DNA Valency Sorting Chromatography for Nanoparticle Purification
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Solution Overview
Problem
Current methods for obtaining valency-defined nanoparticles are limited by the random nature of DNA attachment to nanoparticle surfaces, leading to mixtures rather than specific products, and are ineffective for larger nanoparticles with unique functionalities like plasmonically active metallic nanorods or large nanospheres, due to reliance on physical characteristics rather than specific DNA features.
Innovation Solution
A DNA valency sorting chromatography technique that utilizes complementary DNA sequences to selectively separate nanoparticles based on their DNA valency, independent of nanoparticle characteristics, by binding keyword sequences to a capture sequence immobilized on a solid support and modulating mobile phase conditions to release nanoparticles with defined valency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If physical characteristics (charge, size) are used for nanoparticle separation, then separation can be achieved for spherical nanoparticles up to 30-40 nm, but the method becomes ineffective for larger nanoparticles with unique functionalities
Solution Approach 1:
The patent introduces DNA barcode sequences as an intermediary that mediates the interaction between nanoparticles and the chromatography medium. Instead of relying on physical characteristics of the nanoparticle itself, the DNA barcode serves as a programmable interface that enables specific recognition and separation based on DNA valency, thereby extending applicability to nanoparticles of all sizes and types.
Solution Approach 2:
The invention changes the separation parameter from physical characteristics (size, charge) to DNA sequence complementarity. By modifying the mobile phase conditions (ionic strength, temperature) to modulate DNA hybridization, the system achieves separation based on DNA valency rather than nanoparticle physical properties, enabling universal application across diverse nanoparticle types.
2Ease of manufacture
If DNA attachment proceeds randomly on nanoparticle surfaces, then the process is simple, but it generates a mixture of products rather than a specific valency-defined product
Solution Approach 1:
The patent applies preliminary action by first attaching DNA barcodes with defined sequences to the nanoparticle surfaces in a controlled manner, then using these pre-defined barcodes as recognition elements in the chromatography process. This preliminary encoding of specific DNA sequences enables subsequent high-precision separation based on complementarity, rather than relying on random attachment followed by separation.
Solution Approach 2:
The invention implements feedback through the chromatography process where the DNA barcode sequences provide a readout of the nanoparticle's DNA valency. The complementary capture sequences on the stationary phase selectively bind to nanoparticles with matching DNA barcodes, providing feedback-based separation that enriches for specific valency-defined products while eliminating mixtures.
3Measurement precision
If DNA features are used as the basis for separation selectivity, then specific DNA sequences can be targeted, but the DNA features register as different shades of a continuous analog signal that become indistinguishable as nanoparticle size increases
Solution Approach 1:
The patent segments the continuous analog signal into discrete digital categories by using specific DNA barcode sequences that represent distinct valency states. Instead of measuring continuous variations in DNA features, the system uses discrete complementary base-pairing events that produce distinct binding affinities, effectively converting an analog measurement problem into a digital classification problem with clearly distinguishable states.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables the precise separation and purification of nanoparticles with defined DNA valency, overcoming size limitations and achieving high resolution for a wide range of nanoparticle sizes and shapes, including previously inaccessible large metallic nanospheres and nanorods, facilitating their use in complex nanostructures and applications.
Implementation Method 1
Each keyword sequence may be appended onto a DNA sequence that may be attached to the nanoparticle or molecule. Each capture sequence may be a reverse complement of the keyword sequence. allowing the keyword sequences on each nanoparticle or molecule to bind to a capture sequence coupled to a solid support substrate
Implementation Method 2
releasing the nanoparticle or molecule on the solid support substrate based on a mobile phase strength of a mobile phase passing over the solid support substrate
Data Source
AI summary
Disclosed is DNA valency sorting chromatography, a purification method for separating solutes based on the number of barcoded DNA molecules present on their surface, which can operate using conventional low-pressure chromatography equipment and instrumentation. Solutes can take a variety of forms, including biological macromolecules, polymeric nanoparticles, gold or silver nanospheres, gold nanorods, iron oxide nanoparticles, and semiconducting nanocrystals. In contrast to most existing purification procedures, DNA valency sorting is highly selective for the DNA sequence specifically, rather than the characteristics of the solute as a whole, and uses extremely gentle elution conditions. As a result, it is applicable to a range of solute characteristics, including variable chemical composition, surface charge, and materials with hydrodynamic diameters up to 80 nm, which cannot be purified with a well-defined number of macromolecules by any other existing technique.