NanoDLD Polymer Substrate Synthesis Error Correction
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Solution Overview
Problem
Current chemical synthesis methods face challenges in efficiently purifying molecular products due to limitations in error correction and contamination removal, particularly in solid phase synthesis, where tethered constructs can lead to yield loss and contamination.
Innovation Solution
The use of nanoscale deterministic lateral displacement (nanoDLD) technology, which involves polymer substrates and nanostructured separation devices to separate molecules based on size, allowing for continuous operation and proof-reading of chemical reactions by amplifying the length of polymer constructs, enabling the discernment between reacted and unreacted products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If solid phase synthesis is used to facilitate complex synthesis and purification by immobilizing species on solid support, then synthesis complexity is improved, but yield loss and contamination occur due to tethered constructs that fail to react
Solution Approach 1:
The patent extracts the separation function from the synthesis process by using orthogonal size-based separation (nanoDLD) to remove failed tethered constructs from the reaction mixture. This allows the synthesis to proceed with solid phase immobilization while continuously removing error products, thereby maintaining high yield and preventing contamination without reducing synthesis complexity.
Solution Approach 2:
The patent introduces an intermediary separation step using nanoDLD technology that mediates between the synthesis process and final purification. This intermediary system uses size-based deterministic lateral displacement to selectively separate failed constructs from successful products, resolving the contradiction between maintaining synthesis complexity and preventing yield loss.
2Reliability
If error correction is performed by sealing failed targets with capping reagents in solid phase synthesis, then error limiting capability is improved, but yield loss occurs and contamination must be removed at end stage
Solution Approach 1:
The patent applies preliminary action by performing size-based separation of failed constructs immediately after each synthesis step using nanoDLD, rather than waiting for end-stage purification. This preliminary removal of errors prevents yield loss and contamination accumulation, maintaining both error correction capability and productivity throughout the synthesis process.
Solution Approach 2:
The patent implements continuous error correction and purification by integrating nanoDLD separation with the synthesis workflow, allowing continuous removal of failed constructs rather than batch processing at the end. This continuous action maintains high yield and prevents contamination without sacrificing error correction capability.
3Measurement precision
If nanoscale deterministic lateral displacement is used for size-based fractionation, then separation resolution is improved, but device complexity increases due to asymmetric pillar arrays and nanofluidic structures
Solution Approach 1:
The patent replaces complex mechanical separation systems with a nanofluidic device that uses deterministic lateral displacement based on asymmetric pillar arrays. This substitution achieves high separation resolution through nanoscale geometric effects rather than complex mechanical operations, resolving the contradiction between separation precision and device complexity.
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 error-correction capability of chemical synthesis by using size-dependent separation to purify products, allowing for continuous operation and single-particle interrogation, thereby improving the yield and reducing contamination in molecular synthesis.
Implementation Method 1
nanoscale deterministic lateral displacement (nanoDLD) technology, which involves polymer substrates and nanostructured separation devices to separate molecules based on size
Data Source
AI summary
Methods of liquid-phase synthesis of polymers using polymer substrates and systems for facilitating such methods allow gating of a synthetic reaction into a binary (reacted or unreacted) readout. Polymer substrates are used as carriers for molecular reagents and act as separation tags that allow them to be purified using nanoscale deterministic lateral displacement. Two polymer substrates are linked together by a bond-forming reaction to form a longer polymer that includes a synthetic product. The synthetic product can be purified away from unreacted polymers/reagents using strand-length dependent lateral displacement.