Injectable nanogel can monitor blood-sugar levels and secrete insulin when needed.
Nicole Pellegrini, who will be graduating this week, has capped her undergraduate career with biotechnology research of such quality that she will be presenting the work to the American Chemical Society next month.
At the ACS conference in Vermont the senior in chemical engineering will report promising results for a more efficient way to monitor microorganisms during fermentation, the process in which yeast, animal cells or bacteria are grown to produce useful products such as drugs. Working alone at first as a UROP student and later with other undergraduates in a chemical engineering course, Ms. Pellegrini modified an existing analytical tool so that it could be automated.
During fermentation High Performance Liquid Chromatography (HPLC) is used to determine the concentration of sugars, metabolic products (like organic acids) and other compounds associated with the growth of microorganisms. This information is critical to monitoring-and regulating-the fermentation process.
Yet standard HPLC systems require that samples be collected manually from the bioreactor where the organisms are grown, then centrifuged, filtered, and often diluted before they can be sent through the HPLC unit without damaging it. "This process is time consuming and does not allow for real-time control of the system," Ms. Pellegrini wrote in an abstract for the ACS conference.
Ms. Pellegrini and colleagues succeeded in bypassing most of these steps by interfacing a bioreactor and an HPLC unit with a novel auto-sampling device that "draws out samples from the [bioreactor] through a rapidly rotating" filter. In contrast, the filter used for standard HPLC sampling is fixed, and without steps like centrifugation it clogs within seconds.
Similarly, although automated HPLC sampling is not new, "many of the systems currently available have limited applications because they use a fixed filter," said Ms. Pellegrini's UROP supervisor Jean-Francois Hamel, a research engineer in chemical engineering. "They work only with a dilute fermentation broth [the mixture of microorganisms and associated compounds removed from the bioreactor]."
The new device, however, "proved capable of filtering samples even when the fermentation broth was extremely viscous," Ms. Pellegrini wrote. It also "worked well throughout the course of the [125-hour fermentation] run."
During fermentation, a team of students compared the concentration of glucose sugar detected by the automated system with that detected by a standard system to further validate the system. They found only minor differences.
The new system was tested with a bacterium that produces cellulose for special paper, air filters, high-quality diaphragms for audio equipment and more. The fermentation broth for this bacterium is especially thick, so "it was a good challenge to the system," said Dr. Hamel, who is also a lecturer in chemical engineering and supervised the team of students who worked with Ms. Pellegrini in course 10.27, the Chemical Engineering Projects Laboratory.
Ms. Pellegrini's teammates are juniors Mei-Ling Pan, Heather Lee, and Laura Vojvodich of the Department of Chemical Engineering. All are coauthors of the ACS paper, as are Dr. Hamel and Claire Sahut of the Commissariat A L'Energie Atomique in France. The latter institution developed and provided the auto-sampling device used in the work; the device had never been used for this application before.
Ms. Pellegrini will be attending graduate school this fall at the University of Pennsylvania where she'll "probably continue in biochemical engineering or maybe get into biomedical engineering."
Asked whether her UROP work and hands-on experience in course 10.27 influenced her decision to pursue these studies, she replied: "They definitely, definitely influenced me. It was the first time I actually got to see what's involved in a biotech lab, and I really enjoyed it!"
A version of this article appeared in the May 25, 1994 issue of MIT Tech Talk (Volume 38, Number 34).