Thermoresponsive Aptamer-Polymer Conjugates for Biopharmaceutical Purification
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Solution Overview
Problem
Current biopharmaceutical purification methods, such as centrifugation and column-based chromatography, are complex and prone to system breakdown, especially at high flow capacities, necessitating a simpler and more selective purification technique for polypeptides like antibodies.
Innovation Solution
The use of aptamer-polymer conjugates, specifically thermoresponsive polymers and DNA aptamers, to bind target polypeptides, followed by the addition of thermoresponsive block copolymers to induce liquid-liquid phase separation, allowing for the separation of target polypeptides from contaminants into distinct aqueous and polymer phases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If column-based chromatography is used for purification, then purification selectivity is improved, but device complexity and risk of system breakdown increase
Solution Approach 1:
The patent employs temperature as a critical parameter to control the solubility and phase behavior of the polymer conjugate. By changing temperature, the system transitions between bound and unbound states, enabling purification without complex chromatographic columns. This parameter-based control simplifies the device while maintaining selectivity through the temperature-dependent binding characteristics of the polymer-aptamer conjugate.
Solution Approach 2:
The invention replaces the mechanical chromatography system with a thermally-driven phase separation system. Instead of using complex column mechanics, pumps, and flow control systems, the patent uses temperature-induced liquid-liquid phase separation to achieve purification. This substitution dramatically reduces device complexity while maintaining purification effectiveness.
2Manufacturing precision
If centrifugation and filtration are used, then separation is achieved, but process complexity and opportunities for system breakdown increase
Solution Approach 1:
The patent merges the binding function and separation function into a single integrated system. The polymer-aptamer conjugate both captures the target polypeptide and simultaneously drives phase separation through temperature control. This consolidation eliminates the need for separate centrifugation and filtration steps, reducing process complexity while maintaining separation efficiency.
Solution Approach 2:
The invention utilizes liquid-liquid phase separation induced by temperature changes to achieve separation. The polymer conjugate undergoes a phase transition from a soluble bound state at lower temperatures to an insoluble precipitated state at higher temperatures, naturally separating the target from contaminants without requiring additional mechanical separation steps.
3Manufacturing precision
If affinity purification is performed, then selectivity is improved, but processing time and temperature control requirements increase
Solution Approach 1:
The patent maintains continuous useful action by performing binding and separation in a single continuous process. The temperature-induced phase separation occurs simultaneously with the binding equilibrium, eliminating the need for separate incubation and separation steps. This continuous approach reduces processing time while maintaining affinity selectivity throughout the process.
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 method enhances the efficiency and selectivity of biopharmaceutical purification by enabling the separation and extraction of target polypeptides with reduced background contamination, reducing the risk of system breakdown and improving productivity.
Implementation Method 1
heating the solution comprising the environmentally-responsive block copolymer and the polymer conjugate bound to the target at a second temperature to initiate a liquid-liquid phase separation, wherein the liquid-liquid phase separation produces an aqueous phase and a liquid polymer phase
Implementation Method 2
the polymer conjugate is configured to specifically bind the target
Data Source
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AI summary
A method for purification of a target in a solution includes providing a target in a solution, the solution comprising one or more contaminants, providing a polymer conjugate in the solution, wherein the polymer conjugate is configured to specifically bind the target, incubating the solution at a first temperature to facilitate binding of the polymer conjugate to the target, providing an environmentally-responsive block copolymer in the solution, wherein the environmentally-responsive block copolymer comprises one or more of an ethylene oxide (EO), a propylene oxide (PO), or an EO/PO block copolymer, and heating the solution comprising the environmentally-responsive block copolymer and the polymer conjugate bound to the target at a second temperature to initiate a liquid-liquid phase separation, wherein the liquid-liquid phase separation produces an aqueous phase and a liquid polymer phase, and wherein the liquid polymer phase comprises the polymer conjugate bound to the target.