Microfluidic Isolation of Aptamers with Affinity towards Multiple Myeloma Monoclonal Immunoglobulins (M-Ig)

Abstract

AbstractMultiple myeloma (MM) is a bone marrow cancer of resident plasma cells that affects 125,000 patients in the U.S. with ∼ 30,000 new cases per year. Its signature is the clonal over-proliferation of a single plasma cell that secretes a patient specific monoclonal immunoglobulin (M-Ig). Detecting this patient specific M-Ig could allow sensitive detection of minimal residual disease in multiple myeloma from patient serum. Aptamers, single-stranded oligonucleotides with affinity and specificity to a target molecule, have recently been introduced as affinity reagents able to detect MM M-Igs. Here we adapt these benchtop M-Ig systematic evolution of ligands through exponential enrichment (SELEX) techniques to our bead integrated microfluidic SELEX (BIMS) device to rapidly generate patient specific aptamers. Using MM patient serum, we isolate patient M-Ig specific aptamers rapidly (runtime < 12 hours) with high affinity (KD < 20 nM) while consuming limited quantities of patient M-Ig (< 100 μg).