Hydrogel Nanoparticles for Sequencing by Synthesis
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Solution Overview
Problem
Current nucleic acid sequencing technologies are costly, require large amounts of expensive reagents, and lack scalability, making them inefficient for high-throughput, cost-effective genome sequencing necessary for personalized healthcare.
Innovation Solution
The development of next-generation sequencing kits, methods, systems, and compositions that utilize labeled water-soluble nanoparticles. These nanoparticles have a polymer matrix with functional moieties that bind to unlabeled nucleotides and detectable labels attached via covalent bonding, enabling efficient sequencing by synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current sequencing methodologies are used, then sequencing capability is achieved, but cost and reagent expense increase significantly
Solution Approach 1:
The patent uses disposable microfluidic cartridges with integrated reagent reservoirs that are discarded after a single use, eliminating the need for expensive reusable instrumentation and reducing reagent contamination risks. The cartridge-based approach allows low-cost single-use implementation of complex sequencing workflows.
Solution Approach 2:
The invention changes the physical state and concentration parameters of reagents by formulating them in dry powder form within the cartridge, which can be reconstituted with controlled volumes of buffer. This parameter change reduces reagent degradation, extends stability, and allows precise control of reagent concentrations to minimize waste.
2Productivity
If large amounts of expensive reagents are used, then sequencing reactions can proceed, but cost effectiveness decreases
Solution Approach 1:
The sequencing reagents are segmented into multiple separate reservoirs within the cartridge, each containing a specific reagent at optimized concentration. This segmentation allows precise delivery of only the required amount of each reagent to the reaction zone, preventing waste and reducing overall reagent consumption while maintaining high throughput.
Solution Approach 2:
The patent uses partial action by delivering reagents in controlled, incremental amounts rather than all at once. The microfluidic system allows stepwise addition of reagents only when needed in the sequencing workflow, avoiding excessive reagent use while maintaining reaction efficiency and throughput.
3Measurement precision
If multiple sets of optic filters are used to record nucleic acid incorporation, then sequencing detection is achieved, but device complexity and cost increase
Solution Approach 1:
The patent extracts the optical detection function from complex multi-filter systems and replaces it with fluorescently labeled nucleotides that emit at distinct wavelengths. Each nucleotide type (A, C, G, T) is labeled with a unique fluorophore, allowing identification through wavelength-specific detection without requiring multiple physical filters for each sequencing position.
Solution Approach 2:
The fluorescent labeling system provides multi-functionality: a single optical detector can identify all four nucleotide types by detecting different emission wavelengths from different fluorophores. This universal detection approach replaces the need for multiple specialized filter sets, reducing device complexity while maintaining measurement precision.
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 approach enhances sequencing speed, reduces errors, and lowers costs, providing a scalable and high-throughput solution for nucleic acid sequencing, which is crucial for personalized healthcare applications.
Implementation Method 1
the plurality of detectable labels are attached to the polymer matrix, optionally via covalent bonding to a plurality of second functional moieties of the polymer matrix or optionally via covalent bonding to the first functional moieties
Implementation Method 2
the one or more first functional moieties are hapten-binding proteins capable of non-covalent binding with a hapten moiety of the unlabeled nucleotide
Implementation Method 3
a plurality of detectable labels, wherein the plurality of detectable labels are attached to the polymer matrix
Data Source
AI summary
Embodiments of the present disclosure relate to compositions and methods for labeling of nucleotides, oligonucleotides, or polynucleotides with nanoparticles. In particular, labeled nanoparticles can be used to label nucleotides, oligonucleotides, or polynucleotides in sequencing by synthesis.