Abstract: A method of preparing an antibody therapeutic is provided comprising: (a) providing a dissociated cell sample from at least one solid tumor sample obtained from a patient; (b) loading the dissociated cell sample into a microfluidic device having a flow region and at least one isolation region fluidically connected to the flow region; (c) moving at least one B cell from the dissociated cell sample into at least one isolation region in the microfluidic device, thereby obtaining at least one isolated B cell; and (d) using the microfluidic device to identify at least one B cell that produces antibodies capable of binding to cancer cells. The cancer cells can be the patient's own cancer cells. Also provided are methods of treating patients, methods of labeling or detecting cancer, engineered T or NK cells comprising antibodies or fragments thereof, and engineered antibody constructs.

Abstract: Individual biological micro-objects can be deterministically selected and moved into holding pens in a micro-fluidic device. A flow of a first liquid medium can be provided to the pens. Physical pens can be structured to impede a direct flow of the first medium into a second medium in the pens while allowing diffusive mixing of the first medium and the second medium. Virtual pens can allow a common flow of medium to multiple ones of the pens.

Abstract: Methods of sorting T lymphocytes in a microfluidic device are provided. The methods can include flowing a fluid sample comprising T lymphocytes through a region of a microfluidic device that contains an array of posts. The array of posts can be configured to have a critical size (Dc) that separates activated T lymphocytes from naïve T lymphocytes. Also provided are microfluidic devices having an array of posts configured to separate activated T lymphocytes from naïve T lymphocytes, compositions enriched for T lymphocytes, particularly activated T lymphocytes that are known to be reactive to an antigen of interest, and methods of treating subjects suffering from a pathogenic disorder or cancer by administering such compositions.

Abstract: Biological activity in holding pens in a micro-fluidic device can be assayed by placing in the holding pens capture objects that bind a particular material of interest produced by the biological activity. The biological material of interest that binds to each capture object can then be assessed, either in the micro-fluidic device or after exporting the capture object from the micro-fluidic device. The assessment can be utilized to characterize the biological activity in each holding pen. The biological activity can be production of the biological material of interest. Thus, the biological activity can correspond to or arise from one or more biological cells. Biological cells within a holding pen can be clonal cell colonies. The biological activity of each clonal cell colony can be assayed while maintaining the clonal status of each colony.

Abstract: Individual biological cells can be selected in a micro-fluidic device and moved into isolation pens in the device. The cells can then be lysed in the pens, releasing nucleic acid material, which can be captured by one or more capture objects in the pens. The capture objects with the captured nucleic acid material can then be removed from the pens. The capture objects can include unique identifiers, allowing each capture object to be correlated to the individual cell from which the nucleic acid material captured by the object originated.

Abstract: Systems, methods and kits are described for culturing one or more biological cells in a microfluidic device, including provision of nutrients and gaseous components configured to enhance cell growth, viability, portability, or any combination thereof. In some embodiments, culturing a single cell may produce a clonal population in the microfluidic device.

Abstract: Systems, methods and kits are described for culturing one or more biological cells in a microfluidic device, including provision of nutrients and gaseous components configured to enhance cell growth, viability, portability, or any combination thereof. In some embodiments, culturing a single cell may produce a clonal population in the microfluidic device.

Abstract: Individual biological cells can be selected in a micro-fluidic device and moved into isolation pens in the device. The cells can then be lysed in the pens, releasing nucleic acid material, which can be captured by one or more capture objects in the pens. The capture objects with the captured nucleic acid material can then be removed from the pens. The capture objects can include unique identifiers, allowing each capture object to be correlated to the individual cell from which the nucleic acid material captured by the object originated.

Abstract: Biological activity in holding pens in a micro-fluidic device can be assayed by placing in the holding pens capture objects that bind a particular material of interest produced by the biological activity. The biological material of interest that binds to each capture object can then be assessed, either in the micro-fluidic device or after exporting the capture object from the micro-fluidic device. The assessment can be utilized to characterize the biological activity in each holding pen. The biological activity can be production of the biological material of interest. Thus, the biological activity can correspond to or arise from one or more biological cells. Biological cells within a holding pen can be clonal cell colonies. The biological activity of each clonal cell colony can be assayed while maintaining the clonal status of each colony.

