DNA Valency Sorting Chromatography for Separating Large Solutes
Princeton Docket # 22-3863
Few technologies are available for analyzing or purifying, in a general way, large solutes labeled with a defined number of molecules. Large solutes could be organic or inorganic nanoparticles, large macromolecules, assemblies of macromolecules or nanoparticles, viruses, drug and vaccine delivery nanovesicles, to name a few.
Researchers at Princeton University’s Department of Chemistry have developed DNA valency sorting chromatography, a new method for separating large solutes based on the number of DNA-barcoded molecules displayed on their surface. In contrast to the conventional techniques that are only effective for small solutes, DNA valency sorting chromatography was designed specifically for the purification of large solutes. Two key features enable it to overcome the common limitations and purify a broader range of discrete DNA-tagged solutes. Using nanoparticles as an example: First, the underlying mechanism relies on the highly selective recognition of a short DNA barcode attached to the nanoparticle, rather than the global features of the entire nanoparticle solute. This means that the short DNA barcode can be recognized with high specificity regardless of nanoparticle size or surface chemistry, unlike existing methods. Second, in addition to selectivity, the underlying separation mechanism is programmable because a unique DNA sequence is used as a recognition element and digital encoder. The DNA sequence can be altered to predictably change its thermodynamic, kinetic, and recognition properties. This is advantageous compared to existing mechanisms, which rely on generic and unprogrammable properties like size, charge, or polarity, and it permits the technique to be operated with process conditions that are compatible with biologics or fragile nanomaterials. Importantly, this technology affords large-scale production in a highly programmable way.
- Production of DNA-barcoded large macromolecules, nanoparticles, and nanovesicles
- Analysis and separation of nanoparticle mixtures
- DNA/nanoparticle computation
- Creation of programmable, active materials
- Valency-defined functional materials
- High-value and custom nanomaterials reagents
- High-throughput flow through surface encoding
Selective and programmable separation mechanism
Applicable to a range of sizes (at least 80 nm) and shapes
Independent of solute material (gold, silver, cadmium selenide, protein, iron oxide)
Process conditions compatible with biologics and fragile nanomaterials
Preparative scale production, extensible to industrial scale
Stage of development
Fully functioning DNA valency sorting columns have been operating routinely for multiple years. The purified nanoparticles have been verified experimentally to have the expected number of DNA molecules attached, as well experimentally demonstrated using them to do novel DNA-encoded nanochemistry.
Haw Yang, Ph.D. received a B.S. degree from the National Taiwan University, and a Ph.D. degree from the University of California Berkeley. He was a Post-Doctoral Fellow at Harvard University for two and half years. In 2002, he joined UC Berkeley before moving to Princeton University in 2009. He is currently a Professor of Chemistry with Princeton University. His research is broadly about complex-system chemical dynamics, crosscutting the conventional fields of physical chemistry, chemical and materials biology, and biophysics. Professor Yang is a fellow of the Royal Society of Chemistry, a founding Associate Editor of Chemical Science, and on several Editorial Advisory Boards.
Nyssa Emerson, Ph.D. received a B.S. in Chemistry from the University of Chicago and a Ph.D. in Chemistry from Princeton University. She is currently a post-doctoral research associate at Princeton University in the lab of Prof. Haw Yang, where she led the development of DNA valency sorting technology.
Sorting Nanoparticles by Valency with DNA Barcoding
Nyssa T. Emerson and Haw Yang
Journal of the American Chemical Society, 144, 12915–12923 (2022).
Intellectual Property & Development status
Patent protection is pending.
Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.
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