Corn Active Peptide Additive for Serum-Free Cell Culture
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Solution Overview
Problem
The use of animal-derived additives in cell culture media poses safety risks due to the potential presence of transmissible spongiform encephalopathy viruses and macromolecular proteins, which complicates downstream product separation and increases production costs, while plant-derived alternatives like corn active peptides are challenging to produce with low endotoxin content and consistent quality.
Innovation Solution
A method involving sequential enzymolysis using non-specific and specific proteases to produce corn active peptides with low molecular weight oligopeptides, followed by purification steps like centrifugation, microfiltration, nanofiltration, and ultrafiltration to achieve a product with high oligopeptide content and low endotoxin levels, suitable for serum-free cell culture media.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If animal-derived additives such as serum are used in cell culture medium, then cell growth and metabolism are supported, but safety risks increase due to potential presence of transmissible spongiform encephalopathy viruses and other dangerous substances
Solution Approach 1:
The patent extracts and removes harmful components (macromolecular proteins, potential viruses) from the culture medium system by replacing animal-derived serum with plant-derived corn active peptides. This substitution eliminates the source of TSE viruses and other animal-derived contaminants while maintaining the essential nutritive functions needed for cell growth.
Solution Approach 2:
The patent employs a plant-based alternative (corn active peptides) that is inherently safer and does not carry the same biological risks as animal-derived products. This disposable-like approach replaces potentially hazardous animal serum with a safer plant-derived substance that can be produced without risk of transmissible spongiform encephalopathy.
2Productivity
If animal-derived additives such as serum are used in cell culture medium, then cell growth requirements are met, but downstream separation and purification of biological products becomes more difficult due to presence of macromolecular proteins
Solution Approach 1:
The patent removes macromolecular proteins from the culture medium by substituting serum with corn active peptides that contain primarily small molecular weight peptides. This extraction of harmful macromolecular components simplifies the downstream separation and purification processes for biological products such as antibodies and vaccines, reducing complexity and improving productivity.
Solution Approach 2:
The patent changes the molecular weight distribution of peptides in the culture medium, creating a localized quality difference where small molecular weight peptides (＜1000 Dalton) predominate. This local quality change in the peptide size distribution facilitates easier separation and purification of target biological products while maintaining adequate nutritive function for cell growth.
3Ease of manufacture
If corn active peptide is produced through conventional processes, then peptide product is obtained, but endotoxin content increases which can damage cell membranes and induce cell apoptosis
Solution Approach 1:
The patent segments the peptide production process into distinct stages with specific enzymatic treatments. By using sequential enzymatic hydrolysis with different proteases and implementing multi-stage separation processes, the method achieves both ease of manufacture and effective reduction of endotoxin content to below 200 EU/g, preventing cell damage while maintaining production feasibility.
Solution Approach 2:
The patent converts the potentially harmful effect of endotoxins into a benefit by implementing specific purification steps that selectively remove endotoxins while retaining the beneficial peptide components. The multi-stage separation process transforms the contamination problem into an opportunity to produce a highly purified product with endotoxin content controlled below harmful thresholds.
4Reliability
If corn active peptide is produced with high purification to reduce endotoxin, then safety improves, but production complexity and cost increase
Solution Approach 1:
The patent divides the purification process into logical segments: enzymatic hydrolysis stage, multi-stage separation stage, and concentration stage. Each segment performs a specific function with moderate complexity, achieving cumulative safety improvements without requiring any single overly complex step. This segmented approach controls overall device complexity while ensuring endotoxin reduction to below 200 EU/g.
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
The resulting corn active peptide additive promotes cell proliferation, enhances cell viability, and improves the expression of cell products when used in serum-free culture media, offering a safe and cost-effective alternative to animal-derived additives.
Implementation Method 1
enzymatic hydrolysis, multi-stage separation and purification
Implementation Method 2
sequential enzymolysis using non-specific and specific proteases
Implementation Method 3
purification steps like centrifugation, microfiltration, nanofiltration, and ultrafiltration
Implementation Method 4
purification steps like centrifugation, microfiltration, nanofiltration, and ultrafiltration
Implementation Method 5
purification steps like centrifugation, microfiltration, nanofiltration, and ultrafiltration
Implementation Method 6
purification steps like centrifugation, microfiltration, nanofiltration, and ultrafiltration
Data Source
AI summary
The present invention provides a corn active peptide additive for cell culture medium, wherein in the corn active peptide additive, oligopeptides with molecular weight of lower than 1000 Dalton account for equal to or more than 90 wt % of total proteins, and the oligopeptides at least comprise one or more of AP, SAP, PAL, VNAP, PSSQ, and TQPGPQ. The corn active peptide additive of the present invention can be compounded with various basic culture mediums for serum-free culture of various animal cells, which not only substantially lowers the cost for cell culturing and reduces pollution and other problems caused by an animal derived component, but also can promote cell proliferation, improve cell viability and enhance expression of cell products.