Abstract: A microfluidic device for determining a response of cells comprises a microchannel and a seeding channel. The microchannel is at least partially defined by a porous membrane having cells adhered thereto. The microchannel has a first cross-sectional area. The seeding channel delivers a working fluid to the cells within the microchannel. The seeding channel has a second cross-sectional area that is less than the first cross-sectional area such that a flow of the working fluid produces a substantially higher shear force within the seeding channel to inhibit the attachment of cells within the seeding channel. And when multiple seeding channels are used to deliver fluids to multiple microchannels that define an active cellular layer across the membrane, the seeding channels are spatially offset from each other such that fluid communication between the fluids occurs only at the active region via the membrane, not at the seeding channels.

Abstract: An in vitro microfluidic “organ-on-chip” is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and the associated tissue specific epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory tissue, e.g., autoimmune disorders involving epithelia and diseases involving epithelial layers. These multicellular, layered microfluidic “organ-on-chip”, e.g. “epithelia-on-chip” further allow for comparisons between types of epithelia tissues, e.g., lung (Lung-On-Chip), bronchial (Airway-On-Chip), skin (Skin-On-Chip), cervix (Cervix-On-Chip), blood brain barrier (BBB-On-Chip), etc., in additional to neurovascular tissue, (Brain-On-Chip), and between different disease states of tissue, i.e. healthy, pre-disease and diseased areas.

Abstract: According to aspects of the present invention, a cartridge assembly for transporting fluid into or out of one or more fluidic devices includes a first layer and a second layer. The first layer includes a first surface. The first surface includes at least one partial channel disposed thereon. The second layer abuts the first surface, thereby forming a channel from the at least one partial channel. At least one of the first layer and the second layer is a resilient layer formed from a pliable material. At least one of the first layer and the second layer includes a via hole. The via hole is aligned with the channel to pass fluid thereto. The via hole is configured to pass fluid through the first layer or the second layer substantially perpendicularly to the channel. Embossments are also used to define aspects of a fluidic channel.

Abstract: Systems and methods interconnect cell culture devices and/or fluidic devices by transferring discrete volumes of fluid between devices. A liquid-handling system collects a volume of fluid from at least one source device and deposits the fluid into at least one destination device. In some embodiments, a liquid-handling robot actuates the movement and operation of a fluid collection device in an automated manner to transfer the fluid between the at least one source device and the at least one destination device. In some cases, the at least one source device and the at least one destination device are cell culture devices. The at least one source device and the at least one destination device may be microfluidic or non-microfluidic devices. In some cases, the cell culture devices may be microfluidic cell culture devices. In further cases, the microfluidic cell culture devices may include organ-chips.

Abstract: A device simulates a function of a tissue and includes a first structure defining a first chamber, a second structure defining a plurality of second chambers, and a membrane located at an interface region between the first chamber and the plurality of second chambers. The second structure extends along the first chamber. Each of the second chambers has a fluid therein, with each fluid having an agent of a different concentration and/or flowing at a different flow rate. The membrane, which separates the first chamber from the plurality of second chambers, has cells adhered on a first side facing toward the first chamber and on a second side facing toward the plurality of second chambers.

Abstract: Drop-to-drop connection schemes are described for putting a microfluidic device in fluidic communication with a fluid source or another microfluidic device, including but not limited to, putting a microfluidic device in fluidic communication with the perfusion manifold assembly.

Abstract: Apparatus and methods for use with a blood sample are described. The blood sample is stained with Hoechst stain and Acridine Orange stain. A plurality of images of the blood sample are acquired. An object is identified as being a white blood cell candidate. A first stained area, which is stained by the Hoechst stain and which is disposed within the white blood cell candidate, is identified. A second stained area, which is stained by the Acridine Orange stain and which is disposed within the white blood cell candidate, is identified. A white blood cell is detected by determining that structural features of the stained areas satisfy predetermined criteria associated with a white blood cell. Other applications are also described.

Abstract: This invention is in the field of surface modification. In particular, the invention relates to the surface modification of microfluidic devices to alter surface hydrophobicity characteristics.

Abstract: Methods of removing bubbles from a microfluidic device are described where the flow is not stopped. Methods are described that combine pressure and flow to remove bubbles from a microfluidic device. Bubbles can be removed even where the device is made of a polymer that is largely gas impermeable.

Abstract: Disclosed herein, inter alia, is method, kit and systems for detecting a pathogen infection in a bodily sample, the method comprising (i) staining said bodily sample with two or more dyes, comprising at least one dye predominantly staining DNA to thereby provide differential staining between DNA and at least one other cellular component being different from DNA; (ii) identifying at least a first stained area comprising the DNA, if exists in the sample, and at least one other stained area comprising the other cellular component; (iii) extracting structural features for the first stained area and the at least one other stained area, said structural features comprise at least one of (i) size of at least one of the first stained area and one other stained area and (ii) location of said first stained area and said at least one other stained area one with respect to the other; and (iv) determining the presence of a suspected pathogen in the bodily sample if a first stained area was identified and said structural fe

Abstract: The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.

