Enriched abnormal cells will enable genomic, proteomic, and epigenomic analyses to detect cancer-specific alterations in expressed genes, protein/peptide profiles, and epigenetic markers. The ability to carry out such enrichment in high efficiency in a routine way using body fluids may lead to improvements in cancer detection at early stage. The current enrichment methods rely on fluorescence-activated cell sorting (FACS) and immunomagnetic separation (IMS). FACS is an emerging diagnostic field which offers the isolation of cell subsets with high purity however, its sorting rate (104 cells/s) is slow and its apparatus is large and expensive. IMS is simple and low cost method to separate targeting cells however, the batch operation limits its throughput and its enrichment factor is low. This NIH SBIR Phase I proposal is to develop a simple, high throughput and high enrichment factor system for the enrichment of rare cancer cells. In phase I, we will demonstrate the feasibility of using size tunable iron oxide magnetic nanoparticles (MNPs) for the enrichment of cancer cells with high enrichment factor. In phase II, we will optimize this system by focusing on a specific cancer cell in body fluid. The final deliverables of this project will include columnless kit, column kit, and the magnetic microfluidic concentrator for different level of enrichment.
More than 80 percent of human tumors originate from epithelial cells, often at a mucosal surface, and are clonal in origin (e.g., colon, lung, prostate, oral cavity, esophagus, stomach, uterine cervix, bladder). Their development often becomes apparent when tumor cells exfoliate spontaneously into sputum, urine, or even into various effusions. The molecular and genetic abnormalities within these exfoliated cells could be used to detect and identify precancerous lesions or very early stage cancer if highly sensitive technologies were clinically available to identify the few abnormal cells among millions of normal cells. Successful development of this project will provide a high throughput and high enrichment factor system for the enrichment of rare cancer cells and cell fragments in body fluids for early cancer detection. ? ? ?
| Xu, Hengyi; Aguilar, Zoraida P; Yang, Lily et al. (2011) Antibody conjugated magnetic iron oxide nanoparticles for cancer cell separation in fresh whole blood. Biomaterials 32:9758-65 |
