Particle-Assisted Nucleic Acid Sequencing via Microfluidic Hybridization
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Solution Overview
Problem
Current nucleic acid sequencing methods are inefficient for sequencing entire genomes, requiring significant time and not adequately increasing sequencing throughput despite advancements in smaller nucleic acid fragments.
Innovation Solution
The method involves using a microfluidic system where target nucleic acids are exposed to particles with unique nucleic acid probes, determining binding to sequence the nucleic acid based on hybridization, employing techniques like sequencing by hybridization (SBH) and ligation methods to enhance sequencing efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional sequencing methods are used for entire genomes, then sequencing can be performed, but sequencing time increases by many orders of magnitude
Solution Approach 1:
The invention divides the genome sequencing task into multiple parallel reactions, each targeting specific genomic regions or using specific probe sets. By segmenting the overall sequencing process into concurrent sub-reactions, the system achieves high-throughput sequencing without proportionally increasing total time, directly resolving the contradiction between productivity and time loss.
2Productivity
If arrays of oligonucleotide probes are used, then sequencing capability is provided, but sequencing time is not adequately decreased
Solution Approach 1:
The invention employs dynamic control of reaction conditions, including temperature cycling and phased probe addition, to optimize each sequencing reaction step. This dynamic approach allows the system to maintain high throughput while reducing the time required for each sequencing cycle, addressing the insufficient time reduction achieved by static probe array methods.
3Measurement precision
If multiple particles with unique probes are used, then sequencing accuracy is improved, but system complexity increases
Solution Approach 1:
The invention uses particles that carry copies of unique probe sequences, where each particle type represents a specific genomic target. This copying approach allows parallel processing of multiple sequencing reactions while maintaining accuracy through redundant probe representations, effectively managing the complexity-accuracy trade-off by using standardized particle copies rather than entirely unique complex structures.
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 significantly accelerates the sequencing process by leveraging microfluidic technology and particle-assisted nucleic acid probes, improving throughput and accuracy in determining nucleic acid sequences.
Implementation Method 1
determining the sequence of the target nucleic acid based on binding of the particles to the target nucleic acid
Data Source
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AI summary
This invention generally relates to particle-assisted nucleic acid sequencing. In some embodiments, sequencing may be performed in a microfluidic device, which can offer desirable properties, for example, minimal use of reagents, facile scale-up, and/or high throughput. In one embodiment, a target nucleic acid may be exposed to particles having nucleic acid probes. By determining the binding of the particles to the target nucleic acid, the sequence of the target nucleic acid (or at least a portion of the target nucleic acid) can be determined. The target nucleic acid may be encapsulated within a fluidic droplet with the particles having nucleic acid probes, in certain instances. In some cases, the sequence of the target nucleic acid may be determined, based on binding of the particles, using sequencing by hybridization (SBH) algorithms or other known techniques.