3D Oligonucleotide Array for High-Precision DNA Sequencing
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Solution Overview
Problem
Current cancer diagnosis and treatment face challenges due to inefficiencies in identifying individuals with predisposing genetic risk factors, lack of standardized molecular signatures for cancers, and failure to identify patients who won't respond to therapies, largely due to inadequate nucleic acid amplification and sequencing technologies.
Innovation Solution
A method and device for nucleic acid amplification and sequencing that standardizes molecular diagnostics and individualizes treatment by using a novel three-dimensional array design and solid phase amplification technology, enabling the identification and sequencing of target nucleotide sequences with high precision and cost-effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current nucleic acid amplification and sequencing technology is used, then cancer diagnosis and treatment can be performed, but the technology is not cost effective and cannot identify individuals with predisposing genetic risk factors
Solution Approach 1:
The invention divides the nucleic acid amplification process into multiple discrete steps including hybridization, extension, denaturation, and detection. The device is segmented into multiple components including a solid support with arrayed primers, reaction chambers, and detection systems. This segmentation enables standardized manufacturing procedures for each component, reducing overall cost while maintaining high identification accuracy through specialized optimization of each segment.
Solution Approach 2:
The invention transitions from traditional two-dimensional microarray surfaces to a three-dimensional solid support structure with arrayed oligonucleotide primers extending from the surface. This dimensional change increases the density of primer addresses (up to 1000-fold) while maintaining accessibility for reagent flow and detection, enabling cost-effective high-throughput sequencing with enhanced measurement precision.
2Reliability
If current nucleic acid amplification technology is used, then molecular diagnostics can be performed, but the technology is not standardized across platforms
Solution Approach 1:
The invention employs universal components including a standardized solid support structure, universally applicable oligonucleotide primers with defined sequences, and a standardized polymerase extension reaction system. The method uses consistent thermal cycling parameters and detection protocols across all assays. This universality ensures that molecular diagnostics are standardized across different implementations while the modular device design allows for controlled variability to address specific clinical needs.
3Measurement precision
If traditional sequencing methods are used, then genetic profiles can be obtained, but the technology cannot integrate with clinical trials and properly identify or validate patient responses to therapies
Solution Approach 1:
The invention performs preliminary enrichment of target nucleotide sequences through hybridization with arrayed primers before amplification and sequencing. This preliminary action concentrates the relevant genetic material and removes background noise, enabling more efficient sequencing with higher precision. The standardized protocol allows rapid processing of multiple samples, integrating seamlessly with clinical trial workflows to identify and validate patient responses to therapies with improved diagnostic efficiency.
Solution Approach 2:
The invention replaces traditional mechanical sequencing approaches with a biochemical hybridization-based system using oligonucleotide primers arrayed on a solid support. This substitution enables parallel processing of multiple genetic targets simultaneously through solution-phase hybridization and extension reactions, dramatically increasing productivity while maintaining or improving measurement precision through the specificity of nucleic acid base pairing.
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 allows for the accurate identification of target nucleotide sequences, enabling personalized cancer treatment and improving diagnostic efficiency, reducing costs, and enhancing the ability to sequence only relevant genes for clinical validation, thereby improving patient outcomes.
Implementation Method 1
During the hybridization treatment, the first and third primer portions of the first and second oligonucleotide primers, respectively, hybridize to their respective complementary portions of the target nucleotide sequence and/or complement
Implementation Method 2
During the extension treatment, the hybridized oligonucleotide primers extend to form primary primer extension products
Implementation Method 3
During the denaturation treatment, hybridized nucleic acid sequences are separated
Data Source
AI summary
The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.