Acoustic Frequency Sweeping for Scalable Nonviral Transduction
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Solution Overview
Problem
Current transduction and transfection methods face challenges such as low gene transfer efficiency, high cost, low cell viability, and difficulty in scaling up for large numbers of cells, with viral methods being risky and non-viral methods causing membrane disruption and acoustic methods leading to acoustic streaming that disrupts laminar flow.
Innovation Solution
An acoustophoresis method using a device with controlled frequency sweeping of acoustic waves to confine cells and nucleic acids in a defined volume, avoiding acoustic streaming and enhancing contact probability through acoustic radiation forces, allowing for efficient and scalable transduction or transfection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If acoustic waves are applied to confine cells and nucleic acids, then gene transfer efficiency is improved, but acoustic streaming occurs that disrupts laminar flow and reduces confinement precision
Solution Approach 1:
The patent applies frequency sweeping to dynamically modulate the acoustic field, transitioning from static to dynamic control. By continuously varying the frequency across a range, the system prevents acoustic streaming while maintaining acoustic radiation forces for cell confinement, thus resolving the contradiction between productivity and precision
Solution Approach 2:
The patent changes the frequency parameter of the acoustic waves from a fixed value to a sweeping range. This parameter change eliminates acoustic streaming (which occurs at fixed frequencies) while preserving the confining effect through acoustic radiation forces, thereby maintaining both high gene transfer efficiency and precise confinement
2Productivity
If viral vectors are used for transduction, then gene transfer efficiency is improved, but cost increases and safety risks arise from immune response and insertional mutagenesis
Solution Approach 1:
The patent uses acoustic radiation forces as an intermediary mechanism to facilitate gene transfer without viral vectors. The acoustic field acts as a mediator that confines both cells and nucleic acids in the same focal volume, enabling non-viral transduction with high efficiency while avoiding the harmful effects of viral vectors
Solution Approach 2:
The patent replaces the biological mechanism of viral transduction with a physical acoustic mechanism. By using acoustic radiation forces to confine and mix cells with nucleic acids, the system achieves gene transfer without requiring viral vectors, thereby eliminating immune response and insertional mutagenesis risks
3Productivity
If conventional acoustically induced transfection is applied, then gene delivery is enhanced, but cell membrane disruption occurs causing lethal damage and low cell viability
Solution Approach 1:
The patent applies acoustic radiation forces at optimized frequency ranges that provide sufficient confinement for gene delivery without exceeding the threshold that causes membrane disruption. By carefully controlling the acoustic parameters within a specific frequency sweep range, the system achieves partial action - enough to confine cells and nucleic acids but not enough to cause lethal damage
Solution Approach 2:
The patent uses dynamic frequency sweeping to modulate the acoustic field intensity and distribution over time. This dynamic approach allows the system to maintain effective confinement during parts of the cycle while avoiding sustained exposure at intensities that cause membrane disruption, thereby preserving cell viability
4Adaptability or versatility
If large numbers of cells are treated to meet clinical requirements, then scalability is improved, but cost increases and processing time extends
Solution Approach 1:
The patent employs continuous flow through the acoustic chamber, allowing cells to be processed continuously rather than in batch mode. The acoustic field operates continuously to confine and transduce cells as they flow through, enabling scalable processing without extending overall treatment time
Solution Approach 2:
The patent replaces manual or batch-based transduction methods with an automated continuous flow acoustic system. This mechanical substitution enables high-throughput processing where large numbers of cells can be treated rapidly and continuously, improving scalability while maintaining controlled processing time
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 achieves high gene transfer efficiency, low multiplicity of infection, and high cell viability, enabling rapid modification of large cell numbers with reduced costs and avoiding parasitic fluid flows.
Implementation Method 1
acoustic waves presenting successively all frequencies in a range [f1, f2] from the first frequency f1 to the second frequency f2 during the sweep time
Implementation Method 2
fluid flows that occur within the acoustic chamber when the fluid absorbs the acoustic energy that is transmitted by the acoustic wave generator, known as acoustic streaming
Data Source
AI summary
A method for introducing foreign nucleic acids into cells assisted with acoustophoresis and including a step of continuously sweeping a frequency of acoustic waves from a first frequency f1 to a second frequency f2 using a sweep time ranging from 1 ms to 100 ms, f2 being superior to f1. Also, a method for performing transduction of cells, cells obtained by the method and an acoustophoresis device for introducing foreign nucleic acids into cells including a chamber, at least two inlets, at least two outlets and at least one acoustic wave generator is configured to continuously sweep a frequency of the acoustic waves from a first frequency f1 to a second frequency f2 using a sweep time ranging from 1 ms to 100 ms, f2 being superior to f1.