Current Research Projects
- A microfluidic device for continuous blood plasma separation
Centrifugation is typically used to separate plasma, or collect cells from a sample of whole blood for clinical analysis. Although centrifugation allows a more purified sample volume (either cells or blood plasma), it is a batch process not suitable for applications where continuous real-time sampling or small sample volumes are required. Several studies have clearly shown that cardiac surgery induces systemic inflammatory responses, particularly when cardiopulmonary bypass (CPB) is used. These systemic responses are attributed to several factors, including exposure of blood to nonphysiological surfaces of the heart-lung circuit, ischemia-reperfusion of the involved tissues, surgical trauma and hypothermia. 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. Thus, there is a need for a system, which can separate blood plasma from whole blood and measure the concentration of the clinically relevant proteins in real time while the surgery is proceeding. There are currently research activities related for on-chip biological cell or fluid separations based on a variety of working principles (e.g. Brownian Ratchet, Dielectrophoresis, deterministic lateral displacement, field flow fractionation, etc.). In this study, a microfluidic device for continuous, real time blood plasma separation, which may be integrated with a downstream plasma analysis device, is studied.
Text for figure: Schematic diagram of a microfluidic blood plasma separation device. This device is designed to have a whole blood inlet, a purified plasma outlet, and a concentrated blood cell outlet.
- A side view PIV system for 3 dimensional microflow study
Particle Image Velocimetry (PIV) is a quantitative field measurement technique used to visualize and analyze flow structure using tracer particles. However, due to the planar nature of microfluidic devices and the implementation of a microPIV laser light source through a microscope, most MicroPIV flow profiles are limited by the depth of focus of the microscope objectives. They are simply planar representations of a three dimensional flow profile throughout the depth of the device, where any depth (z axis) directed velocity profiles in nonuniform channel depths must be inferred. These limitations create obstacles when studying the receptor-mediated basis of cell adhesion to vascular endothelium in a shear flow. In a recent development, a side-view flow chamber was devised to study cell deformation and adhesion to various adhesion surfaces in a microcapillary. This design allowed not only the measurement of the effects of flow on cell-surface adhesion strength, but also the visualization of cell deformation and the cell-substrate contact interface in shear flow. This microPIV technique allows the further characterization of full three dimensional flow profiles, especially z-directed velocity profiles during micromixing and the actual shear flow velocity gradient around adherent cells to determine the local shear force acting on those cells adhered on a substrate.
Microdevices for microdialysis and membrane separations
Microdialysis is a commonly used technique for separating small biomolecules. This technique is based upon controlling the mass transfer rate of small biomolecules diffusing across a semipermeable membrane into a dialysis fluid while excluding larger molecules such as proteins. Dialysis is also used commonly in biological laboratories to desalt high ionic strength protein solutions. Using a dialysis membrane is also a quick and inexpensive way of removing salt. Microfluidic channels have the advantage of having an extremely high surface to volume ratio to promote more efficient dialysis. Thus, an on-chip dialysis system is useful for desalting protein solutions.
Text for figure: A perfusion fluid flows through the SU-8 microchannel at a known flow rate. A stock glucose solution is placed within a reservoir separated from the microchannel by the semipermeable membrane. The perfusion fluid is collected at the device outlet fed by the microchannels and analyzed sing a handheld glucose monitor.
Microneedle insertion actuators for minimally invasive insulin delivery to diabetic patients
It is universally recognized that diabetes management could be greatly enhanced if direct feedback control of glucose levels were possible. As a result, there are currently major research efforts to miniaturize and improve biomedical devices for both insulin delivery and glucose sampling and analysis technologies. Microneedles offer an attractive method of drug delivery by mechanically penetrating the skin and injecting insulin just under the stratum corneum, where it is rapidly absorbed by the capillary bed into the bloodstream. The advantage of microneedle enhanced drug delivery is that drug is actively injected into a patient so the dosage and infusion rate may be varied with time to allow complex drug delivery profiles. However, the main issue with microneedles is to achieve a satisfactory balance between structural rigidity and miniaturization. A miniaturized microdialysis probe for continuous glucose sensing will also be designed and coupled to the drug-delivering microneedles. Thus, the ultimate goal of this project is to design a system that will demonstrate the continuous delivery of insulin to a diabetic rat with active glucose monitoring.
Electrohydrodynamic instability micromixing within two phase microfluidic systems for biological purification technology
The goal of this project is to study organic-aqueous two phase microflows and create an autonomous microfluidic device capable of performing liquid-liquid extraction techniques for purification of DNA and other biological samples. Two phase flow behavior will be studied using fluorescent dye localization techniques and microPIV. The flow is destabilized by an electrohydrodynamic (EHD) instability to enhance mixing of the two phases to increase the surface area over which liquid extraction may occur, monitored by a novel sideview microPIV technique for three dimensional profile reconstructions. The flow behavior of the two phase system and EHD mixing will be experimentally studied and compared to the analytical and computational analysis. This technique will enable sample preparation for highly integrated genetic screening diagnostics and holds major promise to enabling on-site biological sample collection and analysis.