University of Central Florida Research Foundation, Inc.

Hesperos, LLC

Science Applications International Corporation

Harvard College

Mass. Institute of Technology

James J Hickman

Mainak Das

Christopher Long

John W Rumsey

Xiufang Guo

Maria Stancescu

Peter Molnar

Kazi Tasneem

Christopher McAleer

George M Whitesides

Chad A Mirkin

Mark S Wrighton

Douglas A Kirkpatrick

Jerry Y Jenkins

Joseph Pancrazio

David Ofer

Otto J Hunt

George L Bergeron, Iii

Michael Lengyel

Lee Kumanchik

Alexander Smith

Alisha Colon

Trevor Sasserath

Mercedes Gonzalez

Daniel Elbrecht

Sandra Rothemund

Megan Aubin

Kristen Pirozzi

Frank Alexander

Stanley E Busby

Anupama Natarajan

Frank Sommerhage

Paul E Laibinis

Navaneetha Santhanam

Jonathan Ernest Hood

James R Valentine

Darin Edwards

Christopher Mcaleer

Jonathan Hood

Jerry Jenkins

The present invention comprises methods, systems and compositions comprising cell culture analog systems, comprising components which optionally comprise biologically functional cells, and the components and systems function similarly to in vivo conditions.

Methods, systems and compositions for functional in vitro cellular models of mammalian systems

Disclosed herein are microfluidic systems with recirculation of fluid and computer-implemented methods of calculating conditions within the microfluidic systems. The microfluidic systems include a computing device and a microfluidic device having first and second reservoirs, at least one chamber, and a fluid path connecting the first reservoir, the chamber, and the second reservoir. The methods for calculating conditions include receiving a first reservoir fluid volume, a second reservoir fluid volume, a first concentration, and a second concentration. The methods further include receiving a time-dependent imposed pressure difference between the first reservoir and the second reservoir, then determining a hydraulic pressure difference and an effective pressure difference. The effective pressure difference is used to account for reactions occurring within the microfluidic device and to determine the value of the condition within the microfluidic device. Methods of performing an experiment using a microfluidic device with recirculation are also disclosed herein.

Model for fluid and mass transport in a recirculating microfluidic system

The method of culturing cells disclosed herein includes printing cells onto a substrate that includes cell adhesive regions and cell repulsive regions. The cells are suspended in a printing medium to create a cell suspension, and a volume of the cell suspension is loaded into a printer. A cell adhesive region of the substrate is aligned beneath the printing channel of the printer, and droplets of the cell suspension are dispensed from the printing channel directly onto the cell adhesive region. Contact of the dispensed droplets with cell repulsive regions of the substrate is limited, either by targeting of the droplets to the cell adhesive regions, by repulsions generated by the cell repulsive areas, or both. The cells adhere to the cell adhesive regions to create a cell pattern, and are maintained thereafter in a physiologically suitable environment.

Method and system for printing cells to a substrate comprising cell adhesive regions

In an aspect, disclosed herein are physiological devices and systems, and components thereof, used to evaluate cardiac parameters and arrhythmogenic mechanisms. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Devices, systems, and methods for evaluating cardiac parameters

A pumpless microfluidic system is disclosed that can be used to mimic the interaction of organ systems with the immune system. Also disclosed is a method for mimicking an immune system, comprising culturing a plurality of organ cells and at least one population of immune cells in the disclosed pumpless microfluidic system under physiological conditions. The method can further comprise activating an immune reaction in the pumpless microfluidic system, continuing the culture for a defined period, collecting a sample of culture medium from the system, and assaying the sample for one or more indicators of an immune response.

Pumpless microfluidic organ-on-a-chip system including a functional immune system

Disclosed herein are cell culture analog devices, systems and methods for applying stimuli to components containing different cell types and recording the cell responses before, during, and after a stimulus (for example, a drug, metabolite, toxin, or electrical stimulus) is introduced. Responses can be stored to a database and compared to previous results. By analyzing how each cell type responds to various stimulation parameters, for example, by using multivariate analyses, cell signaling pathway information can be determined or new pathways can be discovered. In some implementations, an individual component interfaces with a specific cell type. This facilitates readout of the cell response to the stimulation. Various components can also interface with each other, such that the behavior of one cell type can affect a cell type in another component. Once assembled, the system is plugged into readout electronics and a programmable electrical stimulator.

