Available Technology
3D cell culture substrate that enables live-cell imaging
Technology:
Paper synthesized from fibers composed of barium alginate
Markets Addressed
The Whitesides laboratory has designed a new type of paper, which is synthesized from fibers composed of barium alginate. Barium alginate fibers have an index of refraction very close to that of the hydrogel holding the cells, which eliminates light refraction and enables visualization of the cells via microscopy. Barium alginate paper is very simple, rapid and inexpensive to prepare and requires no specialized laboratory equipment.
The simplicity, rapidity and cost-effectiveness of this fabrication process means that barium alginate paper can be used to quickly and conveniently set up live cell cultures. Furthermore, due to the desired optical properties of this paper, these cells can then be imaged in real time. For example, the Whitesides laboratory was able to image GFP-expressing cells via fluorescent microscopy throughout the full thickness of one sheet of barium alginate paper. Other cellular bioassays and techniques, such as paper-based transmittance colorimetric assays (POCKET), will also benefit greatly from the optically transparent nature of this barium alginate paper.
Innovations and Advantages
Dr. George Whitesides’ lab recently developed a novel paper scaffold which can be impregnated with a hydrogel containing cells and then layered, thereby generating a 3D cell culture with easily-controlled spatial distributions, densities, and other desired properties. Layers of sheets containing cells can be stacked to mimic various tissues, and destacked for cellular analyses and assays. This 3D cell culture platform is simple to make in the laboratory, versatile, easy to manipulate, and does not require specific expertise, or uncommon instrumentation. For more information, click here.
It would also be desirable to be able to image cells in-situ once they have been cultured, without having to extract them from their 3D matrix. Ordinary paper, formed from cellulose fibers, has a different index of refraction than the medium containing the cells, and therefore scatters light, which impedes microscopic imaging. The Whitesides laboratory has developed a way of overcoming this obstacle, and has combined the simplicity and versatility of paper-based 3D cell cultures with the desired optical properties that allow live imaging of cells.
Additional Information
Intellectual Property Status: A US Provisional patent application is pending.
Publication:
“Paper-supported 3D cell culture for tissue-based bioassays”, Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18457-62. Epub 2009 Oct 21. PMID: 19846768. Article is available here.
Relevant Technologies: Please also see related 3D Cell Culture technology. Summary is available here.
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Inventor(s):
Barber, Jabulani
Cademartiri, Rebecca
Laromaine Sague, Anna
Mace, Charles R.
Whitesides, George M.
Categories:
For further information, please contact:
Mick Sawka, Director of Business Development
(617) 496-3830
Reference Harvard Case #3718