Acoustic Cell Release from Porous Matrix
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Solution Overview
Problem
Conventional methods for isolating rare cells, such as circulating tumor cells, from whole blood are limited by the need for cell fixation, which reduces cell recovery and viability, and are inefficient due to size and viscoelastic property differences among cell populations, leading to contamination and loss of small cancer cells.
Innovation Solution
Applying sonic energy to a porous matrix surface opposite to the cell-containing area allows for the selective release and collection of biological particles, including rare cells, without the need for fixation, independent of cell diameter and viscoelastic properties, using a frequency of 20 kHz to 200 MHz and a liquid medium to collect the cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If cell fixation is used to improve separation efficiency, then separation efficiency is improved, but cell recovery and viability are reduced
Solution Approach 1:
The patent replaces chemical fixation methods with acoustic radiation force for cell separation. Acoustic waves generate radiation pressure that physically pushes cells through the filter based on their size and density, eliminating the need for chemical fixation while maintaining separation efficiency and preserving cell viability for downstream analysis.
Solution Approach 2:
The patent changes the separation mechanism from chemical (fixation) to physical (acoustic frequency and intensity parameters). By adjusting acoustic frequency and power, the system can separate cells based on their physical properties without chemical modification, thus improving both separation efficiency and cell recovery.
2Manufacturing precision
If filtration based on size differences is used to separate rare cells, then separation efficiency is improved, but small cancer cells are lost due to overlapping diameters with white blood cells
Solution Approach 1:
The patent replaces size-based mechanical filtration with acoustic radiation force-based separation. The acoustic field exerts force on cells proportional to their compressibility and density, not just size, allowing differentiation of small cancer cells from white blood cells that have overlapping dimensions but different physical properties.
Solution Approach 2:
The patent changes the separation criterion from geometric (diameter) to physical (compressibility and density response to acoustic waves). By tuning acoustic frequency and intensity, the system can selectively manipulate cells based on their mechanical properties, reducing loss of small cancer cells.
3Productivity
If higher pressure is applied to pass fixed cells through porous matrix, then cell passage is improved, but capture of undesired cells increases
Solution Approach 1:
The patent replaces pressure-driven filtration with acoustic radiation force-driven cell propulsion. Acoustic waves generate radiation pressure that pushes cells through the matrix without requiring high hydrostatic pressure, thereby maintaining selective capture while improving cell passage efficiency.
Solution Approach 2:
The patent changes the driving force from hydrostatic pressure to acoustic radiation pressure. By controlling acoustic intensity and frequency, the system can achieve cell passage through the matrix without the need for high pressure that would cause non-specific capture of undesired cells.
4Manufacturing precision
If smaller pores are used to improve separation precision, then separation precision is improved, but cell passage is reduced
Solution Approach 1:
The patent replaces passive size-exclusion filtration with active acoustic radiation force propulsion. Smaller pores can be used for higher precision separation while acoustic waves provide the driving force to push cells through the tighter pores, maintaining both separation precision and cell passage.
Solution Approach 2:
The patent changes the cell transport mechanism from pressure-driven flow to acoustic radiation force-driven transport. This allows the use of smaller pores for higher precision separation while the acoustic field ensures adequate cell passage by providing the necessary driving force without requiring larger pores.
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 achieves high cell recovery and separation efficiency, with over 90% of cells being disengaged from the matrix, maintaining cell viability and reducing contamination, and is applicable to both fixed and non-fixed cells.
Implementation Method 1
applying sonic energy to an opposing area on a second surface of the matrix to release the particles
Implementation Method 2
applying sonic energy to an opposing area on a second surface of the matrix to release the particles
Data Source
AI summary
Particles are released from a particle-containing area of a first surface of a porous matrix. The particle-containing area is contacted with a liquid medium and sonic energy is applied to an opposing area on a second surface of the porous matrix, wherein the opposing area is opposite to the particle-containing area. The particles may be biological particles or non-biological particles.