A lung breathing chip and cell stretching culture platform and an operating method thereof are disclosed. The lung breathing chip and cell stretching culture platform controls the output of the motor by programming, stretches the micro-fluidic chip by the cam component, changes the size of the cam component and the frequency of the motor rotation to change the stretching frequency and the amount of stretching to simulate the breathing of the lungs in different states, uses liquid electrophoresis technology to arrange the cells in the biocompatible hydrogel and the hydrogel three-dimensionally to imitate the three-dimensional cell tissue, and injects drugs through the dynamic perfusion system to realize the drug testing platform that the cells of the chip bionic lung tissue are stretched.

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.

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), for example.

The methods described herein are for conserving highly expanded cells that have functional properties such as potential for use in neotissue constructs. For example, highly expanded chondrocytes that can be used to construct neocartilage exhibiting functional properties similar to native articular cartilage. The methods and systems feature processes that form functional, human cartilage using cells that have been expanded to at least 1.5×10.sup.5 times or P3 or greater. This enables a large quantity of engineered cartilage implants to be produced from few cells.

A microfluidic device in which microfluidic channels are embedded in a culture medium chamber and have open sides. The microfluidic device is patterned with a fluid moved along a hydrophilic surface due to capillary force, and the fluid may be rapidly and uniformly patterned along an inner corner path and a microfluidic channel. In the microfluidic device, the microfluidic channel is connected to facilitate fluid flow with a culture medium through open sides thereof and openings, and thus may provide a cell culture environment in which high gas saturation is maintained. In addition, several microfluidic devices formed on one common substrate are described. Such microfluidic devices may be manufactured of a hydrophilic engineering plastic by injection molding.

The present invention relates to microfluidic fluidic systems and methods for the in vitro modeling diseases of the lung and small airway. In one embodiment, the invention relates to a system for testing responses of a microfluidic Small Airway-on-Chip infected with one or more infectious agents (e.g. respiratory viruses) as a model of respiratory disease exacerbation (e.g. asthma exacerbation). In one embodiment, this disease model on a microfluidic chip allows for a) the testing of anti-inflammatory and/or anti-viral compounds introduced into the system, as well as b) the monitoring of the participation, recruitment and/or movement of immune cells, including the transmigration of cells. In particular, this system provides, in one embodiment, an in-vitro platform for modeling severe asthma as “Severe Asthma-on-Chip.” In some embodiments, this invention provides a model of viral-induced asthma in humans for use in identifying potentially effective treatments.

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.

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.

Disclosed herein are compositions, devices, methods, processes, and systems for culturing of large quantities of mammalian cells in suspension culture. Also disclosed are unique and surprising cell populations derived from the disclosed methods, processes, and systems. In many embodiments, the cells are cultured in suspension in liquid culture media that is agitated to maintain the cells in suspension, and agitation increases to maintain cells in suspension while growing and dividing to create cell spheres. The disclosed devices, methods, processes, and systems are useful in tailoring characteristics of the resulting cells based on characteristics of donor subject/initial cells. The disclosed cell populations are useful in treating subjects with cell based therapies in need thereof for various diseases and conditions.

The present invention provides compositions, systems, kits, and methods for analyzing the interaction of T-cells and neoantigen presenting cells (and other cells) via discrete entity (e.g., droplet) microfluids. In certain embodiments, a microfluidic device is used to merge a discrete entity containing a T-cell, and a discrete entity containing a neoantigen presenting cell, at a merger region via a trapping element in order to generate a combined discrete entity. In particular embodiments, at least one thousand of such combined discrete entities are formed in about one second. In some embodiments, whether the receptor on the T-cell sufficiently binds the neoantigen to activate the T-Cell is detected (e.g., via detection of cytokine or granzyme B release). In certain embodiments, provided herein are methods for identifying polyfunctional T-cells or NK-cells, as well as methods of screening for such cells that would be cytotoxic if injected into a subject.

A method for separating cells in a biofluid includes pretreating the biofluid by introducing a predetermined amount of a cocktail of antibodies, flowing the pretreated biofluid through a microfluidic separation channel, and applying acoustic energy to the pretreated biofluid within the microfluidic separation channel. A system for microfluidic cell separation, capable of separating target cells from non-target cells in a biofluid includes at least one microfluidic separation channel, a source of biofluid, a source of an additive including the cocktail of antibodies, and at least one acoustic transducer coupled to the microfluidic separation channel. A kit for microfluidic cell separation is also disclosed. A method of facilitating separation of cells is also disclosed.