Multinode Acoustic Focusing for Parallel Flow Cytometry
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Solution Overview
Problem
Conventional flow cytometry is limited in analysis rate due to detector sensitivity, data acquisition complexity, system pressure, and stochastic cellular arrival, making it inadequate for detecting rare events like circulating tumor cells, and is costly and complex.
Innovation Solution
The use of multi-node acoustic focusing to create multiple parallel streams within a single flow cytometer channel, allowing for higher analysis rates without the need for high-pressure sheath flows, using acoustic waves to focus particles into precise positions, enabling simultaneous analysis of multiple streamlines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional hydrodynamic focusing with high-pressure sheath fluid is used to focus particles into a single stream, then precise particle positioning is achieved, but analysis rate is limited to approximately 50,000 cells per second
Solution Approach 1:
The invention divides the single focused stream into multiple parallel streams (e.g., 4 streams) within the same flow cell. Each stream is focused by acoustic nodes positioned at specific locations, enabling simultaneous analysis of multiple particle streams without requiring multiple independent flow cells or complex hydrodynamic focusing systems for each stream.
Solution Approach 2:
The invention replaces the mechanical hydrodynamic focusing system (which requires high-pressure sheath fluid delivery) with an acoustic focusing system. Acoustic waves generate standing wave patterns that create focal nodes to position particles, eliminating the need for high-pressure fluid delivery and complex hydrodynamic focusing while enabling higher analysis rates.
2Productivity
If high-pressure sheath fluid is used to increase linear velocity for higher analysis rates, then analysis rate increases, but system complexity and cost increase due to greater than 1 MPa pressure requirements
Solution Approach 1:
The invention replaces the mechanical pressure-based hydrodynamic focusing system with an acoustic wave-based focusing system. Acoustic waves generate standing wave patterns that create focal nodes to position particles without requiring high-pressure fluid delivery, thereby simplifying the pressure system and reducing complexity while enabling higher analysis rates through parallel stream processing.
3Device complexity
If conventional single stream focusing is used, then system simplicity is maintained, but analysis rate cannot exceed 50,000 cells per second due to stochastic cellular arrival and coincidence rates
Solution Approach 1:
The invention segments the particle flow into multiple parallel streams within a single flow cell, each stream being focused by acoustic nodes. This allows simultaneous analysis of multiple particles without increasing overall system complexity, as all streams are processed within the same flow cell using a unified acoustic focusing approach.
Solution Approach 2:
The acoustic focusing system serves multiple functions: it focuses particles into multiple parallel streams simultaneously, replaces the need for high-pressure sheath fluid delivery, and enables higher analysis rates all within a single flow cell. This multi-functionality increases productivity without proportionally increasing system complexity.
4Productivity
If multiple independent channels with independent focusing elements are used to achieve higher analysis rates, then analysis rate increases, but device complexity becomes unacceptably high
Solution Approach 1:
The invention merges multiple focusing functions into a single flow cell by using acoustic waves to create multiple focal nodes simultaneously. Instead of requiring multiple independent flow cells or complex hydrodynamic focusing systems for each stream, the acoustic system focuses particles into multiple parallel streams within the same flow cell, thereby increasing analysis rate without unacceptably increasing device complexity.
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 significantly increases analysis rates beyond conventional limits, reduces system complexity and cost, and maintains precise particle positioning for effective detection and analysis, particularly suitable for rare event detection and larger particles.
Implementation Method 1
multi-node acoustic focusing to create multiple parallel streams within a single flow cytometer channel, allowing for higher analysis rates without the need for high-pressure sheath flows, using acoustic waves to focus particles into precise positions
Data Source
AI summary
An analytical device such as a flow cytometer is provided in which a fluid sample flowing through a channel is focused into multiple, parallel particle streams by an acoustic wave field extending across the channel. Each stream is then presented to an individual detector to allow for simultaneous interrogation of the multiple streams and thus, high-throughput analysis of the fluid sample.