Waveguide Monomer Chain Synthesis with Optical Feedback
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Solution Overview
Problem
Current DNA-oligo synthesis is limited by poor yields due to the numerous steps required for base addition, resulting in only about 36% correct 200-base oligos, which hampers reliable scale-up.
Innovation Solution
A method involving immobilizing a monomer chain on a waveguide surface, attaching a capping agent to the monomer, and using a sensor to detect the presence of the monomer, ensuring high-yield construction of monomer chains through controlled monomer addition and detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If traditional DNA-oligo synthesis methods are used with multiple base addition steps, then the process can construct long oligo chains, but the yield decreases significantly due to cumulative errors in each step
Solution Approach 1:
The patent implements real-time feedback detection at each monomer addition step using optical sensors to verify correct incorporation. This allows immediate identification and rejection of incorrect additions, preventing cumulative errors from propagating through the synthesis process and maintaining high fidelity for long oligo chains.
Solution Approach 2:
The patent replaces traditional mechanical/chemical synthesis methods with an optical detection-based verification system. Optical sensors detect monomer incorporation through changes in light transmission or reflection, substituting mechanical verification with optical measurement to achieve more precise and reliable synthesis control.
2Reliability
If detection steps are added to verify each monomer addition, then the yield and fidelity improve, but the device complexity and process time increase
Solution Approach 1:
The patent merges the synthesis and detection functions into a single integrated platform. The optical sensor system is incorporated directly into the synthesis apparatus, allowing simultaneous monitoring of monomer addition without requiring separate detection instruments. This integration reduces overall system complexity despite adding verification capability.
Solution Approach 2:
The optical detection system serves multiple functions: verifying monomer incorporation, monitoring synthesis progress, and providing real-time feedback control. This multi-functionality reduces the need for separate specialized instruments, thereby reducing overall device complexity while maintaining high reliability.
3Manufacturing precision
If real-time detection of each monomer addition is implemented, then the synthesis precision improves, but the synthesis time increases
Solution Approach 1:
The patent employs periodic optical detection cycles that interrupt synthesis operations at strategic intervals to verify monomer incorporation. Rather than continuous monitoring, the system performs rapid periodic checks that confirm correct addition before proceeding to the next step, achieving high precision while minimizing time loss through efficient cycling.
Solution Approach 2:
The optical detection system is designed to provide rapid feedback that immediately guides the next synthesis step, eliminating idle waiting time. The detection and verification processes are continuously integrated with the synthesis workflow, ensuring that useful action continues without unnecessary interruptions or delays.
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 ensures nearly absolute yield of correct monomer chains, even for long sequences, by detecting and confirming each monomer addition step, thereby improving the fidelity and efficiency of DNA-oligo synthesis.
Implementation Method 1
immobilizing, using a surface of a waveguide, a monomer chain
Implementation Method 2
detecting, using a sensor in communication with the waveguide, presence of the first monomer
Data Source
AI summary
Aspects relate to systems and methods for high-contrast cleavage detection. An exemplary method includes a plurality of probes, wherein at least a probe of the plurality of probes comprises a high-contrast agent, a waveguide configured to propagate an electromagnetic (EM) wave, wherein the waveguide includes a surface upon which the plurality of probes are immobilized, wherein the surface is configured to provide communication between the EM wave and the high-contrast agent, a primary cleaving agent proximal the plurality of probes, wherein the primary cleaving agent and the plurality of probes are configured to selectively cleave the at least a probe as a result of the primary cleaving agent being in presence of an analyte, and a sensor in communication with the waveguide and configured to detect cleaving of the at least a probe by way of the EM wave.