Tissue-Resident Extracellular Vesicle Collection via Negative Pressure
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Solution Overview
Problem
Current methods for collecting tissue-derived extracellular vesicles (EVs) often damage the tissue, leading to altered EV contents and poor representation of in vivo conditions, with existing research focusing mainly on blood samples and suffering from low yield and authenticity issues regarding tumor-derived EVs.
Innovation Solution
A method involving a tissue sample placed on a collection device with negative pressure to harvest EVs from the interstitial fluid without using tissue-damaging enzymes, allowing for the retention of tissue integrity for histopathological examination, and administering these EVs to a lymph node to remodel or activate it, potentially containing immune checkpoint inhibitors or mitophagy pathway constituents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If tissue-damaging enzymes are used to collect EVs from tissue, then EV collection yield is improved, but tissue integrity is compromised and EV contents are altered
Solution Approach 1:
The invention extracts EVs from the interstitial fluid of intact tissue sections without using tissue-damaging enzymes. The method involves incubating tissue sections with interstitial fluid collection medium to allow EVs to passively shed into the medium, then collecting and purifying EVs from this medium. This extraction approach maintains tissue integrity while achieving high EV yield.
Solution Approach 2:
The invention introduces an intermediary medium (interstitial fluid collection medium) that facilitates EV collection without directly contacting and damaging the tissue. This medium acts as a buffer between the tissue and the collection process, allowing EVs to transfer passively while preserving tissue structure for subsequent histopathological examination.
2Ease of operation
If EVs are collected from blood samples, then collection process is simplified, but EV yield from tumor tissue is low and authenticity is compromised
Solution Approach 1:
The invention performs preliminary action by collecting interstitial fluid and EVs directly from the tumor tissue before any processing or fixation. This allows capture of EVs in their native state directly from the tumor microenvironment, ensuring high authenticity and quantity of tumor-derived EVs without the need for complex blood processing procedures.
3Reliability
If tissue is fixed and processed for histopathology first, then diagnostic examination is enabled, but EV collection capability is lost
Solution Approach 1:
The invention segments the tissue processing workflow into two independent parallel paths: (1) EV collection path where intact tissue sections are incubated with collection medium to harvest EVs, and (2) histopathology path where separate tissue sections undergo fixation and processing. This segmentation allows both EV collection and diagnostic examination to be performed on the same original tissue sample without interfering with each other.
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 enables high-yield, high-purity EV collection that accurately reflects the in vivo state of the tumor, facilitating real-time metabolic and immunological insights and potential therapeutic applications by maintaining tissue integrity and providing a rich source of tumor-specific biomarkers.
Implementation Method 1
applying a negative pressure on the tissue sample; harvesting extracellular vesicles (EVs) ex vivo from a region within the tissue sample having a tissue interstitial fluid (IF)
Data Source
AI summary
The present invention relates to a non-destructive method comprising placing a tissue sample on a porous matrix, centrifuging the tissue sample under a negative pressure, applying a vacuum on the tissue sample, and collecting extracted extracellular vesicles from the tissue sample. The method does not cause physical rupturing of the tissue sample and maintains integrity of the tissue sample for further histopathological analysis. Moreover, the invention also provides a method of inducing an immune response of a host by immune sensitization using harvested extracellular vesicles.