparatuses that were used to inject approximately 1 microL of 0.1 M methyl nicotinate, and were compared against TA. A Laser Doppler Perfusion Monitor was used to record maximum blood flow and the time to maximum blood flow at the treatment sites. RESULTS: Pointed and symmetric microneedle-injected sites showed a significantly faster time to maximum blood flow than TA. The pointed microneedle injections also resulted in a higher maximum blood flux. Volunteers reported feeling pressure but no pain from the microneedles during the injections. CONCLUSION: The microneedles aid in bypassing the stratum corneum and enhance drug delivery through it. The design of the microneedle influences its delivery capabilities, because the pointed microneedles seem to be less susceptible to clogging during the injection.

Administration, Topical↗

Biomimetic technique for adhesion-based collection and separation of cells in a microfluidic channel.

A basic step in many biological assays is separating and isolating different types of cells from raw samples. To better meet these requirements in microfluidic devices for miniature biomedical analytical systems, an alternative method for separating cells has been devised by mimicking the physiological process of leukocyte recruitment to blood vessel walls: adhesive cell rolling and transient tethering. Reproducing these interactions for cells on surfaces of microstructured fluidic channels can serve to capture and concentrate cells and even to fractionate different cell types from a continuously flowing sample. To demonstrate this principle, two designs for microstructured fluidic channels were fabricated: an array of Square pillars and another with slender, Offset pillars. These structures were coated with E-selectin IgG chimera and the interactions of HL-60 and U-937 cells with these structures were characterized. With inflow of fluidic cell suspensions, the structures were able to efficiently capture and arrest cells directly from the rapid free stream flow. After capture, cells transit through the channel in three phases: cell rolling, cell tethering, and transient re-suspension in free stream flow before re-capture. Under these interactions, captured cells were enriched several hundred-fold from the original concentration. Additionally, among collected cells, the difference in flow-driven, adhesion-mediated cell transit in the Square design suggested that the two cell types could at least be partially fractionated.

Biomimetics↗

Continuous on-chip micropumping for microneedle enhanced drug delivery.

Microneedles are promising microfabricated devices for minimally invasive drug delivery applications. Needles can be integrated into a variety of devices. However, any portable drug delivery device with integrated microneedles will need an equally compact means to deliver therapeutics. This work presents microneedles integrated with an on-chip MEMS positive displacement micropump for continuous drug delivery applications. The generation and collapse of thermally generated bubbles with flow rectified by directional check valves are used to achieve net pumping through the device. Visualization methods have observed net flow rates of water out of a microneedle at approximately 2.0 nl/s with a pressure of 3.9 kPa. In addition, continuous pumping was achieved for more than 6 hours with the heaters actuating for over 18 hours (15,000 cycles) without failing.

Drug Delivery Systems↗

Regulation of vascular smooth muscle cells by micropatterning.

Vascular smooth muscle cells (SMCs) undergo morphological and phenotypic changes when cultured in vitro. To investigate whether SMC morphology regulates SMC functions, bovine aortic SMCs were grown on micropatterned collagen strips (50-, 30-, and 20-microm wide). The cell shape index and proliferation rate of SMCs on 30- and 20-microm strips were significantly lower than those on non-patterned collagen (control), and the spreading area was decreased only for cells patterned on the 20-microm strips, suggesting that SMC proliferation is dependent on cell shape index. The formation of actin stress fibers and the expression of alpha-actin were decreased in SMCs on the 20- and 30-microm collagen strips. SMCs cultured on micropatterned biomaterial poly-(D,L-lactide-co-glycolide) (PLGA) with 30-microm wide grooves also showed lower proliferation rate and less stress fibers than SMCs on non-patterned PLGA. Our findings suggest that micropatterned matrix proteins and topography can be used to control SMC morphology and that elongated cell morphology decreases SMC proliferation but is not sufficient to promote contractile phenotype.

Actin Cytoskeleton↗