Modulated Pulsed Acoustic Field for Controlled Cell Aggregation
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Solution Overview
Problem
Current cell manipulation techniques, particularly ultrasonic cell trapping, face challenges in controlling the aggregation mechanism of cells, especially in forming 2-D or 3-D aggregates, with a narrow concentration margin for 2-D aggregate formation and rapid particle velocities at resonance leading to poor reproducibility.
Innovation Solution
A method involving a modulated pulsed acoustic field is applied, where the acoustic field is modulated in amplitude by repeating groups of acoustic wave pulses with varying durations and amplitudes, allowing for controlled aggregation and selective generation of 2-D or 3-D aggregates without adverse effects on the objects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a continuous acoustic field is used to form aggregates, then aggregation speed is improved, but acoustic field heating and liquid heating increase causing thermodynamic instability
Solution Approach 1:
The patent applies periodic pulsed acoustic fields instead of continuous acoustic fields to form cell aggregates. The acoustic field is activated in pulses with specific durations and intervals, enabling aggregation to proceed while allowing thermal dissipation during off-periods, thus controlling temperature rise and maintaining thermodynamic stability.
Solution Approach 2:
The patent dynamically adjusts the duration and intensity of acoustic pulses based on real-time monitoring of aggregate formation and temperature. By making the acoustic field parameters variable rather than static, the system optimizes aggregation speed while preventing excessive heating that would occur with continuous application.
2Productivity
If high amplitude acoustic waves are used to accelerate aggregation, then aggregation speed is improved, but object damage increases
Solution Approach 1:
The patent uses periodic pulsed acoustic fields with controlled amplitude and duration. The pulsing regime allows cells to experience high-amplitude acoustic waves only during brief intervals, sufficient to drive aggregation, while the intervals between pulses allow cells to recover, minimizing mechanical damage and cavitation effects.
Solution Approach 2:
The patent applies acoustic energy at levels that are sufficient to drive aggregation but not excessively high to cause damage. By using partial action (pulsed rather than continuous) at optimized amplitudes, the system achieves the necessary aggregation speed while staying below damage thresholds.
3Productivity
If resonance frequency is used to maximize acoustic force, then aggregation efficiency is improved, but particle velocity becomes rapid leading to poor reproducibility
Solution Approach 1:
The patent employs periodic pulsed acoustic fields that can be applied at or near resonance frequencies to maximize aggregation efficiency during pulse periods. The pulsing regime controls the timing and duration of resonant excitation, preventing runaway particle velocities while maintaining high aggregation efficiency during active periods, thus improving reproducibility.
4Manufacturing precision
If acoustic field parameters are increased to improve aggregation control, then aggregation precision is improved, but heating effects increase causing thermodynamic instability
Solution Approach 1:
The patent uses periodic pulsed acoustic fields where high-intensity pulses provide the necessary aggregation control and precision, while the intervals between pulses allow thermal dissipation. This temporal separation enables precise aggregation control during pulse periods without accumulating excessive heat that would cause thermodynamic instability.
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 enables more controlled and reproducible aggregation, reducing acoustic field and liquid heating, maintaining thermodynamic stability, and allowing for the formation of aggregates with specific architectures irrespective of initial object concentration, while minimizing object damage.
Implementation Method 1
The acoustic force Fac drives particles towards the nodes or antinodes depending on their acoustic properties. Fac=VkÃac>sin(2kx), where V is the particle volume, k=2π/λ is the wave number, Ã=[3(ρp−ρf/(2ρp+ρf)−(cp2ρp/cf2ρf)] is the acoustic contrast factor
Implementation Method 2
The USWT is an ultrasound resonator where the acoustic path-length in the cell suspension is a single half wavelength. The resonator has a pressure node plane half way through the cell suspension and parallel to the transducer.
Implementation Method 3
A method involving a modulated pulsed acoustic field is applied, where the acoustic field is modulated in amplitude by repeating groups of acoustic wave pulses with varying durations and amplitudes
Data Source
AI summary
A method of forming an aggregate of objects in a channel including a liquid, the method including: a) providing objects in at least a region of the channel, and b) forming an aggregate of the objects by submitting them to a modulated pulsed acoustic field, wherein the modulated pulsed acoustic field applied at step b) is modulated in amplitude.