MagneSensors'collaborative program is centered on a novel nanotechnology based platform that uses ultra-sensitive magnetic sensors and magnetic labels to perform powerful rare cell assays. This magnetic detection platform uses high temperature superconducting quantum interference devices (SQUIDs) to detect the binding to cell surface receptors of antibodies labeled with magnetic nanoparticles. We will apply the platform to the assessment of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) in order to better monitor and guide therapies. A major program thrust is to develop improved magnetic sensors and magnetic nanoparticle labels and incorporate them into next generation instrumentation. This instrumentation will be used to demonstrate magnetic assays capable of rapidly detecting CLL cells.
The specific aims are: 1) Improve magnetic nanoparticle labels and their conjugation to antibodies (d100 nm size with <15% size variability, 10X reduced aggregation after conjugation to detect Ab, low aggregation in serum) 2) Build new instrument for rare cell detection (10X improved sensitivity, 20X higher throughput) 3) Demonstrate ultra-sensitive detection of rare cells in simple CLL model system with new instrument and reagents, compare to flow cytometry (detect 50 cells in background of 107 cells <45 minutes) 4) Demonstrate rapid, sensitive magnetic cell assay for minimal residual disease assessment of chronic lymphocytic leukemia in clinical samples (detect as few as 50 CLL cells in 107 leukocytes in <45 min) The high sensitivity of magnetic platform enables the detection of rare cells (1 in 104-106), or cells expressing a low number of receptors. The mix and measure format significantly reduces assay preparation time and simplifies automation (no wash steps). This ability to work with little or no sample preparation facilitates rapid, high throughput testing on clinical samples. The interdisciplinary effort unites Moores UCSD Cancer Center and Nano Tumor Center of Excellence for Cancer Nanotechnology, UCSD for the leukemia application, Immunicon Corporation for the custom magnetic nanoparticle labels and rare cell detection expertise, SoluLink, Inc. for the bioconjugation chemistry for attaching antibodies to magnetic nanoparticles, and MagneSensors, Inc. for magnetic sensors, instrumentation, and magnetic assay expertise.Project Narrative Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in North America and Europe and accounts for over 30% of all leukemias. CLL remains incurable with the currently available treatments and the prognosis of patients varies substantially. Existing techniques available to assess minimal residual disease to optimize treatment, such as flow cytometry and polymerase chain reaction (PCR), are inadequate for routine clinical use. A magnetic platform capable of rapid, ultra-sensitive, assays to detect rare leukemia cells could assess minimal detectable disease in CLL and have clinical utility for improving patient outcomes by enabling physicians to adjust therapies sooner than is currently possible.