Biomedical subjects

Jeffrey D Zahn

Publications and source records attributed to Jeffrey D Zahn.

8 recordsLinked to original sources

PubMed2006

A microfluidic device for continuous, real time blood plasma separation.

A microfluidic device for continuous, real time blood plasma separation is introduced. The principle of the blood plasma separation from blood cells is supported by the Zweifach-Fung effect and was experimentally demonstrated using simple microchannels. The blood plasma separation device is composed of a blood inlet, a bifurcating region which leads to a purified plasma outlet, and a concentrated blood cell outlet. It was designed to separate blood plasma from an initial blood sample of up to 45% inlet hematocrit (volume percentage of cells). The microfluidic network was designed using an analogous electrical circuit, as well as analytical and numerical studies. The functionality of this device was demonstrated using defibrinated sheep blood. During 30 minutes of continuous blood infusion through the device, all the erythrocytes (red blood cells) traveled through the device toward the concentrated blood outlet while only the plasma was separated at the bifurcating regions and flowed towards the plasma outlet. The device has been operated continuously without any clogging or hemolysis of cells. The experimentally determined plasma selectivity with respect to blood hematocrit level was almost 100% regardless of the inlet hematocrit. The total plasma separation volume percent varied from 15% to 25% with increasing inlet hematocrit. Due to the device's simple structure and control mechanism, this microdevice is expected to be used for highly efficient continuous, real time cell-free blood plasma separation from blood samples for use in lab on a chip applications.

Fluorescent Dyes↗

PubMed2006

Design of a side-view particle imaging velocimetry flow system for cell-substrate adhesion studies.

Experimental models that mimic the flow conditions in microcapillaries have suggested that the local shear stresses and shear rates can mediate tumor cell and leukocyte arrest on the endothelium and subsequent sustained adhesion. However, further investigation has been limited by the lack of experimental models that allow quantitative measurement of the hydrodynamic environment over adherent cells. The purpose of this study was to develop a system capable of acquiring quantitative flow profiles over adherent cells. By combining the techniques of side-view imaging and particle image velocimetry (PIV), an in vitro model was constructed that is capable of obtaining quantitative flow data over cells adhering to the endothelium. The velocity over an adherent leukocyte was measured and the shear rate was calculated under low and high upstream wall shear. The microcapillary channel was modeled using computational fluid dynamics (CFD) and the calculated velocity profiles over cells under the low and high shear rates were compared to experimental results. The drag force applied to each cell by the fluid was then computed. This system provides a means for future study of the forces underlying adhesion by permitting characterization of the local hydrodynamic conditions over adherent cells.

Cell Adhesion↗

PubMed2005

Interfacial stabilization of organic-aqueous two-phase microflows for a miniaturized DNA extraction module.

Organic-aqueous liquid (phenol) extraction is one of many standard techniques to efficiently purify DNA directly from cells. The cell components naturally distribute themselves into the two fluid phases in order to minimize interaction energies of the biological components with the surrounding solvents. The membrane components and protein partition to the interface between the organic and aqueous phases while the DNA stays in the aqueous phase. The aqueous phase is then removed with a purified DNA sample. This work studies the first steps towards miniaturizing this liquid extraction technique in a microfluidic device. The first step is to understand how the two liquid phases behave in microchannels. Due to the interfacial tension between the two liquid phases, novel approaches must be examined in order to obtain interfacial stability under flow conditions. The stability of the organic-aqueous interface is improved by reducing the interfacial tension between the two phases by incorporating a surfactant into the aqueous phase. The variation of the interfacial tension as a function of surfactant concentration is also quantified in this work. This has led to the ability to create stable stratified microflows in both a dual inlet and three inlet microfluidic systems. Also, the first step in understanding biological interactions at the organic-aqueous interface is investigated using a fluorescently labeled bovine serum albumin protein.

Cell Membrane↗

PubMed2005

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↗

PubMed2005

Components of an integrated microfluidic device for continuous glucose monitoring with responsive insulin delivery.

Miniaturized medical diagnostic and treatment devices are currently being developed. Microneedles and miniaturized microdialysis systems are particularly well suited to impact diabetes treatment for continuous glucose monitoring and feedback-controlled insulin delivery. Microneedles are an attractive advanced drug delivery system used to mechanically penetrate the skin and inject insulin intradermally where it is rapidly absorbed by the capillary bed into the bloodstream. The real advantage of microneedle-enhanced drug delivery lies in the fact that drug is actively injected into a patient so the dosage may be varied with time to allow complex drug delivery profiles. The delivery is independent of the drug composition and merely relies on the subsequent drug absorption into the bloodstream. A miniaturized microdialysis probe for continuous glucose sensing has also been designed. Microdialysis is based upon controlling the mass transfer rate of glucose diffusing across a semipermeable membrane into a dialysis fluid while excluding larger molecules such as proteins. Polymer microdialysis membranes are integrated with microfluidic systems. Because of the high surface area to fluid volume ratio of miniaturized fluid channels, faster recovery of glucose to increase glucose sensing frequency is expected. This work highlights recent advances made in the design and fabrication of microneedles to make them more biocompatible and more fracture resistant in order to effectively enter the biomedical market. In addition, the design of a miniaturized microdialysis system for increased glucose sampling frequency is presented. The sensing and infusion technologies may be combined into a miniaturized "artificial pancreas" for minimally invasive feedback-controlled insulin delivery.

Blood Glucose↗

PubMed2004

Microneedle insertion force reduction using vibratory actuation.

The effect of vibratory actuation on microneedle insertion force was investigated. Hollow micro hypodermic injection needles were fabricated by a two-wafer polysilicon micromolding process. A vibratory actuator operating in the kHz range was coupled with the hypodermic microneedles. The force to insert microneedles into excized animal tissue was measured with a load cell. Results showed a greater than 70% reduction in microneedle insertion force by using vibratory actuation. The application of vibratory actuation provides a promising method to precisely control the microneedle insertion forces to overcome microneedle structural material limitations, minimize insertion pain, and enhance the efficiency of drug delivery.

Drug Delivery Systems↗

PubMed2004

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↗

PubMedDate not supplied

Blood plasma separation in microfluidic channels using flow rate control.

Several studies have clearly shown that cardiac surgery induces systemic inflammatory responses, particularly when cardiopulmonary bypass (CPB) is used. CPB induces complex inflammatory responses. Considerable evidence suggests that systemic inflammation causes many postoperative complications. Currently, there is no effective method to prevent this systemic inflammatory response syndrome in patients undergoing CPB. The ability to clinically intervene in inflammation, or even study the inflammatory response to CPB, is limited by the lack of timely measurements of inflammatory responses. In this study, a microfluidic device for continuous, real-time blood plasma separation, which may be integrated with downstream plasma analysis device, is introduced. This device is designed to have a whole blood inlet, a purified plasma outlet, and a concentrated blood cell outlet. The device is designed to separate plasma with up to 45% hematocrit of the inlet blood and is analyzed using computational fluid dynamics simulation. The simulation results show that 27% and 25% of plasma can be collected from the total inlet blood volume for 45% and 39% hematocrit, respectively. The device's functionality was demonstrated using defibrinated sheep blood (hematocrit=39%). During the experiment, all the blood cells traveled through the device toward the concentrated blood outlet while only the plasma flowed towards the plasma outlet without any clogging or lysis of cells. Because of its simple structure and control mechanism, this microdevice is expected to be used for highly efficient, realtime, continuous cell-free plasma separation.

Animals↗