Cornell Research Foundation Inc.

Cornell University

Michael L Shuler

Aaron Sin

Scott Meyers

Gregory T Baxter

Robert Andrew Harrison

David B Wilson

John G Babish

Brian E Johnson

Christopher Prince

Lisa M Sweeney

Kennie U Dee

Jong Hwan Sung

George S Efthymiou

Toohyon Cho

Ying Wang

A device is disclosed that comprises a base having first and second reservoirs, each having an inlet and an outlet, and a channel layer comprising an inlet channel in fluid communication with the inlets of the reservoirs, one or more outlet channels in fluid communication with the outlets of the reservoirs, and a channel network comprising at least one channel extending therebetween. In a forward tilted position, a first fluid circuit is formed from the outlet of the first reservoir, through the one or more outlet channels, through the channel network, through the inlet channel, to the both the inlet and outlet of the second reservoir. In a reverse tilted position a second fluid circuit is formed from the outlet of the second reservoir, through the one or more outlet channels, through the channel network, through the inlet channel, to both the inlet and outlet of the first reservoir. Methods of using the device are also disclosed.

Recirculating unidirectional perfusion flow devices and methods of use thereof

A cell culture device comprising a microscale chamber dimensioned to maintain a cell under conditions that give rise to a value for at least one pharmacokinetic parameter in vitro that is comparable to a value for the same at least one pharmacokinetic parameter obtained with respect to the same type of cell in vivo, wherein the microscale chamber is configured for flow of culture medium, and wherein the at least one pharmacokinetic parameter is selected from tissue size ratio, tissue to blood volume ratio, drug residence time, flow rate, circulatory transit time, liquid residence time, and liquid to cell ratio.

Devices and methods for pharmacokinetic-based cell culture system

A cell culture method using an in vitro microscale cell culture device having a first microscale chamber containing cells attached to an inner surface of the chamber and cell culture medium in contact with the cells. The cells are maintained in culture in the in vitro microscale cell culture device while flowing culture medium through the first chamber at a controlled rate to provide a liquid residence time value for the cells in the first chamber of the in vitro microscale cell culture device that is comparable to a liquid residence time value obtained with respect to comparable cells in vivo, such that metabolism by the cells in culture in the in vitro microscale cell culture device is comparable to metabolism by comparable cells in vivo.

A microfluidic device for culturing cells, termed a microscale cell culture analog (&#x3bc;CCA), is provided. The microfluidic device allows multiple cell or tissue types to be cultured in a physiologically relevant environment, facilitates high-throughput operation and can be used for drug discovery. The microfluidic device uses gravity-induced fluidic flow, eliminating the need for a pump and preventing formation of air bubbles. Reciprocating motion between a pair of connected reservoirs is used to effect the gravity-induced flow in microfluidic channels. Bacterial contamination is reduced and high throughput enabled by eliminating a pump. The microfluidic device integrates a pharmacokinetic-pharmacodynamic (PK-PD) model to enable PK-PD analyses on-chip. This combined in vitro/in silico system enables prediction of drug toxicity in a more realistic manner than conventional in vitro systems.

Microfluidic device for pharmacokinetic-pharmacodynamic study of drugs and uses thereof

Devices, in vitro cell cultures, systems, and methods are provided for microscale cell culture analogous (CCA) device.

A micropump has two chambers separated by an actuator for causing fluid to flow in the chambers. Each chamber is equipped with a ball that acts as a valve for allowing flow in a desired direction. The balls are heavier than the fluid being pumped, and reside at an interface between the chambers and passages feeding fluid into the chambers and provide a tight seal between the chambers and passages feeding the chambers when fluid pressure forces the fluid back toward the feeding passages.

Dual chamber micropump having checkvalves

A single celled organism, vector, and method are provided for continuous production of excreted proteins in the absence of substantial host cell replication and without the necessity for the addition of antibiotics to control cell replication. The vector has (1) an inducible promoter capable of activating a gene for a protein to be produced under conditions that substantially inhibit host cell replication, and (2) a hybrid gene containing a signal sequence fused to a gene for the protein to be produced. Large quantities of the transformed single celled organisms containing the vector can be grown in the absence of inducing conditions, thereby reducing the problem of plasmid loss. Further, the protein is produced under conditions that substantially inhibit host cell replication, thereby allowing immobilization of the single celled organism by entrapment or attachment within or onto a solid support surface. The single celled organism can be immobilized after, before or simultaneously with induction. The single celled organism advantageously may be an encapsulated gram-negative bacterium which has no outer membrane or an outer membrane that is permeable to the proteins to be produced so that the protein products are excreted into the media thereby avoiding difficulty in recovering the desired protein products due to the formation of inclusion bodies or the presence of contaminants produced by cell lyses.

