Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.

The present invention is in the field of microfluidic devices produced with silicon technology wherein at least one 3D microenvironment is present, a method of producing said device using silicon based technology, and a use of said device in various applications, typically a biological cell experiment, such as a cell or organ on a chip experiment, and use o the device as a microreactor.

Devices, systems, and methods can be used for the automated production of dendritic cells (DC) from dendritic cell progenitors, such as monocytes obtained from peripheral blood. The invention makes it possible to obtain sufficient quantities of a subject's own DC for use in preparing and characterizing vaccines, for activating and characterizing the activation state of the subject's immune response, and to aid in preventing and/or treating cancer or infectious disease.

The present disclosure describes a microfluidic chip for culturing and in vitro testing of 3D organotypic cultures. The tests may be performed directly on the organotypic culture in the microfluidic chip. The microfluidic chip includes at least one microfluidic unit which includes two fluidic compartments, such as upper and lower, separated by a permeable supporting structure, one or more access opening for the fluidic compartments, and a set of lids interchangeable with a set of insets. The permeable support structure serves as a support for the organotypic culture. The upper and lower compartments may include inlets and outlets which allow fluids to be perfused into the lower compartment and fluids to be perfused into the upper compartment. The access opening may be closed with a lid or accommodate an inset.

An in vitro microfluidic intestine on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic intestinal cell culture, which is some embodiments is derived from patient's enteroids-derived cells, is described comprising L cells, allowing for interactions between L cells and gastrointestinal epithelial cells, endothelial cells and immune cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal autoimmune tissue, e.g., diabetes, obesity, intestinal insufficiency and other inflammatory gastrointestinal disorders. These multicellular-layered microfluidic intestine on-chips further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal duodenum, small intestinal jejunum, small intestinal ileum, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

A microfluidic device is useful for modelling drug transmission across the vasculature and vascular barriers. The device includes a frame, a fluid-permeable lumen configured to carry a fluid through the frame in a first direction, a first chamber surrounding the lumen, and a second chamber surrounding the first fluid-permeable chamber. At least one surface of the first chamber is configured for deposition of a first population of endothelial cells. An outer surface of the second chamber is configured for deposition a second population of cells. The second chamber is configured to carry a fluid through the frame in a second direction. The fluid-permeable lumen is configured to allow the fluid to permeate through a wall of the lumen into the first chamber, and the first chamber and the second chamber are in fluid communication with each other.

A drug screening platform simulating hyperthermic intraperitoneal chemotherapy including a dielectrophoresis system, a microfluidic chip and a heating system is disclosed. The dielectrophoresis system is used to provide a dielectrophoresis force. The microfluidic chip includes a cell culture array and observation module and a drug mixing module. The cell culture array and observation module are used to arrange the cells into a three-dimensional structure through the dielectrophoresis force to construct a three-dimensional tumor microenvironment. The drug mixing module is coupled to the cell culture array and observation module and used to automatically split and mix the inputted drugs and output the drug combinations into the cell culture array and observation module. The heating system is used for real-time temperature sensing and heating control of the drug combinations on the microfluidic chip to simulate high-temperature drug environment when performing hyperthermic intraperitoneal chemotherapy on the three-dimensional tumor microenvironment.

A method for filling microchambers with a chemistry in a substrate containing a plurality of microchambers comprises forming a channel in the substrate such that the channel is fluidically connected with the plurality of microchambers. The chemistry is delivered into the channel so that the chemistry is delivered to each of the microchambers. The chemistry is then permitted to incubate within each of the microchambers. Excess chemistry is then removed from the microchambers by introducing fluid through the channel to each of the connected microchambers.

In a first aspect, the present invention relates to a method of producing a library of microorganisms, the method comprising the steps of: a. providing a first fluid comprising at least one single cell, b. dispersing said first fluid comprising at least one single cell in a second fluid, thereby obtaining a plurality of single-layer microfluidic droplets, wherein at least one single- layer microfluidic droplet comprises at least one single cell, wherein the second fluid is immiscible with the first fluid, c. optionally, adding to said at least one single-layer microfluidic droplet a third fluid comprising a sensing compound, wherein the third fluid is miscible with said first fluid, and wherein the third fluid is immiscible with said second fluid, d. injecting said at least one single-layer microfluidic droplet optionally comprising the sensing compound into a fourth fluid, wherein said fourth fluid is immiscible with said second fluid, thereby obtaining at least one double-layer microfluidic droplet, e. dispensing said at least one double-layer microfluidic droplet into a culture medium based on the viability of the cell, f. incubating said culture medium, thereby obtaining said library. In a second aspect, the present invention relates to a system comprising: a. a first microfluidic chip for producing a plurality of single-layer microfluidic droplets wherein at least one single-layer microfluidic droplet comprises at least one single cell, b. a first microfluidic device for collecting said plurality of single-layer microfluidic droplets, c. a second device for adding a sensing compound into said at least one single-layer microfluidic droplet comprising at least one single cell, d. a second microfluidic chip for producing a double-layer microfluidic droplet, and e. a dispensing unit. In a third aspect, the present invention relates to the use of the method according to the first aspect of the present invention in a system according to the second aspect of the present invention.

A cell culture apparatus includes: a substrate having a first surface; a pair of structures each having a wall surface intersecting the first surface, the wall surfaces facing each other; and an electrode disposed on the first surface and traversing a space between the wall surfaces, the electrode and each of the wail surfaces forming an angle other than 90 degrees.