Isolating and analyzing rare brain-derived cells and particles

A method of analyzing brain-derived cells or particles from a blood sample from a subject, the method comprising

• obtaining a blood sample from the subject;
• mixing the blood sample with magnetic beads comprising a binding agent that specifically binds to one or more specific types of cells or specific types of particles and not to white blood cells (WBCs), for a time and under conditions sufficient for the binding agent to bind to the brain-derived cells or particles;
• flowing the blood sample through a first module comprising a microfluidic size-based separation system configured to direct small cells and particles such as red blood cells (RBCs) and platelets in the blood sample to a first waste outlet and to direct the remaining blood sample to a second module comprising an inertial focusing channel;
• flowing the remaining blood sample through the second module at a flow rate and for a distance sufficient to cause cells and/or particles in the remaining blood sample to align in one or more streamlines within the remaining blood sample flowing in the inertial focusing channel;
• flowing the remaining blood sample with the cells and/or particles aligned in one or more streamlines through a third module comprising a magnetophoresis system for a time and distance sufficient to separate the specific types of cells or particles bound to magnetic beads from WBCs cells, other cells, and particles not bound to magnetic beads, and flowing the WBCs other cells, and particles not bound to magnetic beads into a second waste outlet and flowing the bound cells or particles to a product outlet;
• obtaining bound cells or particles from the product outlet and determining which of the bound cells or particles originate in brain tissue;
• and
• analyzing the brain-derived cells or particles.

A system for analyzing and/or isolating brain-derived cells or particles, from a blood sample from a subject, the system comprising

• a mixer for combining the blood sample with magnetic beads comprising a binding agent that specifically binds to either
• (i) brain-derived cells or particles and not to white blood cells (WBCs), or
• (ii) WBCs and not to other cells or particles,
• for a time and under conditions sufficient for the binding agent to bind;
• a first module comprising a microfluidic size-based separation system configured to direct small cells and particles such as red blood cells and platelets in the blood sample to a first waste outlet;
• a second module comprising an inertial focusing channel, wherein the remaining blood sample is controlled to flow through the second module at a flow rate and for a distance sufficient to cause cells and particles in the remaining blood sample to align in one or more streamlines within the remaining blood sample flowing in the inertial focusing channel;
• a third module comprising a magnetophoresis system configured to separate cells or particles bound to magnetic beads from cells and particles not bound to magnetic beads, thus separating bound cells or particles from unbound cells and/or particles and flowing the WBCs into a second waste outlet and flowing unbound cells and/or particles to a product outlet;
• and
• a fourth module comprising a cell or particle analyzer configured to determine which of the cells or particles originate in brain tissue and, optionally, to separate cells or particles originating in brain tissue from cells or particles originating in other tissues, thereby analyzing and/or isolating brain-derived cells or particles from the blood sample.