Micro-organ device
Inventors
Gonda, Steve R. • Chang, Robert C. • Starly, Binil • Culbertson, Christopher • Holtorf, Heidi L. • Sun, Wei • Leslie, Julia
Assignees
National Aeronautics and Space Administration NASA
Publication Number
US-8580546-B2
Publication Date
2013-11-12
Expiration Date
2028-03-28
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Abstract
A method for fabricating a micro-organ device comprises providing a microscale support having one or more microfluidic channels and one or more micro-chambers for housing a micro-organ and printing a micro-organ on the microscale support using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, wherein the cell suspension comprises cells suspended in a solution containing a material that functions as a three-dimensional scaffold. The printing is performed with the computer-aided tissue engineering system according to a particular pattern. The micro-organ device comprises at least one micro-chamber each housing a micro-organ; and at least one microfluidic channel connected to the micro-chamber, wherein the micro-organ comprises cells arranged in a configuration that includes microscale spacing between portions of the cells to facilitate diffusion exchange between the cells and a medium supplied from the at least one microfluidic channel.
Core Innovation
The invention relates to methods for fabricating micro-organ devices (MODs) and the micro-organ devices themselves, which comprise microscale three-dimensional tissue analogs integrated within devices having microfluidic channels and micro-chambers. The method involves providing a microscale support that has microfluidic channels and micro-chambers to house micro-organs, and printing micro-organs on this support using a cell suspension controlled by a computer-aided tissue engineering (CATE) system. The cell suspension contains cells in a solution with a material that functions as a three-dimensional scaffold, and the printing is performed according to a particular pattern.
The problem addressed by the invention stems from limitations in the testing of pharmaceuticals and biological compounds. Traditional in vitro assays like cell cultures do not always faithfully mimic in vivo conditions because of the absence of cell-cell and tissue interactions and unrealistic liquid-to-cell ratios. Animal testing, while more relevant to human responses, is costly and time-consuming, and translating in vitro data to in vivo outcomes is often difficult. Related art devices do not produce reproducible organs and fail to mimic physiological conditions adequately, thus there remains a need for in vitro organ devices and fabrication methods that can closely mimic in vivo organs or systems.
To solve this problem, the invention provides methods to fabricate micro-organ devices by combining microscale supports with bioprinting technology using a CATE system to deposit cells encapsulated within scaffold materials into micro-chambers in defined architectures. These architectures include microscale spacing between portions of cells to facilitate effective diffusion exchange with media supplied via microfluidic channels. The MODs can mimic the structure and function of in vivo organs more effectively through controlled three-dimensional arrangements and interconnections among multiple micro-organs.
Claims Coverage
The patent includes one independent claim directed to a micro-organ device prepared by a specific process. The main inventive features focus on device structure and the method of fabrication involving printing micro-organs with a cell suspension in a scaffold material using a computer-aided tissue engineering system.
Micro-organ device comprising microfluidic-connected micro-chamber
The device comprises at least one micro-chamber for housing a micro-organ and at least one microfluidic channel connected to the micro-chamber.
Micro-organ with microscale cell spacing for diffusion exchange
The micro-organ comprises cells arranged with microscale spacing between portions to facilitate diffusion exchange between the cells and medium supplied from the microfluidic channel.
Method of fabricating micro-organ device involving microscale support and substrate bonding
The microscale support having the microfluidic channel and micro-chamber is bonded to a substrate by covering their contact surfaces with titanium tetra(isopropoxide).
Bioprinting micro-organ using cell suspension with scaffold material and computer control
Printing the micro-organ is done on the microscale support using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, with the cell suspension comprising cells suspended in a solution containing a three-dimensional scaffold material, and printing performed according to a particular pattern.
The independent claim covers a micro-organ device structurally defined by microfluidic channels and micro-chambers housing microscopically spaced cells, prepared via controlled bioprinting on a microscale support bonded to a substrate with chemical modification. The inventive features combine precise device architecture with a method of fabrication that ensures functional micro-organs suitable for diffusion exchange.
Stated Advantages
Provides precise and reproducible biopatterning and bioprinting of cells, extracellular matrices, and scaffolds directly on microfluidic microchips.
Minimizes variations in local cell seeding densities and reduces selection pressures favoring aggressive cells.
Enables precise and simultaneous coupling of multiple microfluidic channels on the same microchip.
Allows control of volumetric and quantitative parameters suitable for pharmacodynamics, pharmacokinetics, and toxicity studies.
Enables reproduction of in vivo circulation profiles within and between micro-organs.
The micro-organ devices can be automated, have minimal footprint and power requirements, use small fluid volumes generating minimal waste, and provide high-throughput parallel analyses.
Reduces resource requirements by mimicking in vivo situations without the use of human or animal subjects, potentially improving predictive accuracy and reducing costs associated with animal studies.
Documented Applications
Experimental pharmaceutical screening for efficacy, absorption, distribution, metabolism, elimination, and toxicity assessment.
Studying drug metabolism and enzyme activities, including conversion of pro-drugs to active or inactive metabolites by micro-liver devices.
Pharmacokinetic and pharmacodynamic studies simulating interactions between multiple organs via interconnected micro-organ devices.
Assessing therapeutic benefits and toxic effects of drug compounds in vitro with multi-organ microdevices.
Drug screening systems for use both on Earth and in space with human cell micro-organs to supplement or reduce animal studies.
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