Affinity SCODA Separation of Differentially Methylated DNA
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Solution Overview
Problem
There is a need for improved methods and apparatus capable of selectively separating and purifying molecules, including identical molecules that are differentially modified, such as differentially methylated DNA, which is crucial for diagnosing and treating diseases like cancer.
Innovation Solution
The use of affinity SCODA (Synchronous Coefficient Of Drag Alteration) technology, which involves a method for concentrating and separating molecules by applying a time-varying driving field in combination with a time-varying mobility altering field, utilizing an affinity matrix with immobilized probes that bind differentially to target molecules, allowing for the separation of molecules with subtle chemical modifications like methylation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional separation methods are used to separate molecules with subtle chemical modifications, then separation capability is limited, but device complexity and cost increase
Solution Approach 1:
The patent applies parameter changes by utilizing the non-linear electrophoretic response of DNA molecules to time-varying electric fields. By changing the temporal and spatial parameters of the electric field (applying alternating fields at specific frequencies and phases), the system generates a time-averaged net force that enables separation of differentially modified DNA without requiring complex physical or chemical modifications to the separation medium
Solution Approach 2:
The patent employs periodic action through the application of time-varying electric fields that alternate in direction and magnitude. The periodic modulation of field strength creates cycles of mobility alteration that, when synchronized with the driving force, produce net directional motion. This periodic approach replaces complex continuous separation mechanisms with a simpler oscillating field system
2Measurement precision
If affinity matrices with immobilized probes are used to separate differentially modified molecules, then separation precision improves, but processing time increases
Solution Approach 1:
The patent maintains continuity of useful action by applying electric fields continuously throughout the separation process. Rather than using discrete steps of binding and washing that characterize conventional affinity methods, the SCODA system applies continuous time-varying fields that constantly drive separated molecules through the medium, eliminating idle time between operational phases
Solution Approach 2:
The patent substitutes mechanical affinity-based separation with an electrophoretic field-based system. Instead of relying on physical binding to immobilized probes followed by mechanical washing steps, the system uses electric field-induced mobility differences to achieve separation, replacing multi-step mechanical processes with a continuous field-based mechanism
3Productivity
If time-varying electric fields are applied to achieve net motion of molecules, then separation efficiency improves, but energy consumption increases
Solution Approach 1:
The patent uses periodic action to achieve separation with reduced energy consumption. By modulating the electric field periodically and synchronizing mobility alterations with the field cycles, the system generates net motion during only the productive phases of each cycle, minimizing energy waste during reverse or idle phases while maintaining continuous separation activity
Solution Approach 2:
The patent optimizes energy efficiency through parameter changes in the electric field configuration. By adjusting field strength, frequency, and phase relationships, the system maximizes the time-averaged net force during productive phases while minimizing energy dissipation during transition phases, achieving high separation efficiency at lower overall energy consumption
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 enables efficient enrichment and separation of differentially modified molecules, even those with small differences in binding affinity, facilitating the detection of biomarkers and improving diagnostic capabilities for diseases.
Implementation Method 1
SCODA based transport is used to produce net motion of a molecule of interest by synchronizing a time-varying driving force, which would otherwise impart zero net motion, with a time-varying drag (or mobility) alteration
Implementation Method 2
SCODA, known in some embodiments as scodaphoresis, is an approach that may be applied for purifying, separating, or concentrating particles. SCODA may be applied, for example, to DNA, RNA and other molecules including proteins and polypeptides
Implementation Method 3
The affinity matrix has an immobilized affinity agent that has a first binding affinity for the molecule of interest and a second binding affinity for at least some of the other molecules in the biological sample
Data Source
AI summary
Methods and apparatus for separating, concentrating and/or detecting molecules based on differences in binding affinity to a probe are provided. The molecules may be differentially modified. The molecules may be differentially methylated nucleic acids. The methods can be used in fields such as epigenetics or oncology to selectively concentrate or detect the presence of specific biomolecules or differentially modified biomolecules, to provide diagnostics for disorders such as fetal genetic disorders, to detect biomarkers in cancer, organ failure, disease states, infection or the like.