Abstract: Systems for operating a microfluidic device are described. The systems comprise a first surface configured to interface and operatively couple with a microfluidic device and a lid configured to retain the microfluidic device on the first surface. The lid comprises a first portion having a first fluid port configured to operatively couple with and flow fluidic medium into and/or out of a first fluid inlet/outlet of the microfluidic device and a second portion having a second fluid port configured to operatively couple with and flow fluidic medium into and/or out of a second fluid inlet/outlet of the microfluidic device. The second portion of the lid is separable from the first portion and movable between a closed position in which the second fluid port of the second portion of the cover is operatively coupled with the second fluid inlet/outlet of the microfluidic device and an open position in which a portion of the microfluidic device that contains the second fluid inlet/outlet is exposed.

Abstract: Methods, systems and kits are described herein for detecting the results of an assay. In particular, the methods, systems and devices of the present disclosure rely on a difference between the diffusion rates of a reporter molecule and an analyte of interest in order to quantify an amount of analyte in a microfluidic device. The analyte may be a secreted product of a biological micro-object.

Abstract: Methods, systems and kits are described herein for detecting the results of an assay. In particular, the methods, systems and devices of the present disclosure rely on a difference between the diffusion rates of a reporter molecule and an analyte of interest in order to quantify an amount of analyte in a microfluidic device. The analyte may be a secreted product of a biological micro-object.

Abstract: Methods, systems and kits are described herein for detecting the results of an assay. In particular, the methods, systems and devices of the present disclosure rely on a difference between the diffusion rates of a reporter molecule and an analyte of interest in order to quantify an amount of analyte in a microfluidic device. The analyte may be a secreted product of a biological micro-object.

Abstract: Cartridge for manufacturing a population of cells suitable for formulation as a cellular therapeutic are disclosed herein, along with systems for operating the cartridges and performing methods to generate the population of cells suitable for formulation as a cellular therapeutic. The population of cells suitable for formulation as a cellular therapeutic can be T-cells, including CAR T-cells. The systems and methods can be largely automated.

Abstract: A bioreactor for expanding a population of biological cells comprises a housing having an interior cavity and a first membrane affixed within the housing. The first membrane divides the interior cavity into a chamber and a first flow channel. The bioreactor further comprises a cell culture surface contained within the chamber on which the population of biological cells may be disposed, a first inlet port fluidly coupled to the first flow channel, such that first media can be flowed into the first flow channel, and a first outlet port fluidly coupled to the first flow channel, such that the first media can be flowed out of the first flow channel. The first membrane is substantially permeable to one or more of nutrient, reagent, and gas contained within the first media and waste produced by the population of biological cells, while being substantially impermeable to the population of biological cells.

Abstract: Systems for operating a microfluidic device are described. The systems comprise a first surface configured to interface and operatively couple with a microfluidic device and a lid configured to retain the microfluidic device on the first surface. The lid comprises a first portion having a first fluid port configured to operatively couple with and flow fluidic medium into and/or out of a first fluid inlet/outlet of the microfluidic device and a second portion having a second fluid port configured to operatively couple with and flow fluidic medium into and/or out of a second fluid inlet/outlet of the microfluidic device. The second portion of the lid is separable from the first portion and movable between a closed position in which the second fluid port of the second portion of the cover is operatively coupled with the second fluid inlet/outlet of the microfluidic device and an open position in which a portion of the microfluidic device that contains the second fluid inlet/outlet is exposed.

Abstract: Methods, systems and kits are described herein for detecting the results of an assay. In particular, the methods, systems and devices of the present disclosure rely on a difference between the diffusion rates of a reporter molecule and an analyte of interest in order to quantify an amount of analyte in a microfluidic device. The analyte may be a secreted product of a biological micro-object.

Abstract: Methods for laser-assisted repositioning of a micro-object and for culturing an attachment-dependent biological cell within a microfluidic device are described herein. Laser illumination is used to controllably create a bubble which repositions the micro-object. Further, methods of culturing an attachment-dependent biological cell are described, where the methods may include laser-assisted repositioning.

