SELF-ADDRESSED PARTICLES FOR MOLECULAR CANCER ANALYSIS

The molecular analysis of cancer spans two extremes in sample volume: detailed characterization of a few cancerous cells is constrained to microliters of material, whereas in vivo molecular profiling in humans ideally samples the entire blood supply. Neither chromatographic or electrophoretic separation methods are functional at both extremes. Accordingly, we propose a radically new approach to molecular separation based on multiplexed nanoscale extraction that is both exceedingly efficient and scaleable to any sample volume. In this method, segmented nanoparticles with oligonucleotide ?addresses? and harboring different capture chemistries- some with very high affinity/selectivity like antibodies, others with relatively low affinity/selectivity like alkyl stationary phases- are simultaneously introduced into a sample. After equilibration, the particles are separated for subsequent MALD1 mass spectrometric analysis via self-assembly onto a DNA chip containing complementary oligonucleotides. These "self-addressed," sub-100 nm diameter nanoparticles offer extraordinary functionality: the capacity to derivatize different segments with different chemistries (e.g., oligonucleotide addresses and stationary phases for analyte capture) and enhanced sensitivity for mass spectrometry. In addition, the particles can be made superparamagnetic for facile processing. As such, their preparation and characterization, the foci of this proposal, should be viewed as an enabling step toward comprehensive molecular analysis of cancer.