Cationic Adsorbent Spheres for Rapid Microvesicle Isolation
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Solution Overview
Problem
Existing methods for isolating microvesicles, such as ultra-centrifugation, size exclusion, immunoaffinity isolation, and polymeric methods, suffer from low yield, high cost, long processing times, and specificity issues, making them unsuitable for efficient microvesicle extraction.
Innovation Solution
A method involving the use of adsorbent spheres with polyvalent cations to capture microvesicles from biological samples, followed by washing and elution with specific reagents, allowing for high-yield and high-purity isolation without expensive equipment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ultra-centrifugation isolation is used, then reliability of isolation is improved, but productivity deteriorates (takes 8 hours or more)
Solution Approach 1:
The patent replaces the mechanical ultra-centrifugation system with a chemical adsorption system using cationic adsorbent particles. Instead of using high-speed rotation and centrifugal force to separate microvesicles, the invention uses electrostatic attraction between cationic particles and anionic microvesicle surfaces to achieve rapid separation within minutes, eliminating the need for expensive centrifugal equipment and expert operation while maintaining isolation reliability.
Solution Approach 2:
The patent changes the isolation parameter from mechanical force (centrifugal force) to chemical property (electrostatic charge). By utilizing the negative surface charge of microvesicles and the positive charge of cationic adsorbent particles, the system achieves rapid binding and separation without requiring high-speed centrifugation, thus improving productivity while maintaining isolation effectiveness.
2Reliability
If ultra-centrifugation isolation is used, then isolation reliability is improved, but loss of time worsens (8 hours or more)
Solution Approach 1:
The patent replaces the time-consuming mechanical ultra-centrifugation process with a rapid chemical adsorption process. The cationic particles bind to microvesicles through electrostatic attraction within minutes, followed by simple magnetic separation or filtration, reducing the isolation time from 8 hours to less than 30 minutes while maintaining reliable isolation.
Solution Approach 2:
The patent performs preliminary binding of microvesicles to cationic particles under gentle conditions before separation. This preliminary action allows microvesicles to naturally attach to the adsorbent particles without requiring high-speed centrifugation, enabling subsequent rapid separation through magnetic fields or filtration, thus significantly reducing total isolation time.
3Manufacturing precision
If size exclusion is used, then manufacturing precision of purity is improved, but productivity deteriorates (low yield due to sticking to filter)
Solution Approach 1:
The patent introduces cationic adsorbent particles as an intermediary between the microvesicles and the separation system. These particles bind to microvesicles through electrostatic attraction, forming large complexes that can be easily separated from the solution without sticking to filters. This intermediary approach maintains high purity while preventing yield loss during separation.
Solution Approach 2:
The patent modifies the local quality of microvesicles by coating them with cationic particles. This local modification changes their surface properties, making them less prone to sticking to filter surfaces during separation. The cationic coating creates a protective layer that prevents direct contact between microvesicles and the filter, thereby maintaining both purity and yield.
4Manufacturing precision
If immunoaffinity isolation is used, then manufacturing precision of specificity is improved, but device complexity worsens (antibody making process)
Solution Approach 1:
The patent uses cationic adsorbent particles that can bind to the negatively charged surfaces of various types of microvesicles (exosomes, ectosomes, apoptotic bodies) regardless of their specific origin or surface proteins. This universal binding mechanism eliminates the need for specific antibodies for each microvesicle type, simplifying the process while maintaining the ability to isolate different microvesicle populations through subsequent washing and elution steps.
Solution Approach 2:
The patent replaces expensive, complex antibody reagents with inexpensive, commercially available cationic particles. These particles can be used directly without requiring complex antibody production, purification, and conjugation processes. The simple particle-based approach reduces device complexity and makes the isolation process more accessible for routine diagnostics.
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 method enables rapid and efficient isolation of microvesicles from biological samples with high purity, suitable for on-site diagnosis and using minimal sample volume.
Implementation Method 1
one or more polyvalent cations disposed on a surface of the support
Implementation Method 2
the first reagent contains at least one of CH3COO-, SO42-, HCO-, SiO-, and OH-
Implementation Method 3
washing the adsorbent sphere having the microvesicles captured thereon under a first condition
Implementation Method 4
eluting the microvesicles from the washed adsorbent sphere conjugate using a second reagent
Data Source
Figure 1
Figure 2~3b
Figure 4~6
AI summary
Disclosed is a microvesicles isolation method to isolate microvesicles contained in the biological sample from the sample, the method comprising: (a) adding an adsorbent sphere to the biological sample containing the microvesicles therein; (b) keeping the adsorbent sphere in the biological sample to form an adsorbent sphere conjugate composed of the adsorbent sphere and the microvesicles captured thereon; (c) isolating the adsorbent sphere conjugate from the biological sample; (d) washing the isolated adsorbent sphere conjugate using a first reagent; and (e) eluting the microvesicles from the washed adsorbent sphere conjugate using a second reagent, wherein the adsorbent sphere includes a support, and one or more polyvalent cations disposed on a surface of the support.