Fluidic device for producing platelets
Inventors
Baruch, Dominique • Blin, Antoine Pierre Marin • Magniez, Aurelie • Chassac, Sonia • Le Goff, Anne • Reyssat, Mathilde
Assignees
Hemostod SA • Ecole Superieure de Physique et Chimie Industrielles de Ville de Paris ESPCI • ESPCI Innov SAS
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Publication Number
US-9909102-B2
Publication Date
2018-03-06
Expiration Date
Abstract
The invention relates to a fluidic device for producing platelets from a suspension of megakaryocytes or their fragments, comprising a production chamber comprising at least one channel in which a suspension of megakaryocytes is introduced to flow from its inlet to its outlet wherein said channel is textured with a plurality of obstacles on at least one portion of its inner surface. The invention is further directed to an ex vivo method for producing platelets from megakaryocytes using a fluidic device as defined above.
Core Innovation
The invention relates to an ex vivo platelet-production system that produces platelets from a suspension of megakaryocytes. A fluidic production chamber includes at least one channel delimited by non-porous walls with an inlet opening for introducing the suspension of megakaryocytes and an outlet opening for collecting the produced platelets.
At least a portion of the inner surface of the walls of the channel is textured with a plurality of obstacles. The textured inner surface is configured to enhance megakaryocyte capture and platelet/proplatelet shedding in the channel during fluidic processing, and embodiments include obstacles arranged in a regular hexagonal periodic structure such as regular hexagonal lattices.
The system can include additional upstream and downstream handling components. Upstream functionality may include megakaryocyte sorting/enrichment and mixing, and downstream functionality may include platelet sorting/purification or other separating steps. The inner textured surface can optionally be provided with a ligand coating, including von Willebrand factor (VWF) and functional variants, to increase cell adhesion.
Claims Coverage
The partial content identifies one independent claim for the fluidic device. The associated dependent claims refine the obstacle geometry, optional ligand coating, downstream handling, an operational wall-shear-rate constraint, and platelet sorting/purification options.
Fluidic device with textured non-porous channel walls for platelet production
A fluidic device for producing platelets from a suspension of megakaryocytes, comprising a production chamber, at least one channel delimited by non-porous walls, at least one inlet opening for introducing the suspension, and at least one outlet opening for collecting platelets, wherein at least one portion of the inner surface of the walls of said channel is textured with a plurality of obstacles.
Hexagonal lattice obstacle geometry on the channel inner surface
The inner surface of the walls of a channel is textured with obstacles configured as substantially circular posts arranged in a regular hexagonal Bravais-lattice pattern.
Ligand coating on the textured inner surface to bind megakaryocytes
A coated ligand is applied to the textured portion of the inner surface of the channel, where the ligand binds megakaryocytes.
Maximum wall shear rate in the textured portion
A flow rate setting results in megakaryocytes in the textured portion experiencing a maximum wall shear rate no greater than 30000 s−1.
Downstream purification/enrichment/separation of collected platelets
Collected platelets at the outlet of the channel are purified, enriched or separated from the suspension, and the collected fraction can contain naked nuclei and/or intact megakaryocytes.
Outlet platelet sorting using one or more specified sorting techniques
Platelets are sorted at the outlet of a channel using one of several specified techniques selected from cross flow filtration, laminar flow, dielectrophoresis, optical force sorting, magnetic force sorting, acoustic force sorting, and inertial forces.
Across the identified claim coverage, the core inventive concept is a fluidic device with non-porous channel walls textured with a plurality of obstacles to support ex vivo platelet production from a megakaryocyte suspension. Dependent refinements include a regular hexagonal obstacle arrangement, optional ligand coating, a maximum wall shear-rate threshold in the textured portion, and downstream purification/enrichment/separation and outlet sorting using specified techniques.
Stated Advantages
Increased capture and platelet yield versus control systems lacking the microfluidic textured chip.
Functional platelet characteristics including receptor expression and TRAP-induced activation, and adhesion/aggregation.
Documented Applications
Ex vivo platelet production from a suspension of megakaryocytes using a fluidic channel with a textured obstacle array and collection at a channel outlet, with optional upstream and downstream handling such as sorting/purification and ligand coating.
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