Apparatus for efficient genetic modification of cells
Inventors
Kotz, Kenneth T. • Teece, Bryan D. • Truslow, James Gillett • Moore, Nathan Francis • Borenstein, Jeffrey T. • Tandon, Vishal
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Assignees
Charles Stark Draper Laboratory Inc
Member
DraperDraper is an independent nonprofit engineering innovation company with a legacy spanning over 90 years, dedicated to delivering transformative solutions for national security, prosperity, and global challenges. Renowned for its pioneering work in guidance, navigation, and control (GN&C) systems, Draper partners with government, industry, and academia to engineer advanced technologies in space, defense, biotechnology, and electronic systems. The company leverages multidisciplinary expertise, digital engineering, and a collaborative approach to provide field-ready prototypes, mission-critical systems, and innovative research. Draper’s mission is to ensure the nation's security and prosperity by delivering sustainable, cutting-edge solutions that address the toughest problems of today and tomorrow, while fostering an inclusive and diverse workforce. Draper also invests in the next generation of innovators through robust educational programs, including internships, co-ops, and the Draper Scholars Program, integrating academic research with real-world problem-solving.
Draper is an independent nonprofit engineering innovation company with a legacy spanning over 90 years, dedicated to delivering transformative solutions for national security, prosperity, and global challenges. Renowned for its pioneering work in guidance, navigation, and control (GN&C) systems, Draper partners with government, industry, and academia to engineer advanced technologies in space, defense, biotechnology, and electronic systems. The company leverages multidisciplinary expertise, digital engineering, and a collaborative approach to provide field-ready prototypes, mission-critical systems, and innovative research. Draper’s mission is to ensure the nation's security and prosperity by delivering sustainable, cutting-edge solutions that address the toughest problems of today and tomorrow, while fostering an inclusive and diverse workforce. Draper also invests in the next generation of innovators through robust educational programs, including internships, co-ops, and the Draper Scholars Program, integrating academic research with real-world problem-solving.
Publication Number
US-12139697-B2
Publication Date
2024-11-12
Expiration Date
Abstract
A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.
Core Innovation
The invention provides a device for treatment of cells with particles comprising a semi-permeable membrane having a plurality of pores dimensioned to allow passage of a fluid and prevent passage of the cells and the particles, and a substrate material constructed and arranged to give structural support to the semi-permeable membrane, with the semi-permeable membrane and the substrate material positioned between first and second plates, the first plate defining a first flow chamber adjacent to a first side of the semi-permeable membrane and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber being constructed and arranged to deliver the fluid in a substantially transverse direction along the first side of the semi-permeable membrane, and the second plate defining a second flow chamber adjacent to a second side of the semi-permeable membrane and comprising a port.
The patent also discloses methods and systems that use the device to co-localize and concentrate cells and particles at the membrane surface to effect transduction or activation, and to recover and separate cells from particles after treatment, including use of a second device having a semi-permeable membrane dimensioned to allow passage of fluid and particles and prevent passage of cells. [procedural detail omitted for safety]
Claims Coverage
One independent claim was identified and the following main inventive features are extracted from that claim.
Semi-permeable membrane dimensioned to allow fluid passage and prevent cell and particle passage
a semi-permeable membrane having a plurality of pores dimensioned to allow passage of a fluid and prevent passage of the cells and the particles
Substrate material providing structural support with lower hydraulic resistance
a substrate material having a lower hydraulic resistance than the semi-permeable membrane, the substrate material constructed and arranged to give structural support to the semi-permeable membrane
First plate with transverse flow architecture
the first plate defining a first flow chamber adjacent to a first side of the semi-permeable membrane and comprising a port configured to deliver the fluid to the first flow chamber, a flow channel extending between the port and the first flow chamber, a transverse port configured to discharge the fluid, and a transverse flow channel extending between the transverse port and the first flow chamber, the first flow chamber being constructed and arranged to deliver the fluid in a substantially transverse direction along the first side of the semi-permeable membrane
Second plate defining second flow chamber with discharge port
the second plate defining a second flow chamber adjacent to a second side of the semi-permeable membrane and comprising a port configured to discharge the fluid from the second flow chamber
Combination of membrane, substrate and plate assembly
the semi-permeable membrane and the substrate material positioned between first and second plates
The independent claim centers on a layered assembly comprising a semi-permeable membrane and supporting substrate sandwiched between first and second plates, where the first plate provides transverse fluid delivery and discharge ports and the second plate provides a discharge port, with the membrane pores dimensioned to pass fluid while retaining cells and particles.
Stated Advantages
Increases the probability that a virus will interact with a cell before it naturally decays by transporting cells and virus into a confined area to increase interaction likelihood.
Improves the efficient use of viral particles and reduces waste of viral particles used for gene transfer.
Reduces time for transducing cells relative to standard static transduction methods.
Co-localizes and concentrates cells and particles on a membrane surface, including monolayer deposition, to enhance diffusion-based transport interaction and reaction efficiency.
Reduces operational complexity and enables visualization of cells within the flow chamber.
Uses hydrophilic, low protein-binding membranes to limit membrane fouling and improve cell recovery.
Documented Applications
Transduction of cells with viral particles (gene transfer/ex vivo gene therapy applications).
Activation of cells with activation particles, including antigens or antibodies optionally coated on beads.
Separation of cells from viral particles using a second device with a membrane that passes fluid and particles but not cells.
Buffer exchange or changing the fluid that cells and/or particles are suspended in (buffer exchange).
Differential separation of particles based on size by exchanging the membrane to pass particles of a particular size while retaining others.
Integration into gene therapy workflows for steps including extraction, selection/activation, gene transfer, washing/reperfusion, and selection of modified cells for infusion.
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