Multi-component in vitro system to deduce cell signaling pathways by electronic stimulation patterns

Disclosed herein are devices comprising one or more cantilevers comprising one or more neuromuscular junctions formed by a co-culture of myotubes and motoneurons. Disclosed herein are methods of using the disclosed devices comprising one or more cantilevers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Devices and methods comprising neuromuscular junctions

The invention discloses a bio-MEMS transducer comprising a cultured myotube and a piezoelectric microcantilever having the myotube attached thereto along a lengthwise extent of said microcantilever. The transducer may include an input/output processor operably connected with said piezoelectric microcantilever to process electrical signals received therefrom and to send electrical signals thereto. The invention may operate as a biosensor wherein the attached myotube contracts on contact with a sensed agent, the myotube contraction deflecting the microcantilever to generate a piezoelectric signal therefrom. The invention may also be used as a biosensor for quantitating physiologic response to an agent by measuring deflection of the cantilever caused by myotube contraction elicited by contact with the agent; and correlating the measurement to effectiveness of the sensed agent in causing a myotube physiologic response. The bio-transducer is a bioactuator when an applied electrical signal causes the piezoelectric microcantilever to deflect, thereby actuating the attached myotube.

Bio-microelectromechanical system transducer and associated methods

The invention provides a method of co-culturing mammalian muscle cells and mammalian motoneurons. The method comprises preparing one or more carriers coated with a covalently bonded monolayer of trimethoxysilylpropyl diethylenetriamine (DETA); suspending isolated fetal mammalian skeletal muscle cells in serum-free medium according to medium composition 1; suspending isolated fetal mammalian spinal motoneurons in serum-free medium according to medium composition 1; plating the suspended muscle cells onto the one or more carriers at a predetermined density and allowing the muscle cells to attach; plating the suspended motoneurons at a predetermined density onto the one or more carriers and allowing the motoneurons to attach; covering the one or more carriers with a mixture of medium composition 1 and medium composition 2; and incubating the carriers covered in the media mixture.

Method of co-culturing mammalian muscle cells and motoneurons

The invention provides a nutrient medium composition and associated methods for lengthening the useful life of a culture of muscle cells. Disclosed is a method of culturing mammalian muscle cells, including preparing one or more carriers coated with a covalently bonded monolayer of trimethoxy-silylpropyl-diethylenetriamine (DETA); verifying DETA monolayer formation by one or more associated optical parameters; suspending isolated fetal rat skeletal muscle cells in serum-free medium according to medium composition 1; plating the suspended cells onto the prepared carriers at a predetermined density; leaving the carriers undisturbed for cells to adhere to the DETA monolayer; covering the carriers with a mixture of medium 1 and medium 2; and incubating. A cell nutrient medium composition includes Neurobasal, an antibiotic-antimycotic composition, cholesterol, human TNF-alpha, PDGF BB, vasoactive intestinal peptides, insulin-like growth factor 1, NAP, r-Apolipoprotein E2, purified mouse Laminin, beta amyloid, human tenascin-C protein, rr-Sonic hedgehog Shh N-terminal, and rr-Agrin C terminal.

Method for culturing skeletal muscle for tissue engineering

A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more rat muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a rat muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.

Formation of neuromuscular junctions in a co-culture comprising rat muscle cells overlayered with differentiated human spinal cord stem cells in a serum free medium

The invention provides a model for generating predicted action potentials of an electrically active cell. The disclosed model includes three operatively coupled submodels. A first submodel contains Hodgkin-Huxley elements generating action potentials based on electrical equivalent circuits. A second submodel is based on reaction kinetics of cell metabolism and is operatively coupled with the first submodel. A third submodel is based on Boolean dynamics representing signaling and associated cellular processes and is operatively coupled with the first and second submodels. The invention includes storing a library of calculated action potentials and associated cellular parameters generated by the model, applying a stimulus to the electrically active cell in vitro so that the cell generates an action potential; and comparing the cell-generated action potential with those stored in the library, wherein a match is predictive of the cellular point of action of the applied stimulus according to the parameters stored.

Model and methods for identifying points of action in electrically active cells

The invention provides a culture of patterned cardiomyocytes, the culture including a support substrate bearing a multielectrode array, a negative surface resistant to cell attachment and deposited on the support substrate covering the multi-electrode array, a pattern ablated on the negative surface, a positive surface promoting cell attachment deposited on the pattern ablated on the negative surface; and cardiomyocytes adherent to the positive surface and growing aligned along the pattern ablated on the negative surface. The invention also includes a method of making the culture of patterned cardiomyocytes and a method of in vitro method of testing the effect of a compound on cardiac function by measuring electrical output from the patterned cardiomyocytes.

Patterned cardiomyocyte culture on microelectrode array

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Pendleton, SC, United States of America

James J Hickman