Pancreatic Islet Separation via Cryoprotectant-Freezing Disruption
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Solution Overview
Problem
Current methods for isolating pancreatic islets for diabetes treatment, such as enzymatic digestion, are harsh, toxic, and inconsistent, leading to loss of valuable cells and high costs due to the need for pure enzymes, and fail to effectively separate desired cells from unwanted tissue.
Innovation Solution
A method using differential freezing and cryopreservation techniques to selectively preserve desired pancreatic islets by making them less prone to destructive freezing, while making unwanted cells more prone, allowing for their separation without enzymatic digestion, involving pre-treatment with cryoprotectants, controlled freezing, and mechanical disruption to release the islets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If enzymatic digestion is used to release islets from tissue, then islets can be separated from unwanted cells, but the process is harsh and toxic causing loss of valuable cells
Solution Approach 1:
The patent replaces the chemical/enzymatic digestion system with a mechanical disruption system. Tissue is frozen to a brittle state and then mechanically disrupted by passing through a grinder or homogenizer, which physically breaks apart the tissue matrix to release islets without using toxic enzymes.
Solution Approach 2:
The patent utilizes the phase transition of water from liquid to solid by freezing the tissue. This phase change makes the tissue brittle and facilitates mechanical disruption, while also preserving islet viability through cryoprotection. The frozen state allows for clean mechanical separation without chemical damage.
2Reliability
If enzymatic digestion is used to isolate islets, then cells can be released, but the process is inconsistent and expensive due to batch variations in enzymes
Solution Approach 1:
The patent replaces the complex enzymatic digestion process with a simple mechanical disruption process. This eliminates the need for expensive, batch-variable enzymes and provides a more reliable, consistent method that can be easily standardized and scaled.
Solution Approach 2:
The patent uses a disposable mechanical disruption device (grinder/homogenizer) that is simple and inexpensive compared to expensive enzymatic reagents. The mechanical system can be easily replaced or cleaned, providing consistent results without the cost and variability of enzymatic batches.
3Quantity of substance
If crude cutting of tissue is used to separate cells, then the process is simple, but it fails to effectively separate desired cells from unwanted cells
Solution Approach 1:
The patent uses freezing-induced brittleness to enable effective mechanical separation. The frozen tissue can be thoroughly disrupted by grinding, which completely breaks apart the tissue matrix and releases islets, allowing for effective separation that is more complete than crude cutting while still using simple mechanical equipment.
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 results in a more consistent, reliable, and less toxic method for isolating functional islet cells, reducing cell loss and variability, and enabling the preservation and shipment of frozen tissue for therapeutic use.
Implementation Method 1
infusing islet tissue with a cryoprotectant solution comprising a cryoprotective agent (CPA)
Implementation Method 2
freezing the tissue
Implementation Method 3
warming the tissue
Data Source
AI summary
Methods of isolating cellular products, such as pancreatic islets, may be used in diabetes research and therapeutic transplantation. The methods may involve providing a tissue having desired cells that are less prone to destructive freezing and undesired cells that are more prone to destructive freezing, or pre-treating a tissue to have such characteristics. The methods may involve freezing the tissue, disrupting the tissue, warming the tissue, and separating the desired cells from undesired cellular material to obtain the cellular product. The methods may thereby provide an enzyme-free or reduced-enzyme method of isolating a cellular product that is more consistent, reliable and less toxic than conventional methods. The methods may also yield an optimum quantity of cellular product that retain sufficient functional integrity to be useful as a transplantation resource.