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 present invention provides an extracellular anti-linker/label epitope chimeric antigen receptor (anti-LLE CAR) comprising I) a linker/label epitope (LLE) binding domain, II) a transmembrane domain, and III) a signal transduction domain, wherein said extracellular LLE binding domain binds a target cell binding molecule (TCBM) comprising i) an antigen binding moiety (ABM), wherein said ABM binds specifically to an antigen expressed on a target cell, ii) a label moiety (LaM), wherein said LaM is a naturally occurring molecule in a subject or a derivative thereof, iii) a linker moiety (LiM) conjugating said ABM and said LaM, thereby forming a linker/label epitope (LLE), wherein said extracellular LLE binding domain binds said LLE with a higher preference than said naturally occurring molecule.

Abstract: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

Abstract: A multilevel, disposable cartridge may have a plurality of fluid wells or reservoirs holding a plurality of reagents, and a sample viewing area to view a biological sample. The reagents may be applied sequentially to the sample by opening a specific valve formed in an elastomeric, flexible layer under the fluid well. The fluid channels may be formed in a first rigid plastic layer to conduct the reagent to the sample. Pneumatic channels for applying suction or pressure to the valves may be formed in a second rigid, plastic layer.

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: Described here is a microfabricated particle sorting device that uses a transient pulse of fluidic pressure to deflect the target particle. The transient pulse may be generated by a microfabricated (MEMS) actuator, which pushes a volume of fluid into a channel, or sucks a volume of fluid from the channel. The transient pressure pulse may divert a target particle into a sort channel.

Abstract: The invention is directed to an connector comprising a first part and a second part, each provided with a contact surface and at least one non-contact surface facing away from the contact surface, at least one opening in the contact surface having an fluid connection to at least one opening of the non-contact surface, a releasable covering of the opening in the contact surface, and complementary means for mechanically coupling the parts at the contact surfaces to form the connector. The complementary means for mechanically coupling the parts are configured to mechanically interlock with each other.

Abstract: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

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 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: 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 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: Described here is a microfabricated particle sorting device that uses a transient pulse of fluidic pressure to deflect the target particle. The transient pulse may be generated by a microfabricated (MEMS) actuator, which pushes a volume of fluid into a channel, or sucks a volume of fluid from the channel. The transient pressure pulse may divert a target particle into a sort channel.

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: 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 is directed to a method for the preparation of a cell population from a sample originating from bone marrow or blood, comprising the steps a) dividing the sample into a first fraction containing 50 to 99% of the cells of the sample and a second fraction containing 50 to 1% of the cells of the sample, b) labeling the cells of the first fraction with a first marker against TCR alpha/beta, c) labeling the cells of the second fraction with a second marker against CD45RA, d) removing the labeled cells from the first and second fraction and combining the remaining cells to a cell population.

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: 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. In an embodiment, the device is used as a point-of-care and/or portable device. Further, the present disclosure describes software that, when executed by a processor, causes the device to perform the disclosed functions.

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 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.