Abstract: The invention is directed to a detection reagent for CAR expressing cells according to general formula (1) Xn—Sm—Do wherein X is a polypeptide comprising at least 20 amino acids of which at least two amino acids are connected by at least one disulfide group S is a spacer comprising at least 15 carbon atoms D is a detection moiety m, o are integers independently between 1 and 200 n is an integer between 4 and 200 with the provisio that X binds to the antigen binding domain of a chimeric antigen receptor of a cell. The detection agent can be used in a method to detect cells having an antigen binding domain of a chimeric antigen receptor (CAR) binding the detection reagent and preferable to remove the detection moiety D from the detected cell.

Abstract: Systems and methods are described for analyzing a plurality of biological samples with a plurality of fluorescent reagents in an automated fashion. The system may include two optical systems, a fluorescence imaging system and an optical quenching system. These two systems may be placed laterally adjacent to one another, and generally beneath one of the wells of sample-containing microtiter plate. The biological sample contained therein may be stained with a series of fluorescent reagents, with the fluorescence quenched between stainings. By precise positioning of the sample with respect to the imaging system, the sample may be imaged with a plurality of serially applied reagents.

Abstract: The invention relates to a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135?45° to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g.

Abstract: The invention relates to a centrifuge for separating a sample into at least two components, comprising a chamber for receiving a sample to be centrifuged. According to the invention, the centrifuge further comprises a means for controlling the progress of the sample separation is located at the chamber.

Abstract: The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

Abstract: The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

Abstract: The invention is directed to disposable for electroporation of cells, comprising a fluid compartment in an interior of the disposable; a first fluid port for providing cell suspension to the fluid compartment, and a second fluid port for delivering a fluid comprising at least one compound to be electroporated into the cells to the fluid compartment; a first electrode and a second electrode disposed in the fluid compartment; at least one exit port which delivers the fluid from the fluid compartment wherein the first and second fluid port have a fluid communication to a mixing channel which has a fluid communication to the fluid compartment.

Abstract: A centrifuge chamber for separating a sample into at least two components, including a cylinder having a base plate and a cover plate, and a rotational axis assembly having at least one port for input and/or output of the sample, the port being connected to a tube located on or in the base plate and/or cover plate, and the tube having one or more openings into the centrifuge chamber, where at least one opening of the tube is provided with at least one flat-shaped deflector having a surface lying substantially parallel with the cylinder, and a width at its base of at most 1/10 of the inner circumference of the cylinder.

Abstract: The invention is directed to a process for sorting target cells and non-target cells from a sample by a cell sorting valve microfabricated on a surface of a silicon substrate, with microfabricated channels leading from the cell sorting valve, wherein the cell sorting valve separates the target particles from non-target material; a disposable cartridge containing a sample reservoir, a sort reservoir and a waste reservoir; wherein the sample is provided in a buffer comprising nuclease.

Abstract: The invention relates to a process for generation of genetically modified stem cells comprising the steps a) providing a cell sample in suspension comprising stem cells in a centrifugation chamber comprising a base plate and cover plate connected by a cylinder b) adjusting the volumetric concentration of stem cells in the cell sample to at least 1×105 stem cells per mL cell sample by centrifugation c) introducing viral and/or non-viral vectors to the centrifugation chamber for genetically modifying the stem cells d) adjusting the spatial concentration of stem cells in the centrifugation chamber by rotating the centrifugation chamber at a speed where the cell sample is located at the outermost 35% of the radius of the base plate of the centrifugation chamber, thereby inducing gene modification of the stem cells.

