Replacing current manual processing of leukapheresis samples for cell therapy production with a robust, high-precision, automatable, closed system.

GPB Scientific has developed a prototype system that reduces cost and the risk of human error and contamination for the front-end of cell therapy manufacturing... providing lower-variability and higher quality cells for the input to the cell engineering and production processes for CAR-T and other therapies.

The microfluidic chip-based technology that GPB has licensed exclusively from Princeton University and further developed is Deterministic Lateral Displacement (DLD). The underlying innovative principle of the microfluidic DLD chip is the ability to gently and uniformly fractionate and harvest viable cells with virtually no cell loss from a fluid flow based on their hydrodynamic size independent of their mass. A mixture of fluid and particles flows through an array of microposts, in which the micropost axis is tilted at a small angle from the direction of the fluid flow. Particles larger than a certain critical size (e.g. WBCs) gently bump off the posts to flow in a direction along the tilted array axis (see figure), while smaller particles, e.g. red blood cells (RBCs), platelets (PLTs), flow straight ahead with the fluid stream. Thus, larger WBCs flow out of the fluid stream of the original input cell suspension and can be collected separately. This process results in an exceptionally pure, gentle separation based on size. This process can be used in a label free manner, or can be used in combination with magnetic or other labelled separation techniques.

The process eliminates the need for ficoll and higher force processes such as standard or counterflow centrifugation. It replaces the current operator-intensive approaches for WBC purification and enrichment with a robust, high-precision, automated closed system... improving efficiency, lowering costs, reducing variability and potential for contamination from manual operations. This produces high quality cells ready for further steps in cell therapy manufacturing.

The DLD process has been used to fractionate whole blood to harvest components including white blood cells, red blood cells, platelets, rare cells including circulating tumor cells (CTCs), T cells, NK cells, etc. The critical size determining which path the cells or other objects follow is controlled by the design of the micropost array (e.g. post size and shape, gaps between posts and axis tilt angle).

Our product strategy is to offer a turnkey, closed benchtop system using consumable DLD microfluidic chips to process leukapheresis samples.

Target specifications for the CAR-T therapy DLD system are:

  • Closed Benchtop unit
  • Fully Automated
  • Single-use multi-channel polymer DLD microchips using high-precision/low-cost commercial chip production
  • Up to 5x1010 WBCs in up to 500mL in one hour (10-15L apheresis procedure targeting 1-2x109 mononuclear cells, starting WBC concentration up to 2x108 WBCs/mL)
  • >70% WBC and T-lymphocyte recovery
  • >90% RBC depletion
  • >80% platelet depletion
  • >70% recovery of T-cell expansion capacity
  • Compatible with routine blood collection and storage bags

This system will also be able to enrich WBCs for other cell therapies, e.g., stem cell therapies, hematopoetic cell transplantation, NK cells, and others.