Degradable Nanoparticle Core and Polymer Shell for Nucleic Acid Arrays
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Solution Overview
Problem
Current technologies face challenges in maximizing the output of sequencing information due to the limitations of feature dimensions approaching submicron domains in arrays used for next-generation sequencing.
Innovation Solution
The development of particles with a degradable particle core and a polymer shell, where oligonucleotide moieties are covalently linked to the polymer shell via a polymeric bioconjugate linker, allowing for efficient immobilization and hybridization on solid supports.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If feature dimensions are miniaturized to submicron domains to increase cluster density and scale, then reagent consumption is reduced and data acquisition rate is enhanced, but manufacturing precision and reliability become more difficult to maintain
Solution Approach 1:
A polymer shell acts as an intermediary structure between the degradable particle core and the solid support. The shell provides a stable platform for oligonucleotide attachment while the core can be degraded to release or activate the functional elements, enabling precise control at submicron scales without directly manipulating the fragile features themselves
Solution Approach 2:
The particle system divides the sequencing feature into separate functional components: a degradable core that can be processed independently and a polymer shell that provides the stable attachment interface. This segmentation allows each component to be optimized separately, maintaining manufacturing precision while enabling miniaturization
2Quantity of substance
If feature dimensions are miniaturized to submicron domains to increase cluster density, then the scale and density of clusters are increased, but manufacturing precision and stability become more difficult to maintain
Solution Approach 1:
The degradable particle core is nested within the polymer shell structure. This nested configuration allows the core to be protected during manufacturing and handling, while the outer shell maintains structural integrity and stability. The core can subsequently be degraded in situ to release functional elements without compromising the overall feature stability
Solution Approach 2:
The particle system uses composite materials combining a degradable core material with a stable polymer shell material. This composite structure provides both the density and scalability benefits of miniaturization while maintaining compositional stability through the protective shell that preserves the core until activation
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
This solution enables increased density and scale of clusters in arrays, reducing reagent consumption and enhancing data acquisition rates, while maintaining the stability and specificity of oligonucleotide hybridization.
Implementation Method 1
contacting the one or more particles with a degrading agent thereby decomposing the degradable particle core and forming a polymer composition attached to the well
Implementation Method 2
The oligonucleotide moiety is capable of hybridizing to a complementary sequence of a template nucleic acid
Data Source
AI summary
Arrays are an important tool in biomedical research, providing a platform that arranges biological samples and enables high-throughput analyses. Delivering breakthroughs in proteomics, multiplexed immunoassays, and complex genomic analyses, arrays (e.g., microarrays and nanoarrays) can be designed to host thousands, millions, or even billions, of features that are subjected to simultaneous reaction conditions. Disclosed herein, inter alia, are degradable nanoparticles, nanoarrays, and methods of use thereof.