Abstract: The present disclosure relates to systems and methods for flow-through separation of paramagnetic particle-bound cells in a cell suspension containing both bound and unbound cells as well as systems and methods for removing paramagnetic particles from paramagnetic particle-bound cells or from a cell suspension with unbound cells. It further relates to a flow-through magnetic separation/debeading module and a flow-through spinning membrane debeading module.

Abstract: The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), and compositions and reaction mixtures comprising the same.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: The present disclosure provides, among other things, a method of engineering genetically modified cells comprising, maintaining the cells in a collection chamber, contacting the cells with a fluid flow of a composition comprising viral or non-viral particles, thereby engineering genetically modified cells. The present disclosure also provides, among other things, a method of engineering genetically modified cells comprising, subjecting the cells to a centrifugal force, contacting the cells with a fluid flow of a composition comprising viral or non-viral particles, thereby engineering genetically modified cells.

Abstract: A system for introducing a vector into includes a filter module defining an intra-capillary space and an extra-capillary space separated from the intra-capillary space by a porous membrane. The system also includes a pair of intra-capillary ports fluidly coupled to opposite ends of the intra-capillary space and each receiving a transduction media, cells, and a vector. The system also includes a pair of extra-capillary ports coupled to opposite ends of the extra-capillary space and in fluid-communication with a source of extra-capillary media and a waste container.

Abstract: The present disclosure relates to systems and methods for flow-through separation of paramagnetic particle-bound cells in a cell suspension containing both bound and unbound cells as well as systems and methods for removing paramagnetic particles from paramagnetic particle-bound cells or from a cell suspension with unbound cells. It further relates to a flow-through magnetic separation/debeading module and a flow-through spinning membrane debeading module.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: The present disclosure relates to systems and methods for flow-through separation of paramagnetic particle-bound cells in a cell suspension containing both bound and unbound cells as well as systems and methods for removing paramagnetic particles from paramagnetic particle-bound cells or from a cell suspension with unbound cells. It further relates to a flow-through magnetic separation/debeading module and a flow-through spinning membrane debeading module.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: The present disclosure relates to systems and methods for flow-through separation of paramagnetic particle-bound cells in a cell suspension containing both bound and unbound cells as well as systems and methods for removing paramagnetic particles from paramagnetic particle-bound cells or from a cell suspension with unbound cells. It further relates to a flow-through magnetic separation/debeading module and a flow-through spinning membrane debeading module.

Abstract: The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), and compositions and reaction mixtures comprising the same.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: In one aspect, a method of processing a cell is disclosed, which includes passing a cell through a pore of a membrane comprising a plurality of pores while exposing the cell to an agent so as to cause a change in the cell, thereby allowing said agent to enter the cell, where each of said pores extends from an input opening to an output opening and has at least one cross-sectional dimension, and in many embodiments a maximum cross-sectional dimension, less than a diameter of said cell. For example, at least one cross-sectional dimension of the pore, and in many embodiment the maximum cross-sectional dimension of the pore, can be less than about 40 microns, or less than about 30 microns, or less than about 20 microns, or less than about 15 microns, or less than about 10 microns.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: The present disclosure relates to systems and methods for flow-through separation of paramagnetic particle-bound cells in a cell suspension containing both bound and unbound cells as well as systems and methods for removing paramagnetic particles from paramagnetic particle-bound cells or from a cell suspension with unbound cells. It further relates to a flow-through magnetic separation/debeading module and a flow-through spinning membrane debeading module.

Abstract: A microfluidic device for manipulating particles can include a substrate and one or more obstacles, each obstacle comprising a plurality of aligned nanostructures including a plurality of nanoparticles or a plurality of polymer layers, or a combination thereof. The obstacle on a substrate can be forests with intra-carbon nanotube spacing ranging between 5-100 nm for isolation of particles such as very small viruses and proteins.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: The devices and systems described herein include one or more fluid paths, e.g., channels, and one or more selectively permeable obstacles arranged in the fluid path(s), each including a plurality of aligned nanostructures, e.g., nanotubes or nanorods, defining an outer surface of the obstacle and an internal network of voids. The obstacle(s) can further include binding moieties applied to the outer surface and/or to the surfaces of the individual nanostructures within the obstacle(s). The devices can be manufactured by forming the dense groupings of nanostructures to extend outwards and upwards from a substrate; forming a fluidic channel, bonding the fluidic channel to the substrate; and optionally applying binding moieties to the obstacles. The devices can be used to manipulate cells within fluid samples.

Abstract: A microfluidic device for manipulating particles can include a substrate and one or more obstacles, each obstacle comprising a plurality of aligned nanostructures including a plurality of nanoparticles or a plurality of polymer layers, or a combination thereof. The obstacle on a substrate can be forests with intra-carbon nanotube spacing ranging between 5-100 nm for isolation of particles such as very small viruses and proteins.

Abstract: The devices and systems described herein include one or more fluid paths, e.g., channels, and one or more selectively permeable obstacles arranged in the fluid path(s), each including a plurality of aligned nanostructures, e.g., nanotubes or nanorods, defining an outer surface of the obstacle and an internal network of voids. The obstacle(s) can further include binding moieties applied to the outer surface and/or to the surfaces of the individual nanostructures within the obstacle(s). The devices can be manufactured by forming the dense groupings of nanostructures to extend outwards and upwards from a substrate; forming a fluidic channel, bonding the fluidic channel to the substrate; and optionally applying binding moieties to the obstacles. The devices can be used to manipulate cells within fluid samples.