This proposal is submitted in response to NIH Notice 98-086, entitled: """"""""Development of High Throughput Assays for Exfolated Cells in Tumor Detection"""""""" The goal of this project is to automate a new technology for use in experimental cell biology and potentially as a screening tool for disease. The approach is based on the methods of Coprocytobiology (CCB), in which living exfoliated epithelial cells from the colonic mucosa are recovered from stools and then examined for micronutrient uptake, cell- surface markers, and disease biomarkers. In particular, the technique may prove useful for the detection of colorectal cancer well before the appearance of bleeding tumors. Possibly within the next decade this technique will become established as a fundamental tool for both gastrointestinal research and as a screening tool for clinical use. The CCB methodology is a highly developed but tedious manual process and is extremely time-consuming (approx. 1.4 samples/hr). This proposal presents an approach to automate this cell isolation technique, increasing throughput to 24 samples/hr. Our long-term goal is to produce a machine for no more than 20% the cost of an average flow cytometer. Additionally, a programmable version of this machine will allow researchers to test modified versions of CCB methodology. Industrial design and robotic automation methods will be employed in the construction of the machine. Major tasks will be component selection, mechanical and electrical design, and hardware-software system integration. Validation of results will be performed using microscopy and flow cytometry.
There are two main areas for commercial application of CCB automation: first in human cell biology research and second as a screening tool for preventative health care. The second application is dependent on the first, since CCB has been neglected by researchers, particularly by the gastroenterology community. A low cost automated device will make CCB application in research and human studies easier and attractive. If such studies prove CCB capable of sensitive and accurate screening tests for the early detection of colon cancer and other diseases, the market for an automated device will include most hospitals, HMOs, and clinical/pathology labs.