Integrated Systems for the Analysis of Circulating Multiple Myeloma Cells (CMMCs)

? DESCRIPTION (provided by applicant): Multiple myeloma (MM) is a plasma cell malignancy and comprises about 1% of malignant tumors and 15% of all hematopoietic neoplasms. According to the American Cancer Society, in 2014 an estimated 24,050 new cases were diagnosed in the U.S. with the estimated deaths being 11,090. Monoclonal gammopathy of undetermined significance (MGUS) is associated with a 1% per year risk of progression to overt malignancy, most commonly MM and is found in approximately 3% of individuals over 50 with the prevalence increasing with age. Without a clear diagnostic test to monitor MGUS malignancy progression, a range of factors are currently monitored including changes in serum free light chains ratio, elevated serum M protein level and high bone marrow plasma cell percentage . Recent studies have demonstrated that circulating multiple myeloma cells (CMMCs) secured from bone marrow biopsies measured by immuno-?uorescence microscopy or ?ow cytometry are useful for diagnosis, prognosis and measuring therapeutic response for MM. However, securing a bone marrow biopsy is painful to the patient prohibiting frequent testing required for monitoring disease progression, drug response and/or recurrence. Development of novel instrumentation and techniques for CMMC selection and analysis directly from peripheral blood is essential to improve the management of patients with MM or its early disease stages. Building on extensive preliminary data secured from a Phase I type study, this Phase II project is focused on the development of an integrated system that uses a disposable fluidic cartridge and the associated instrument peripherals for the rapid and fully automated processing of CMMCs directly from whole blood obviating the need for bone marrow biopsies and thus, allowing for more frequent testing especially those with MGUS. The instrument will be able to select CMMCs at >80% recovery and >80% purity, release the selected cells and electronically enumerate them and prepare them for FISH analysis or immunophenotyping. The system can also off-load the selected CMMCs for molecular profiling, such as searching for KRAS mutations. Operation of the instrument will be automated with an overall sample- to-answer processing time of ~1.5 h. The system will be subjected to both internal validation by BioFluidica staff as well as external validation by collaborators at the University of North Carolina at Chapel Hill. While MM will be used as a case study for clinical performance verification of the instrument, it can easily be utilized in different cancer-related diseases by programming in the correct selection antibody to search for the relevant blood-borne biological cells.