Research Projects

Micro-Electrodes with High Charge Injection Capabilities for Neural stimulation (Sahin): Emerging applications of functional electrical stimulation benefit from electrodes with small surface areas that minimize the volume of neural tissue activated during stimulation and permit fabrication of multi-electrode structures that minimize the tissue disruption during implantation. However, small-area electrodes must deliver higher current densities without introducing electrochemical reactions that degrade the electrode or result in reaction products that damage the tissue around the electrode electrode. Activated iridium is one of the materials of choice for small electrodes with large current injection capabilities. Iridium oxide surfaces can also be obtained by directly electroplating it onto other metals such as gold and platinum. In this project, circular micro-surfaces (diameter 70 micron) made of gold will be electroplated with iridium oxide and the change in its impedance due to plating will be measured using an AC impedance meter. Secondly, similar size surfaces made of iridium will be activated using cyclic voltammetry (CV) and the reduction in the electrode AC impedance will be observed. The experimenter will become familiar with: 1. The importance of the materials used for electrode-electrolyte interfaces in neural stimulation in terms of their charge injection capabilities and, 2. The methods of obtaining small surfaces with equal current specifications without causing irreversible faradaic reactions that can cause tissue damage.

Protein Substrates for Platelet Function Monitoring (Jones): Platelets in the blood are responsible for the formation of clots during injury, but they can also form clots within the blood stream that directly cause stroke,[1] heart attack[2-4], and complications in artificial organs. We are studying methods to assess platelet function by examining their behavior in protein-coated microchannels. Such methods would enable the use of therapies that would directly target specific platelet defects. Lithography techniques are used to generate the channels, and the layer-by-layer assembly technique is used to apply the protein coatings. For this research, a large number of questions must be answered before the method can be considered practical. The behavior of platelets over a given protein substrate must be characterized, and there are dozens of candidates for substrates. Several undergraduate projects will be designed to measure adhesion on different substrates. For a given protein, the student will create and coat the channels, perform the experiments under flow at well-controlled shear stresses, and compare the results to what is known from the literature about the interaction of platelets with the protein. The platelets will be labeled with acridine orange, and overall platelet coverage, aggregate size, separation and orientation will be determined through image analysis. Other projects will use the same methods to compare the adhesion patterns for different types of blood, such as different animal species or breeds. In addition, because the measurements are to be made under flow conditions, it is important to determine how susceptible the coating is to removal by shear stresses. Again, the micro channels will be molded and coated with fibrinogen. An FITC-labeled antibody to fibrinogen will be used to tag the coating, and the surface coating will be examined microscopically and quantified by fluorescent intensity. The channels will then be subjected to flow rates that provide physiological shear stresses, and the surface coatings will be re-examined microscopically. The understanding of the resistance to shear provided by this study will determine modifications that may be necessary to the coating procedure and limitations of the microchannel method.

Construction and testing of polymer microdevices (Selmic): The discovery of the first silicon transistor has dramatically changed the modern world. However, there are some applications where silicon cannot be used, such as where an electronic device may come into contact with a biological system and the lack of biocompatibility of silicon is problematic. Furthermore, polymers are often more suitable for some micromanufacturing applications than is silicon. We have been developing new methods for the design of electronic components that are based on polymers rather than silicon. This project lends itself to several undergraduate projects, such as the construction and testing of an idea for a new polymer-based diode. Such a device would take advantage of the alternating charge composition inherent in the layer-by-layer assembly process.

Embedded sensors for long-term monitoring of infrastructure (Tayebi): Civil Infrastructure is deteriorating rapidly, and substantial investments are being made for its upgrade. The size of investment implies a much longer life of upgraded structures than what is now standard. Composite materials present the almost unique solution for this problem. However, their performance in civil infrastructure environments is unknown and they need to be monitored closely and inexpensively. This project incorporates MEMS sensors inside composites as part of their manufacture so that these sensors can be interrogated during service life. The student will be provided with a specific sensor and asked to test the viability of the sensor for long-term implantation in a specified composite material. The student will be asked to compare sensors of different sizes and measure both the intelligibility of the remotely transmitted signal from the embedded sensor. Next, the student will determine the impact of the sensor on structural integrity through accelerated life testing.

