Abstract: A method for micro-molding a polymeric membrane and including pouring a predetermined volume of curable polymer unto a micro-fabricated mold having a post array with pillars, and overlaying the polymer with a support substrate. A spacer, such as a rubber spacer, is placed in contact with the support substrate and a force is applied to an exposed side of the spacer to compress the support substrate and the polymer together. While applying the force, the polymer is cured on the mold for a predetermined time period and at a predetermined temperature to form a polymeric membrane having a pore array with a plurality of pores corresponding to the plurality of pillars of the post array. The polymeric membrane is removed from the support substrate.

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 analyzing nucleic acids of a cell are provided.

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: Methods of analyzing nucleic acids of a cell are provided.

Abstract: Methods of making a three-dimensional matrix of nucleic acids within a cell is provided.

Abstract: A culture module is contemplated that allows the perfusion and optionally mechanical actuation of one or more microfluidic devices, such as organ-on-a-chip microfluidic devices comprising cells that mimic at least one function of an organ in the body. A method for pressure control is contemplated to allow the control of flow rate (while perfusing cells) despite limitations of common pressure regulators. The method for pressure control 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.

Abstract: Methods of making a three-dimensional matrix of nucleic acids within a cell is provided.

Abstract: Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Abstract: Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Abstract: A device for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.

Abstract: Apparatus and methods are described including preparing a blood sample for analysis by depositing the blood sample within a sample chamber (52), and placing the sample chamber, with the blood sample deposited therein, within a microscopy unit (24). One or more microscopic images of the sample chamber (52) with the blood sample deposited therein are acquired, using a microscope of the microscopy unit. Based upon the one or more images, an amount of one or more cell types within the sample chamber that had already settled within the sample chamber, prior to acquisition of the one or more microscopic images is determined. A characteristic of the sample is determined, at least partially in response thereto. Other applications are also described.

Abstract: Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Abstract: Apparatus and methods are described including placing at least a portion of a blood sample within a sample chamber (52), and acquiring microscopic images of the portion of the blood sample. Candidates of a given entity within the blood sample are identified, within the microscopic image. At least some of the candidates as being the given entity are validated, by performing further analysis of the candidates. A count of the candidates of the given entity is compared to a count of the validated candidates of the given entity, and at least the portion of the sample is invalidated from being used for performing at least some measurements upon the sample, at least partially based upon a relationship between the count of candidates and the count of validated candidates. Other applications are also described.

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 for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.

Abstract: Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Abstract: Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

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: 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.