Abstract: The present disclosure provides methods of preparing tumor infiltrating cells engineered to express a pro-inflammatory polypeptide. The pro-inflammatory polypeptide is expressed from the tumor infiltrating cell to counter a generally immunosuppressive state in and around tumors resulting from an imbalance between the number and activation state of immune effector cells versus those of suppressor cells. Delivering the proinflammatory polypeptide via expression from the TICs, as distinct from systemic administration, reduces side effects from increased inflammation at sides remote from a tumor to be treated.

Abstract: A method of processing and storing biological cells includes introducing a flowable medium into a microfluidic device, the flowable medium including biological cells; sequestering one or more biological cells from the flowable medium in one or more isolation regions of the microfluidic device; and freezing the microfluidic device including the one or more biological cells sequestered therein.

Abstract: Disclosed herein is a method for assaying binding affinity between a first molecule and a second molecule in a micro-fluidic device.

Abstract: A method of processing and storing biological cells includes introducing a flowable medium into a microfluidic device, the flowable medium including biological cells; sequestering one or more biological cells from the flowable medium in one or more isolation regions of the microfluidic device; and freezing the microfluidic device including the one or more biological cells sequestered therein.

Abstract: This disclosure relates to the production and use of an isolated, purified and/or recombinant T cell receptor (TCR) that specifically binds to a mutant IDH1 protein, or a fragment thereof, wherein the mutant IDH1 protein or fragment thereof comprises an R132H mutation.

Abstract: Functional assays using reporter cell assays are described which probe the activity of at least one cell of interest. The ability to probe at least one cell is provided by using the microfluidic methods, devices and kits described herein. Assays combining both reporter cell signaling as well as binding assay signaling for at least one cell is also described herein.

Abstract: Systems, methods and kits are described for culturing one or more biological cells in a microfluidic device, including provision of nutrients and gaseous components configured to enhance cell growth, viability, portability, or any combination thereof. In some embodiments, culturing a single cell may produce a clonal population in the microfluidic device.

Abstract: A method of preparing an antibody therapeutic is provided comprising: (a) providing a dissociated cell sample from at least one solid tumor sample obtained from a patient; (b) loading the dissociated cell sample into a microfluidic device having a flow region and at least one isolation region fluidically connected to the flow region; (c) moving at least one B cell from the dissociated cell sample into at least one isolation region in the microfluidic device, thereby obtaining at least one isolated B cell; and (d) using the microfluidic device to identify at least one B cell that produces antibodies capable of binding to cancer cells. The cancer cells can be the patient's own cancer cells. Also provided are methods of treating patients, methods of labeling or detecting cancer, engineered T or NK cells comprising antibodies or fragments thereof, and engineered antibody constructs.

Abstract: Disclosed herein are methods for performing assays, including general functional assays, on a biological cell. The methods can include contacting a biological cell with a test agent for a period of time; lysing the biological cell while the biological cell is disposed within a sequestration pen located within an enclosure of a microfluidic device; and allowing RNA molecules released from the lysed biological cell to be captured by capture oligonucleotides linked to a capture object disposed within the sequestration pen of the microfluidic device. Each capture oligonucleotide can include a priming sequence that binds a primer, and a capture sequence. Each cDNA transcribed from a captured RNA can have an oligonucleotide sequence complementary to the captured RNA molecule, with the complementary oligonucleotide sequence being covalently linked to one of the capture oligonucleotides of the capture object.

Abstract: In biosciences and related fields, it can be useful to modify surfaces of apparatuses, devices, and materials that contact biomaterials such as biomolecules and biological micro-objects. Described herein are surface modifying and surface functionalizing reagents, preparation thereof, and methods for modifying surfaces to activate T Lymphocytes.

Abstract: Individual biological micro-objects can be deterministically selected and moved into holding pens in a micro-fluidic device. A flow of a first liquid medium can be provided to the pens. Physical pens can be structured to impede a direct flow of the first medium into a second medium in the pens while allowing diffusive mixing of the first medium and the second medium. Virtual pens can allow a common flow of medium to multiple ones of the pens.