Researchers have created a new kind of barcode that uses DNA origami technology. Colored-dots can be arranged into geometric patterns or fluorescent linear DNA barcodes, and the combinations are almost limitless -- substantially increasing the number of distinct molecules or cells scientists can observe in a sample. Credit: Chenxiang Lin, Ralf Jungmann, Andrew M. Leifer, Chao Li, Daniel Levner, George M. Church, William M. Shih, Peng Yin, Wyss Institute for Biologically Inspired Engineering, Harvard Medical School

Much like the checkout clerk uses a machine that scans the barcodes on packages to identify what customers bought at the store, scientists use powerful microscopes and their own kinds of barcodes to help them identify various parts of a cell, or types of molecules at a disease site. But their barcodes only come in a handful of "styles," limiting the number of objects scientists can study in a cell sample at any one time.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have created a new kind of barcode that could come in an almost limitless array of styleswith the potential to enable scientists to gather vastly more vital information, at one given time, than ever before. The method harnesses the natural ability of DNA to self-assemble, as reported today in the online issue of Nature Chemistry.

"We hope this new method will provide much-needed molecular tools for using fluorescence microscopy to study complex biological problems," says Peng Yin, Wyss core faculty member and study co-author who has been instrumental in the DNA origami technology at the heart of the new method.

Fluorescence microscopy has been a tour de force in biomedical imaging for the last several decades. In short, scientists couple fluorescent elementsthe barcodesto molecules they know will attach to the part of the cells they wanted to investigate. Illuminating the sample triggers each kind of barcode to fluoresce at a particular wavelength of light, such as red, blue, or greenindicating where the molecules of interest are.

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Researchers have created a new kind of barcode that uses DNA origami technology. Shown here are the color combinations resulting from attaching just three colors to a DNA nanotube using origami technology -- underscoring the potential of this new method. Credit: C. Lin, Wyss Institute for Biologically Inspired Engineering, Harvard University

Here's how it works: DNA origami follows the basic principles of the double helix in which the molecular bases A (adenosine) only bind to T (thymine), and C (cytosine) bases only bind to G (guanine). With those "givens" in place, a long strand of DNA is programmed to self-assemble by folding in on itself with the help of shorter strands to create predetermined formsmuch like a single sheet of paper is folded to create a variety of designs in the traditional Japanese art.

To these more structurally complex DNA nano-structures, researchers can then attach fluorescent molecules to the desired spots, and use origami technology to generate a large pool of barcodes out of only a few fluorescent molecules. That could add a lot to the cellular imaging "toolbox" because it enables scientists to potentially light up more cellular structures than ever possible before.

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Scientists engineer novel DNA barcode