Abstract: The invention is directed to a centrifuge chamber comprising a cylinder having a base plate and a cover plate, a rotational axis with at least one port for input and/or output of liquids, at least one port for input of gases and at least one layer for cell culturing, wherein the layer for cell culturing comprises a gas-permeable membrane on which cells can be cultured and wherein the at least one port for input and/or output of gases is connected to the gas-permeable membrane.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has an inlet channel, output channels, and a movable member formed on a substrate. The movable member moves parallel to the fabrication plane, as does fluid flowing in the inlet channel. The movable member separates a target particle from the rest of the particles, diverting it into an output channel. However, at least one output channel is not parallel to the fabrication plane. The device may be used to separate a target particle from non-target material in a sample stream. The target particle may be, for example, a stem cell, zygote, a cancer cell, a T-cell, a component of blood, bacteria or DNA sample, for example. The particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the inlet channel.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has an inlet channel, output channels, and a movable member formed on a substrate. The movable member moves parallel to the fabrication plane, as does fluid flowing in the inlet channel. The movable member separates a target particle from the rest of the particles, diverting it into an output channel. However, at least one output channel is not parallel to the fabrication plane. The device may be used to separate a target particle from non-target material in a sample stream. The target particle may be, for example, a stem cell, zygote, a cancer cell, a T-cell, a component of blood, bacteria or DNA sample, for example. The particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the inlet channel.

Abstract: The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

Abstract: The invention is directed to a method for detecting a target moiety in a sample of biological specimens by: a) providing at least one conjugate with the general formula (I) Xn-P-Ym, with X is an detection moiety, P an enzymatically degradable spacer and Y an antigen recognizing moiety and n, m are integers between 1 and 100 and wherein X and Y are covalently bound to P; b) contacting the sample of biological specimens with at least one conjugate, thereby labeling the target moiety recognized by the antigen recognizing moiety Y; c) detecting the target moiety labeled with the conjugate with the detecting moiety X; and d) enzymatically degrading spacer P, thereby cleaving the detection moiety X from the conjugate. The method is useful to identify target moieties on the biological specimens. The biological specimens detected by the conjugate can be subsequently removed from the sample.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has an inlet channel, output channels, and a movable member formed on a substrate. The movable member moves parallel to the fabrication plane, as does fluid flowing in the inlet channel. The movable member separates a target particle from the rest of the particles, diverting it into an output channel. However, at least one output channel is not parallel to the fabrication plane. The device may be used to separate a target particle from non-target material in a sample stream. The target particle may be, for example, a stem cell, zygote, a cancer cell, a T-cell, a component of blood, bacteria or DNA sample, for example. The particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the inlet channel.

Abstract: The invention provides a system that comprises pharmaceutical agents for use in immunotherapy for reducing the side-effects of an antigen-recognizing receptor against antigen-expressing non-target cells in an individual. The system includes an antigen-recognizing receptor that specifically recognizes an antigen on target cells and at least on one hematopoietic cell type in the individual. The antigen-recognizing receptor is exemplified by chimeric antigen receptors (CAR) be expressed on the surface of an immune effector cells. The system also includes hematopoietic cells resistant to recognition of the same antigen by the antigen-recognizing receptor.

Abstract: The invention is directed to a homogenization device for cell suspensions, comprising a first rotating magnet; a shaft on which a propeller mixer is attached which rotates around the longitudinal axis of the shaft and is movable in lateral direction of the axis of the shaft; the propeller mixer being provided with at least two propeller blades of which at least one is provided with a second magnet; wherein the propeller mixer is rotated by magnetic interaction of the second magnet with the first rotating magnet.

Abstract: The invention relates to a process for generation of genetically modified stem cells comprising the steps a) providing a cell sample in suspension comprising stem cells in a centrifugation chamber comprising a base plate and cover plate connected by a cylinder b) adjusting the volumetric concentration of stem cells in the cell sample to at least 1×105 stem cells per mL cell sample by centrifugation c) introducing viral and/or non-viral vectors to the centrifugation chamber for genetically modifying the stem cells d) adjusting the spatial concentration of stem cells in the centrifugation chamber by rotating the centrifugation chamber at a speed where the cell sample is located at the outermost 35% of the radius of the base plate of the centrifugation chamber, thereby inducing gene modification of the stem cells.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device, which has an inlet channel, output channels, and a movable member formed on a substrate. The movable member moves parallel to the fabrication plane, as does fluid flowing in the inlet channel. The movable member separates a target particle from the rest of the particles, diverting it into an output channel. However, at least one output channel is not parallel to the fabrication plane. The device may be used to separate a target particle from non-target material in a sample stream. The target particle may be, for example, a stern cell, zygote, a cancer cell, a component of blood, bacteria or DNA sample, for example. The particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the inlet channel.