Acoustic Cell Sorting via Bubble-Enhanced Radiation Forces
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Solution Overview
Problem
Current flow cytometry methods for differentiating and sorting cells are time-consuming and costly, particularly due to the need for multiple lasers and fluorophores, and face challenges in sensitivity and additional differentiation parameters.
Innovation Solution
The use of ultrasound technology to activate cells by applying acoustic waves, causing volumetric changes and displacement, allowing for the differentiation and sorting of cells based on these changes without the need for expensive lasers and fluorophores, by attaching bubbles to cells of interest to enhance interaction with acoustic waves.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If flow cytometry uses multiple lasers and fluorophores to differentiate cell types, then measurement precision and differentiation capability are improved, but device complexity and cost increase
Solution Approach 1:
The patent replaces optical detection systems (lasers and fluorophores) with an acoustic detection system using ultrasound waves. Acoustic waves interact with cells based on their mechanical properties such as stiffness, density, and compressibility, enabling cell differentiation without complex optical instrumentation. This substitution maintains measurement precision while significantly reducing device complexity.
Solution Approach 2:
The invention changes the detection parameter from optical properties (fluorescence emission) to mechanical properties (acoustic impedance, stiffness, density). By measuring how cells respond to acoustic waves in terms of their mechanical characteristics, the system achieves accurate cell differentiation using simpler, more cost-effective equipment.
2Loss of information
If flow cytometry uses multiple lasers and fluorophores to achieve multi-parametric analysis, then information gathering capability is improved, but cost increases
Solution Approach 1:
The patent replaces expensive optical detection systems with acoustic detection using ultrasound. The acoustic waves provide multiple measurement parameters including cell stiffness, density, and compressibility, enabling multi-parametric analysis without the high costs associated with multiple lasers and fluorophores.
Solution Approach 2:
The invention utilizes the inherent mechanical properties of cells themselves as the detection mechanism. Cells naturally respond to acoustic waves based on their physical characteristics, eliminating the need for external fluorescent labels or complex optical systems. This self-service approach reduces costs while maintaining information gathering capability.
3Productivity
If flow cytometry analyzes cells rapidly at high rates, then productivity is improved, but measurement precision may deteriorate
Solution Approach 1:
The patent replaces optical detection with acoustic detection, which can operate at high cell throughput rates while maintaining precision. The acoustic waves can rapidly interact with cells flowing through the system, providing accurate mechanical property measurements without the speed limitations of optical methods.
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 improves sensitivity and sorting capabilities, reduces costs, and enhances accessibility by enabling efficient differentiation and separation of specific cell types, such as leukemia cells, using acoustic radiation forces and standing waves in a flow cell system.
Implementation Method 1
causing volumetric changes and displacement, allowing for the differentiation and sorting of cells based on these changes
Implementation Method 2
using acoustic radiation forces and standing waves in a flow cell system
Implementation Method 3
applying acoustic waves, causing volumetric changes and displacement, allowing for the differentiation and sorting of cells based on these changes
Data Source
AI summary
Embodiments are generally related to differentiating and/or separating portions of a sample that are of interest from the remainder of the sample. Embodiments may be directed towards separating cells of interest from a cell sample. In some embodiments, acoustic impedances of the cells of interest may be modified. For example, the acoustic properties of the cells of interest may be modified by attaching bubbles to the cells of interest. The cell sample may then be subjected to an acoustic wave. The cells of interest may be differentiated and/or separated from the remainder of the sample based on relative displacements and/or volumetric changes experienced by the cells of interest in response thereto. The cells of interest may be separated using a standing wave and sorted into separate channels of a flow cell. Optionally, the cells may be interrogated by a light source and differentiated by signals generated in response thereto.