Joseph Flinders and Dr. Kenneth Solen, Chemical Engineering Department
When blood contacts man-made biomaterials such as those used in artificial organs (e.g. hemodialyzers, oxygenators, etc.) a chain of events occurs that can lead to medical complications as serious as a stroke. These events include proteins (particularly fibrinogen) adhering to the biomaterial’s surface, the accumulation of blood platelets on the fibrinogen to form “Thrombi”, and then the dislodging of the thrombi to form particles (microemboli) that can block downstream arteries or capillaries causing a “stroke” or other cardiovascular event.
Dr. Horbett of the University of Washington developed three chemical coatings for biomaterials with the purpose of resisting protein adsorption and minimizing the sequence of events leading to thromboembolism. Using instruments and measuring techniques, developed by Dr. Solen, our research team evaluated the efficacy of these three coatings in reducing formation of thrombi and microemboli by simulating blood flow conditions in cardiovascular devices.
Conditions for blood flow through cardiovascular devices were simulated by flowing donors’ blood through flow cells. These flow cells had expanding and constricting diameters to increase disturbance in the flow; thus increasing blood and biomaterial interaction and inducing a greater amount of thromboembolism. These flow cells were fabricated using quite small tubing (outer diameter <1.3 mm). The tubing was small and clear as to enable obseravation of the formation and dislodging of thrombi using a video microscope. When thrombi dislodged (embolized) they were dected by a Light Scattering Microemboli Detector (LSMD) downstream of the flow cells. As a group our most time intensive task was fabricating flow cells. Making consistent flow cells required a lot of trial and error and team work. We regularly looked for ways to speed up production of our flow cells. After many changes in tubing size, cell design, and fabrication tools and methods we were able to make our desired flow cells at a reasonable rate. As we ran the experiments we found many unforeseen challenges and opportunities. We were constantly looking for ways to decrease noise in the experiment by maintaining consistent conditions. This was accomplished by activities ranging from laser calibrations to temperature controls. As we continued to labor we divided up tasks and specialized in certain activities. Developing and following a standard protocol caused us to grow confident in our procedure and the accuracy of our results. For each coating we tested at least 5 donors’ blood. Each donors’ blood was simultaneously flowed through a control flow cell and a coated flow cell. This approach was very valuable because it allowed us to use basic statistical tools to test for a difference between Dr. Horbett’s coating and the control group. The findings determined there was not a significant decrease in the amount of thromboemboli. In fact, there was evidence to imply an increase in thromboembolism in the coated tubing. Although results were somewhat disappointing many important lessons were learned. Our research team did not have our own agenda in trying to prove Dr. Horbett’s coatings would make a significant difference. Our task was to gather data to see the actual effects of the coating. Our procedures and protocol can easily be adapted for further testing. Individually, I found our work was very valuable just by being involved in a scientific environment. I was surprised to realize the challenges involved in implementing experiments because of basic logistical difficulties. I saw the value in hands on experience and the usefulness of many“less scientific” labor and skills (e.g. fabricating flow cells by hand). Also, there were many areas of study that I was exposed to for the first time. I was introduced practical uses of statistical analysis. I develop interest in concepts outside of my normal curriculum. I found this research to be an important step in understanding applications of chemical engineering particularly in the biomedical field. I am interested in applying my knowledge to the biomedical or pharmaceutical industry and this has been an important step. This has helped me understand this industry more clearly and has given me valuable experience in preparing for my future. Overall one of the most valuable parts of the research experience was the association with the research group. I was amazed by each of the motivated, innovative, and hard working members of our team. I found the positive environment was crucial to our success. Most of all I felt privileged to work with Dr. Solen. He is an excellent role model because of his focus, determination, spirituality, and kindness. This was a great scientific research opportunity and an excellent mentoring program.