Polymerase-Nucleic Acid Complex Modification via Chemical Dissociation
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Solution Overview
Problem
Current nucleic acid sequencing technologies face challenges with short read lengths and errors, requiring increased time and resources for accurate DNA sequencing, particularly in identifying nucleotides for genetic analysis and diagnostics.
Innovation Solution
A method involving polymerase-nucleic acid complexes is used, where an aqueous solution containing polyols, diols, sulfones, or sulfoxides is employed to dissociate nucleotides from the complexes, allowing for the retention of polymerases and nucleic acids, enabling efficient identification and replacement of nucleotides without substantial polymerase loss.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If massively parallel processing is used to increase the number of reads, then sequencing throughput is improved, but time and resource consumption increases
Solution Approach 1:
The patent changes the chemical parameters of the reaction environment by introducing polyols, diols, sulfones, or sulfoxides to the aqueous solution. These chemical modifications enable selective dissociation of nucleotides from polymerase-nucleic acid complexes, allowing for more efficient sequencing cycles that reduce overall processing time and resource requirements while maintaining high throughput
Solution Approach 2:
The patent implements periodic delivery and removal of nucleotides in controlled cycles. By using chemical agents to selectively dissociate nucleotides at specific intervals, the system enables repeated sequencing cycles with the same polymerase molecules, increasing throughput without proportionally increasing time and resource consumption
2Speed
If short reads are used for sequencing, then sequencing speed is improved, but read length and accuracy deteriorate
Solution Approach 1:
The patent performs preliminary dissociation of nucleotides using polyols, diols, sulfones, or sulfoxides before extending the nucleic acid strand. This preliminary chemical treatment ensures that only properly bound nucleotides remain, improving the accuracy of each sequencing read while maintaining fast sequencing speeds through efficient cycle turnover
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 the accuracy and length of sequencing reads, reducing time and resource consumption by allowing for the serial delivery and removal of nucleotides while retaining polymerases, thus improving the efficiency of nucleic acid analysis.
Implementation Method 1
contacting the plurality of polymerase-nucleic acid complexes with an aqueous solution comprising a polyol, alcohol, aliphatic diol, sulfone, sulfoxide, or a combination thereof, thereby dissociating the nucleotides from the subset of polymerase-nucleic acid complexes
Data Source
AI summary
Provided herein include a method for modifying polymerase-nucleic acid complexes, including (a) providing a plurality of surface-immobilized polymerase-nucleic acid complexes in a vessel, wherein the nucleic acid includes a primed-template nucleic acid, wherein at least a subset of the surface-immobilized polymerase-nucleic acid complexes include ternary complexes further including nucleotides; and (b) washing the surface with an aqueous solution including a diol, sulfoxide or polyol, thereby removing the nucleotides from the vessel and retaining the surface-immobilized polymerase-nucleic acid complexes in the vessel.