Abstract: Systems and methods for measuring dynamic hydraulic conductivity and permeability associated with a cell layer are disclosed. Some systems include a microfluidic device, one or more working-fluid reservoirs, and one or more fluid-resistance element. The microfluidic device includes a first microchannel, a second microchannel, and a barrier therebetween. The barrier includes a cell layer adhered thereto. The working fluids are delivered to the microfluidic device. The fluid-resistance elements are coupled to one or more of the fluid paths and provide fluidic resistance to cause a pressure drop across the fluid-resistance elements. Mass transfer occurs between the first microchannel and the second microchannel, which is indicative of the hydraulic conductivity and/or dynamic permeability associated with the cells.

Abstract: Systems and methods interconnect cell culture devices and/or fluidic devices by transferring discrete volumes of fluid between devices. A liquid-handling system collects a volume of fluid from at least one source device and deposits the fluid into at least one destination device. In some embodiments, a liquid-handling robot actuates the movement and operation of a fluid collection device in an automated manner to transfer the fluid between the at least one source device and the at least one destination device. In some cases, the at least one source device and the at least one destination device are cell culture devices. The at least one source device and the at least one destination device may be microfluidic or non-microfluidic devices. In some cases, the cell culture devices may be microfluidic cell culture devices. In further cases, the microfluidic cell culture devices may include organ-chips.

Abstract: Systems and methods for improved flow properties in fluidic and microfluidic systems are disclosed. The system includes a microfluidic device having a first microchannel, a fluid reservoir having a working fluid and a pressurized gas, a pump in communication with the fluid reservoir to maintain a desired pressure of the pressurized gas, and a fluid-resistance element located within a fluid path between the fluid reservoir and the first microchannel. The fluid-resistance element includes a first fluidic resistance that is substantially larger than a second fluidic resistance associated with the first microchannel.

Abstract: According to aspects of the present invention, a cartridge assembly for transporting fluid into or out of one or more fluidic devices includes a first layer and a second layer. The first layer includes a first surface. The first surface includes at least one partial channel disposed thereon. The second layer abuts the first surface, thereby forming a channel from the at least one partial channel. At least one of the first layer and the second layer is a resilient layer formed from a pliable material. At least one of the first layer and the second layer includes a via hole. The via hole is aligned with the channel to pass fluid thereto. The via hole is configured to pass fluid through the first layer or the second layer substantially perpendicularly to the channel. Embossments are also used to define aspects of a fluidic channel.

Abstract: The inventions provided herein relate to detection reagents, compositions, methods, and kits comprising the detection reagents for use in detection, identification, and/or quantification of analytes in a sample. Such detection reagents and methods described herein allow multiplexing of many more labeled species in the same procedure than conventional methods, in which multiplexing is limited by the number of available and practically usable colors.

Abstract: The inventions provided herein relate to detection reagents, compositions, methods, and kits comprising the detection reagents for use in detection, identification, and/or quantification of analytes in a sample. Such detection reagents and methods described herein allow multiplexing of many more labeled species in the same procedure than conventional methods, in which multiplexing is limited by the number of available and practically usable colors.

Abstract: Methods of removing bubbles from a microfluidic device are described where the flow is not stopped. Methods are described that combine pressure and flow to remove bubbles from a microfluidic device. Bubbles can be removed even where the device is made of a polymer that is largely gas impermeable.

Abstract: A perfusion manifold assembly is described that allows for perfusion of a microfluidic device, such as an organ on a chip microfluidic device comprising cells that mimic cells in an organ in the body, that is detachably linked with said assembly so that fluid enters ports of the microfluidic device from a fluid reservoir, optionally without tubing, at a controllable flow rate. Drop-to-drop connection schemes are described for putting a microfluidic device in fluidic communication with a fluid source or another microfluidic device, including but not limited to, putting a microfluidic device in fluidic communication with the perfusion manifold assembly.

Abstract: According to aspects of the present invention, a cartridge assembly for transporting fluid into or out of one or more fluidic devices includes a first layer and a second layer. The first layer includes a first surface. The first surface includes at least one partial channel disposed thereon. The second layer abuts the first surface, thereby forming a channel from the at least one partial channel. At least one of the first layer and the second layer is a resilient layer formed from a pliable material. At least one of the first layer and the second layer includes a via hole. The via hole is aligned with the channel to pass fluid thereto. The via hole is configured to pass fluid through the first layer or the second layer substantially perpendicularly to the channel. Embossments are also used to define aspects of a fluidic channel.