Abstract: Method of evaluating a virus-producing cell on a microfluidic device is described therein. The method comprises culturing the virus-producing cell thereby producing a viral particle in a chamber of the microfluidic device; and evaluating a productivity of the virus-producing cell in producing the viral particle. Additionally, method for preserving a subset of biological micro-objects within a microfluidic device is also described herein so that the subset of biological micro-objects can be protected from being affected by the assays performed on the microfluidic device.

Abstract: Systems, methods, and kits therefor, enabling rapid protein evolution are described herein. A system useful in the methods described herein include a DNA synthesis component; a microfluidic system including a microfluidic device having a microfluidic channel and sequestration pens; and a computing component, which is configured to analyze assay results and, based upon the analysis, design improved DNA sequences for iterative protein evolution. The microfluidic system is configured to permit correlation of DNA sequence on a bead to its location within the microfluidic device, permit cell free protein expression of a DNA sequence captured to a bead, and to permit assay of the protein so produced.

Abstract: Apparatuses, compositions and processes for DNA barcode deconvolution are described herein. A DNA barcode may be used to provide a bead specific identifier, which may be detected in situ using hybridization strategies. The DNA barcode provides identification by sequencing analysis. The dual mode of detection may be used in a wide variety of applications to link positional information with assay information including but not limited to genetic analysis. Methods are described for generation of barcoded single cell sequencing libraries. Isolation of nucleic acids from a single cell within a microfluidic environment can provide the foundation for cell specific sequencing library preparation.

Abstract: Microfluidic devices having a circuit substrate with a control unit, a switching mechanism associated with a dielectrophoresis (DEP) electrode, and a memory unit are described. Switching instructions may be received, stored, and retrieved by the control unit and used to control the DEP electrode via the switching mechanism. Systems comprising the described microfluidic devices and methods of controlling the described microfluidic devices are included herein.

Abstract: Incubators including an enclosure with an internal chamber configured to support a cell culture plate comprising a plurality of wells are disclosed. The enclosure includes a plurality of openings configured to allow access to the wells. The incubators include a sealing element configured to seal the plurality of openings in the enclosure. The sealing element comprises a plurality of openings corresponding to at least a subset of the plurality of openings in the enclosure. Access to the internal chamber can be provided by aligning the plurality of openings in the sealing element with the plurality of openings in the enclosure. Methods for using the incubators are also provided.

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 provide improved or altered performance with biomaterials.

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: Methods are described herein for screening an antibody producing cell within a microfluidic environment. The antibody producing cell may be a B cell lymphocyte, which may be a memory B cell or a plasma cell. An antigen of interest may be brought into proximity with the antibody producing cell and binding of the antigen by an antibody produced by the antibody producing cell may be monitored. Methods of obtaining a sequencing library from an antibody producing cell are also described.

Abstract: This application describes systems and methods for assaying micro-objects in a microfluidic device. These methods include contacting a reagent with a micro-object by introducing a reagent in a first fluidic medium to a flow region of a microfluidic device, wherein the microfluidic device comprises the flow region and a chamber comprising a proximal opening fluidically connecting the chamber to the flow region, diffusing the reagent from the flow region into the chamber; introducing a micro-object into the flow region of the microfluidic device, and diffusing the reagent from the chamber to the flow region to contact the reagent with the micro-object within the flow region. Other embodiments are described.

Abstract: In biosciences and related fields, it can be useful to study cells in isolation so that cells having unique and desirable properties can be identified within a heterogenous mixture of cells. Processes and methods disclosed herein provide for encapsulating cells within a microfluidic device and assaying the encapsulated cells. Encapsulation can, among other benefits, facilitate analyses of cells that generate secretions of interest which would otherwise rapidly diffuse away or mix with the secretions of other cells.

Abstract: Some configurations of a microfluidic apparatus can comprise a fluidic circuit of interconnected fluidic structures into which a plurality of different media can be introduced or extracted. A variety of operations can be performed with the different media including isolating with a second medium one or more of the fluidic structures that is filled partially or fully with a first medium. Discrete volumes of a medium can be moved through the isolating second medium to deliver materials or micro-objects to or remove micro-objects or materials from a fluidic structure that is otherwise isolated by the second medium. Some configurations of a microfluidic apparatus can isolate microfluidic structures in a microfluidic apparatus using flow rates or blocking structures, and some configurations can manage bubbles in fluidic structures.