System useful for the production of proteins from recombinant DNA in

Non-carboxylated sulfated polyanions have been successfully used to rapidly obtain and maintain stable single-cell suspension of BTI-TN5B1-4 cells, a cell line which has a high intrinsic capacity for the expression of recombinant protein, but which clumps severely in suspension reducing its effectiveness as a host for foreign protein production with the baculovirus expression vector system. The three most effective polyanions for inducing a single-cell suspension were dextran sulfate, polyvinyl sulfate, and pentosan sulfate. The cost of dextran sulfate treatment is low compared to heparin treatment, which required a 20-fold higher lever to induce single-cell suspension. More importantly, dextran sulfate does not block vital infection at MOI.gtoreq.1 whereas heparin is known to seriously inhibit infection. To overcome this effect, the cells can be subcultured to a fresh culture medium without the sulfated polyanion, or the sulfated polyanion is neutralized with a polycation, then the cells are inoculated with the baculovirus. Once the cells are infected with the baculovirus, the sulfate polyanion is added back to the fresh culture medium. Inducing single-cell suspension with dextran sulfate, a highly sulfated polyanion, resulted in an increased volumetric yield of recombinant protein. Examples chosen for experimentation included, human secreted alkaline phosphatase, and b-galactosidase. Optimum volumetric yield of 6 to 11 fold higher than attached cells for the production of alkaline phosphatase in BTI-TN5B1-4 dextran sulfate cells under elevated oxygen. More importantly, cells can be infected at high density without complications from aggregation, which has important implications for scale-up.

Methods and culture media for inducing single cell suspension in insect

The present invention relates to an in vitro system for physiological and metabolic evaluation of substances for use in living beings. The system includes one or more cell culture chambers, each containing cells in a culture medium and a gas-liquid exchange device for contacting the culture medium with oxygen-containing gas so that the culture medium absorbs that gas and desorbs carbon dioxide-containing gas. The conduit system conducts culture medium between the gas-liquid exchange device and the cell culture chambers. A circulation mechanism is used to circulate culture medium through the conduit system, the cell culture chambers, and the gas-liquid exchange device. In use, the substance to be evaluated is added to the culture medium of the system and circulated through the system. The cells in each of the cell culture chambers are then evaluated for effects resulting from the presence of the substance.

Automated, multicompartmental cell culture system

Root organ cultures of the monocot genus Allium were successfully grown in culture medium. In a preferred bioreactor system, the roots themselves can be grown and harvested as a source of various Allium flavors and/or the growing roots can be reacted with various nutrients to produce Allium flavor compounds independent of the root harvesting. The root cultures of the present invention produce quantities of onion and onion-like flavor compounds comparable to those found in onion bulbs. Flavor precursors ar

Flavor compounds from allium root cultures

An immobilized liquid membrane is employed to allow use of a product-extracting solvent which is normally toxic toward a cell layer which produces the product in a membrane-moderated biological reaction.

Use of inhibitory solvents in multi-membrane bioreactor

An improved multilayer continuous biological membrane reactor and a process to eliminate diffusional limitations in membrane reactors in achieved by causing a convective flux of nutrient to move into and out of an immobilized biocatalyst cell layer. In a pressure cycled mode, by increasing and decreasing the pressure in the respective layers, the differential pressure between the gaseous layer and the nutrient layer is alternately changed from positive to negative. The intermittent change in pressure differential accelerates the transfer of nutrient from the nutrient layers to the biocatalyst cell layer, the transfer of product from the cell layer to the nutrient layer and the transfer of byproduct gas from the cell layer to the gaseous layer. Such intermittent cycling substantially eliminates mass transfer gradients in diffusion inhibited systems and greatly increases product yield and throughput in both inhibited and noninhibited systems.

Growing community of inventors

Ithaca, NY, United States of America

Michael L Shuler