Microscaffolds for tissue engineering (McShane): Tissue growth is highly dependent on geometry and the chemical environment. Current tissue engineering methods suffer from a lack of control over these two requirements and inability to assess cell function. Consequently, we are studying methods to fabricate structures with precise dimensions and chemical components to control cell adhesion, alignment, and growth, and we are incorporating sensing elements into these structures. However, many micro/nanofabrication methods involve harsh chemicals that can destroy both nanosensing elements and biological molecules. It is important to establish simple, mild, and cost-effective processes to produce such structures that will be useful in biological research and biotechnological applications. The students involved will develop novel techniques for 1) patterning polymeric materials, 2) integrating optical sensing elements into these structures, and 3) determining the biocaompatibility of the final structures for different cell types. The student will be asked to apply microlithography and LbL assembly to generate a specific pattern on a given substrate (e.g. multilayer thin film, photosensitive polymer, or elastomer). He/she will integrate fluorescent indicators into the structures, and test these indicators for response to known concentrations of analytes. Finally, he/she will perform cell viability studies on the structure. This paradigm will be repeated for various patterns, substrates and sensing dyes by a number of students. The understanding of the cell-material interactions provided by this study will be useful in designing surface and devices with topographical and chemical features to achieve desired behavior.

Encapsulation of hemoglobin for red blood cell substitutes (Haynie): As a result of the AIDS crisis, Hepatitis C, and other threats to the blood supply, interest in red blood cell substitutes has increased substantially in the past few years. We are using human genome information, bioinformatics data mining methods, and nanofabrication techniques to develop inherently biocompatible polypeptide-based microcapsules for the encapsulation of recombinant human hemoglobin. Such artificial red blood cells will serve as vehicles for gas transport in a blood substitute. A student researcher, under the supervision of a graduate mentor, will help investigate the feasibility of fabrication strategies. The student will purify polypeptide chains of proprietary design, and use them to self-assemble microshells on a suitable spherical "core" on the micron length scale. The core will be dissolved, yielding a microcapsule. The capsule will be "loaded" with FITC-labeled hemoglobin. The student will assess loading using confocal fluorescence microscopy. All the techniques required for this work are available in the IfM. A second student will investigate the breakdown of these microcapsules. Because hemoglobin itself is toxic, it is necessary that these capsules break down in a controlled manner so that the hemoglobin is released in amounts that are small enough to be processed by the body. A related project is the design of the capsule so that the capsule breakdown products themselves are not toxic to the body.

Controlled release of nano-encapsulated drugs (Lvov): Time release of drugs is now commonplace technology. However, in targeted drug delivery it is desirable to be able to inject encapsulated drugs into the bloodstream. Because current methods of encapsulation generate relatively thick shells, time release is possible only in drugs that are taken orally and hence systemically administered. We have succeeded in encapsulating the drug furosemide through layer-by-layer assembly and substantially increasing the release time. If this technique is to be used for targeted delivery, it will be necessary to know how the release rate is related to nanoshell composition and also how the amount of microcapsule attachment is related to the surface concentration of specific antigen-targeted antibodies on the capsule surface. The undergraduate student will be responsible for collecting the necessary data to answer these questions. Drug release under a variety of conditions (pH and shell composition) will be monitored by UV-vis spectrometry. Adhesion in antigen-coated flow channel will be monitored by fluorescent microscopy.

Modification of surface coatings for cellular adhesion (Mills): As research in tissue engineering progresses, it has become increasingly important to be able to develop artificial surfaces that have properties that encourage the growth of specific cells along with the expression of specific proteins from these cells. Dr. Mills is working closely with Drs Lvov, McShane Jones in examining the interaction of cells with their microenvironment. The LbL technique is ideal for the required surface modification. Dr. Mills’ primary interest is in the chondrocytes found in the tempero-mandibular joint of the jaw. The undergraduate student on this project will grow chondrocytes on these nano-engineered surfaces, measure cell viability, and determine, through immunohistochemistry, the proteins that are produced by these cells. Another student will assess cytotoxic effects (inflammation, foreign body response, and formation of new tissue during wound healing) of the various materials and structures used in the sensor technology. A third student project will be undertaken to examine the effect of mechanical stress on the chondrocytes. Again, the cells will be cultured on a nano-coated surface and then subjected to tensile stresses in a device custom made in Dr. Mills’ laboratory for this purpose. Cell products and cytotoxicity will be assessed.